A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes

Abstract

We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.

Keywords: Birth weight; Fetal growth; Genetically informed designs; Gestational age; Maternal age at childbearing; Quasi-experiments.

Figure 1

Gestational age. Model 1 is a population model, which controlled for offspring birth order. Model 2 is a population model, which controlled for all available covariates. Model 3 is a cousin comparison model, which controlled for all available covariates (except for maternal race in the U.S. analyses). Model 4 is a sibling comparison model, which controlled for offspring birth order in both samples as well as paternal covariates in the Swedish sample. Ninety-five percent confidence intervals are shown for the binned Swedish models. The shaded regions on the Swedish and U.S. continuous models represent 95% confidence intervals.

Figure 2

Birth weight for gestational age. Model 1 is a population model, which controlled for offspring birth order. Model 2 is a population model, which controlled for all available covariates. Model 3 is a cousin comparison model, which controlled for all available covariates (except for maternal race in the U.S. analyses). Model 4 is a sibling comparison model, which controlled for offspring birth order in both samples as well as paternal covariates in the Swedish sample. Ninety-five percent confidence intervals are shown for the binned Swedish models. The shaded regions on the Swedish and U.S. continuous models represent 95% confidence intervals.