Objective: To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity.

Research Design and Methods: Eligible pregnant women underwent a standard 75 gm OGTT between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skinfolds > 90th percentile or percent body fat > 90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's gender.

Results: Among 23,316 HAPO study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-hour, and 2-hour plasma glucose higher by one standard deviation.

Conclusions: These findings confirm the link between maternal glucose and neonatal adiposity, and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biologic relationship influencing fetal growth.

/pdf/hyperglycemia-and-adverse-pregnancy-outcome-hapo-study-381yjrphc0.pdf

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Associations with Neonatal Anthropometrics

OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m 2 ), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93, 2.47), for obesity alone 1.73 (1.50, 2.00), and for both GDM and obesity 3.62 (3.04, 4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

/pdf/the-hyperglycemia-and-adverse-pregnancy-outcome-study-13183z20al.pdf

The Hyperglycemia and Adverse Pregnancy Outcome Study: Associations of GDM and obesity with pregnancy outcomes

Gestational diabetes: The consequences of not treating

Rising rates of gestational diabetes mellitus (GDM) and related complications have prompted calls to identify potentially modifiable risk factors that are associated with gestational diabetes mellitus (GDM). We systematically reviewed the scientific literature for observational studies examining specific dietary and/or physical activity (PA) factors and risk of GDM. Our search included PubMed, Medline, CINAHL/EBSCO, Science Direct and EMBASE, and identified 1167 articles, of which 40 met our inclusion criteria (e.g., singleton pregnancy, reported diet or PA data during pre-pregnancy/early pregnancy and GDM as an outcome measure). Studies were assessed for quality using a modified Quality Criteria Checklist from American Dietetic Association. Of the final 40 studies, 72% obtained a positive quality rating and 28% were rated neutral. The final analysis incorporated data on 30,871 pregnant women. Dietary studies were categorised into either caffeine, carbohydrate, fat, protein, calcium, fast food and recognized dietary patterns. Diets such as Mediterranean Diet (MedDiet), Dietary Approaches to Stop Hypertension (DASH) diet and Alternate Healthy Eating Index diet (AHEI) were associated with 15–38% reduced relative risk of GDM. In contrast, frequent consumption of potato, meat/processed meats, and protein (% energy) derived from animal sources was associated with an increased risk of GDM. Compared to no PA, any pre-pregnancy or early pregnancy PA was associated with 30% and 21% reduced odds of GDM, respectively. Engaging in >90 min/week of leisure time PA before pregnancy was associated with 46% decreased odds of GDM. We conclude that diets resembling MedDiet/DASH diet as well as higher PA levels before or in early pregnancy were associated with lower risks or odds of GDM respectively. The systematic review was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO) as CRD42016027795.

https://www.mdpi.com/2072-6643/10/6/698/pdf

Associations of Diet and Physical Activity with Risk for Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.

/pdf/genome-wide-association-study-of-offspring-birth-weight-in-3rtcq96h8p.pdf

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

Medellín Morales A

Papers

Diabetes and pregnancy