Antepartum and intrapartum stillbirth rates across gestation: a cross-sectional study using the revised foetal death reporting system in the U.S.

BACKGROUND: There is a renewed call to address preventable foetal deaths in high-income countries, especially where progress has been slow. The Centers for Disease Control and Prevention released publicly, for the first time, the initiating cause and estimated timing of foetal deaths in 2014. The objective of this study is to describe risk and characteristics of antepartum versus intrapartum stillbirths in the U.S., and frequency of pathological examination to determine cause. METHODS: We conducted a cross-sectional study of singleton births (24-43 weeks) using 2014 U.S. Fetal Death and Natality data available from the National Center for Health Statistics. The primary outcome was timing of death (antepartum (n = 6200), intrapartum (n = 453), and unknown (n = 5403)). Risk factors of interest included maternal sociodemographic, behavioural, medical and obstetric factors, along with foetal sex. We estimated gestational week-specific stillbirth hazard, risk factors for intrapartum versus antepartum stillbirth using multivariable log-binomial regression models, conditional probabilities of intrapartum and antepartum stillbirth at each gestational week, and frequency of pathological examination by timing of death. RESULTS: The gestational age-specific stillbirth hazard was approximately 2 per 10,000 foetus-weeks among preterm gestations and > 3 per 10,000 foetus-weeks among term gestations. Both antepartum and intrapartum stillbirth risk increased in late-term and post-term gestations. The risk of intrapartum versus antepartum stillbirth was higher among those without a prior live birth, relative to those with at least one prior live birth (RR 1.32; 95% CI 1.08-1.61) and those with gestational hypertension, relative to those with no report of gestational hypertension (RR 1.47; 95% CI 1.09-1.96), and lower among Black, relative to white, individuals (RR 0.70; 95% CI 0.55-0.89). Pathological examination was not performed/planned in 25% of known antepartum stillbirths and 29% of known intrapartum stillbirths. CONCLUSION: These findings suggest greater stillbirth risk in the late-term and post-term periods. Primiparous mothers had greater risk of intrapartum than antepartum still birth, suggesting the need for intrapartum interventions for primiparous mothers in this phase of pregnancy to prevent some intrapartum foetal deaths. Efforts are needed to improve understanding, prevention and investigation of foetal deaths as well as improve stillbirth data quality and completeness in the United States.

Body mass index restrictions in fertility treatment: a national survey of OB/GYN subspecialists.

PURPOSE: To explore the attitudes of reproductive endocrinology and infertility (REI) and maternal-fetal medicine (MFM) subspecialists regarding the necessity and appropriateness of body mass index (BMI) cutoffs for women seeking fertility treatment. METHODS: Members of the Society for Reproductive Endocrinology and Infertility (SREI) and the Society for Maternal Fetal Medicine (SMFM) were invited to participate in a survey querying their knowledge of existing institutional or clinic BMI policies and personal opinions regarding upper and lower BMI cutoffs for a range of fertility treatments, including oral ovulation agents, gonadotropins, and in vitro fertilization. RESULTS: Respondents included 398 MFMs and 201 REIs. The majority of REI and MFM providers agreed with upper limit BMI cutoffs (72.5% vs 68.2%, p = 0.29), but REIs were twice as likely to support lower limit BMI restrictions compared to MFMs (56.2% vs 28.4%, p < 0.0001). Those who supported upper BMI restrictions were more likely to be female and report existing institutional BMI cutoffs. The majority of respondents (99.3%) believed that an official statement to guide clinicians should be issued by a national professional organization. CONCLUSIONS: Although practice patterns widely vary, the majority of REIs and MFMs believe that there should be a BMI cutoff above which women should not be offered immediate fertility treatment. Furthermore, there is a reported need for a written statement by a national professional organization to guide clinical practice and to ensure that OB/GYN subspecialists are providing consistent, fair, and safe recommendations to infertile women at the extremes of BMI.

Maternal sedentary behavior during pre-pregnancy and early pregnancy and mean offspring birth size: a cohort study.

