Yair Blumenfeld, MD

All Publications

• Data-driven longitudinal characterization of neonatal health and morbidity. Science translational medicine De Francesco, D., Reiss, J. D., Roger, J., Tang, A. S., Chang, A. L., Becker, M., Phongpreecha, T., Espinosa, C., Morin, S., Berson, E., Thuraiappah, M., Le, B. L., Ravindra, N. G., Payrovnaziri, S. N., Mataraso, S., Kim, Y., Xue, L., Rosenstein, M. G., Oskotsky, T., Marić, I., Gaudilliere, B., Carvalho, B., Bateman, B. T., Angst, M. S., Prince, L. S., Blumenfeld, Y. J., Benitz, W. E., Fuerch, J. H., Shaw, G. M., Sylvester, K. G., Stevenson, D. K., Sirota, M., Aghaeepour, N. 2023; 15 (683): eadc9854

  Abstract

  Although prematurity is the single largest cause of death in children under 5 years of age, the current definition of prematurity, based on gestational age, lacks the precision needed for guiding care decisions. Here, we propose a longitudinal risk assessment for adverse neonatal outcomes in newborns based on a deep learning model that uses electronic health records (EHRs) to predict a wide range of outcomes over a period starting shortly before conception and ending months after birth. By linking the EHRs of the Lucile Packard Children's Hospital and the Stanford Healthcare Adult Hospital, we developed a cohort of 22,104 mother-newborn dyads delivered between 2014 and 2018. Maternal and newborn EHRs were extracted and used to train a multi-input multitask deep learning model, featuring a long short-term memory neural network, to predict 24 different neonatal outcomes. An additional cohort of 10,250 mother-newborn dyads delivered at the same Stanford Hospitals from 2019 to September 2020 was used to validate the model. Areas under the receiver operating characteristic curve at delivery exceeded 0.9 for 10 of the 24 neonatal outcomes considered and were between 0.8 and 0.9 for 7 additional outcomes. Moreover, comprehensive association analysis identified multiple known associations between various maternal and neonatal features and specific neonatal outcomes. This study used linked EHRs from more than 30,000 mother-newborn dyads and would serve as a resource for the investigation and prediction of neonatal outcomes. An interactive website is available for independent investigators to leverage this unique dataset: https://maternal-child-health-associations.shinyapps.io/shiny_app/.

  View details for DOI 10.1126/scitranslmed.adc9854

  View details for PubMedID 36791208

• Prepregnancy body mass index and gestational diabetes mellitus across Asian and Pacific Islander subgroups in California. AJOG global reports Sperling, M. M., Leonard, S. A., Blumenfeld, Y. J., Carmichael, S. L., Chueh, J. 2023; 3 (1): 100148

  Abstract

  The American College of Obstetricians and Gynecologists recommends early screening for gestational diabetes mellitus among pregnant Asian people with a prepregnancy body mass index ≥23.0 kg/m2, in contrast with the recommended screening at a body mass index ≥25 kg/m2 for other races and ethnicities. However, there is significant heterogeneity within Asian and Pacific Islander populations, and gestational diabetes mellitus and its association with body mass index among Asian and Pacific Islander subgroups may not be uniform across all groups.This study aimed to analyze the association between body mass index and gestational diabetes mellitus among Asian and Pacific Islander subgroups in California, specifically gestational diabetes mellitus rates among those with a body mass index above vs below 23 kg/m2, which is the cutoff point for the designation of being overweight among Asians populations.Using a linked delivery hospitalization discharge and vital records database, we identified patients who gave birth in California between 2007 and 2017 and who self-reported to be 1 of 13 Asian and Pacific Islander subgroups, which was collected from birth and fetal death certificates. In each subgroup, we evaluated the association between body mass index and gestational diabetes mellitus using multivariable logistic regression models adjusted for age, education, parity, payment method, the trimester in which prenatal care was initiated, and nativity. We fit body mass index nonlinearly with splines and categorized body mass index as being above or below 23 kg/m2. Predicted probabilities of gestational diabetes mellitus with 95% confidence intervals were calculated across body mass index values using the nonlinear regression models.The overall prevalence of gestational diabetes mellitus was 14.3% (83,400/584,032), ranging between 8.4% and 17.1% across subgroups. The highest prevalence was among Indian (17.1%), Filipino (16.7%), and Vietnamese (15.5%) subgroups. In these subgroups, gestational diabetes mellitus was diagnosed in 10% to 13% of those with a body mass index <23.0 kg/m2 and in 22% of those with a body mass index ≥23 kg/m2. Gestational diabetes mellitus was least common among Korean (8.4%), Japanese (9.0%), and Samoan (9.8%) subgroups with a gestational diabetes mellitus rate of 5% to 7% among those with a body mass index <23.0 kg/m2 and in 10% to 15% among those with a body mass index ≥23 kg/m2. Although Samoan patients had the highest rate of obesity, defined as body mass index ≥30 kg/m2 (57.4%), they had the third lowest prevalence of gestational diabetes mellitus. Conversely, Vietnamese patients had the second lowest rate of obesity (2.4%) but the highest rate of gestational diabetes mellitus at a body mass index of ≥23 kg/m2 (22.3%).Gestational diabetes mellitus and its association with body mass index varied among Asian subgroups but increased as body mass index increased. Subgroups with the lowest prevalence of obesity trended toward a higher prevalence of gestational diabetes mellitus and those with a higher prevalence of obesity trended toward a lower prevalence of gestational diabetes mellitus.

  View details for DOI 10.1016/j.xagr.2022.100148

  View details for PubMedID 36632428

  View details for PubMedCentralID PMC9826825

• Fasting Compared With Fed and Oral Intake Before the 1-Hour Oral Glucose Tolerance Test: A Randomized Controlled Trial. Obstetrics and gynecology Sperling, M. M., Leonard, S. A., Miller, S. E., Hurtado, J., El-Sayed, Y. Y., Herrero, T., Faig, J., Carter, S., Blumenfeld, Y. J. 2023; 141 (1): 126-133

  Abstract

  OBJECTIVE: To evaluate the effect of fasting compared with eating before the 1-hour oral glucose tolerance test (OGTT) on gestational diabetes mellitus (GDM) screening results.METHODS: In a single-center, prospective randomized trial, participants were randomized to: 1) fasting for 6 or more hours or 2) oral intake ("fed") within 2 hours of the 50-g, 1-hour OGTT. The 1-hour OGTT was administered after 24 weeks of gestation. A positive screen result was defined as a serum glucose level of 140 mg/dL or higher. Protocol adherence was assessed by a survey administered immediately after the OGTT. We planned to enroll 100 participants in each group to detect an absolute difference of 20 percentage points or more on the 1-hour OGTT screen-positive rate using Fisher exact test, assuming an estimated screen-positive rate of 45% in the fasting and 25% in the fed group and 10% attrition, with a two-sided alpha=0.05, power=0.8. The primary outcome was the 1-hour OGTT screen-positive rate. Secondary outcomes included mean 1-hour OGTT glucose values, GDM diagnosis, maternal and neonatal outcomes, and patient perceptions regarding the 1-hour OGTT.RESULTS: From November 2020 through April 2021, 200 participants were randomized. One hundred ninety-five completed the 1-hour OGTT (97 fasting, 98 fed). Participant surveys confirmed 97.9% (n=95) adherence to the fasting and 91.8% (n=90) adherence to the fed groups. The screen-positive rate was significantly higher in the fasting than the fed group (32.0% vs 13.3%, respectively, P=.002), as was the mean glucose value (127.7 mg/dL vs 113.3 mg/dL, P=.002). The incidence of GDM in the fasting group was 12.4% (n=12) and in the fed group was 5.1% (n=5) (P=.08). There were no significant differences in maternal or neonatal outcomes.CONCLUSION: Fasting for 6 or more hours doubled the incidence of a positive 1-hour OGTT result when compared with eating within 2 hours of the test.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04547023.

  View details for DOI 10.1097/AOG.0000000000005013

  View details for PubMedID 36701613

• Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial. Clinical therapeutics Atkinson, M. A., Jelin, E. B., Baschat, A., Blumenfeld, Y. J., Chmait, R. H., O'Hare, E., Moldenhauer, J. S., Zaretsky, M. V., Miller, R. S., Ruano, R., Gonzalez, J. M., Johnson, A., Mould, W. A., Davis, J. M., Hanley, D. F., Keiser, A. M., Rosner, M., Miller, J. L. 2022

  Abstract

  PURPOSE: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days.METHODS: A consortium of 9 North American Fetal Therapy Network (NAFTNet) centers was formed, and the RAFT protocol was refined in collaboration with the NAFTNet Scientific Committee. Enrollment in the trial began in April 2020. Participants may elect to receive amnioinfusions or to join the nonintervention observational expectant management group. Eligible pregnant women must be at least 18 years of age with a fetal diagnosis of isolated early-pregnancy renal anhydramnios.FINDINGS: In addition to the primary study objective stated above, secondary objectives include (1) to assess maternal safety and feasibility of the serial amnioinfusion intervention (2) to perform an exploratory study of the natural history of untreated early pregnancy renal anhydramnios (3) to examine correlations between prenatal imaging and lung specific factors in amniotic fluid as predictive of the efficacy of serial percutaneous amnioinfusions and (4) to determine short- and long-term outcomes and quality of life in surviving neonates and families enrolled in RAFT IMPLICATIONS: The RAFT trial is the first clinical trial to investigate the efficacy, safety, and feasibility of amnioinfusions to treat the survival-limiting pulmonary hypoplasia associated with anhydramnios. Although the intervention offers an opportunity to treat a condition known to be almost universally fatal in affected neonates, the potential burdens associated with end-stage kidney disease from birth must be acknowledged.CLINICALTRIALS: gov identifier: NCT03101891.

  View details for DOI 10.1016/j.clinthera.2022.07.001

  View details for PubMedID 35918190

• Impact of a Potential 20-Week Abortion Ban on Likelihood of Completing Required Views in Second-Trimester Fetal Anatomy Ultrasound. American journal of perinatology Henkel, A., Beshar, I., Cahill, E. P., Blumenfeld, Y. J., Chueh, J., Shaw, K. A. 2022

  Abstract

   The aim of this study was to quantify the likelihood of assessing all mandated fetal views during the second-trimester anatomy ultrasound prior to the proposed federal 20-week abortion ban. Retrospective cohort study of a random sample of 1,983 patients undergoing anatomy ultrasound in 2017 at a tertiary referral center. The difference in proportion of incomplete anatomic surveys prior compared with after 20-week gestation was analyzed using X 2 and adjusted logistic regression; difference in mean days elapsed from anomaly diagnosis to termination tested using t-tests and survival analysis. Incomplete views were more likely with initial ultrasound before 20 weeks (adjusted relative risk: 1.70; 95% confidence interval: 1.50-1.94); 43.5% versus 26.1% were incomplete before and after 20 weeks, respectively. Fetal structural anomalies were identified in 6.4% (n = 127/1,983) scans, with 38.0% (n = 49) identified at follow-up after initial scan was incomplete. 22.8% (n = 29) with an anomaly terminated. A complete assessment of fetal views during an anatomy ultrasound prior to 20-week gestation is often not technically feasible. Legislation limiting abortion to this gestational age would greatly impact patient's ability to make informed choices about their pregnancies.· It is often not technically possible to complete anatomy ultrasound prior to 20-week gestation.. · Often, anomalies are missed during early, incomplete anatomy ultrasounds.. · After the diagnosis of a structural anomaly, one in five chose to terminate the pregnancy..

  View details for DOI 10.1055/s-0042-1749138

  View details for PubMedID 35576967

• A data-driven health index for neonatal morbidities. iScience De Francesco, D., Blumenfeld, Y. J., Maric, I., Mayo, J. A., Chang, A. L., Fallahzadeh, R., Phongpreecha, T., Butwick, A. J., Xenochristou, M., Phibbs, C. S., Bidoki, N. H., Becker, M., Culos, A., Espinosa, C., Liu, Q., Sylvester, K. G., Gaudilliere, B., Angst, M. S., Stevenson, D. K., Shaw, G. M., Aghaeepour, N. 2022; 25 (4): 104143

  Abstract

  Whereas prematurity is a major cause of neonatal mortality, morbidity, and lifelong impairment, the degree of prematurity is usually defined by the gestational age (GA) at delivery rather than by neonatal morbidity. Here we propose a multi-task deep neural network model that simultaneously predicts twelve neonatal morbidities, as the basis for a new data-driven approach to define prematurity. Maternal demographics, medical history, obstetrical complications, and prenatal fetal findings were obtained from linked birth certificates and maternal/infant hospitalization records for 11,594,786 livebirths in California from 1991 to 2012. Overall, our model outperformed traditional models to assess prematurity which are based on GA and/or birthweight (area under the precision-recall curve was 0.326 for our model, 0.229 for GA, and 0.156 for small for GA). These findings highlight the potential of using machine learning techniques to predict multiple prematurity phenotypes and inform clinical decisions to prevent, diagnose and treat neonatal morbidities.

  View details for DOI 10.1016/j.isci.2022.104143

  View details for PubMedID 35402862

• Virtual reality experience for in utero fetal surgery: a new era of patient counselling and medical education BMJ INNOVATIONS Blumenfeld, Y. J., Axelrod, D. M., Sarno, D., Hintz, S. R., Sylvester, K. G., Grant, G. A., Belfort, M. A., Shamshirsaz, A. A., El-Sayed, Y. Y. 2022; 8 (2): 95-97

  View details for DOI 10.1136/bmjinnov-2021-000799

  View details for Web of Science ID 000823101300005

• Maternal-fetal medicine fellows' perception and comfort with obstetrical ultrasound and prenatal diagnosis. American journal of obstetrics & gynecology MFM Holliman, K., Pluym, I. D., Grechukhina, O., Blumenfeld, Y. J., Plattmd, L. D., Copel, J. A., Han, C. S. 2022: 100601

  Abstract

  BACKGROUND: Ultrasound training is a vital component of maternal-fetal medicine (MFM) fellowships in the United States. Of the 18 months of core clinical training, the American Board of Obstetrics and Gynecology (ABOG) currently requires a minimum of three months dedicated to ultrasound in order to be eligible for board certification. However, the experience and degree of hands-on training differs among fellowship programs and has not been reassessed for nearly a decade.OBJECTIVE: To assess regional heterogeneity in ultrasound (US) training experience during maternal-fetal medicine (MFM) fellowship in the United States.STUDY DESIGN: A survey was distributed to postgraduate year (PGY)-6 MFM fellows registered to attend an annual ultrasound training course prior to the conference (n=114). For programs with >1 fellow attending (n=39), only one fellow completed the survey to represent the program. Questions included demographics of the program, ultrasound training structure, fellows' self-perception of ultrasound capabilities, research, mentorship and technical aspects of sonography.RESULTS: Seventy-two PGY-6 fellows completed the survey (96% response rate), with wide geographic distribution: 10 (14%) West, 16 (22%) Midwest, 17 (24%) South, 29 (40%) Northeast. Respondents undergoing training in the South were less likely to report feeling comfortable performing nuchal translucency (NT) and detailed anatomic surveys when compared to other regions (NT: p=0.046; anatomy: p=0.011). The majority of respondents reported feeling comfortable performing growth (78%) and umbilical artery Doppler (58%) and uncomfortable with 3 dimensional (3D) US, neurosonography and fetal echocardiography. Respondents in the Northeast were more likely to report feeling comfortable performing chorionic villus sampling (CVS) (p=0.001). There was no difference among fellowship programs in the presence or absence of US curriculum, bedside teaching, US-focused research mentorship or months of US training.CONCLUSION: Despite the standardization of US training structure across the United States, there remains regional heterogeneity in fellow self-reported comfort with specific US techniques and CVS at a mid-point in their fellowship training. MFM attending involvement at the bedside did not affect fellow self-reported comfort with US surveys. This study highlights the need for further optimization of MFM fellowship US training, especially in advanced sonography and diagnostic procedures.

  View details for DOI 10.1016/j.ajogmf.2022.100601

  View details for PubMedID 35217235

• Development and in-vitro characterization of a novel fetal vesicoamniotic shunt - the Vortex Shunt. Prenatal diagnosis Sheth, K. R., Danzer, E., Johnson, E., Wall, J. K., Blumenfeld, Y. J. 1800

  Abstract

  OBJECTIVES: To develop and test a novel vesicoamniotic shunt (VAS) to treat fetal lower urinary tract obstruction (LUTO), decrease dislodgement and optimize shunt deployment in-vitro.METHODS: VAS design objectives included: 1) robust and atraumatic fixation elements, 2) kink resistant conduit to adjust to fetal movement and growth, 3) one-way pressure valve to facilitate bladder cycling, and 4) echogenic deployment visualization aids. The force to dislodge the novel Vortex shunt was compared with existing commercially available shunts in a bench-top porcine bladder model. Sonographic echogenicity was evaluated with ultrasound-guided deployment, and the shunt valve pressure measured.RESULTS: A prototype novel Vortex shunt was developed using braided nitinol "umbrella-type" ends with a kink-resistant stem incorporating an internal one-way valve. The peak force required to dislodge the Vortex shunt was significantly higher than commercially available shunts (p<0.01). Shunt deployment in the bench-top model was easily confirmed with ultrasound guidance and the brisk decompression of the inflated porcine bladder thereafter. In-vitro valve gauge pressure testing mirrored bladder pressures in human LUTO cases.CONCLUSION: In-vitro testing shows that the Vortex shunt may improve deployment, sonographic visualization, kink resistance, and dynamic size adjustment. Validation in preclinical animal models are warranted and currently underway. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/pd.6096

  View details for PubMedID 35048376

• Maternal Hyperoxygenation Testing in Fetuses with Hypoplastic Left-Heart Syndrome: Association with Postnatal Atrial Septal Restriction. Fetal diagnosis and therapy Mardy, C., Kaplinski, M., Peng, L., Blumenfeld, Y. J., Kwiatkowski, D. M., Tacy, T. A., Maskatia, S. A. 2021: 1-12

  Abstract

  INTRODUCTION: In fetuses with hypoplastic left-heart syndrome (HLHS), maternal hyperoxygenation (MHO) may aid risk stratification. We hypothesized that pulmonary vein (Pvein) velocity time integral (VTI) change with MHO would more reliably identify neonates who undergo emergent atrial septoplasty (EAS) than changes in pulmonary arterial pulsatility index (PA PI).METHODS: Fetuses with HLHS who underwent MHO testing at our institution between 2014 and 2019 were identified. Data were reviewed in a blinded, retrospective manner. Pvein VTI ratio (prograde:retrograde) was calculated. The primary outcome was neonatal EAS.RESULTS: Twenty-seven HLHS fetuses underwent MHO, and 5 (19%) underwent EAS. Without MHO, a Pvein VTI ratio <3 conferred 60% sensitivity and 100% specificity for EAS. With MHO, a Pvein VTI ratio <6.5 conferred 100% sensitivity and specificity. For an intermediate group of fetuses with a baseline Pvein VTI ratio 3-7, the ratio decrease with MHO conferred 100% sensitivity and specificity. Compared to the Pvein VTI ratio, PA PI was less accurate in identifying EAS neonates.DISCUSSION/CONCLUSION: Addition of MHO appears to improve the diagnostic ability of the Pvein VTI ratio to identify HLHS fetuses who undergo EAS. The Pvein VTI ratio change may more accurately identify fetuses who undergo EAS than change in PA PI and has less interobserver variability.

