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Mediation of the association between maternal pre-pregnancy overweight/obesity and childhood overweight/obesity by birth anthropometry.

ABSTRACT: The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother-child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.

SUBMITTER: Stevens DR

PROVIDER: S-EPMC7438242 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMaternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations.MethodsThis study included 903 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses.ResultsThe study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1-18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B).ConclusionsThis prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.

Project description:BackgroundThe relation between maternal pre-pregnancy obesity and preterm birth is controversial and inconclusive. We aimed to clarify the association between pre-pregnancy obesity and preterm birth by maternal age and race or ethnicity in a large, multiracial, multiethnic, and diverse population in the USA.MethodsWe did a population-based cohort study using nationwide birth certificate data from the US National Vital Statistics System for 2016 and 2017. We included all mothers who had a live singleton birth and who did not have pre-existing hypertension or diabetes. Pre-pregnancy obesity was defined as a pre-pregnancy BMI of at least 30 kg/m2. Preterm birth was defined as gestational age of less than 37 weeks. We used logistic regression models adjusted for maternal age, race or ethnicity, parity, education levels, smoking during pregnancy, previous history of preterm birth, marital status, infant sex, and timing of initiation of prenatal care to estimate the odds ratio (OR) of preterm birth.FindingsWe included 7 141 630 singleton livebirths in our analysis, 527 637 (7·4%) of which were preterm births. 127 611 (7·5%) Hispanic mothers, 244 578 (6·6%) non-Hispanic white mothers, and 102 509 (10·4%) non-Hispanic black mothers had preterm births. In the overall population, maternal pre-pregnancy obesity was significantly associated with an increased risk of preterm birth compared with maternal pre-pregnancy healthy weight (ie, BMI of 18·5-24·9 kg/m2; adjusted OR 1·18 [95% CI 1·18-1·19]). In non-Hispanic white women, maternal obesity was inversely associated with preterm birth among those younger than 20 years (adjusted OR 0·92 [95% CI 0·88-0·97]), but positively associated with preterm birth among those aged 20 years or older (1·04 [1·01-1·06], 1·20 [1·18-1·23], 1·34 [1·31-1·37], 1·40 [1·36-1·43], and 1·39 [1·31-1·46] among those aged 20-24 years, 25-29 years, 30-34 years, 35-39 years, and ≥40 years, respectively). In Hispanic women, maternal obesity was not associated with preterm birth among those younger than 20 years (0·98 [0·93-1·04]), but positively associated with preterm birth among those aged 20 years or older (1·06 [1·03-1·09], 1·21 [1·17-1·24], 1·32 [1·28-1·36], 1·38 [1·33-1·43], and 1·30 [1·22-1·40] among those aged 20-24 years, 25-29 years, 30-34 years, 35-39 years, and ≥40 years, respectively). In non-Hispanic black women, maternal obesity was inversely associated with preterm birth among those younger than 30 years (0·76 [0·71-0·81] in those <20 years, 0·83 [0·80-0·86] in those aged 20-24 years, and 0·98 [0·95-1·01] among those aged 25-29 years), but positively associated with preterm birth among those aged 30 years or older (1·15 [1·11-1·19], 1·26 [1·20-1·32], and 1·29 [1·18-1·42] among those aged 30-34 years, 35-39 years, and ≥40 years, respectively).InterpretationMaternal pre-pregnancy obesity is significantly associated with the risk of preterm birth in the general population, but the risk differs according to maternal age and race or ethnicity. Future investigation is warranted to understand the underlying mechanisms.FundingUS National Institutes of Health.

Project description:ImportanceThe first pediatric lead screening typically occurs at 1-year well-child care visits. However, data on the extent of maternal lead exposure and its long-term consequences for child health are lacking.ObjectiveTo investigate the associations between maternal red blood cell (RBC) lead levels and intergenerational risk of overweight or obesity (OWO) and whether adequate maternal folate status is associated with a reduction in OWO risk.Design, setting, and participantsProspective birth cohort study. The analysis was conducted from July 14, 2018, to August 2, 2019, at Johns Hopkins Bloomberg School of Public Health. This study included 1442 mother-child pairs recruited at birth from October 27, 2002, to October 10, 2013, and followed up prospectively at Boston Medical Center.Main outcomes and measuresChild body mass index (BMI) z score, calculated according to US national reference data, and OWO, defined as BMI at or exceeding the 85th percentile for age and sex. Maternal RBC lead levels and plasma folate levels were measured in samples obtained 24 to 72 hours after delivery; child whole-blood lead level was obtained from the first pediatric lead screening.ResultsThe mean (SD) age of mothers and children was 28.6 (6.5) years and 8.1 (3.1) years, respectively; 50.1% of children were boys. The median maternal RBC lead level and plasma folate level were 2.5 (interquartile range [IQR], 1.7-3.8) μg/dL and 32.2 (IQR, 22.1-44.4) nmol/L, respectively. The median child whole-blood lead level and child BMI z score were 1.4 (IQR, 1.4-2.0) μg/dL and 0.78 (IQR, -0.08 to 1.71), respectively. Maternal RBC lead level was associated with child OWO risk in a dose-response fashion, with an odds ratio (OR) of 1.65 (95% CI, 1.18-2.32) for high maternal RBC lead level (≥5.0 μg/dL) compared with low maternal RBC lead level (<2.0 μg/dL). Child OWO was highest among children of OWO mothers with high RBC lead levels (adjusted OR, 4.24; 95% CI, 2.64-6.82) compared with children of non-OWO mothers with low RBC lead levels. Children of OWO mothers with high RBC lead levels had 41% lower OWO risk (OR, 0.59; 95% CI, 0.36-0.95; P = .03) if their mothers had adequate plasma folate levels (≥20.4 nmol/L) compared with their counterparts.Conclusions and relevanceIn this sample of a US urban population, findings suggest that maternal elevated lead exposure was associated with increased risk of intergenerational OWO independent of postnatal blood lead levels. Adequate maternal folate status appeared to be associated with lower OWO risk. If confirmed by additional studies, these findings have implications for prenatal lead screening and management to minimize adverse health consequences on children.

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Mediation of the association between maternal pre-pregnancy overweight/obesity and childhood overweight/obesity by birth anthropometry.

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