Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study

Abstract

Maternal infection and stress during the prenatal period have been associated with adverse neurodevelopmental outcomes in offspring, suggesting that biomarkers of increased inflammation in the mothers may associate with poorer developmental outcomes. In 491 mother–child pairs from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we investigated the association between maternal levels of two inflammatory biomarkers; interleukin-8 (IL-8) and C-Reactive Protein (CRP) during early (10–18 wks) and late (32–38 wks) pregnancy with offspring scores in the five domains of the Ages and Stages Questionnaire, a validated screening tool for assessing early life development. We identified a robust association between early pregnancy IL-8 levels and decreased fine-motor (β: −0.919, 95%CI: −1.425, −0.414, p = 3.9 × 10−4) and problem-solving skills at age two (β: −1.221, 95%CI: −1.904, −0.414, p = 4.9 × 10−4). Associations between IL-8 with other domains of development and those for CRP did not survive correction for multiple testing. Similarly, while there was some evidence that the detrimental effects of early pregnancy IL-8 were strongest in boys and in those who were not breastfed, these interactions were not robust to correction for multiple testing. However, further research is required to determine if other maternal inflammatory biomarkers associate with offspring neurodevelopment and work should continue to focus on the management of factors leading to increases in IL-8 levels in pregnant women.

Early exposure to maternal stress and risk for atopic dermatitis in children: A systematic review and meta‐analysis

“…Pregnancy has its unique biology and is a critical period for the biological transfer between mothers and infants 39 . Elevated inflammatory and pro‐inflammatory biomarkers were observed when mothers experienced stress during the prenatal period 40,41 . AD is an inflammatory skin disease predominantly characterized by CD4+ T‐cell infiltrate in the lesional skin 42 .…”

“…39 Elevated inflammatory and pro-inflammatory biomarkers were observed when mothers experienced stress during the prenatal period. 40,41 AD is an inflammatory skin disease predominantly characterized by CD4þ T-cell infiltrate in the lesional skin. 42 AD is now recognized as a biphasic disease with Th2 cells predominating in the acute phase and a transition to Th1 cells characterizing the chronic phase.…”

Prenatal maternal immune activation predicts observed fearfulness in infancy.

“…There is considerable evidence linking MIA to the clinical phenotypes of autism and schizophrenia (Beversdorf et al, 2019; Brown et al, 2004; Goldstein et al, 2014; Nielsen et al, 2021). However, with few exceptions (Camerota et al, 2022; Ghassabian et al, 2018; Kelly et al, 2022; Nazzari & Frigerio, 2020; T. G. O’Connor et al, 2022), research has not considered normative variability in cognitive and behavioral outcomes or assessments from young children.…”

IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions

“…Chemokines can cross the placental and brain barriers, regulating the communication between neurons and microglia in the CNS [208]. During healthy gestation, IL-8 undergoes tight regulation and reaches higher peripheral concentrations during preterm compared to term labor [209].…”

“…Given that externalizing symptoms in children are tied to cognitive difficulties, it is possible that fetal exposure to IL-8 increases the risk of developing externalizing symptoms through cognitive impairment [220]. Moreover, higher IL-8 levels during early pregnancy (10-18 weeks) were linked to notable decreases in fine motor skills and problem-solving abilities in children at age two [208].…”