  View details for DOI 10.1159/000519322

  View details for PubMedID 34673647

• PretermConnect: Leveraging mobile technology to mitigate social disadvantage in the NICU and beyond. Seminars in perinatology Jani, S. G., Nguyen, A. D., Abraham, Z., Scala, M., Blumenfeld, Y. J., Morton, J., Nguyen, M., Ma, J., Hsing, J. C., Moiwa-Grant, M., Profit, J., Wang, C. J. 2021: 151413

  Abstract

  Preterm birth (PTB) - delivery prior to 37-weeks gestation - disproportionately affects low-income and minority populations and leads to substantial infant morbidity and mortality. The time following a PTB represents an optimal window for targeted interventions that encourage mothers to prioritize their own health and that of their babies. Healthcare teams can leverage digital strategies to address maternal and infant needs in this postpartum period, both in the neonatal intensive care unit and beyond. We therefore developed PretermConnect, a mobile app designed to educate, engage, and empower women at risk for PTB. This article describes the participant-centered design approach of PretermConnect, with preliminary findings from focus groups and co-design sessions in different community settings and suggested future directions for mobile technologies in population health. Apps such as PretermConnect can mitigate social disadvantage by serving as remote monitoring tools, providing social support, preventing recurrent PTB and lowering infant mortality rates.

  View details for DOI 10.1016/j.semperi.2021.151413

  View details for PubMedID 33888330

• Postpartum depression in mothers with pregnancies complicated by fetal cardiac anomaly. Journal of perinatology : official journal of the California Perinatal Association Waldrop, A. R., Sherwin, E. B., Anderson, J. N., Boissiere, J. C., Hintz, S. R., Maskatia, S. A., Girsen, A. I., Blumenfeld, Y. J. 2021

  Abstract

  OBJECTIVE: To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly.STUDY DESIGN: We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit.RESULTS: Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p=0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p=0.02) were significantly higher among women with a positive PPD screen.CONCLUSION: In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

  View details for DOI 10.1038/s41372-021-01017-6

  View details for PubMedID 33712713

• Data-Driven Modeling of Pregnancy-Related Complications. Trends in molecular medicine Espinosa, C. n., Becker, M. n., Marić, I. n., Wong, R. J., Shaw, G. M., Gaudilliere, B. n., Aghaeepour, N. n., Stevenson, D. K. 2021

  Abstract

  A healthy pregnancy depends on complex interrelated biological adaptations involving placentation, maternal immune responses, and hormonal homeostasis. Recent advances in high-throughput technologies have provided access to multiomics biological data that, combined with clinical and social data, can provide a deeper understanding of normal and abnormal pregnancies. Integration of these heterogeneous datasets using state-of-the-art machine-learning methods can enable the prediction of short- and long-term health trajectories for a mother and offspring and the development of treatments to prevent or minimize complications. We review advanced machine-learning methods that could: provide deeper biological insights into a pregnancy not yet unveiled by current methodologies; clarify the etiologies and heterogeneity of pathologies that affect a pregnancy; and suggest the best approaches to address disparities in outcomes affecting vulnerable populations.

  View details for DOI 10.1016/j.molmed.2021.01.007

  View details for PubMedID 33573911

• Individualized growth assessment in pregnancies complicated by fetal gastroschisis. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Sherwin, E., Deter, R., Joudi, N., Trepman, P., Lee, W., El-Sayed, Y. Y., Girsen, A. I., Datoc, I., Hintz, S. R., Blumenfeld, Y. J. 2021: 1-11

  Abstract

  Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases.Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements.Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (n = 19), there was 84% agreement between IGA and conventional methods in determining pathological growth in both the 3rd trimester and at birth. In the growth restriction and recovery group (n = 7), there was 71% agreement both in the 3rd trimester and at birth between IGA and conventional methods. In the progressive growth restriction group (n = 5), there was 100% agreement in the 3rd trimester and 60% agreement at birth between IGA and conventional methods.We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

  View details for DOI 10.1080/14767058.2021.1926976

  View details for PubMedID 34098833

• A Peripheral Immune Signature of Labor Induction. Frontiers in immunology Ando, K., Hédou, J. J., Feyaerts, D., Han, X., Ganio, E. A., Tsai, E. S., Peterson, L. S., Verdonk, F., Tsai, A. S., Marić, I., Wong, R. J., Angst, M. S., Aghaeepour, N., Stevenson, D. K., Blumenfeld, Y. J., Sultan, P., Carvalho, B., Stelzer, I. A., Gaudillière, B. 2021; 12: 725989

  Abstract

  Approximately 1 in 4 pregnant women in the United States undergo labor induction. The onset and establishment of labor, particularly induced labor, is a complex and dynamic process influenced by multiple endocrine, inflammatory, and mechanical factors as well as obstetric and pharmacological interventions. The duration from labor induction to the onset of active labor remains unpredictable. Moreover, prolonged labor is associated with severe complications for the mother and her offspring, most importantly chorioamnionitis, uterine atony, and postpartum hemorrhage. While maternal immune system adaptations that are critical for the maintenance of a healthy pregnancy have been previously characterized, the role of the immune system during the establishment of labor is poorly understood. Understanding maternal immune adaptations during labor initiation can have important ramifications for predicting successful labor induction and labor complications in both induced and spontaneous types of labor. The aim of this study was to characterize labor-associated maternal immune system dynamics from labor induction to the start of active labor. Serial blood samples from fifteen participants were collected immediately prior to labor induction (baseline) and during the latent phase until the start of active labor. Using high-dimensional mass cytometry, a total of 1,059 single-cell immune features were extracted from each sample. A multivariate machine-learning method was employed to characterize the dynamic changes of the maternal immune system after labor induction until the establishment of active labor. A cross-validated linear sparse regression model (least absolute shrinkage and selection operator, LASSO) predicted the minutes since induction of labor with high accuracy (R = 0.86, p = 6.7e-15, RMSE = 277 min). Immune features most informative for the model included STAT5 signaling in central memory CD8+ T cells and pro-inflammatory STAT3 signaling responses across multiple adaptive and innate immune cell subsets. Our study reports a peripheral immune signature of labor induction, and provides important insights into biological mechanisms that may ultimately predict labor induction success as well as complications, thereby facilitating clinical decision-making to improve maternal and fetal well-being.

  View details for DOI 10.3389/fimmu.2021.725989

  View details for PubMedID 34566984

  View details for PubMedCentralID PMC8458888

• Association between Neuraxial Labor Analgesia and Neonatal Morbidity after Operative Vaginal Delivery. Anesthesiology Butwick, A. J., Wong, C. A., Lee, H. C., Blumenfeld, Y. J., Guo, N. n. 2021; 134 (1): 52–60

  Abstract

  Up to 84% of women who undergo operative vaginal delivery receive neuraxial analgesia. However, little is known about the association between neuraxial analgesia and neonatal morbidity in women who undergo operative vaginal delivery. The authors hypothesized that neuraxial analgesia is associated with a reduced risk of neonatal morbidity among women undergoing operative vaginal delivery.Using United States birth certificate data, the study identified women with singleton pregnancies who underwent operative vaginal (forceps- or vacuum-assisted delivery) in 2017. The authors examined the relationships between neuraxial labor analgesia and neonatal morbidity, the latter defined by any of the following: 5-min Apgar score less than 7, immediate assisted ventilation, assisted ventilation greater than 6 h, neonatal intensive care unit admission, neonatal transfer to a different facility within 24 h of delivery, and neonatal seizure or serious neurologic dysfunction. The authors accounted for sociodemographic and obstetric factors as potential confounders in their analysis.The study cohort comprised 106,845 women who underwent operative vaginal delivery, of whom 92,518 (86.6%) received neuraxial analgesia. The proportion of neonates with morbidity was higher in the neuraxial analgesia group than the nonneuraxial group (10,409 of 92,518 [11.3%] vs. 1,271 of 14,327 [8.9%], respectively; P < 0.001). The unadjusted relative risk was 1.27 (95% CI, 1.20 to 1.34; P < 0.001); after accounting for confounders using a multivariable model, the adjusted relative risk was 1.19 (95% CI, 1.12 to 1.26; P < 0.001). In a post hoc analysis, after excluding neonatal intensive care unit admission and neonatal transfer from the composite outcome, the effect of neuraxial analgesia on neonatal morbidity was not statistically significant (adjusted relative risk, 1.07; 95% CI, 1.00 to 1.16; P = 0.054).In this population-based cross-sectional study, a neonatal benefit of neuraxial analgesia for operative vaginal delivery was not observed. Confounding by indication may explain the observed association between neuraxial analgesia and neonatal morbidity, however this dataset was not designed to evaluate such considerations.

  View details for DOI 10.1097/ALN.0000000000003589

  View details for PubMedID 33045040

• Proteomic signatures predict preeclampsia in individual cohorts but not across cohorts - implications for clinical biomarker studies. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Ghaemi, M. S., Tarca, A. L., Romero, R. n., Stanley, N. n., Fallahzadeh, R. n., Tanada, A. n., Culos, A. n., Ando, K. n., Han, X. n., Blumenfeld, Y. J., Druzin, M. L., El-Sayed, Y. Y., Gibbs, R. S., Winn, V. D., Contrepois, K. n., Ling, X. B., Wong, R. J., Shaw, G. M., Stevenson, D. K., Gaudilliere, B. n., Aghaeepour, N. n., Angst, M. S. 2021: 1–8

  Abstract

  Early identification of pregnant women at risk for preeclampsia (PE) is important, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analyses of plasma proteins feature prominently among molecular approaches used for risk prediction. However, derivation of protein signatures of sufficient predictive power has been challenging. The recent availability of platforms simultaneously assessing over 1000 plasma proteins offers broad examinations of the plasma proteome, which may enable the extraction of proteomic signatures with improved prognostic performance in prenatal care.The primary aim of this study was to examine the generalizability of proteomic signatures predictive of PE in two cohorts of pregnant women whose plasma proteome was interrogated with the same highly multiplexed platform. Establishing generalizability, or lack thereof, is critical to devise strategies facilitating the development of clinically useful predictive tests. A second aim was to examine the generalizability of protein signatures predictive of gestational age (GA) in uncomplicated pregnancies in the same cohorts to contrast physiological and pathological pregnancy outcomes.Serial blood samples were collected during the first, second, and third trimesters in 18 women who developed PE and 18 women with uncomplicated pregnancies (Stanford cohort). The second cohort (Detroit), used for comparative analysis, consisted of 76 women with PE and 90 women with uncomplicated pregnancies. Multivariate analyses were applied to infer predictive and cohort-specific proteomic models, which were then tested in the alternate cohort. Gene ontology (GO) analysis was performed to identify biological processes that were over-represented among top-ranked proteins associated with PE.The model derived in the Stanford cohort was highly significant (p = 3.9E-15) and predictive (AUC = 0.96), but failed validation in the Detroit cohort (p = 9.7E-01, AUC = 0.50). Similarly, the model derived in the Detroit cohort was highly significant (p = 1.0E-21, AUC = 0.73), but failed validation in the Stanford cohort (p = 7.3E-02, AUC = 0.60). By contrast, proteomic models predicting GA were readily validated across the Stanford (p = 1.1E-454, R = 0.92) and Detroit cohorts (p = 1.1.E-92, R = 0.92) indicating that the proteomic assay performed well enough to infer a generalizable model across studied cohorts, which makes it less likely that technical aspects of the assay, including batch effects, accounted for observed differences.Results point to a broader issue relevant for proteomic and other omic discovery studies in patient cohorts suffering from a clinical syndrome, such as PE, driven by heterogeneous pathophysiologies. While novel technologies including highly multiplex proteomic arrays and adapted computational algorithms allow for novel discoveries for a particular study cohort, they may not readily generalize across cohorts. A likely reason is that the prevalence of pathophysiologic processes leading up to the "same" clinical syndrome can be distributed differently in different and smaller-sized cohorts. Signatures derived in individual cohorts may simply capture different facets of the spectrum of pathophysiologic processes driving a syndrome. Our findings have important implications for the design of omic studies of a syndrome like PE. They highlight the need for performing such studies in diverse and well-phenotyped patient populations that are large enough to characterize subsets of patients with shared pathophysiologies to then derive subset-specific signatures of sufficient predictive power.

  View details for DOI 10.1080/14767058.2021.1888915

  View details for PubMedID 33653202

• A Fetal Risk Stratification Pathway for Neonatal Aortic Coarctation Reduces Medical Exposure. The Journal of pediatrics Maskatia, S. A., Kwiatkowski, D., Bhombal, S., Davis, A. S., McElhinney, D. B., Tacy, T. A., Algaze, C., Blumenfeld, Y., Quirin, A., Punn, R. 2021

  Abstract

  To test the hypothesis that a fetal stratification pathway will effectively discriminate between infants at different levels of risk for surgical coarctation and reduce unnecessary medicalization.We performed a pre-post non-randomized study in which we prospectively assigned fetuses with prenatal concern for coarctation to one of three risk categories and implemented a clinical pathway for postnatal management. Postnatal clinical outcomes were compared with a historical control group that were not triaged based on the pathway.The study cohort included 109 fetuses, 57 treated along the fetal coarctation pathway, and 52 historical controls. Among mild-risk fetuses, 3% underwent surgical coarctation repair (0% of those without additional heart defects), compared with 27% of moderate-risk and 63% of high-risk. Combined fetal aortic, mitral and isthmus z-score best discriminated which patients underwent surgery, AUC=0.78(0.66,0.91). Patients triaged according to the fetal coarctation pathway had reduced delivery location changes (76% vs 55%, p=0.025), and umbilical venous catheter placement (74% vs 51%, p=0.046) compared with historical controls. Trends towards shorter intensive care unit stay, hospital stay and time to enteral feeding did not reach statistical significance.A stratified risk-assignment pathway effectively identifies a group of fetuses with low rate of surgical coarctation, and reduces unnecessary medicalization in infants who do not undergo aortic surgery. Incorporation of novel measurements or imaging techniques may improve specificity of high-risk criteria.

  View details for DOI 10.1016/j.jpeds.2021.06.047

  View details for PubMedID 34181988

• RASopathies: A significant cause of polyhydramnios? Prenatal diagnosis Mangels, R., Blumenfeld, Y. J., Homeyer, M., Mrazek-Pugh, B., Hintz, S. R., Hudgins, L. 2020

  Abstract

  OBJECTIVE: The aim of the study is to determine the prevalence of RASopathies in a polyhydramnios cohort selected by postnatal medical genetics evaluation.METHODS: In this retrospective study, we reviewed 622 pregnancies with polyhydramnios seen at Lucile Packard Children's Hospital between 2008-2017. The findings from 131 cases evaluated by Medical Genetics were included in our final analysis. Genetic testing information was extracted to determine the rate of chromosomal or single gene conditions focusing on the RASopathies. Additional variables collected were: maternal characteristics, ultrasound findings, and the severity and timing of diagnosis of polyhydramnios.RESULTS: Postnatal genetic testing or clinical examination identified a genetic disorder in 63 (48.1%) cases, more than half (n=33) of which had a single gene condition. Postnatal testing revealed an underlying RASopathy in 15 (11.5%) cases. An underlying RASopathy was significantly associated with the severity and timing of polyhydramnios (p<0.05).CONCLUSION: Focusing on a selected cohort postnatally evaluated by Medical Genetics, our study identified a chromosomal or genetic disorder in almost half of pregnancies complicated by polyhydramnios. Specifically, an underlying RASopathy was found in 11.5% of cases with 13/15 of these cases having additional ultrasound findings. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/pd.5862

  View details for PubMedID 33150592

• Response to "Contemporary Outcomes of Patients with Isolated Bilateral Renal Agenesis with and without Fetal Intervention" by RAFT Investigators. Fetal diagnosis and therapy Jelin, E. B., Atkinson, M., Keiser, A., Blumenfeld, Y. J., Baschat, A. A. 2020: 1–2

  View details for DOI 10.1159/000509749

  View details for PubMedID 32772023

• New approaches to congenital diaphragmatic hernia. Current opinion in obstetrics & gynecology Blumenfeld, Y. J., Belfort, M. A. 2020

  Abstract

  PURPOSE OF REVIEW: Congenital diaphragmatic hernia (CDH) is a structural birth defect that results in significant neonatal morbidity and mortality. CDH occurs in 2-4 per 10 000 pregnancies, and despite meaningful advances in neonatal intensive care, the mortality rate in infants with isolated CDH is still 25-30%. In this review, we will present data on the molecular underpinnings of pathological lung development in CDH, prenatal diagnosis, and prognostication in CDH cases, existing fetal therapy modalities, and future directions.RECENT FINDINGS: Developments in the prenatal assessment and in-utero therapy of pregnancies complicated by congenital diaphragmatic hernia are rapidly evolving. Although ultrasound has been the mainstay of prenatal diagnosis, fetal MRI appears to be an increasingly important modality for severity classification. While fetal endoscopic tracheal occlusion (FETO) may have a role in the prenatal management of severe CDH cases, it is possible that future therapeutic paradigms will incorporate adjunct medical interventions with either stem cells or sildenafil in order to address the vascular effects of CDH on the developing lung.SUMMARY: Both animal and human data have shown that the pathophysiological underpinnings of CDH are multifactorial, and it appears that future prenatal assessments and therapies will likely be as well.

