Trends in racial/ethnic disparities in postpartum hospital readmissions in California from 1997 to 2018.

BACKGROUND: Postpartum readmission is an important indicator of postpartum morbidity. The likelihood of postpartum readmission is highest for Black individuals. However, it is unclear whether the likelihood of postpartum readmission has changed over time according to race/ethnicity. Little is also known about the factors that contribute to these trends. OBJECTIVE: This study aimed to: (1) examine trends in postpartum readmission by race/ethnicity, (2) examine if prenatal or clinical factors explain the trends, and (3) investigate if racial/ethnic disparities changed over time. STUDY DESIGN: We examined trends in postpartum readmission, defined as hospitalization within 42 days after birth hospitalization discharge, using live birth and fetal death certificates linked to delivery discharge records from 10,711,289 births in California from 1997 to 2018. We used multivariable logistic regression models that included year and year-squared (to allow for nonlinear trends), overall and stratified by race/ethnicity, to estimate the annual change in postpartum readmission during the study period, represented by odds ratios and 95% confidence intervals. We then adjusted models for prenatal (eg, patient demographics) and clinical (eg, gestational age, mode of birth) factors. To determine whether racial/ethnic disparities changed over time, we calculated risk ratios for 1997 and 2018 by comparing the predicted probabilities from the race-specific, unadjusted logistic regression models. RESULTS: The overall incidence of postpartum readmission was 10 per 1000 births (17.4/1000 births for non-Hispanic Black, 10/1000 for non-Hispanic White, 7.9/1000 for non-Hispanic Asian/Pacific Islander, and 9.6/1000 for Hispanic individuals). Odds of readmission increased for all groups during the study period; the increase was greatest for Black individuals (42% vs 21%-29% for the other groups). After adjustment for prenatal and clinical factors, the increase in odds was similar for Black and White individuals (12%). The disparity in postpartum readmission rates relative to White individuals increased for Black individuals (risk ratio, 1.68 in 1997 and 1.90 in 2018) and more modestly for Hispanic individuals (risk ratio, 1.02 in 1997 and 1.05 in 2018) during the study period. Asian/Pacific Islander individuals continued to have lower risk than White individuals during the study period (risk ratio, 0.87 in 1997 and 0.82 in 2018). CONCLUSION: The rate of postpartum readmissions increased from 1997 to 2018 in California across all racial/ethnic groups, with the greatest increase observed for Black individuals. Racial/ethnic differences in the trend were more modest after adjustment for prenatal and clinical factors. It is important to find ways to prevent further increases in postpartum readmission, especially among groups at highest risk.

Near-miss and maternal sepsis mortality: A qualitative study of survivors and support persons.

BACKGROUND: Prior studies have shown that maternal deaths due to sepsis occur due to delays in recognition, treatment, and escalation of care through medical chart reviews. This study was conducted to obtain the patient perspective for near-miss and maternal mortality cases due to sepsis. OBJECTIVE: To identify quality improvement opportunities for improving maternal sepsis through patient and support person experiences. STUDY DESIGN: Twenty semi-structured interviews and three follow-up focus groups with patients who experienced critical illness from maternal sepsis in the United States and their support persons (when available) were conducted from May 23, 2022, through October 14, 2022. In this qualitative study, data were analyzed using inductive thematic analysis. RESULTS: In this qualitative study of patients with maternal sepsis and their support persons, four main quality improvement themes were identified. The themes were the following: (1) participants reported a lack of awareness of pregnancy-related warning signs and symptoms of when to seek care, (2) many of the presenting symptoms participants experienced were not typical of expected warning signs of maternal sepsis, such as severe pain, overwhelming tiredness, and lack of fever (3) participant concerns were met with dismissal leading to delays in diagnosis, (4) participants experienced long-term sequelae but had difficulty receiving screening and referrals for treatment. CONCLUSIONS: The findings of this study suggest that standardized patient education about the warning signs of maternal sepsis and provider education about the presentation of maternal sepsis, improved listening to patients, and follow-up for sequalae of sepsis are needed.

