Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status

Abstract

Abstract Background Epidemiological studies that have simultaneously explored the effects of placental and cord blood inflammatory cytokine levels on neurodevelopment in offspring, as well as the role of maternal vitamin D in these associations, are lacking. To investigate the associations of placental and cord blood inflammatory cytokine levels with neurodevelopment in 18-month-old children, and the potential modification effect by maternal vitamin D. Methods Based on the Ma’anshan birth cohort, the current study involved 1241 mother–child pairs. The placental inflammatory cytokine mRNA expression levels, cord serum inflammatory cytokine concentrations, and maternal serum vitamin D concentrations were determined. Children’s neurodevelopmental outcomes were defined as the Chinese version of the Ages and Stages Questionnaire (Third Edition) subdomain scores below the established cutoff scores. Generalized linear models were utilized to assess the effects of placental and cord serum inflammatory cytokines on neurodevelopmental outcomes and to examine the modification effects of maternal vitamin D. Results After adjusting for confounders, each one-unit increase in placental IL-6 (OR = 1.30, 95% CI: 1.09, 1.55, P-FDR = 0.024), IL-8 (OR = 1.25, 95% CI: 1.05, 1.49, P-FDR = 0.036), and IFN-γ level in the cord serum (OR = 1.74, 95% CI: 1.16, 2.61, P-FDR = 0.042) was associated with an increased risk of fine motor delay. Elevated levels of placental TNF-α (OR = 1.38, 95% CI: 1.12, 1.69, P-FDR = 0.012), IL-6 (OR = 1.29, 95% CI: 1.04, 1.61, P-FDR = 0.042), and IL-8 (OR = 1.31, 95% CI: 1.06, 1.62, P-FDR = 0.036) were associated with an increased risk of personal-social delay. Stratified analyses showed that lower maternal vitamin D levels (< 20 ng/mL) moderated the associations between inflammatory markers and delays in fine motor, gross motor, and personal-social subdomains. Conclusions Elevated levels of specific inflammatory cytokines in the placenta and umbilical cord blood were associated with developmental delays on a parental-reported screening tool. Maternal vitamin D status can modify the adverse effects of the intrauterine pro-inflammatory milieu on the neurodevelopment of children.

Keywords

• Placenta
• Umbilical cord blood
• Cytokine
• Neurodevelopment
• Vitamin D
• Birth cohort