  View details for DOI 10.1097/GCO.0000000000000615

  View details for PubMedID 32073442

• Racial and Ethnic Disparities in Hospital-Based Care Associated with Postpartum Depression. Journal of racial and ethnic health disparities Chan, A. L., Guo, N. n., Popat, R. n., Robakis, T. n., Blumenfeld, Y. Y., Main, E. n., Scott, K. A., Butwick, A. J. 2020

  Abstract

  To estimate racial and ethnic differences in rates of hospital-based care associated with postpartum depression.This is a retrospective cohort study using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes within data from the Office of Statewide Planning and Development in California. We included primiparous women who underwent delivery hospitalization from 2008 to 2012. The primary outcome was the first postpartum hospital encounter with a ICD-9-CM code for depression over a 9-month period after delivery. We examined the cumulative incidence of hospital-based care for postpartum depression by race/ethnicity. Logistic regression was used to estimate relative risk.The study cohort consisted of 984,167 primiparous women: 314,037 (32%) were non-Hispanic White; 59,754 (6%) were non-Hispanic Black; 150,855 (15%) were non-Hispanic Asian; 448,770 (46%) were Hispanic; and 10,399 (1%) were other races. The cumulative incidence of hospital-based care for postpartum depression was highest for Black women (39; 95% CI = 34-44 per 10,000 deliveries) and lowest for Asian women (7; 95% CI = 5-8 per 10,000 deliveries). Compared with White women, hospital-based care for postpartum depression was more likely to be provided to Black women (OR = 2.3; 95% CI = 1.9-2.7), whereas care was less likely for Asians (OR = 0.4; 95% CI = 0.3-0.5) and Hispanics (OR = 0.8; 95% CI = 0.7-1.0). Similar findings were observed after excluding women with antepartum depression, adjusting for sociodemographic and clinical variables, and stratifying according to care settings.Compared with White women, hospital-based care for postpartum depression more frequently impacts Black women. Identifying and improving inequities in access to and utilization of mental health care for postpartum women should be a maternal health priority.

  View details for DOI 10.1007/s40615-020-00774-y

  View details for PubMedID 32474833

• In fetuses with congenital lung masses, decreased ventricular and atrioventricular valve dimensions are associated with lesion size and clinical outcome. Prenatal diagnosis Mardy, C., Blumenfeld, Y. J., Arunamata, A. A., Girsen, A. I., Sylvester, K. G., Halabi, S., Rubesova, E., Hintz, S. R., Tacy, T. A., Maskatia, S. A. 2019

  Abstract

  INTRODUCTION: The clinical importance of mass effect from congenital lung masses on the fetal heart is unknown. We aimed to report cardiac measurements in fetuses with congenital lung masses, and correlate lung mass severity/size with cardiac dimensions and clinical outcomes.METHODS: Cases were identified from our institutional database between 2009 and 2016. We recorded: atrioventricular valve (AVVz) annulus dimensions and ventricular widths (VWz) converted into z-scores, ratio of aortic to total cardiac output (AoCO), lesion side, and congenital pulmonary airway malformation volume ratio (CVR). Respiratory intervention (RI) was defined as: intubation, ECMO use or surgical intervention prior to discharge.RESULTS: Fifty-two fetuses comprised the study cohort. Mean AVVz and VWz were below expected for gestational age. CVR correlated with ipsilateral AVVz (RS =-0.59, p<0.001) and ipsilateral VWz (-0.59, p<0.001). Lower AVVz, AoCO, and higher CVR were associated with RI. No patient had significant structural heart disease identified postnatally.CONCLUSION: In fetuses with left-sided lung masses, ipsilateral cardiac structures tend to be smaller, but in our cohort there were no patients with structural heart disease. However, smaller left-sided structures may contribute to the need for RI that affects a portion of these fetuses.

  View details for DOI 10.1002/pd.5612

  View details for PubMedID 31742724

• Single Cell Transcriptomes Derived from Human Cervical and Uterine Tissue during Pregnancy ADVANCED BIOSYSTEMS Koh, W., Wu, A., Penland, L., Treutlein, B., Neff, N. F., Mantalas, G. L., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M., Quake, S. R. 2019; 3 (11)

  View details for DOI 10.1002/adbi.201800336

  View details for Web of Science ID 000498192300005

• Single Cell Transcriptomes Derived from Human Cervical and Uterine Tissue during Pregnancy. Advanced biosystems Koh, W., Wu, A., Penland, L., Treutlein, B., Neff, N. F., Mantalas, G. L., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M., Quake, S. R. 2019; 3 (11): e1800336

  Abstract

  This work presents the workflow for generating single cell transcriptomes derived from primary human uterine and cervical tissue obtained during planned cesarean hysterectomies. In total, a catalogue of 310 single cell transcriptomes are obtained, cell types present in these biopsies are inferred, and specific genes defining each of the cellular types present in the tissue are identified. Further validation of the inferred cell identity is also demonstrated via meta-analysis of independent repositories in literature generated by bulk sequenced data of fluorescence-activated cell sorting sorted cells.

  View details for DOI 10.1002/adbi.201800336

  View details for PubMedID 32648692

• Development and validation of a machine learning model for prediction of shoulder dystocia. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology Tsur, A., Batsry, L., Toussia-Cohen, S., Rosenstein, M. G., Barak, O., Brezinov, Y., Yoeli-Ullman, R., Sivan, E., Sirota, M., Druzin, M. L., Stevenson, D. K., Blumenfeld, Y. J., Aran, D. 2019

  Abstract

  OBJECTIVE: We sought to develop a machine learning (ML) model for prediction of shoulder dystocia (ShD) and to externally validate the model accuracy and potential clinical efficacy in optimizing the use of cesarean delivery (CD) in the context of suspected macrosomia.STUDY DESIGN: We used electronic health records (EHR) from the Sheba Medical Center in Israel to develop the model (derivation cohort) and EHR from the University of California San Francisco Medical Center to validate the model accuracy and clinical efficacy (validation cohort). Subsequent to inclusion and exclusion criteria, the derivation cohort consisted of 686 deliveries [131 complicated by ShD], and the validation cohort of 2,584 deliveries [31 complicated by ShD]. For each of these deliveries, we collected maternal and neonatal delivery outcomes coupled with maternal demographics, obstetric clinical data and sonographic biometric measurements of the fetus. Biometric measurements and their derived estimated fetal weight were adjusted (aEFW) to the date of the delivery. A ML pipeline was utilized to develop the model.RESULTS: In the derivation cohort, the ML model provided significantly better prediction than the current paradigm: using nested cross validation the area under the receiver operator characteristics curve (AUC) of the model was 0.793 ±0.041, outperforming aEFW and diabetes (0.745 ±0.044, p-value =1e-16). The following risk modifiers had a positive beta >0.02 increasing the risk of ShD: aEFW (0.164), pregestational diabetes (0.047), prior ShD (0.04), female fetal sex (0.04) and adjusted abdominal circumference (0.03). The following risk modifiers had a negative beta < -0.02 protective of ShD: adjusted biparietal diameter (-0.08) and maternal height (-0.03). In the validation cohort the model outperformed aEFW and diabetes (AUC=0.866 vs. 0.784, p-value =0.00007). Additionally, in the validation cohort, among the subgroup of 273 women carrying a fetus with aEFW above 4,000 g, the aEFW had no predictive power (AUC=0.548), and the model performed significantly better (0.775, p-value =0.0002). A risk-score threshold of 0.5 stratified 42.9% of deliveries to the high-risk group that included 90.9% of ShD cases and all cases accompanied by maternal or newborn complications. A more specific threshold of 0.7 stratified only 27.5% of the deliveries to the high-risk groups that included 72.7% of ShD cases, and all those accompanied by newborn complications.CONCLUSION: We developed a ML model for prediction of ShD. We externally validated the model performance in a different cohort. The model predicted ShD better than EFW+ maternal diabetes and was able to stratify the risk of ShD and neonatal injury in the context of suspected macrosomia. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/uog.21878

  View details for PubMedID 31587401

• Effects of gestational age at delivery and type of labor on neonatal outcomes among infants with gastroschisis. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Girsen, A. I., Davis, A. S., Hintz, S. R., Fluharty, E., Sherwin, K., Trepman, P., Desai, A., Mansour, T., Sylvester, K. G., Oshiro, B., Blumenfeld, Y. J. 2019: 1–191

  Abstract

  Objective: To investigate the effect of preterm gestational age on neonatal outcomes of gastroschisis and to compare the neonatal outcomes after spontaneous labor versus iatrogenic delivery both in the preterm and early term gestational periods. Study design: A retrospective study of prenatally-diagnosed gastroschisis cases born at Loma Linda University Medical Center and Lucile Packard Children's Hospital (CA, USA) between January 2009 and October 2016. A total of 194 prenatally diagnosed gastroschisis cases were identified and included in the analysis. We compared infants delivered < 37 0/7 to those ≥ 37 0/7 weeks' gestation. Adverse neonatal outcome was defined as any of: sepsis, short bowel syndrome, prolonged ventilation or death. Prolonged length of stay (LOS) was defined as ≥ 75th percentile value. Outcomes following spontaneous versus iatrogenic delivery were compared. Analyses were performed using chi-squared test or Fisher's exact test for categorical variables, and Student's t-test or Wilcoxon rank-sum test for continuous variables. Results: One hundred six neonates were born < 37weeks and 88 at ≥ 37weeks. Adverse outcome was statistically similar among those born < 37weeks compared to ≥ 37weeks (48 versus 34%, p = 0.07). Prolonged LOS was more frequent among neonates delivered < 37weeks (p = 0.03). Among neonates born < 37weeks, bowel atresia was more frequent in those with spontaneous versus iatrogenic delivery (p = 0.04). There was no significant difference in the adverse neonatal composite outcome between those with spontaneous preterm labor versus planned iatrogenic delivery at < 37weeks (n = 30 (58%) versus n = 21 (39%), p = 0.08). Conclusion: Neonates with gastroschisis delivered < 37weeks had prolonged LOS whereas the rate of adverse neonatal outcomes was similar between those delivered preterm versus term. Neonates born after spontaneous preterm labor had a higher rate of bowel atresia compared to those born after planned iatrogenic preterm delivery.

  View details for DOI 10.1080/14767058.2019.1656191

  View details for PubMedID 31409162

• Prenatally diagnosed omphalocele: characteristics associated with adverse neonatal outcomes. Journal of perinatology : official journal of the California Perinatal Association Chock, V. Y., Davis, A. S., Cho, S., Bax, C., Fluharty, E., Weigel, N., Homeyer, M., Hudgins, L., Jones, R., Rubesova, E., Sylvester, K. G., Blumenfeld, Y. J., Hintz, S. R. 2019

  Abstract

  OBJECTIVE: To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases.STUDY DESIGN: Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed.RESULTS: Out of 63 fetal cases, 33 were live-born, >50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach toomphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3-422), p=0.006).CONCLUSION: Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

  View details for DOI 10.1038/s41372-019-0410-1

  View details for PubMedID 31227786

• Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia. Frontiers in immunology Han, X., Ghaemi, M. S., Ando, K., Peterson, L. S., Ganio, E. A., Tsai, A. S., Gaudilliere, D. K., Stelzer, I. A., Einhaus, J., Bertrand, B., Stanley, N., Culos, A., Tanada, A., Hedou, J., Tsai, E. S., Fallahzadeh, R., Wong, R. J., Judy, A. E., Winn, V. D., Druzin, M. L., Blumenfeld, Y. J., Hlatky, M. A., Quaintance, C. C., Gibbs, R. S., Carvalho, B., Shaw, G. M., Stevenson, D. K., Angst, M. S., Aghaeepour, N., Gaudilliere, B. 2019; 10: 1305

  Abstract

  Preeclampsia is one of the most severe pregnancy complications and a leading cause of maternal death. However, early diagnosis of preeclampsia remains a clinical challenge. Alterations in the normal immune adaptations necessary for the maintenance of a healthy pregnancy are central features of preeclampsia. However, prior analyses primarily focused on the static assessment of select immune cell subsets have provided limited information for the prediction of preeclampsia. Here, we used a high-dimensional mass cytometry immunoassay to characterize the dynamic changes of over 370 immune cell features (including cell distribution and functional responses) in maternal blood during healthy and preeclamptic pregnancies. We found a set of eight cell-specific immune features that accurately identified patients well before the clinical diagnosis of preeclampsia (median area under the curve (AUC) 0.91, interquartile range [0.82-0.92]). Several features recapitulated previously known immune dysfunctions in preeclampsia, such as elevated pro-inflammatory innate immune responses early in pregnancy and impaired regulatory T (Treg) cell signaling. The analysis revealed additional novel immune responses that were strongly associated with, and preceded the onset of preeclampsia, notably abnormal STAT5ab signaling dynamics in CD4+T cell subsets (AUC 0.92, p = 8.0E-5). These results provide a global readout of the dynamics of the maternal immune system early in pregnancy and lay the groundwork for identifying clinically-relevant immune dysfunctions for the prediction and prevention of preeclampsia.

  View details for DOI 10.3389/fimmu.2019.01305

  View details for PubMedID 31263463

  View details for PubMedCentralID PMC6584811

• Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia FRONTIERS IN IMMUNOLOGY Han, X., Ghaemi, M. S., Ando, K., Peterson, L. S., Ganio, E. A., Tsai, A. S., Gaudilliere, D. K., Stelzer, I. A., Einhaus, J., Bertrand, B., Stanley, N., Culos, A., Tanada, A., Hedou, J., Tsai, E. S., Fallahzadeh, R., Wong, R. J., Judy, A. E., Winn, V. D., Druzins, M. L., Blumenfeld, Y. J., Hlatky, M. A., Quaintance, C. C., Gibbs, R. S., Carvalho, B., Shaw, G. M., Stevenson, D. K., Angst, M. S., Aghaeepour, N., Gaudilliere, B. 2019; 10

  View details for DOI 10.3389/fimmu.2019.01305

  View details for Web of Science ID 000470999000001

• Update on the Prenatal Diagnosis and Outcomes of Fetal Bilateral Renal Agenesis. Obstetrical & gynecological survey Huber, C., Shazly, S. A., Blumenfeld, Y. J., Jelin, E., Ruano, R. 2019; 74 (5): 298–302

  Abstract

  Importance: Bilateral renal agenesis is a rare congenital anomaly associated with poor prognosis.Objective: The aims of this article are to review and summarize evidence on prenatal diagnosis and outcomes of bilateral renal agenesis.Evidence Acquisition: A search was undertaken using PubMed and ClinicalTrials.gov databases from January 1, 1998, to September 1, 2018. Search terms include "prenatal diagnosis" OR "outcomes" AND "bilateral renal agenesis." Search was limited to English language.Results: Fetal ultrasonography is the primary imaging modality for prenatal diagnosis of fetal urogenital tract abnormalities. However, ultrasonography is limited by several factors; it is operator dependent and associated with small field of view, has limited soft-tissue acoustic contrast, and is also influenced by patient habitus and fetal position. Color Doppler ultrasonography can be used as an adjunct to exclude bilateral renal agenesis by visualizing renal arteries. In the literature, prenatal magnetic resonance imaging has been reported to be equal to or superior to prenatal ultrasonography. Bilateral renal agenesis with oligohydramnios/anhydramnios is associated with a poor prognosis; perinatal death occurs secondary to pulmonary hypoplasia in the majority of cases.Conclusions: Ultrasonography in combination with color Doppler ultrasonography permits the fetal urinary tract to be assessed in the first and early second trimester of gestation. The magnetic resonance imaging can be used as a complementary adjunctive modality in equivocal or inconclusive ultrasonographic findings.

  View details for DOI 10.1097/OGX.0000000000000670

  View details for PubMedID 31098643

• Stillbirth and Live Birth at Periviable Gestational Age: A Comparison of Prevalence and Risk Factors AMERICAN JOURNAL OF PERINATOLOGY Carmichael, S. L., Blumenfeld, Y. J., Mayo, J. A., Profit, J., Shaw, G. M., Hintz, S. R., Stevenson, D. K. 2019; 36 (5): 537–44

  View details for DOI 10.1055/s-0038-1670633

  View details for Web of Science ID 000463944600016

• Benefits of and variability within a nationwide CHD screening program. BJOG : an international journal of obstetrics and gynaecology Blumenfeld, Y. 2019

  Abstract

  Approximately 0.8% of all pregnancies are complicated by congenital heart disease (CDH) (Zhao QM etal. J Pediatr 2019 Jan;204:53-58). Prenatal diagnosis of CHD has been shown to reduce neonatal morbidity when compared with postnatal diagnosis, and significant efforts have been made by experts and leading professional societies to educate sonographers in optimal cardiac imaging techniques (Friedberg MK etal. J Pediatr 2009 Jul;155(1):26-31, ISUOG Practice Guideline, Ultrasound Obstet Gynecol 2013;41:348-359), Despite such efforts many CHD cases are still undetected during prenatal ultrasound exams. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/1471-0528.15639

  View details for PubMedID 30697900

• Vasa previa and extreme prematurity: a population-based study. Journal of perinatology : official journal of the California Perinatal Association Yeaton-Massey, A., Girsen, A. I., Mayo, J. A., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M. 2019

  Abstract

  OBJECTIVE: To determine population-based risks of preterm birth associated with vasa previa.STUDY DESIGN: Included were 945,950 singleton, live birth cesarean deliveries with and without vasa previa (gestational ages 24-41 weeks) in California between 2007 and 2012. Odds ratios (ORs) of preterm birth were estimated using logistic regression.RESULTS: In total, 586 were complicated by vasa previa (0.06%). In total, 369 (63%) of those with vasa previa were delivered <37 weeks, compared with 91,662 (10%) of those without. Odds of extreme and very preterm birth were substantially higher for pregnancies with vasa previaeven after controlling for comorbidities known to contribute to prematurity, with ORs of 4.6 (95% confidence interval, CI: 1.7-12.5) and 16.0 (95% CI: 10.3-24.8), respectively.CONCLUSION: Based on these population-based data, most patients with vasa previa are delivered between 32 and 36 weeks gestation; however, a clinically significant portion occur before 32 weeks. These data are helpful in counseling patients with vasa previa regarding prematurity risk.