BACKGROUND: Sedentary behavior is associated with adverse health outcomes in the general population. Whether sedentary behavior during pregnancy is associated with newborn outcomes, such as birth size, is not established, and previous studies have been inconsistent. While previous research suggests that male and female fetuses respond differently to maternal behaviors, such as physical activity, the role of infant sex in sedentary behavior-birth size associations has not been examined. METHODS: Participants in the Omega study, a cohort in Washington State (1996-2008), reported leisure time sedentary behavior (non-work time spent sitting), light intensity physical activity, and moderate/vigorous leisure time physical activity duration in the year before pregnancy (N = 1373) and in early pregnancy (N = 1535, mean 15 weeks). Offspring birth size was abstracted from delivery records. Non-parametric calibration weighting was used to assign adjustment weight (matching the distribution of sociodemographic and medical characteristics of the full cohort (N = 4128)) to participants with available sedentary behavior data. Weighted linear regression models were used to estimate mean differences in offspring birthweight, head circumference, and ponderal index (birthweight/length3) associated with leisure time sedentary behavior. Regression models were run overall and stratified by offspring sex. Isotemporal substitution modeling was used to determine mean differences in birthweight associated with replacing sedentary behavior with light or moderate/vigorous physical activity. RESULTS: On average, women spent 2.3 and 2.6 h/day in leisure time sedentary behavior during pre- and early pregnancy, respectively. There were no associations of pre-pregnancy leisure time sedentary behavior with mean birthweight, head circumference, or ponderal index (adjusted ß = - 12, 95% CI: -28, 4.1; ß = 0.0, 95% CI: -0.04, 0.1; and ß = 0.1, 95% CI: -0.2, 0.4, respectively). Early pregnancy sedentary behavior was not associated with mean birth size. Associations of sedentary behavior with mean birth size did not differ by offspring sex. Replacing sedentary time with light or moderate/vigorous physical activity was not associated with mean birthweight. CONCLUSIONS: We did not observe associations of maternal sedentary behavior during pre- or early pregnancy with mean offspring birth size. Pre-pregnancy and early pregnancy sedentary behavior may have important adverse effects on maternal health, but our results do not support associations with mean offspring birth size.

Healthy Lifestyle During Early Pregnancy and Risk of Gestational Diabetes Mellitus.

Previous studies have found associations between individual healthy behaviors and reduced risk of gestational diabetes mellitus (GDM); however, the association of composite healthy lifestyle during pregnancy with GDM has not been examined. Participants in the Omega Study (n = 3,005), a pregnancy cohort study conducted in Washington State (1996-2008), reported information on diet, physical activity, smoking, and stress during early pregnancy. Lifestyle components were dichotomized into healthy/unhealthy and then combined into a total lifestyle score (range, 0-4). Regression models were used to determine relative risk of GDM (n = 140 cases) in relation to healthy lifestyle. Twenty percent of participants had a healthy diet, 66% were physically active, 95% were nonsmokers, and 55% had low stress. Each 1-point increase in lifestyle score was associated with a 21% lower risk of GDM (95% confidence interval: 0.65, 0.96) after adjustment for age, race, and nulliparity. Adjustment for prepregnancy body mass index, prepregnancy physical activity, and prepregnancy smoking attenuated the associations slightly. Associations were similar in normal-weight and overweight/obese women. In this study, a composite measure of healthy lifestyle during early pregnancy was associated with substantially lower GDM risk. Public health messaging and interventions promoting multiple aspects of a healthy lifestyle during early pregnancy should be considered for GDM prevention.

Maternal Leisure Time Physical Activity and Infant Birth Size.

BACKGROUND: Associations of maternal leisure time physical activity with birth size are inconsistent. Roles of infant sex and maternal prepregnancy body mass index (BMI) in these associations have not been studied. METHODS: Participants (N = 3,310) in the Omega study, a cohort in Washington State (1996-2008), reported leisure time physical activity duration and energy expenditure in the year prepregnancy and in early pregnancy (mean 15 weeks gestation). Regression models estimated mean differences in infant head circumference, birthweight, and ponderal index (birthweight/length) across quartiles of pre- or early-pregnancy leisure time physical activity. We assessed effect modification by infant sex or prepregnancy overweight/obese status (BMI ≥ 25 kg/m). RESULTS: We observed positive associations between prepregnancy leisure time physical activity and head circumference overall and among male infants. Among males, each quartile increase in prepregnancy physical activity duration was associated with 0.14 cm (95% confidence interval = 0.046, 0.24; trend P = 0.004) greater head circumference. We did not observe associations between leisure time physical activity and birthweight or ponderal index overall. Each quartile increase in pre- or early-pregnancy physical activity duration was associated with 17-23 g lower birthweight among female infants and among women with normal prepregnancy BMI. CONCLUSIONS: We observed positive associations between prepregnancy leisure time physical activity and head circumference among male infants, and inverse associations of pre- and early-pregnancy physical activity with birthweight among female infants and women with normal prepregnancy BMI. Future studies should confirm results and elucidate mechanisms of observed associations.

