Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age

Graham, Alice M.; Rasmussen, Jerod; Rudolph, Marc D.; Heim, Christine; Gilmore, John H.; Styner, Martin; Potkin, Steven G.; Entringer, Sonja; Wadhwa, Pathik D.; Fair, Damien A.; Buß, Claudia

doi:10.1016/j.biopsych.2017.05.027

Cited by 221 publications

(239 citation statements)

References 155 publications

(148 reference statements)

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“…Other studies have also show that third trimester maternal IL‐6 levels, are associated with neonatal functional connectivity and with both fetal heart rate variability and toddler cognitive development (Spann et al, 2018). This is in agreement with the report that higher average maternal IL‐6 was prospectively associated with larger right amygdala volume and selected stronger bilateral amygdala connectivity (Graham et al, 2018). Interestingly, larger newborn right amygdala volume and stronger left amygdala connectivity mediated the association between higher maternal IL‐6 concentrations and lower impulse control at 24 months of age (Graham et al, 2018).…”

Section: How Might Maternal Inflammation In Pre‐eclampsia Alter Neurosupporting

confidence: 93%

A perspective on pre‐eclampsia and neurodevelopmental outcomes in the offspring: Does maternal inflammation play a role?

Maher

McCarthy

et al. 2018

Intl J of Devlp Neuroscience

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Pre‐eclampsia is a leading cause of maternal death and maternal and perinatal morbidity. Whilst the clinical manifestations of pre‐eclampsia often occur in late pregnancy, the molecular events leading into the onset of this disease are thought to originate in early pregnancy and result in insufficient placentation. Although the causative molecular basis of pre‐eclampsia remains poorly understood, maternal inflammation is recognised as a core clinical feature. While the adverse effects of pre‐eclampsia on maternal and fetal health in pregnancy is well‐recognised, the long‐term impact of pre‐eclampsia exposure on the risk of autism spectrum disorder (ASD) in exposed offspring is a topic of on‐going debate. In particular, a recent systematic review has reported an association between exposure to pre‐eclampsia and increased risk of ASD, however the molecular basis of this association is unknown. Here we review recent evidence for; 1) maternal inflammation in pre‐eclampsia; 2) epidemiological evidence for alterations in neurodevelopmental outcomes in offspring exposed to pre‐eclampsia; 3) long‐term changes in the brains of offspring exposed to pre‐eclampsia; and 4) how maternal inflammation may lead to altered neurodevelopmental outcomes in pre‐eclampsia exposed offspring. Finally, we discuss the implications of this for the development of future studies in this field.

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Section: How Might Maternal Inflammation In Pre‐eclampsia Alter Neurosupporting

confidence: 93%

A perspective on pre‐eclampsia and neurodevelopmental outcomes in the offspring: Does maternal inflammation play a role?

Maher

McCarthy

et al. 2018

Intl J of Devlp Neuroscience

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show abstract

“…Thus, alterations in IL-6 concentrations could represent a mediating pathway between acculturation and subsequent birth and offspring health outcomes. The mean IL-6 concentrations are all within a normal range of a non-clinical sample, however, we have recently shown that variation of IL-6 concentrations within this range across pregnancy are significantly and prospectively related to newborn brain development and infant child behavior at 2 yrs age (Graham et al, 2018; Rudolph et al, 2018), thus supporting the potential clinical significance of our current findings.…”

Section: Discussionsupporting

confidence: 79%

Acculturation and interleukin (IL)-6 concentrations across pregnancy among Mexican-American women

Scholaske

Buß

Wadhwa

et al. 2018

Brain, Behavior, and Immunity

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“…For example, excessive inflammation during pregnancy is associated with increased risk for gestational hypertension, preeclampsia, spontaneous abortion, preterm birth, and perinatal depression (Blair et al, 2015; Christian et al, 2009; Coussons-Read et al, 2012; Romero et al, 2007). In addition to being associated with pregnancy complications, excessive inflammation in pregnant women also increases the offspring’s risk for developing chronic illnesses and psychopathology during childhood (Gaillard et al, 2016; Graham et al, 2018; Lee et al, 2015). Given the adverse impact of inflammation on both the health of the mother and her offspring, it is important to identify the factors and processes that contribute to systemic inflammation during pregnancy for treatment and prevention efforts.…”

Section: Introductionmentioning

confidence: 99%

Pathways linking childhood abuse history and current socioeconomic status to inflammation during pregnancy

Finy

Christian

2018

Brain, Behavior, and Immunity

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Women who have experienced significant adversities during childhood and adulthood are at risk for excessive inflammation during pregnancy, but the mechanisms are unclear. Using structural equation modeling, we examined pathways from childhood abuse history and current socioeconomic status (SES) to inflammatory markers through indicators of health risk, recent stressors, and psychological distress in 214 women assessed at mid-pregnancy (5-31 weeks gestation). Self-reported data on socioeconomic indicators, childhood trauma history, pre-pregnancy body mass index (BMI), smoking, sleep quality, interpersonal conflict, recent life events, perceived stress, and depressive symptoms were collected, and serum levels of C-reactive protein (CRP) and interleukin (IL)-6 were determined. In separate models, pre-pregnancy BMI, sleep quality, and interpersonal conflict statistically explained the relationship between adversity and inflammation. These three intermediate variables were then entered into a multiple mediation analysis to examine unique effects. Childhood abuse history and current SES both demonstrated significant indirect effects on CRP through pre-pregnancy BMI, and current SES showed a significant indirect effect on IL-6 through all intermediate variables. When examining each indirect pathway individually, pre-pregnancy BMI and interpersonal conflict emerged as parallel pathways by which low current SES leads to elevated IL-6; the indirect pathway through sleep quality was no longer significant. Pre-pregnancy BMI and interpersonal conflict are two independent mechanisms by which adversity is associated with increased inflammation during pregnancy. Women who have been exposed to significant adversity may be at particular risk for obesity, sleep disruption, and interpersonal conflict, with implications for immune dysregulation during pregnancy.

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Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age

Cited by 221 publications

References 155 publications

A perspective on pre‐eclampsia and neurodevelopmental outcomes in the offspring: Does maternal inflammation play a role?

A perspective on pre‐eclampsia and neurodevelopmental outcomes in the offspring: Does maternal inflammation play a role?

Acculturation and interleukin (IL)-6 concentrations across pregnancy among Mexican-American women

Pathways linking childhood abuse history and current socioeconomic status to inflammation during pregnancy

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