Ronald Gibbs
Clinical Professor, Obstetrics & Gynecology - Maternal Fetal Medicine
All Publications
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Performance Characteristics of Sepsis Screening Tools During Delivery Admissions.
Obstetrics and gynecology
2023
Abstract
To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions.This was a case-control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality Care Collaborative), SIRS (Systemic Inflammatory Response Syndrome), the MEWC (the Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System), and the MEWT (Maternal Early Warning Trigger Tool). Sensitivity, false-positive rates, and C-statistics were reported for each screening tool. Analyses were stratified into cohort 1, which excluded patients with chorioamnionitis-endometritis, and cohort 2, which included those patients.Delivery admissions at 59 hospitals were extracted for patients with sepsis. Cohort 1 comprised 647 patients with sepsis, including 228 with end-organ injury, matched with a control group of 2,588 patients without sepsis. Cohort 2 comprised 14,591 patients with chorioamnionitis-endometritis, of whom 1,049 had sepsis and 238 had end-organ injury. In cohort 1, the CMQCC and the UKOSS pregnancy-adjusted criteria had the lowest false-positive rates (6.9% and 9.6%, respectively) and the highest C-statistics (0.92 and 0.91, respectively). Although other screening criteria, such as SIRS and the MEWC, had similar sensitivities, it was at the cost of much higher false-positive rates (21.3% and 38.3%, respectively). In cohort 2, including all patients with chorioamnionitis-endometritis, the highest C-statistics were again for the CMQCC (0.67) and UKOSS (0.64). All screening tools had high false-positive rates, but the false-positive rates for the CMQCC and UKOSS were substantially lower than those for SIRS and the MEWC.During delivery admissions, the CMQCC and UKOSS pregnancy-adjusted screening criteria have the lowest false-positive results while maintaining greater than 90% sensitivity rates. Performance of all screening tools was degraded in the setting of chorioamnionitis-endometritis.
View details for DOI 10.1097/AOG.0000000000005477
View details for PubMedID 38086055
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Performance Characteristics of Sepsis Screening Tools During Antepartum and Postpartum Admissions.
Obstetrics and gynecology
2023
Abstract
To evaluate the performance characteristics of existing screening tools for the prediction of sepsis during antepartum and postpartum readmissions.This was a case-control study using electronic health record data obtained between 2016 and 2021 from 67 hospitals for antepartum sepsis admissions and 71 hospitals for postpartum readmissions up to 42 days. Patients in the sepsis case group were matched in a 1:4 ratio to a comparison cohort of patients without sepsis admitted antepartum or postpartum. The following screening criteria were evaluated: the CMQCC (California Maternal Quality Care Collaborative) initial sepsis screen, the non-pregnancy-adjusted SIRS (Systemic Inflammatory Response Syndrome), the MEWC (Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System) obstetric SIRS, and the MEWT (Maternal Early Warning Trigger Tool). Time periods were divided into early pregnancy (less than 20 weeks of gestation), more than 20 weeks of gestation, early postpartum (less than 3 days postpartum), and late postpartum through 42 days. False-positive screening rates, C-statistics, sensitivity, and specificity were reported for each overall screening tool and each individual criterion.We identified 525 patients with sepsis during an antepartum hospitalization and 728 patients with sepsis during a postpartum readmission. For early pregnancy and more than 3 days postpartum, non-pregnancy-adjusted SIRS had the highest C-statistics (0.78 and 0.83, respectively). For more than 20 weeks of gestation and less than 3 days postpartum, the pregnancy-adjusted sepsis screening tools (CMQCC and UKOSS) had the highest C-statistics (0.87-0.94). The MEWC maintained the highest sensitivity rates during all time periods (81.9-94.4%) but also had the highest false-positive rates (30.4-63.9%). The pregnancy-adjusted sepsis screening tools (CMQCC, UKOSS) had the lowest false-positive rates in all time periods (3.9-10.1%). All tools had the lowest C-statistics in the periods of less than 20 weeks of gestation and more than 3 days postpartum.For admissions early in pregnancy and more than 3 days postpartum, non-pregnancy-adjusted sepsis screening tools performed better than pregnancy-adjusted tools. From 20 weeks of gestation through up to 3 days postpartum, using a pregnancy-adjusted sepsis screening tool increased sensitivity and minimized false-positive rates. The overall false-positive rate remained high.
View details for DOI 10.1097/AOG.0000000000005480
View details for PubMedID 38086052
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Alliance for Innovation on Maternal Health: Consensus Bundle on Sepsis in Obstetric Care.
Obstetrics and gynecology
2023; 142 (3): 481-492
Abstract
Sepsis in obstetric care is one of the leading causes of maternal death in the United States, with Black, Asian/Pacific Islander, and American Indian/Alaska Native obstetric patients experiencing sepsis at disproportionately higher rates. State maternal mortality review committees have determined that deaths are preventable much of the time and are caused by delays in recognition, treatment, and escalation of care. The "Sepsis in Obstetric Care" patient safety bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people by preventing infection and recognizing and treating infection early to prevent progression to sepsis. This is one of several core patient safety bundles developed by AIM (the Alliance for Innovation on Maternal Health) to provide condition- or event-specific clinical practices that should be implemented in all appropriate care settings. As with other bundles developed by AIM, the "Sepsis in Obstetric Care" patient safety bundle is organized into five domains: Readiness, Recognition and Prevention, Response, Reporting and Systems Learning, and Respectful, Equitable, and Supportive Care. The Respectful, Equitable, and Supportive Care domain provides essential best practices to support respectful, equitable, and supportive care to all patients. Further health equity considerations are integrated into the elements of each domain.
View details for DOI 10.1097/AOG.0000000000005304
View details for PubMedID 37590980
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Persistent Bacterial Vaginosis and Risk for Spontaneous Preterm Birth.
American journal of perinatology
2023
Abstract
The aim of this study was to determine the association between persistent bacterial vaginosis (BV) in pregnancy and risk for spontaneous preterm birth (sPTB). Retrospective data from IBM MarketScan Commercial Database were analyzed. Women aged between 12 and 55 years with singleton gestations were included and linked to an outpatient medications database and medications prescribed during the pregnancy were analyzed. BV in pregnancy was determined based on both a diagnosis of BV and treatment with metronidazole and/or clindamycin, and persistent treatment of BV was defined as BV in more than one trimester or BV requiring more than one antibiotic prescription. Odds ratios were calculated comparing sPTB frequencies in those with BV, or persistent BV, to women without BV in pregnancy. Survival analysis using Kaplan-Meier curves for the gestational age at delivery was also performed. Among a cohort of 2,538,606 women, 216,611 had an associated International Classification of Diseases, 9th Revision or 10th Revision code for diagnosis of BV alone, and 63,817 had both a diagnosis of BV and were treated with metronidazole and/or clindamycin. Overall, the frequency of sPTB among women treated with BV was 7.5% compared with 5.7% for women without BV who did not receive antibiotics. Relative to those without BV in pregnancy, odds ratios for sPTB were highest in those treated for BV in both the first and second trimester (1.66 [95% confidence interval [CI]: 1.52, 1.81]) or those with three or more prescriptions in pregnancy (1.48 [95% CI: 1.35, 1.63]. Persistent BV may have a higher risk for sPTB than a single episode of BV in pregnancy.· Persistent BV beyond one trimester may increase the risk for sPTB.. · Persistent BV requiring more than one prescription may increase the risk for sPTB.. · Almost half of antibiotic prescriptions treating BV in pregnancy are filled after 20 weeks gestation..
View details for DOI 10.1055/s-0043-1770703
View details for PubMedID 37379861
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Multiomic signals associated with maternal epidemiological factors contributing to preterm birth in low- and middle-income countries.
