Bio


Over 17 years of experience in the medical science field including Director of Research, Clinical Researcher, and Primary Care Physician positions. Track record of success in team building and leadership. Experience on conduct and oversight of a wide array of research studies from basic and translational science to population-based studies and randomized controlled trials.

Current Role at Stanford


Leads the basic, translational and clinical research functions across the department including oversight of over 50 research staff members.

Education & Certifications


  • MD, PhD, UNIVERSITY OF OULU, FINLAND, Medical Science Dissertation: Preeclampsia and maternal type-1 diabetes: new insights into maternal and fetal pathophysiology (2009)

All Publications


  • Early postpartum hospital encounters among patients with genitourinary and wound infections during hospitalization for birth. American journal of perinatology Leonard, S. A., Girsen, A., Trepman, P., Carmichael, S. L., Darmawan, K., Butwick, A., Gibbs, R. 2023

    Abstract

    To assess the associations between genitourinary and wound infections during the birth hospitalization and early postpartum hospital encounters, and to evaluate clinical risk factors for early postpartum hospital encounters among patients with a genitourinary or wound infection during the birth hospitalization.We conducted a population-based cohort study of births in California during 2016-2018 and postpartum hospital encounters. We identified genitourinary and wound infections using diagnosis codes. Our main outcome was early postpartum hospital encounter, defined as a readmission or ED visit within 3 days after discharge from the birth hospitalization. We evaluated the association of genitourinary and wound infections (overall and subtypes) with early postpartum hospital encounter using logistic regression, adjusting for sociodemographic factors and comorbidities and stratified by mode of birth. We then evaluated factors associated with early postpartum hospital encounter among patients with genitourinary and wound infections.Among 1,217,803 birth hospitalizations, 5.5% were complicated by genitourinary and wound infections and 1.8% resulted in an early postpartum hospital encounter. Genitourinary or wound infection was associated with an early postpartum hospital encounter among patients with both vaginal births (aRR 1.26, 95% CI 1.17, 1.36) and cesarean births (aRR 1.23, 95% CI 1.15, 1.32). Major puerperal infection, followed by wound infection, among patients with a cesarean birth conferred the highest risk of an early postpartum hospital encounter (6.4% and 4.3%, respectively). Among patients with genitourinary and wound infections at birth hospitalization, factors associated with an early postpartum hospital encounter included severe maternal morbidity, major mental health condition, prolonged postpartum hospital stay, and, among cesarean births, postpartum hemorrhage (P-value < 0.05).Genitourinary and wound infections during hospitalization for birth may increase risk of a readmission or ED visit within the first few days after discharge, particularly among patients who have a major puerperal infection or wound infection.

    View details for DOI 10.1055/a-2097-1584

    View details for PubMedID 37216972

  • Vaginal Progesterone is Associated with Intrahepatic Cholestasis of Pregnancy. American journal of perinatology Tsur, A., Leonard, S. A., Kan, P., Datoc, I., Girsen, A., Shaw, G. M., Stevenson, D. K., El-Sayed, Y. Y., Druzin, M. L., Blumenfeld, Y. J. 2023

    Abstract

    Background The frequency of intrahepatic cholestasis of pregnancy peaks during the third trimester of pregnancy when plasma progesterone levels are highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons, and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Objectives Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17alpha-hydroxyprogesterone caproate for the prevention of preterm birth. Study design We identified 1,776,092 live-born singleton pregnancies between 2010-2014. We confirmed 2nd and 3rd trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events, or progesterone treatment prescribed only during the 1st trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17alpha-hydroxyprogesterone caproate compared to those not treated with any type of progestogen (the reference group). Results The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the 2nd and 3rd trimester, the frequency of cholestasis was significantly higher than the reference group (0.75% vs 0.23%, aOR 3.16, 95% CI 2.23-4.49). In contrast, there was no significant association between 17alpha-hydroxyprogesterone caproate and cholestasis (0.27%, aOR 1.12, 95% CI 0.58-2.16) Conclusions Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17alpha-hydroxyprogesterone caproate was associated with an increased risk for intrahepatic cholestasis of pregnancy.

    View details for DOI 10.1055/a-2081-2573

    View details for PubMedID 37100422

  • Increased rates of postpartum emergency department visits and inpatient readmissions in people with epilepsy Darmawan, K. F., Leonard, S. A., Meador, K., McElrath, T. F., Carmichael, S. L., Lyell, D. J., El-Sayed, Y. Y., Herrero, T., Druzin, M. L., Panelli, D. M. MOSBY-ELSEVIER. 2023: S163
  • Postpartum care visits among commercially insured women in the United States. AJOG global reports Butwick, A. J., Bentley, J., Daw, J., Sultan, P., Girsen, A., Gibbs, R. S., Guo, N. 2022; 2 (4): 100106

    Abstract

    To reduce postpartum morbidity and mortality, optimizing routine outpatient postpartum care has become a focus of national attention and a healthcare priority.This study aimed to examine the timing, content, and predictors of routine outpatient postpartum visit attendance within a large, commercially insured patient population.We performed a retrospective cohort study using a national US database of commercial insurance beneficiaries with a delivery hospitalization between 2011 and 2015. We calculated the proportion of patients who had an outpatient postpartum visit within 8 weeks of hospital discharge. Using a multivariable logistic regression model, we identified independent predictors of an outpatient postpartum visit. To gain insight into the nature and extent of any postpartum medical or surgical morbidity, we also identified the most frequent International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with postpartum visits.The study cohort comprised 431,969 patients who underwent delivery hospitalization, of whom 257,727 (59.7%; 95% confidence interval, 59.5-59.8) had at least 1 outpatient postpartum visit within 8 weeks of hospital discharge. The distribution of postpartum visits was bimodal, occurring most frequently in the first week (23.2%) and sixth week (21.7%) after hospital discharge. The median period between hospital discharge and the postpartum visit was 28 days (interquartile range, 8-41 days). In our multivariable model, patient-level factors that were most strongly associated with a postpartum visit were preexisting medical morbidities, which included: thyroid disease (adjusted odds ratio, 1.62; 95% confidence interval, 1.40-1.52), seizure disorder (adjusted odds ratio, 1.50; 95% confidence interval, 1.33-1.70), chronic hypertension (adjusted odds ratio, 1.46; 95% confidence interval, 1.58-1.67), and psychiatric disease (adjusted odds ratio, 1.41; 95% confidence interval, 1.36-1.47). Between 29% and 42% of patients with preexisting medical morbidity and between 35% and 41% of patients who experienced peri- or postpartum complications did not attend a postpartum visit.Our findings indicate that among a large, commercially-insured patient population, postpartum visit attendance was suboptimal. A high proportion with preexisting medical and peripartum morbidities was not evaluated within 8 weeks of hospital discharge. Multifaceted interventions and healthcare reform are suggested to address patients' concerns and healthcare needs after delivery.

