Ambient air pollution and rate of spontaneous abortion.

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013-2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM2.5, NO2, and O3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 µg/m3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO2 and O3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM2.5, NO2, and O3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM2.5 with SAB incidence in Canada.

Neonatal Outcomes Are Similar between Patients with Resolved and Those with Persistent Oligohydramnios.

OBJECTIVE: Oligohydramnios (defined as amniotic fluid volume < 5 cm or deepest vertical pocket < 2 cm) is regarded as an ominous finding on prenatal ultrasound. Amniotic fluid, however, is not static, and to date, there have been no studies comparing perinatal outcomes in patients who are diagnosed with oligohydramnios that resolves and those who have persistent oligohydramnios. STUDY DESIGN: This is a secondary analysis of a National Institutes of Health-funded retrospective cohort study of singleton gestations delivered at a tertiary care hospital between 2002 and 2013 with mild hypertensive disorders and/or fetal growth restriction (FGR). Maternal characteristics, delivery, and neonatal information were abstracted by trained research nurses. Patients with a diagnosis of oligohydramnios were identified, and those with resolved versus persistent oligohydramnios at the time of delivery were compared. The primary outcome was a composite of neonatal resuscitation at delivery: administration of oxygen, bag-mask ventilation, continuous positive airway pressure, intubation, chest compression, or cardiac medication administration. Secondary outcomes included FGR, timing, and mode of delivery. RESULTS: Of 527 women meeting study criteria, 42 had oligohydramnios that resolved prior to delivery, whereas 485 had persistent oligohydramnios. There were no significant differences in patient demographics between groups. The gestational age at diagnosis was significantly lower for patients with resolved versus persistent oligohydramnios (median: 33.0 [interquartile range, IQR: 29.1-35.9] vs. 38.0 [IQR: 36.4-39.3], p < 0.001). There was not a substantial difference in rate of neonatal resuscitation (41 vs. 32%, p = 0.31). Patients with resolved oligohydramnios were more likely to have developed FGR than those with persistent oligohydramnios (55 vs. 36%, p < 0.02). There were no significant differences for gestational age at delivery, birth weight, or neonatal intensive care unit admission. CONCLUSION: Patients whose oligohydramnios resolved were diagnosed earlier yet had similar rates of neonatal resuscitation but higher rates of FGR than those who had persistent oligohydramnios. KEY POINTS: · When diagnosed earlier in pregnancy, oligohydramnios was more likely to resolve prenatally.. · Patients who were diagnosed with oligohydramnios earlier in pregnancy had higher rates of FGR.. · There were no differences in the rates of the composite outcome of need for neonatal resuscitation when comparing those with resolved versus those with persistent oligohydramnios. No differences in composite neonatal morbidity were noted between those with resolved versus persistent oligohydramnios..

Enhancing Epidemiology's Impact on Policy: Mediation by Expert Committees.

Epidemiologic evidence is often a key source of information used by expert committees to guide policy decisions, yet epidemiologists rarely consider this audience for their research. For a better understanding of the pipeline from epidemiologic research to expert committee assessment to policy, several reports from the National Academies of Sciences, Engineering, and Medicine were reviewed and discussed with staff and committee members. The topics of these consensus committee assessments included health behaviors, medical care, and military exposures. The focus was often on emerging issues of immediate concern for which there was little relevant research available but a need for prompt action. Committees generally sought a comprehensive assessment of potential health effects of a given product or exposure, which often included social and behavioral health outcomes that are rarely addressed by epidemiologists. To enhance epidemiology's contribution to societal decisions, the choice of research topics should expand to consider emerging societal concerns. Research funding agencies need to be engaged as mediators between committee needs and the research community to stimulate contributory research. Improved communication of research needs to the epidemiology community would be beneficial to researchers aspiring to have an impact and to those who use epidemiologic information to help guide policy decisions.

Can Cross-Sectional Studies Contribute to Causal Inference? It Depends.

