Prepregnancy body mass index and other risk factors for early-onset and late-onset haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome: a population-based retrospective cohort study in British Columbia, Canada.

BACKGROUND: Obesity increases risk of pre-eclampsia, but the association with haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is understudied. OBJECTIVE: To examine the association between prepregnancy body mass index (BMI) and HELLP syndrome, including early-onset versus late-onset disease. STUDY DESIGN: A retrospective cohort study using population-based data. SETTING: British Columbia, Canada, 2008/2009-2019/2020. POPULATION: All pregnancies resulting in live births or stillbirths at ≥20 weeks' gestation. METHODS: BMI categories (kg/m2) included underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30.0). Rates of early-onset and late-onset HELLP syndrome (<34 vs ≥34 weeks, respectively) were calculated per 1000 ongoing pregnancies at 20 and 34 weeks' gestation, respectively. Cox regression was used to assess the associations between risk factors (eg, BMI, maternal age and parity) and early-onset versus late-onset HELLP syndrome. MAIN OUTCOME MEASURES: Early-onset and late-onset HELLP syndrome. RESULTS: The rates of HELLP syndrome per 1000 women were 2.8 overall (1116 cases among 391 941 women), and 1.9, 2.5, 3.2 and 4.0 in underweight, normal BMI, overweight and obese categories, respectively. Overall, gestational age-specific rates of HELLP syndrome increased with prepregnancy BMI. Obesity (compared with normal BMI) was more strongly associated with early-onset HELLP syndrome (adjusted HR (AHR) 2.24 (95% CI 1.65 to 3.04) than with late-onset HELLP syndrome (AHR 1.48, 95% CI 1.23 to 1.80) (p value for interaction 0.025). Chronic hypertension, multiple gestation, bleeding (<20 weeks' gestation and antepartum) also showed differing AHRs between early-onset versus late-onset HELLP syndrome. CONCLUSIONS: Prepregnancy BMI is positively associated with HELLP syndrome and the association is stronger with early-onset HELLP syndrome. Associations with early-onset and late-onset HELLP syndrome differed for some risk factors, suggesting possible differences in aetiological mechanisms.

Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy among the multiple causes of death on the death certificate. The frequencies of major cause-of-death categories among deaths of female patients aged 15 to 44 years, maternal deaths, deaths due to obstetrical causes (ie, direct obstetrical deaths), and deaths due to maternal medical conditions aggravated by pregnancy or its management (ie, indirect obstetrical deaths) were quantified. RESULTS: Maternal deaths, per National Vital Statistics System methodology, increased by 144% (95% confidence interval, 130-159) from 9.65 in 1999-2002 (n=1550) to 23.6 per 100,000 live births in 2018-2021 (n=3489), with increases occurring among all race and ethnicity groups. Direct obstetrical deaths increased from 8.41 in 1999-2002 to 14.1 per 100,000 live births in 2018-2021, whereas indirect obstetrical deaths increased from 1.24 to 9.41 per 100,000 live births: 38% of direct obstetrical deaths and 87% of indirect obstetrical deaths in 2018-2021 were identified because of a positive pregnancy checkbox. The pregnancy checkbox was associated with increases in less specific and incidental causes of death. For example, maternal deaths with malignant neoplasms listed as a multiple cause of death increased 46-fold from 0.03 in 1999-2002 to 1.42 per 100,000 live births in 2018-2021. Under the alternative formulation, the maternal mortality rate was 10.2 in 1999-2002 and 10.4 per 100,000 live births in 2018-2021; deaths from direct obstetrical causes decreased from 7.05 to 5.82 per 100,000 live births. Deaths due to preeclampsia, eclampsia, postpartum hemorrhage, puerperal sepsis, venous complications, and embolism decreased, whereas deaths due to adherent placenta, renal and unspecified causes, cardiomyopathy, and preexisting hypertension increased. Maternal mortality increased among non-Hispanic White women and decreased among non-Hispanic Black and Hispanic women. However, rates were disproportionately higher among non-Hispanic Black women, with large disparities evident in several causes of death (eg, cardiomyopathy). CONCLUSION: The high and rising rates of maternal mortality in the United States are a consequence of changes in maternal mortality surveillance, with reliance on the pregnancy checkbox leading to an increase in misclassified maternal deaths. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows lower, stable maternal mortality rates and declines in maternal deaths from direct obstetrical causes.