Science advances
2023; 9 (21): eade7692
Abstract
Preterm birth (PTB) is the leading cause of death in children under five, yet comprehensive studies are hindered by its multiple complex etiologies. Epidemiological associations between PTB and maternal characteristics have been previously described. This work used multiomic profiling and multivariate modeling to investigate the biological signatures of these characteristics. Maternal covariates were collected during pregnancy from 13,841 pregnant women across five sites. Plasma samples from 231 participants were analyzed to generate proteomic, metabolomic, and lipidomic datasets. Machine learning models showed robust performance for the prediction of PTB (AUROC = 0.70), time-to-delivery (r = 0.65), maternal age (r = 0.59), gravidity (r = 0.56), and BMI (r = 0.81). Time-to-delivery biological correlates included fetal-associated proteins (e.g., ALPP, AFP, and PGF) and immune proteins (e.g., PD-L1, CCL28, and LIFR). Maternal age negatively correlated with collagen COL9A1, gravidity with endothelial NOS and inflammatory chemokine CXCL13, and BMI with leptin and structural protein FABP4. These results provide an integrated view of epidemiological factors associated with PTB and identify biological signatures of clinical covariates affecting this disease.
View details for DOI 10.1126/sciadv.ade7692
View details for PubMedID 37224249
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Early postpartum hospital encounters among patients with genitourinary and wound infections during hospitalization for birth.
American journal of perinatology
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
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Effect of gestational age at first delivery and interpregnancy interval on the recurrence of clinical chorioamnionitis.
AJOG global reports
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
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Early postpartum readmissions: identifying risk factors at birth hospitalization.
AJOG global reports
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
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Postpartum care visits among commercially insured women in the United States.
AJOG global reports
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
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Using Longitudinally Linked Data to Measure Severe Maternal Morbidity Beyond the Birth Hospitalization in California.
Obstetrics and gynecology
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
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Incidence, prevalence, and timing of postpartum complications and mortality in Canada and the United States: a systematic review and meta-analysis protocol.
JBI evidence synthesis
2022
Abstract
The goal of this systematic review is to assess the incidence, prevalence, and timing of common postpartum (up to one year after delivery) medical, surgical/procedural, and psychosocial complications and mortality.Childbirth is the most common cause for hospitalization, and cesarean delivery is the most commonly performed inpatient surgery. After delivery, mothers are at risk of short- and long-term complications that can impact their well-being. The results of this review will inform evidence-based recommendations for patient education, monitoring, and follow-up.We will include studies performed in Canada and/or the United States that report the incidence or prevalence of medical, procedural/surgical, and psychosocial complications within one year postpartum. Observational studies (analytical cross-sectional studies, retrospective and prospective cohorts), randomized or non-randomized controlled trials with a control or standard of care group, systematic reviews, and meta-analyses will be included. Studies with <100 patients, age <18 years, no reporting of duration, and focus on patients with a specific condition rather than a general postpartum population will be excluded.The search strategy was co-developed with a medical librarian and included full-text English-language articles published within the past 10 years (2011-2021) in PubMed, CINHAL, Web of Science, and Cochrane Database of Systematic Reviews. Screening, critical appraisal, and data extraction will be performed by two independent reviewers using Covidence, standardized JBI tools, and a standardized form, respectively. For each complication, the incidence or prevalence, timing of the frequency measurement, and duration of follow-up from individual studies will be determined. Meta-analysis will be performed if feasible.PROSPERO CRD42022303047.
View details for DOI 10.11124/JBIES-21-00437
View details for PubMedID 35975310
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Hospital Readmissions after Postpartum Emergency Department Visit
MOSBY-ELSEVIER. 2022: S517-S518
View details for Web of Science ID 000737459401161
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Perinatal infection, inflammation, preterm birth, and brain injury: A review with proposals for future investigations.
Experimental neurology
2022: 113988
Abstract
Preterm newborns are exposed to several risk factors for developing brain injury. Clinical studies have suggested that the presence of intrauterine infection is a consistent risk factor for preterm birth and white matter injury. Animal models have confirmed these associations by identifying inflammatory cascades originating at the maternofetal interface that penetrate the fetal blood-brain barrier and result in brain injury. Acquired diseases of prematurity further potentiate the risk for cerebral injury. Systems biology approaches incorporating ante- and post-natal risk factors and analyzing omic and multiomic data using machine learning are promising methodologies for further elucidating biologic mechanisms of fetal and neonatal brain injury.
View details for DOI 10.1016/j.expneurol.2022.113988
View details for PubMedID 35081400
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A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection
OBSTETRICAL & GYNECOLOGICAL SURVEY
2022; 77 (1): 16-18
View details for Web of Science ID 000739995400008
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Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset.
Science translational medicine
2021; 13 (592)
Abstract
Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 * 10-40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 * 10-7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.
View details for DOI 10.1126/scitranslmed.abd9898
View details for PubMedID 33952678
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Risk Factors for Postpartum Readmission Among Women After Having a Stillbirth.
American journal of obstetrics & gynecology MFM
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
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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
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
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Evaluation of Hypoglycemia in Neonates of Women at Risk for Late Preterm Delivery: An Antenatal Late Preterm Steroids Trial Cohort Study.
American journal of perinatology
2021
Abstract
In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia. Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate. Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46-1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03-7.03) vs. 3.74 (interquartile range: 2.15-15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure.· Hypoglycemia was transient and approximately two-thirds received no treatment.. · Neonates in the ALPS trial who received betamethasone had a shorter time to resolution than those with hypoglycemia in the placebo group.. · Prolonged hypoglycemia occurred in approximately 2 out of 100 late preterm newborns, irrespective of antenatal steroid exposure..
View details for DOI 10.1055/s-0041-1729561
View details for PubMedID 34044454
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A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.
The New England journal of medicine
2021; 385 (5): 436-444
Abstract
Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection.In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed.From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo.Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
View details for DOI 10.1056/NEJMoa1913569
View details for PubMedID 34320288
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Lactate and Procalcitonin Levels in Peripartum Women with Intraamniotic Infection.
American journal of obstetrics & gynecology MFM
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
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Elective Labor Induction at 39 Weeks of Gestation Compared With Expectant Management: Factors Associated With Adverse Outcomes in Low-Risk Nulliparous Women.
Obstetrics and gynecology
2020
Abstract
OBJECTIVE: To evaluate characteristics associated with adverse outcomes in low-risk nulliparous women randomized to elective labor induction at 39 weeks of gestation or expectant management.METHODS: We conducted a secondary analysis of women randomized during the 38th week to induction at 39 weeks of gestation or expectant management. Deliveries before 39 weeks of gestation and those not adherent to study protocol or with fetal anomalies were excluded. A composite of adverse outcomes (perinatal death or severe neonatal complications), third- or fourth-degree lacerations, and postpartum hemorrhage were evaluated. Log binomial regression models estimated relative risks and 95% CIs for associations of outcomes with patient characteristics including randomly assigned treatment group. Interactions between patient characteristics and treatment group were tested.RESULTS: Of 6,096 women with outcome data, 5,007 (82.1%) met criteria for inclusion in this analysis. Frequency of the perinatal composite was 252 (5.0%), 166 (3.3%) for third- or fourth-degree perineal laceration, and 237 (4.7%) for postpartum hemorrhage. In multivariable analysis, intended labor induction at 39 weeks of gestation was associated with a reduced perinatal composite outcome (4.1% vs 6.0%; adjusted relative risk [aRR] 0.71; 95% CI 0.55-0.90), whereas increasing body mass index (BMI) was associated with an increased perinatal composite outcome (aRR 1.04/unit increase; 95% CI 1.02-1.05). Decreased risk of third- or fourth-degree perineal laceration was observed with increasing BMI (aRR 0.96/unit increase; 95% CI 0.93-0.98) and in Black women compared with White women (1.2% vs 3.9%; aRR 0.34; 95% CI 0.19-0.60). Increased risk of postpartum hemorrhage was observed in Hispanic women compared with White women (6.3% vs 4.0%; aRR 1.64; 95% CI 1.18-2.29). Patient characteristics associated with adverse outcomes were similar between treatment groups (P for interaction >.05).CONCLUSION: Compared with expectant management, intended induction at 39 weeks of gestation was associated with reduced risk of adverse perinatal outcome. Patient characteristics associated with adverse outcomes were few and similar between groups.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01990612.