Cross-sectional studies-often defined as those in which exposure and outcome are assessed at the same point in time-are frequently viewed as minimally informative for causal inference. While cross-sectional studies may be susceptible to reverse causality, may be limited to assessment of disease prevalence rather than incidence, or may only provide estimates of current rather than past exposures, not all cross-sectional studies suffer these limitations. Moreover, none of these concerns are unique to or inherent in the structure of a cross-sectional study. Regardless of when exposure and disease were ascertained relative to one another, a cross-sectional study may provide insights into the causal effects of exposure on disease incidence. Simply labeling a study as "cross-sectional" and assuming that 1 or more of these limitations exist and are materially important fails to recognize the need for a more nuanced assessment and risks discarding evidence that may be useful in assessing causal relationships.

A prospective cohort study of preconception COVID-19 vaccination and miscarriage.

STUDY QUESTION: To what extent is preconception maternal or paternal coronavirus disease 2019 (COVID-19) vaccination associated with miscarriage incidence? SUMMARY ANSWER: COVID-19 vaccination in either partner at any time before conception is not associated with an increased rate of miscarriage. WHAT IS KNOWN ALREADY: Several observational studies have evaluated the safety of COVID-19 vaccination during pregnancy and found no association with miscarriage, though no study prospectively evaluated the risk of early miscarriage (gestational weeks [GW] <8) in relation to COVID-19 vaccination. Moreover, no study has evaluated the role of preconception vaccination in both male and female partners. STUDY DESIGN, SIZE, DURATION: An Internet-based, prospective preconception cohort study of couples residing in the USA and Canada. We analyzed data from 1815 female participants who conceived during December 2020-November 2022, including 1570 couples with data on male partner vaccination. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible female participants were aged 21-45 years and were trying to conceive without use of fertility treatment at enrollment. Female participants completed questionnaires at baseline, every 8 weeks until pregnancy, and during early and late pregnancy; they could also invite their male partners to complete a baseline questionnaire. We collected data on COVID-19 vaccination (brand and date of doses), history of SARS-CoV-2 infection (yes/no and date of positive test), potential confounders (demographic, reproductive, and lifestyle characteristics), and pregnancy status on all questionnaires. Vaccination status was categorized as never (0 doses before conception), ever (≥1 dose before conception), having a full primary sequence before conception, and completing the full primary sequence ≤3 months before conception. These categories were not mutually exclusive. Participants were followed up from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss to follow-up, 20 weeks' gestation), whichever occurred first. We estimated incidence rate ratios (IRRs) for miscarriage and corresponding 95% CIs using Cox proportional hazards models with GW as the time scale. We used propensity score fine stratification weights to adjust for confounding. MAIN RESULTS AND THE ROLE OF CHANCE: Among 1815 eligible female participants, 75% had received at least one dose of a COVID-19 vaccine by the time of conception. Almost one-quarter of pregnancies resulted in miscarriage, and 75% of miscarriages occurred <8 weeks' gestation. The propensity score-weighted IRR comparing female participants who received at least one dose any time before conception versus those who had not been vaccinated was 0.85 (95% CI: 0.63, 1.14). COVID-19 vaccination was not associated with increased risk of either early miscarriage (GW: <8) or late miscarriage (GW: 8-19). There was no indication of an increased risk of miscarriage associated with male partner vaccination (IRR = 0.90; 95% CI: 0.56, 1.44). LIMITATIONS, REASONS FOR CAUTION: The present study relied on self-reported vaccination status and infection history. Thus, there may be some non-differential misclassification of exposure status. While misclassification of miscarriage is also possible, the preconception cohort design and high prevalence of home pregnancy testing in this cohort reduced the potential for under-ascertainment of miscarriage. As in all observational studies, residual or unmeasured confounding is possible. