Sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development: The Ma'anshan birth cohort study

Jixing Zhou; Yuzhu Teng; Fu Zhang; Xue Ru; Peixuan Li; Jianqing Wang; Shuangqin Yan; Peng Zhu; Fangbiao Tao; Kun Huang

doi:10.1016/j.bbi.2022.05.017

Sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development: The Ma'anshan birth cohort study

Brain Behav Immun. 2022 Aug:104:110-121. doi: 10.1016/j.bbi.2022.05.017. Epub 2022 Jun 1.

Authors

Jixing Zhou¹, Yuzhu Teng¹, Fu Zhang¹, Xue Ru¹, Peixuan Li¹, Jianqing Wang², Shuangqin Yan³, Peng Zhu¹, Fangbiao Tao¹, Kun Huang⁴

Affiliations

¹ Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University; Key Laboratory of Population Health Across Life Cycle (AHMU), MOE, Hefei 230032, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei 230032, China.
² Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University.
³ Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University; Maternal and Child Health Care Center of Ma'anshan, No 24 Jiashan Road, Ma'anshan 243011, Anhui, China.
⁴ Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University; Key Laboratory of Population Health Across Life Cycle (AHMU), MOE, Hefei 230032, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei 230032, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei 230032, China; Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, Anhui Province, China. Electronic address: ahmuhuangk@163.com.

PMID: 35661681
DOI: 10.1016/j.bbi.2022.05.017

Abstract

Background: Placental inflammation may contribute to brain abnormalities and childhood neuropsychiatric disorders, but limited knowledge is available on the association of placental inflammatory cytokine levels and offspring's behavioral development. This study aimed to examine the sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development.

Methods: 3474 pregnant women were recruited as the initial study population in the Ma'anshan birth cohort (MABC) study. Placentas (n = 2519) were collected during childbirth, and the mRNA expression of IL-8, IL-1β, CRP, TNF-α, IL-6, IL-10, and IL-4 was assessed. The Child Behavior Checklist 1.5-5 (CBCL 1.5-5) was used to assess children's behavioral development at 4 years old. A T-score ≥ 60 on summary scales or a score ≥ 65 on syndrome scales was regarded as the borderline clinical range. Multiple linear regression models and binary logistic regression models were applied to explore the sex-specific associations between placental inflammatory cytokines mRNA transcript levels and preschoolers' behavioral development.

Results: Sex-specific associations between placental inflammatory cytokines mRNA expression and preschoolers' behavioral development were observed. There was a positive association between IL-8 and CBCL scores for boys on anxious/depressed problems, aggressive behaviors, externalizing problems and total problems. Logistic regression models showed that high levels of IL-8 were associated with a higher risk of girls' emotionally reactive problems and sleep problems compared to low/medium levels. High TNF-α was correlated with increased sleep problem scores in boys, and medium TNF-α (vs. low levels) was associated with an increased risk of girls' externalizing problems. Medium levels of CRP, IL-1β, and IL-6 were found to be associated with a decreased risk of girls' behavioral problems compared to low/high levels. For anti-inflammatory cytokines, medium IL-10 and IL-4 (vs. low levels) were observed to be associated with a lower risk of internalizing problems in boys and externalizing problems in girls, respectively. High IL-10 was correlated with decreased attention problem scores in boys.

Conclusion: This study indicates that placental inflammatory cytokine mRNA expression of IL-8, CRP, TNF-α, IL-1β, IL-4 and IL-10 may be associated with preschoolers' behavioral development in a sex-specific manner.

Keywords: Behavioral development; Cytokine; Placenta; Sex-specific; mRNA.