Persistent Bacterial Vaginosis and Risk for Spontaneous Preterm Birth.

OBJECTIVE: The aim of this study was to determine the association between persistent bacterial vaginosis (BV) in pregnancy and risk for spontaneous preterm birth (sPTB). STUDY DESIGN: 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. RESULTS: 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]. CONCLUSION: Persistent BV may have a higher risk for sPTB than a single episode of BV in pregnancy. KEY POINTS: · 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..

Multiomic signals associated with maternal epidemiological factors contributing to preterm birth in low- and middle-income countries.

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.

Early Postpartum Hospital Encounters among Patients with Genitourinary and Wound Infections during Hospitalization for Birth.

OBJECTIVES: This study aimed 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 genitourinary and wound infections during the birth hospitalization. STUDY DESIGN: We conducted a population-based cohort study of births in California during 2016 to 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 emergency department (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. RESULTS: Among 1,217,803 birth hospitalizations, 5.5% were complicated by genitourinary and wound infections. Genitourinary or wound infection was associated with an early postpartum hospital encounter among patients with both vaginal births (2.2%; adjusted risk ratio [aRR[: 1.26; 95% confidence interval [CI]: 1.17-1.36) and cesarean births (3.2%; aRR: 1.23; 95% CI: 1.15-1.32). Patients with a cesarean birth and a major puerperal infection or wound infection had the highest risk of an early postpartum hospital encounter (6.4 and 4.3%, respectively). Among patients with genitourinary and wound infections during the 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). CONCLUSION: 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 cesarean birth and a major puerperal infection or wound infection. KEY POINTS: · In all, 5.5% of patients giving birth had a genitourinary or wound infection (GWI).. · A total of 2.7% of GWI patients had a hospital encounter within 3 days of discharge after birth.. · Major puerperal infection and wound infection had the highest risk of an early hospital encounter.. · Among GWI patients, several birth complications were associated with an early hospital encounter..

Evaluation of Hypoglycemia in Neonates of Women at Risk for Late Preterm Delivery: An Antenatal Late Preterm Steroids Trial Cohort Study.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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. KEY POINTS: · 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..

Early postpartum readmissions: identifying risk factors at birth hospitalization.

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.

Effect of gestational age at first delivery and interpregnancy interval on the recurrence of clinical chorioamnionitis.

BACKGROUND: 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. OBJECTIVE: This study aimed to evaluate how gestational age of delivery in a first pregnancy and interpregnancy interval affect the odds of recurrent clinical chorioamnionitis. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Postpartum care visits among commercially insured women in the United States.

BACKGROUND: To reduce postpartum morbidity and mortality, optimizing routine outpatient postpartum care has become a focus of national attention and a healthcare priority. OBJECTIVE: This study aimed to examine the timing, content, and predictors of routine outpatient postpartum visit attendance within a large, commercially insured patient population. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Incidence, prevalence, and timing of postpartum complications and mortality in Canada and the United States: a systematic review and meta-analysis protocol.

OBJECTIVE: The goal of this systematic review is to assess the incidence, prevalence, and timing of common postpartum (up to 1 year after delivery) medical, surgical/procedural, and psychosocial complications and mortality. INTRODUCTION: 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. INCLUSION CRITERIA: 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 1 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 fewer than 100 patients, participants younger than 18 years, no reporting of duration, or focus on patients with a specific condition rather than a general postpartum population will be excluded. METHODS: The search strategy was codeveloped 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. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022303047.

Using Longitudinally Linked Data to Measure Severe Maternal Morbidity Beyond the Birth Hospitalization in California.

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.

Perinatal infection, inflammation, preterm birth, and brain injury: A review with proposals for future investigations.

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.

Proteomic signatures predict preeclampsia in individual cohorts but not across cohorts - implications for clinical biomarker studies.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset.

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.

Lactate and procalcitonin levels in peripartum women with intraamniotic infection.

