Maternal body mass index in early pregnancy and offspring mortality up to early adulthood: A nationwide cohort study
Background Obesity is increasingly common among women of childbearing age worldwide. Maternal obesity during pregnancy may have long-term implications for offspring health, but its association with offspring mortality remains not well understood. In this nationwide cohort study, we examined the associations of maternal body mass index (BMI) in early pregnancy with all-cause and cause-specific mortality in offspring. Methods and findings We included 2,606,684 live births in Sweden during 1982–2014 (except for 1990 and 1991) and followed them from birth until death, emigration from Sweden, or December 31, 2023, whichever came first. Information on maternal BMI during early pregnancy was obtained from the Medical Birth Register and was categorized as: underweight (BMI <18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), obesity grade I (30.0–34.9 kg/m2), obesity grade II (35.0–39.9 kg/m2), and obesity grade III (≥40.0 kg/m2). Data on all-cause and cause-specific mortality in offsprings were obtained from the Cause of Death Register. Cox proportional hazard models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for offspring mortality according to maternal BMI (both as a continuous and as a categorical variable), adjusting for maternal characteristics (age, education, and income at the childbirth, marital status, country of birth, smoking status in early pregnancy, psychiatric disorders and cardiovascular diseases before the childbirth). We used cousin comparison analysis to explore the potential influence of familial confounding factors. During a median follow-up of 22.4 years (interquartile range 14.9–30.7 years), 21,981 (0.8%) offspring died. Maternal BMI was positively associated with all-cause mortality in offspring: HR 1.03 (95% CI [1.02, 1.03]; p < 0.001) per 1 unit increase in BMI. Offspring of mothers with overweight or obesity (regardless of grade) during early pregnancy had higher risks of all-cause mortality than their counterparts with normal maternal BMI at the reference category; the corresponding HRs were HR 1.11 (95% CI [1.07, 1.15]; p < 0.001) for overweight, HR 1.27 (95% CI [1.20, 1.35]; p < 0.001) for obesity grade I, HR 1.68 (95% CI [1.52, 1.86]; p < 0.001) for obesity grade II, and HR 1.92 (95% CI [1.59, 2.33]; p < 0.001) for obesity grade III, respectively. The associations were similar for several of the most common underlying causes of death in young age, i.e., respiratory diseases, cardiovascular diseases, and congenital anomalies. The associations were attenuated but remained in the cousin comparison analysis. The main limitation was the potential for residual confounding; the observed associations should not be interpreted as evidence of a causal effect of maternal BMI in early pregnancy on offspring mortality. Conclusions Offspring born to mothers with overweight or obesity during early pregnancy had an increased risk of premature mortality up to early adulthood. Given the rising obesity rate in women of childbearing age, our findings underscore the need to better understand the underlying mechanisms for this association. If confirmed by further studies, these results highlight the importance of achieving a healthy maternal BMI prior to conception as a potential strategy to improve child health.