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Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort.

ABSTRACT: Maternal smoking during pregnancy is associated with low fetal growth and adverse cardiometabolic health in offspring. However, hormonal pathways underlying these associations are unclear. Therefore, we examined maternal smoking habits and umbilical cord blood hormone profiles in a large, prospective cohort.We studied 978 mother/infant pairs in Project Viva, a Boston-area cohort recruited 1999-2002. We categorized mothers as early pregnancy smokers, former smokers, or never smokers. Outcomes were cord blood concentrations of IGF-1, IGF-2, IGFBP-3, leptin, adiponectin, insulin, and C-peptide. We used linear regression models adjusted for maternal pre-pregnancy body mass index (BMI), race/ethnicity, parity, education, and infant sex. We conducted analyses in the full cohort and stratified by infant sex.Thirteen percent of women were early pregnancy smokers, 20% former smokers, and 68% never smokers. Infants of early pregnancy smokers had lower IGF-1 adjusted for IGFBP-3 [-5.2ng/mL (95% CI: -8.6, -1.7)], with more pronounced associations in girls [-10.7ng/mL (95% CI: -18.5, -2.9) vs. -4.0ng/mL (95% CI: -8.4, 0.4) for boys]. Early pregnancy smoking was not associated with cord blood hormones other than IGF-1. Infants of former smokers had a cord blood hormone profile similar to infants of never smokers.As compared to mothers who never smoked, early pregnancy smokers had infants with lower cord blood IGF-1 which could prime adverse metabolic outcomes. This provides further reason to support smoking cessation programs in women of reproductive age.

SUBMITTER: Fleisch AF

PROVIDER: S-EPMC5497769 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort.

Fleisch Abby F AF Rifas-Shiman Sheryl L SL Rokoff Lisa B LB Hivert Marie-France MF Mantzoros Christos S CS Oken Emily E

Metabolism: clinical and experimental 20170408

<h4>Background</h4>Maternal smoking during pregnancy is associated with low fetal growth and adverse cardiometabolic health in offspring. However, hormonal pathways underlying these associations are unclear. Therefore, we examined maternal smoking habits and umbilical cord blood hormone profiles in a large, prospective cohort.<h4>Methods</h4>We studied 978 mother/infant pairs in Project Viva, a Boston-area cohort recruited 1999-2002. We categorized mothers as early pregnancy smokers, former smok ...[more]

PMID: 28641780

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Project description:CONTEXT:Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk. OBJECTIVES:To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics. METHODS:Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components ("factors"). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns. RESULTS:Mean BW/GA z-score was 0.27±0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.87] ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern. CONCLUSIONS:Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3.

Project description:BACKGROUND:Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. METHODS:This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20 weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. RESULTS:We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNF? concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1?, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. CONCLUSIONS:Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. TRIAL REGISTRATION:Clinical Trial Registration: registration number NCT00711971 7/7/2008.

Project description:BackgroundEarly-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking.ObjectivesWe investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U.S.-based prebirth cohort with relatively low levels of lead exposure.MethodsAmong 268 mother-infant pairs, we measured lead concentrations in red blood cells (RBC) from prenatal maternal blood samples, and using HumanMethylation450 Bead Chips, we measured genome-wide methylation levels at 482,397 CpG loci in umbilical cord blood and retained 394,460 loci after quality control. After adjustment for batch effects, cell types, and covariates, we used robust linear regression models to examine associations of prenatal lead exposure with DNA methylation in cord blood at epigenome-wide significance level [false discovery rate (FDR)<0.05].ResultsThe mean [standard deviation (SD)] maternal RBC lead level was 1.22 (0.63) ?g/dL. CpG cg10773601 showed an epigenome-wide significant negative association with prenatal lead exposure (-1.4% per doubling increase in lead exposure; p=2.3×10-7) and was annotated to C-Type Lectin Domain Family 11, Member A (CLEC11A), which functions as a growth factor for primitive hematopoietic progenitor cells. In sex-specific analyses, we identified more CpGs with FDR<0.05 among female infants (n=38) than among male infants (n=2). One CpG (cg24637308), which showed a strong negative association with prenatal lead exposure among female infants (-4.3% per doubling increase in lead exposure; p=1.1×10-06), was annotated to Dynein Heavy Chain Domain 1 gene (DNHD1) which is highly expressed in human brain. Interestingly, there were strong correlations between blood and brain methylation for CpG (cg24637308) based on another independent set of samples with a high proportion of female participants.ConclusionPrenatal low-level lead exposure was associated with newborn DNA methylation, particularly in female infants. https://doi.org/10.1289/EHP1246.

Dataset Information

Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort.

Publications

Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort.

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