Separating Family-Level and Direct Exposure Effects of Smoking During Pregnancy on Offspring Externalizing Symptoms: Bridging the Behavior Genetic and Behavior Teratologic Divide

Abstract

Maternal smoking during pregnancy (MSDP) has been robustly associated with externalizing problems and their developmental precursors in offspring in studies using behavioral teratologic designs (Wakschlag, et al, 2002; Espy, et al, 2011). In contrast, the use of behavior genetic approaches has shown that the effects commonly attributed to MSDP can be explained by family-level variables (D'Onofrio, et al, 2008). Reconciling these conflicting findings requires integration of these study designs. We utilize longitudinal data on a preschool proband and his/her sibling from the Midwest Infant Development Study-Preschool (MIDS-P) to test for teratologic and family level effects of MSDP. We find considerable variation in prenatal smoking patterns both within and across pregnancies within families, indicating that binary smoking measures are not sufficiently capturing exposure. Structural equation models indicate that both conduct disorder and oppositional defiant disorder symptoms showed unique effects of MSDP over and above family level effects. Blending high quality exposure measurement with a within-family design suggests that it is premature to foreclose the possibility of a teratologic effect of MSDP on externalizing problems. Implications and recommendations for future studies are discussed.

The Importance of the Prenatal Environment in Behavioral Genetics: Introduction to Special Issue

“…Estabrook et al (2016) focused on examining how maternal SDP is linked with externalizing symptoms in preschool-aged children using a within-family design that assesses variation in smoking across multiple children in the same family. This report found unique effects of maternal SDP on disruptive externalizing behaviors after genetic and familial factors were accounted for.…”

Maternal smoking during pregnancy and offspring antisocial behaviour: findings from a longitudinal investigation of discordant siblings

“…As such, this measure does not capture changes in exposure over time (reductions in smoking levels, quitting) 13. It also does not permit us to examine a ‘windows-of-vulnerability’ hypothesis that allows for MSP effects to vary by trimester.…”

Does MAOA increase susceptibility to prenatal stress in young children?

“…Indeed, as maternal cigarette smoking during pregnancy is an increasingly stigmatized behavior, under-reporting leading to misclassification of exposed versus non-exposed children is a well-established source of error (Estabrook et al , 2015, Pickett et al , 2005, Pickett et al , 2003). Moreover, as frequency, patterns, and topography of cigarette smoking are known to fluctuate significantly across gestation, prospective measurement of PTE that includes biomarker confirmation of reports is needed to most accurately capture this environmental exposure (Dukic et al , 2007, Estabrook et al , 2015, Pickett et al , 2005). Yet, even with ideal measurement of PTE, disentangling this particular exposure from the concomitant exposures is critical (Chiarella et al , 2015).…”

“…One of the primary challenges of causal modeling of prenatal exposures is the potential for genetic confounding (D'onofrio et al , 2010, D'onofrio et al , 2012, D'onofrio et al , 2008, Estabrook et al , 2015). In the present case, associations among PSE, PTE and disruptive behavior could result from underlying genetic factors that simultaneously influence parental traits, and by association, parental behaviors that influence the prenatal intrauterine environment, postnatal environment, and child traits (Gaysina et al , 2013, Harold et al , 2013, Jaffee & Price, 2007).…”