Dataset Information

In utero exposure to parabens and early childhood BMI z-scores - Associations between placental ethyl paraben, longitudinal BMI trajectories and cord blood metabolic biomarkers.

ABSTRACT:

Background

Parabens are used as antimicrobial preservatives in personal care products. Few studies have dealt with adverse health outcomes, transplacental transfer, and obesogenic effects of prenatal exposure to parabens. We examined the association between placental paraben levels and cord blood metabolic biomarkers, considering modulating effects of maternal pre-pregnancy BMI and underlying epigenetic mechanisms, and investigated longitudinal effects of in utero paraben exposure on early childhood trajectories of BMI z-scores.

Methods

Placental concentrations of four parabens [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 229 placentas of the ENVIRONAGE birth cohort. The association with cord blood metabolic biomarkers [glucose, insulin, γ-glutamyltransferase (GGT), high-density and low-density lipoprotein (HDL and LDL)] was analyzed in multiple regression models with two different sets of, a priori selected potential confounders, additionally stratified for different maternal BMI groups and assessed by causal mediation analysis. The association between placental paraben concentration and differential DNA methylation of CpGs annotated to GGT and longitudinal measurements of BMI z-scores were investigated with adjusted linear mixed models.

Results

The geometric means of placental MeP, EtP, PrP, and BuP levels above the limit of detection (LOD) were 4.42, 1.32, 1.51, and 0.35 ng/g respectively, with only EtP showing sufficient (88%) measurements above LOD for further analyses. An interquartile ratio (IQR) increase in placental EtP was associated with an increase of 12.61 % (95% CI: 1.80 24.57) in the geometric mean of cord GGT activity, and with a decrease of -3.64 % (95% CI: -6.80 to -0.39) in the geometric mean of cord glucose. Placental EtP levels were significantly associated with hypermethylation of cg08612779 annotated to GGT7 after correcting for multiple testing (ß = 0.0017, p = 0.049). An interquartile ratio (IQR) increment in placental EtP was associated with a decrease in longitudinal BMI z-score of 0.27 points (95% CI: -0.46 to -0.088).

Conclusion

Prenatal EtP exposure may affect early childhood BMI. The association of placental EtP with cord blood GGT and glucose levels provides a starting point for further research on mechanisms of paraben-related metabolic processes in utero.

SUBMITTER: Reimann B

PROVIDER: S-EPMC8484768 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo examine associations of parental socioeconomic position with early-life offspring body mass index (BMI) trajectories in a middle-income country.SubjectsOverall, 12,385 Belarusian children born 1996-97 and enrolled in a randomised breastfeeding promotion trial at birth, with 3-14 measurements of BMI from birth to 7 years.MethodsCohort analysis in which exposures were parental education (common secondary or less; advanced secondary or partial university; completed university) and occupation (manual; non-manual) at birth, and the outcome was BMI z-score trajectories estimated using multilevel linear spline models, controlling for trial arm, location, parental BMI, maternal smoking status and number of older siblings.ResultsInfants born to university-educated mothers were heavier at birth than those born to secondary school-educated mothers [by 0.13 BMI z-score units (95% confidence interval, CI: 0.07, 0.19) for girls and 0.11 (95% CI: 0.05, 0.17) for boys; equivalent for an infant of average birth length to 43 and 38 g, respectively]. Between the ages of 3-7 years children of the most educated mothers had larger BMI increases than children of the least educated mothers. At age 7 years, after controlling for trial arm and location, children of university-educated mothers had higher BMIs than those born to secondary school-educated mothers by 0.11 z-score (95% CI: 0.03, 0.19) among girls and 0.18 (95% CI: 0.1, 0.27) among boys, equivalent to differences in BMI for a child of average height of 0.19 and 0.26 kg/m2, respectively. After further controlling for parental BMI, these differences attenuated to 0.08 z-score (95% CI: 0, 0.16) and 0.16 z-score (95% CI: 0.07, 0.24), respectively, but changed very little after additional adjustment for number of older siblings and mother's smoking status. Associations were similar when based on paternal educational attainment and highest household occupation.ConclusionsIn Belarus, consistent with some middle-income countries, higher socioeconomic position was associated with greater BMI trajectories from age 3 onwards.

Project description:BackgroundPoor placental function is a common cause of intrauterine growth restriction, which in turn is associated with increased risks of adverse health outcomes. Our prior work suggests that birthweight and childhood obesity-associated genetic variants functionally impact placental function and that placental microRNA are associated with birthweight. To address the influence of the placenta beyond birth, we assessed the relationship between placental microRNAs and early childhood growth.MethodsUsing the SITAR package, we generated two parameters that describe individual weight trajectories of children (0-5 years) in the New Hampshire Birth Cohort Study (NHBCS, n = 238). Using negative binomial generalized linear models, we identified placental microRNAs that relate to growth parameters (FDR < 0.1), while accounting for sex, gestational age at birth, and maternal parity.ResultsGenes targeted by the six growth trajectory-associated microRNAs are enriched (FDR < 0.05) in growth factor signaling (TGF/beta: miR-876; EGF/R: miR-155, Let-7c; FGF/R: miR-155; IGF/R: Let-7c, miR-155), calmodulin signaling (miR-216a), and NOTCH signaling (miR-629).ConclusionsGrowth-trajectory microRNAs target pathways affecting placental proliferation, differentiation and function. Our results suggest a role for microRNAs in regulating placental cellular dynamics and supports the Developmental Origins of Health and Disease hypothesis that fetal environment can have impacts beyond birth.ImpactWe found that growth trajectory associated placenta microRNAs target genes involved in signaling pathways central to the formation, maintenance and function of placenta; suggesting that placental cellular dynamics remain critical to infant growth to term and are under the control of microRNAs. Our results contribute to the existing body of research suggesting that the placenta plays a key role in programming health in the offspring. This is the first study to relate molecular patterns in placenta, specifically microRNAs, to early childhood growth trajectory.