The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study.

Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contribute to the fetal size at birth. To define the genetic architecture underlying the newborn size, we performed a genome-wide association study (GWAS) in 4281 newborns in four ethnic groups from the Hyperglycemia and Adverse Pregnancy Outcome Study. We tested for association with newborn anthropometric traits (birth length, head circumference, birth weight, percent fat mass and sum of skinfolds) and newborn metabolic traits (cord glucose and C-peptide) under three models. Model 1 adjusted for field center, ancestry, neonatal gender, gestational age at delivery, parity, maternal age at oral glucose tolerance test (OGTT); Model 2 adjusted for Model 1 covariates, maternal body mass index (BMI) at OGTT, maternal height at OGTT, maternal mean arterial pressure at OGTT, maternal smoking and drinking; Model 3 adjusted for Model 2 covariates, maternal glucose and C-peptide at OGTT. Strong evidence for association was observed with measures of newborn adiposity (sum of skinfolds model 3 Z-score 7.356, P = 1.90×10⁻¹³, and to a lesser degree fat mass and birth weight) and a region on Chr3q25.31 mapping between CCNL and LEKR1. These findings were replicated in an independent cohort of 2296 newborns. This region has previously been shown to be associated with birth weight in Europeans. The current study suggests that association of this locus with birth weight is secondary to an effect on fat as opposed to lean body mass.

Associations of Early and Late Gestational Weight Gain with Infant Birth Size.

OBJECTIVES: Associations of gestational weight gain (GWG) during specific periods of pregnancy with infant birth size have been inconsistent. Infant sex-specific differences in these associations are unknown METHODS: Information on GWG (kg) [total, early (<20 weeks gestation), and late (≥20 weeks gestation)] and indices of infant birth size including birthweight (BW), ponderal index (PI), crown-heel length (CHL), and head circumference (HC) was collected from 3,621 pregnant women. We calculated adjusted mean differences and 95 % confidence intervals (CIs) relating total, early and late GWG to infant birth size using multivariable linear regression procedures. We used stratified analyses and interaction terms to test whether associations differed by infant sex. RESULTS: One-kg increases in total, early or late GWG were associated with BW increases of 17.2 g (95 % CI 13.8-18.9), 14.1 g (95 % CI 10.3-18.0), and 21.0 g (95 % CI 16.7-25.4), respectively. Early GWG-BW and late GWG-BW associations were different (p = 0.026). Sex-stratified total GWG-BW associations were similar to overall results. There were sex-specific differences in early GWG-BW and late GWG-BW associations. Among females, early GWG-BW (12.0 g, 95 % CI 6.7-17.2) and late GWG-BW (24.2 g, 95 % CI 18.2-30.3) associations differed (p = 0.0042); the corresponding associations did not differ among males. Total, early, and late GWG were associated with CHL and HC, but not with PI. Associations did not differ for early or late GWG. CONCLUSIONS FOR PRACTICE: For comparable GWG, late-GWG-related BW increase is greater than early-GWG-related BW increase, particularly among female infants.

Behavior reallocations within 24-h movement profiles and change in cardiometabolic biomarkers during pregnancy.