View details for DOI 10.1097/AOG.0000000000004055
View details for PubMedID 32925628
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Customized Probability of Vaginal Delivery With Induction of Labor and Expectant Management in Nulliparous Women at 39 Weeks of Gestation.
Obstetrics and gynecology
2020
Abstract
OBJECTIVE: To develop models to predict vaginal delivery in low-risk, nulliparous women contemplating elective induction of labor or expectant management at 39 weeks of gestation.METHODS: We conducted a secondary analysis of a randomized controlled trial of planned elective induction of labor at 39 weeks of gestation compared with expectant management for low-risk nulliparous women. Two groups were included for this analysis: 1) women who were randomized to the induction of labor group and underwent elective induction at 39 0/7-39 4/7 weeks of gestation and 2) women who were randomized to the expectant management group who experienced spontaneous labor or medically indicated delivery (including postterm). Multivariable logistic regression models were developed for each group using patient characteristics that would be available at the time of counseling. Model selection was based on k-fold cross-validation using backward elimination and variables that remained significant at P<.05 were retained. To compare estimated with observed rates, the elective induction of labor model was then applied to each woman in both groups to estimate individualized predicted probabilities of vaginal delivery with elective induction of labor.RESULTS: Of 6,106 women enrolled in the trial, 4,661 met criteria for this analysis. Vaginal delivery occurred in 80.6% of the 2,153 women in the elective induction of labor group and 77.2% of the 2,508 women in the expectant management group (P=.005). The final elective induction of labor model included age, height, weight, and modified Bishop score (area under the receiver operating characteristic curve [AUROC] 0.72, 95% CI 0.70-0.75). The same variables were included in the final expectant management model (AUROC 0.70, 95% CI 0.67-0.72). Across the range of predicted probability deciles derived from the elective induction of labor model, almost all women who underwent elective induction of labor at 39 weeks of gestation had a higher observed chance of vaginal delivery than expectant management.CONCLUSION: Irrespective of the individual predicted chance of vaginal delivery from elective induction of labor at 39 weeks of gestation, vaginal delivery is generally more frequent if elective induction of labor is undertaken rather than expectant management. These data can be used to counsel nulliparous women regarding their "customized" chances of vaginal delivery as they choose between elective induction of labor or expectant management at 39 weeks of gestation.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01990612.
View details for DOI 10.1097/AOG.0000000000004046
View details for PubMedID 32925634
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Towards personalized medicine in maternal and child health: integrating biologic and social determinants.
Pediatric research
2020
View details for DOI 10.1038/s41390-020-0981-8
View details for PubMedID 32454518
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Hepatitis C Virus Antibody Screening in a Cohort of Pregnant Women: Identifying Seroprevalence and Risk Factors.
Obstetrics and gynecology
2020
Abstract
OBJECTIVE: To describe the prevalence of hepatitis C virus (HCV) antibody, evaluate current risk factors associated with HCV antibody positivity, and identify novel composite risk factors for identification of groups most likely to demonstrate HCV antibody seropositivity in an obstetric population from 2012 to 2015.METHODS: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network initiated an observational study of mother-to-child transmission of HCV in 2012 that included offering HCV antibody screening to their entire obstetric population. Women presenting for prenatal care before 23 weeks of gestation without a known multifetal gestation were eligible. For each woman who was HCV antibody-positive, two women at similar gestational age who were HCV antibody-negative were identified and included for comparison. Risk factors were evaluated by patient interview and chart review. Women in the case group were identified to have a signal-to-cutoff value of at least 5 on the Abbott ARCHITECT platform. RNA status was evaluated for women in the case group.RESULTS: Of 106,842 women screened for the HCV antibody, 254 had positive results. The HCV antibody seroprevalence rate was 2.4 cases per 1,000 women (95% CI 2.1-2.7). One hundred thirty-one women in the case group and 251 women in the control group were included in the case-control analysis. Factors associated with HCV antibody positivity included injection drug use (adjusted odds ratio [aOR] 22.9, 95% CI 8.2-64.0), blood transfusion (aOR 3.7, 95% CI 1.3-10.4), having a partner with HCV (aOR 6.3, 95% CI 1.8-22.6), more than three lifetime sexual partners (aOR 5.3, 95% CI 1.4-19.8), and smoking (aOR 2.4, 95% CI 1.2-4.6). A composite of any of these potential risk factors provided the highest sensitivity for detecting HCV antibody (75/82 cases, 91%).CONCLUSION: In this cohort, the seroprevalence of HCV antibody was low, and the current risk factors for HCV screening were not identified. These findings may be useful in defining new strategies for identifying mothers with the HCV antibody and the neonates susceptible to maternal transmission of HCV.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01959321.
View details for DOI 10.1097/AOG.0000000000003754
View details for PubMedID 32168224
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Health resource utilization of labor induction versus expectant management: Resource utilization at induction of labor.
American journal of obstetrics and gynecology
2020
Abstract
BACKGROUND: Although induction of labor (IOL) of low-risk nulliparous women at 39 weeks reduces the risk of cesarean delivery compared with expectant management, concern regarding more frequent use of labor induction remains given that this intervention historically has been thought to incur greater resource utilization.OBJECTIVE: To determine whether planned elective labor induction at 39 weeks among low-risk nulliparous women, compared with expectant management, was associated with differences in health care resource utilization from the time of randomization through 8 weeks postpartum.STUDY DESIGN: This is a planned secondary analysis of a multi-center randomized trial in which low-risk nulliparous women were assigned to IOL at 39 weeks or expectant management. We assessed resource utilization post-randomization in three time periods: antepartum (AP), delivery admission, and discharge through 8 weeks postpartum (PP).RESULTS: Of 6096 women with data available, those in the IOL group (n = 3059) were significantly less likely in the AP period after randomization to have at least one ambulatory visit for routine prenatal care (32.4% vs. 68.4%), unanticipated care (0.5% vs. 2.6%), or urgent care (16.2% vs. 44.3%), or at least one antepartum hospitalization (0.8% vs. 2.2%, p<0.001 for all). They also had fewer tests (e.g., sonograms, blood tests) and treatments (e.g., antibiotics, intravenous hydration) prior to delivery. During the delivery admission, women in the IOL group spent a longer time in labor and delivery (median: 0.83 vs. 0.57 days), but both women (p=0.002) and their neonates (p<0.001) had shorter postpartum stays. Women and neonates in both groups had similar frequencies of PP urgent care and hospital readmissions (p>0.05 for all).CONCLUSIONS: Women randomized to IOL had longer durations in labor and delivery, but significantly fewer AP visits, tests, and treatments, and shorter maternal and neonatal hospital durations post-delivery. These results demonstrate that the health outcome advantages associated with IOL are gained without incurring uniformly greater health care resource use.
View details for DOI 10.1016/j.ajog.2020.01.002
View details for PubMedID 31930993
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Maternal genitourinary and wound infections: Early postpartum readmissions and emergency department visits
MOSBY-ELSEVIER. 2020: S169
View details for DOI 10.1016/j.ajog.2019.11.261
View details for Web of Science ID 000504997300245
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Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.
JAMA network open
2020; 3 (12): e2029655
Abstract
Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies.To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB.This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019.Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites.The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation.Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways.This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.
View details for DOI 10.1001/jamanetworkopen.2020.29655
View details for PubMedID 33337494
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Maternal Health after Stillbirth: Postpartum Hospital Readmission in California.