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to evaluate prospectively the relation between preconception COVID-19 vaccination in both partners and miscarriage, with more complete ascertainment of early miscarriages than earlier studies of vaccination. The findings are informative for individuals planning a pregnancy and their healthcare providers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Health [R01-HD086742 (PI: L.A.W.); R01-HD105863S1 (PI: L.A.W. and M.L.E.)], the National Institute of Allergy and Infectious Diseases (R03-AI154544; PI: A.K.R.), and the National Science Foundation (NSF-1914792; PI: L.A.W.). The funders had no role in the study design, data collection, analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. L.A.W. is a fibroid consultant for AbbVie, Inc. She also receives in-kind donations from Swiss Precision Diagnostics (Clearblue home pregnancy tests) and Kindara.com (fertility apps). M.L.E. received consulting fees from Ro, Hannah, Dadi, VSeat, and Underdog, holds stock in Ro, Hannah, Dadi, and Underdog, is a past president of SSMR, and is a board member of SMRU. K.F.H. reports being an investigator on grants to her institution from UCB and Takeda, unrelated to this study. S.H.-D. reports being an investigator on grants to her institution from Takeda, unrelated to this study, and a methods consultant for UCB and Roche for unrelated drugs. The authors report no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Predicting primary cesarean delivery in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Prediction models have shown promise in helping clinicians and patients engage in shared decision-making by providing quantitative estimates of individual risk of important clinical outcomes. Gestational diabetes mellitus is a common complication of pregnancy, which places patients at higher risk of primary CD. Suspected fetal macrosomia diagnosed on prenatal ultrasound is a well-known risk factor for primary CD in patients with gestational diabetes mellitus, but tools incorporating multiple risk factors to provide more accurate CD risk are lacking. Such tools could help facilitate shared decision-making and risk reduction by identifying patients with both high and low chances of intrapartum primary CD. OBJECTIVE: This study aimed to develop and internally validate a multivariable model to estimate the risk of intrapartum primary CD in pregnancies complicated by gestational diabetes mellitus undergoing a trial of labor. STUDY DESIGN: This study identified a cohort of patients with gestational diabetes mellitus derived from a large, National Institutes of Health-funded medical record abstraction study who delivered singleton live-born infants at ≥34 weeks of gestation at a large tertiary care center between January 2002 and March 2013. The exclusion criteria included previous CD, contraindications to vaginal delivery, scheduled primary CD, and known fetal anomalies. Candidate predictors were clinical variables routinely available to a practitioner in the third trimester of pregnancy found to be associated with an increased risk of CD in gestational diabetes mellitus. Stepwise backward elimination was used to build the logistic regression model. The Hosmer-Lemeshow test was used to demonstrate goodness of fit. Model discrimination was evaluated via the concordance index and displayed as the area under the receiver operating characteristic curve. Internal model validation was performed with bootstrapping of the original dataset. Random resampling with replacement was performed for 1000 replications to assess predictive ability. An additional analysis was performed in which the population was stratified by parity to evaluate the model's predictive ability among nulliparous and multiparous individuals. RESULTS: Of the 3570 pregnancies meeting the study criteria, 987 (28%) had a primary CD. Of note, 8 variables were included in the final model, all significantly associated with CD. They included large for gestational age, polyhydramnios, older maternal age, early pregnancy body mass index, first hemoglobin A1C recorded in pregnancy, nulliparity, insulin treatment, and preeclampsia. Model calibration and discrimination were satisfactory with the Hosmer-Lemeshow test (P=.862) and an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.74-0.77). Internal validation demonstrated similar discriminatory ability. Stratification by parity demonstrated that the model worked well among both nulliparous and multiparous patients. CONCLUSION: Using information routinely available in the third trimester of pregnancy, a clinically pragmatic model can predict intrapartum primary CD risk with reasonable reliability in pregnancies complicated by gestational diabetes mellitus and may provide quantitative data to guide patients in understanding their individual primary CD risk based on preexisting and acquired risk factors.

Association Between Change in Physical Activity During Pregnancy and Infant Birth Weight.

