A Genetically Informed Study of the Associations Between Maternal Age at Childbearing and Adverse Perinatal Outcomes
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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.
KeywordsGestational age Birth weight Fetal growth Maternal age at childbearing Genetically informed designs Quasi-experiments
This work was supported by a National Science Foundation Graduate Research Fellowship (Grand No. 1342962) awarded to the first author, the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework (Grant No. 340-2013-5867), and the National Institute of Child Health and Human Development (HD061817). This study was approved by the Institutional Review Board at Indiana University and the Karolinska Institute.
Compliance with Ethical Standards
Conflict of Interest
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, and Brian M. D’Onofrio declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
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