Maternal Obesity and Risk of Cardiovascular Diseases in Offspring: Population-Based Cohort and Sibling-Controlled Studies

Abstract

Background: Maternal overweight and obesity may increase offspring risks of adiposity, cardiovascular and metabolic diseases in childhood. We examined the associations between maternal overweight and obesity severity on risks of cardiovascular diseases (CVD) in offspring during childhood and early adulthood. Methods: In this population-based cohort study, we identified 2,412,100 non-malformed live singleton infants in the Swedish Medical Birth Register between 1992 and 2016. The diagnoses of CVD, pregnancy and neonatal complications were based on information from the nation-wide Medical Birth and Patient Registers. Multivariable Cox proportional hazards regression was used to estimate association between maternal body mass index (BMI) and CVD risk with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). We further calculated the proportion of the association mediated through known consequences of obesity that also predicted CVD. To account for unmeasured genetic or environmental factors, we conducted sibling-controlled analyses. Findings: The overall incidence of CVD in offspring aged 1-25 years, was 0·75 per 10,000 child-years. Compared with offspring of normal weight mothers (BMI 18·5 to <25), aHRs (95% CIs) of CVD by maternal BMI categories were as follows: overweight (BMI 25 to <30), 1·07 (0·96, 1·19); obesity grade I (BMI 30 to <35), 1·11 (0·93-1·32); obesity grade II (BMI 35 to<40), 1·67 (1·28-2·19); and obesity grade III (BMI ≥40) 2·68 (1·85-3·89). Increasing maternal BMI was related to elevated risks of heart failure and cerebrovascular diseases in dose-response fashions (P for trend <0·001). Part of the observed association was mediated through asphyxia-related neonatal complications. The sibling-cohort analysis indicated a similar positive trend between maternal BMI and rates of CVD as the cohort analysis. Interpretations: Rates of CVD in offspring increase with maternal BMI in a dose-response manner. The association may be partly mediated through asphyxia-related neonatal complications. Funding Statement: The study was supported by grants from the Swedish Research Council for Health, Working Life and Welfare (grant No 2017-00134) and an unrestricted grant from Karolinska Institutet, Stockholm, Sweden (No. 2368/10-221 Distinguished Professor Award to Dr Cnattingius). Drs Razaz and Muraca are supported by a fellowship award from the Canadian Institutes of Health Research (CIHR). Declaration of Interests: All authors have no financial disclosures to state. Ethics Approval Statement: The study was approved by the Research Ethics Committee at Karolinska Institutet, Stockholm, Sweden (No. 2012/365-32 and No. 2017/1937-32).