Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

Abstract

The HAPO Study Cooperative Research Group* 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 pregnantwomen underwent a standard 75-g oral glucose tolerance test 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 skin folds Ͼ90th percentile or percent body fat Ͼ90th 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 sex.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-h, and 2-h plasma glucose higher by 1 SD.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 biological relationship influencing fetal growth.

The identification and treatment of women with hyperglycaemia in pregnancy: an analysis of individual participant data, systematic reviews, meta-analyses and an economic evaluation

“…The studies fall into four categories: (1) 28 studies (including BiB and Atlantic DIP) 6,61, reported associations between glucose levels (from OGTT or OGCT) split into three or more categories and adverse perinatal outcomes (see Table 7); (2) 20 studies [88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107] reported associations between glucose levels (from OGTT or OGCT) split into two categories with adverse perinatal outcomes (see Table 8) -these studies were mostly comparisons of women with lower glucose levels at OGCT [typically < 140 mg/dl (7.8 mmol/l)] compared with women with higher glucose levels at OGCT; (3) five studies 36,41,65,108,109 reported longer-term outcomes in either mother or offspring (see Table 9) (it was not possible to pool studies reporting longer-term outcomes because they were too diverse); and (4) the remaining five studies [110][111][112][113] did not present numerical data that were suitable for analysis and therefore could not be included in any of the meta-analyses (see Appendix 2, Table 63). One study 114 used a 75-g OGTT in a non-fasted population.…”

“…Six studies 22,36,41,65,108,109 reported longer-term and/or anthropometric outcomes, either measures of adiposity or incidence of diabetes. The characteristics of these studies are presented in Table 9.…”

“…Three studies 7,36,65 (see Chapter 2) reported neonatal obesity (skinfold thickness and percentage body fat of > 90th centile), one study 41 reported obesity at age 2 year and one study 108 reported obesity at age 5-7 years. One study, 109 in Pima Indians, reported longer-term incidence of diabetes in offspring.…”

“…Five studies 36,41,65,108,109 examined maternal glucose level and longer-term outcomes, although they investigated diabetes and adiposity, the timing of the measurements and methods of assessment varied, preventing pooling of estimates. Data for the 100-g OGTT, and particularly the 1-hour post-load measure, were more limited than the 75-g OGTT, therefore less confidence should be placed on these results.…”

Is consumption of sugar‐sweetened soft drinks during pregnancy associated with birth weight?

“…High maternal body mass index (BMI), large pregnancy weight gains, and high maternal blood glucose levels are associated with increased risk of giving birth to large infants (Clausen et al, 2005, HAPO Study Cooperative Research Group, 2009), and high birth weight (BW) is associated with OWOB later in life (Yu et al, 2011). Insights into epigenetic mechanisms and fetal programming may imply that preventive measures before or during pregnancy may make important contributions to curtail the future risk of OWOB (Hanson & Gluckman, 2014).…”