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Journal Article Epublish 2 citations

PubMed: 40307787 DOI: 10.1186/s12916-025-04096-w

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

BMC Med 23(1):252

Authors: Menglong Geng, Zhen Yu, Yafei Wang, Juan Tong, Hui Gao, Hong Gan, Jixing Zhou, Baolin Wang, Peng Ding, Shuangqin Yan, Kun Huang, Xiaoyan Wu, Fangbiao Tao

Affiliations

  • Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China. Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui, 230032, China. Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
  • Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230022, China.
  • Department of Nursing, Anhui Medical College, Hefei, Anhui, 230601, China.
  • Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China. Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
  • School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
  • Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China. Ma'anshan Maternal and Child Healthcare (MCH) Center, Ma'anshan, 243011, China.
  • Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
  • Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
  • NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui, 230032, China.
  • Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China. Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui, 230032, China. Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. Department of Maternal, School of Public Health, Anhui Medical University, Child & Adolescent HealthNo. 81 Meishan Road, Hefei, Anhui Province, 230032, China.
  • Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China. Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China. NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui, 230032, China. Department of Maternal, School of Public Health, Anhui Medical University, Child & Adolescent HealthNo. 81 Meishan Road, Hefei, Anhui Province, 230032, China.

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- = 0.024), IL-8 (OR = 1.25, 95% CI: 1.05, 1.49, P- = 0.036), and IFN-γ level in the cord serum (OR = 1.74, 95% CI: 1.16, 2.61, P- = 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- = 0.012), IL-6 (OR = 1.29, 95% CI: 1.04, 1.61, P- = 0.042), and IL-8 (OR = 1.31, 95% CI: 1.06, 1.62, P- = 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.

MeSH

Cytokines, Vitamin D, Blood, Serum, Vitamins, Placenta, Child, Neurodevelopment