American journal of perinatology
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
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Maternal and Neonatal Outcomes Associated with Amniotomy among Nulliparous Women Undergoing Labor Induction at Term.
American journal of perinatology
2020
Abstract
The aim of the study is to evaluate the association between amniotomy at various time points during labor induction and maternal and neonatal outcomes among term, nulliparous women. Secondary analysis of a randomized trial of term labor induction versus expectant management in low-risk, nulliparous women (2014-2017) was conducted. Women met inclusion criteria if they underwent induction ≥38 weeks' gestation using oxytocin with documented time and type of membrane rupture. Women with antepartum stillbirth or fetal anomaly were excluded. The primary outcome was cesarean delivery. Secondary outcomes included maternal and neonatal complications. Maternal and neonatal outcomes were compared among women with amniotomy versus women with intact membranes and no amniotomy at six 2-hour time intervals: before oxytocin initiation, 0 to <2 hours after oxytocin, 2 to <4 hours after, 4 to <6 hours after, 6 to <8 hours after, and 8 to <10 hours after. Multivariable logistic regression adjusted for maternal age, body mass index, race/ethnicity, modified Bishop score on admission, treatment group, and hospital (as a random effect). Of 6,106 women in the parent trial, 2,854 (46.7%) women met inclusion criteria. Of these 2,340 (82.0%) underwent amniotomy, and majority of the women had amniotomy performed between 2 and <6 hours after oxytocin. Cesarean delivery was less frequent among women with amniotomy 6 to <8 hours after oxytocin compared with women without amniotomy (21.9 vs. 29.7%; adjusted odds ratio 0.61, 95% confidence interval 0.42-0.89). Amniotomy at time intervals ≥4 hours after oxytocin was associated with lower odds of labor duration >24 hours. Amniotomy at time intervals ≥2 hours and <8 hours after oxytocin was associated with lower odds of maternal hospitalization >3 days. Amniotomy was not associated with postpartum or neonatal complications. Among a contemporary cohort of nulliparous women undergoing term labor induction, amniotomy was associated with either lower or similar odds of cesarean delivery and other adverse outcomes, compared with no amniotomy.
View details for DOI 10.1055/s-0040-1709464
View details for PubMedID 32299106
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Early postpartum readmissions or emergency department visits: Identifying risk factors
MOSBY-ELSEVIER. 2020: S351–S352
View details for DOI 10.1016/j.ajog.2019.11.562
View details for Web of Science ID 000504997300545
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A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants
AMERICAN JOURNAL OF PERINATOLOGY
2019; 36 (14): 1453–58
View details for DOI 10.1055/s-0038-1677503
View details for Web of Science ID 000499481500005
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Risk Factors for Maternal Readmission with Sepsis.
American journal of perinatology
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
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Association Between Features of Spontaneous Late Preterm Labor and Late Preterm Birth.
American journal of perinatology
2019
Abstract
OBJECTIVE: This study aimed to evaluate the association between clinical and examination features at admission and late preterm birth.STUDY DESIGN: The present study is a secondary analysis of a randomized trial of singleton pregnancies at 340/7 to 365/7 weeks' gestation. We included women in spontaneous preterm labor with intact membranes and compared them by gestational age at delivery (preterm vs. term). We calculated a statistical cut-point optimizing the sensitivity and specificity of initial cervical dilation and effacement at predicting preterm birth and used multivariable regression to identify factors associated with late preterm delivery.RESULTS: A total of 431 out of 732 (59%) women delivered preterm. Cervical dilation≥4cm was 60% sensitive and 68% specific for late preterm birth. Cervical effacement≥75% was 59% sensitive and 65% specific for late preterm birth. Earlier gestational age at randomization, nulliparity, and fetal malpresentation were associated with late preterm birth. The final regression model including clinical and examination features significantly improved late preterm birth prediction (81% sensitivity, 48% specificity, area under the curve=0.72, 95% confidence interval [CI]: 0.68-0.75, and p-value<0.01).CONCLUSION: Four in 10 women in late-preterm labor subsequently delivered at term. Combination of examination and clinical features (including parity and gestational age) improved late-preterm birth prediction.
View details for DOI 10.1055/s-0039-1696641
View details for PubMedID 31529452
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Rate and causes of severe maternal morbidity at readmission: California births in 2008-2012.
Journal of perinatology : official journal of the California Perinatal Association
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
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Severe Maternal Morbidity Among Stillbirth and Live Birth Deliveries in California.
Obstetrics and gynecology
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
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Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia.
Frontiers in immunology
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
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Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia
FRONTIERS IN IMMUNOLOGY
2019; 10
View details for DOI 10.3389/fimmu.2019.01305
View details for Web of Science ID 000470999000001
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Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery A Secondary Analysis of a Randomized Clinical Trial
JAMA PEDIATRICS
2019; 173 (5): 462–68
View details for DOI 10.1001/jamapediatrics.2019.0032
View details for Web of Science ID 000467505200014
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Maternal sepsis: new concepts, new practices
CURRENT OPINION IN OBSTETRICS & GYNECOLOGY
2019; 31 (2): 90–96
View details for DOI 10.1097/GCO.0000000000000523
View details for Web of Science ID 000480728000002
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Cost-effectiveness of Antenatal Corticosteroid Therapy vs No Therapy in Women at Risk of Late Preterm Delivery: A Secondary Analysis of a Randomized Clinical Trial.
JAMA pediatrics
2019
Abstract
Importance: Administration of corticosteroids to women at high risk for delivery in the late preterm period (34-36 weeks' gestation) improves short-term neonatal outcomes. The cost implications of this intervention are not known.Objective: To compare the cost-effectiveness of treatment with antenatal corticosteroids with no treatment for women at risk for late preterm delivery.Design, Setting, and Participants: This secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter randomized clinical trial of antenatal corticosteroids vs placebo in women at risk for late preterm delivery conducted from October 30, 2010, to February 27, 2015. took a third-party payer perspective. Maternal costs were based on Medicaid rates and included those of betamethasone, as well as the outpatient visits or inpatient stay required to administer betamethasone. All direct medical costs for newborn care were included. For infants admitted to the neonatal intensive care unit, comprehensive daily costs were stratified by the acuity of respiratory illness. For infants admitted to the regular newborn nursery, nationally representative cost estimates from the literature were used. Effectiveness was measured as the proportion of infants without the primary outcome of the study: a composite of treatment in the first 72 hours of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, supplemental oxygen with a fraction of inspired oxygen of 30% or more for 4 hours or more, and extracorporeal membrane oxygenation or mechanical ventilation. This secondary analysis was initially started in June 2016 and revision of the analysis began in May 2017.Exposures: Bethamethasone treatment.Main Outcomes and Measures: Incremental cost-effectiveness ratio.Results: Costs were determined for 1426 mother-infant pairs in the betamethasone group (mean [SD] maternal age, 28.6 [6.3] years; 827 [58.0%] white) and 1395 mother-infant pairs in the placebo group (mean [SD] maternal age, 27.9 [6.2] years; 794 [56.9%] white). Treatment with betamethasone was associated with a total mean (SD) woman-infant-pair cost of $4681 ($5798), which was significantly less than the mean (SD) amount of $5379 ($8422) for women and infants in the placebo group (difference, $698; 95% CI, $186-$1257; P=.02). The Antenatal Late Preterm Steroids trial determined that betamethasone use is effective: respiratory morbidity deceased by 2.9% (95% CI, -0.5% to -5.4%). Thus, the cost-effectiveness ratio was -23 986. Inspection of the bootstrap replications confirmed that treatment was the dominant strategy in 5000 samples (98.8%). Sensitivity analyses showed that these results held under most assumptions.Conclusions and Relevance: The findings suggest that antenatal betamethasone treatment is associated with a statistically significant decrease in health care costs and with improved outcomes; thus, this treatment may be an economically desirable strategy.