COVID-19 Pandemic-Related Changes in Rates of Neonatal Abstinence Syndrome.

This cross-sectional study examines COVID-19 pandemic­related changes in rates of neonatal abstinence syndrome (NAS) and whether infants in urban or rural areas and those with low socioeconomic status were disproportionately affected.

Pregnancy-associated mortality due to cardiovascular disease: Impact of hypertensive disorders of pregnancy.

BACKGROUND: Reported rates of maternal mortality in the United States have been staggeringly high and increasing, and cardiovascular disease (CVD) is a chief contributor to such deaths. However, the impact of hypertensive disorders of pregnancy (HDP) on the short-term risk of cardiovascular death is not well understood. OBJECTIVES: To evaluate the association between HDP (chronic hypertension, gestational hypertension, preeclampsia, eclampsia, and superimposed preeclampsia) and pregnancy-associated mortality rates (PMR) from all causes, CVD-related causes both at delivery and within 1 year following delivery. METHODS: We used the Nationwide Readmissions Database (2010-2018) to examine PMRs for females 15-54 years old. International Classification of Disease 9 and 10 diagnosis codes were used to identify pregnancy-associated deaths due to HDP and CVD. Discrete-time Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality at delivery (0 days) and at <30, <60, <90, <180, and <365 days after delivery in relation to HDP. RESULTS: Of 33,417,736 hospital deliveries, the rate of HDP was 11.0% (n = 3,688,967), and the PMR from CVD was 6.4 per 100,000 delivery hospitalisations (n = 2141). Compared with normotensive patients, HRs for CVD-related PMRs increased with HDP severity, reaching over 58-fold for eclampsia patients. HRs were higher for stroke-related (1.2 to 170.9) than heart disease (HD)-related (0.99 to 39.8) mortality across all HDPs. Except for gestational hypertension, the increased risks of CVD mortality were evident at delivery and persisted 1 year postpartum for all HDPs. CONCLUSIONS: HDPs are strong risk factors for pregnancy-associated mortality due to CVD at delivery and within 1 year postpartum; the risks are stronger for stroke than HD-related PMR. While absolute PMRs are low, this study supports the importance of extending postpartum care beyond the traditional 42-day postpartum visit for people whose pregnancies are complicated by hypertension.

Variation in Episiotomy Use Among Nulliparous Individuals by Maternity Care Provider and Associated Rates of Obstetric Anal Sphincter Injury.

OBJECTIVES: To quantify variation in the association between episiotomy and obstetric anal sphincter injury (OASI) by maternity care provider in spontaneous and operative vaginal deliveries (SVDs and OVDs). METHODS: Population-based retrospective cohort study of vaginal, term deliveries among nullipara in Canada (2004-2015). Adjusted rate ratios (ARRs) and 95% CIs were estimated using log-binomial regression to quantify the associations between episiotomy and OASI, stratified by care provider (obstetrician [OB], family physician [FP], or registered midwife [RM]) while adjusting for potential confounders. RESULTS: The study included 631 642 deliveries. Episiotomy use varied by provider: among SVDs, the episiotomy rate was 19.6%, 14.4%, and 8.4% in the OB, FP, and RM groups, respectively. The rate of OASI was higher among SVDs with versus without episiotomy (5.8% vs 4.6%). Conversely, OASI occurred less frequently in operative vaginal deliveries with episiotomy (15.3%) compared with those without (16.7%). In all provider groups, the ARR for OASI was increased with episiotomy in SVD and decreased with episiotomy with forceps delivery. No differences in these associations were observed by provider except among vacuum delivery (ARR with episiotomy vs. without, OB: 0.88, 95% CI 0.84-0.92; FP: 0.89, 95% CI 0.83-0.96, RM: 1.22, 95% CI 1.02-1.48). CONCLUSIONS: In nullipara, irrespective of maternity care provider, there is a positive association between episiotomy and OASI among SVDs and an inverse association between episiotomy and deliveries with forceps. The relationship between episiotomy and OASI is modified by maternity care providers among vacuum deliveries.