  View details for PubMedID 30692614

• Obstetric and neonatal outcomes in pregnancies complicated by fetal lung masses: does final histology matter? The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Anderson, J. N., Girsen, A. I., Hintz, S. R., El-Sayed, Y. Y., Davis, A. S., Barth, R. A., Halabi, S. n., Hazard, F. K., Sylvester, K. G., Bruzoni, M. n., Blumenfeld, Y. J. 2019: 1–7

  Abstract

  Purpose: Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology.Materials and methods: A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher's exact test was used for categorical variables and the Kruskal-Wallis test was used for continuous variables. The level of significance was p<.05.Results: Of 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (p = .12). There were no differences in any of the maternal or obstetric outcomes including gestational age at delivery and mode of delivery between the groups. The primary outcome of neonatal respiratory distress was not statistically different between groups (p = .66). Median neonatal length of stay following delivery ranged from 3 to 4 days, and time to postnatal resection was similar as well, with a median of 126 days for CPAM type 1, 122 days for CPAM type 2, and 132 days for bronchopulmonary sequestration (p = .76).Conclusions: In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.

  View details for DOI 10.1080/14767058.2019.1689559

  View details for PubMedID 31722592

• Data-driven queries between medications and spontaneous preterm birth among 2.5 million pregnancies. Birth defects research Marić, I. n., Winn, V. D., Borisenko, E. n., Weber, K. A., Wong, R. J., Aziz, N. n., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M. 2019

  Abstract

  Our goal was to develop an approach that can systematically identify potential associations between medication prescribed in pregnancy and spontaneous preterm birth (sPTB) by mining large administrative "claims" databases containing hundreds of medications. One such association that we illustrate emerged with antiviral medications used for herpes treatment.IBM MarketScan® databases (2007-2016) were used. A pregnancy cohort was established using International Classification of Diseases (ICD-9/10) codes. Multiple hypothesis testing and the Benjamini-Hochberg procedure that limited false discovery rate at 5% revealed, among 863 medications, five that showed odds ratios (ORs) <1. The statistically strongest was an association between antivirals and sPTB that we illustrate as a real example of our approach, specifically for treatment of genital herpes (GH). Three groups of women were identified based on diagnosis of GH and treatment during the first 36 weeks of pregnancy: (a) GH without treatment; (b) GH treated with antivirals; (c) no GH or treatment.We identified 2,538,255 deliveries. 0.98% women had a diagnosis of GH. Among them, 60.0% received antiviral treatment. Women with treated GH had OR < 1, (OR [95% CI] = 0.91 [0.85, 0.98]). In contrast, women with untreated GH had a small increased risk of sPTB (OR [95% CI] =1.22 [1.14, 1.32]).Data-driven approaches can effectively generate new hypotheses on associations between medications and sPTB. This analysis led us to examine the association with GH treatment. While unknown confounders may impact these findings, our results indicate that women with untreated GH have a modest increased risk of sPTB.

  View details for DOI 10.1002/bdr2.1580

  View details for PubMedID 31433567

• Stillbirth and Live Birth at Periviable Gestational Age: A Comparison of Prevalence and Risk Factors. American journal of perinatology Carmichael, S. L., Blumenfeld, Y. J., Mayo, J. A., Profit, J., Shaw, G. M., Hintz, S. R., Stevenson, D. K. 2018

  Abstract

  OBJECTIVE: We compared the prevalence of and risk factors for stillbirth and live birth at periviable gestational age (20-25 weeks).STUDY DESIGN: This is a cohort study of 2.5 million singleton births in California from 2007 to 2011. We estimated racial-ethnic prevalence ratios and used multivariable logistic regression for risk factor comparisons.RESULTS: In this study, 42% of deliveries at 20 to 25 weeks' gestation were stillbirths, and 22% were live births who died within 24 hours. The prevalence of delivery at periviable gestation was 3.4 per 1,000 deliveries among whites, 10.9 for blacks, 3.5 for Asians, and 4.4 for Hispanics. Nonwhite race-ethnicity, lower education, uninsured status, being U.S. born, older age, obesity, smoking, pre-pregnancy hypertension, nulliparity, interpregnancy interval, and prior preterm birth or stillbirth were all associated with increased risk of both stillbirth and live birth at 20 to 25 weeks' gestation, compared with delivery of a live birth at 37 to 41 weeks.CONCLUSION: Inclusion of stillbirths and live births in studies of deliveries at periviable gestations is important.

  View details for PubMedID 30208499

• Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly. Journal of perinatology : official journal of the California Perinatal Association Katz, J. A., Chock, V. Y., Davis, A. S., Blumenfeld, Y. J., Hahn, J. S., Barnes, P., Barth, R. A., Rubesova, E., Hintz, S. R. 2018

  Abstract

  OBJECTIVE: Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM).STUDY DESIGN: Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children's Hospital Stanford 1/1/2009-6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated.RESULTS: A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related.CONCLUSION: Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.

  View details for PubMedID 30158676

• Erratum to: A Double-Blind, Randomized, Placebo-Controlled Trial of 17 Alpha-hydroxyprogesterone Caproate in the Management of Preterm Premature Rupture of Membranes. American journal of perinatology Langen, E. S., Sit, A., Sherwin, K., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y. 2018

  View details for PubMedID 29925090

• Updates in fetal spina bifida repair CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Blumenfeld, Y. J., Belfort, M. A. 2018; 30 (2): 123–29

  Abstract

  To examine updates in fetal spina bifida surgical repair, as well as promising results emerging from translational medicine.Although the Management of Myelomeningocele Study sponsored by the National Institutes of Health helped establish the neonatal benefits of prenatal spina bifida repair via uterine hysterotomy, also known as 'open' fetal surgery, fetoscopic approaches may yield better maternal and obstetric outcomes.Spina bifida is a severe congenital malformation associated with significant neonatal and childhood morbidity and mortality. Although 'open' fetal spina bifida repair has become the standard prenatal surgical approach due to proven neonatal benefit, this approach is associated with significant maternal and obstetric risks. Recent developments from multidisciplinary clinical and translational research have highlighted the potential for novel fetoscopic surgical approaches to decrease maternal morbidity and reduce obstetric risks. Moreover, novel stem cell therapies coupled with in-utero medical approaches targeting the pathophysiological pathways associated with spina bifida are likely to make additional significant impact.

  View details for PubMedID 29489502

• Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease. Journal of perinatology : official journal of the California Perinatal Association Balasundaram, M., Chock, V. Y., Wu, H. Y., Blumenfeld, Y. J., Hintz, S. R. 2018

  Abstract

  OBJECTIVE: Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher's exact test and Mann-Whitney test.RESULTS: A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p<0.0001).CONCLUSIONS: Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.

  View details for PubMedID 29572458

• Noninvasive Prenatal Diagnosis of Single-Gene Disorders by Use of Droplet Digital PCR CLINICAL CHEMISTRY Camunas-Soler, J., Lee, H., Hudgins, L., Hintz, S. R., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2018; 64 (2): 336–45

  View details for DOI 10.1373/clinchem.2017.278101

  View details for Web of Science ID 000424396200017

• Noninvasive Prenatal Diagnosis of Single-Gene Disorders by Use of Droplet Digital PCR. Clinical chemistry Camunas-Soler, J., Lee, H., Hudgins, L., Hintz, S. R., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2018; 64 (2): 336-345

  Abstract

  Prenatal diagnosis in pregnancies at risk of single-gene disorders is currently performed using invasive methods such as chorionic villus sampling and amniocentesis. This is in contrast with screening for common aneuploidies, for which noninvasive methods with a single maternal blood sample have become standard clinical practice.We developed a protocol for noninvasive prenatal diagnosis of inherited single-gene disorders using droplet digital PCR from circulating cell-free DNA (cfDNA) in maternal plasma. First, the amount of cfDNA and fetal fraction is determined using a panel of TaqMan assays targeting high-variability single-nucleotide polymorphisms. Second, the ratio of healthy and diseased alleles in maternal plasma is quantified using TaqMan assays targeting the mutations carried by the parents. Two validation approaches of the mutation assay are presented.We collected blood samples from 9 pregnancies at risk for different single-gene disorders, including common conditions and rare metabolic disorders. We measured cases at risk of hemophilia, ornithine transcarbamylase deficiency, cystic fibrosis, β-thalassemia, mevalonate kinase deficiency, acetylcholine receptor deficiency, and DFNB1 nonsyndromic hearing loss. We correctly differentiated affected and unaffected pregnancies (2 affected, 7 unaffected), confirmed by neonatal testing. We successfully measured an affected pregnancy as early as week 11 and with a fetal fraction as low as 3.7% (0.3).Our method detects single-nucleotide mutations of autosomal recessive diseases as early as the first trimester of pregnancy. This is of importance for metabolic disorders in which early diagnosis can affect management of the disease and reduce complications and anxiety related to invasive testing.

  View details for DOI 10.1373/clinchem.2017.278101

  View details for PubMedID 29097507

• A Double-Blind, Randomized, Placebo-Controlled Trial of 17 Alpha-hydroxyprogesterone Caproate in the Management of Preterm Premature Rupture of Membranes. American journal of perinatology Langen, E. S., Sit, A., Sherwin, K., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y. 2018

  Abstract

  OBJECTIVE: The objective of this study was to evaluate whether weekly administration of 17 alpha-hydroxyprogesterone caproate (17-OHPC) increases the number of women who achieve 34 weeks of gestation after preterm premature rupture of membranes (PPROM).STUDY DESIGN: We conducted a multicenter double-blind, randomized controlled trial of 17-OHPC versus placebo among women with PPROM. Women with singleton pregnancy, clinically confirmed PPROM, and without evidence of active infection or major fetal malformation between 240/7 and 320/7 weeks of pregnancy were offered enrollment. Women received weekly injections of 17-OHPC versus placebo until 340/7 weeks of gestation or delivery. The remainder of care was per hospital protocol. The primary outcome was achievement of 34 weeks of gestation. Secondary outcomes included length of latency and maternal and fetal outcomes.RESULTS: In this study, 21 women were enrolled. Eleven women received placebo and 10 received 17-OHPC. The study was closed prematurely secondary to poor enrollment. None of the women remained pregnant until 34 weeks of gestation. The median latency periods were 8 and 14.5 days for the placebo and 17-OHPC groups, respectively (p=0.14). There were no differences in maternal or neonatal outcomes.CONCLUSION: We did not identify any benefit from administration of 17-OHPC in pregnancies complicated by PPROM.

  View details for PubMedID 29298456

• Prenatal treatment of ornithine transcarbamylase deficiency. Molecular genetics and metabolism Wilnai, Y. n., Blumenfeld, Y. J., Cusmano, K. n., Hintz, S. R., Alcorn, D. n., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W. n., Cowan, T. M., Cox, K. L., Lyell, D. J., Esquivel, C. O., Homeyer, M. n., Hudgins, L. n., Hurwitz, M. n., Palma, J. P., Schelley, S. n., Akula, V. P., Summar, M. L., Enns, G. M. 2018

  Abstract

  Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor.Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery.Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years.Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

  View details for PubMedID 29396029

• Simultaneously Monitoring Immune Response and Microbial Infections during Pregnancy through Plasma cfRNA Sequencing CLINICAL CHEMISTRY Pan, W., Ngo, T. M., Camunas-Soler, J., Song, C., Kowarsky, M., Blumenfeld, Y. J., Wong, R. J., Shaw, G. M., Stevenson, D. K., Quake, S. R. 2017; 63 (11): 1695–1704

  Abstract

  Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods.We assessed several recently developed RNA-seq methods on cfRNA samples. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women.cfRNA reflects a well-orchestrated immune modulation during pregnancy: an up-regulation of antiinflammatory genes and an increased abundance of antimicrobial genes. We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria Ureaplasma shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection. We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of human parvovirus B19 virus (B19V), which is known to be a potential cause of complications in pregnancy.Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy.

  View details for PubMedID 28904056

• Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kowarsky, M., Camunas-Soler, J., Kertesz, M., De Vlaminck, I., Koh, W., Pan, W., Martin, L., Neff, N. F., Okamoto, J., Wong, R. J., Kharbanda, S., El-Sayed, Y., Blumenfeld, Y., Stevenson, D. K., Shaw, G. M., Wolfe, N. D., Quake, S. R. 2017; 114 (36): 9623–28

  Abstract

  Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.

  View details for PubMedID 28830999

• Response to "Prediction of neonatal respiratory distress in pregnancies complicated by fetal lung masses". Prenatal diagnosis Girsen, A., Blumenfeld, Y. 2017; 37 (6): 632

  View details for DOI 10.1002/pd.5032

  View details for PubMedID 28608602

• Association between small-for-gestational age and neurocognitive impairment at two years of corrected age among infants born at preterm gestational ages: a cohort study. Journal of perinatology Girsen, A. I., Do, S. C., El-Sayed, Y. Y., Hintz, S. R., Blumenfeld, Y. J. 2017

  Abstract

  To investigate the association between small-for-gestational age (SGA) and neurocognitive impairment at 2 years of corrected age among infants born at preterm gestational ages.A secondary analysis of a prospectively conducted NICHD/Maternal-Fetal Medicine Units BEAM trial. Non-anomalous pregnancies delivered before 37 weeks of gestation were included in the analysis. Neurocognitive outcomes at 2 years of corrected age were compared between infants who were SGA (<10% for gestational age) and those appropriately grown (AGA). The primary outcome was a severe or moderate neurocognitive impairment at 2 years of corrected age among survivors, defined as either mental (MDI) or psychomotor (PDI) developmental index score <70 for severe and <85 for moderate impairment.Of 2299 preterm neonates 67 (3%) were SGA. SGA infants were more often twin pregnancies (31% vs 17%, P=0.003) and delivered more often by cesarean section (63% vs 40%, P<0.001) at similar gestational ages (30.0±2.6 vs 29.5±2.8 weeks, P=0.11). At 2 years of corrected age, SGA and AGA survivors had similar rates of neurocognitive impairment (MDI <70: 18% vs 18%, P=1.0; MDI <85: 44% vs 46%, P=0.96; PDI <70: 20% vs 15%, P=0.51; PDI <85: 40% vs 34%, P=0.48).In this cohort, SGA at preterm gestational ages was associated with similar rates of neurocognitive impairment at two years of corrected age among surviving infants.Journal of Perinatology advance online publication, 27 April 2017; doi:10.1038/jp.2017.58.

  View details for DOI 10.1038/jp.2017.58

  View details for PubMedID 28448062

• . journal of maternal-fetal & neonatal medicine Shachar, B. Z., Mayo, J. A., Lyell, D. J., Stevenson, D. K., Shaw, G. M., Blumenfeld, Y. J. 2017: 1-7

  Abstract

  Approximately 10% of US couples are inter-racial/ethnic. Substantial variation in preterm birth (PTB) rates is seen when stratified by race/ethnicity, although most studies focused solely on maternal racial/ethnic demographics. Our aims were to analyze the contribution of paternal in addition to maternal race/ethnicity, and to evaluate risk of spontaneous PTB for previously understudied inter-racial/ethnic couples.California singleton live births from 2007 to 2010 were included. Race/ethnicity was determined based on self-report, obtained from birth certificates and defined as African American (AA), Hispanic, Asian, and White. Logistic regression was used to estimate odds ratios of spontaneous PTB at 20-23, 24-31, 32-36 and <37 weeks of gestation, with White-White couples as reference. Results were stratified by previous PTB, pre-gestational and gestational diabetes and hypertension. To investigate the paternal contribution to the risk for any given maternal race/ethnicity we assessed the rates of PTB among inter-racial/ethnic couples compared to the respective same-race couple. Odds ratios were adjusted for maternal age, parity, BMI, prenatal care, payor status, education and smoking.Among 1,664,939 live births, 13% (n = 216,417) were born to inter-racial/ethnic couples. Compared to White-White couples, risk for spontaneous PTB was increased across all inter-racial/ethnic couples with a non-White mother, except when the father was Asian. Patterns of association were similar after stratification by previous PTB, hypertension and diabetes. Paternal race/ethnicity was also a significant risk factor for PTB.Increased risks for spontaneous PTB were seen in most inter-racial/ethnic couple groupings. In addition to maternal race/ethnicity, paternal race/ethnicity was a significant risk factor in many inter-racial/ethnic couplings. Identifying such different risk profiles based on both maternal and paternal race/ethnicity may offer new lines of research inquiry for the underlying etiologies of PTB.

  View details for DOI 10.1080/14767058.2017.1293029

  View details for PubMedID 28399669

• Postpartum hemorrhage following vaginal delivery: risk factors and maternal outcomes. Journal of perinatology Miller, C. M., Cohn, S., Akdagli, S., Carvalho, B., Blumenfeld, Y. J., Butwick, A. J. 2017; 37 (3): 243-248

  Abstract

  Limited understanding of risk factors exists for postpartum hemorrhage (PPH) post-vaginal delivery. The aim of this study was to identify risk factors for PPH post-vaginal delivery within a contemporary obstetric cohort.Retrospective case-control study. PPH was classified by an estimated blood loss ⩾500 ml. Risk factors for PPH were identified using univariable and multivariable logistic regression. We secondarily investigated maternal outcomes and medical and surgical interventions for PPH management.The study cohort comprised 159 cases and 318 controls. Compared with a second-stage duration <2 h, a second stage⩾3 h was associated with PPH (adjusted odds ratio=2.3; 95% CI=1.2 to 4.6). No other clinical or obstetric variables were identified as independent risk factors for PPH. Among cases, 4% received red blood cells and 1% required intensive care admission.Although PPH-related morbidity may be uncommon after vaginal delivery, PPH should be anticipated for women after a second stage ⩾3 h.

  View details for DOI 10.1038/jp.2016.225

  View details for PubMedID 27977018

  View details for PubMedCentralID PMC5334143

• Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis. Journal of perinatology Blumenfeld, Y. J., Do, S., Girsen, A. I., DAVIS, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Shamshirsaz, A. A., Lee, H. C. 2017

  Abstract

  To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis.Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations.Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity.A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.Journal of Perinatology advance online publication, 26 January 2017; doi:10.1038/jp.2016.275.

