Dataset Information

Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries.

ABSTRACT: CONTEXT:Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance. OBJECTIVE:To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns. DESIGN:Cross-sectional, observational study. SETTING:Hyperglycemia and Adverse Pregnancy Outcome study. PARTICIPANTS:One thousand six hundred multiethnic mother-newborn pairs. MAIN OUTCOME MEASURE:Cord blood C-peptide, birthweight, and newborn sum of skinfolds. RESULTS:Meta-analyses across four ancestry groups (Afro-Caribbean, Northern European, Thai, and Mexican American) demonstrated significant associations of cord blood metabolites with cord blood C-peptide, birthweight, and newborn sum of skinfolds. Several metabolites, including branched-chain amino acids (BCAAs), medium- and long-chain acylcarnitines, nonesterified fatty acids, and triglycerides were negatively associated with cord C-peptide but positively associated with birthweight and/or sum of skinfolds. 1,5-Anhydroglucitol, an inverse marker of recent maternal glycemia, was significantly inversely associated with birthweight and sum of skinfolds. Network analyses revealed groups of interrelated amino acid, acylcarnitine, and fatty acid metabolites associated with all three newborn outcomes. CONCLUSIONS:Cord blood metabolites are associated with newborn size and cord blood C-peptide levels after adjustment for maternal body mass index and glucose during pregnancy. Negative associations of metabolites with C-peptide at birth were observed. 1,5-Anhydroglucitol appears to be a marker of adiposity in newborns. BCAAs were individually associated with birthweight and demonstrated possible associations with newborn adiposity in network analyses.

SUBMITTER: Kadakia R

PROVIDER: S-EPMC6735762 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries.

Kadakia Rachel R Talbot Octavious O Kuang Alan A Bain James R JR Muehlbauer Michael J MJ Stevens Robert D RD Ilkayeva Olga R OR Lowe Lynn P LP Metzger Boyd E BE Newgard Christopher B CB Scholtens Denise M DM Lowe William L WL

The Journal of clinical endocrinology and metabolism 20191001 10

<h4>Context</h4>Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance.<h4>Objective</h4>To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns.<h4>Design</h4>Cross-sectional, observational study.<h4>Setting</h4>Hyperglycemia and Adverse Pregnancy Outcome study.<h4>Participants</h4>One t ...[more]

PMID: 31498869

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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:BackgroundCathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications.MethodsSingleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48-72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed.ResultsCord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37.ConclusionCord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

Dataset Information

Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries.

Publications

Cord Blood Metabolomics: Association With Newborn Anthropometrics and C-Peptide Across Ancestries.

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