Association between Fetal Adipokines and Child Behavioral Problems at Preschool Age: The Hokkaido Study on Environment and Children’s Health

Abstract

Studies have suggested associations between maternal obesity and mental health problems of their children. However, the underlying mechanism is largely unknown. A possible mechanism can be via inflammatory states and the other possible mechanism is metabolic hormone-induced programming. Cross-talk between adipokines, including inflammatory cytokines and metabolic hormones secreted from adipose tissue and the central nervous system needs to be further investigated to elucidate the mechanism. Thus, the aim of this study was to investigate the association between fetal adipokine levels and child behavioral problems at preschool age. Cord blood adiponectin, leptin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels were measured and child behavioral problems were assessed using the Strengths and Difficulties Questionnaire at preschool age. Logistic regression models adjusted by related maternal factors were performed to examine the association between cord blood adipokines and child behavioral problems. Three hundred and sixty-one children were included in the final analysis. A significant association between decreased hyperactivity/inattention and increased leptin was found (OR = 0.22, 95% CI: 0.06–0.89). Cord blood adiponectin, TNF-α and IL-6 levels were not associated with child behavioral problems. Our findings suggested that cord blood adipokines, particularly, leptin level, may be a predictor of hyperactivity/inattention problems at preschool age.

Metabolic proteins at birth predict early childhood mental health symptoms

“…To our knowledge, this is among the first few studies to prospectively predict mental health symptoms from cord blood adipocytokines, and the first examining a leptin-to-adiponectin ratio. The majority of research investigating cord blood adipocytokines has been primarily concerned with predicting metabolic health (Stocker & Cawthorne, 2008); however, our results provide support for the possibility that metabolic proteins at birth also forecast risk for mental health symptoms in early childhood (e.g., Li et al, 2019;Minatoya et al, 2018;Raghavan et al, 2019). Additionally, our data revealed that higher adiponectin was associated with a decreased chance of being rated higher in ability in the "managing feelings and behaviors" domain.…”

Associations of cord blood leptin and adiponectin with children’s cognitive abilities

“…Two previous studies that investigated the associations between early-life adiponectin and neurobehavioral outcomes found null associations (Camargos et al, 2017; Minatoya et al, 2018). One study examined behaviors rather than cognition, and found that cord blood adiponectin was not associated with behavior problems among Japanese preschool children (Minatoya et al, 2018). The other study found that adiponectin concentrations were not associated with cognitive or motor development in 50 Brazilian infants at ages 6-24 months (Camargos et al, 2017).…”

“…One study found that higher placental leptin methylation (i.e., reduced leptin gene expression) was associated with increased risk of lethargy and hypotonicity among boys (Lesseur et al, 2014). Among Japanese preschool children, cord blood leptin was inversely associated with hyperactivity/inattention (Minatoya et al, 2018). In validating the WPPSI-III, the developers reported that children with attention deficit hyperactivity disorder had slightly lower FSIQ and PIQ scores compared to their matched controls, but the differences were not statistically significant (Wechsler, 2003).…”

“…Few epidemiologic studies have examined the impact of fetal adipocytokines on neurodevelopment, and the findings are inconclusive. Two studies found that fetal leptin was inversely associated with the risk of neurobehavioral problems in children, with one study reporting sex-specific associations (Lesseur et al, 2014; Minatoya et al, 2018). In contrast, a cross-sectional study found that plasma leptin concentrations were associated with lower cognitive scores among infants at age 6-24 months (Camargos et al, 2017).…”

A Review of Recent Studies on Bisphenol A and Phthalate Exposures and Child Neurodevelopment

“…Prenatal exposure to bisphenol A and phthalates is linked to alterations in DNA methylation and gene expression in the blood of rodent offspring, modulated by an underlying genetic profile [ 99 ]. Accumulating evidence suggests that exposure to both bisphenol A and phthalates may contribute to important epigenetic effects [ 100 ]. In a recent review article, placental epigenetic consequences such as genomic imprinting, DNA methylation, and the expression of non-coding RNAs in association with maternal exposure to bisphenol A and phthalate were described [ 101 ].…”