Temporal changes in pre-existing health conditions five years prior to pregnancy in British Columbia, Canada, 2000-2019.

BACKGROUND: Pre-existing health conditions increase the risk of obstetric complications during pregnancy and birth. However, the prevalence and recent changes in the frequency of pre-existing health conditions in the childbearing population remain unknown. OBJECTIVES: To estimate the temporal changes in the prevalence of pre-existing health conditions among pregnant women in British Columbia, Canada. METHODS: We carried out a population-based cross-sectional study of 825,203 deliveries in BC between 2000 and 2019 and examined 17 categories of physical and psychiatric health conditions recorded within 5 years before childbirth. We also undertook age-period-cohort analyses to evaluate temporal changes in pre-existing health conditions. RESULTS: The prevalence of any pre-existing health condition was 26.2% (n = 216,214) with overall trends remaining stable during the study period. Between 2000 and 2019, the prevalence rates of anxiety (5.6%-9.6%), bipolar (1.6%-3.4%), psychosis (0.7%-0.8%), and eating disorders (0.2%-0.3%) increased. The prevalence of hypertension increased sharply from 0.06% in 2000 to 0.3% in 2019. Diabetes mellitus and stroke rates increased, as did the prevalence of systemic lupus, multiple sclerosis, and chronic kidney disease. Advanced maternal age was strongly associated with both psychiatric and circulatory/metabolic conditions. A strong birth cohort effect was evident, with rates of psychiatric conditions increasing among women born after 1985. CONCLUSIONS: In British Columbia, Canada, 1 in 4 mothers had a pre-existing health condition 5 years prior to pregnancy. These findings underscore the need for multi-disciplinary care for women with pre-existing health conditions to improve maternal, foetal, and infant health.

Obesity, Twin Pregnancy, and the Role of Assisted Reproductive Technology.

Importance: The prevalence of overweight and obesity (body mass index [BMI] ≥25) has increased globally, and high BMI has been linked to higher rates of twin birth. However, evidence from large population-based studies is lacking; the issue needs careful study, as women with obesity are also more likely to use assisted reproductive technology (ART), which frequently results in twin pregnancy. Objective: To examine the association between BMI and twin birth and the role of ART as a potential mediator in this association. Design, Setting, and Participants: This retrospective cohort study included all live births and stillbirths with gestational age of 20 weeks or longer in British Columbia, Canada, from 2008 to 2020, using data from the British Columbia Perinatal Database Registry. Data analysis was conducted from November 2022 to June 2023. Exposures: Prepregnancy BMI, calculated as weight in kilograms divided by height in meters squared, and use of ART. Main Outcomes and Measures: The study assessed whether prepregnancy BMI is associated with the rate of twin vs singleton delivery and whether this association is explained by the differential use of ART in women with obesity. Results: A total of 524 845 deliveries at 20 weeks' or longer gestation occurred in British Columbia during the study period, and 392 046 women had complete data on prepregnancy BMI. The median (IQR) age was 31.4 (27.7-35.0) years, approximately half were nulliparous (243 443 [46.4%]) and less than 10% smoked during pregnancy (36 894 [7.1%]). Overall, 8295 women had a twin delivery (15.8 per 1000 deliveries), and rates per 1000 deliveries by prepregnancy BMI categories were 11.9 (underweight), 15.1 (normal), 16.0 (overweight), 16.0 (obesity class I), 16.7 (obesity class II), and 18.9 (obesity class III). After adjustment for other covariates, women with underweight had relatively 16% fewer twins compared with women with normal BMI (adjusted risk ratio [aRR], 0.84; 95% CI, 0.74-0.95), while women with overweight, class I obesity, class II obesity, and class III obesity had 14% (aRR, 1.14; 95% CI, 1.07-1.21), 16% (aRR, 1.16; 95% CI, 1.06-1.27), 17% (aRR, 1.17; 95% CI, 1.02-1.34), and 41% higher rates (aRR, 1.41; 95% CI, 1.19-1.66), respectively. The proportion of women who conceived by ART increased with increasing BMI, and ART was associated with nearly a 12-fold higher rate of twin delivery (aRR, 11.80; 95% CI 11.10-12.54). ART explained about a quarter of the association between obesity class I and II and twin delivery (eg, obesity class I, 23% mediated; 95% CI, 7%-39% mediated), but none of this association was mediated by ART in women with class III obesity. Conclusions and relevance: In this cohort study of 524 845 births, the rate of twin birth increased with increasing prepregnancy BMI. In women with a BMI between 30 and 40, approximately one-quarter of this association was explained by higher use of ART; however, there was no evidence of such mediation in women with BMI of 40 or greater.

