Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology

Abstract

Background The effects of exposure to childhood trauma (CT) may be transmitted across generations, however the time period(s) and mechanism(s) have yet to be clarified. We address the hypothesis that intergenerational transmission may begin during intrauterine life via the effect of maternal CT exposure on placental-fetal stress physiology, specifically placental corticotrophin-releasing hormone (pCRH). Methods The study was conducted in a sociodemographically-diverse cohort of 295 pregnant women. CT exposure was assessed using the Childhood Trauma Questionnaire. Placental CRH concentrations were quantified in maternal blood collected serially over the course of gestation. Linear mixed effects and Bayesian piecewise linear models were employed to test hypothesized relationships. Results Maternal CT exposure (CT+) was significantly associated with pCRH production. Compared to non-exposed women, CT+ was associated with an almost 25% increase in pCRH towards the end of gestation, and the pCRH trajectory of CT+ women exhibited an approximately two-fold steeper increase after the pCRH inflection point at 19 wks gestation. Conclusions To the best of our knowledge, this finding represents the first report linking maternal CT exposure with placental-fetal stress physiology, thus identifying a potential novel biological pathway of intergenerational transmission that may operate as early as during intrauterine life.

Sex as a Biological Variable: Who, What, When, Why, and How

“…In this sample, amygdala volume mediated the relationship between levels of maternal cortisol during pregnancy and affective problems during childhood (Buss et al, 2012). Similarly, intergenerational transmission of parental experience of childhood adversity has been reported for both females and males in rodents and for female parents in humans (Moog et al, 2016). Maternal history of childhood trauma is associated with higher levels of placental corticotropin-releasing factor across pregnancy with a steeper rise in levels in the late second trimester to parturition.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…Some preliminary evidence supports the notion that MPF endocrine stress biology is altered in the context of maternal ELS. It has been shown that ELS-exposure predicts alterations of placental CRH (Moog et al, 2015) and cortisol concentrations in saliva (Bublitz and Stroud, 2012) and hair (Schreier et al, 2015) during pregnancy. As discussed earlier, OT has the potential to down-regulate HPA-axis mediators and an ELS-associated lower OT activity and/or reduced OTR sensitivity may partly explain the elevated cortisol levels in pregnant women.…”

“…It is important to acknowledge however, that postnatal behavioral pathways, like postpartum depression and/or altered maternal behavior, are already primed during pregnancy (Feldman et al, 2007; Skrundz et al, 2011). Moreover, initial empirical evidence reveals ELS-associated alterations in maternal-fetal-placental (MPF) stress physiology that have been shown to alter fetal developmental trajectories (Moog et al, 2015). We therefore propose a continuous intergenerational transmission of maternal ELS that likely occurs during both the pre- and postnatal period via ELS-associated alterations in stress-sensitive biological systems, which may affect fetal development as well as the quality of postnatal dyadic mother-child interactions.…”

Childhood maltreatment is associated with increased risk of subclinical hypothyroidism in pregnancy

“…Based on the consideration that the onset and course of hypothyroidism is often insidious and may be precipitated by maternal states and conditions that precede pregnancy, we were particularly interested in considering the role of stress exposure from a maternal life course perspective. We selected exposure to childhood maltreatment (CM) as our primary variable of interest for the following reasons: a) CM represents among the most pervasive and pernicious stressors affecting around one third of the general population, with life-long biological, psychological and behavioral consequences (e.g., Heim et al, 2010); b) we and others have previously demonstrated that a woman’s exposure to CM can produce alterations in several features of gestational biology that relate to embryonic/fetal development (Cammack et al, 2011; Mason et al, 2016; Moog et al, 2016; Shea et al, 2007); c) CM exposure has been associated with reduced thyroid activity in the non-pregnant state (Haviland et al, 2006; Machado et al, 2015; Sinai et al, 2014), with thyroid dysfunction in the postpartum period (Plaza et al, 2010; Plaza et al, 2012), and, more generally, with a higher risk of autoimmune disorders (Dube et al, 2009; Goodwin and Stein, 2004); and d) children of women exposed to CM exhibit an increased risk of developing some of the same behavioral disorders that have been observed in children with moderate maternal thyroid dysfunction (Miranda et al, 2013; Rijlaarsdam et al, 2014; Thompson, 2007). In light of these observations, we hypothesized that women exposed to CM may exhibit an increased likelihood of thyroid dysfunction in pregnancy, a time period of particular importance for not only the mother but also for her developing fetus.…”