OBJECTIVE: The goal of this study was to investigate associations of reallocations within 24-h movement profiles and changes in cardiometabolic biomarkers from early to late pregnancy. METHODS: In 137 individuals with prepregnancy overweight/obesity, waking movement was measured using wrist-worn accelerometers, sleep was self-reported, and biomarkers were measured in fasting serum samples at 12 and 32 weeks' gestation. We used compositional isotemporal substitution models. RESULTS: On average, biomarkers increased 21%-83% across pregnancy. For those with guideline-recommended moderate/vigorous-intensity physical activity (MVPA) in early pregnancy, reallocating 30 min from MVPA to sleep, sedentary behavior, or light-intensity physical activity (LPA) was associated with a 0.6 mmol/L greater increase in total cholesterol (95% CI: -0.1 to 1.2) and a 0.7 mmol/L greater increase in low-density lipoprotein (LDL) cholesterol (95% CI: 0.1 to 1.3) from early to late pregnancy. For those with low MVPA in early pregnancy, reallocating 30 min from sleep, sedentary behavior, or LPA to MVPA was associated with a 0.6 mmol/L lower increase in total cholesterol (95% CI: -1.3 to 0.1) and a 0.8 mmol/L lower increase in LDL cholesterol (95% CI: -1.4 to -0.1) from early to late pregnancy. There were no associations with change in glucose, insulin, homeostatic model assessment for insulin resistance, very low-density lipoprotein, or high-density lipoprotein cholesterol, triglycerides, or free fatty acids. CONCLUSIONS: Maintaining or achieving a 24-h movement profile with guideline-recommended amounts of MVPA may be beneficial for reducing pregnancy-induced increases in total and LDL cholesterol.

Theoretical Behavior Substitutions during the 24-Hour Day in Pregnancy and Infant Growth Outcomes.

PURPOSE: To assess associations of theoretically reallocating time from sleep, sedentary behavior, or light intensity physical activity (LPA) to moderate/vigorous intensity physical activity (MVPA) during pregnancy with infant growth outcomes. METHODS: We used data from a cohort of pregnant individuals with overweight or obesity (n = 116). At 9-15 and 30-36 weeks gestation, waking movement was measured using wrist-worn accelerometers and sleep duration was self-reported. Outcomes were obtained from delivery electronic health records (birth) and study visits (12 months). We used compositional isotemporal substitution models. RESULTS: In early pregnancy, reallocating 10 minutes of sleep, sedentary behavior, or LPA to MVPA was associated with 20% (RR = 0.80; 95%CI: 0.75,0.85), 21% (RR = 0.79; 95%CI: 0.75,0.84), and 25% (RR = 0.75; 95%CI: 0.70,0.81) lower risk of large-for-gestational age (LGA) birthweight, respectively, and 17% (RR = 0.83; 95%CI: 0.75,0.91), 18% (RR = 0.82; 95%CI: 0.75,0.91), and 22% (RR = 0.78; 95%CI: 0.70,0.88) lower risk of rapid infant growth (birth to 12 months), respectively. In late pregnancy, reallocating 10 minutes to MVPA was associated with 18% to 22% lower risk of LGA birthweight, but was not associated with rapid infant growth. Reallocating time to MVPA in early or late pregnancy was not associated with high newborn body fat percent. CONCLUSIONS: Our findings suggest beneficial associations of theoretically reallocating time from sleep, sedentary behavior, or LPA to MVPA, especially during early pregnancy, for reducing LGA birthweight and rapid infant growth.

Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. RESEARCH DESIGN AND METHODS: We followed 2,952 participants in the Study of Women's Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log-based discrete-time survival models anchored at baseline. RESULTS: Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87-0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] -92.3 to -1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> -1.5 to -0.2 nmol/L] HR 0.33, 95% CI 0.23-0.48; Q3 [> -0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25-0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30-0.63). CONCLUSIONS: Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.

Racial Residential Segregation and Mental Health During Pregnancy.