Project description:Aims/hypothesisThe aim of this study was to characterise longitudinal profiles of BMI from childhood and to examine the impact of level-independent childhood BMI trajectories on adult type 2 diabetes.MethodsThe longitudinal cohort consisted of 2449 adults (1613 white and 836 black) who had their BMI measured between four and 15 times from childhood (4-19 years) to adulthood (20-51 years) and fasting glucose measured in adulthood. Model-estimated levels and linear slopes of BMI at childhood age points were calculated in 1-year intervals using growth-curve parameters and their first derivatives, respectively.ResultsBMI from childhood to adulthood fit cubic growth curves; linear and non-linear curve parameters differed significantly between race-sex groups. BMI showed race and sex differences from 15 years onwards. Individuals with hyperglycaemia had higher long-term BMI levels than those who were normoglycaemic in race-sex groups. Linear and non-linear slope parameters of BMI differed consistently and significantly between adult hyperglycaemia groups. The OR of childhood BMI levels for ages 4-19 years was 1.45-1.83 (p < 0.001 for all) for adult hyperglycaemia after adjustment for confounders. Level-adjusted linear slopes of BMI at ages 10-19 years showed significantly positive associations with adult hyperglycaemia (OR 1.17-1.50, p < 0.01 for all). The associations of childhood BMI linear slopes with adult hyperglycaemia were not significant during the age period 5-9 years. The trends in these associations were consistent across race-sex groups.Conclusions/interpretationThese observations indicate that childhood BMI trajectories have a significant impact on adult diabetes, independent of BMI levels. The adolescence age period is a crucial window for the development of diabetes in later life, which has implications for early-life prevention.Data availabilityAll data and materials are publicly available at the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository and can be accessed at https://biolincc.nhlbi.nih.gov/studies/bhs .

Project description:Background and objectivesBy age 5, 20% of British children are classed as overweight or obese, suggesting that early childhood is crucial for lifelong body mass index (BMI) trajectories. In this paper, we identify latent trajectories of early-childhood BMI from ages 3 to 11 years. Given the current context of growing socio-economic inequalities in childhood and adult overweight and obesity, we examine the socio-economic characteristics and mechanisms during pregnancy and infancy which underscore these trajectories.Subject and methodsWe use a nationally representative, prospective cohort study of 9699 children born in 2000-2002, living in the United Kingdom shortly after birth, with complete information on height and weight (measured by an interviewer) at ages 3, 5, 7 and 11. Trajectories of BMI are calculated using latent growth mixture models. Multinomial models characterize these trajectories by their socio-economic profiles and mechanisms during pregnancy and infancy.ResultsFour trajectories were identified: two separate trajectories where BMI remains within a normal range (85% of the sample), an overweight trajectory (14.4%), and an obese trajectory (3.1%). No 'declining BMI' or late-onset groups were found. The obese group is already distinct from the other trajectories by age 3. The overweight group diverges from the normal groups around age 5. Strong socio-economic inequalities emerged; for the obese group, part of this disadvantage is mediated through early mechanisms such as pregnancy smoke and not initiating breastfeeding.ConclusionsThis study provides strong evidence for the idea that childhood BMI trajectories develop early, especially for children who will follow an obese trajectory. Strong socio-economic patterns in these trajectories suggest that the observed trend in growing inequalities may be rooted in early life. Mediating mechanisms for the obese appear to be in the pregnancy and infant period, further research should explore mechanisms occurring around age 5 when the overweight trajectory diverges.

Project description:ObjectiveTo assess the relationship between in utero and concurrent child urinary exposures to bisphenol A (BPA) and phthalates with BMI z-score, waist circumference, and sum of triceps and subscapular skinfold thickness in Mexican children.MethodsAmong participants (N=249) from the Early Life Exposure in Mexico to ENvironmental Toxicants study, we evaluated associations between maternal third trimester and concurrent urinary BPA and individual and summed phthalates metabolites (∑Di(2-ethylhexyl phthalate), ∑high molecular weight, ∑low molecular weight) with measures of weight status and adiposity in children aged 8-14 years. Linear regressions with specific-gravity corrected and natural log-transformed urinary concentrations were estimated, adjusting for covariates. Effect modification by sex was explored.ResultsPrenatal urinary exposure to monobenzyl phthalate (MBzP) was inversely associated with child's BMI z-score (β=-0.21, 95%CI: -0.41, -0.02) and child urinary exposure to mono(2-ethylhexyl)phthalate (MEHP) was inversely associated with waist circumference (β=-1.85, 95%CI: -3.36, -0.35) and sum of skinfold thicknesses (β=-2.08, 95%CI: -3.80, -0.37) after adjusting for confounders. In the childhood exposure period, sex modified the relationships with BPA, MEHP, MBzP, monoethyl phthalate (MEP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP). In girls, increased BPA exposure was positively associated with sum of skinfold thickness (β=3.47, 95%CI: 0.05, 6.40) while increased MEHP was inversely associated with sum of skinfold thicknesses in boys (β=-2.95, 95%CI: -5.08, -0.82); these results remained in sensitivity analyses after excluding children who had initiated pubertal development (Tanner stage >1 for pubic hair). We did not observe relationships between summed phthalates metabolites at any exposure period with outcome measures.ConclusionOur results identified associations between urinary BPA and phthalates metabolites with measures of weight status and adiposity that differed by timing of exposure, sex, and pubertal status. Additional studies are needed to explore how associations may differ between those who are pre- and post-pubertal.