OBJECTIVE: We assessed whether total, recreational, and non-recreational physical activity (PA) assessed twice during pregnancy, and its change, were associated with infant birth weight and small for gestational age (SGA). METHODS: We included 1467 Pregnancy, Infection, and Nutrition 3 Study participants who self-reported PA at time 1 (T1: 17-22 weeks' gestation) and time 2 (T2: 27-30 weeks' gestation). We assessed last week absolute intensities of PA (moderate: 4.7-7.1 METs; and vigorous: > 7.1 METs) and perceived intensities. Change in hours/week of PA was assessed continuously or categorically (increase or decrease ≥ 1 hour, and no change). Associations of continuous PA hours/week at T1, T2, and its change, with sex-specific z-scores of birth weight, were assessed using multivariable linear robust regressions. We used logistic regressions to assess categorical PA measures with SGA. Models were adjusted for adequacy of maternal weight gain, general health, maternal age, parity, race/ethnicity, and smoking. RESULTS: Hours/week of total and recreational absolute intensities of PA at T1, T2, and its change were generally not associated with birth weight, although two measures of non-recreational PA at T2 and its change were associated with increased birth weight. Perceived intensities of PA (at T1, T2, and its change) were largely not associated with sex-specific z-scores of infant birth weight. Absolute and perceived intensity PA were not associated with SGA. CONCLUSIONS FOR PRACTICE: In this observational cohort, increases and decreases in PA during pregnancy were not associated with differential changes in birthweight or SGA.

Outcomes among Neonates after a Diagnosis of Persistent or Transient Fetal Growth Restriction Delivered at Term.

OBJECTIVE: This study aimed to evaluate whether transient fetal growth restriction (FGR) that resolves prior to delivery confers a similar risk of neonatal morbidity as uncomplicated FGR that persists at term. STUDY DESIGN: This is a secondary analysis of a medical record abstraction study of singleton live-born pregnancies delivered at a tertiary care center between 2002 and 2013. Patients with fetuses that had either persistent or transient FGR and delivered at 38 weeks or later were included. Patients with abnormal umbilical artery Doppler studies were excluded. Persistent FGR was defined as estimated fetal weight (EFW) <10th percentile by gestational age from diagnosis through delivery. Transient FGR was defined as EFW <10th percentile on at least one ultrasound, but not on the last ultrasound prior to delivery. The primary outcome was a composite of neonatal morbidity: neonatal intensive care unit admission, Apgar's score <7 at 5 minutes, neonatal resuscitation, arterial cord pH <7.1, respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, sepsis, or death. Baseline characteristics and obstetric and neonatal outcomes were compared using Wilcoxon's rank-sum and Fisher's exact test. Log binomial regression was used to adjust for confounders. RESULTS: Of 777 patients studied, 686 (88%) had persistent FGR and 91 (12%) had transient FGR. Patients with transient FGR were more likely to have a higher body mass index, gestational diabetes, diagnosed with FGR earlier in pregnancy, have spontaneous labor, and deliver at later gestational ages. There was no difference in the composite neonatal outcome (relative risk = 1.03, 95% confidence interval [CI] 0.72, 1.47) for transient versus persistent FGR after adjusting for confounders (adjusted relative risk = 0.79, 95% CI 0.54, 1.17). There were no differences in cesarean delivery or delivery complications between groups. CONCLUSION: Neonates born at term after transient FGR do not appear to have differences in composite morbidity compared with those where uncomplicated FGR persists at term. KEY POINTS: · No differences in neonatal outcomes in uncomplicated persistent versus transient FGR at term.. · Transient FGR pregnancies more likely to deliver at later gestational ages.. · No differences in mode of delivery or obstetric complications in persistent versus transient FGR at term..

Neonatal and Maternal Outcomes of Pregnancies following Stillbirth.