Importance: Research suggests the social, physical, and socioeconomic contexts of residing in segregated neighborhoods may negatively affect mental health. Objective: To assess the association between racial residential segregation and prenatal mental health among Asian, Black, Hispanic, and White individuals. Design, Setting, and Participants: This population-based cross-sectional study was conducted in Kaiser Permanente Northern California (KPNC), an integrated health care delivery system. Participants included self-identified Asian, Black, Hispanic, and White pregnant individuals who attended at least 1 prenatal care visit at KPNC between January 1, 2014, and December 31, 2019. Data were analyzed from January 14, 2023, to August 15, 2024. Exposures: Racial residential segregation, defined by the local Getis-Ord Gi* statistic, was calculated in each racial and ethnic group and categorized as low (<0), medium (0-1.96), or high (>1.96). A positive Gi* statistic indicates overrepresentation (greater clustering or segregation) of the racial and ethnic group in an index census tract and neighboring tracts compared with the larger surrounding geographic area. Main Outcomes and Measures: Prenatal depression and anxiety defined by diagnoses codes documented in the electronic health record between the first day of the last menstrual period and the day prior to birth. Results: Among the 201 115 participants included in the analysis (mean [SD] age, 30.8 [5.3] years; 26.8% Asian, 6.6% Black, 28.0% Hispanic, and 38.6% White), prenatal depression and anxiety were highest in Black individuals (18.3% and 18.4%, respectively), followed by White (16.0% and 18.2%, respectively), Hispanic (13.0% and 14.4%, respectively), and Asian (5.7% and 6.4%, respectively) individuals. Asian (40.8% vs 31.1%) and Black (43.3% vs 22.6%) individuals were more likely to live in neighborhoods with high vs low segregation, while Hispanic individuals were equally likely (34.3% vs 34.7%). High compared with low segregation was associated with greater odds of prenatal depression (adjusted odds ratio [AOR], 1.25 [95% CI, 1.10-1.42]) and anxiety (AOR, 1.14 [95% CI, 1.00-1.29]) among Black individuals. High segregation was associated with lower odds of prenatal depression among Asian (AOR, 0.75 [95% CI, 0.69-0.82]), Hispanic (AOR, 0.88 [95% CI, 0.82-0.94]), and White (AOR, 0.91 [95% CI, 0.86-0.96]) individuals. Similar associations were found for anxiety among Asian (AOR, 0.80 [95% CI, 0.73-0.87]) and Hispanic (AOR, 0.88 [95% CI, 0.82-0.93]) but not White (AOR, 0.95 [95% CI, 0.90-1.00]) individuals. Conclusions and Relevance: In this cross-sectional study, racial and ethnic residential segregation was associated with worse prenatal mental health for Black individuals but better mental health for Asian, Hispanic, and White individuals. Policies reducing segregation and its impact may improve mental health outcomes in pregnant Black individuals.

Optimal Instruments for Measurement of Dietary Intake, Physical Activity, and Sleep Among Adults in Population-Based Studies: Report of a National Heart, Lung, and Blood Institute Workshop.

The National Heart, Lung, and Blood Institute convened a virtual workshop in September 2022 to discuss "Optimal Instruments for Measurement of Diet, Physical Activity, and Sleep." This report summarizes the proceedings, identifying current research gaps and future directions for measuring different lifestyle behaviors in adult population-based studies. Key discussions centered on integrating report-based methods, like questionnaires, with device-based assessments, including wearables and physiological measures such as biomarkers and omics to enhance self-reported metrics and better understand the underlying biologic mechanisms of chronic diseases. Emphasis was placed on the need for data harmonization, including the adoption of standard terminology, reproducible metrics, and accessible raw data, to enhance the analysis through artificial intelligence and machine learning techniques. The workshop highlighted the importance of standardizing procedures for integrated behavioral phenotypes using time-series data. These efforts aim to refine data accuracy and comparability across studies and populations, thereby advancing our understanding of lifestyle behaviors and their impact on chronic disease outcomes over the life course.

Daytime napping and nighttime sleep in pregnant individuals with insomnia disorder.

STUDY OBJECTIVES: Examine bidirectional associations between daytime napping and nighttime sleep among pregnant individuals with insomnia disorder. METHODS: We used baseline data from a randomized controlled trial of insomnia treatment during pregnancy (n = 116). Participants in their second or third trimester of pregnancy self-reported daytime napping and nighttime sleep parameters using a sleep diary and wore an Actiwatch-2 during the same 7-day period. Linear regression models, accounting for intraindividual correlation, were used to estimate associations between daytime napping and nighttime sleep parameters (duration, efficiency, quality, awakenings). Models were also stratified by trimester of pregnancy. RESULTS: Sixty-three percent of participants reported napping on at least 1 day. Among participants in the second trimester (65%), napping 15-59 minutes was associated with 6.3% greater self-reported sleep efficiency (95% confidence interval: 2.3, 10.2) and 0.5 units greater self-reported sleep quality (95% confidence interval: 0.0, 0.9) that night; napping 60+ minutes was associated with 0.6 hours shorter actigraphy-measured sleep duration (95% confidence interval: -1.0, -0.2). Napping was not associated with nighttime sleep overall or during the third trimester. Nighttime sleep parameters were not associated with napping duration the following day. CONCLUSIONS: Among pregnant individuals with insomnia in the second trimester, short napping duration was associated with higher self-reported sleep efficiency and quality; long napping duration was associated with shorter actigraphy-measured sleep duration. Additional research is needed to examine the interaction between nap duration and nap timing. In the future, these results may lead to more nuanced recommendations for daytime napping among pregnant individuals with insomnia disorder. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Treatment for Insomnia during Pregnancy; URL: https://clinicaltrials.gov/ct2/show/NCT01846585; Identifier: NCT01846585. CITATION: Badon SE, Dietch R, Simpson N, Lyell DJ, Manber R. Daytime napping and nighttime sleep in pregnant individuals with insomnia disorder. J Clin Sleep Med. 2023;19(2):371-377.

