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.

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.

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.

How interventions to maintain services during the COVID-19 pandemic strengthened systems for delivery of maternal and child health services: a case-study of Wakiso District, Uganda.

BACKGROUND: Health systems are resilient if they absorb, adapt, and transform in response to shocks. Although absorptive and adaptive capacities have been demonstrated during the COVID-19 response, little has been documented about their transformability and strengthened service delivery systems. We aimed to describe improvements in maternal and child health service delivery as a result of investments during the COVID-19 response. METHODS: This was a descriptive case study conducted in Wakiso District in central Uganda. It included 21 nurses and midwives as key informants and 32 mothers in three focus group discussions. Data were collected using an interview guide following the Systems Engineering Initiative for Patient Safety theoretical framework for service delivery. RESULTS: Maternal and child health service delivery during the pandemic involved service provision without changes, service delivery with temporary changes and outcomes, and service delivery that resulted into sustained changes and outcomes. Temporary changes included patient schedule adjustments, community service delivery and negative outcomes such as increased workload and stigma against health workers. Sustained changes that strengthened service delivery included new infrastructure and supplies such as ambulances and equipment, new roles involving infection prevention and control, increased role of community health workers and outcomes such as improved workplace safety and teamwork. CONCLUSIONS: In spite of the negative impact the COVID-19 pandemic had on health systems, it created the impetus to invest in system improvements. Investments such as new facility infrastructure and emergency medical services were leveraged to improve maternal and child health services delivery. The inter-departmental collaboration during the response to the COVID-19 pandemic resulted into an improved intra-hospital environment for other service delivery. However, there is a need to evaluate lessons beyond health facilities and whether these learnings are deliberately integrated into service delivery. Future responses should also address the psychological and physical impacts suffered by health workers to maintain service delivery.

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.

Neurological development in children born moderately or late preterm: national cohort study.

OBJECTIVE: To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term). DESIGN: Nationwide cohort study. SETTING: Sweden. PARTICIPANTS: 1 281 690 liveborn singleton children without congenital malformations born at 32+0 to 41+6 weeks between 1998 and 2012. MAIN OUTCOME MEASURES: The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment. RESULTS: During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term. CONCLUSIONS: The findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.

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.

Association of pre-existing maternal cardiovascular diseases with neurodevelopmental disorders in offspring: a cohort study in Sweden and British Columbia, Canada.

BACKGROUND: We aimed to investigate the associations of pre-existing maternal cardiovascular disease (CVD) with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in offspring. METHODS: This population-based cohort study included singletons live-born without major malformations in Sweden (n = 2 699 675) and British Columbia (BC), Canada (n = 887 582) during 1990-2019, with follow-up from age 1 year until the outcome, death, emigration or December 2020, whichever came first. The primary exposure was defined as a composite CVD diagnosed prior to conception: cerebrovascular disease, arrhythmia, heart failure, valvular and congenital heart diseases. The incidences of ADHD, ASD and ID, comparing offspring of mothers with versus without CVD, were calculated as adjusted hazard ratios (aHRs). These results were compared with models using paternal CVD as negative control exposure. RESULTS: Compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD [95% confidence interval (CI): 1.10-1.20] and ASD (95% CI 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (HR 1.31, 95% CI 1.02-1.61), cerebrovascular disease (HR 1.20, 95% CI 1.08-1.32), congenital heart disease (HR 1.18, 95% CI 1.08-1.27), arrhythmia (HR 1.13, 95% CI 1.08-1.19) and valvular heart disease (HR 1.12, 95% CI 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (HR 1.25, 95% CI 1.04-1.46), congenital heart disease (HR 1.17, 95% CI 1.01-1.33) and arrythmia (HR 1.12, 95% CI 1.01-1.21). Paternal CVD did not show associations with ADHD, ASD or ID, except for cerebrovascular disease which showed associations with ADHD and ASD. CONCLUSIONS: In this large cohort study, pre-existing maternal CVD was associated with increased risk of ADHD and ASD in offspring.

Stillbirths: Contribution of preterm birth and size-for-gestational age for 125.4 million total births from nationwide records in 13 countries, 2000-2020.

OBJECTIVE: To examine the contribution of preterm birth and size-for-gestational age in stillbirths using six 'newborn types'. DESIGN: Population-based multi-country analyses. SETTING: Births collected through routine data systems in 13 countries. SAMPLE: 125 419 255 total births from 22+0 to 44+6 weeks' gestation identified from 2000 to 2020. METHODS: We included 635 107 stillbirths from 22+0 weeks' gestation from 13 countries. We classified all births, including stillbirths, into six 'newborn types' based on gestational age information (preterm, PT, <37+0 weeks versus term, T, ≥37+0 weeks) and size-for-gestational age defined as small (SGA, <10th centile), appropriate (AGA, 10th-90th centiles) or large (LGA, >90th centile) for gestational age, according to the international newborn size for gestational age and sex INTERGROWTH-21st standards. MAIN OUTCOME MEASURES: Distribution of stillbirths, stillbirth rates and rate ratios according to six newborn types. RESULTS: 635 107 (0.5%) of the 125 419 255 total births resulted in stillbirth after 22+0 weeks. Most stillbirths (74.3%) were preterm. Around 21.2% were SGA types (PT + SGA [16.2%], PT + AGA [48.3%], T + SGA [5.0%]) and 14.1% were LGA types (PT + LGA [9.9%], T + LGA [4.2%]). The median rate ratio (RR) for stillbirth was highest in PT + SGA babies (RR 81.1, interquartile range [IQR], 68.8-118.8) followed by PT + AGA (RR 25.0, IQR, 20.0-34.3), PT + LGA (RR 25.9, IQR, 13.8-28.7) and T + SGA (RR 5.6, IQR, 5.1-6.0) compared with T + AGA. Stillbirth rate ratios were similar for T + LGA versus T + AGA (RR 0.7, IQR, 0.7-1.1). At the population level, 25% of stillbirths were attributable to small-for-gestational-age. CONCLUSIONS: In these high-quality data from high/middle income countries, almost three-quarters of stillbirths were born preterm and a fifth small-for-gestational age, with the highest stillbirth rates associated with the coexistence of preterm and SGA. Further analyses are needed to better understand patterns of gestation-specific risk in these populations, as well as patterns in lower-income contexts, especially those with higher rates of intrapartum stillbirth and SGA.

Neonatal mortality risk of large-for-gestational-age and macrosomic live births in 15 countries, including 115.6 million nationwide linked records, 2000-2020.

OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

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.

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.