OBJECTIVE: Prior stillbirth increases risk of subsequent stillbirth but has unclear effect on subsequent liveborn pregnancies. We examined associations between prior stillbirth, adverse neonatal outcomes, and maternal morbidity in subsequent liveborn pregnancies. STUDY DESIGN: This is a secondary analysis of a large, National Institutes of Health-funded retrospective cohort study of parturients who delivered a singleton infant at a tertiary-care hospital from January 2002 to March 2013 and had a past medical/obstetric history of diabetic, and/or hypertensive disorders, and/or pregnancy with fetal growth restriction. Our analysis included all multiparous patients from the parent study. The primary outcome was a neonatal morbidity composite (neonatal resuscitation, neonatal birth injury, respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, sepsis). Secondary outcomes included a maternal morbidity composite (venous thromboembolism, intensive care unit admission, disseminated intravascular coagulation, sepsis, hysterectomy, pulmonary edema, renal failure, blood transfusion), other maternal/delivery complications, and neonatal intensive care unit (NICU) admission. Outcomes were compared between those with versus without prior stillbirth. Negative binomial regression controlled for maternal comorbidities and delivery year. RESULTS: Among 171 and 5,245 multiparous parturients with versus without prior stillbirth, respectively, those with prior stillbirth had higher rates of pregestational diabetes, autoimmune disease, and clotting disorders. After controlling for these differences and delivery year, infants of parturients with prior stillbirth had similar risk of composite neonatal morbidity (adjusted relative ratio [aRR] 1.19; 95% confidence interval [CI] 0.99-1.45) but higher risk of NICU admission (aRR 1.42; 95% CI 1.06-1.91) compared with infants of parturients without prior stillbirth, despite delivering at similar gestational ages. Multiparous patients with prior stillbirth had equal maternal morbidity risk but higher risk of developing preeclampsia with severe features (aRR 2.11; 95% CI 1.19-3.72). CONCLUSION: Compared with high-risk multiparous patients without prior stillbirth, those with prior stillbirth have higher risk of NICU admission and preeclampsia with severe features. KEY POINTS: · Prior stillbirth increases risk in subsequent livebirth for NICU admission and neonatal morbidity.. · Prior stillbirth increased the risk of severe preeclampsia for mothers in subsequent livebirth.. · Additional monitoring of pregnancies of patients with prior history of demise may be warranted..

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. METHODS: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants' first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. RESULTS: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants' first RSV season occurred among term infants without known comorbidities. CONCLUSIONS: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants' first RSV season. Future prevention efforts should consider all infants.

Health Outcomes Associated With Clinician-initiated Delivery for Hypertensive Disorders at 34-38 Weeks' Gestation.

BACKGROUND: Clinicians caring for the nearly 10% of patients in the United States with nonsevere hypertensive disorders in late pregnancy need better evidence to balance risks and benefits of clinician-initiated delivery. METHODS: We conducted a record-based cohort study of maternal and infant health outcomes among deliveries from 2002-2013 at Women & Infants Hospital of Rhode Island. Participants had gestational hypertension or nonsevere preeclampsia before 39 weeks' gestation (N=4,295). For each gestational week from 34 to 38, we compared outcomes between clinician-initiated deliveries (induction of labor or prelabor cesarean) and those not initiated in that week, using propensity score models to control confounding by indication. RESULTS: The analysis predicted an increment in risk of adverse maternal and infant outcomes sustained through week 37 if all patients underwent clinician-initiated delivery, with risk differences on the order of 0.2 for maternal outcomes and 0.3 for infant outcomes weeks 34 and 35. For women undergoing clinician-initiated delivery, the analysis identified increased risk of progression to severe disease in weeks 35 and 36, increases in all adverse infant outcomes only in week 34, increases in Neonatal Intensive Care Unit admission and infant hospital stay in weeks 35 and 36, and no meaningful increase in any of the adverse outcomes in weeks 37 or 38. CONCLUSIONS: We estimate that hypertensive pregnancies chosen for intervention were minimally harmed by early delivery after 34 weeks' gestation but predict benefit from extension to 37 weeks. Our study also showed adverse infant health consequences associated with routine delivery prior to 37 weeks.