The clinical performance and population health impact of birthweight-for-gestational age indices at term gestation.

BACKGROUND: The assessment of birthweight for gestational age and the identification of small- and large-for-gestational age (SGA and LGA) infants remain contentious, despite the recent creation of the Intergrowth 21st Project and World Health Organisation (WHO) birthweight-for-gestational age standards. OBJECTIVE: We carried out a study to identify birthweight-for-gestational age cut-offs, and corresponding population-based, Intergrowth 21st and WHO centiles associated with higher risks of adverse neonatal outcomes, and to evaluate their ability to predict serious neonatal morbidity and neonatal mortality (SNMM) at term gestation. METHODS: The study population was based on non-anomalous, singleton live births between 37 and 41 weeks' gestation in the United States from 2003 to 2017. SNMM included 5-min Apgar score <4, neonatal seizures, need for assisted ventilation, and neonatal death. Birthweight-specific SNMM was modelled by gestational week using penalised B-splines. The birthweights at which SNMM odds were minimised (and higher by 10%, 50% and 100%) were estimated, and the corresponding population, Intergrowth 21st, and WHO centiles were identified. The clinical performance and population impact of these cut-offs for predicting SNMM were evaluated. RESULTS: The study included 40,179,663 live births and 991,486 SNMM cases. Among female singletons at 39 weeks' gestation, SNMM odds was lowest at 3203 g birthweight, and 10% higher at 2835 g and 3685 g (population centiles 11th and 82nd, Intergrowth centiles 17th and 88th and WHO centiles 15th and 85th). Birthweight cut-offs were poor predictors of SNMM, for example, the cut-offs associated with 10% and 50% higher odds of SNMM among female singletons at 39 weeks' gestation resulted in a sensitivity, specificity, and population attributable fraction of 12.5%, 89.4%, and 2.1%, and 2.9%, 98.4% and 1.3%, respectively. CONCLUSIONS: Reference- and standard-based birthweight-for-gestational age indices and centiles perform poorly for predicting adverse neonatal outcomes in individual infants, and their associated population impact is also small.

Severe maternal morbidity surveillance, temporal trends and regional variation: A population-based cohort study.

OBJECTIVE: To quantify temporal trends and regional variation in severe maternal morbidity (SMM) in Sweden. DESIGN: Cohort study. POPULATION: Live birth and stillbirth deliveries in Sweden, 1999-2019. METHODS: Types and subtypes of SMM were identified, based on a standard list (modified for Swedish clinical setting after considering the frequency and validity of each indicator) using diagnoses and procedure codes, among all deliveries at ≥22 weeks of gestation (including complications within 42 days of delivery). Contrasts between regions were quantified using rate ratios (RRs) and 95% confidence intervals (95% CIs). Temporal changes in SMM types and subtypes were described. MAIN OUTCOME MEASURES: Types and subtypes of SMM. RESULTS: There were 59 789 SMM cases among 2 212 576 deliveries, corresponding to 270.2 (95% CI 268.1-272.4) per 10 000 deliveries. Composite SMM rates increased from 236.6 per 10 000 deliveries in 1999 to 307.3 per 10 000 deliveries in 2006, before declining to 253.8 per 10 000 deliveries in 2019. Changes in composite SMM corresponded with temporal changes in severe haemorrhage rates, which increased from 94.9 per 10 000 deliveries in 1999 to 169.3 per 10 000 deliveries in 2006, before declining to 111.2 per 10 000 deliveries in 2019. Severe pre-eclampsia, eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome (103.8 per 10 000 deliveries), severe haemorrhage (133.7 per 10 000 deliveries), sepsis, embolism, disseminated intravascular coagulation, shock and severe mental health disorders were the most common SMM types. Rates of embolism, disseminated intravascular coagulation and shock, acute renal failure, cardiac complications, sepsis and assisted ventilation increased, whereas rates of surgical complications, severe uterine rupture and anaesthesia complications declined. CONCLUSIONS: The observed spatiotemporal variations in composite SMM and SMM types provide substantive insights and highlight regional priorities for improving maternal health.

