High Maternal Body Mass Index in Early Pregnancy and Risks of Stillbirth and Infant Mortality-A Population-Based Sibling Study in Sweden

Abstract

In a population-based case-control study, we investigated whether familial confounding influenced the associations between maternal overweight/obesity and risks of stillbirth and infant mortality by including both population and sister controls. Using nationwide data from the Swedish Medical Birth Register (1992-2011), we included all primiparous women with singleton births who also had a sister with a first birth during that time period. We used logistic regression analyses to calculate odds ratios (and 95% confidence intervals) adjusted for maternal age, height, smoking habits, education, and time period (5-year groups) of child's birth. Body mass index (BMI) was calculated as weight (kg)/height (m)(2) Compared with population controls with a normal BMI (18.5-24.9), stillbirth risk increased with increasing BMI (BMI 25-29.9: odds ratio (OR) = 1.51 (95% confidence interval (CI): 1.21, 1.89); BMI 30-34.9: OR = 1.77 (95% CI: 1.24, 2.50); BMI ≥35: OR = 3.16 (95% CI: 2.10, 4.76)). The sister case-control analyses revealed similar results. Offspring of obese women (BMI ≥30) had an increased risk of infant mortality when population controls were used (OR = 2.41, 95% CI: 1.83, 3.16), and an even higher risk was obtained when sister controls were used (OR = 4.04, 95% CI: 2.25, 7.25). We conclude that obesity in early pregnancy is associated with increased risks of stillbirth and infant mortality independently of genetic and early environmental risk factors shared within families.

Keywords: body mass index; familial confounding; infant mortality; neonatal mortality; postneonatal mortality; sibling-design studies; stillbirth.

Figure 1.

Selection of participants for a study of associations between early-pregnancy body mass index and risks of stillbirth and infant mortality using 2 reference groups: population controls and sister controls. The study population included all singleton first births taking place in Sweden during 1992–2011 to mothers born in Sweden who had a sister who also gave birth to her first child during that time period.

Figure 2.

Risk of stillbirth in singleton first births according to early-pregnancy body mass index (weight (kg)/height (m)²) among mothers born in Sweden who gave birth during 1992–2011, derived using population controls (A) and sister controls (B). Odds ratios were estimated using complete covariate information (n = 174,199 in the population control analysis and n = 889 in the sister control analysis) and after multiple imputation of missing values. Odds ratios were adjusted for maternal age, maternal height, smoking, education, and time period (5-year groups) of child's birth. Bars, 95% confidence intervals.

Figure 3.

Risk of infant mortality in singleton first births according to early-pregnancy body mass index (weight (kg)/height (m)²) among mothers born in Sweden who gave birth during 1992–2011, derived using population controls (A) and sister controls (B). Odds ratios were estimated using complete covariate information (n = 174,141 in the population control analysis and n = 917 in the sister control analysis) and after multiple imputation of missing values. Odds ratios were adjusted for maternal age, maternal height, smoking, education, and time period (5-year groups) of child's birth. Bars, 95% confidence intervals.