  View details for DOI 10.1038/jp.2016.275

  View details for PubMedID 28125100

• Prediction of neonatal respiratory distress in pregnancies complicated by fetal lung masses. Prenatal diagnosis Girsen, A. I., Hintz, S. R., Sammour, R., Naqvi, A., El-Sayed, Y. Y., Sherwin, K., Davis, A. S., Chock, V. Y., Barth, R. A., Rubesova, E., Sylvester, K. G., Chitkara, R., Blumenfeld, Y. J. 2017

  Abstract

  The objective of this article is to evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress.Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as intubation and mechanical ventilation at birth, surgery before discharge, or extracorporeal membrane oxygenation (ECMO). The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation volume ratio by ultrasound (US) and magnetic resonance imaging (MRI) was analyzed.Forty-seven fetal lung mass cases were included; of those, eight (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 ± 5.6 vs 22.3 ± 3 weeks, p = 0.09); however, those with respiratory distress had higher congenital volume ratio at that time (1.0 vs 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume >24.0 cm(3) by MRI (100% sensitivity, 91% specificity, 60% positive predictive value, and 100% negative predictive value) and maximal volume >34.0 cm(3) by US (100% sensitivity, 85% specificity, 54% positive predictive value, and 100% negative predictive value).Ultrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.5002

  View details for PubMedID 28061000

• Opportunities for maternal transport for delivery of very low birth weight infants JOURNAL OF PERINATOLOGY Robles, D., Blumenfeld, Y. J., Lee, H. C., Gould, J. B., Main, E., Profit, J., Melsop, K., Druzin, M. 2017; 37 (1): 32-35

  Abstract

  To assess frequency of very low birth weight (VLBW) births at non-level III hospitals.Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models.Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively.Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.Journal of Perinatology advance online publication, 29 September 2016; doi:10.1038/jp.2016.174.

  View details for DOI 10.1038/jp.2016.174

  View details for Web of Science ID 000391517000007

• A Proteomic Clock of Human Pregnancy. American journal of obstetrics and gynecology Aghaeepour, N. n., Lehallier, B. n., Baca, Q. n., Ganio, E. A., Wong, R. J., Ghaemi, M. S., Culos, A. n., El-Sayed, Y. Y., Blumenfeld, Y. J., Druzin, M. L., Winn, V. D., Gibbs, R. S., Tibshirani, R. n., Shaw, G. M., Stevenson, D. K., Gaudilliere, B. n., Angst, M. S. 2017

  Abstract

  Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging. An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome.The recent availability of a highly-multiplexed platform affording the simultaneous measurement of 1,310 plasma proteins opens the door for a more explorative approach. The major aim of this study was to examine whether analysis of plasma collected during gestation of term pregnancy would allow identifying a set of proteins that tightly track gestational age. Establishing precisely-timed plasma proteomic changes during term pregnancy is a critical step in identifying deviations from regular patterns due to fetal and maternal maladaptations. A second aim was to gain insight into functional attributes of identified proteins, and link such attributes to relevant immunological changes.Pregnant women participated in this longitudinal study. In two subsequent subsets of 21 (training cohort) and 10 (validation cohort) women, specific blood specimens were collected during the first (7-14 wks), second (15-20 wks), and third (24-32 wks) trimesters, and 6 wks post-partum for analysis with a highly-multiplexed aptamer-based platform. An elastic net algorithm was applied to infer a proteomic model predicting gestational age. A bootstrapping procedure and piece-wise regression analysis was used to extract the minimum number of proteins required for predicting gestational age without compromising predictive power. Gene ontology analysis was applied to infer enrichment of molecular functions among proteins included in the proteomic model. Changes in abundance of proteins with such functions were linked to immune features predictive of gestational age at the time of sampling in pregnancies delivering at term.An independently validated model consisting of 74 proteins strongly predicted gestational age (p = 3.8x10-14, R = 0.97). The model could be reduced to eight proteins without losing its predictive power (p = 1.7x10-3, R = 0.91). The three top ranked proteins were glypican 3, chorionic somatomammotropin hormone, and granulins. Proteins activating the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway were enriched in the proteomic model, chorionic somatomammotropin hormone being the top ranked protein. Abundance of chorionic somatomammotropin hormone strongly correlated with STAT5 signaling activity in CD4 T cells, the endogenous cell-signaling event most predictive of gestational age.Results indicate that precisely timed changes in the plasma proteome during term pregnancy mirror a "proteomic clock". Importantly, the combined use of several plasma proteins was required for accurate prediction. The exciting promise of such a "clock" is that deviations from its regular chronological profile may assist in the early diagnoses of pregnancy-relate pathologies and point to underlying pathophysiology. Functional analysis of the proteomic model generated the novel hypothesis that somatomammotropin hormone may critically regulate T-cell function during pregnancy.

  View details for PubMedID 29277631

• Trends in the delivery route of twin pregnancies in the United States, 2006-2013. European journal of obstetrics, gynecology, and reproductive biology Bateni, Z. H., Clark, S. L., Sangi-Haghpeykar, H., Aagaard, K. M., Blumenfeld, Y. J., Ramin, S. M., Lee, H. C., Fox, K. A., Moaddab, A., Shamshirsaz, A. A., Salmanian, B., Hosseinzadeh, P., Racusin, D. A., Erfani, H., Espinoza, J., Dildy, G. A., Belfort, M. A., Shamshirsaz, A. A. 2016; 205: 120-126

  Abstract

  To determine the trends of cesarean delivery rate among twin pregnancies from 2006 to 2013.This is a population-based, cross-sectional analysis of twin live births from United State birth data files of the National Center for Health Statistics for calendar years 2006 through 2013. We stratified the population based on the gestational age groups, maternal race/ethnicity, advanced maternal age (AMA) which was defined by age more than 35 years and within the standard birth weight groups (group 1: birth weight 500-1499g, group 2: birth weight 1500-2499g and group 3: birth weight >2500g). We also analyzed the effect of different risk factors for cesarean delivery in twins.There were 1,079,102 infants born of twin gestations in the U.S. from 2006 to 2013, representing a small but significant increase in the proportion of twin births among all births (3.2% in 2006 versus 3.4% in 2013). The rate of cesarean delivery in twin live births peaked at 75.3% in 2009, and was significantly lower (74.8%) in 2013. The rate of the twin live birth with the breech presentation increased steadily from 26.3% in 2006 to 29.1% in 2013. For the fetus of the twin pregnancy presented as breech, the cesarean delivery rate peaked at 92.2% in 2010, falling slightly but significantly in the ensuing 3 years. The results demonstrated that the decrease in cesarean delivery rate was due to fewer cesareans in non-Hispanic white patients; all other ethnic subgroups showed increasing rates of cesarean delivery throughout the study. Gestational diabetes, gestational hypertension, previous cesarean delivery and breech presentation were all significant risk factors for cesarean delivery during the entire study period. Induction of labor and premature rupture of the membranes were associated with lower rates of cesarean delivery in twins.The recent decrease in the cesarean delivery rate in twin gestation appears to be largely attributable to a decline in cesarean among pregnancies complicated by breech presentation in non-Hispanic white women, and may reflect a health care disparity that deserves further research.

  View details for DOI 10.1016/j.ejogrb.2016.08.031

  View details for PubMedID 27591713

• Trends in the delivery route of twin pregnancies in the United States, 2006-2013. European journal of obstetrics, gynecology, and reproductive biology Bateni, Z. H., Clark, S. L., Sangi-Haghpeykar, H., Aagaard, K. M., Blumenfeld, Y. J., Ramin, S. M., Lee, H. C., Fox, K. A., Moaddab, A., Shamshirsaz, A. A., Salmanian, B., Hosseinzadeh, P., Racusin, D. A., Erfani, H., Espinoza, J., Dildy, G. A., Belfort, M. A., Shamshirsaz, A. A. 2016; 205: 120-126

  View details for DOI 10.1016/j.ejogrb.2016.08.031

  View details for PubMedID 27591713

• Opportunities for maternal transport for delivery of very low birth weight infants. Journal of perinatology Robles, D., Blumenfeld, Y. J., Lee, H. C., Gould, J. B., Main, E., Profit, J., Melsop, K., Druzin, M. 2016

  Abstract

  To assess frequency of very low birth weight (VLBW) births at non-level III hospitals.Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models.Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively.Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.Journal of Perinatology advance online publication, 29 September 2016; doi:10.1038/jp.2016.174.

  View details for DOI 10.1038/jp.2016.174

  View details for PubMedID 27684426

• HDlive imaging of a giant omphalocele. Ultrasound in obstetrics & gynecology Blumenfeld, Y. J., E Milan, K., Rubesova, E., Sylvester, K. G., DAVIS, A. S., Chock, V. Y., Hintz, S. R. 2016; 48 (3): 407-408

  View details for DOI 10.1002/uog.15993

  View details for PubMedID 27299988

• Prenatally Diagnosed Cases of Binder Phenotype Complicated by Respiratory Distress in the Immediate Postnatal Period. Journal of ultrasound in medicine Blumenfeld, Y. J., Davis, A. S., Hintz, S. R., Milan, K., Messner, A. H., Barth, R. A., Hudgins, L., Chueh, J., Homeyer, M., Bernstein, J. A., Enns, G., Atwal, P., Manning, M. 2016; 35 (6): 1353-1358

  Abstract

  Binder phenotype, or maxillonasal dysostosis, is a distinctive pattern of facial development characterized by a short nose with a flat nasal bridge, an acute nasolabial angle, a short columella, a convex upper lip, and class III malocclusion. We report 3 cases of prenatally diagnosed Binder phenotype associated with perinatal respiratory impairment.

  View details for DOI 10.7863/ultra.15.02050

  View details for PubMedID 27162279

• Does Time of Delivery Influence the Risk of Neonatal Morbidity? American journal of perinatology Brookfield, K. F., O'Malley, K., El-Sayed, Y. Y., Blumenfeld, Y. J., Butwick, A. J. 2016; 33 (5): 502-509

  Abstract

  Objective To examine whether time of delivery influences the risk of neonatal morbidity among women with singleton pregnancies. Study Design Secondary analysis of data from the Maternal Fetal Medicine Units Network Factor V Leiden Mutation study. We categorized time of delivery as day (07:00-16:59), evening (17:00-23:59), and overnight (midnight-06:59). Severe neonatal morbidity was defined by at least one of the following: respiratory distress syndrome, transient tachypnea of the newborn, sepsis, seizures, neonatal intensive care admission, or a 5-minute APGAR ≤3. We calculated frequencies of severe neonatal morbidity by time of delivery. Multivariate analysis was performed to determine whether time of delivery was independently associated with severe neonatal morbidity. Results Among 4,087 women, 1,917 (46.9%) delivered during the day, 1,140 (27.9%) delivered in the evening, and 1,030 (25.2%) delivered overnight. We observed no significant differences in the rates of neonatal morbidity between delivery time periods (day: 12.3%; evening: 12.8%; overnight: 12.6%; p = 0.9). No significant association was observed between time of delivery and neonatal morbidity after adjustment for maternal, obstetric, and peripartum factors. Conclusion Our findings suggest that time of delivery is not associated with severe neonatal morbidity.

  View details for DOI 10.1055/s-0035-1567891

  View details for PubMedID 26595143

• Does Time of Delivery Influence the Risk of Neonatal Morbidity? AMERICAN JOURNAL OF PERINATOLOGY Brookfield, K. F., O'Malley, K., Ei-Sayed, Y. Y., Blumenfeld, Y. J., Butwick, A. J. 2016; 33 (5): 502-509

  Abstract

  Objective To examine whether time of delivery influences the risk of neonatal morbidity among women with singleton pregnancies. Study Design Secondary analysis of data from the Maternal Fetal Medicine Units Network Factor V Leiden Mutation study. We categorized time of delivery as day (07:00-16:59), evening (17:00-23:59), and overnight (midnight-06:59). Severe neonatal morbidity was defined by at least one of the following: respiratory distress syndrome, transient tachypnea of the newborn, sepsis, seizures, neonatal intensive care admission, or a 5-minute APGAR ≤3. We calculated frequencies of severe neonatal morbidity by time of delivery. Multivariate analysis was performed to determine whether time of delivery was independently associated with severe neonatal morbidity. Results Among 4,087 women, 1,917 (46.9%) delivered during the day, 1,140 (27.9%) delivered in the evening, and 1,030 (25.2%) delivered overnight. We observed no significant differences in the rates of neonatal morbidity between delivery time periods (day: 12.3%; evening: 12.8%; overnight: 12.6%; p = 0.9). No significant association was observed between time of delivery and neonatal morbidity after adjustment for maternal, obstetric, and peripartum factors. Conclusion Our findings suggest that time of delivery is not associated with severe neonatal morbidity.

  View details for DOI 10.1055/s-0035-1567891

  View details for Web of Science ID 000373660900012

• Patient preferences for prenatal testing of microdeletion and microduplication syndromes PRENATAL DIAGNOSIS Calonico, E., Blumenfeld, Y. J., Hudgins, L., Taylor, J. 2016; 36 (3): 244-251

  Abstract

  To assess pregnant women's preferences regarding prenatal testing for microdeletion and microduplication conditions, and to identify what factors might influence their decisions.A written questionnaire was administered to pregnant women presenting for prenatal ultrasound. The questionnaire described the salient features of six microdeletion and microduplication syndromes of varying penetrance. Women were asked to indicate whether they would choose to test for each condition via an invasive diagnostic procedure, a non-invasive blood test, or not at all. Demographic and obstetrical data were also obtained.One hundred twenty-four women returned the questionnaire (response rate 89.2%). More than half of women (50.8%) made distinctions between conditions, and would choose a mixture of invasive testing, non-invasive testing, and no testing, depending on the condition. Testing preferences differed based on penetrance and features of the conditions. Prior prenatal testing, ethnicity, and education level were significantly associated (p<0.05) with testing decisions.Pregnant women do not perceive all microdeletion and microduplication conditions to be equal, and prenatal testing for such conditions is not always considered an all or none process. A test menu or filtering process may be a more optimal method of offering prenatal testing for microdeletion and microduplication conditions.

  View details for DOI 10.1002/pd.4760

  View details for Web of Science ID 000372555000007

• Racial and Ethnic Disparities in Mode of Anesthesia for Cesarean Delivery ANESTHESIA AND ANALGESIA Butwick, A. J., Blumenfeld, Y. J., Brookfield, K. F., Nelson, L. M., Weiniger, C. F. 2016; 122 (2): 472-479

  Abstract

  Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD).Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates.The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI], 1.5-1.8; P < 0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P < 0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05).Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.

  View details for DOI 10.1213/ANE.0000000000000679

  View details for Web of Science ID 000368646500001

  View details for PubMedCentralID PMC4724639

• Racial and Ethnic Disparities in Mode of Anesthesia for Cesarean Delivery. Anesthesia and analgesia Butwick, A. J., Blumenfeld, Y. J., Brookfield, K. F., Nelson, L. M., Weiniger, C. F. 2016; 122 (2): 472-9

  Abstract

  Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD).Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates.The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI], 1.5-1.8; P < 0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P < 0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05).Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.

  View details for DOI 10.1213/ANE.0000000000000679

  View details for PubMedID 26797554

  View details for PubMedCentralID PMC4724639

• Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Girsen, A. I., Wallenstein, M. B., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Druzin, M. L., Oshiro, B. T., Blumenfeld, Y. J. 2016; 29 (15): 2499-2503

  View details for DOI 10.3109/14767058.2015.1090971

  View details for Web of Science ID 000374775200021

  View details for PubMedID 26445130

• Patient preferences for prenatal testing of microdeletion and microduplication syndromes. Prenatal diagnosis Calonico, E., Blumenfeld, Y. J., Hudgins, L., Taylor, J. 2015

  Abstract

  To assess pregnant women's preferences regarding prenatal testing for microdeletion and microduplication conditions, and to identify what factors might influence their decisions.A written questionnaire was administered to pregnant women presenting for prenatal ultrasound. The questionnaire described the salient features of six microdeletion and microduplication syndromes of varying penetrance. Women were asked to indicate whether they would choose to test for each condition via an invasive diagnostic procedure, a non-invasive blood test, or not at all. Demographic and obstetrical data were also obtained.One hundred twenty-four women returned the questionnaire (response rate 89.2%). More than half of women (50.8%) made distinctions between conditions, and would choose a mixture of invasive testing, non-invasive testing, and no testing, depending on the condition. Testing preferences differed based on penetrance and features of the conditions. Prior prenatal testing, ethnicity, and education level were significantly associated (p<0.05) with testing decisions.Pregnant women do not perceive all microdeletion and microduplication conditions to be equal, and prenatal testing for such conditions is not always considered an all or none process. A test menu or filtering process may be a more optimal method of offering prenatal testing for microdeletion and microduplication conditions.

  View details for DOI 10.1002/pd.4760

  View details for PubMedID 26687911

• Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis ULTRASOUND IN OBSTETRICS & GYNECOLOGY GRANDE, M., Jansen, F. A., Blumenfeld, Y. J., Fisher, A., Odibo, A. O., Haak, M. C., Borrell, A. 2015; 46 (6): 650-658

  View details for DOI 10.1002/uog.14880

  View details for Web of Science ID 000365855700004

  View details for PubMedID 25900824

• Prenatal Diagnosis and Perinatal Outcomes of Congenital Megalourethra: A Multicenter Cohort Study and Systematic Review of the Literature. Journal of ultrasound in medicine Moaddab, A., Sananes, N., Hernandez-Ruano, S., Werneck Britto, I. S., Blumenfeld, Y., Stoll, F., Favre, R., Ruano, R. 2015; 34 (11): 2057-2064

  Abstract

  The purpose of this study was to evaluate the prenatal findings and postnatal outcomes in fetuses with congenital megalourethra.This retrospective study reviewed our experience and the literature between 1989 and 2014. Prenatal findings were evaluated and compared with postnatal findings, including neonatal mortality and abnormal renal function (need for dialysis or renal transplantation).Fifty fetuses with congenital megalourethra were analyzed, including 6 cases diagnosed in our centers. Most cases (n = 43 [86.0%]) were diagnosed in the second trimester. Only 1 case was diagnosed in the first trimester, whereas 6 cases (12.0%) were diagnosed in the third trimester. Thirty-five fetuses (70.0%) survived. Bilateral hydroureters were associated with perinatal death (P= .024). Among the survivors, 41.9% of the neonates had renal impairment. The following factors were associated with postnatal renal impairment: presence of severe oligohydramnios/anhydramnios (P = .033), bilateral hydronephrosis (P = .008), and earlier gestational age at delivery (P = .022).In fetal megalourethra, bilateral hydroureters, bilateral hydronephrosis, and severe oligohydramnios/anhydramnios are associated with neonatal mortality and renal impairment.