Effect of the COVID-19 Pandemic on Stillbirths in Canada and the United States.

OBJECTIVE: There is uncertainty regarding the effect of the COVID-19 pandemic on population rates of stillbirth. We quantified pandemic-associated changes in stillbirth rates in Canada and the United States. METHODS: We carried out a retrospective study that included all live births and stillbirths in Canada and the United States from 2015 to 2020. The primary analysis was based on all stillbirths and live births at ≥20 weeks gestation. Stillbirth rates were analyzed by month, with March 2020 considered to be the month of pandemic onset. Interrupted time series analyses were used to determine pandemic effects. RESULTS: The study population included 18 475 stillbirths and 2 244 240 live births in Canada and 134 883 stillbirths and 22 963 356 live births in the United States (8.2 and 5.8 stillbirths per 1000 total births, respectively). In Canada, pandemic onset was associated with an increase in stillbirths at ≥20 weeks gestation of 1.01 (95% confidence interval [CI] 0.56-1.46) per 1000 total births and an increase in stillbirths at ≥28 weeks gestation of 0.35 (95% CI 0.16-0.54) per 1000 total births. In the United States, pandemic onset was associated with an increase in stillbirths at ≥20 weeks gestation of 0.48 (95% CI 0.22-0.75) per 1000 total births and an increase in stillbirths at ≥28 weeks gestation of 0.22 (95% CI 0.12-0.32) per 1000 total births. The increase in stillbirths at pandemic onset returned to pre-pandemic levels in subsequent months. CONCLUSION: The COVID-19 pandemic's onset was associated with a transitory increase in stillbirth rates in Canada and the United States.

Obstetric Intervention and Perinatal Outcomes During the Coronavirus Disease 2019 (COVID-19) Pandemic.

OBJECTIVE: To quantify pandemic-related changes in obstetric intervention and perinatal outcomes in the United States. METHODS: We carried out a retrospective study of all live births and fetal deaths in the United States, 2015-2021, with data obtained from the natality, fetal death, and linked live birth-infant death files of the National Center for Health Statistics. Analyses were carried out among all singletons; singletons of patients with prepregnancy diabetes, prepregnancy hypertension, and hypertensive disorders of pregnancy; and twins. Outcomes of interest included preterm birth, preterm labor induction or preterm cesarean delivery, macrosomia, postterm birth, and perinatal death. Interrupted time series analyses were used to estimate changes in the prepandemic period (January 2015-February 2020), at pandemic onset (March 2020), and in the pandemic period (March 2020-December 2021). RESULTS: The study population included 26,604,392 live births and 155,214 stillbirths. The prepandemic period was characterized by temporal increases in preterm birth and preterm labor induction or cesarean delivery rates and temporal reductions in macrosomia, postterm birth, and perinatal mortality. Pandemic onset was associated with absolute decreases in preterm birth (decrease of 0.322/100 live births, 95% CI 0.506-0.139) and preterm labor induction or cesarean delivery (decrease of 0.190/100 live births, 95% CI 0.334-0.047) and absolute increases in macrosomia (increase of 0.046/100 live births), postterm birth (increase of 0.015/100 live births), and perinatal death (increase of 0.501/1,000 total births, 95% CI 0.220-0.783). These changes were larger in subpopulations at high risk (eg, among singletons of patients with prepregnancy diabetes). Among singletons of patients with prepregnancy diabetes, pandemic onset was associated with a decrease in preterm birth (decrease of 1.634/100 live births) and preterm labor induction or cesarean delivery (decrease of 1.521/100 live births) and increases in macrosomia (increase of 0.328/100 live births) and perinatal death (increase of 9.840/1,000 total births, 95% CI 3.933-15.75). Most changes were reversed in the months after pandemic onset. CONCLUSION: The onset of the coronavirus disease 2019 (COVID-19) pandemic was associated with a transient decrease in obstetric intervention (especially preterm labor induction or cesarean delivery) and a transient increase in perinatal mortality.

