Maternal Body Mass Index, Gestational Weight Gain, and Cardiovascular Disease in Offspring

Importance: The long-term association of maternal body mass index (BMI) in early pregnancy and gestational weight gain (GWG) with offspring cardiovascular disease (CVD) risk remains unclear. Objective: To analyze the associations of maternal BMI and GWG with offspring CVD risk. Design, Setting, and Participants: This cohort study used data from national registers in Sweden for individuals born from January 1, 1982, to December 31, 2014. Participants were followed up from birth until the first diagnosis of CVD, death, emigration from Sweden, or December 31, 2023, whichever came first. Data were analyzed from February 1, 2025, to June 16, 2026. Exposures: Data were obtained on maternal BMI in early pregnancy and GWG from the Swedish Medical Birth Register. BMI was categorized as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obesity classes 1 (30.0-34.9), 2 (35.0-39.9), and 3 (≥40.0). GWG was standardized for gestational age into z scores. Main Outcome and Measures: Data on offspring CVD were retrieved from the Patient Register and the Cause of Death Register. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Sibling analyses were conducted to assess the potential association of shared familial factors. Results: Among 2 496 335 offspring, 1 283 648 (51.4%) were male. At the end of follow-up, the mean (SD) age of the offspring was 23.3 (9.8) years. During a median (IQR) follow-up of 22.0 (14.7-30.4) years, 22 510 offpsring (0.9%) were diagnosed with CVD. Compared with offspring of mothers with normal BMI, the CVD HRs were 1.29 (95% CI, 1.24-1.33) for maternal overweight, 1.66 (95% CI, 1.57-1.75) for maternal obesity class 1, 2.16 (95% CI, 1.96-2.39) for maternal obesity class 2, and 2.74 (95% CI, 2.29-3.28) for maternal obesity class 3. Greater GWG was associated with higher CVD risk across BMI groups; among offspring of mothers with normal BMI, the HR for higher GWG (z score ≥1) was 1.16 (95% CI, 1.09-1.22). In the sibling analyses, higher maternal BMI and GWG were associated with attenuated risk of offspring CVD, but the associations remained generally evident. Conclusions and Relevance: This Swedish national cohort study found that high maternal BMI and greater GWG were associated with increased risks of early-onset offspring CVD, highlighting the importance of managing maternal weight during pregnancy.