    View details for DOI 10.1016/j.xagr.2022.100106

    View details for PubMedID 36275400

    View details for PubMedCentralID PMC9563203

  • Addressing postpartum contraception practices utilizing a multidisciplinary Pregnancy Heart Team approach. AJOG global reports Miller, H. E., Do, S. C., Cruz, G., Panelli, D. M., Leonard, S. A., Girsen, A., Lee, C. J., Khandelwal, A., Shaw, K. A., Bianco, K. 2022; 2 (4): 100100

    Abstract

    BACKGROUND: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital.OBJECTIVE: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease.STUDY DESIGN: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum.RESULTS: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum.Compared with the cardiac cohort, by 8 weeks postpartum,the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49-1.17).The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38-0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4-0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35-0.71).CONCLUSION: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease.

    View details for DOI 10.1016/j.xagr.2022.100100

    View details for PubMedID 36536840

  • Early postpartum readmissions: identifying risk factors at birth hospitalization. AJOG global reports Girsen, A. I., Leonard, S. A., Butwick, A. J., Joudi, N., Carmichael, S. L., Gibbs, R. S. 2022; 2 (4): 100094

    Abstract

    BACKGROUND: The high maternal mortality and severe morbidity rates in the United States compared with other high-income countries have received national attention. Characterization of postpartum hospital readmissions within the first days after delivery hospitalization discharge could help to identify patients who need additional preparedness for discharge.OBJECTIVE: This study aimed to investigate conditions at birth associated with postpartum readmissions occurring within 0 to 6 days and at 7 to 29 days after discharge from the delivery hospitalization.STUDY DESIGN: We analyzed linked vital statistics and hospital discharge records of patients who gave birth in California during 2007 to 2018. We investigated hospital readmissions within 30 days after birth hospitalization discharge. We used multivariable logistic regression to investigate factors associated with early readmission (0-6 days) and later readmission (7-29 days) compared with no readmission within 30 days (reference). The risk factors assessed included maternal medical or obstetrical conditions before and at birth, birth hospitalization length of stay, and mode of delivery. Severe maternal morbidity was defined as the presence of any of the 21 indicators recommended by the Centers for Disease Control and Prevention.RESULTS: Among 5,248,746 pregnant patients, 23,636 (0.45%) had an early postpartum readmission, whereas 24,712 (0.47%) had a later postpartum readmission. After adjustments, early readmission was most strongly associated with sepsis (adjusted odds ratio, 4.63; 95% confidence interval, 3.87-5.53), severe maternal morbidity (adjusted odds ratio, 3.46; 95% confidence interval, 3.28-3.65) at birth hospitalization, or preeclampsia before birth hospitalization (adjusted odds ratio, 3.67; 95% confidence interval, 3.54-3.81). The associations between later readmission and sepsis and severe maternal morbidity were similar, whereas the association between preeclampsia and later readmission was less strong (adjusted odds ratio, 1.65; 95% confidence interval, 1.57-1.73).CONCLUSION: Pregnant patients with sepsis or severe maternal morbidity during delivery hospitalization or preeclampsia before birth hospitalization were at the highest risk for readmission within 6 days of discharge. These findings may be informative for efforts to improve postpartum care.

    View details for DOI 10.1016/j.xagr.2022.100094

    View details for PubMedID 36536841

  • Effect of gestational age at first delivery and interpregnancy interval on the recurrence of clinical chorioamnionitis. AJOG global reports Sperling, M. M., Sie, L., Leonard, S. A., Girsen, A. I., Lee, H. C., Gibbs, R. S. 2022; 2 (4): 100116

    Abstract

    There is an increased odds of having a recurrence of clinical chorioamnionitis in patients with a diagnosis of clinical chorioamnionitis compared with those without clinical chorioamnionitis in a previous pregnancy. However, it is unclear how gestational age at delivery of the first pregnancy or interpregnancy interval may contribute to this increased risk.This study aimed to evaluate how gestational age of delivery in a first pregnancy and interpregnancy interval affect the odds of recurrent clinical chorioamnionitis.Using maternally linked birth record files, Nulliparous patients from California with at least 2 consecutive deliveries between the gestational ages of 20 and 44 weeks from 2007 to 2012 were identified. The rates of clinical chorioamnionitis in the second pregnancy for patients with clinical chorioamnionitis vs those without clinical chorioamnionitis in the first pregnancy, stratified by the gestational age at delivery of the first pregnancy were determined. As a secondary analysis, the analysis by interpregnancy interval (<18 months vs ≥18 months) was stratified. Corresponding crude and adjusted odds ratios for each stratum were calculated to assess the association of clinical chorioamnionitis in the first and second pregnancies.Among 31,571 nulliparous patients with clinical chorioamnionitis in the first pregnancy, the frequency of clinical chorioamnionitis in the next pregnancy was 4.0% (1257 cases). This was in comparison with the 1.0% (9177 of 896,154) of nulliparous patients without clinical chorioamnionitis in the first pregnancy who were diagnosed with clinical chorioamnionitis in the next pregnancy (adjusted odds ratio, 2.78; 95% confidence interval, 2.61-2.96). The absolute frequency of recurrence was the highest (54 cases [8.2%]) in those who delivered at 20 to 24 weeks of gestation in the first pregnancy with the diagnosis of clinical chorioamnionitis (adjusted odds ratio, 1.76; 95% confidence interval, 1.25-2.48). For pregnancies delivered at term in the first pregnancy, the frequency of clinical chorioamnionitis in the next pregnancy was higher in those diagnosed with clinical chorioamnionitis in the first pregnancy than in those without clinical chorioamnionitis in the first pregnancy (4.0% vs 1.0%; adjusted odds ratio, 2.85; 95% confidence interval, 2.66-3.05). An interpregnancy interval of <18 months was not associated with increased odds of recurrent clinical chorioamnionitis.The odds of recurrence of clinical chorioamnionitis were the strongest when a patient delivered in the term to postterm period in the first pregnancy, with the absolute risk being the highest when the first pregnancy was delivered in the periviable period (20-24 weeks of gestation). The interpregnancy interval did not seem to modify the risk of recurrent clinical chorioamnionitis.

    View details for DOI 10.1016/j.xagr.2022.100116

    View details for PubMedID 36316994

    View details for PubMedCentralID PMC9617201

  • Postpartum Readmission for Hypertension After Discharge on Labetalol or Nifedipine. Obstetrics and gynecology Do, S. C., Leonard, S. A., Kan, P., Panelli, D. M., Girsen, A. I., Lyell, D. J., El-Sayed, Y. Y., Druzin, M. L., Herrero, T. 2022

    Abstract

    To assess whether readmission for hypertension by 6 weeks postpartum differed between patients discharged on nifedipine or labetalol.This cohort study included patients with delivery admissions from 2006 to 2017 who were discharged from the hospital on nifedipine or labetalol and were included in a large, national adjudicated claims database. We identified patients' discharge medication based on filled outpatient prescriptions. We compared rates of hospital readmission for hypertension between patients discharged postpartum on labetalol alone, nifedipine alone, or combined nifedipine and labetalol. Patients with chronic hypertension without superimposed preeclampsia were excluded. Comparisons based on medication were performed using logistic regression models with adjustment for prespecified confounders. Comparisons were also stratified by hypertensive disorder of pregnancy severity.Among 1,582,335 patients overall, 14,112 (0.89%) were discharged postpartum on labetalol, 9,001 (0.57%) on nifedipine, and 1,364 (0.09%) on both medications. Postpartum readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine (641 patients vs 185 patients, 4.5% vs 2.1%, adjusted odds ratio [aOR] 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine for both mild (4.5% vs 2.7%, aOR 1.57, 95% CI 1.29-1.93) and severe hypertensive disorders of pregnancy (261 patients vs 72 patients, 5.7% vs 3.2%, aOR 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent on combined nifedipine and labetalol compared with nifedipine (3.1% vs 2.1%), but the odds were lower after confounder adjustment (aOR 0.80, 95% CI 0.64-0.99).Postpartum discharge on labetalol was associated with increased risk of readmission for hypertension compared with discharge on nifedipine.