  View details for DOI 10.7863/ultra.14.12064

  View details for PubMedID 26446816

• Prepregnancy Obesity and Risks of Stillbirth PLOS ONE Carmichael, S. L., Blumenfeld, Y. J., Mayo, J., Wei, E., Gould, J. B., Stevenson, D. K., Shaw, G. M. 2015; 10 (10)

  Abstract

  We examined the association of maternal obesity with risk of stillbirth, focusing on whether the pattern of results varied by gestational age or maternal race-ethnicity or parity.Analyses included 4,012 stillbirths and 1,121,234 liveborn infants delivered in California from 2007-2010. We excluded stillbirths due to congenital anomalies, women with hypertensive disorders or diabetes, and plural births, to focus on fetuses and women without these known contributing conditions. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI). Separate models were run for stillbirths delivered at 20-23, 24-27, 28-31, 32-36, 37-41 weeks, relative to liveborn deliveries at 37-41 weeks.For stillbirth at 20-23 weeks, RRs were elevated for all race-ethnicity and parity groups. The RR for a 20-unit change in BMI (which reflects the approximate BMI difference between a normal weight and an Obese III woman) was 3.5 (95% CI 2.2, 5.6) for nulliparous white women and ranged from 1.8 to 5.0 for other sub-groups. At 24-27 weeks, the association was significant (p<0.05) only for multiparous non-Hispanic whites; at 28-31 weeks, for multiparous whites and nulliparous whites and blacks; at 32-36 weeks, for multiparous whites and nulliparous blacks; and at 37-41 weeks, for all groups except nulliparous blacks. The pattern of results was similar when restricted to stillbirths due to unknown causes and somewhat stronger when restricted to stillbirths attributable to obstetric causes.Increased risks were observed across all gestational ages, and some evidence of heterogeneity of the associations was observed by race-ethnicity and parity.

  View details for DOI 10.1371/journal.pone.0138549

  View details for PubMedID 26466315

• Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth. BJOG : an international journal of obstetrics and gynaecology Jelliffe-Pawlowski, L. L., Baer, R. J., Blumenfeld, Y. J., Ryckman, K. K., O'Brodovich, H. M., Gould, J. B., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Stevenson, D. K., Shaw, G. M., Currier, R. J. 2015; 122 (11): 1484-1493

  Abstract

  To examine the relationship between maternal characteristics, serum biomarkers and preterm birth (PTB) by spontaneous and medically indicated subtypes.Population-based cohort.California, United States of America.From a total population of 1 004 039 live singleton births in 2009 and 2010, 841 665 pregnancies with linked birth certificate and hospital discharge records were included.Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models and 95% confidence intervals. First-trimester and second-trimester serum marker levels were analysed in a subset of 125 202 pregnancies with available first-trimester and second-trimester serum biomarker results.PTB by subtype.In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, pre-existing hypertension with and without pre-eclampsia, gestational hypertension with pre-eclampsia, pre-existing diabetes, anaemia, previous PTB, one or two or more previous caesarean section(s), interpregnancy interval ≥ 60 months, low first-trimester pregnancy-associated plasma protein A, high second-trimester α-fetoprotein, and high second-trimester dimeric inhibin A). These risks occurred in 51.6-86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically indicated PTB <32 weeks in women with pre-existing hypertension and pre-eclampsia (adjusted odds ratio 89.7, 95% CI 27.3-111.2).Our findings suggest a shared aetiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies.Findings suggest a shared aetiology across preterm birth subtypes. Patterns may inform risk reduction efforts.

  View details for DOI 10.1111/1471-0528.13495

  View details for PubMedID 26111589

• Fetofetal Transfusion Syndrome in Monochorionic-Triamniotic Triplets Treated with Fetoscopic Laser Ablation: Report of Two Cases and A Systematic Review. AJP reports Blumenfeld, Y. J., Shamshirsaz, A. A., Belfort, M. A., Hintz, S. R., Moaddab, A., Ness, A., Chueh, J., El-Sayed, Y. Y., Ruano, R. 2015; 5 (2): e153-60

  Abstract

  Objective This study aims to determine the clinical outcomes of monochorionic-triamniotic (MT) pregnancies complicated by severe fetofetal transfusion undergoing laser photocoagulation. Study Design We report two cases of MT triplets complicated by fetofetal transfusion syndrome (FFTS) and a systematic review classifying cases into different subtypes: MT with two donors and one recipient, MT with one donor and two recipients, MT with one donor, one recipient, and one unaffected triplet. The number of neonatal survivors was analyzed based on this classification as well as Quintero staging. Results A total of 26 cases of MT triples complicated by FFTS were analyzed. In 56% of the cases, the FFTS involved all three triplets, 50% of whom had an additional donor and 50% an additional recipient. Among the 24 cases that survived beyond 1 week after the procedure, the average gestational age of delivery was 29.6 weeks, and the average interval from procedure to delivery was 10.1 weeks. The overall neonatal survival rate was 71.7%, with demises occurring equally between donor and recipient triplets. Overall neonatal survival including survival of at least two fetuses occurred with equal frequency between the different groups. Conclusion Significant neonatal survival can be achieved in most cases of MT triplets with FFTS.

  View details for DOI 10.1055/s-0035-1552931

  View details for PubMedID 26495175

  View details for PubMedCentralID PMC4603872

• Mode of anaesthesia for preterm Caesarean delivery: secondary analysis from the Maternal-Fetal Medicine Units Network Caesarean Registry†‡. British journal of anaesthesia Butwick, A. J., El-Sayed, Y. Y., Blumenfeld, Y. J., Osmundson, S. S., Weiniger, C. F. 2015; 115 (2): 267-274

  Abstract

  Preterm delivery is often performed by Caesarean section. We investigated modes of anaesthesia and risk factors for general anaesthesia among women undergoing preterm Caesarean delivery.Women undergoing Caesarean delivery between 24(+0) and 36(+6) weeks' gestation were identified from a multicentre US registry. The mode of anaesthesia was classified as neuraxial anaesthesia (spinal, epidural, or combined spinal and epidural) or general anaesthesia. Logistic regression was used to identify patient characteristic, obstetric, and peripartum risk factors associated with general anaesthesia.Within the study cohort, 11 539 women had preterm Caesarean delivery; 9510 (82.4%) underwent neuraxial anaesthesia and 2029 (17.6%) general anaesthesia. In our multivariate model, African-American race [adjusted odds ratio (aOR)=1.9; 95% confidence interval (CI)=1.7-2.2], Hispanic ethnicity (aOR=1.5; 95% CI=1.2-1.8), other race (aOR=1.4; 95% CI=1.1-1.9), and haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or eclampsia (aOR=2.8; 95% CI=2.2-3.5) were independently associated with receiving general anaesthesia for preterm Caesarean delivery. Women with an emergency Caesarean delivery indication had the highest odds for general anaesthesia (aOR=3.5; 95% CI=3.1-3.9). For every 1 week decrease in gestational age at delivery, the adjusted odds of general anaesthesia increased by 13%.In our study cohort, nearly one in five women received general anaesthesia for preterm Caesarean delivery. Although potential confounding by unmeasured factors cannot be excluded, our findings suggest that early gestational age at delivery, emergent Caesarean delivery indications, hypertensive disease, and non-Caucasian race or ethnicity are associated with general anaesthesia for preterm Caesarean delivery.

  View details for DOI 10.1093/bja/aev108

  View details for PubMedID 25956901

• Maternal serum markers, characteristics and morbidly adherent placenta in women with previa JOURNAL OF PERINATOLOGY Lyell, D. J., Faucett, A. M., Baer, R. J., Blumenfeld, Y. J., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2015; 35 (8): 570-574

  Abstract

  To examine associations with morbidly adherent placenta (MAP) among women with placenta previa.Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236 714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls.In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ⩾95th percentile (⩾2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ⩾95th percentile (⩾1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ⩾2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively).Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

  View details for DOI 10.1038/jp.2015.40

  View details for Web of Science ID 000358684100008

• Risk Factors for Prolonged Postpartum Length of Stay Following Cesarean Delivery AMERICAN JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., El-Sayed, Y. Y., Lyell, D. J., Nelson, L. M., Butwick, A. J. 2015; 32 (9): 825-832

  Abstract

  Objective This study aims to identify risk factors for prolonged postpartum length of stays (LOS) after cesarean delivery (CD). Study Design Patients undergoing CD were sourced from a multicenter registry of 19 academic centers between 1999 and 2002 (n = 57,067). Prolonged postpartum LOS was defined as a hospitalization duration ≥ 90th centile. Maternal, antepartum, perioperative, and neonatal variables were compared between women with and without prolonged postpartum LOS. Results The 90th centile for postpartum LOS was 4 days, with 14,954 women experiencing prolonged postpartum LOS. Women with perioperative complications had the highest independent risk for a prolonged postpartum LOS: ileus (adjusted odds ratio [aOR] = 12.28; 95% confidence interval CI = 8.98-16.8); endometritis (aOR = 10.45; 95% CI = 9.51-11.5), and wound complications (aOR = 5.49; 95% CI = 4.54-6.63). Several antepartum, perioperative, and neonatal variables were associated with a prolonged postpartum LOS. Conclusion Perioperative complications had the highest risk for prolonged LOS after CD. Strategies to reduce perioperative complications are needed to decrease the health care burden of prolonged post-CD LOS.

  View details for DOI 10.1055/s-0034-1543953

  View details for Web of Science ID 000358571000004

• Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin AMERICAN JOURNAL OF PERINATOLOGY Jelliffe-Pawlowski, L. L., Baer, R. J., Currier, R. J., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y., Shaw, G. M., Druzin, M. L. 2015; 32 (7): 703-711

  Abstract

  This study aims to evaluate the relationship between early-onset severe preeclampsia and first trimester serum levels of pregnancy-associated plasma protein A (PAPP-A) and total human chorionic gonadotropin (hCG).The association between early-onset severe preeclampsia and abnormal levels of first trimester PAPP-A and total hCG in maternal serum were measured in a sample of singleton pregnancies without chromosomal defects that had integrated prenatal serum screening in 2009 and 2010 (n = 129,488). Logistic binomial regression was used to estimate the relative risk (RR) of early-onset severe preeclampsia in pregnancies with abnormal levels of first trimester PAPP-A or total hCG as compared with controls.Regardless of parity, women with low first trimester PAPP-A or high total hCG were at increased risk for early-onset severe preeclampsia. Women with low PAPP-A (multiple of the median [MoM] ≤ the 10th percentile in nulliparous or ≤ the 5th percentile in multiparous) or high total hCG (MoM ≥ the 90th percentile in nulliparous or ≥ the 95th percentile in multiparous) were at more than a threefold increased risk for early-onset severe preeclampsia (RR, 4.2; 95% confidence interval [CI], 3.0-5.9 and RR, 3.3; 95% CI, 2.1-5.2, respectively).Routinely collected first trimester measurements of PAPP-A and total hCG provide unique risk information for early-onset severe preeclampsia.

  View details for DOI 10.1055/s-0034-1396697

  View details for Web of Science ID 000355418600014

  View details for PubMedID 25519199

• Second-line uterotonics and the risk of hemorrhage-related morbidity AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5)

  Abstract

  Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for Web of Science ID 000353598500025

  View details for PubMedID 25582104

• Obstetric Ultrasound Quality Improvement Initiative-Utilization of a Quality Assurance Process and Standardized Checklists AMERICAN JOURNAL OF PERINATOLOGY Mrazek-Pugh, B., Blumenfeld, Y. J., Lee, H. C., Chueh, J. 2015; 32 (6): 599-604

  Abstract

  Objective Our aim was to assess whether mandated completion of an electronic checklist and a quality assurance (QA) process improved obstetric (OB) ultrasound image documentation. Study Design A checklist of mandated images based on the American Institute of Ultrasound in Medicine guidelines was created. A baseline QA assessment was performed with a lead senior sonographer reviewing eight random OB examinations for each sonographer. An electronic checklist was then instituted for all OB examinations on each ultrasound machine. It was mandated that each anatomical structure be checked off during real-time image acquisition. A repeat QA assessment of each sonographer was then performed quarterly. Results Baseline assessments were performed between September 2011 and November 2011. Out of the 110 examinations analyzed, only 49% were deemed "complete" with none of the sonographers having a 100% complete examination rate. Following institution of the mandated electronic checklist, a repeat assessment revealed an 81% complete examination rate for the next quarter, and 90% were complete at the end of a year. All sonographers improved their image acquisition regardless of baseline skill level at the initial QA. Conclusion A QA process and a mandated standardized electronic checklist improved the image documentation.

  View details for DOI 10.1055/s-0035-1545667

  View details for Web of Science ID 000354342400013

  View details for PubMedID 25730132

• Peripartum and neonatal outcomes of small- for- gestational- age infants with gastroschisis PRENATAL DIAGNOSIS Girsen, A. I., Do, S., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Blumenfeld, Y. J. 2015; 35 (5): 477-482

  Abstract

  Neonates with gastroschisis are often small-for-gestational-age (SGA) based on population nomograms. Our objective was to evaluate the effect of SGA on perinatal and neonatal outcomes in cases of gastroschisis.Retrospective study of neonates with prenatally diagnosed gastroschisis from two academic centers between 2008-13. Perinatal and neonatal outcomes of neonates with SGA at birth were compared with appropriate for gestational age (AGA) neonates. The primary composite outcome was defined as any of: neonatal sepsis, short bowel syndrome at discharge, prolonged mechanical ventilation (upper quartile for the cohort), bowel atresia, or death.We identified 112 cases of gastroschisis, 25 of whom (22%) were SGA at birth. There were no differences in adverse peripartum outcomes between SGA and AGA infants. No difference was found in the primary composite neonatal outcome (52% vs. 36%, p=0.21), but SGA infants were more likely to have prolonged mechanical ventilation (44% vs. 22%, p=0.04) and prolonged LOS (52% vs. 22%, p=0.007). After adjusting for GA at delivery, SGA remained associated with prolonged LOS (OR=4.3, CI:1.6 - 11.8).Among infants with gastroschisis, SGA at birth is associated with a 4-fold increase in odds for prolonged LOS, independent of GA. © 2015 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.4562

  View details for Web of Science ID 000353987100011

  View details for PubMedID 25613462

• Reply. Journal of ultrasound in medicine Blumenfeld, Y. J., Rouse, D. J. 2015; 34 (4): 743-?

  View details for DOI 10.7863/ultra.34.4.742.1

  View details for PubMedID 25792594

• Risk Factors for Prolonged Postpartum Length of Stay Following Cesarean Delivery. American journal of perinatology Blumenfeld, Y. J., El-Sayed, Y. Y., Lyell, D. J., Nelson, L. M., Butwick, A. J. 2015

  Abstract

  Objective This study aims to identify risk factors for prolonged postpartum length of stays (LOS) after cesarean delivery (CD). Study Design Patients undergoing CD were sourced from a multicenter registry of 19 academic centers between 1999 and 2002 (n = 57,067). Prolonged postpartum LOS was defined as a hospitalization duration ≥ 90th centile. Maternal, antepartum, perioperative, and neonatal variables were compared between women with and without prolonged postpartum LOS. Results The 90th centile for postpartum LOS was 4 days, with 14,954 women experiencing prolonged postpartum LOS. Women with perioperative complications had the highest independent risk for a prolonged postpartum LOS: ileus (adjusted odds ratio [aOR] = 12.28; 95% confidence interval CI = 8.98-16.8); endometritis (aOR = 10.45; 95% CI = 9.51-11.5), and wound complications (aOR = 5.49; 95% CI = 4.54-6.63). Several antepartum, perioperative, and neonatal variables were associated with a prolonged postpartum LOS. Conclusion Perioperative complications had the highest risk for prolonged LOS after CD. Strategies to reduce perioperative complications are needed to decrease the health care burden of prolonged post-CD LOS.

  View details for DOI 10.1055/s-0034-1543953

  View details for PubMedID 25594218

• Array comparative genomic hybridization and fetal congenital heart defects: a systematic review and meta-analysis ULTRASOUND IN OBSTETRICS & GYNECOLOGY Jansen, F. A., Blumenfeld, Y. J., Fisher, A., Cobben, J. M., Odibo, A. O., Borrell, A., Haak, M. C. 2015; 45 (1): 27-35

  Abstract

  Array comparative genomic hybridization (aCGH) is a molecular cytogenetic technique that is able to detect the presence of copy number variants (CNVs) within the genome. The detection rate of imbalances by aCGH compared to standard karyotyping and 22q11 microdeletion analysis by fluorescence in-situ hybridization (FISH), in the setting of prenatally-diagnosed cardiac malformations, has been reported in several studies. The objective of our study was to perform a systematic literature review and meta-analysis to document the additional diagnostic gain of using aCGH in cases of congenital heart disease (CHD) diagnosed by prenatal ultrasound examination, with the aim of assisting clinicians to determine whether aCGH analysis is warranted when an ultrasonographic diagnosis of CHD is made, and to guide counseling in this setting.Articles in PubMed, EMBASE and Web of Science databases from January 2007 to September 2014 describing CNVs in prenatal cases of CHD were included. Search terms were: 'array comparative genomic hybridization', 'copy number variants' and 'fetal congenital heart defects'. Articles regarding karyotyping or 22q11 deletion only were excluded.Thirteen publications (including 1131 cases of CHD) met the inclusion criteria for the analysis. Meta-analysis indicated an incremental yield of 7.0% (95% CI, 5.3-8.6%) for the detection of CNVs using aCGH, excluding aneuploidy and 22q11 microdeletion cases. Subgroup results showed a 3.4% (95% CI, 0.3-6.6%) incremental yield in isolated CHD cases, and 9.3% (95% CI,  6.6-12%) when extracardiac malformations were present. Overall, an incremental yield of 12% (95% CI, 7.6-16%) was found when 22q11 deletion cases were included. There was an additional yield of 3.4% (95% CI, 2.1-4.6%) for detecting variants of unknown significance (VOUS).In this review we provide an overview of published data and discuss the benefits and limitations of using aCGH. If karyotyping and 22q11 microdeletion analysis by FISH are normal, using aCGH has additional value, detecting pathogenic CNVs in 7.0% of prenatally diagnosed CHD, with a 3.4% additional yield of detecting VOUS. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

  View details for DOI 10.1002/uog.14695

  View details for Web of Science ID 000347233300005

  View details for PubMedID 25319878

• Accuracy of Sonographic Chorionicity Classification in Twin Gestations JOURNAL OF ULTRASOUND IN MEDICINE Blumenfeld, Y. J., Momirova, V., Rouse, D. J., Caritis, S. N., Sciscione, A., Peaceman, A. M., Reddy, U. M., Varner, M. W., Malone, F. D., Iams, J. D., Mercer, B. M., Thorp, J. M., Sorokin, Y., Carpenter, M. W., Lo, J., Ramin, S. M., Harper, M. 2014; 33 (12): 2187-2192

  Abstract

  To evaluate the accuracy of sonographic classification of chorionicity in a large cohort of twins and investigate which factors may be associated with sonographic accuracy.We conducted a secondary analysis of a randomized trial of preterm birth prevention in twins. Sonographic classification of chorionicity was compared with pathologic examination of the placenta. Maternal (age, body mass index, diabetes, and hypertension), obstetric (prior cesarean delivery, gestational age at the first sonographic examination, and antepartum bleeding), and sonographic (oligohydramnios, polyhydramnios, and twin-twin transfusion syndrome) factors were assessed for their possible association with accuracy.A total of 545 twin sets in which chorionicity was classified by sonography before 20 weeks' gestation were included; 455 were dichorionic and 90 were monochorionic based on pathologic examination. Sonography misclassified 35 of 545 twin pregnancies (6.4%): 18 of 455 dichorionic twins (4.0%) and 17 of 90 monochorionic twins (19.0%). The sensitivity and specificity of sonographic diagnosis of monochorionicity were 81.1% and 96.0%, respectively. In a multivariable analysis, pregnancies with initial sonographic examinations before 14 weeks' gestation were less likely to have misclassified chorionicity than those with sonographic examinations at 15 to 20 weeks (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.23-0.96). For each week increase in gestational age, the odds of misclassification rose by 10% (OR, 1.10; 95% CI, 1.01-1.2). In the multivariable analysis, maternal age, body mass index, parity, and prior cesarean delivery were not associated with sonographic accuracy.Sonography before 20 weeks incorrectly classified chorionicity in 6.4% of twin gestations. Those with first sonographic examinations performed at earlier gestational ages had improved chorionicity diagnosis.

