Transgenerational Effects of Maternal Obesity on Pregnancy Outcomes and Infant Health

母亲超重和肥胖已取代吸烟成为不良儿童的一些最重要的危险因素

Maternal overweight and obesity have displaced smoking as some of the most significant risk factors for adverse pregnancy, perinatal, and infant outcomes in many high-income countries, including the United States. Recent evidence suggests that the effects of maternal obesity on birth weight can extend to the grandoffspring, but the studies have not had sufficiently large samples to examine dose-response associations with grandmaternal obesity severity, to include the most critical neonatal and infant outcomes such as survival and morbidity, or to interrogate potential mechanistic pathways. Using linkage of nation-wide registries, we propose to conduct a population-based cohort study of 220,000 singleton children born 1999-2016 in Sweden, to examine the associations of grandmaternal overweight and obesity severity with the risks of grandoffspring neonatal and infant mortality, stillbirth, fetal growth, length of gestation, and infant morbidity. We will implement causal mediation analysis to estimate the proportion of the associations that may be mediated through offspring’s parental characteristics, including maternal overweight and obesity; and will have an opportunity to explore the potential role of both maternal and paternal grandmaternal exposures. The Swedish nationwide registries constitute the largest and most complete data source worldwide to address these questions.