    View details for DOI 10.1097/AOG.0000000000004918

    View details for PubMedID 36075068

  • Using Longitudinally Linked Data to Measure Severe Maternal Morbidity Beyond the Birth Hospitalization in California. Obstetrics and gynecology Carmichael, S. L., Girsen, A. I., Ma, C., Main, E. K., Gibbs, R. S. 2022

    Abstract

    Most studies of severe maternal morbidity (SMM) include only cases that occur during birth hospitalizations. We examined the increase in cases when including SMM during antenatal and postpartum (within 42 days of discharge) hospitalizations, using longitudinally linked data from 1,010,250 births in California from September 1, 2016, to December 31, 2018. For total SMM, expanding the definition resulted in 22.8% more cases; for nontransfusion SMM, 45.1% more cases were added. Sepsis accounted for 55.5% of the additional cases. The increase varied for specific indicators, for example, less than 2% for amniotic fluid embolism, 7.0% for transfusion, 112.9% for sepsis, and 155.6% for acute myocardial infarction. These findings reiterate the importance of considering SMM beyond just the birth hospitalization and facilitating access to longitudinally linked data to facilitate a more complete understanding of SMM.

    View details for DOI 10.1097/AOG.0000000000004902

    View details for PubMedID 35926198

  • Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress. BMC pregnancy and childbirth Panelli, D. M., Leonard, S. A., Wong, R. J., Becker, M., Mayo, J. A., Wu, E., Girsen, A. I., Gotlib, I. H., Aghaeepour, N., Druzin, M. L., Shaw, G. M., Stevenson, D. K., Bianco, K. 2022; 22 (1): 381

    Abstract

    Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

    View details for DOI 10.1186/s12884-022-04693-0

    View details for PubMedID 35501726

  • Treatment for Mild Chronic Hypertension during Pregnancy. The New England journal of medicine Tita, A. T., Szychowski, J. M., Boggess, K., Dugoff, L., Sibai, B., Lawrence, K., Hughes, B. L., Bell, J., Aagaard, K., Edwards, R. K., Gibson, K., Haas, D. M., Plante, L., Metz, T., Casey, B., Esplin, S., Longo, S., Hoffman, M., Saade, G. R., Hoppe, K. K., Foroutan, J., Tuuli, M., Owens, M. Y., Simhan, H. N., Frey, H., Rosen, T., Palatnik, A., Baker, S., August, P., Reddy, U. M., Kinzler, W., Su, E., Krishna, I., Nguyen, N., Norton, M. E., Skupski, D., El-Sayed, Y. Y., Ogunyemi, D., Galis, Z. S., Harper, L., Ambalavanan, N., Geller, N. L., Oparil, S., Cutter, G. R., Andrews, W. W., Chronic Hypertension and Pregnancy (CHAP) Trial Consortium 2022

    Abstract

    BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth.METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth.RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 0.82 to 1.31; P=0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99).CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

    View details for DOI 10.1056/NEJMoa2201295

    View details for PubMedID 35363951

  • Hospital Readmissions after Postpartum Emergency Department Visit Girsen, A., Leonard, S. A., Carmichael, S. L., Gibbs, R. S., Butwick, A. MOSBY-ELSEVIER. 2022: S517-S518
  • Homelessness in pregnancy: perinatal outcomes. Journal of perinatology : official journal of the California Perinatal Association St Martin, B. S., Spiegel, A. M., Sie, L., Leonard, S. A., Seidman, D., Girsen, A. I., Shaw, G. M., El-Sayed, Y. Y. 2021

    Abstract

    OBJECTIVE: Investigate the association between maternal homelessness at the time of delivery and perinatal outcomes, with a focus on neonatal health outcomes.STUDY DESIGN: Population-based cohort using California's statewide database included 1,520,253 women with linked birth and maternal discharge data, 2008-2012. Multivariable analysis assessed homelessness at time of delivery on perinatal outcomes, preterm delivery, and neonatal intensive care unit admission.RESULT: A total of 672 women (0.05%) were homeless at the time of delivery. Homelessness was associated with premature delivery at multiple gestational age cutoffs (34w0d-36w6d; 32w0d-33w6d; 28w0d-31w6d; <28w0d) (range of aORs:1.62-2.19), and neonatal intensive care unit admission (aOR=1.66, 95% CI:1.31-2.09). Among term infants, homelessness remained associated with increased odds of neonatal intensive care unit admission (aOR=1.84, 95% CI:1.34-2.53), low birthweight (aOR=1.99, 95% CI:1.36-2.90), neonatal abstinence syndrome (aOR=2.13, 95% CI:1.35-2.53), hypoxic-ischemic encephalopathy (aOR=14.38, 95% CI:3.90-53.01), and necrotizing enterocolitis (aOR=14.94, 95% CI:2.68-83.20).CONCLUSION: Homelessness in pregnancy was associated with adverse perinatal outcomes including increased odds of preterm delivery across all gestational ages, and increased risk of neonatal intensive care unit admission and low birth weight independent of preterm delivery.

    View details for DOI 10.1038/s41372-021-01187-3

    View details for PubMedID 34404925

  • Novel Approaches to Develop Critical Reference Materials for Noninvasive Prenatal Testing: A Pilot Study. The journal of applied laboratory medicine Bianco, K., Sherwin, E. B., Konigshofer, Y., Girsen, A. I., Sylvester, K. G., Garlick, R. K. 2021

    Abstract

    BACKGROUND: Highly characterized reference materials are required to expand noninvasive prenatal testing (NIPT) for low incidence aneuploidies and microdeletions. The goal of this study was to develop reference materials for the development of next generation circulating cell-free DNA (ccfDNA) assays.METHODS: This was a prospective study of pregnancies complicated by positive prenatal genetic screening. ccfDNA was isolated from maternal plasma and amplified. Lymphoblastoid cell lines were prepared from maternal peripheral blood mononuclear cells and fetal cord blood cells. Cells were Epstein-Barr virus immortalized and expanded. Amplified DNA and to a limited extent formulated lymphoblastoid-derived ccfDNA was tested in SNP-based and chromosome counting (CC) based massively parallel sequencing assays.RESULTS: Enrolled cases included fetuses with: T21 (2), T18 (1), T18-XXX (1), XYY (1), microdeletions (1), and euploid (2). Three lymphoblastoid cells lines were prepared. Genomic DNA was extracted from cell lines and fragmented to simulate ccfDNA. ccfDNA isolation yielded about 2000 usable genome equivalents of DNA for each case for amplification. Although the sonicated genomic DNA derived from lymphoblastoid cell lines did not yield results compatible with NIPT assays, when blinded, NIPT platforms correctly identified the amplified ccfDNA isolated from blood in the majority of cases.CONCLUSIONS: This study showed that maternal blood samples from pregnancies complicated by common chromosomal abnormalities can be used to generate materials for the development and evaluation of NIPT assays.