  View details for DOI 10.7863/ultra.33.12.2187

  View details for Web of Science ID 000346232600017

  View details for PubMedID 25425377

  View details for PubMedCentralID PMC4246197

• Elective ceasarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial reply BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY Cho, Y., Carvalho, B., Butwick, A., Blumenfeld, Y., Riley, E. 2014; 121 (13): 1748-1749

  View details for DOI 10.1111/1471-0528.13080

  View details for Web of Science ID 000345508600045

• Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. American journal of obstetrics and gynecology Blumenfeld, Y. J., Baer, R. J., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Faucett, A. M., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2014; 211 (2): 144 e1-9

  View details for DOI 10.1016/j.ajog.2014.03.027

  View details for PubMedID 24631707

• Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia GENETICS IN MEDICINE Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

  View details for DOI 10.1038/gim.2013.194

  View details for Web of Science ID 000338601400012

• Caesarean delivery for twin gestation at 32-38 weeks does not lead to improved clinical outcomes for neonates or mothers. Evidence-based medicine Lee, H. C., Blumenfeld, Y. J. 2014; 19 (3): 119-?

  View details for DOI 10.1136/eb-2013-101655

  View details for PubMedID 24361755

• Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proceedings of the National Academy of Sciences of the United States of America Koh, W., Pan, W., Gawad, C., Fan, H. C., Kerchner, G. A., Wyss-Coray, T., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2014; 111 (20): 7361-7366

  Abstract

  Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA and to monitor changes in tissue development and health. As one application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the analysis of mRNA, we observed and characterized noncoding species such as long noncoding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma. We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron-specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer's disease and showed that disease specific neural transcripts are present at increased levels in the blood of affected individuals. Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.

  View details for DOI 10.1073/pnas.1405528111

  View details for PubMedID 24799715

• Urine culture results and adverse outcomes in women with pyelonephritis. Obstetrics and gynecology Berger, V. K., Yeaton-Massey, A., Kassis, J., Blumenfeld, Y. J., Lee, H. C., Druzin, M. 2014; 123: 138S-?

  Abstract

  A retrospective cohort study of patients with pyelonephritis in pregnancy and immediately postpartum was conducted. Participants delivered between 2005 and 2009 at a single university center (Lucile Packard Children's Hospital at Stanford) were reviewed. Pyelonephritis was defined by a temperature greater than 38.0°C, flank pain or costovertebral angle tenderness, and bacteruria or pyuria on urinalysis. All patients with pyelonephritis and urine culture results were included. Univariate analyses were performed with the χ test. Means were compared with the Student's t test.One hundred thirteen patients were admitted with pyelonephritis and had a urine culture performed. Of the entire cohort, 70% of patients were Hispanic, 53% were nulliparous, and most were diagnosed in the third trimester. A total of 94 patients (83%) had positive urine cultures. There were no differences in adverse outcomes (preterm birth, anemia, bacteremia, acute respiratory distress syndrome, and hospital stay) between those with positive and negative urine cultures. Among those with positive cultures, there was a statistically significant increase in preterm birth (less than 37 weeks of gestation) between those with resistant uropathogens and those with pan-sensitive pathogens (26.5% compared with 7.6%, P=.01) ().(Table is included in full-text article.): Among women with pyelonephritis, complications did not differ between those with positive and negative urine culture results. Women with resistant bacterial uropathogens are at increased risk for preterm birth compared with those with sensitive pathogens.

  View details for DOI 10.1097/01.AOG.0000447112.69038.68

  View details for PubMedID 24770006

• On-time scheduled cesarean delivery start time process-improvement initiative. Obstetrics and gynecology Blumenfeld, Y. J., Riley, E., Hilton, G., Lee, H. C., El-Sayed, Y. Y., Druzin, M. L. 2014; 123: 138S-9S

  Abstract

  Cesarean deliveries comprise approximately 30% of all births, many of which are scheduled. Given the labile nature of labor and delivery units, scheduled cesarean deliveries are often delayed. Our aim was to improve on-time scheduled cesarean delivery start times.A multidisciplinary team (obstetrician-gynecologist, nursing, anesthesia, and hospital administration) met to review scheduled cesarean delivery data, identify logistic barriers to on-time starts, and develop a plan to improve cesarean delivery start times. After identifying possible barriers to on-time starts, the following process was instituted: planned preoperative visit 1-2 days before scheduled cesarean delivery, mandatory submission of History & Physical and consent forms by the time of the preoperative visit, and initial preparation of the first scheduled patient for cesaren delivery by nighttime nursing before morning change of shift. The process launched on March 1, 2013. Data from scheduled cesarean deliveries 6 months before and 3 months after the initiative were reviewed and analyzed.Of 1,298 total cesarean deliveries, 423 were scheduled, defined as cesarean delivery scheduled at least 24 hours in advance (300 before and 123 after the initiative). Sixty-four of 300 scheduled cesarean deliveries (21.3%) were on time before compared with 67 of 123 (54.5%) after the initiative began (P<.001). Among delayed cases, there was no difference in the average delay time between those before and after the initiative (55.7 compared with 54.4 minutes P=.93); however, 50.7% of cases were either on time or delayed by 15 minutes or less before the initiative compared with 69.9% of cases after (P<.001).A multidisciplinary initiative significantly increased scheduled cesarean delivery on-time start times.

  View details for DOI 10.1097/01.AOG.0000447113.07157.f3

  View details for PubMedID 24770007

• Oral misoprostol versus vaginal dinoprostone for labor induction in nulliparous women at term. Journal of perinatology Faucett, A. M., Daniels, K., Lee, H. C., El-Sayed, Y. Y., Blumenfeld, Y. J. 2014; 34 (2): 95-99

  Abstract

  Objective:To compare the efficacy of oral misoprostol to vaginal dinoprostone for labor induction in nulliparous women.Study design:Admissions for labor induction from January 2008 to December 2010 were reviewed. Patients receiving oral misoprostol were compared with those receiving vaginal dinoprostone. The primary outcome was time from induction agent administration to vaginal delivery. Secondary outcomes included vaginal delivery within 24 h, mode of delivery and maternal and fetal outcomes.Result:A total of 680 women were included: 483 (71%) received vaginal dinoprostone and 197 (29%) received oral misoprostol. Women who received oral misoprostol had a shorter interval to vaginal delivery (27.2 vs 21.9 h, P<0.0001) and were more likely to deliver vaginally in <24 h (47% vs 64%, P=0.001). There was no increase in the rate of cesarean delivery or adverse maternal or neonatal outcomes.Conclusion:Labor induction with oral misoprostol resulted in shorter time to vaginal delivery without increased adverse outcomes in nulliparous women.

  View details for DOI 10.1038/jp.2013.133

  View details for PubMedID 24157494

• Isolated umbilical vein varix with a poor outcome despite close fetal surveillance. Journal of ultrasound in medicine Brookfield, K. F., Osmundson, S. S., Chetty, S., Chueh, J., Blumenfeld, Y. J., Barth, R. A., El-Sayed, Y. Y. 2013; 32 (9): 1680-1682

  View details for DOI 10.7863/ultra.32.9.1680

  View details for PubMedID 23980233

• Maternal-fetal medicine fellowship 3- and 4-dimensional ultrasound experience: room for improvement. Journal of ultrasound in medicine Ness, A., Blumenfeld, Y. J., Platt, L. D. 2013; 32 (6): 949-953

  Abstract

  The purpose of this study was to assess maternal-fetal medicine (MFM) fellowship 3- and 4-dimensional (3D/4D) ultrasound experience and training.A 53-item prenatal diagnosis survey was emailed to 458 associate members of the Society for Maternal-Fetal Medicine. Associate members include both MFM fellows and recent graduates who are not yet board certified in MFM.A total of 148 associate members completed the survey (32% response rate); 92% were at least in their second year of a fellowship, and 48.1% had completed a fellowship. About half (50.8%) were capable of performing 3D/4D ultrasound examinations ("performers"), whereas 49.2% were not ("nonperformers"). Among performers, about 80% were capable of only basic image acquisition. Overall, 39.5% of respondents received no official 3D/4D ultrasound training, and 55.5% stated that fewer than 1 in 5 of their MFM faculty routinely performed 3D/4D ultrasound examinations. Compared with performers, nonperformers had less formal 3D/4D ultrasound training (53% versus 26%; P = .018) and fewer MFM faculty who performed 3D/4D ultrasound examinations (43% versus 68%; P = .005), and fewer nonperformers were taught by ultrasound mentors (25% versus 47.8%; P = .011).Most fellows are not trained in 3D/4D ultrasound. Greater emphasis on ultrasound mentorship and formalized ultrasound training by MFM faculty during fellowships is needed.

  View details for DOI 10.7863/ultra.32.6.949

  View details for PubMedID 23716515

• Maternal-fetal medicine fellowship obstetrical ultrasound experience: results from a fellowship survey PRENATAL DIAGNOSIS Blumenfeld, Y. J., Ness, A., Platt, L. D. 2013; 33 (2): 158-161

  Abstract

  To assess maternal-fetal medicine (MFM) fellowship obstetrical ultrasound training, scope of practice and research.A 52-item prenatal diagnosis survey was e-mailed to 458 associate members of the Society for Maternal-Fetal Medicine on two separate occasions. Associate members include both MFM fellows and recent graduates who are not yet board certified in MFM.A total of 148 associate members completed the survey (32% response rate), 92% of whom were at least in their second year of fellowship. A total of 58% of fellows spend at least 20% of their fellowship time performing prenatal ultrasounds, and most begin their ultrasound training in their first year. Most fellows describe being comfortable performing routine fetal anatomy surveys, growth ultrasounds and umbilical artery Doppler measurements, but only 48% are nuchal translucency (NT) certified, most through Nuchal Translucency Quality Review. A total of 7% of fellows do not receive structured training in 2D ultrasound, 39% receive no structured training in 3D/4D ultrasound, and 28% receive no structured training in fetal echocardiography. Only 38% can identify an ultrasound mentor during fellowship.Most fellows are trained in ultrasound during their first year of fellowship and feel comfortable performing routine exams. However, ultrasound mentorship, structured training and research in prenatal ultrasound are limited in some programs.

  View details for DOI 10.1002/pd.4029

  View details for Web of Science ID 000314493500010

  View details for PubMedID 23229275

• Conservatively Managed Fetal Goiter: An Alternative to in utero Therapy. Fetal diagnosis and therapy Blumenfeld, Y. J., Davis, A., Milan, K., Chueh, J., Hudgins, L., Barth, R. A., Hintz, S. R. 2013; 34 (3): 184-187

  Abstract

  Fetal goiter may arise from a variety of etiologies including iodine deficiency, overtreatment of maternal Graves' disease, inappropriate maternal thyroid replacement and, rarely, congenital hypothyroidism. Fetal goiter is often associated with a retroflexed neck and polyhydramnios, raising concerns regarding airway obstruction in such cases. Prior reports have advocated for cordocentesis and intra-amniotic thyroid hormone therapy in order to confirm the diagnosis of fetal thyroid dysfunction, reduce the size of the fetal goiter, reduce polyhydramnios, aid with the assistance of maternal thyroid hormone therapy and reduce fetal malpresentation. We report two cases of conservatively managed fetal goiter, one resulting in a vaginal delivery, and no evidence of postnatal respiratory distress despite the presence of polyhydramnios and a retroflexed neck on prenatal ultrasound. © 2013 S. Karger AG, Basel.

  View details for DOI 10.1159/000353387

  View details for PubMedID 23920148

• Infants with Prenatally Diagnosed Anomalies Special Approaches to Preparation and Resuscitation CLINICS IN PERINATOLOGY Colby, C. E., Carey, W. A., Blumenfeld, Y. J., Hintz, S. R. 2012; 39 (4): 871-887

  Abstract

  When a fetal anomaly is suspected, a multidisciplinary approach to diagnosis, counseling, pregnancy management, surveillance, delivery planning, and neonatal care is critical to creating a comprehensive management plan. This article provides a basic framework for integrating prenatal diagnostic and maternal-fetal care considerations, delivery planning, special resuscitation needs, and immediate and later neonatal care and evaluation into developing a thoughtful management plan for infants with prenatally diagnosed complex anomalies including congenital heart disease, intrathoracic masses, fetal airway obstruction, neural tube defects, abdominal wall defects, and skeletal dysplasia.

  View details for DOI 10.1016/j.clp.2012.09.012

  View details for Web of Science ID 000312623900011

  View details for PubMedID 23164184

• Utilization of available prenatal screening and diagnosis: effects of the California screen program JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., Taylor, J., Lee, H. C., Hudgins, L., Sung, J. F., El-Sayed, Y. Y. 2012; 32 (12): 907-912

  Abstract

  In 2009, the California Genetic Disease Branch introduced an aneuploidy screening program allowing Medi-Cal (state insured) patients access to state-sponsored first-trimester screening. The objective of this study was to assess the effect of greater access to prenatal screening on available resources at a single center.Data of prenatal screening and diagnostic procedures performed 4 months before the introduction of the program were compared with those of 12 months following the introduction.Between December 2008 and March 2010, 7689 women underwent first trimester screening, 1286 underwent amniocentesis and 398 underwent chorionic villus sampling. When a comparison was made between the 4 months before and the 12 months after the program's introduction, a greater number of nuchal translucency (NT) examinations was seen to have been performed (384 per month vs 513 per month, P=0.001). Prenatal diagnostic procedures did not increase, but a greater proportion was performed for positive screen results.Introduction of the California screening program was associated with increased NT procedures and fewer invasive procedures for advanced maternal age.

  View details for DOI 10.1038/jp.2012.8

  View details for Web of Science ID 000311831700002

  View details for PubMedID 22402484

• Erratum: Non-invasive prenatal measurement of the fetal genome. Nature Fan, H. C., Gu, W., Wang, J., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2012

  View details for DOI 10.1038/nature11423

  View details for PubMedID 22878723

• Non-invasive prenatal measurement of the fetal genome NATURE Fan, H. C., Gu, W., Wang, J., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2012; 487 (7407): 320-?

  Abstract

  The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.

  View details for DOI 10.1038/nature11251

  View details for Web of Science ID 000306506500033

  View details for PubMedID 22763444

  View details for PubMedCentralID PMC3561905

• Noninvasive prenatal diagnosis: pregnant women's interest and expected uptake PRENATAL DIAGNOSIS Tischler, R., Hudgins, L., Blumenfeld, Y. J., Greely, H. T., Ormond, K. E. 2011; 31 (13): 1292-1299

  Abstract

  To investigate pregnant women's level of future interest in noninvasive prenatal diagnosis (NIPD) and what factors might affect expected uptake of this testing.Written questionnaires were administered to women in their third trimester.One hundred fourteen women returned the questionnaire (80.9% response rate). Of these, 71.9% reported interest in NIPD, 22.7% were ambivalent, and 5.4% were uninterested. Safety of the fetus was the single most important factor in 75% of women's decisions. Factors associated with increased interest in NIPD included: older age (p = 0.036), higher education (p = 0.013), Caucasian or Asian ethnicity (p = 0.011), and higher likelihood to terminate an affected pregnancy (p = 0.002). Nearly 20% of women reported that they would do whatever their doctor recommended regarding NIPD, and 94.4% of women wished to meet with a genetic counselor at some point to discuss NIPD.The majority of pregnant women report hypothetical interest in NIPD, primarily because of increased safety for the fetus, although a significant minority are uninterested or ambivalent. Discussions with healthcare providers regarding NIPD, and their recommendations, are likely to be an important factor in women's decisions about this testing. As such, adequate discussion of the implications of prenatal diagnostic testing will be critical.

  View details for DOI 10.1002/pd.2888

  View details for Web of Science ID 000298566900013

  View details for PubMedID 22028097

  View details for PubMedCentralID PMC3225485

• Trends in Cesarean Delivery for Twin Births in the United States 1995-2008 OBSTETRICS AND GYNECOLOGY Lee, H. C., Gould, J. B., Boscardin, W. J., El-Sayed, Y. Y., Blumenfeld, Y. J. 2011; 118 (5): 1095-1101

  Abstract

  To estimate trends and risk factors for cesarean delivery for twins in the United States.This was a cross-sectional study in which we calculated cesarean delivery rates for twins from 1995 to 2008 using National Center for Health Statistics data. We compared cesarean delivery rates by year and for vertex compared with breech presentation. The order of presentation for a given twin pair could not be determined from the available records and therefore analysis was based on individual discrete twin data. Multivariable logistic regression was used to estimate independent risk factors, including year of birth and maternal factors, for cesarean delivery.Cesarean delivery rates for twin births increased steadily from 53.4% to 75.0% in 2008. Rates rose for the breech twin category (81.5%-92.1%) and the vertex twin category (45.1%-68.2%). The relative increase in the cesarean delivery rate for preterm and term neonates was similar. After risk adjustment, there was an average increase noted in cesarean delivery of 5% each year during the study period (risk ratio 1.05, 95% confidence interval 1.04-1.05).Cesarean delivery rates for twin births increased dramatically from 1995 to 2008. This increase is significantly higher than that which could be explained by an increase in cesarean delivery for breech presentation of either the presenting or second twin.