A Prospective Cohort Study of Seasonal Variation in Spontaneous Abortion.

BACKGROUND: Up to 30% of pregnancies end in spontaneous abortion, yet few risk factors have been identified. Examining seasonal patterns in risk of spontaneous abortion can generate new hypotheses regarding environmental and lifestyle determinants. METHODS: We used data from Pregnancy Study Online-a preconception cohort study of pregnancy planners from the United States and Canada-to examine seasonal variation in spontaneous abortion risk. We enrolled 12,197 women during 2013 to 2020, 6104 of whom reported a conception within 12 months of enrollment. On follow-up questionnaires, participants reported date of spontaneous abortion and weeks gestation at time of loss. We used periodic regression to estimate two aspects of seasonal occurrence: peak/low ratio-a measure of intensity of seasonal variation-and peak timing. We examined season at risk (from the date of each gestational week) in relation to spontaneous abortion; in a secondary analysis, we examined season of conception in relation to spontaneous abortion. We controlled for seasonal patterns in attempt initiation via month the pregnancy attempt began. RESULTS: Almost 20% of women experienced spontaneous abortion. Risk was highest in late August, with a peak/low ratio of 1.3 (95% confidence interval [CI] = 1.1, 1.6). This seasonal pattern was evident almost exclusively for spontaneous abortion at <8 weeks since the last menstrual period date (peak/low ratio = 1.4; 95% CI = 1.2, 1.8), and associations were stronger among women living in the Southern and Midwestern United States. CONCLUSIONS: Environmental or lifestyle factors more prevalent in late summer may be associated with increased risk of early spontaneous abortion.

Term Labor Induction and Cesarean Delivery Risk among Obese Women with and without Comorbidities.

OBJECTIVE: Findings of the recent ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial, showing reduced cesarean risk with elective labor induction among low-risk nulliparous women at 39 weeks' gestation, have the potential to change interventional delivery practices but require examination in wider populations. The aim of this study was to identify whether term induction of labor was associated with reduced cesarean delivery risk among women with obesity, evaluating several maternal characteristics associated with obesity, induction, and cesarean risk. STUDY DESIGN: We studied administrative records for 66,280 singleton, term births to women with a body mass index ≥30, without a prior cesarean delivery, in New York City from 2008 to 2013. We examined elective inductions in 39 and 40 weeks' gestation and calculated adjusted risk ratios for cesarean delivery risk, stratified by parity and maternal age. We additionally evaluated medically indicated inductions at 37 to 40 weeks among women with obesity and diabetic or hypertensive disorders, comorbidities that are strongly associated with obesity. RESULTS: Elective induction of labor was associated with a 25% (95% confidence interval: 19-30%) lower adjusted risk of cesarean delivery as compared with expectant management at 39 weeks of gestation and no change in risk at 40 weeks. Patterns were similar when stratified by parity and maternal age. Risk reductions in week 39 were largest among women with a prior vaginal delivery. Women with comorbidities had reduced cesarean risk with early term induction and in 39 weeks. CONCLUSION: Labor induction at 39 weeks was consistently associated with reduced risk of cesarean delivery among women with obesity regardless of parity, age, or comorbidity status. Cesarean delivery findings from induction trials at 39 weeks among low-risk nulliparous women may generalize more broadly across the U.S. obstetric population, with potentially larger benefit among women with a prior vaginal delivery. KEY POINTS: · We found reduced cesarean risk with induction at 39 weeks.. · Results were consistent for age and comorbidity subgroups.. · Risk reductions were largest among multiparous women..

Point: Reconciling Epidemiology's Aspirations and Capabilities.