View details for PubMedID 30855640
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Understanding health disparities
JOURNAL OF PERINATOLOGY
2019; 39 (3): 354–58
View details for DOI 10.1038/s41372-018-0298-1
View details for Web of Science ID 000459549600003
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Preparing for a post-Roe world
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2019; 220 (3)
View details for DOI 10.1016/j.ajog.2018.11.1097
View details for Web of Science ID 000460115700006
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Maternal sepsis: new concepts, new practices.
Current opinion in obstetrics & gynecology
2019
Abstract
PURPOSE OF REVIEW: Sepsis is a leading cause of severe maternal morbidity and maternal death. As pregnancy-related sepsis can be difficult to recognize, clinicians should maintain a low threshold for early evaluation and treatment.RECENT FINDINGS: Definitions and treatment guidelines for maternal sepsis were recently revised in 2016 and 2017 by the Surviving Sepsis Campaign and WHO. Multiple clinical decision tools have been created to aid clinicians in early recognition and risk prediction for sepsis in obstetric populations, but currently, an optimal screening tool does not exist. Early recognition and urgent treatment is paramount for patient survival. Antibiotics should be started within 1 h and fluid resuscitation should be initiated if sepsis-induced hypoperfusion is present. Care should be escalated to appropriate settings and source control provided.SUMMARY: Obstetricians have a heightened understanding of the physiologic changes in pregnancy and play a vital role in coordinating patient care and improving outcomes. The recent 2016 and 2017 revisions of definitions for maternal sepsis and treatment should be incorporated into clinical practice.
View details for PubMedID 30789841
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A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants.
American journal of perinatology
2019
Abstract
OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with clinical chorioamnionitis among preterm infants.STUDY DESIGN: We reanalyzed a genome-wide association study (GWAS) from preterm newborns at less than 30 weeks' gestation. Cases and control definitions were determined using administrative records. There were 213 clinical chorioamnionitis cases and 707 clinically uninfected controls. We compared demographic and clinical outcomes of cases and controls. We performed a GWAS and compared the distribution of SNPs from the background genes and from the immunome genes. We used a Wilcoxon's rank-sum test to compare the SNPs normalized odds ratio and used odds ratios and p-values to determine candidate genes.RESULTS: Infants affected by clinical chorioamnionitis were more likely to have periventricular leukomalacia, high-grade retinopathy, and high-grade intraventricular hemorrhage (IVH). Although a GWAS did not identify SNPs associated with clinical chorioamnionitis at the genome-wide significance level, a direct test on the exonic variants in the human immunome revealed their significant increase of risk in clinical chorioamnionitis.CONCLUSION: Among very preterm infants, clinical chorioamnionitis was associated with periventricular leukomalacia, high-grade retinopathy, and IVH. Our analysis of variants in the human immunome indicates an association with clinical chorioamnionitis in very preterm pregnancies.
View details for PubMedID 30674050
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Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.
Bioinformatics (Oxford, England)
2019; 35 (1): 95–103
Abstract
Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary information: Supplementary data are available at Bioinformatics online.
View details for PubMedID 30561547
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Readmission following discharge on labetalol or nifedipine for management of hypertensive disorders of pregnancy
MOSBY-ELSEVIER. 2019: S341
View details for DOI 10.1016/j.ajog.2018.11.530
View details for Web of Science ID 000454249401294
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Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy
BIOINFORMATICS
2019; 35 (1): 95–103
View details for DOI 10.1093/bioinformatics/bty537
View details for Web of Science ID 000459313900012
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Understanding health disparities.
Journal of perinatology : official journal of the California Perinatal Association
2018
Abstract
Based upon our recent insights into the determinants of preterm birth, which is the leading cause of death in children under five years of age worldwide, we describe potential analytic frameworks that provides both a common understanding and, ultimately the basis for effective, ameliorative action. Our research on preterm birth serves as an example that the framing of any human health condition is a result of complex interactions between the genome and the exposome. New discoveries of the basic biology of pregnancy, such as the complex immunological and signaling processes that dictate the health and length of gestation, have revealed a complexity in the interactions (current and ancestral) between genetic and environmental forces. Understanding of these relationships may help reduce disparities in preterm birth and guide productive research endeavors and ultimately, effective clinical and public health interventions.
View details for PubMedID 30560947
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Preparing For A Post-Roe World.
American journal of obstetrics and gynecology
2018
Abstract
Changes in the make-up of the Supreme Court make an overturn of the Roe v Wade decision a realistic possibility. In order to mitigate any adverse health consequences that could result from a change in the law, all stakeholders in women's health have to start to plan for that contingency. These stakeholders include physicians, nurse midwives, nurses, their professional organizations, health advocacy groups, health policy experts, and legislators. Among the tasks for physicians and their professional organization, we include education about the management of women injured by unsafe abortions, post residency training for physicians with reduced access to residency training in abortion, and planning for the management of medically complicated pregnancies that are often currently terminated (e.g. Eisenmenger's syndrome). In this piece we argue for preparation for a potential post-Roe world.
View details for PubMedID 30471257
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Intrapartum Fetal Heart Rate Tracing Among Small-for-Gestational Age Compared With Appropriate-for-Gestational-Age Neonates
OBSTETRICS AND GYNECOLOGY
2018; 132 (4): 1019–25
View details for DOI 10.1097/AOG.0000000000002855
View details for Web of Science ID 000454041500033
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Intrapartum Fetal Heart Rate Tracing Among Small-for-Gestational Age Compared With Appropriate-for-Gestational-Age Neonates.
Obstetrics and gynecology
2018
Abstract
OBJECTIVE: To compare fetal heart rate (FHR) patterns during the last hour of labor between small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age) and appropriate-for-gestational-age (AGA; birth weight at the 10-90th percentile) neonates at 36 weeks of gestation or greater. We also compared the rate of cesarean delivery and composite neonatal morbidity among SGA and AGA newborns.METHODS: This is a secondary analysis of a randomized trial of intrapartum fetal electrocardiographic ST-segment analysis. We excluded women with chorioamnionitis, insufficient duration of FHR tracing in the hour before delivery, and anomalous newborns. Fetal heart rate patterns were categorized by computerized pattern recognition software (PeriCALM Patterns). Composite neonatal morbidity was defined as any of the following: intrapartum fetal death, Apgar score 3 or less at 5 minutes, cord artery pH 7.05 or less, base deficit 12 mmol/L or greater, neonatal seizure, intubation at delivery, neonatal encephalopathy, and neonatal death. Logistic regression was used to evaluate the association between FHR patterns and SGA adjusted for magnesium sulfate exposure and stage of labor.RESULTS: Of the 11,108 women randomized, 85% (n=9,402) met inclusion criteria, of whom 9% were SGA. In the last hour, the likelihood of accelerations was significantly lower among SGA than AGA neonates (72.4% vs 66.8%; P=.001). Variable decelerations lasting greater than 60 seconds, with depth greater than 60 beats per minute (bpm) or nadir less than 60 bpm, were significantly more common with SGA than AGA (all P<.001). The rate of late decelerations, prolonged decelerations, or bradycardia were similar between SGA and AGA (all P>.05). Cesarean delivery for fetal indications was significantly more common with SGA (7.0%) than AGA (4.0%; P<.001). The composite neonatal morbidity was 1.4% among SGA and 1.0% among AGA (odds ratio 1.40, 95% CI 0.74-2.64).CONCLUSION: Although the FHR patterns in the last hour of labor differ among SGA and AGA neonates, as does the rate of cesarean delivery, the composite neonatal morbidity was similar.
