Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort.

Importance: Recent studies suggest that cesarean delivery (CD) is associated with increased risk of neurodevelopmental disorders in children, although they were unable to control for indications for CD or familial confounding beyond full siblings. Objective: To examine the association between CD and neurodevelopmental and psychiatric disorders in children. Design, Setting, and Participants: This Swedish register-based cohort study included 1 179 341 term-birth singletons born between January 1, 1990, and December 31, 2003, and followed up through December 31, 2013. All individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins. Statistical analyses were performed from September 26, 2019, to January 16, 2021. Exposures: Birth by CD recorded at birth, stratified into planned and intrapartum CD. Main Outcomes and Measures: Registered diagnoses of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, tic disorders, communication disorders, learning disorders, and any neurodevelopmental disorder; and psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, depressive disorders, eating disorders, bipolar disorders, psychotic disorders, and any psychiatric disorder. Results: Of 1 179 341 individuals, 1 048 838 (533 140 boys [50.8%]) were delivered vaginally, 59 514 (30 138 boys [50.6%]) were delived via planned CD, and 70 989 (39 191 boys [55.2%]) were delivered via intrapartum CD. Mean (SD) age at follow-up was 17.7 (4.1) years for vaginal delivery, 16.6 (4.2) years for planned CD, and 16.8 (4.1) years for intrapartum CD. Compared with vaginal delivery, and after controlling for measured covariates (parental and neonatal characteristics, maternal comorbidities, and pregnancy complications), CD was associated with higher risk in children of any neurodevelopmental disorder (planned CD, hazard ratio [HR], 1.17; 95% CI, 1.13-1.22; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.14), ADHD (planned CD, HR, 1.17; 95% CI, 1.12-1.23; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.15), and intellectual disability (planned CD, HR, 1.26; 95% CI, 1.14-1.39; intrapartum CD, HR, 1.17; 95% CI, 1.06-1.28). Only planned CD was associated with a higher risk of ASD (HR, 1.20; 95% CI, 1.10-1.31), communication disorders (HR, 1.14; 95% CI, 1.02-1.28), and learning disorders (HR, 1.15; 95% CI, 1.01-1.30). Cesarean delivery was not associated with the remaining disorders. The associations between CD and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated (became nonsignificant) in maternal half siblings and full siblings (risk of any neurodevelopmental disorder in full siblings, planned CD, HR, 0.93; 95% CI, 0.81-1.06; intrapartum CD, HR, 1.07; 95% CI, 0.96-1.21). Conclusions and Relevance: The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding.

Weight gain during pregnancy and the black-white disparity in preterm birth.

PURPOSE: To quantify the relationship between pregnancy weight gain with early and late preterm birth and evaluate whether associations differed between non-Hispanic (NH) black and NH white women. METHODS: We analyzed a retrospective cohort of all live births to NH black and NH white women in the United States 2011-2015 (n = 10,714,983). We used weight gain z-scores in multiple logistic regression models stratified by prepregnancy body mass index (BMI) and race to calculate population attributable risk (PAR) percentages for the contribution of high and low pregnancy weight gain to early and late preterm birth. RESULTS: Pregnancy weight gain was related to early and late preterm birth, but associations varied by BMI and race. For early preterm birth, the PAR percentage for high pregnancy weight gain ranged from 8 to 10% in NH black women and from 6 to 8% in NH white women. There was little evidence of racial differences in late preterm birth: PAR percentages ranged from 2 to 7% in NH black women and from 3 to 7% in NH white women. CONCLUSIONS: Moderate gestational weight gain is associated with lower rate of preterm birth, with greatest reductions for early preterm birth in NH black women.

Registers of the Swedish total population and their use in medical research.

The primary aim of the Swedish national population registration system is to obtain data that (1) reflect the composition, relationship and identities of the Swedish population and (2) can be used as the basis for correct decisions and measures by government and other regulatory authorities. For this purpose, Sweden has established two population registers: (1) The Population Register, maintained by the Swedish National Tax Agency ("Folkbokföringsregistret"); and (2) The Total Population Register (TPR) maintained by the government agency Statistics Sweden ("Registret över totalbefolkningen"). The registers contain data on life events including birth, death, name change, marital status, family relationships and migration within Sweden as well as to and from other countries. Updates are transmitted daily from the Tax Agency to the TPR. In this paper we describe the two population registers and analyse their strengths and weaknesses. Virtually 100 % of births and deaths, 95 % of immigrations and 91 % of emigrations are reported to the Population Registers within 30 days and with a higher proportion over time. The over-coverage of the TPR, which is primarily due to underreported emigration data, has been estimated at up to 0.5 % of the Swedish population. Through the personal identity number, assigned to all residents staying at least 1 year in Sweden, data from the TPR can be used for medical research purposes, including family design studies since each individual can be linked to his or her parents, siblings and offspring. The TPR also allows for identification of general population controls, participants in cohort studies, as well as calculation of follow-up time.

Mothers with alcoholic liver disease and the risk for preterm and small-for-gestational-age birth.

AIMS: To study pregnancy outcome in women with alcoholic liver disease (ALD). METHODS: Using the Swedish nation-wide Patient and Medical Birth Registers, we investigated risk of adverse pregnancy outcome in 720 women diagnosed with ALD before and 1720 diagnosed after birth and compared them with 24 460 population-based control births. RESULTS: Women with ALD diagnosed before or after birth were generally of higher age and body mass index, more likely to smoke cigarettes during pregnancy and to have a low socio-economic status compared with controls. Women diagnosed with ALD before birth had an increased risk of moderately and very preterm birth, adjusted odd ratio (OR) = 1.53 (95% confidence interval (CI): 1.37-1.72 and 1.15-2.06 95%), respectively. Infants of mothers with ALD before birth were more often small-for-gestational age, adjusted OR = 1.22 (95% CI: 1.05-1.43), and were at increased risk for low Apgar scores (<7) at 5 min, adjusted OR = 1.49 (95% CI: 1.15-1.92) compared with controls. Similar associations with slightly lower-risk estimates were found among women diagnosed with ALD after birth. CONCLUSIONS: ALD is associated with adverse-birth outcomes, highlighting the importance of screening women for alcohol dependence in antenatal care.