BACKGROUND: Pregnant women are vulnerable to infection as their immune response is modulated. OBJECTIVE: 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 an intraamniotic infection to determine whether they are useful biomarkers for infection during labor. STUDY DESIGN: We performed a prospective, observational cohort study of term, singleton pregnancies admitted with planned vaginal delivery in 2019 at a university medical center. The lactate and procalcitonin levels were determined during early labor, within 2 hours following delivery, and on postpartum day 1. Women with an intraamniotic infection in addition had their lactate and procalcitonin levels determined following an intraamniotic infection diagnosis. Samples were processed immediately in the hospital clinical laboratory. The primary outcome was the mean lactate level following delivery. The secondary outcomes were the lactate and procalcitonin levels at other time points. Comparisons based on infection status were performed using multivariate linear regressions. RESULTS: A total of 22 women with intraamniotic infection and 29 uninfected women were included. The mean early labor 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 the uninfected and intraamniotic infection groups. The mean lactate level was highest following delivery for women in both the uninfected and intraamniotic infection groups (2.00 vs 2.33 mmol/L; adjusted P=.08; 95% confidence interval, 0.98-1.53). The lactate level returned to normal by postpartum day 1 and did not differ significantly based on the infection status at any time point in the adjusted models. The procalcitonin level following delivery was higher among women with vs without an intraamniotic infection (0.142 vs 0.091 ng/mL; adjusted P=.03). The procalcitonin level rose further in both the intraamniotic infection and uninfected groups on postpartum day 1 (0.737 vs 0.408 ng/mL; adjusted P=.05). CONCLUSION: The lactate level is not significantly elevated in pregnant women with an intraamniotic infection above the physiological increase that is observed in women without infection at delivery. The procalcitonin level is elevated at delivery in women with an intraamniotic infection and warrants further investigation as a peripartum infection marker.

Risk factors for postpartum readmission among women after having a stillbirth.

BACKGROUND: Compared to women with a live birth, 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 was a population-based cohort study of 29,654 women with a stillbirth in California from 1997 to 2011. Using logistic regression models, we examined the association of maternal patient-level factors with postpartum readmission among women after a stillbirth within 6 weeks of hospital discharge and between 6 weeks and 9 months after delivery. RESULTS: Within 6 weeks after a stillbirth, 642 women (2.2%) had a postpartum readmission. Risk factors for postpartum readmission after a stillbirth were severe maternal morbidity excluding transfusion (adjusted odds ratio, 3.02; 95% confidence interval, 2.28-4.00), transfusion at delivery but no other indication of severe maternal morbidity (adjusted odds ratio, 1.95; 95% confidence interval, 1.35-2.81), gestational hypertension or preeclampsia (adjusted odds ratio, 1.93; 95% confidence interval, 1.54-2.42), prepregnancy hypertension (adjusted odds ratio, 1.80; 95% confidence interval, 1.36-2.37), diabetes mellitus (adjusted odds ratio, 1.78; 95% confidence interval, 1.33-2.37), antenatal hospitalization (adjusted odds ratio, 1.78; 95% confidence interval, 1.43-2.21), cesarean delivery (adjusted odds ratio, 1.73; 95% confidence interval, 1.43-2.21), long length of stay in the hospital after delivery (>2 days for vaginal delivery and >4 days for cesarean delivery) (adjusted odds ratio, 1.59; 95% confidence interval, 1.33-1.89), non-Hispanic black race and ethnicity (adjusted odds ratio, 1.38; 95% confidence interval, 1.08-1.76), and having less than a high school education (adjusted odds ratio, 1.35; 95% confidence interval, 1.02-1.80). From 6 weeks to 9 months, 1169 women (3.90%) had a postpartum readmission; significantly associated risk factors were largely similar to those for earlier readmission. CONCLUSION: Women with comorbidities, with birth-related complications, of non-Hispanic black race and 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 discharge from the hospital.

Maternal and Neonatal Outcomes Associated with Amniotomy among Nulliparous Women Undergoing Labor Induction at Term.

OBJECTIVE: 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. STUDY DESIGN: 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). RESULTS: 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. CONCLUSION: 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.

Maternal Health after Stillbirth: Postpartum Hospital Readmission in California.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: · 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..