    View details for DOI 10.1093/jalm/jfab037

    View details for PubMedID 34080621

  • 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

  • Risk Factors for Postpartum Readmission Among Women After Having a Stillbirth. American journal of obstetrics & gynecology MFM DiTosto, J. D., Liu, C., Wall-Wieler, E., Gibbs, R. S., Girsen, A. I., El-Sayed, Y. Y., Butwick, A. J., Carmichael, S. L. 2021: 100345

    Abstract

    BACKGROUND: Compared to women with a livebirth, women with a stillbirth are more likely to have maternal complications during pregnancy and at birth, but risk factors related to their postpartum health are uncertain.OBJECTIVE: This study aimed to identify patient-level risk factors for postpartum hospital readmission among women after having a stillbirth.STUDY DESIGN: This is a population-based cohort study of 29,654 women with a stillbirth in California from 1997-2011. Using logistic regression models, we examined the association of maternal patient-level factors with postpartum readmission among women after a stillbirth within six weeks of hospital discharge and between six weeks and nine months after birth.RESULTS: Within six weeks after a stillbirth, 642 (2.2%) women had a postpartum readmission. Risk factors for postpartum readmission after a stillbirth were: severe maternal morbidity excluding transfusion (aOR= 3.02, 95% CI 2.28-4.00), transfusion at delivery but no other indication of severe maternal morbidity (aOR= 1.95, 95% CI 1.35-2.81), gestational hypertension or preeclampsia (aOR=1.93, 95% CI 1.54-2.42), pre-pregnancy hypertension (aOR= 1.80, 95% CI 1.36-2.37), diabetes (aOR= 1.78, 95% CI = 1.33-2.37), an antenatal hospitalization (aOR= 1.78, 95% CI 1.43-2.21), cesarean birth (aOR= 1.73, 95% CI 1.43-2.21), long (> 2 days for vaginal birth, > 4 days for cesarean birth) birth hospitalization length of stay (aOR= 1.59, 95% CI 1.33-1.89), non- Hispanic black race/ ethnicity (aOR= 1.38, 95% CI 1.08-1.76), and having less than a high school education (aOR= 1.35, 95% CI 1.02-1.80). From 6 weeks to 9 months, 1,169 (3.90%) women had a postpartum readmission; significantly associated risk factors were largely similar to those for earlier readmission.CONCLUSION: Women with comorbidities, birth-related complications, of non-Hispanic black race/ ethnicity, or with less education had increased odds of postpartum readmission after having a stillbirth, highlighting the importance of continued care for these women after birth hospitalization.TRIAL REGISTRATION: Not applicable.

    View details for DOI 10.1016/j.ajogmf.2021.100345

    View details for PubMedID 33705999

  • Perceived stress and spontaneous preterm birth in twin gestations Blumenfeld, Y. J., Leonard, S. A., Wilson, H. W., Girsen, A., Datoc, I., Lyell, D. J. MOSBY-ELSEVIER. 2021: S418–S419
  • Severe maternal and neonatal morbidity after attempted operative vaginal delivery. American journal of obstetrics & gynecology MFM Panelli, D. M., Leonard, S. A., Joudi, N. n., Girsen, A. I., Judy, A. E., El-Sayed, Y. Y., Gilbert, W. M., Lyell, D. J. 2021: 100339

    Abstract

    Operative vaginal delivery (OVD) is a critical tool in reducing primary cesarean birth, but declining OVD rates and concerns about provider skill necessitate a clear understanding of risks. These risks are ambiguous because most studies compare outcomes with OVD to spontaneous vaginal delivery, rather than to second stage cesarean which is usually the realistic alternative.Our objective was to compare severe maternal and neonatal morbidity by mode of delivery among patients with a prolonged second stage of labor who had a successful OVD, a cesarean birth after failed OVD, or a cesarean birth without an OVD attempt.We used a population-based database to evaluate nulliparous, term, singleton, vertex livebirths in California between 2007 and 2012 among patients with a prolonged second stage of labor. Birth certificate and ICD-9-CM coded diagnoses and procedures were used for ascertainment of exposure, outcome, and demographics. Exposure was mode of delivery among patients who had any OVD attempt versus cesarean without OVD attempt. The outcomes were severe maternal morbidity (SMM) and severe unexpected newborn morbidity (UNM), defined using established indices. Anticipating that the code for prolonged second stage of labor would represent only a fraction of true OVD candidates, a secondary analysis was conducted removing this restriction in order to explore granular outcomes in a larger cohort with unsuccessful labor. Multivariable logistic regression was used to compare outcomes by mode of delivery adjusted for measured confounders. Sensitivity analyses were done excluding patients with combined vacuum-forceps and birthweight >4000g.9,239 prolonged second stage births were included; 6,851 (74.1%) were successful OVDs, 301 (3.3%) were failed OVDs, and 2,087 (22.6%) were cesareans without OVD attempts. Of successful OVDs, 6,195 (90.4%) were vacuums and 656 (10.6%) were forceps. Of failed OVDs where OVD type was specified, 83 (47.4%) were vacuums, 38 (21.7%) were forceps, and 54 (30.9%) were combined vacuum-forceps. Of note, all 54 combined vacuum-forceps OVD attempts that we identified failed. Patients with failed OVD differed from those with successful OVD, with higher rates of comorbidities, use of combined OVD, and birthweight >4000 g. Successful OVD was associated with reduced SMM (aOR 0.55, 95% CI 0.39-0.78) without a difference in severe UNM (aOR 0.99, 95% CI 0.78-1.26). In contrast, failed OVD was associated with increased SMM (aOR 2.14, 95% CI 1.20-3.82) and severe UNM (aOR 1.78, 95% CI 1.09-2.86). Findings were similar in secondary analysis of 260,585 patients with unsuccessful labor.In this large cohort of nulliparous, term, singleton, vertex births, successful OVD was associated with a 45% reduction in SMM without differences in severe UNM when compared to cesarean birth after prolonged second stage of labor. OVD failed infrequently, but when it did it was associated with a 214% increase in SMM and a 78% increase in severe UNM; combined OVDs were major contributors to this, since all combined OVDs failed. Optimization of OVD success rates through means such as improved patient selection, enhanced provider skill, and dissuasion against combined OVD could reduce maternal and neonatal complications.