Interpreting the results of epidemiologic studies calls for objectivity and rigorous scrutiny, acknowledging the limitations that temper the applicability of the findings to public health action. Current trends have posed new challenges to balancing goals of scientific objectivity and validity with public health applications. The ongoing tension between epidemiology's aspirations and capability has several sources: the need to overpromise in research proposals, compromising methodological rigor because of public health importance, defending findings in the face of hostile critics, and appealing to core constituencies who have specific expectations from the research.

Invited Commentary: The Epidemiology of Electronic Cigarettes and Reproductive Health Begins.

Harlow et al. (Am J Epidemiol. 2021;190(3):353-361) are among the first to tackle the complex subject of electronic cigarette use and reproductive health, focused on fecundity but pertinent to the full spectrum of reproductive health concerns. Despite extensive documentation of the health harm from tobacco use and a shared exposure to nicotine, electronic cigarette (e-cigarette) users have a markedly different exposure profile. Because e-cigarettes might help to curtail or eliminate tobacco smoking, the health comparisons of interest for e-cigarettes should include cigarette smoking as well as no use of such products. These researchers confront significant methodological challenges in the study of reproductive health effects of e-cigarettes: addressing confounding with little information on the characteristics of e-cigarette users, a complex connection between e-cigarette and tobacco use, multiple and poorly understood exposure to e-cigarette vapors, and lack of a standard method for quantifying exposure. Evidence is urgently needed to inform regulation and individual decisions regarding the use of this potentially harmful product that might well entice new users of nicotine, some of whom progress to tobacco use, but that also has the potential to enable otherwise recalcitrant smokers to substitute a less harmful product.

Accuracy of self-reported birth outcomes relative to birth certificate data in an Internet-based prospective cohort study.

BACKGROUND: The accuracy of birth outcome data provided by Internet-based cohort study participants has not been well studied. METHODS: We compared self-reported data on birth characteristics in Pregnancy Study Online (PRESTO), an Internet-based prospective cohort study of North American pregnancy planners, with birth certificate data. At enrolment, participants were aged 21-45 years, attempting conception, and not using fertility treatment. Women completed online questionnaires during preconception, early and late pregnancy, and postpartum. We requested birth certificate data during 2014-2019 from seven health departments in states with the most participants. After restricting to singleton births, we assessed specificity, sensitivity, and agreement comparing self-reported data from postpartum questionnaires with birth certificate data for gestational age at delivery (GA) and birthweight (grams). Our primary measure of self-reported GA (weeks) was calculated as [280-(due date-birth date)]/7. We used log-binomial regression to assess predictors of agreement. RESULTS: We linked 85% (771/909) of women in selected states. Median age of women was 30 years (range: 21-42), 84% had ≥ 16 years of education, nearly 96% were married, 12% had household incomes <$50 000, 32% were parous, and 85% identified as non-Hispanic White. Median recall interval was 6 months. Among those with self-reported data, 89% reported the same GA as the birth certificate and 98% reported GA within 1 week of the birth certificate. Self-report of preterm birth (GA < 37 weeks) agreed with information from birth certificates for 100% of women; sensitivity was 100%, and specificity was 99%. Self-reported low birthweight (<2500 grams) agreed with birth certificates for 93% of women; sensitivity and specificity were 93% and ≥99%, respectively. Predictors of poorer agreement included higher parity and longer pregnancy attempt time for GA, and lower education and longer recall interval for birthweight. CONCLUSION: Self-reported data on GA and birthweight from an Internet-based cohort showed high accuracy compared with birth certificates.

Ambient heat and stillbirth in Northern and Central Florida.

