The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

Contreras, M; Sacks, David A.; Bowling, Francis; Cowley, D M; Liley, Helen; McIntyre, H. David; Tudehope, DI

doi:10.1016/s0020-7292(02)00092-9

Cited by 312 publications

(83 citation statements)

References 29 publications

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“…All participants gave written informed consent. Medical caregivers and participants were “blinded” to glucose tolerance test results, unless glucose values exceeded predefined thresholds, meriting further follow-up (12). For this secondary analysis, we limited the data to the 6,159 participants who had blinded data and who participated only through one of the North American centers (members of the HAPO Study Cooperative Research Group North American Field Centers: Kaiser Foundation Hospital, Bellflower, CA; Prentice Women’s Hospital of Northwestern Memorial Hospital–Northwestern University Feinberg School of Medicine, Chicago, IL; MetroHealth Medical Center–Case Western Reserve University, Cleveland, OH; Women and Infants’ Hospital of Rhode Island–Brown University Medical School, Providence, RI; Sunnybrook and Women’s College Health Sciences Centre–University of Toronto, Toronto, Ontario, Canada).…”

Section: Methodsmentioning

confidence: 99%

Maternal and Neonatal Morbidity for Women Who Would Be Added to the Diagnosis of GDM Using IADPSG Criteria: A Secondary Analysis of the Hyperglycemia and Adverse Pregnancy Outcome Study

et al. 2016

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OBJECTIVETo assess the frequency of adverse outcomes for women who are diagnosed with gestational diabetes mellitus (GDM) by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.RESEARCH DESIGN AND METHODSThis is a secondary analysis from the North American HAPO study centers. Glucose measurements from a 75-g oral glucose tolerance test were used to group participants into three nonoverlapping categories: GDM based on Carpenter-Coustan (CC) criteria (also GDM based on IADPSG criteria), GDM diagnosed based on IADPSG criteria but not CC criteria, and no GDM. Newborn outcomes included birth weight, cord C-peptide, and newborn percentage fat above the 90th percentile; maternal outcomes included primary cesarean delivery and preeclampsia. Outcome frequencies were compared using multiple logistic regression, adjusting for predefined covariates.RESULTSAmong 25,505 HAPO study participants, 6,159 blinded participants from North American centers were included. Of these, 81% had normal glucose testing, 4.2% had GDM based on CC criteria, and 14.3% had GDM based on IADPSG criteria but not CC criteria. Compared with women with no GDM, those diagnosed with GDM based on IADPSG criteria had adjusted odds ratios (95% CIs) for birth weight, cord C-peptide, and newborn percentage fat above the 90th percentile, as well as primary cesarean delivery and preeclampsia, of 1.87 (1.50–2.34), 2.00 (1.54–2.58), 1.73 (1.35–2.23), 1.31 (1.07–1.60), and 1.73 (1.32–2.27), respectively.CONCLUSIONSWomen diagnosed with GDM based on IADPSG criteria had higher adverse outcome frequencies compared with women with no GDM. These data underscore the need for research to assess the effect of treatment to improve outcomes in such women.

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Section: Methodsmentioning

confidence: 99%

Maternal and Neonatal Morbidity for Women Who Would Be Added to the Diagnosis of GDM Using IADPSG Criteria: A Secondary Analysis of the Hyperglycemia and Adverse Pregnancy Outcome Study

et al. 2016

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“…HAPO methods were described previously [11, 15]. Eligible women underwent a 75 g OGTT at 24–32 weeks gestation after an overnight fast of at least 8 h. Fasting (FPG) and 1 h plasma glucose were measured, and fasting and 1 h serum samples were stored at −80°C until the metabolomics assays.…”