Pre-pregnancy and pregnancy disorders, pre-term birth and the risk of cerebral palsy: a population-based study.

BACKGROUND: Cerebral palsy (CP) is the most common cause of childhood physical disability whose aetiology remains unclear in most cases. Maternal pre-existing and pregnancy complications are recognized risk factors of CP but the extent to which their effects are mediated by pre-term birth is unknown. METHODS: Population-based cohort study in Sweden including 2 055 378 singleton infants without congenital abnormalities, born between 1999 and 2019. Data on maternal and pregnancy characteristics and diagnoses of CP were obtained by individual record linkages of nationwide Swedish registries. Exposure was defined as maternal pre-pregnancy and pregnancy disorders. Inpatient and outpatient diagnoses were obtained for CP after 27 days of age. Adjusted rate ratios (aRRs) were calculated, along with 95% CIs. RESULTS: A total of 515 771 (25%) offspring were exposed to maternal pre-existing chronic disorders and 3472 children with CP were identified for a cumulative incidence of 1.7 per 1000 live births. After adjusting for potential confounders, maternal chronic cardiovascular or metabolic disorders, other chronic diseases, mental health disorders and early-pregnancy obesity were associated with 1.89-, 1.24-, 1.26- and 1.35-times higher risk (aRRs) of CP, respectively. Most notably, offspring exposed to maternal antepartum haemorrhage had a 6-fold elevated risk of CP (aRR 5.78, 95% CI, 5.00-6.68). Mediation analysis revealed that ∼50% of the effect of these associations was mediated by pre-term delivery; however, increased risks were also observed among term infants. CONCLUSIONS: Exposure to pre-existing maternal chronic disorders and pregnancy-related complications increases the risk of CP in offspring. Although most infants with CP were born at term, pre-term delivery explained 50% of the overall effect of pre-pregnancy and pregnancy disorders on CP.

Pregnancy, Delivery, and Neonatal Outcomes Associated With Maternal Obsessive-Compulsive Disorder: Two Cohort Studies in Sweden and British Columbia, Canada.