View details for PubMedID 30204687
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The role of the maternal and fetal inflammatory response in retinopathy of prematurity
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
2018; 80 (3): e12986
Abstract
There is a paucity of research on the contribution of placental inflammation to severe retinopathy of prematurity (ROP).A retrospective cohort study (n = 1217) was conducted of infants screened for ROP (2006-2016). The outcomes of the study were severe ROP (type 1 or type 2 ROP) and low grade ROP. We categorized the placental pathology as the presence of (i) maternal plus fetal inflammatory response, (ii) maternal inflammatory response only, (iii) fetal inflammatory response only and, (iv) no evidence of a maternal or fetal inflammatory response. The data were analyzed using univariate and multivariate logistic regression analyses (P < .05).In this cohort, the number of infants with the maternal plus fetal inflammatory response, the maternal inflammatory response only, the fetal inflammatory response only, and no maternal or fetal inflammatory response was 305 (25%), 82 (7%), 8 (1%), and 822 (67%), respectively. Adjusted for covariates, the maternal plus fetal inflammatory response was a significant risk factor for severe ROP (AOR = 2.6, 95% CI 1.1-5.9, P = .03). None of the categories of placental inflammation were significantly associated with low grade ROP.Placental pathology distinguished by the maternal plus fetal inflammatory response was a significant risk factor for severe ROP. Our study supports a link between intrauterine inflammatory events and the subsequent development of severe ROP.
View details for PubMedID 29797537
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Labor Induction versus Expectant Management in Low-Risk Nulliparous Women
NEW ENGLAND JOURNAL OF MEDICINE
2018; 379 (6): 513–23
View details for DOI 10.1056/NEJMoa1800566
View details for Web of Science ID 000441110600005
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Characteristics of women with multiple postpartum hospital admissions
MOSBY-ELSEVIER. 2018: S461–S462
View details for Web of Science ID 000423616600271
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Labor Induction versus Expectant Management in Low-Risk Nulliparous Women.
The New England journal of medicine
2018; 379 (6): 513–23
Abstract
Background The perinatal and maternal consequences of induction of labor at 39 weeks among low-risk nulliparous women are uncertain. Methods In this multicenter trial, we randomly assigned low-risk nulliparous women who were at 38 weeks 0 days to 38 weeks 6 days of gestation to labor induction at 39 weeks 0 days to 39 weeks 4 days or to expectant management. The primary outcome was a composite of perinatal death or severe neonatal complications; the principal secondary outcome was cesarean delivery. Results A total of 3062 women were assigned to labor induction, and 3044 were assigned to expectant management. The primary outcome occurred in 4.3% of neonates in the induction group and in 5.4% in the expectant-management group (relative risk, 0.80; 95% confidence interval [CI], 0.64 to 1.00). The frequency of cesarean delivery was significantly lower in the induction group than in the expectant-management group (18.6% vs. 22.2%; relative risk, 0.84; 95% CI, 0.76 to 0.93). Conclusions Induction of labor at 39 weeks in low-risk nulliparous women did not result in a significantly lower frequency of a composite adverse perinatal outcome, but it did result in a significantly lower frequency of cesarean delivery. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ARRIVE ClinicalTrials.gov number, NCT01990612 .).
View details for PubMedID 30089070
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Adverse pregnancy outcomes among women with urinary tract infections: comparison of sensitive and resistant organisms
MOSBY-ELSEVIER. 2017: 734
View details for Web of Science ID 000416950700088
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An immune clock of human pregnancy
SCIENCE IMMUNOLOGY
2017; 2 (15)
View details for DOI 10.1126/sciimmunol.aan2946
View details for Web of Science ID 000434327200004
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Adverse Pregnancy Outcomes Among Women With Urinary Tract Infections: Comparing Sensitive and Resistant Organisms
LIPPINCOTT WILLIAMS & WILKINS. 2017: 37S
View details for DOI 10.1097/01.AOG.0000514324.24913.bb
View details for Web of Science ID 000402705800129
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An immune clock of human pregnancy.
Science immunology
2017; 2 (15)
Abstract
The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.
View details for PubMedID 28864494
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The relationship of the subtypes of preterm birth with retinopathy of prematurity.
American journal of obstetrics and gynecology
2017; 217 (3): 354.e1–354.e8
Abstract
Retinopathy of prematurity is an adverse outcome of preterm birth and is a leading cause of childhood blindness. The relationship between the subtypes of preterm birth with retinopathy of prematurity is understudied.To investigate whether there is a difference in the incidence of type 1 or type 2 retinopathy of prematurity in infants with preterm birth resulting from spontaneous preterm labor, a medical indication of preterm birth, or preterm premature rupture of the membranes.A retrospective cohort study was conducted of 827 infants screened for retinopathy of prematurity who were delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for retinopathy of prematurity defined as "infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for retinopathy of prematurity." Two independent reviewers masked to retinopathy of prematurity outcomes determined whether preterm birth resulted from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes. Discrepancies were resolved by a third reviewer. Data were analyzed with univariate and multivariable logistic regression.In our cohort, the frequency of preterm birth resulting from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes was 34%, 40%, and 26%, respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the preterm birth subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days - 36 weeks, 4 days); spontaneous preterm labor, 28 weeks 1 day ± 2 weeks, 3 days (23 weeks, 3 days - 33 weeks, 4 days); medical indication of preterm birth, 29 weeks, 1 day ± 2 weeks, 2 days (24-36 weeks, 4 days); preterm premature rupture of the membranes, 28 weeks, 4 days ± 2 weeks, 1 day (24-33 weeks, 1 day). Among infants with type 1, type 2, or no retinopathy of prematurity, the incidence of type 1 or type 2 retinopathy of prematurity in births from spontaneous preterm labor, medical indication of preterm birth, and preterm premature rupture of the membranes was 37 of 218 (17%), 27 of 272 (10%), and 10 of 164 (6%), respectively. Adjusted for gestational age, birth weight, and multiparity and compared with the preterm premature rupture of the membranes group, the odds ratios of spontaneous preterm labor and medical indication of preterm birth for type 1 or type 2 retinopathy of prematurity were 6.1 (95% confidence interval, 1.8 to 20, P = .003) and 5.5 (95% confidence interval, 1.4 to 21, P = .01), respectively. Among neonates born after preterm premature rupture of the membranes, the probability of developing type 1 or type 2 retinopathy of prematurity was greatest in infants with rupture of membrane duration of up to 24 hours. After 24 hours, the probability of developing type 1 or type 2 retinopathy of prematurity declined. The odds of developing type 1 or type 2 retinopathy of prematurity was 9.0 (95% confidence interval 2.3 to 34, P = .002) in infants who had preterm premature rupture of the membranes ≤ 24 hours compared with infants who had preterm premature rupture of the membranes > 24 hours.Type 1 or type 2 retinopathy of prematurity are adverse ocular outcomes linked with not only lower gestational age and birth weight at delivery but also with events in the intrauterine environment that trigger a preterm birth. The reduced incidence of type 1 or type 2 retinopathy of prematurity in the preterm premature rupture of the membranes group compared with other causes of preterm birth may be related to the perinatal therapies associated with preterm premature rupture of the membranes (such as corticosteroids, antibiotics, maternal-fetal surveillance), which may have an inhibitory effect on the development of retinopathy of prematurity. We suggest that the physiologic events that predispose infants to type 1 or type 2 retinopathy of prematurity begin before delivery.
View details for PubMedID 28545834
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A Proteomic Clock of Human Pregnancy.
American journal of obstetrics and gynecology
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
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Postpartum readmission and severe maternal morbidity in California
MOSBY-ELSEVIER. 2017: S112
View details for Web of Science ID 000414256401118
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The Relationship of Longitudinal Levels of Complement Bb During Pregnancy with Preeclampsia.