    View details for DOI 10.1016/j.ajogmf.2021.100339

    View details for PubMedID 33631384

  • 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

  • Lactate and Procalcitonin Levels in Peripartum Women with Intraamniotic Infection. American journal of obstetrics & gynecology MFM DO, S. C., Miller, H. n., Leonard, S. A., Datoc, I. A., Girsen, A. I., Kappagoda, S. n., Gibbs, R. S., Aziz, N. n. 2021: 100367

    Abstract

    Serum biomarkers are used to diagnose and manage severe infections, but data on their utility during labor are limited. We compared lactate and procalcitonin levels in women with and without intraamniotic infection to determine if they are useful biomarkers for infection during labor.We performed a prospective observational cohort study of term, singleton pregnancies admitted with planned vaginal delivery in 2019 at a university medical center. Lactate and procalcitonin levels were drawn in early labor, within 2 hours following delivery, and postpartum day 1. Women with intraamniotic infection additionally had lactate and procalcitonin levels drawn following intraamniotic infection diagnosis. Samples were processed immediately in the hospital clinical laboratory. Primary outcome was mean lactate level following delivery. Secondary outcomes were lactate and procalcitonin levels at other time points. Comparisons based on infection status were performed using multivariate linear regression.22 women with intraamniotic infection and 29 uninfected women were included. Early labor mean lactate level (1.47 vs 1.49 mmol/L) and mean procalcitonin level (0.048 vs 0.039 ng/mL) did not differ and were normal in uninfected and intraamniotic infection groups. Mean lactate level was highest following delivery for women in uninfected and intraamniotic infection groups (2.00 vs 2.33 mmol/L, adjusted p=0.08, 95% CI 0.98-1.53). Lactate level returned to normal by postpartum day 1 and did not significantly differ based on the infection status at any time point in adjusted models. Procalcitonin level following delivery was higher among women with intraamniotic infection versus without infection (0.142 vs 0.091 ng/mL, adjusted p=0.03). Procalcitonin level rose further in both intraamniotic infection and uninfected groups on postpartum day 1 (0.737 vs 0.408 ng/mL, adjusted p=0.05).Lactate level is not significantly elevated in intraamniotic infection above the physiologic increase at delivery observed in women without infection. Procalcitonin level is elevated at delivery in women with intraamniotic infection and warrants further investigation as a peripartum infection marker.

    View details for DOI 10.1016/j.ajogmf.2021.100367

    View details for PubMedID 33831586

  • Cellular Aging in Pregnancy: Telomere Dynamics Across Gestation. Panelli, D. M., Leonard, S. A., Wong, R. J., Girsen, A. I., Baskovic, M., Stevenson, D. K., Bianco, K. SPRINGER HEIDELBERG. 2020: 127A–128A
  • Preterm birth outcomes among Asian women by maternal place of birth. Journal of perinatology : official journal of the California Perinatal Association Girsen, A. I., Mayo, J. A., Datoc, I. A., Karakash, S. n., Gould, J. B., Stevenson, D. K., El-Sayed, Y. Y., Shaw, G. M. 2020

    Abstract

    To investigate overall, spontaneous, and medically indicated preterm birth (PTB) rates between US-born and non-US-born Asian women living in California.Nulliparous women with a singleton livebirth and Asian race in California between 2007 and 2011 were investigated. The prevalence of overall (<37 weeks), spontaneous, and medically indicated PTB was examined by self-reported race and place of birth among ten Asian subgroups.There were marked differences in PTB rates between the individual Asian subgroups. After adjustments, non-US-born Chinese, Japanese, Vietnamese, and Indian women had lower odds of overall PTB and Chinese, Vietnamese, Cambodian, and Indian women had lower odds of spontaneous PTB compared with their US-born counterparts.Further investigation of biological and social factors contributing to these lower odds of spontaneous PTB among the non-US-born Asian population could potentially offer clues for reducing the burden of PTB among the US born.

    View details for DOI 10.1038/s41372-020-0633-1

    View details for PubMedID 32094480

  • The obstetric research landscape: a cross-sectional analysis of clinical trials from 2007-2020. American journal of obstetrics & gynecology MFM Steinberg, J. R., Weeks, B. T., Reyes, G. A., Conway Fitzgerald, A. n., Zhang, W. Y., Lindsay, S. E., Anderson, J. N., Chan, K. n., Richardson, M. T., Magnani, C. J., Igbinosa, I. n., Girsen, A. n., El-Sayed, Y. Y., Turner, B. E., Lyell, D. J. 2020: 100253

    Abstract

    Obstetric complications impact over a third of women globally, but are underrepresented in clinical research. Little is known about the comprehensive obstetric clinical trial landscape, how it compares to other fields, or factors associated with the successful completion of obstetric trials.To characterize obstetric clinical trials registered on ClinicalTrials.gov with the primary objective of identifying features associated with early discontinuation and results reporting.This is a cross-sectional study with descriptive, logistic regression and cox regression analyses of clinical trials registered on ClinicalTrials.gov. Our primary exposure variables were trial focus (obstetric or non-obstetric) and trial funding (industry, United States government or academic). We conducted additional exploratory analyses of other trial features including design, enrollment, and therapeutic focus. We examined the associations of exposure variables and other trial features with two primary outcomes: early discontinuation and results reporting.We downloaded data for all studies (n=332,417) registered on ClinicalTrials.gov from October 1, 2007 to March 9, 2020 from the Aggregate Analysis of the ClinicalTrials.gov database. We excluded studies with a non-interventional design (n=63,697) and those registered before October 1, 2007 (n=45,209). 4,276 (1.9%) obstetric trials (i.e. interventional studies), and 219,235 (98.1%) non-obstetric trials were compared. Among all trials, 2.8% of academic-funded trials, 1.9% of United States government-funded trials, and 0.4% of industry-funded trials focused on obstetrics. The quantity of obstetric trials increased over time (10.8% annual growth rate). Compared to non-obstetric trials, obstetric trials had a greater risk of early discontinuation (adjusted hazard ratio 1.40, 95% confidence interval: 1.21 to 1.62, p<0.0001) and similar odds of results reporting (adjusted odds ratio 0.89, 95% confidence interval: 0.72 to 1.10, p=0.19). Among obstetric trials funders after controlling for confounding variables, United States government-funded trials were at lowest risk of early discontinuation (US government adjusted hazard ratio 0.23, 95% confidence interval 0.07 to 0.69, p=0.009, industry reference; academic adjusted hazard ratio 1.04, 95% confidence interval 0.62 to 1.74, p=0.88). Academic-funded trials had the lowest odds of results reporting after controlling for confounding variables (academic institutions adjusted odds ratio 0.39, 95% confidence interval 0.22 to 0.68, p=0.0009; industry reference; US government adjusted odds ratio 1.06 95% confidence interval 0.53 to 2.09, p=0.87).Obstetric trials represent only 1.9% of all clinical trials in ClinicalTrials.gov and have comparatively poor completion. All stakeholders should commit to increasing the number of obstetric trials and improving their completion and dissemination to ensure clinical research reflects the obstetric burden of disease and advances maternal health.

