Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms

Abstract

Objective Fetal exposure to maternal prenatal stress hormones such as cortisol exerts influences on the developing nervous system that persist and include risk for internalizing symptoms later in life. Placental corticotropin-releasing hormone (pCRH) is a feto-placental stress signal that also shapes fetal neurodevelopment and may be a more direct indicator of the fetal experience than maternal stress hormones. The programming effects of pCRH on child development are unknown. The current investigation examined associations between prenatal maternal and placental stress hormone exposures (maternal cortisol and pCRH) and child self-reported internalizing symptoms at age 5. Method Maternal plasma cortisol and pCRH levels were measured at 15, 19, 25, 31, and 36 weeks’ gestation in a sample of 83 women and their 91 children (8 sibling pairs from separate pregnancies), who were born full-term. Child self-reported internalizing symptoms at age 5 were obtained using scales of the Berkeley Puppet Interview. Results Placental CRH profiles (including elevations in mid-gestation) were associated with higher levels of internalizing symptoms at age 5. This effect was not explained by critical prenatal or postnatal influences, including obstetric risk, concurrent maternal psychological state, and family socio-economic status. Prenatal maternal cortisol was not significantly associated with child self-reported internalizing symptoms. Conclusions Findings suggest that elevated exposures to the feto-placental stress signal pCRH exert programming effects on the developing fetal central nervous system, with lasting consequences for child mental health.

Severe nausea and vomiting in pregnancy: psychiatric and cognitive problems and brain structure in children

“…pCRH represents an integrative pathway through which diverse prenatal environmental insults inform the fetus of the condition and shape the fetal developmental trajectories [ 77 ]. Considerable evidence indicates that fetal exposure to excessive pCRH concentrations is associated with behavioral consequences during infancy and neuropsychiatric outcomes in childhood [ 78 , 79 ]. Another plausible interpretation is that maternal stress induced by HG could result in elevated maternal cortisol levels during pregnancy [ 12 ].…”

Developmental origins of the human hypothalamic-pituitary-adrenal axis

“…For example, administration of CRH to the brains of immature rodents results in progressive loss of hippocampal neurons, which may impair hippocampal negative feedback regulation of the HPA axis [144]. Several human studies provide additional support for programming effects of placental CRH on the fetal brain, linking placental CRH exposures with fetal neurodevelopment [166–168] and with stress-related outcomes in infancy and childhood [169, 170].…”

Maternal infection and stress during pregnancy and depressive symptoms in adolescent offspring

“…In particular, accumulating research suggests that maternal stress during pregnancy is related to childhood cognitive difficulties frequently seen in the histories of depressed populations (Hofstra et al, 2002; Wood et al, 2013), such as lower scores on tests of intellectual functioning and language abilities (Laplante et al, 2008; Slykerman et al, 2005), problems of attention/concentration (Brouwers et al, 2001; Gutteling et al, 2006), and difficultites in academic performance (Niederhofer and Reiter, 2004). Additionally, prenatal maternal stress has been associated with increases in offspring behavioral/emotional problems during childhood that are linked to risk of later depression (Zahn-Waxler et al, 2000), such as childhood anixety (Davis and Sandman, 2012; Loomans et al, 2011), parental report of behavioral maladjustment (Gutteling et al, 2005; O'Connor et al, 2002), internalizing problems (Howland et al, 2016; Park et al, 2014), and temperaments associated with increased frustration, crying, and negative reactivity (Davis et al, 2007; Gutteling et al, 2005; Werner et al, 2007). Evidence also suggests sex differences in fetal exposure to prenatal stress with females showing an increased risk for later affective problems compared to males, following fetal exposure to maternal stress (Quarini et al, 2016; Sandman et al, 2013).…”