American journal of reproductive immunology (New York, N.Y. : 1989)
2016; 75 (2): 104-11
Abstract
To determine the understudied relationship between complement Bb during pregnancy in subjects with preeclampsia compared with normotensive controls.Nested case-control study.Average Bb levels significantly decreased over time in pregnancy [weekly slope (S.E.): -0.0094 (0.0005), P < 0.01]. Cross-sectionally, at less than 10 weeks, Bb levels decreased with increasing gestational age in women who remained normotensive [weekly slope (S.E.): -0.007 (0.02) and for women who developed preeclampsia (weekly slope (S.E.): -0.059 (0.03) P = 0.12]. Among women who developed preeclampsia, Bb levels were greatest when samples were drawn in the gestational window of 15-20 weeks [(weekly slope (S.E.): 0.06 (0.02)], while levels among normotensive women were inversely related with gestational age [weekly slope (S.E.): -0.02 (0.01)]. The differences in slopes between cases and controls between 10 and 21 weeks' gestation were statistically significant (P = 0.003).We suggest dysregulation of Bb activation between 10 and 20 weeks' gestation in women who develop preeclampsia.
View details for DOI 10.1111/aji.12439
View details for PubMedID 26510395
View details for PubMedCentralID PMC5145263
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Effect of obesity on neonatal outcomes in pregnancies with preterm premature rupture of membranes.
American journal of obstetrics and gynecology
2016; 214 (2): 287.e1-287.e5
Abstract
Maternal obesity is associated with increased systemic inflammation and an increased risk of preterm premature rupture of membranes. There is an established association between an inflammatory intrauterine environment and adverse neonatal outcomes that is independent of gestational age and mediated by the fetal inflammatory response. It is unknown whether the maternal systemic inflammation that is present in obese women influences the intrauterine environment and predisposes the fetus to adverse neonatal outcomes after preterm premature rupture of membranes.The purpose of this study was to determine whether maternal obesity is associated with adverse neonatal outcomes in pregnancies that are complicated by preterm premature rupture of membranes.This was a secondary analysis of the Maternal-Fetal Medicine Units Network Randomized Clinical Trial on the Beneficial Effects of Antenatal Magnesium Sulfate. Women with singleton pregnancies that were affected by preterm premature rupture of membranes who delivered live-born infants between 24 + 0 and 33 + 6 weeks of gestation were included. An adverse neonatal outcome was defined as a composite outcome of neonatal death, severe necrotizing enterocolitis, respiratory distress syndrome, sepsis, or severe intraventricular hemorrhage. The rates of the composite outcome were compared between obese (body mass index, ≥30 kg/m(2)) and nonobese women. Multivariable logistic regression was used to evaluate the independent effect of obesity on neonatal outcomes. Magnesium sulfate administration, steroid administration, maternal diabetes mellitus, gestational age at delivery, indomethacin exposure, birthweight, and chorioamnionitis were all considered as possible covariates in the multivariable regression models.Three hundred twenty-five of the 1288 women (25.2%) who were included were obese, and 202 of these women (62.2%) had neonates with adverse outcomes. In univariable analysis, maternal prepregnancy obesity was associated with increased odds of an adverse neonatal outcome (odds ratio, 0.30, 95% confidence interval, 1.00-1.68). However, in our multivariable logistic regression model, gestational age at delivery (odds ratio, 0.93, 95% confidence interval, 0.92-0.94 per day), but not maternal obesity (odds ratio, 1.02, 95% confidence interval, 0.75-1.38), was associated with adverse neonatal outcomes. Obese African American women experienced preterm premature rupture of membranes (189 vs 196 days; p < .001) and delivery (199 vs 205 days; p < .001) earlier than nonobese African American women. This difference was not seen in non-African American women.Maternal obesity was not associated independently with adverse neonatal outcomes in pregnancies that were affected by preterm premature rupture of membranes after adjustment for gestational age at birth. However, obese African American women rupture and deliver earlier than other women, which causes increased neonatal morbidity.
View details for DOI 10.1016/j.ajog.2015.09.093
View details for PubMedID 26435047
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Antenatal Betamethasone for Women at Risk for Late Preterm Delivery.
The New England journal of medicine
2016; 374 (14): 1311–20
Abstract
Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities.We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001).Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).
View details for PubMedID 26842679
View details for PubMedCentralID PMC4823164
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A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis EDITORIAL COMMENT
OBSTETRICAL & GYNECOLOGICAL SURVEY
2015; 70 (12): 735–37
View details for DOI 10.1097/OGX.0000000000000276
View details for Web of Science ID 000366327900003
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A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis
NEW ENGLAND JOURNAL OF MEDICINE
2015; 373 (7): 632-641
Abstract
It is unclear whether using fetal electrocardiographic (ECG) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes.We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor. The open system displayed additional information for use when uncertain fetal heart-rate patterns were detected. The primary outcome was a composite of intrapartum fetal death, neonatal death, an Apgar score of 3 or less at 5 minutes, neonatal seizure, an umbilical-artery blood pH of 7.05 or less with a base deficit of 12 mmol per liter or more, intubation for ventilation at delivery, or neonatal encephalopathy.A total of 11,108 patients underwent randomization; 5532 were assigned to the open group, and 5576 to the masked group. The primary outcome occurred in 52 fetuses or neonates of women in the open group (0.9%) and 40 fetuses or neonates of women in the masked group (0.7%) (relative risk, 1.31; 95% confidence interval, 0.87 to 1.98; P=0.20). Among the individual components of the primary outcome, only the frequency of a 5-minute Apgar score of 3 or less differed significantly between neonates of women in the open group and those in the masked group (0.3% vs. 0.1%, P=0.02). There were no significant between-group differences in the rate of cesarean delivery (16.9% and 16.2%, respectively; P=0.30) or any operative delivery (22.8% and 22.0%, respectively; P=0.31). Adverse events were rare and occurred with similar frequency in the two groups.Fetal ECG ST-segment analysis used as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Neoventa Medical; ClinicalTrials.gov number, NCT01131260.).
View details for DOI 10.1056/NEJMoa1500600
View details for PubMedID 26267623
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Association between gelatin-thrombin matrix use and abscesses in women undergoing pelvic surgery.
Obstetrics and gynecology
2014; 124 (3): 589-95
Abstract
To assess the association between the use of gelatin-thrombin matrix and the development of pelvic abscess during hysterectomy as well as factors associated with surgeons' use of this product.Data for patients undergoing hysterectomy for obstetric-gynecologic pathology were abstracted from databases at a tertiary hospital between 2009 and 2012. Open and minimally invasive hysterectomies were included and vaginal hysterectomies were excluded. Blood loss, surgery type, comorbidities, abscess formation, and use of gelatin-thrombin matrix were examined. Abscess was defined as a walled-off fluid collection (documented with computed tomography scan) with fever (greater than 38°C) or leukocytosis (greater than 11,000/microliter). Standard statistical models were used.Of the 413 patients identified, 213 (51%) underwent surgery for malignancy. Gelatin-thrombin matrix was used in 166 patients (40%). The overall rate of abscess was low (3%). In bivariate analyses, blood loss greater than 500 mL (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-12.9, P=.021], ascites (OR 6.5, 95% CI 1.6-26.1, P=.023), drain placement (OR 4.5, 95% CI 1.3-15.1, P=.009), and gelatin-thrombin matrix use (OR 7.0, 95% CI 1.5-32.9, P=.009) were significantly associated with abscess formation. Multivariate logistic regression revealed that only gelatin-thrombin matrix use predicted the development of pelvic abscess (OR 7.0, 95% CI 1.5-32.9, P=.013).We found that gelatin-thrombin matrix use was associated with an increased risk of pelvic abscess. Although these products are important in the setting of bleeding, these data suggest that the liberal use of sealants is not without risk.III.
View details for DOI 10.1097/AOG.0000000000000406
View details for PubMedID 25162261
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Aligning academic continuing medical education with quality improvement: a model for the 21st century.