Associations between antidepressant use patterns during pregnancy and birth outcomes among periconception antidepressant users.

BACKGROUND: Little is known about antidepressant medication use patterns during pregnancy among periconception (before and immediately following conception) users. Additionally, the associations between these patterns and birth outcomes is unclear, after taking into account underlying depression severity. OBJECTIVE: This study describes patterns of antidepressant use among periconception users and examines associations between usage patterns and birth outcomes. STUDY DESIGN: This retrospective cohort study included pregnant Kaiser Permanente Northern California (KPNC) members with a live birth between 2014 and 2017 and an antidepressant medication fill that overlapped the 8th week of pregnancy. Outcomes were preterm birth and neonatal intensive care unit (NICU) admission. Data were extracted from KPNC's electronic health records. Modified Poisson regression was conducted. RESULTS: Of the 3637 pregnancies meeting inclusion criteria, 33% (n = 1204) continued antidepressant use throughout the pregnancy (refilled throughout pregnancy), 47% (n = 1721) discontinued use (no refills), and 20% (n = 712) stopped and reinitiated use (refill after 30+ day gap in supply). Women who continued use had 1.86 (95% confidence interval (CI) 1.53, 2.27) times the risk of preterm birth and 1.76 (95% CI: 1.42, 2.19) times the risk of NICU admission, compared to women who discontinued use during pregnancy. Similarly, women with continued use had 1.66 (95% CI: 1.27, 2.18) times the risk of preterm birth and 1.85 (95% CI: 1.39, 2.46) times the risk of NICU admission, compared to women who stopped and reinitiated use. This relationship held when examining continuous exposure; the relationship between continuous exposure and preterm delivery was stronger in later trimesters. CONCLUSIONS: Periconception antidepressant users who continue use during pregnancy, particularly into the second and third trimesters, may be at higher risk of adverse birth outcomes. This evidence should be considered alongside the risks associated with depression relapse.

Racial-Ethnic Differences in Treatment Initiation for New Diagnoses of Perinatal Depression.

OBJECTIVE: The adverse consequences of untreated perinatal depression highlight the need to identify populations to target in order to increase treatment rates. The authors sought to evaluate treatment initiation for a new diagnosis of depression during pregnancy or postpartum and to describe racial-ethnic differences in initiation and type (psychotherapy, antidepressants) of treatment in a large health care system with universal perinatal depression screening. METHODS: This retrospective cohort study included women who delivered a live birth in the Kaiser Permanente Northern California system between October 2012 and May 2017. Black, Latina, Asian, and White women ages ≥15 years were eligible. New depression diagnoses were defined by using ICD-9 and ICD-10 codes from electronic health records. Treatment initiation was defined as receiving at least one antidepressant medication dispensation or psychotherapy visit up to 90 days after the diagnosis. Modified Poisson regression was used to estimate the risk for initiating treatment and the type of treatment initiated. RESULTS: In total, 13,637 women with a new depression diagnosis (prenatal: N=7,041, 51.6%; postpartum: N=6,596, 48.4%) were identified. Of the pregnant women, 31.4% initiated treatment, and of the postpartum women, 73.1% initiated treatment. Latina and Asian women were less likely than White women to initiate treatment postpartum. During pregnancy and postpartum, non-White women were more likely to initiate psychotherapy. White women were more likely to initiate antidepressant medication during pregnancy and postpartum or a combination of antidepressant medication and psychotherapy during the postpartum period. CONCLUSIONS: Research is warranted to identify patient-, provider-, and system-level barriers that contribute to racial-ethnic disparities in perinatal mental health care.

Method for Activity Sleep Harmonization (MASH): a novel method for harmonizing data from two wearable devices to estimate 24-h sleep-wake cycles.

