TESTING CAUSAL HYPOTHESES AND ASSOCIATIONS BETWEEN PERINATAL RISK FACTORS AND OFFSPRING MORBIDITY AND MORTALITY

The Developmental Origins of Health and Disease (DOHaD) hypothesis is a broad theoretical framework that highlights how early risk factors have a causal influence on later physical and psychopathological outcomes. Numerous studies have documented such associations and underlying mechanisms have been hypothesized. Most existing studies, however, have not been able to rule out the possibility of environmental and genetic confounding. Thus, concerns exist about causal interpretations of the statistical associations identified between early risk factors and later outcomes. The six projects in my dissertation use quasi-experimental designs to rigorously test causal inferences across perinatal risk factors and offspring outcomes. The first two projects use a natural experiment approach to compare risk and hypothesized mechanisms across sensitive periods of development. In particular, the random occurrence of maternal bereavement stress across the preconception, prenatal, and postnatal periods was studied as a risk factor for offspring infant mortality and child and adult psychiatric problems. The next pair of projects examined birth weight and physical, psychiatric, educational, and socioeconomic problems using a sibling-comparison design. The final two projects used cousin-comparisons to explore the parental correlates and offspring psychiatric and education problems associated with interpregnancy interval, or the duration between the birth of an earlier born sibling and the conception of following sibling. Across these projects, findings both support and refute previous causal claims and important novel associations are identified. These studies allowed for a thorough examination of the nature of the associations between several perinatal risk factors and offspring physical, psychiatric, educational, and socioeconomic problems. The projects illustrate how combining several quasi-experimental designs can specifically test the DOHaD hypothesis by ruling out plausible alternative hypotheses. My findings also inform the direction future DOHaD-based studies should pursue

A genetically informed study of the associations between maternal age at childbearing and adverse perinatal outcomes

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.NonePublishe

Outcome-dependent associations between short interpregnancy interval and offspring psychological and educational problems : a population-based quasi-experimental study

National Institute of Child Health and DevelopmentNational Institute of Mental HealthIndiana University Mabel LaDuke Lauder FundNational Science Foundation Graduate Research FellowshipSwedish Council for Working Life and Social ResearchSwedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) framework grantInternational Postdoc GrantAccepte

Obesity and the increasing odds of cesarean delivery

Background Knowledge of the associations between obesity and cesarean delivery (CD) is limited by previous research that does not separate the highest BMI classes. Methods We identified 25,604 pregnancies in retrospective electronic medical records at an inner-city academic hospital between 2000 and 2015. We examined the association between BMI at pre-pregnancy and delivery, as well as gestational weight gain (GWG), and rates of CD, gestational diabetes mellitus (GD), and pregnancy-induced hypertension (PIH) using logistic regression and chi-square. Results CD increased with each increase in delivery BMI class [X2 (7, N = 25,604) =151.40, p < .0001]. GD and PIH also significantly increased across each BMI class. Each increasing BMI class predicted 1.21 times greater odds of CD even after adjusting for maternal age, year of birth, GD, and PIH [OR = 1.21 (95% CI, 1.07–1.37)]. As compared with the IOM recommended GWG, less weight gain offered mitigation of CD and GD, though less than the recommended GWG for women who were obese pre-pregnancy also increased odds of preterm birth, low birth weight, and stillbirth. Conclusions Increasing BMI is associated with increasing rates of adverse obstetric outcomes. There exists a “dose-dependent” effect of BMI on CD and limiting GWG may be associated with mitigated risk for this outcome, but increased risk for offspring adverse birth outcomes