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

Ayesha C. Sujan, Martin E. Rickert, Quetzal A. Class, Claire A. Coyne, Paul Lichtenstein, Catarina Almqvist, Henrik Larsson, Arvid Sjölander, Benjamin B. Lahey, Carol van Hulle, Irwin Waldman, A. Sara Öberg, Brian M. D’Onofrio

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.