Background: Daily 24-h sleep-wake cycles have important implications for health, however researcher preferences in choice and location of wearable devices for behavior measurement can make 24-h cycles difficult to estimate. Further, missing data due to device malfunction, improper initialization, and/or the participant forgetting to wear one or both devices can complicate construction of daily behavioral compositions. The Method for Activity Sleep Harmonization (MASH) is a process that harmonizes data from two different devices using data from women who concurrently wore hip (waking) and wrist (sleep) devices for ≥ 4 days. Methods: MASH was developed using data from 1285 older community-dwelling women (ages: 60-72 years) who concurrently wore a hip-worn ActiGraph GT3X + accelerometer (waking activity) and a wrist-worn Actiwatch 2 device (sleep) for ≥ 4 days (N = 10,123 days) at the same time. MASH is a two-tiered process using (1) scored sleep data (from Actiwatch) or (2) one-dimensional convolutional neural networks (1D CNN) to create predicted wake intervals, reconcile sleep and activity data disagreement, and create day-level night-day-night pairings. MASH chooses between two different 1D CNN models based on data availability (ActiGraph + Actiwatch or ActiGraph-only). MASH was evaluated using Receiver Operating Characteristic (ROC) and Precision-Recall curves and sleep-wake intervals are compared before (pre-harmonization) and after MASH application. Results: MASH 1D CNNs had excellent performance (ActiGraph + Actiwatch ROC-AUC = 0.991 and ActiGraph-only ROC-AUC = 0.983). After exclusions (partial wear [n = 1285], missing sleep data proceeding activity data [n = 269], and < 60 min sleep [n = 9]), 8560 days were used to show the utility of MASH. Of the 8560 days, 46.0% had ≥ 1-min disagreement between the devices or used the 1D CNN for sleep estimates. The MASH waking intervals were corrected (median minutes [IQR]: -27.0 [-115.0, 8.0]) relative to their pre-harmonization estimates. Most correction (-18.0 [-93.0, 2.0] minutes) was due to reducing sedentary behavior. The other waking behaviors were reduced a median (IQR) of -1.0 (-4.0, 1.0) minutes. Conclusions: Implementing MASH to harmonize concurrently worn hip and wrist devices can minimizes data loss and correct for disagreement between devices, ultimately improving accuracy of 24-h compositions necessary for time-use epidemiology.

Maternal and neonatal outcomes associated with treating hypertension in pregnancy at different thresholds.

INTRODUCTION: In the United States, there has been controversy over whether treatment of mild-to-moderate hypertension during pregnancy conveys more benefit than risk. OBJECTIVE: The objective of the study was to compare risks and benefits of treatment of mild-to-moderate hypertension during pregnancy. METHODS: This retrospective cohort study included 11,871 pregnant women with mild-to-moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small-for-gestational-age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre-pregnancy body mass index) analyses were also conducted. RESULTS: In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: -0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results. CONCLUSIONS: Initiation of antihypertensive medication at mild-to-moderate BP thresholds (140-155/90-105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence.

Changes in 24-Hour Movement Behaviors From Early to Late Pregnancy in Individuals With Prepregnancy Overweight or Obesity.

BACKGROUND: Understanding how sleep, sedentary behavior (SED), and physical activity (PA) (24-h movement profile) changes across pregnancy in individuals with prepregnancy overweight or obesity and how parity (previous births) impacts these changes can help inform interventions. METHODS: In 155 participants, movement was measured using wrist-worn accelerometers, and sleep was self-reported in early (8-15 wk) and late (29-38 wk) pregnancy. The 24-hour movement profiles were analyzed using compositional analyses. RESULTS: Nulliparous participants (no previous births) spent 33.95%, 38.14%, 25.32%, and 2.58% of the 24-hour day in early pregnancy in sleep, SED, light-intensity PA, and moderate/vigorous-intensity PA, respectively. Multiparous participants (≥1 previous birth) spent 2.50 percentage points less in SED (mean log-ratio difference = -0.068; 95% confidence interval [CI], -0.129 to -0.009) and 2.73 percentage points more in light-intensity PA (mean log-ratio difference = 0.102; 95% CI, 0.035 to 0.180). From early to late pregnancy, participants decreased the proportion of the 24-hour day spent asleep by 1.67 percentage points (mean log-ratio difference = -0.050; 95% CI, -0.092 to -0.011) and increased light-intensity PA by 1.56 percentage points (mean log-ratio difference = 0.057; 95% CI, 0.003 to 0.108), with no change in other behaviors. CONCLUSIONS: Nulliparous and multiparous individuals with prepregnancy overweight or obesity both had high levels of SED, with no change across pregnancy, and may require interventions to reduce  SED.

