The mediating effect of DNA methylation in the association between maternal sleep during pregnancy and offspring adiposity status: a prospective cohort study

Abstract

Background Childhood overweight/obesity is a global public health concern. It is important to identify its early-life risk factors. Maternal poor sleep is common in late pregnancy, and previous studies indicated that poor sleep may influence the offspring’s adiposity status. However, very few studies in humans investigated the effect of the different sleep parameters (sleep quantity, quality, and timing) on the offspring’s adiposity indicators, and long-term studies are even more scarce. In addition, the underlying mechanism remains unclear. The present study therefore aimed to examine the association between the three maternal sleep dimensions in the late pregnancy and the offspring adiposity indicators and to explore the potential mediating effect of the cord blood DNA methylation in the above association. Methods Included participants in the current study were 2211 healthy pregnant women with singleton gestation from the Shanghai Birth Cohort (SBC) and Shanghai Sleep Birth Cohort (SSBC). Maternal nighttime sleep duration, quality, and midpoint (an indicator of circadian rhythm) were assessed by the same instrument in both cohorts during late pregnancy, and the offspring’s body mass index (BMI) and subcutaneous fat (SF) were measured at 2 years old. Additionally, in 231 SSBC samples, the genome-wide DNA methylation levels were measured using the Illumina Infinium Methylation EPIC BeadChip. The multivariate linear regression was used to determine the associations between the maternal sleep parameters and the offspring adiposity indicators. The epigenome-wide association study was conducted to identify the maternal sleep-related CpG sites. The mediation analysis was performed to evaluate the potential intermediate role of DNA methylation in the association between maternal sleep and offspring adiposity indicators. Results The mean maternal nighttime sleep duration and the sleep midpoint for combined cohorts were 9.24 ± 1.13 h and 3.02 ± 0.82, respectively, and 24.5% of pregnant women experienced poor sleep quality in late pregnancy. After adjusting for the covariates, the maternal later sleep midpoint was associated with the increased SF in offspring (Coef. = 0.62, 95% CI 0.37–0.87, p < 0.001) at 2 years old. However, no significant associations of the nighttime sleep duration or sleep quality with the offspring adiposity indicators were found. In the SSBC sample, 45 differential methylated probes (DMPs) were associated with the maternal sleep midpoint, and then, we observed 10 and 3 DMPs that were also associated with the offspring’s SF and BMI at 2 years, of which cg04351668 (MARCH9) and cg12232388 significantly mediated the relationship of sleep midpoint and SF and cg12232388 and cg12225226 mediated the sleep midpoint–BMI association, respectively. Conclusions Maternal later sleep timing in late pregnancy was associated with higher childhood adiposity in the offspring. Cord blood DNA methylation may play a mediation role in that relationship.

A análise de fatores para o desenvolvimento da obesidade infantil como uma medida para a sua prevenção

“…Foi realizado um estudo de coorte, entre os anos de 2012 a 2016 com 2.211 mulheres que tiveram uma única gestação, e as medidas de IMC da sua respectiva prole aos 02 anos de idade. Essa pesquisa demonstrou que o sono deficiente da mãe no final da gestação, interfere na metilação do DNA do cordão umbilical, e consequentemente isso pode estar associado a um aumento no estado de adiposidade fetal (Meng et al, 2022).…”

The Importance of Sleep in Overcoming Childhood Obesity and Reshaping Epigenetics

“…Building upon prior research, Meng et al (2022) embarked to elucidate the association between three distinct maternal sleep dimensions during late pregnancy and offspring adiposity markers [ 106 ]. Their investigation further aimed to explore the potential mediating effect of cord blood DNA methylation [ 98 ].…”

“…Their investigation further aimed to explore the potential mediating effect of cord blood DNA methylation [ 98 ]. Employing an epigenome-wide association study design, they sought to identify maternal sleep-related CpG sites potentially linked to maternal sleep patterns [ 106 ]. Notably, the study revealed a significant association between later maternal sleep timing in late pregnancy and increased childhood adiposity in offspring, with cord blood DNA methylation emerging as a putative mediator in this relationship [ 106 ].…”

“…Employing an epigenome-wide association study design, they sought to identify maternal sleep-related CpG sites potentially linked to maternal sleep patterns [ 106 ]. Notably, the study revealed a significant association between later maternal sleep timing in late pregnancy and increased childhood adiposity in offspring, with cord blood DNA methylation emerging as a putative mediator in this relationship [ 106 ]. This groundbreaking research offers the first human-based evidence for cord blood methylation acting as a mediator between the midpoint of maternal sleep during late pregnancy and the child’s adiposity status [ 106 ].…”

“…Notably, the study revealed a significant association between later maternal sleep timing in late pregnancy and increased childhood adiposity in offspring, with cord blood DNA methylation emerging as a putative mediator in this relationship [ 106 ]. This groundbreaking research offers the first human-based evidence for cord blood methylation acting as a mediator between the midpoint of maternal sleep during late pregnancy and the child’s adiposity status [ 106 ]. Furthermore, this demonstrates how alterations arising from later maternal sleep timing could serve as a mechanism for the fetal programming of adiposity [ 106 ].…”