Importance: Obsessive-compulsive disorder (OCD) is associated with adverse health-related outcomes. However, pregnancy and neonatal outcomes among women with OCD have been sparsely studied. Objective: To evaluate associations of maternal OCD with pregnancy, delivery, and neonatal outcomes. Design, Setting, and Participants: Two register-based cohort studies in Sweden and British Columbia (BC), Canada, included all singleton births at 22 weeks or more of gestation between January 1, 1999 (Sweden), or April 1, 2000 (BC), and December 31, 2019. Statistical analyses were conducted between August 1, 2022, and February 14, 2023. Exposure: Maternal OCD diagnosis recorded before childbirth and use of serotonin reuptake inhibitors (SRIs) during pregnancy. Main Outcomes and Measures: Pregnancy and delivery outcomes examined were gestational diabetes, preeclampsia, maternal infection, antepartum hemorrhage or placental abruption, premature rupture of membranes, induction of labor, mode of delivery, and postpartum hemorrhage. Neonatal outcomes included perinatal death, preterm birth, small for gestational age, low birth weight (<2500 g), low 5-minute Apgar score, neonatal hypoglycemia, neonatal jaundice, neonatal respiratory distress, neonatal infections, and congenital malformations. Multivariable Poisson log-linear regressions estimated crude and adjusted risk ratios (aRRs). In the Swedish cohort, sister and cousin analyses were performed to account for familial confounding. Results: In the Swedish cohort, 8312 pregnancies in women with OCD (mean [SD] age at delivery, 30.2 [5.1] years) were compared with 2 137 348 pregnancies in unexposed women (mean [SD] age at delivery, 30.2 [5.1] years). In the BC cohort, 2341 pregnancies in women with OCD (mean [SD] age at delivery, 31.0 [5.4] years) were compared with 821 759 pregnancies in unexposed women (mean [SD] age at delivery, 31.3 [5.5] years). In Sweden, maternal OCD was associated with increased risks of gestational diabetes (aRR, 1.40; 95% CI, 1.19-1.65) and elective cesarean delivery (aRR, 1.39; 95% CI, 1.30-1.49), as well as preeclampsia (aRR, 1.14; 95% CI, 1.01-1.29), induction of labor (aRR, 1.12; 95% CI, 1.06-1.18), emergency cesarean delivery (aRR, 1.16; 95% CI, 1.08-1.25), and postpartum hemorrhage (aRR, 1.13; 95% CI, 1.04-1.22). In BC, only emergency cesarean delivery (aRR, 1.15; 95% CI, 1.01-1.31) and antepartum hemorrhage or placental abruption (aRR, 1.48; 95% CI, 1.03-2.14) were associated with significantly higher risk. In both cohorts, offspring of women with OCD were at elevated risk of low Apgar score at 5 minutes (Sweden: aRR, 1.62; 95% CI, 1.42-1.85; BC: aRR, 2.30; 95% CI, 1.74-3.04), as well as preterm birth (Sweden: aRR, 1.33; 95% CI, 1.21-1.45; BC: aRR, 1.58; 95% CI, 1.32-1.87), low birth weight (Sweden: aRR, 1.28; 95% CI, 1.14-1.44; BC: aRR, 1.40; 95% CI, 1.07-1.82), and neonatal respiratory distress (Sweden: aRR, 1.63; 95% CI, 1.49-1.79; BC: aRR, 1.47; 95% CI, 1.20-1.80). Women with OCD taking SRIs during pregnancy had an overall increased risk of these outcomes, compared with those not taking SRIs. However, women with OCD not taking SRIs still had increased risks compared with women without OCD. Sister and cousin analyses showed that at least some of the associations were not influenced by familial confounding. Conclusion and Relevance: These cohort studies suggest that maternal OCD was associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. Improved collaboration between psychiatry and obstetric services and improved maternal and neonatal care for women with OCD and their children is warranted.

A flexible approach to modelling stillbirths using the foetuses at risk approach.

BACKGROUND: Survival analysis methods are increasingly used to model the gestational age-specific risk of perinatal phenomena such as stillbirth. OBJECTIVES: To compare two types of survival analysis models, and highlight differences by estimating the relationships between pre-pregnancy BMI and gestational age-specific rates of stillbirth. METHODS: The study was based on singleton live births and stillbirths in the United States in 2016-2017, with data obtained from the natality and fetal death files of the National Center for Health Statistics. We compared Cox regression versus piecewise exponential additive mixed models (PAMMs) for modelling the relationship between BMI and stillbirth across gestational age. In a second analysis, we illustrated the performance of both models for assessing the relationship between the trimester-specific number of cigarettes smoked, a time-dependent covariate, and stillbirth. RESULTS: The study population included 7,567,316 births, of which 42,739 were stillbirths (5.6 per 1000 total births). Stillbirth rates increased with increasing pre-pregnancy BMI and increasing gestational age. In analyses with BMI as a categorical variable, the Cox model and PAMM models yielded similar results. Analyses of BMI as a continuous variable also showed similar results when BMI associations were assumed to be linear, and the changes in gestational age-specific rates were modelled parametrically. However, results differed slightly when PAMMs, modelled with data-driven approaches, were used to estimate changes in BMI effects across gestational age; PAMMs provided a more nuanced modelling of time-varying effects. PAMM models showed an approximately linear increase in the effect of smoking on stillbirth with increasing gestational age. CONCLUSIONS: For survival analyses using the foetuses-at-risk approach, PAMMs provide a valuable alternative to the traditional Cox model, with increased modelling flexibility when proportional hazards assumptions are violated.