C-reactive protein across pregnancy in individuals exposed to childhood maltreatment: The role of psychological and physical sequelae of maltreatment.

BACKGROUND: Childhood maltreatment (CM) has long-term consequences for the regulation of stress biology which are particularly pronounced when mental and physical health sequelae have manifested. C-reactive protein (CRP) has been shown to be elevated in the non-pregnant state in association with CM as well as in the setting of CM-associated mental and physical health sequelae. In pregnancy, however, the association between CM and CRP is less clear. We sought to examine this association and consider the moderating role of four common health sequelae of CM (maternal depressive symptoms, overweight/obesity, smoking, and hypertensive disorders during pregnancy). METHODS: A prospective, longitudinal study of 744 healthy pregnant participants was conducted, with analyses focusing on a sample of 643 participants. CM was assessed with the Childhood Trauma Questionnaire (CTQ) and categorized by whether no vs. one or more moderate to severe CM experiences were reported. Blood serum concentrations of CRP, maternal depression severity (continuous scores of the Center for Epidemiologic Studies Depression Scale, CES-D) and smoking during pregnancy were assessed in early (16.52 ± 2.50 weeks gestation) and late (33.65 ± 1.18 weeks gestation) pregnancy. Pre-pregnancy body mass index (BMI) was obtained at the first study visit and hypertensive disorders diagnosed during pregnancy were obtained from the medical record. Linear mixed effects models were employed to assess main effects of CM as well as interactive effects of CM and four common CM-associated sequelae as well as a sum score of these sequelae on repeatedly measured CRP concentration. In secondary analyses, we conducted latent class analyses to classify participants based on their specific experiences of childhood abuse and/or neglect and to assess the association of these CM subgroups with CM sequelae and CRP. All analyses were adjusted for potential confounders (maternal race and ethnicity and education/income). RESULTS: CRP concentration decreased from early to late pregnancy (B = -0.06, SE = 0.01, p < 0.001). While there was no main effect of CM on CRP (p = 0.49), the interaction of CM and depressive symptoms was associated with CRP concentration (B = 0.08, SE = 0.04, p < 0.05), indicating higher CRP across pregnancy with increasing levels of depressive symptoms during pregnancy in participants with CM experience. This interaction was mainly driven by participants with co-occurring physical and emotional maltreatment. For none of the other CM-associated sequelae a statistically significant interaction with CM on CRP concentration was observed. CONCLUSIONS: These results add to the growing empirical evidence suggesting higher inflammation during pregnancy in participants exposed to CM who experience depressive symptoms and highlight the detrimental effects of multiple co-occurring experiences of maltreatment. Given the negative consequences of chronic inflammatory state for the mother and the developing fetus, monitoring and treating psychiatric sequelae during pregnancy among participants exposed to CM is potentially an important opportunity to dampen long-term detrimental effects of CM, serving at least two generations.

Exposure to childhood maltreatment and systemic inflammation across pregnancy: The moderating role of depressive symptomatology.

BACKGROUND: Childhood maltreatment (CM) has long-term consequences for dysregulation of the immune system which is particularly pronounced when mental and physical health sequelae have manifested. Higher proinflammatory state has been shown in non-pregnant state in association with CM as well as with depression, one of the most frequent and pernicious psychiatric sequelae of CM. During pregnancy, however, this association is less clear. Given the important role of maternal inflammatory state during pregnancy for fetal, pregnancy, and birth outcomes, we sought to examine the association between CM and proinflammatory state during pregnancy considering the moderating role of maternal depressive symptoms characterized serially across pregnancy. METHODS: A prospective, longitudinal study of 180 healthy pregnant women was conducted with serial assessments in early (12.98 ± 1.71 weeks gestation), mid (20.53 ± 1.38 weeks gestation) and late (30.42 ± 1.4 weeks gestation) pregnancy. Maternal history of CM was assessed with the Childhood Trauma Questionnaire (CTQ) and the total score was used as an indicator of CM experience. Maternal depressive symptoms were assessed at each pregnancy visit with the Center for Epidemiologic Studies Depression Scale (CES-D). Serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were obtained at each pregnancy visit and combined to a composite maternal proinflammatory score. Linear mixed effects models were employed to assess the association between CTQ score, CES-D score, and proinflammatory score during pregnancy, adjusting for potential confounders. RESULTS: Gestational age was associated with the proinflammatory score (B = 0.02; SE = 0.00; p < .001), indicating an increase in inflammation across gestation. Neither CTQ score nor depressive symptoms were independently associated with the proinflammatory score (ps > 0.28). However, the interaction between CTQ score and depressive symptoms was associated with the proinflammatory score (B = 0.03, SE = 0.01, p < .05), indicating higher inflammation across pregnancy with increasing levels of depressive symptoms during pregnancy in women with higher CTQ scores. Exploratory analyses suggested that this interaction was mainly driven by CTQ subscale scores assessing experiences of abuse rather than neglect. CONCLUSIONS: These findings suggest a moderating role of maternal depressive symptoms during pregnancy on the association of early life stress with inflammation and thus highlight the importance of the timely assessment of both CM exposure and depressive symptoms which might allow for the development of targeted and individualized interventions to impact inflammation during pregnancy and to ameliorate the detrimental long-term effects of CM. The current findings add to a better understanding of the prenatal biological pathways that may underlie intergenerational transmission of maternal CM.

Prospective association of maternal psychosocial stress in pregnancy with newborn hippocampal volume and implications for infant social-emotional development.

Maternal psychosocial stress during pregnancy can impact the developing fetal brain and influence offspring mental health. In this context, animal studies have identified the hippocampus and amygdala as key brain regions of interest, however, evidence in humans is sparse. We, therefore, examined the associations between maternal prenatal psychosocial stress, newborn hippocampal and amygdala volumes, and child social-emotional development. In a sample of 86 mother-child dyads, maternal perceived stress was assessed serially in early, mid and late pregnancy. Following birth, newborn (aged 5-64 postnatal days, mean: 25.8 ± 12.9) hippocampal and amygdala volume was assessed using structural magnetic resonance imaging. Infant social-emotional developmental milestones were assessed at 6- and 12-months age using the Bayley-III. After adjusting for covariates, maternal perceived stress during pregnancy was inversely associated with newborn left hippocampal volume (ß = -0.26, p = .019), but not with right hippocampal (ß = -0.170, p = .121) or bilateral amygdala volumes (ps > .5). Furthermore, newborn left hippocampal volume was positively associated with infant social-emotional development across the first year of postnatal life (B = 0.01, p = .011). Maternal perceived stress was indirectly associated with infant social-emotional development via newborn left hippocampal volume (B = -0.34, 95% CIBC [-0.97, -0.01]), suggesting mediation. This study provides prospective evidence in humans linking maternal psychosocial stress in pregnancy with newborn hippocampal volume and subsequent infant social-emotional development across the first year of life. These findings highlight the importance of maternal psychosocial state during pregnancy as a target amenable to interventions to prevent or attenuate its potentially unfavorable neural and behavioral consequences in the offspring.