    View details for DOI 10.1016/j.ajogmf.2020.100253

    View details for PubMedID 33043288

    View details for PubMedCentralID PMC7537600

  • Maternal Health after Stillbirth: Postpartum Hospital Readmission in California. American journal of perinatology Wall-Wieler, E. n., Butwick, A. J., Gibbs, R. S., Lyell, D. J., Girsen, A. I., El-Sayed, Y. Y., Carmichael, S. L. 2020

    Abstract

     The aim of this study is to assess whether the risk of postpartum readmission within 6 weeks of giving birth differs for women who had stillbirths compared with live births. Using data from the Office of Statewide Health Planning and Development in California, we performed a population-based cohort study of 7,398,640 births between 1999 and 2011. We identified diagnoses and procedures associated with the first postpartum hospital readmission that occurred within 6 weeks after giving birth. We used log-binomial models to estimate relative risk (RR) of postpartum readmission for women who had stillbirth compared with live birth deliveries, adjusting for maternal demographic, prepregnancy, pregnancy, and delivery characteristics. The rate of postpartum readmission was higher among women who had stillbirths compared with women who had live births (206 and 96 per 10,000 births, respectively). After adjusting for maternal demographic and medical characteristics, the risk of postpartum readmission for women who had stillbirths was nearly 1.5 times greater (adjusted RR = 1.47, 95% confidence interval: 1.35-1.60) compared with live births. Among women with stillbirths, the most common indications at readmission were uterine infection or pelvic inflammatory disease, psychiatric conditions, hypertensive disorder, and urinary tract infection. Based on our findings, women who have stillbirths are at higher risk of postpartum readmissions within 6 weeks of giving birth than women who have live births. Women who have stillbirths may benefit from additional monitoring and counseling after hospital discharge for potential postpartum medical and psychiatric complications.· Women who have stillbirths are at nearly 1.5 times greater risk of postpartum readmission than women who have live births.. · Uterine infections and pelvic inflammatory disease, and psychiatric conditions are the most common reasons for readmission among women who had a stillbirth.. · Women who have stillbirths may benefit from additional monitoring and counseling after hospital discharge for potential postpartum medical and psychiatric complications..

    View details for DOI 10.1055/s-0040-1708803

    View details for PubMedID 32365389

  • A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants AMERICAN JOURNAL OF PERINATOLOGY Spiegel, A. M., Li, J., Oehlert, J. W., Mayo, J. A., Quaintance, C. C., Girsen, A. I., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M., Stevenson, D. K., Gibbs, R. S. 2019; 36 (14): 1453–58
  • 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

  • Risk Factors for Maternal Readmission with Sepsis. American journal of perinatology Foeller, M. E., Sie, L., Foeller, T. M., Girsen, A. I., Carmichael, S. L., Lyell, D. J., Lee, H. C., Gibbs, R. S. 2019

    Abstract

    OBJECTIVE: Our primary objective was to identify risk factors for maternal readmission with sepsis. Our secondary objectives were to (1) assess diagnoses and infecting organisms at readmission and (2) compare early (<6 weeks) and late (6 weeks to 9 months postpartum) maternal readmission with sepsis.STUDY DESIGN: We identified our cohort using linked hospital discharge data and birth certificates for California deliveries from 2008 to 2011. Consistent with the 2016 sepsis classification, we defined sepsis as septicemia plus acute organ dysfunction. We compared women with early or late readmission with sepsis to women without readmission with sepsis.RESULTS: Among 1,880,264 women, 494 (0.03%) were readmitted with sepsis, 61% after 6 weeks. Risk factors for readmission with sepsis included preterm birth, hemorrhage, obesity, government-provided insurance, and primary cesarean. For both early and late sepsis readmissions, the most common diagnoses were urinary tract infection and pyelonephritis, and the most frequently identified infecting organism was gram-negative bacteria. Women with early compared with late readmission with sepsis shared similar obstetric characteristics.CONCLUSION: Maternal risk factors for both early and late readmission with sepsis included demographic characteristics, cesarean, hemorrhage, and preterm birth. Risks for sepsis after delivery persist beyond the traditional postpartum period of 6 weeks.

    View details for DOI 10.1055/s-0039-1696721

    View details for PubMedID 31529451

  • Rate and causes of severe maternal morbidity at readmission: California births in 2008-2012. Journal of perinatology : official journal of the California Perinatal Association Girsen, A. I., Sie, L., Carmichael, S. L., Lee, H. C., Foeller, M. E., Druzin, M. L., Gibbs, R. S. 2019

    Abstract

    OBJECTIVE: To determine the rate, maternal characteristics, timing, and indicators of severe maternal morbidity (SMM) that occurs at postpartum readmission.STUDY DESIGN: Women with a birth in California during 2008-2012 were included in the analysis. Readmissions up to 42 days after delivery were investigated. SMM was defined as presence of any of the 21 indicators defined by ICD-9 codes.RESULTS: Among 2,413,943 women with a birth, SMM at readmission occurred in 4229 women. Of all SMM, 12.1% occurred at readmission. Over half (53.5%) of the readmissions with SMM occurred within the first week after delivery hospitalization. The most common indicators of SMM were blood transfusion, sepsis, and pulmonary edema/acute heart failure.CONCLUSION: Twelve percent of SMM was identified at readmission with the majority occurring within 1 week after discharge from delivery hospitalization. Because early readmission may reflect lack of discharge readiness, there may be opportunities to improve care.

    View details for DOI 10.1038/s41372-019-0481-z

    View details for PubMedID 31462721

  • 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

  • Severe Maternal Morbidity Among Stillbirth and Live Birth Deliveries in California. Obstetrics and gynecology Wall-Wieler, E., Carmichael, S. L., Gibbs, R. S., Lyell, D. J., Girsen, A. I., El-Sayed, Y. Y., Butwick, A. J. 2019

    Abstract

    OBJECTIVE: To assess the prevalence and risk of severe maternal morbidity among delivery hospitalization for stillbirth compared with live birth deliveries.METHODS: Using data from the Office of Statewide Health Planning and Development in California, we performed a population-based cross-sectional study of 6,459,842 deliveries between 1999 and 2011. We identified severe maternal morbidity using an algorithm comprising diagnoses and procedures developed by the Centers for Disease Control and Prevention and used log-binomial regression models to examine the relative risk (RR) of severe maternal morbidity for stillbirth compared with live birth deliveries, adjusting for maternal demographic, medical, and obstetric characteristics. We also examined severe maternal morbidity prevalence by cause of fetal death among stillbirth deliveries.RESULTS: The prevalence of severe maternal morbidity for stillbirth and live birth was 578 and 99 cases per 10,000 deliveries, respectively. After adjusting for maternal demographic, medical, and obstetric characteristics, the risk of severe maternal morbidity among stillbirth deliveries was more than fourfold higher (adjusted RR 4.77; 95% CI 4.53-5.02) compared with live birth deliveries. The severe maternal morbidity prevalence was highest among stillbirths caused by hypertensive disorders and placental conditions (24 and 19 cases/100 deliveries, respectively), and lowest among stillbirths caused by fetal malformations or genetic abnormalities (1 case per 100 deliveries).CONCLUSION: Women who have stillbirths are at substantially higher risk for severe maternal morbidity than women who have live births, regardless of cause of fetal death. The prevalence of severe maternal morbidity varies by cause of fetal death.