BACKGROUND: Elevated temperature is well-recognized as a health hazard, and may be particularly harmful to pregnant women, including increasing risk of stillbirth. We conducted a study in Northern and Central Florida, an area prone to periodic extreme heat but with significant seasonal variation, focusing on the most socioeconomically vulnerable populations least able to mitigate the impact of heat. METHODS: We obtained electronic health records data from the OneFlorida Data Trust for the period 2012-2017, with 1876 stillbirths included in the analysis. We used a case-crossover design to examine the risk of stillbirth associated with acute exposures to elevated heat prior to the outcome, contrasting the case period (the week preceding the stillbirth) with a control period (the week prior to the case period and the week after the stillbirth). Average heat index and maximum warning level during the case and control periods of each woman were assigned by ZIP code. Conditional logistic regression models were used to assess the association between stillbirth and heat exposure, controlling for PM2.5 and O3. RESULTS: The adjusted odds ratio showed no overall association with stillbirth except for a weak association for exposure above the 90th percentile which was larger among the most socioeconomically deprived and non-Hispanic Black women. In the hot months, there was a clear association for all indices of heat exposure, but largest again for the most socioeconomically deprived population (aOR = 2.4, 95% CI: 1.2-5.2 in the 4th vs. 1st quartile) and among non-Hispanic Black women (aOR = 1.8, 95% CI: 1.0-3.2 in the 4th vs. 1st quartile). CONCLUSIONS: Our results provide further evidence that elevated ambient heat is related to stillbirth and encourage a focus on the most susceptible individuals and possible clinical pathways.

Risk Factors for Progression From Gestational Diabetes to Postpartum Type 2 Diabetes: A Review.

Gestational diabetes mellitus (GDM) complicates 6% to 8% of pregnancies and up to 50% of women with GDM progress to type 2 diabetes mellitus (DM) within 5 years postpartum. Clinicians have little guidance on which women are most at risk for DM progression or when evidence-based prevention strategies should be implemented in a woman's lifecycle. To help address this gap, the authors review identifiable determinants of progression from GDM to DM across the perinatal period, considering prepregnancy, pregnancy, and postpartum periods. The authors categorize evidence by pathways of risk including genetic, metabolic, and behavioral factors that influence progression to DM among women with GDM.

The association between perfluoroalkyl substances and lipid profile in exposed pregnant women in the Veneto region, Italy.

BACKGROUND: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Serum PFAS levels have been consistently associated with elevated serum lipids, but few studies have been conducted among pregnant women, and none has stratified analyses by trimester of gestation. Elevated serum lipid levels during pregnancy can have both immediate and long-lasting effects on pregnant women and the developing fetus. We evaluated the association between perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoro-hexanesulfonate (PFHxS) levels in relation to lipid profiles in highly-exposed pregnant women. METHODS: A cross-sectional analysis was conducted in 319 pregnant women (age 14-48 years) enrolled in the Regional health surveillance program. Non-fasting blood samples were obtained in any trimester of pregnancy and analyzed for PFOA, PFOS and PFHxS, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFAS (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. RESULTS: The geometric means of PFOA, PFOS and PFHxS were 14.78 ng/mL, 2.67 ng/mL and 1.89 ng/mL, respectively. The plasma levels of TC, HDL-C and LDL-C increased steadily throughout the trimesters. In the 1st trimester, PFOS was positively associated with TC and PFHxS with HDL-C. In the 3rd trimester, instead, an inverse relationship was seen between PFOA and PFHxS and both TC and LDL-C. CONCLUSIONS: Results suggest the associations between PFAS concentrations and lipid profiles in pregnant women might differ by trimesters of pregnancy. In the first trimester, patterns are similar to those of non-pregnant women, while they differ late in pregnancy. Different independent behavior of PFAS and lipid levels throughout the pregnancy might explain our observations. These findings support the ubiquitous exposure to PFAS and possible influence on lipid metabolisms during pregnancy and suggest a careful evaluation of the timing of PFAS measurement, when examining effects of PFAS during pregnancy on gestational outcomes related to serum lipids amounts.

Effects of prenatal bacterial infection on cognitive performance in early childhood.

BACKGROUND: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up. OBJECTIVES: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection. METHODS: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models. RESULTS: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters. CONCLUSIONS: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring.