Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status
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 placen...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12916-025-04096-w |
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| author | 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 |
| author_facet | 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 |
| author_sort | Menglong Geng |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-39bd58eeda6c468ca2bda886ccf0376f |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-39bd58eeda6c468ca2bda886ccf0376f2025-08-20T03:52:19ZengBMCBMC Medicine1741-70152025-04-0123111310.1186/s12916-025-04096-wPlacental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D statusMenglong Geng0Zhen Yu1Yafei Wang2Juan Tong3Hui Gao4Hong Gan5Jixing Zhou6Baolin Wang7Peng Ding8Shuangqin Yan9Kun Huang10Xiaoyan Wu11Fangbiao Tao12Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Nursing, Anhui Medical CollegeKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaSchool of Public Health, Anhui Medical UniversitySchool of Public Health, Anhui Medical UniversitySchool of Public Health, Anhui Medical UniversityKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People’s Republic of ChinaAbstract 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.https://doi.org/10.1186/s12916-025-04096-wPlacentaUmbilical cord bloodCytokineNeurodevelopmentVitamin DBirth cohort |
| spellingShingle | 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 Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status BMC Medicine Placenta Umbilical cord blood Cytokine Neurodevelopment Vitamin D Birth cohort |
| title | Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status |
| title_full | Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status |
| title_fullStr | Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status |
| title_full_unstemmed | Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status |
| title_short | Placental and cord serum inflammatory cytokines and children’s domain-specific neurodevelopment at 18 months: effect modification by maternal vitamin D status |
| title_sort | placental and cord serum inflammatory cytokines and children s domain specific neurodevelopment at 18 months effect modification by maternal vitamin d status |
| topic | Placenta Umbilical cord blood Cytokine Neurodevelopment Vitamin D Birth cohort |
| url | https://doi.org/10.1186/s12916-025-04096-w |
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