    View details for DOI 10.1097/AOG.0000000000003370

    View details for PubMedID 31306335

  • Vasa previa and extreme prematurity: a population-based study JOURNAL OF PERINATOLOGY Yeaton-Massey, A., Girsen, A., Mayo, J. A., Blumenfeld, Y. J., El-Sayed, Y. Y., Stevenson, D. K., Shaw, G. M. 2019; 39 (3): 475–80
  • 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

  • Preterm birth occurrence among Asian women relative to their place of birth Girsen, A., Mayo, J. A., Datoc, I., Karakash, S., El-Sayed, Y. Y., Shaw, G. M. MOSBY-ELSEVIER. 2019: S352
  • 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

  • Characteristics of women with multiple postpartum hospital admissions Girsen, A. I., Sie, L., Carmichael, S., Foeller, M. E., Druzin, M. L., Lee, H. C., Gibbs, R. S. MOSBY-ELSEVIER. 2018: S461–S462
  • 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

  • Postpartum readmission and severe maternal morbidity in California Girsen, A., Lee, L. C., Carmichael, S. L., Foeller, M., Druzin, M. L., Gibbs, R. MOSBY-ELSEVIER. 2017: S112
  • 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): 2500-2504

    Abstract

    To investigate the association between meconium staining and perinatal and neonatal outcomes in pregnancies with gastroschisis.Retrospective analysis of infants with prenatally diagnosed gastroschisis born in two academic medical centers between 2008 and 2013. Neonatal outcomes of deliveries with and without meconium staining were compared. Primary outcome was defined as any of the following: neonatal sepsis, prolonged mechanical ventilation, bowel atresia or death. Secondary outcomes were preterm delivery, preterm-premature rupture of membranes (PPROM) and prolonged hospital length of stay.One hundred and eight infants with gastroschisis were included of which 56 (52%) had meconium staining at delivery. Infants with meconium staining had a lower gestational age at delivery (36.3 (±1.4) versus 37.0 (±1.2) weeks, p = 0.007), and a higher rate of PPROM (25% versus 8%, p = 0.03) than infants without meconium. Meconium staining was not significantly associated with the primary composite outcome or with any of its components. After adjustments, meconium staining remained significantly associated with preterm delivery at <36 weeks [odds ratio OR = 4.0, 95% confidence intervals (CI): 1.5-11.4] and PPROM (OR = 3.8, 95%CI: 1.2-14.5).Among infants with gastroschisis, meconium staining was associated with prematurity and PPROM. No significant increase in other adverse neonatal outcomes was seen among infants with meconium staining, suggesting a limited prognostic value of this finding.

    View details for DOI 10.3109/14767058.2015.1090971

    View details for PubMedID 26445130

  • Association between small-for-gestational-age and neurodevelopmental impairment at two years of life among infants born at preterm gestational ages Girsen, A., Do, S., El-Sayed, Y. Y., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2016: S76
  • Twin gestation and neurodevelopmental outcomes: is there a difference at two years of life between the first and the second twin? Girsen, A., El-Sayed, Y. Y., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2016: S216
  • Temporal and geographic patterns of home births in California 1991-2010 Girsen, A., Mayo, J. A., Blumenfeld, Y. J., Lyell, D. J., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M. MOSBY-ELSEVIER. 2016: S395
  • 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
  • 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

  • In reply. Obstetrics and gynecology Girsen, A. I., Osmundson, S. S., Garabedian, M. J., Naqvi, M., Lyell, D. J. 2015; 125 (3): 740-?

    View details for DOI 10.1097/AOG.0000000000000712

    View details for PubMedID 25730244

  • Does the Ratio of Membrane Rupture To Labor Duration Predict Maternal Morbidity Among Women With a Successful VBAC? Girsen, A. I., Shachar, B., Blumenfeld, Y. J., Aziz, N., El-Sayed, Y. Y., Butwick, A. J. SAGE PUBLICATIONS INC. 2015: 341A
  • Factors Associated With Recurrent Preterm Birth Among Underweight Women Girsen, A. I., Mayo, J., Matthew, W. B., Gould, J. B., Carmichael, S. L., Lyell, D. J., Shaw, G. M. SAGE PUBLICATIONS INC. 2015: 150A
  • Body Mass Index and Operative Times at Cesarean Delivery OBSTETRICS AND GYNECOLOGY Girsen, A. I., Osmundson, S. S., Naqvi, M., Garabedian, M. J., Lyell, D. J. 2014; 124 (4): 684-689

    Abstract

    To examine the relationship between body mass index (BMI, kg/m) and incision-to-delivery interval and total operative time at cesarean delivery.Women with singleton gestations undergoing uncomplicated primary and repeat cesarean deliveries were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Women were classified by BMI category at time of delivery (normal 18.5-24.9, overweight 25.0-29.9, obese 30.0-39.9, and morbidly obese 40 or greater). Incision-to-delivery interval and total operative times during cesarean delivery were compared among the three groups. Primary outcome was prolonged incision-to-delivery interval as defined by 90th percentile or greater of the study population or 18 minutes or longer.Of the 21,372 women included in the analysis, 9,928 were obese (46.5%) and 2,988 (14.0%) were morbidly obese. Longer operative times were found among women with overweight (median [interquartile range] incision-to-delivery: 9.0 [6.0] and total operative time: 45.0 [21.0] minutes), obese (10.0 [7.0]; 48.0 [22.0] minutes), and morbidly obese BMIs (12.0 [8.0]; 55.0 [26.0] minutes) compared with women with normal BMI at delivery (9.0 [5.0]; 43.0 [20.0] minutes) (P<.001). Morbidly obese women had a more frequent incision-to-delivery interval that was 18 minutes or longer (n=602 [20%] compared with 127 [6%] in normal BMI). After adjustments including number of prior cesarean deliveries, incision-to-delivery interval 18 minutes or longer was significantly related to obese (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.31-2.03) and morbidly obese (OR 2.81, 95% CI 2.24-3.56) BMI at delivery.Increasing BMI is related to increased incision-to-delivery interval and total operative time at cesarean delivery with morbidly obese BMI exposing women to the highest risk of prolonged incision-to-delivery interval.: II.

    View details for DOI 10.1097/AOG.0000000000000462

    View details for Web of Science ID 000342753000006

    View details for PubMedCentralID PMC4447195

  • Predictors for Perioperative Injury at Cesarean Delivery. Girsen, A. I., Butwick, A., Faucett, A. M., Lyell, D. J. SAGE PUBLICATIONS INC. 2014: 158A–159A
  • Predictors of Severe Perineal Complication among Women with Vaginal Birth after Cesarean Section. Girsen, A. I., Shachar, B., Lyell, D. J. SAGE PUBLICATIONS INC. 2014: 159A
  • Total weight gain and incision to delivery interval during cesarean delivery 33rd Annual Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) Girsen, A., Osmundson, S., Lyell, D. MOSBY-ELSEVIER. 2013: S331–S331
  • BMI and operative times at cesarean delivery Girsen, A., Osmundson, S., Naqvi, M., Lyell, D. MOSBY-ELSEVIER. 2013: S331
  • Magnesium sulfate exposure and neonatal intensive care unit admission Girsen, A., Greenberg, M., El-Sayed, Y., Carvalho, B., Lyell, D. MOSBY-ELSEVIER. 2013: S56
  • Comprehensive Maternal Serum Proteomic Profiles of Preclinical and Clinical Preeclampsia JOURNAL OF PROTEOME RESEARCH Rasanen, J., Girsen, A., Lu, X., Lapidus, J. A., Standley, M., Reddy, A., Dasari, S., Thomas, A., Jacob, T., Pouta, A., Surcel, H., Tolosa, J. E., Gravett, M. G., Nagalla, S. R. 2010; 9 (8): 4274-4281

    Abstract

    We systematically characterized maternal serum proteome in women with clinical preeclampsia (PE) and asymptomatic women in early pregnancy that subsequently developed PE. Clinical PE cohort comprised 30 patients with mild PE, 30 with severe PE, and 58 normotensive women. Preclinical PE cohort included 149 women whose serum samples were collected at 8-14 gestational weeks and in whom 30 women later developed mild and 40 severe PE. Serum proteome was analyzed and enzyme-linked immunosorbent assays were used for protein quantification. In Clinical PE, fibronectin, pappalysin-2, choriogonadotropin-beta, apolipoprotein C-III, cystatin-C, vascular endothelial growth factor receptor-1, and endoglin were more abundant compared to normotensive women. In preclinical PE, differently expressed proteins included placental, vascular, transport, matrix, and acute phase proteins. Angiogenic and antiangiogenic proteins were not significant. We conclude that placental and antiangiogenic proteins are abundant in clinical PE. In preclinical PE, proteomic profile is distinct and different from that in clinical PE.

