Maternal and neonatal 3-epi-25-hydroxyvitamin D concentration and factors influencing their concentrations

Background Little is known about the presence of 3-epi-25 hydroxyvitamin D in the maternal and neonatal circulation, the extent of its contribution to total 25 hydroxyvitamin D, as well as factors influencing its levels. Methods 1502 and 1321 archived maternal and umbilical cord serum samples from the HAPO Study cohort from Hong Kong were assayed for 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 by an LC-MS/MS method. Results Vitamin D deficiency [total serum 25(OH)D level < 50 nmol/l] and severe vitamin D deficiency [total serum 25(OH)D level < 25 nmol/l] occurred in 590 (39.3%) and 25 (1.7%) mothers, respectively. 3-epi-25(OH)D3 could be detected in 94.5% of maternal and 92.1% of neonatal umbilical sera, with the highest 3-epi-25(OH)D3 levels contributing to 19.9% and 15.3% of the maternal and umbilical cord sera 25(OH)D3 levels, respectively. Pregnancy with a male fetus, ambient solar radiation, and maternal glycemia and 25(OH)D3 levels were independent factors associated with maternal 3-epi-25(OH)D3 level. Advanced maternal age, multiparity, maternal gestational weight gain below the IOM recommendation, maternal glycaemic status, and earlier gestational age at delivery were significantly associated with higher umbilical cord serum 3-epi-25(OH)D3. Conclusions 3-epi-25(OH)D3 accounted for a significant portion of total 25(OH)D in the maternal and neonatal circulations. Further study is needed to determine the possible mechanism underlying this observation.

Cord serum leptin in infants born to diabetic mothers

In genetically diabetes-prone populations, maternal diabetes during pregnancy increases the risk of their children developing diabetes and obesity (the vicious cycle of type 2 diabetes). Fetal hyperinsulinemia at birth acts as a marker of this risk. The objective of this study is to find out whether cord blood leptin concentrations are increased in offspring of mothers with type 2 and gestational diabetes mellitus (GDM) and to evaluate gender differences if any, in their levels.Cord Serum Leptin measured by ELISA: 1. Cord Blood from 40 babies (20M, 20F) born to GDM Mothers. 2: Cord Blood from 20 babies (9M, 11F) born to Type 2 DM Mothers. 3. Cord Blood from 30 babies (15M, 15F) born to Non Diabetic Mothers. Babies born to mothers with both type 2 diabetes and GDM had higher birth weight. They also had higher Leptin concentrations [ng/ml] compared to Controls; Leptin concentrations in Type 2 Diabetes -Mean [42.32+24.09], in GDM – Mean [40.31+22.71] & in Control subjects – Mean [23.87+15.48]. Birth weight of the female babies were also higher than that of male babies.Leptin concentrations were not significantly higher in the female babies in comparison to the male babies.High cord leptin, birth weight and ponderal index (kilograms per cm), in babies born to Type 2 diabetes and GDM mothers.

Umbilical cord serum concentrations of perfluorooctane sulfonate, perfluorooctanoic acid, and the body mass index changes from birth to 5 1/2 years of age

Prenatal exposure to perfluoroalkyl substances (PFAS) has been reported to affect body weight from birth to childhood, but the results remain inconclusive. We investigated whether umbilical cord blood concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are associated with children’s risk trajectory for obesity. 600 children were randomly selected from the Hamamatsu Birth Cohort for Mothers and Children (HBC study) and their umbilical cord serum PFAS concentrations were quantified. Participants underwent BMI measurements at ages 1, 4, 10, 18, 24, 32, 40, 50, and 66 months. Growth curve modeling with random intercept was performed with standardized BMI as outcome variable. PFOS was negatively associated with standardized BMI (β = − 0.34; p = 0.01), with a marginally significant interaction with the child’s age (β = 0.0038; p = 0.08). PFOA was negatively associated with standardized BMI (β = − 0.26, 95% CI − 0.51, 0; p = 0.05), with a significant interaction with the child’s age (β = 0.005; p = 0.01). Stratified analysis by sex revealed that these effects were significant only among girls. Prenatal exposure to PFAS initially was associated with lower standardized BMI during infancy, but this effect dissipated over time and reversed in direction during later childhood. The effects of prenatal PFAS on higher standardized BMI is stronger in girls.

