Transgenerational Effects of Maternal Obesity on Pregnancy Outcomes and Infant Health

母亲超重和肥胖已经取代吸烟成为不良妊娠的一些最重要的危险因素。 包括美国在内的许多高收入国家的妊娠、围产期和婴儿结局。最近 有证据表明，母亲肥胖对出生体重的影响可以延伸到后代， 研究还没有足够大的样本来检查与祖母的剂量反应关系。 肥胖严重程度，包括最关键的新生儿和婴儿结局，如存活率和发病率，或 询问潜在的机械路径。我们建议利用全国登记处的联系， 一项基于人群的队列研究，对1999-2016年在瑞典出生的220，000名独生子女进行了研究， 外祖母超重和肥胖严重程度与外祖父新生儿和 婴儿死亡率、死产、胎儿生长、妊娠期和婴儿发病率。我们将实施因果 中介分析，以估计可能通过后代的 父母的特征，包括母亲超重和肥胖;并将有机会探讨 母亲和父亲的祖母暴露的潜在作用。瑞典全国登记处 构成了全球最大和最完整的数据源，以解决这些问题。

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.