  View details for DOI 10.1097/AOG.0b013e3182318651

  View details for Web of Science ID 000296292600018

  View details for PubMedID 22015878

  View details for PubMedCentralID PMC3202294

• Sextuplet heterotopic pregnancy presenting as ovarian hyperstimulation syndrome and hemoperitoneum FERTILITY AND STERILITY Fisher, S. L., Massie, J. A., Blumenfeld, Y. J., Lathi, R. B. 2011; 95 (7)

  Abstract

  To describe a case of bilateral ruptured heterotopic pregnancies presenting as persistent ovarian hyperstimulation syndrome in a quadruplet pregnancy.Case report.University hospital and clinic.An infertile patient who conceived using gonadotropin therapy.Culdocentesis with resultant aspiration of sanguinous fluid prompted laparoscopic exploration and bilateral salpingectomies.Not applicable.Gross hemoperitoneum and ruptured bilateral heterotopic sextuplet pregnancy.Patients who conceive after gonadotropin therapy should be closely monitored during treatment and in early pregnancy to recognize and minimize morbidity and complications. After superovulation, the presence of an intrauterine pregnancy, either single or multiple, does not rule out the possibility of ectopic pregnancy, and this should always be considered as a possibility in the setting of acute anemia.

  View details for DOI 10.1016/j.fertnstert.2011.01.172

  View details for Web of Science ID 000290791000088

  View details for PubMedID 21406303

• Prenatal Diagnosis of Cross-Fused Renal Ectopia: Does Color Doppler and 3-Dimensional Sonography Help? JOURNAL OF ULTRASOUND IN MEDICINE Chang, P. L., Mrazek-Pugh, B., Blumenfeld, Y. J. 2011; 30 (4): 578-580

  View details for Web of Science ID 000291126800019

  View details for PubMedID 21460160

• MR imaging in cases of antenatal suspected appendicitis - a meta-analysis JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Blumenfeld, Y. J., Wong, A. E., Jafari, A., Barth, R. A., El-Sayed, Y. Y. 2011; 24 (3): 485-488

  Abstract

  Appendicitis is the most common surgical emergency in pregnancy. Acute appendicitis is often difficult to diagnose clinically, and concerns regarding antenatal CT imaging limit its use resulting in high false negative rates at laparotomy. MRI has recently been reported as a reasonable alternative to CT imaging in cases of suspected appendicitis. Our objective was to perform a meta-analysis of recently published data regarding the utility of MR imaging in cases of antenatal suspected acute appendicitis.We searched the PubMed database using keywords 'MRI', 'appendicitis', and 'pregnancy'. Five case series describing the role of MRI in cases of antenatal appendicitis were included. The sensitivity, specificity, positive, and negative predictive values were calculated.Two hundred twenty-nine patients were included in the study. In the first analysis in which non-diagnostic scans were excluded, the sensitivity, specificity, positive and negative predictive values of MRI for diagnosing appendicitis were 95.0%, 99.9%, 90.4%, and 99.5%, respectively. In the second analysis, which included non-diagnostic scans, the sensitivity, specificity, positive and negative predictive values were 90.5%, 98.6%, 86.3%, and 99.0%, respectivelyMR imaging may be useful in cases of suspected antenatal appendicitis. Data are still limited and larger prospective studies are necessary to confirm this finding.

  View details for DOI 10.3109/14767058.2010.506227

  View details for Web of Science ID 000286993000020

  View details for PubMedID 20695758

• Antenatal Steroid Administration for Premature Neonates in California OBSTETRICS AND GYNECOLOGY Lee, H. C., Lyndon, A., Blumenfeld, Y. J., Dudley, R. A., Gould, J. B. 2011; 117 (3): 603-609

  Abstract

  To estimate risk factors for premature neonates not receiving antenatal steroids in a population-based cohort and to determine whether the gains of a quality-improvement collaborative project on antenatal steroid administration were sustained long-term.Clinical data for premature neonates born in 2005–2007 were obtained from the California Perinatal Quality Care Collaborative, which collects data on more than 90% of neonatal admissions in California. Eligible neonates had a birth weight of less than 1,500 g or gestational age less than 34 weeks and were born at a Collaborative hospital. These data were linked to administrative data from California Vital Statistics. Sociodemographic and medical risk factors for not receiving antenatal steroids were determined. We also examined the effect of birth hospital participation in a previous quality-improvement collaborative project. A random effects logistic regression model was used to determine independent risk factors.Of 15,343 eligible neonates, 23.1% did not receive antenatal steroids in 2005–2007. Hispanic mothers (25.6%), mothers younger than age 20 (27.6%), and those without prenatal care (52.2%) were less likely to receive antenatal steroids. Mothers giving birth vaginally (26.8%) and mothers with a diagnosis of fetal distress (26.5%) were also less likely to receive antenatal steroids. Rupture of membranes before delivery and multiple gestations were associated with higher likelihood of antenatal steroid administration. Hospitals that participated in a quality-improvement collaborative in 1999– 2000 had higher rates of antenatal steroid administration (85% compared with 69%, P<.001).A number of eligible mothers do not receive antenatal steroids. Quality-improvement initiatives to improve antenatal steroid administration could target specific high-risk groups.

  View details for DOI 10.1097/AOG.0b013e31820c3c9b

  View details for Web of Science ID 000287649400013

  View details for PubMedID 21446208

  View details for PubMedCentralID PMC3072287

• Maternal-fetal and neonatal pharmacogenomics: a review of current literature JOURNAL OF PERINATOLOGY Blumenfeld, Y. J., Reynolds-May, M. F., Altman, R. B., El-Sayed, Y. Y. 2010; 30 (9): 571-579

  Abstract

  Pharmacogenomics, the study of specific genetic variations and their effect on drug response, will likely give rise to many applications in maternal-fetal and neonatal medicine; yet, an understanding of these applications in the field of obstetrics and gynecology and neonatal pediatrics is not widespread. This review describes the underpinnings of the field of pharmacogenomics and summarizes the current pharmacogenomic inquiries in relation to maternal-fetal medicine-including studies on various fetal and neonatal genetic cytochrome P450 (CYP) enzyme variants and their role in drug toxicities (for example, codeine metabolism, sepsis and selective serotonin reuptake inhibitor (SSRI) toxicity). Potential future directions, including alternative drug classification, improvements in drug efficacy and non-invasive pharmacogenomic testing, will also be explored.

  View details for DOI 10.1038/jp.2009.183

  View details for Web of Science ID 000281388500002

  View details for PubMedID 19924131

  View details for PubMedCentralID PMC3098749

• Analysis of the Size Distributions of Fetal and Maternal Cell-Free DNA by Paired-End Sequencing CLINICAL CHEMISTRY Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L., Quake, S. R. 2010; 56 (8): 1279-1286

  Abstract

  Noninvasive prenatal diagnosis with cell-free DNA in maternal plasma is challenging because only a small portion of the DNA sample is derived from the fetus. A few previous studies provided size-range estimates of maternal and fetal DNA, but direct measurement of the size distributions is difficult because of the small quantity of cell-free DNA.We used high-throughput paired-end sequencing to directly measure the size distributions of maternal and fetal DNA in cell-free maternal plasma collected from 3 typical diploid and 4 aneuploid male pregnancies. As a control, restriction fragments of lambda DNA were also sequenced.Cell-free DNA had a dominant peak at approximately 162 bp and a minor peak at approximately 340 bp. Chromosome Y sequences were rarely longer than 250 bp but were present in sizes of <150 bp at a larger proportion compared with the rest of the sequences. Selective analysis of the shortest fragments generally increased the fetal DNA fraction but did not necessarily increase the sensitivity of aneuploidy detection, owing to the reduction in the number of DNA molecules being counted. Restriction fragments of lambda DNA with sizes between 60 bp and 120 bp were preferentially sequenced, indicating that the shotgun sequencing work flow introduced a bias toward shorter fragments.Our results confirm that fetal DNA is shorter than maternal DNA. The enrichment of fetal DNA by size selection, however, may not provide a dramatic increase in sensitivity for assays that rely on length measurement in situ because of a trade-off between the fetal DNA fraction and the number of molecules being counted.

  View details for DOI 10.1373/clinchem.2010.144188

  View details for Web of Science ID 000280501400016

  View details for PubMedID 20558635

• Ultrasound estimation of fetal weight in small for gestational age pregnancies JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Blumenfeld, Y. J., Lee, H. C., Pullen, K. M., Wong, A. E., Pettit, K., Taslimi, M. M. 2010; 23 (8): 790-793

  Abstract

  Approximately half of small for gestational age (SGA) cases are due to maternal or fetal pathology, and may result in significant neonatal morbidity and mortality. The estimated fetal weight (EFW) measurement is the cornerstone of ultrasonographic findings when diagnosing and managing SGA pregnancies. Our objective was to determine the ultrasound accuracy of EFW in SGA pregnancies.A retrospective chart review was performed of all pregnancies complicated by SGA from a single institution (Stanford University) over a 2-year-period (2004-2006). SGA was defined as EFW < or = 10%. 98 neonates whose last ultrasound for EFW occurred within 7 days of delivery were included in the study. The absolute differences between the EFW and birthweight (BW) were analyzed, and the absolute percent errors were calculated as (EFW - BW)/BW x 100. The mean absolute differences and mean absolute percent errors were analyzed across all gestational ages (GA) and EFWs using one-way analysis of variance.The mean absolute percent error for the entire cohort was 8.7% (+/-6.3%). There was no statistically significant difference in the mean absolute percent error across all GAs (<32 weeks, 32-36 weeks, >36 weeks), and EFWs (<1500 g, 1500-2000 g, >2000 g).Ultrasound measurement of EFW in SGA pregnancies is consistent across all GAs and EFW measurements.

  View details for DOI 10.3109/14767050903387052

  View details for Web of Science ID 000280592200006

  View details for PubMedID 19968588

• Single- versus double-layer hysterotomy closure at primary caesarean delivery and bladder adhesions BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY Blumenfeld, Y. J., Caughey, A. B., El-Sayed, Y. Y., Daniels, K., Lyell, D. J. 2010; 117 (6): 690-694

  Abstract

  To determine the association between single-layer (one running suture) and double-layer (second layer or imbricating suture) hysterotomy closure at primary caesarean delivery and subsequent adhesion formation.A secondary analysis from a prospective cohort study of women undergoing first repeat caesarean section.Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.One hundred and twenty-seven pregnant women undergoing first repeat caesarean section.Patient records were reviewed to identify whether primary caesarean hysterotomies were closed with a single or double layer. Data were analysed by Fisher's exact tests and multivariable logistic regression.Prevalence rate of pelvic and abdominal adhesions.Of the 127 women, primary hysterotomy closure was single layer in 56 and double layer in 71. Single-layer hysterotomy closure was associated with bladder adhesions at the time of repeat caesarean (24% versus 7%, P = 0.01). Single-layer closure was associated in this study with a seven-fold increase in the odds of developing bladder adhesions (odds ratio, 6.96; 95% confidence interval, 1.72-28.1), regardless of other surgical techniques, previous labour, infection and age over 35 years. There was no association between single-layer closure and other pelvic or abdominal adhesions.Primary single-layer hysterotomy closure may be associated with more frequent bladder adhesions during repeat caesarean deliveries. The severity and clinical implications of these adhesions should be assessed in large prospective trials.

  View details for DOI 10.1111/j.1471-0528.2010.02529.x

  View details for Web of Science ID 000276509100007

  View details for PubMedID 20236104

• The Effects of Respiratory Failure on Delivery in Pregnant Patients With H1N1 2009 Influenza OBSTETRICS AND GYNECOLOGY Jafari, A., Langen, E. S., Aziz, N., Blumenfeld, Y. J., Mihm, F., Druzin, M. L. 2010; 115 (5): 1033-1035

  Abstract

  The majority of hospitalizations for H1N1 complications have been in people with high-risk comorbidities, including pregnancy. Here we describe the obstetric and critical care treatment of three patients with confirmed H1N1 influenza virus infection complicated by acute respiratory failure.We describe the clinical and therapeutic courses of three patients with confirmed H1N1 2009 influenza virus infection complicating singleton, twin, and triplet gestations, each of which were complicated by respiratory failure.These three cases illustrate that a high index of suspicion, prompt treatment, timing and mode of delivery considerations, and interdisciplinary treatment are integral to the care of pregnant patients with H1N1 influenza infections complicated by acute respiratory failure.

  View details for DOI 10.1097/AOG.0b013e3181da85fc

  View details for PubMedID 20410779

• Chorionic villus sampling: technique and training CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Blumenfeld, Y. J., Chueh, J. 2010; 22 (2): 146-151

  Abstract

  Over the past decade, first trimester screening has become the gold standard prenatal screening modality in the developed world. This shift toward earlier screening would not be possible without the availability of early diagnosis, namely, chorionic villus sampling (CVS). The purpose of this review is to highlight recent updates related to CVS technique, potential complications, and training.Recent data highlight the importance of operator experience in reducing CVS-related complications and argues for the 'centralization' of CVS in experienced centers. On the other hand, despite over 30 years of clinical practice, there is still no consensus regarding optimal CVS technique and some variation exists between CVS providers. Moreover, there is a deficiency in adequate infrastructure geared toward the training and certification of future CVS providers.CVS is the gold standard method of first trimester prenatal diagnosis. Recent data suggest that CVS loss rates are lower than what was previously reported and are lowest in centers that perform a large number of procedures. The 'centralization' of this specialized procedure also offers the perfect opportunity for the safe, ongoing training of future CVS providers.

  View details for DOI 10.1097/GCO.0b013e3283372365

  View details for Web of Science ID 000276562900010

  View details for PubMedID 20154617

• Prematurity prevention: the role of acute tocolysis CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Blumenfeld, Y. J., Lyell, D. J. 2009; 21 (2): 136-141

  Abstract

  The preterm birth rate in the United States remains at an all-time high and continues to rise. Acute tocolysis has potential to delay preterm birth for 48 h, the critical period of antenatal steroid administration, or to arrest an episode of preterm labor, thus delaying birth and improving neonatal outcomes. It is therefore paramount that medical providers remain up-to-date regarding the usefulness, indications and contraindications, and side-effects and adverse effects of all tocolytics.Magnesium sulfate remains the most common tocolyic agent in the United States. Recent evidence comparing oral nifedipine with magnesium sulfate suggests equal efficacy with fewer maternal side-effects, thus supporting this oral medication as first-line treatment. This review will summarize the most common acute tocolytic drugs, their methods of action, and clinical data regarding their utility.All tocolytic medications have side-effects, some of them potentially life-threatening. Decisions regarding whether to use a tocolytic and which tocolytic to use require the diagnosis of preterm labor, knowledge of the patient's gestational age, medical conditions, and cost. Once tocolysis is initiated, attention must be paid to the patient's response, side-effects, and adverse events. Larger studies are needed which incorporate, in addition to efficacy, data on safety and side-effect profiles and cost.

  View details for DOI 10.1097/GCO.0b013e3283292455

  View details for Web of Science ID 000265320800006

  View details for PubMedID 19996866

• Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L., Quake, S. R. 2008; 105 (42): 16266-16271

  Abstract

  We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.

  View details for DOI 10.1073/pnas.0808319105

  View details for Web of Science ID 000260597400037

  View details for PubMedID 18838674

  View details for PubMedCentralID PMC2562413

• Uterine exteriorization compared with in situ repair at cesarean delivery: A randomized controlled trial OBSTETRICS AND GYNECOLOGY Blumenfeld, Y., Caughey, A. B., Lyell, D. J. 2008; 112 (1): 183-183

  View details for Web of Science ID 000257279600027

  View details for PubMedID 18591325

• Single- versus double-layer uterine incision closure and uterine rupture JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Gyamfi, C., Juhasz, G., Gyamfi, P., Blumenfeld, Y., Stone, J. L. 2006; 19 (10): 639-643

  Abstract

  To evaluate whether closure of the uterine incision with one or two layers changes uterine rupture or vaginal birth after cesarean section (VBAC) success rates.Subjects with one previous cesarean section by documented transverse uterine incision that attempted VBAC were identified. Exclusion criteria included lack of documentation of the type of closure of the previous uterine incision, multiple gestation, more than one previous cesarean section, and previous scar other than low transverse. Uterine rupture and VBAC success rates were compared between those with single-layer and double-layer uterine closure. Time interval between deliveries, birth weight, body mass index (BMI), and history of previous VBAC were evaluated as possible confounders.Of 948 subjects identified, 913 had double-layer closure and 35 had single-layer closure. The uterine rupture rate was significantly higher in the single-layer closure group (8.6% vs. 1.3%, p = 0.015). This finding persisted when controlling for previous VBAC, induction, birth weight >4000 g, delivery interval >19 months, and BMI >29 (OR 8.01, 95% CI 1.96-32.79). There was no difference in VBAC success rate (74.3% vs. 77%, p = 0.685).Single-layer uterine closure may be more likely to result in uterine rupture.

  View details for DOI 10.1080/14767050600849383

  View details for Web of Science ID 000242992000007

  View details for PubMedID 17118738

• Fetal urinoma as a sign of a dysplastic kidney PEDIATRIC NEPHROLOGY Miller, M., Korzets, Z., Blumenfeld, Y., Pomeranz, M., Aviram, R., Rathaus, V., Pomeranz, A. 2003; 18 (1): 65-67

  Abstract

  We describe a female neonate in whom a urinoma was first diagnosed at 20 weeks of gestation without any evidence of underlying urinary tract obstruction. The urinoma became apparent following the performance of a "bloody tap" amniocentesis. Sequential ultrasonography, both fetal and up to 3 months after birth, showed eventual resorption of the urinoma in parallel with the development of a shrunken, non-functioning kidney. Except for the onset of high-renin hypertension, which spontaneously remitted at 1 year of age, the baby's postnatal course was uneventful. Renal function was normal. The presence of a fetal urinoma as a sign of a dysplastic kidney is discussed.

  View details for DOI 10.1007/s00467-002-0862-x

  View details for Web of Science ID 000180591500014

  View details for PubMedID 12488994