Academic medicine : journal of the Association of American Medical Colleges
2013; 88 (10): 1437-41
Abstract
The recent health care quality improvement (QI) movement has called for significant changes to the way that health care is delivered and taught in academic medical centers (AMCs). This movement also has affected academic continuing medical education (CME). In January 2011, to better align the CME and QI efforts of AMCs, the Association of American Medical Colleges (AAMC) launched a pilot initiative called Aligning and Educating for Quality (ae4Q). The goal of this pilot was to assist 11 AMCs as they moved to a more integrated model of continuous performance improvement by aligning their quality measurement and improvement with their continuing education endeavors. In this article, the authors describe the development of the ae4Q pilot and the resulting outcomes that have led to ongoing improvements.During the 18-month pilot, AAMC consultants conducted readiness assessments and on-site visits and provided consultation services and Web-based resources based on the AMC's needs. Following these interventions at each site, they then conducted both interviews with participants and postintervention assessment surveys to measure the impact of the pilot. Findings included demonstrated increases in the alignment of CME and QI, a greater use of quality data in CME design and delivery, and a greater use of CME as an intervention for clinical improvement. Two sites also attributed measureable improved clinical outcomes to their participation in the ae4Q pilot. The AAMC has used these findings to create resources and ongoing services to support AMCs as they pursue efforts to align QI and CME.
View details for DOI 10.1097/ACM.0b013e3182a34ae7
View details for PubMedID 23969360
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Rate of change in cervical length in women with vaginal bleeding during pregnancy.
Obstetrics and gynecology
2013; 121 (2 Pt 1): 260-4
Abstract
To evaluate whether women with known risk factors for preterm birth will manifest different rates of cervical shortening preceding a spontaneous preterm birth.We conducted a secondary analysis of data from the Maternal--Fetal Medicine Units Network Preterm Prediction Study. Known risk factors for preterm birth were recorded. Cervical lengths were measured between 22+0 weeks and 24+6 weeks, and again 4 weeks later. Cervical slope was defined as the change in cervical length between these visits divided by time (millimeters per week). Preterm birth was defined as preterm premature rupture of membranes or spontaneous preterm labor leading to delivery before 37 weeks of gestation. We analyzed the data for 2,584 women using logistic regression and tested for interaction between risk factors in the model to determine whether cervical shortening preceded preterm births in all variable groups.Cervical slope was not significantly associated with preterm birth (P=.9) in women with vaginal bleeding. Cervical slope was significantly associated with preterm birth in women without a history of vaginal bleeding (odds ratio 1.2, 95% confidence interval 1.1-1.4).Pregnancies without vaginal bleeding have a 20% increase in the risk of preterm birth for each additional millimeter per week increase in cervical slope. Pregnancies with vaginal bleeding are at risk for preterm birth but do not appear to undergo progressive cervical shortening. This suggests that women with vaginal bleeding undergo a different mechanism leading to preterm birth.II.
View details for DOI 10.1097/aog.0b013e31827d8e1b
View details for PubMedID 23344274
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Pandemic influenza A H1N1 2009 infection versus vaccination: a cohort study comparing immune responses in pregnancy.
PloS one
2012; 7 (3): e33048
Abstract
With the emergence of H1N1 pandemic (pH1N1) influenza, the CDC recommended that pregnant women be one of five initial target groups to receive the 2009 monovalent H1N1 vaccine, regardless of prior infection with this influenza strain. We sought to compare the immune response of pregnant women to H1N1 infection versus vaccination and to determine the extent of passive immunity conferred to the newborn.During the 2009-2010 influenza season, we enrolled a cohort of women who either had confirmed pH1N1 infection during pregnancy, did not have pH1N1 during pregnancy but were vaccinated against pH1N1, or did not have illness or vaccination. Maternal and umbilical cord venous blood samples were collected at delivery. Hemagglutination inhibition assays (HAI) for pH1N1 were performed. Data were analyzed using linear regression analyses. HAIs were performed for matched maternal/cord blood pairs for 16 women with confirmed pH1N1 infection, 14 women vaccinated against pH1N1, and 10 women without infection or vaccination. We found that pH1N1 vaccination and wild-type infection during pregnancy did not differ with respect to (1) HAI titers at delivery, (2) HAI antibody decay slopes over time, and (3) HAI titers in the cord blood.Vaccination against pH1N1 confers a similar HAI antibody response as compared to pH1N1 infection during pregnancy, both in quantity and quality. Illness or vaccination during pregnancy confers passive immunity to the newborn.
View details for PubMedID 22457731
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Magnesium for fetal neuroprotection.
American journal of obstetrics and gynecology
2011; 204 (3): 202.e1-4
Abstract
Available evidence now suggests that magnesium sulfate administered to mothers prior to early preterm delivery reduces the risk of cerebral palsy in surviving neonates. The American College of Obstetricians and Gynecologists along with the Society for Maternal-Fetal Medicine state that physicians who choose to administer magnesium sulfate for neuroprotection should do so in accordance with one of the larger randomized trials. Due to the heterogeneity of the methods, many clinicians may find it difficult to proceed with a therapeutic protocol that adheres to the available literature. Here, we present one reasonable approach that identifies the specific patients who qualify for magnesium sulfate therapy, and it outlines a treatment algorithm while addressing retreatment and concomitant tocolysis.
View details for DOI 10.1016/j.ajog.2011.01.014
View details for PubMedID 21376159
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Case records of the Massachusetts General Hospital. Case 27-2007. A 30-year-old pregnant woman with intrauterine fetal death.
The New England journal of medicine
2007; 357 (9): 918-25
View details for DOI 10.1056/NEJMcpc079021
View details for PubMedID 17761596
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Perinatal infections due to group B streptococci.
Obstetrics and gynecology
2004; 104 (5 Pt 1): 1062-76
Abstract
Group B streptococci (GBS) emerged dramatically in the 1970s as the leading cause of neonatal infection and as an important cause of maternal uterine infection. We review the epidemiology, diagnosis, and therapy of GBS perinatal infection. In 1996, the first national consensus guidelines were released. Since then, there has been a 70% reduction in early-onset neonatal GBS infection, but no decrease in late-onset neonatal GBS disease. In 2002, new national guidelines were released recommending 1) solely a screen-based prevention strategy, 2) a new algorithm for patients with penicillin allergy, and 3) more specific practices in certain clinical scenarios. Yet many clinical issues remain, including implementation of new diagnostic techniques, management of preterm rupture of membranes, use of alternative antibiotic approaches, improvement of compliance, prevention of low birth weight infants, emergence of resistant organisms, and vaccine development.
View details for DOI 10.1097/01.AOG.0000144128.03913.c2
View details for PubMedID 15516403
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Chronic intrauterine infection and inflammation in the preterm rabbit, despite antibiotic therapy.
American journal of obstetrics and gynecology
2002; 186 (2): 234-9
Abstract
In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days.New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn. At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam. Primary outcomes were positive cultures and histologic inflammation score. Tumor necrosis factor-alpha levels in the amniotic fluid were determined by bioassay.A total of 60 animals were inoculated with E coli. At the endpoint, uterine cultures were positive more commonly than in the fetus or amniotic fluid (41.8% vs 27.5% vs 17.3%, respectively), which was consistent with an ascending pathway of infection. Inflammation scores were similar in uterus and placenta but lower in fetal lung and absent in fetal brain (2.8 vs 3.1 vs 0.84 vs 0.0, respectively). Comparing the durations of delay in antibiotic administration, we found a significant increase in positive uterine cultures and a significant increase in histologic inflammation score with increasing delay. The proportion of dead pups within a litter was significantly associated with the log of the tumor necrosis factor-alpha concentration in amniotic fluid and the degree of histologic inflammation in the uterus, but not with amniotic fluid or other culture positivity.The administration of therapeutic doses of antibiotic does not consistently eradicate bacteria from the rabbit uterus nor, more importantly, from the fetus and the amniotic fluid. Obtaining a negative amniotic fluid culture does not exclude either infection in the decidua or the fetus or histologic inflammation with tumor necrosis factor-alpha elaboration.
View details for DOI 10.1067/mob.2002.119640
View details for PubMedID 11854641