Section: Methodsmentioning

confidence: 99%

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes

Sandler¹,

Reisetter²,

Bain

et al. 2016

Diabetologia

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Aims/hypothesis Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine environment. We aimed to characterise the maternal metabolic milieu associated with maternal BMI and its relationship to newborn birthweight and adiposity. Methods Fasting and 1 h serum samples were collected from 400 European-ancestry mothers in the Hyperglycaemia and Adverse Pregnancy Outcome Study who underwent an OGTT at ~28 weeks gestation and whose offspring had anthropometric measurements at birth. Metabolomics assays were performed using biochemical analyses of conventional clinical metabolites, targeted MS-based measurement of amino acids and acylcarnitines and non-targeted GC/MS. Results Per-metabolite analyses demonstrated broad associations with maternal BMI at fasting and 1 h for lipids, amino acids and their metabolites together with carbohydrates and organic acids. Similar metabolite classes were associated with insulin resistance with unique associations including branched-chain amino acids. Pathway analyses indicated overlapping and unique associations with maternal BMI and insulin resistance. Network analyses demonstrated collective associations of maternal metabolite subnetworks with maternal BMI and newborn size and adiposity, including communities of acylcarnitines, lipids and related metabolites, and carbohydrates and organic acids. Random forest analyses demonstrated contribution of lipids and lipid-related metabolites to the association of maternal BMI with newborn outcomes. Conclusions/interpretation Higher maternal BMI and insulin resistance are associated with broad-based changes in maternal metabolites, with lipids and lipid-related metabolites accounting, in part, for the association of maternal BMI with newborn size at birth.

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“…To validate our seven most significant findings in the Cambridge cohorts we tested the same associations between maternal mean arterial blood pressures and the fetal imprinted gene alleles in 1,367 HAPO study participants 15, 16 of European descent whose single nucleotide polymorphism (SNP) genotypes were derived from a GWAS of maternal glycemic and neonatal anthropometric traits 17 . Study participant characteristics are shown in Table 1C.…”

Section: Methodsmentioning

confidence: 99%

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy

et al. 2016

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In addition to maternal genes and environmental exposures, variation in fetal imprinted genes could also affect maternal blood pressure during pregnancy. Our objective was to test the associations between polymorphic variants in 16 imprinted genes and maternal mean arterial blood pressures in 1,160 DNA trios from two established birth cohorts (the Cambridge Baby Growth and Wellbeing Studies), and seek replication in 1,367 Hyperglycemia and Adverse Pregnancy Outcome Study participants. Significant univariate associations, all independent of fetal sex, were observed in the Cambridge cohorts, including: FAM99A rs1489945 transmitted from the mother (p=2×10−4), DLK1 rs10139403 (mother; p=9×10−4), DLK1 rs12147008 (mother; p=1×10−3), H19 rs217222 (father; p=1×10−3), SNRPN rs1453556 (father; p=1×10−3), IGF2 rs6356 (father; p=1×10−3) and NNAT rs6066671 (father; p=1×10−3). In meta-analysis including additional independent Hyperglycemia and Adverse Pregnancy Outcome Study data, the association with maternally-transmitted fetal DLK1 rs10139403 reached genome-wide significance (p=6.3×10−10). With the exception of fetal rs1489945 and rs217222, all of other associations were unidirectional and most were statistically significant. To further explore the significance of these relationships we developed an allele score based on the univariate findings. The score was strongly associated with maternal blood pressure at 31 weeks (p=4.1×10−8; adjusted r2=5.6%) and 37 weeks of pregnancy (p=1.1×10−4; r2=3.6%), and during the last 2 weeks prior to parturition (p=1.1×10−10; r2=8.7%). It was also associated with gestational hypertension (odds ratio 1.54 (1.14, 2.09) per allele; p=0.005; 45 cases and 549 controls). These data support the concept that fetal imprinted genes are related to the development of gestational hypertension.

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The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

Cited by 312 publications

References 29 publications

Maternal and Neonatal Morbidity for Women Who Would Be Added to the Diagnosis of GDM Using IADPSG Criteria: A Secondary Analysis of the Hyperglycemia and Adverse Pregnancy Outcome Study

Maternal and Neonatal Morbidity for Women Who Would Be Added to the Diagnosis of GDM Using IADPSG Criteria: A Secondary Analysis of the Hyperglycemia and Adverse Pregnancy Outcome Study

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes

Associations Between Fetal Imprinted Genes and Maternal Blood Pressure in Pregnancy

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