Determinants of cord blood adipokines and association with neonatal abdominal adipose tissue distribution

Background Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother–offspring cohort. Methods Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother–offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed. Results Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only. Conclusions Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.

Interrelationships Among Vitamin D Status and Body Composition in Mother-Infant Dyads

Background: Vitamin D status of pregnant women is associated with body composition of the offspring. The objective of this study was to assess whether the association between maternal vitamin D status and neonatal adiposity is modified by maternal adiposity preconception.Methods: Healthy mothers and their term appropriate weight for gestational age (AGA) infants (n=142; 59% male, Greater Montreal, March 2016-2019) were studied at birth and 1 month postpartum (2-6 weeks). Newborn (24-36 hour) serum was collected to measure total 25-hydroxyvitamin D [25(OH)D] (immunoassay); maternal pre-pregnancy BMI was obtained from the medical record. Anthropometry, body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D were measured at 2-6 weeks postpartum in mothers and infants. Mothers were grouped into 4 categories based on their vitamin D status (sufficient 25(OH)D ≥50 nmol/L vs. at risk of being insufficient <50 nmol/L) and pre-pregnancy BMI (<25 vs. ≥25 kg/m2): insufficient-recommended weight (I-RW, n=24); insufficient-overweight/obese (I-OW/O, n=21); sufficient-recommended weight (S-RW, n=69); and sufficient-overweight/obese (S-OW/O, n=28). Partial correlation and mixed model ANOVA were used while adjusting for covariates.Results: At birth, infant serum 25(OH)D mean concentrations were below the cut-point for sufficiency of 50 nmol/L for both maternal pre-pregnancy BMI categories; 47.8 [95%CI: 43.8, 51.9] nmol/L if BMI <25 kg/m2 and 38.1 [95%CI: 33.5, 42.7] nmol/L if BMI ≥25 kg/m2. Infant serum 25(OH)D concentrations at birth (r=0.77; p<0.0001) and 1 month (r=0.59, p<0.0001) were positively correlated with maternal postpartum serum 25(OH)D concentrations. Maternal serum 25(OH)D concentration was inversely associated with maternal percent whole body fat mass (r=-0.26, p=0.002). Infants of mothers in I-OW/O had higher fat mass versus those of mothers in S-OW/O (914.0 [95%CI: 766.4, 1061.6] vs. 780.7 [95%CI: 659.3, 902.0] g; effect size [Hedges' g: 0.42]; p=0.04) with magnitude of difference of 220.4 g or ~28% difference (adjusting for covariates). Conclusions: Maternal vitamin D status is positively correlated with neonatal vitamin D. In this study, maternal adiposity and serum 25(OH)D <50 nmol/L are dual exposures for neonatal adiposity. These findings reinforce the importance of vitamin D supplementation early in infancy irrespective of vitamin D stores acquired in utero and maternal weight status.

Placental miR-3940-3p is associated with maternal insulin resistance in late pregnancy

Context An increase in maternal insulin resistance (IR) during pregnancy is essential for normal fetal growth. The mechanisms underlying this metabolic adaptation to pregnancy are poorly understood. Placenta factors are believed to instigate and maintain these metabolic changes, as IR decreases shortly after delivery. Methylation of placental gene loci that are common targets for miRNAs, are associated with maternal IR. Objective We hypothesized that placental miRNAs targeting methylated loci are associated with maternal IR during late pregnancy. Methods We collected placentas from 132 elective cesarean sections and fasting blood sample at delivery to estimate maternal HOMA-IR. Placental miRNA expression was measured via whole genome small RNA-sequencing in a subset of 40 placentas selected by maternal pre-gravid BMI and neonatal adiposity. Five miRNAs that correlated with maternal HOMA-IR and were previously identified as targeting methylated genes were selected for validation in all 132 placenta samples via RT-qPCR. Multiple regression was used to adjust for relevant clinical variables. Results Median maternal age was 27.5 years, with a median pre-pregnancy BMI of 24.7 kg/m 2, and median HOMA-IR of 2.9. Among the five selected miRNA, maternal HOMA-IR correlated with the placental expression of miRNA-371b-3p (r=0.25; p=0.008) and miRNA-3940-3p (r=0.32; p=0.0004) across the 132 individuals. After adjustment for confounding variables, placental miRNA-3940-3p expression remained significantly associated with HOMA-IR (β=0.16; p=0.03). Conclusion Placental miRNA-3940-3p was associated with maternal IR at delivery. This placental miRNA may have an autocrine or paracrine effect - regulating placental genes which play a role in modulating maternal IR.

Do Lifestyle Interventions in Pregnant Women with Overweight or Obesity Have an Effect on Neonatal Adiposity? A Systematic Review with Meta-Analysis

Excessive body fat at birth is a risk factor for the development of childhood obesity. The aim of the present systematic review with meta-analysis was to evaluate the effect of lifestyle interventions in pregnant women with overweight or obesity on neonatal adiposity. The PubMed, Embase, Web of Science, Scopus, and Virtual Health Library databases were used as information sources. Original articles from randomized clinical trials of lifestyle intervention studies on pregnant women with excessive body weight and the effect on neonatal adiposity were considered eligible. The risk of bias was assessed using Cochrane criteria. The meta-analysis was calculated using the inverse variance for continuous data expressed as mean difference (MD), using the random effect model with a 95% confidence interval (CI). The outcomes were submitted to the GRADE evaluation. Of 2877 studies, four were included in the qualitative and quantitative synthesis (n = 1494). All studies were conducted in developed countries, with three including pregnant women with overweight or obesity, and one only pregnant women with obesity. The interventions had no effect on neonatal adiposity (Heterogeneity = 56%, MD = −0.21, CI = (−0.92, 0.50)) with low confidence in the evidence, according to GRADE. Studies are needed in low- and medium-developed countries with different ethnic-racial populations. PROSPERO (CRD42020152489).

Metabolic flexibility during late pregnancy is associated with neonatal adiposity

The aim of this study was to determine the relationships between maternal metabolic flexibility during pregnancy and neonatal health outcomes. Percent change in lipid oxidation (before and after a high-fat meal) was calculated as the measure of “metabolic flexibility”. Neonatal adiposity was assessed within 48 h of delivery by skinfold anthropometry. Metabolic flexibility (r = −0.271, p = 0.034), maternal HOMA-IR (r = 0.280, p = 0.030), and maternal body mass index (r = 0.299, p = 0.018) were correlated with neonatal subscapular skinfold (i.e., measure of neonatal adiposity). Clinical Trail Registration Number: NCT03504319. Novelty: This is the first study to link maternal metabolic flexibility, body mass index, and insulin resistance during pregnancy to neonatal adiposity at parturition.