Association of Glyburide and Subcutaneous Insulin With Perinatal Complications Among Women With Gestational Diabetes.

Importance: Nearly 30% of individuals with gestational diabetes (GDM) do not achieve glycemic control with lifestyle modification alone and require medication treatment. Oral agents, such as glyburide, have several advantages over insulin for the treatment of GDM, including greater patient acceptance; however, the effectiveness of glyburide for the treatment of GDM remains controversial. Objective: To compare the perinatal and neonatal outcomes associated with glyburide vs insulin using causal inference methods in a clinical setting with information on glycemic control. Design, Setting, and Participants: The population-based cohort study included patients with GDM who required medication treatment from 2007 to 2017 in Kaiser Permanente Northern California. Machine learning and rigorous casual inference methods with time-varying exposures were used to evaluate associations of exposure to glyburide vs insulin with perinatal outcomes. Data analysis was conducted from March 2018 to July 2017. Exposures: Time-varying exposure to glyburide vs insulin during pregnancy. Main Outcomes and Measures: Outcomes evaluated separately included neonatal hypoglycemia, jaundice, shoulder dystocia, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, size-for-gestational age, and cesarean delivery. Inverse probability weighting (IPW) estimation was used to separately compare perinatal outcomes between those initiating glyburide and insulin. This approach was combined with Super Learning for propensity score estimation to account for both baseline and time-dependent confounding in both per-protocol (primary) and intention-to-treat (secondary) analyses to evaluate sustained exposure to the same therapy. Results: From 2007 to 2017, 11 321 patients with GDM (mean [SD] age, 32.9 [4.9] years) initiated glyburide or insulin during pregnancy. In multivariate models, the risk of neonatal respiratory distress was 2.03 (95% CI, 0.13-3.92) per 100 births lower and the risk of NICU admission was 3.32 (95% CI, 0.20-6.45) per 100 births lower after continuous exposure to glyburide compared with insulin. There were no statistically significant differences in glyburide vs insulin initiation in risk for neonatal hypoglycemia (0.85 [95% CI, -1.17 to 2.86] per 100 births), jaundice (0.02 [95% CI, -1.46 to 1.51] per 100 births), shoulder dystocia (-1.05 [95% CI, -2.71 to 0.62] per 100 births), or large-for-gestational age categories (-2.75 [95% CI, -6.31 to 0.80] per 100 births). Conclusions and Relevance: Using data from a clinical setting and contemporary causal inference methods, our findings do not provide evidence of a difference in the outcomes examined between patients with GDM initiating glyburide compared with those initiating insulin.

Coping strategies for COVID-19 pandemic-related stress and mental health during pregnancy.

BACKGROUND: Increased stress has likely contributed to the observed high prevalence of depression and anxiety in pregnant individuals during the COVID-19 pandemic. The objective of this study was to assess the prevalence of coping strategies for COVID-19 pandemic-related stress and associations of these coping strategies with depression and anxiety symptoms during pregnancy. METHODS: 8320 members of Kaiser Permanente Northern California who were pregnant between June 22, 2020 and May 10, 2021 completed an online survey including questions about coping strategies since the start of the COVID-19 pandemic and current depression and anxiety symptoms. We used weighted regression to estimate prevalence ratios for moderate/severe depression and anxiety symptom severity associated with coping strategies. RESULTS: The most common coping strategies for COVID-19 pandemic-related stress were talking with friends and family (77%), outdoor physical activity (54%), and increasing screen time activities (52%). Exercising using online programs or videos, outdoor physical activity, talking with friends and family, and engaging in more family activities were associated with 29% to 38% lower prevalence of moderate/severe depression symptom severity and 16% to 34% lower prevalence of moderate/severe anxiety symptom severity. LIMITATION: We are unable to rule out reverse temporality as an explanation for the observed results because of the cross-sectional design; depression or anxiety symptom severity may influence use of specific coping strategies. CONCLUSION: Our results suggest that physical activity and connecting with others are coping strategies for COVID-19 pandemic-related stress that may be associated with better mental health in pregnant individuals.