    View details for DOI 10.1021/pr100198m

    View details for Web of Science ID 000280583700049

    View details for PubMedID 20568817

  • MATERNAL SERUM BIOMARKERS OF PLACENTAL INSUFFICIENCY IN PREECLAMPSIA Rasanen, J., Girsen, A., Thomas, A., Standley, M., Jacob, T., Michaels, J., Reddy, A., Lu, X., Lapidus, J., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2008: S201
  • MATERNAL SERUM BIOMARKERS OF GESTATIONAL HYPERTENSION DISTINCT FROM PREECLAMPSIA Rasanen, J., Girsen, A., Reddy, A., Standley, M., Thomas, A., Jacob, T., Michaels, J., Lu, X., Lapidus, J., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2008: S6
  • Increased fetal cardiac natriuretic peptide secretion in type-1 diabetic pregnancies ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA Girsen, A., Ala-Kopsala, M., Makikallio, K., Vuolteenaho, O., Rasanen, J. 2008; 87 (3): 307-312

    Abstract

    We hypothesised that human fetal cardiac natriuretic peptide secretion is increased in type-1 diabetic pregnancies with normal placental hemodynamics, and this increase is related to the first trimester maternal glycemic control.Thirty-two neonates of type-1 diabetic mothers and 60 neonates born after uncomplicated pregnancy and labour (control group) were included in this study. Diabetic pregnancies were divided into two subgroups based on the first trimester HbA1c value. Group 1 pregnancies (n =22) had a good glycemic control (HbA1c <7.5%) and Group 2 pregnancies (n =10) had a poor glycemic control (HbA1c > or =7.5%). At delivery, an umbilical artery (UA) blood sample was obtained for assessment of N-terminal peptide of proatrial (NT-proANP) and proB-type (NT-proBNP) natriuretic peptide levels. In diabetic pregnancies, each fetus had normal UA Doppler velocimetry for gestational age.The newborn UA NT-proANP and NT-proBNP concentrations were significantly higher in type-1 diabetic pregnancies than in the control group. Group 2 fetuses with poor glycemic control showed significantly higher UA NT-proANP levels than Group 1 fetuses. UA NT-proANP levels correlated significantly with maternal HbA1c values in the first, second and third trimesters, while UA NT-proBNP levels did not correlate with maternal HbA1c values.In type-1 diabetic pregnancies, fetal cardiac natriuretic peptide secretion is increased, even in the presence of good glycemic control and normal placental hemodynamics. In addition, fetal NT-proANP levels are already related to maternal glycemic control in the first trimester of pregnancy.

    View details for DOI 10.1080/00016340801899990

    View details for Web of Science ID 000253644400008

    View details for PubMedID 18307070

  • First trimester maternal serum biomarkers for prediction of preeclampsia Rasanen, J., Girsen, A., Lu, X., Lapidus, J., Tolosa, J. E., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2007: S10
  • Maternal serum biomarkers in preeclampsia Rasanen, J., Girsen, A., Lu, X., Lapidus, J., Tolosa, J. E., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2007: S138
  • Comprehensive proteomic analysis of first, second and third trimester maternal serum: Gestational age-dependent changes in the maternal serum proteome Stephenson-Famy, A., Hitti, J., Lu, X., Lapidus, J., Girsen, A., Rasanen, J., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2007: S93
  • The relationship between human fetal cardiovascular hemodynamics and serum erythropoietin levels in growth-restricted fetuses Girsen, A., Makikallio, K., Hiilesmaa, V., Hamalainen, E., Teramo, K., Rasanen, J. MOSBY-ELSEVIER. 2007: 467.e1-6

    Abstract

    We hypothesized that in growth restricted fetuses, erythropoietin (EPO) secretion is increased in proportion to the severity of cardiovascular compromise.Thirty-eight growth restricted fetuses underwent Doppler ultrasonography of cardiovascular hemodynamics. An umbilical artery (UA) blood sample was taken at delivery for EPO analysis. Group 1 fetuses (n=9) had normal UA and ductus venosus (DV) velocimetries. Group 2 fetuses (n=18) showed an abnormal UA and a normal DV velocimetry. Group 3 fetuses (n=11) had abnormal UA and DV velocimetries. Normal EPO values were determined in 19 uncomplicated pregnancies (control group).In group 3, EPO levels were higher (P<.05) than in groups 1 and 2. All fetuses in group 3 had EPO concentrations above the 90th percentile EPO value in the control group. The corresponding incidences were 44% and 50% in groups 1 and 2. Fetuses with retrograde aortic isthmus net blood flow had greater (P<.001) EPO levels than fetuses with antegrade net blood flow. Descending aorta, UA, DV and left hepatic vein pulsatility index values correlated significantly with EPO concentrations.In fetal growth restriction, serum EPO concentration is increased in proportion to the severity of fetal cardiovascular compromise. Furthermore, in fetuses with retrograde aortic isthmus net blood flow, EPO levels are increased.

    View details for DOI 10.1016/j.ajog.2006.12.032

    View details for Web of Science ID 000246346200016

    View details for PubMedID 17466705

  • Fetal cardiac natriuretic peptides are increased in type I diabetic pregnancies Girsen, A., Makikalllio, K., Ala-Kopsala, M., Vuolteenaho, O., Rasanen, J. MOSBY-ELSEVIER. 2006: S167
  • Prediction of preeclampsia during early gestation using proteomic analysis of maternal serum Rasanen, J., Tolosa, J. E., Girsen, A., Pereira, L., Fang, L., Lapidus, J., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2006: S145
  • First-trimester detection of preeclampsia by serum glycoproteome analysis Girsen, A., Rasanen, J., Tolosa, J., Pereira, L., Gravett, M., Nagalla, S. MOSBY-ELSEVIER. 2006: S160
  • Umbilical artery erythropoietin and human fetal cardiovascular hemodynamics in intrauterine growth restriction Girsen, A., Makikallio, K., Teramo, K., Hamalainen, E., Hiilesmaa, Rasanen, J. MOSBY, INC. 2005: S25
  • Human fetal cardiovascular hemodynamics and umbilical artery N-terminal peptide of prob-type natriuretic peptide in placental insufficiency Girsen, A., Ala-Kopsala, M., Makikallio, K., Vuolteenaho, O., Rasanen, J. MOSBY, INC. 2004: S22