Ontogeny of plasma lipid metabolism in pregnancy and early childhood: a longitudinal population study

Background: There is mounting evidence that in utero and early life exposures may predispose an individual to metabolic disorders in later life; and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. In this study, we aim to understand the lipid metabolism in pregnancy, and from birth to four years. Methods and findings: We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population based pre-birth cohort and measured 776 distinct lipid species across 42 lipid classes using ultra high-performance liquid chromatography (UHPLC). We measured lipids in 1032 maternal serum samples at 28 weeks’ gestation, 893 cord serum samples at birth, 793, 735, and 511 plasma samples at six, twelve months, and four years, respectively. The lipidome differed between mother and newborn and changed markedly with increasing postnatal age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenyl-phosphatidylethanolamine species containing LC-PUFAs increased with postnatal age, whereas the corresponding lysophospholipids and triglycerides decreased. We performed regression analyses to investigate the associations of cord serum lipid species with birth factors: gestational age, birth weight, mode of birth and duration of labor. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids.Conclusions: There were marked changes in the plasma lipidome over the first four years of life. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood.Funding Statement: This work was supported by the A*STAR-NHMRC joint call funding (1711624031).

DNA Hypermethylation of Brain-Derived Neurotrophic Factor is Associated with High Levels of Polybrominated Diphenyl Ethers in the Cord Serum: A Laizhou Wan Birth Cohort Study From China

Background Recent studies have suggested that in utero exposure to environmental organic pollutants, such polybrominated diphenyl ethers (PBDEs) and bisphenol A may induce epigenetic alterations, specifically by modifying the patterns of DNA methylation. We investigated the relationship between PBDE exposure and BDNF DNA methylation. Methods We measured the levels of eight PBDE congeners in umbilical cord serum samples using gas chromatography/mass spectrometry. Genomic DNA was extracted from whole cord blood samples. The methylation status of the BDNF gene was determined using methylation-specific PCR with primers specific for either methylated or unmethylated alleles. The unconditional logistic regression model was used to investigate the relationship between PBDE levels and BDNF DNA methylation. Results The total PBDE congener level (range) in cord serum samples was 23.17 (4.17–2459.46) ng/g lipid. After adjusting for potential confounders, the incidence of BDNF DNA methylation status may increase when cord serum BDE-28, BDE-47, BDE-99 and BDE-100 levels increased (OR = 3.32, 95% CI: 1.01, 10.85; OR = 7.89, 95% CI: 1.75, 35.66; OR = 7.34, 95% CI: 1.79, 30.09; OR = 3.96, 95% CI: 1.15, 13.68; respectively). Conclusions We found that the levels of BDE-28, -47, -99, and − 100 were positively associated with BDNF DNA hypermethylation. Changes in cord blood BDNF DNA methylation may be a part of the biological pathway underlying in utero PBDE exposure and adverse foetal growth.

Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune Implications

Urinary tract infections (UTI) during pregnancy are frequently associated with hypertensive disorders, increasing the risk of perinatal morbidity. Calcitriol, vitamin D3’s most active metabolite, has been involved in blood pressure regulation and prevention of UTIs, partially through modulating vasoactive peptides and antimicrobial peptides, like cathelicidin. However, nothing is known regarding the interplay between placental calcitriol, cathelicidin, and maternal blood pressure in UTI-complicated pregnancies. Here, we analyzed the correlation between these parameters in pregnant women with UTI and with normal pregnancy (NP). Umbilical venous serum calcitriol and its precursor calcidiol were significantly elevated in UTI. Regardless of newborn’s sex, we found strong negative correlations between calcitriol and maternal systolic and diastolic blood pressure in the UTI cohort (p < 0.002). In NP, this relationship was observed only in female-carrying mothers. UTI-female placentas showed higher expression of cathelicidin and CYP27B1, the calcitriol activating-enzyme, compared to male and NP samples. Accordingly, cord-serum calcitriol from UTI-female neonates negatively correlated with maternal bacteriuria. Cathelicidin gene expression positively correlated with gestational age in UTI and with newborn anthropometric parameters. Our results suggest that vitamin D deficiency might predispose to maternal cardiovascular risk and perinatal infections especially in male-carrying pregnancies, probably due to lower placental CYP27B1 and cathelicidin expression.