Hyperglycemia And Adverse Pregnancy Outcome Study Research Articles

The Association of Prenatal Vitamin D Status With Pregnancy and Neonatal Outcomes.

Vitamin D inadequacy is globally prevalent among pregnant women; however, its impact on pregnancy remains inconclusive. This study aims to explore the associations of maternal and umbilical cord serum 25-hydroxyvitamin D (25(OH)D) levels with pregnancy and neonatal outcomes. We used archived serum samples from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study participants in the Hong Kong center and assayed maternal 25(OH)D levels at midgestation and umbilical cord 25(OH)D at birth using liquid chromatography-tandem mass spectroscopy. Data regarding pregnancy and perinatal outcomes were extracted from the HAPO study dataset and the hospital computerized medical system. Only 247 (16.4%) mothers and 66 (5.0%) neonates met the criteria for vitamin D sufficiency (ie, 25(OH)D ≥ 75 nmol/L). The ratio of umbilical cord to maternal vitamin D levels was positively associated with maternal age and ambient solar radiation at the month of delivery, while negatively associated with maternal serum total 25(OH)D at midgestation (all P < .001). Umbilical cord serum 25(OH)D was independently associated with a lower primary cesarean section rate (OR 0.990, 95% CI 0.982-0.999; P = .032). There were no associations of maternal and umbilical cord 25(OH)D levels with other adverse pregnancy and neonatal outcomes. Placental vitamin D transfer was found to be higher with a lower maternal vitamin D level, older maternal age, and higher ambient solar radiation at the time of the delivery. The protective effect of sufficient vitamin D in a cesarean section will require further studies.

Oral glucose tolerance test to diagnose gestational diabetes mellitus: Impact of variations in specimen handling

To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.

Residual risk associations between initial hyperglycemia and adverse pregnancy outcomes in a large cohort including 6709 women with gestational diabetes

AimsTo estimate the residual risk associations between hyperglycemia and adverse pregnancy outcomes after glycemia-controlling intervention. MethodsAmong 41,067 Chinese women, those with gestational diabetes mellitus (GDM), according to the IADPSG criteria, received standard interventions to control glycemia. Risk associations of plasma glucose (PG) levels with excess newborn birth weight, primary cesarean section, and preterm delivery were estimated and compared with those in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, where hyperglycemia was left untreated. ResultsA total of 6,709 (16.3%) women developed GDM and thus received predominantly lifestyle interventions. The incidence of excess newborn birth weight, primary cesarean section, and preterm delivery was 6.1%, 19.1%, and 4.0%, respectively. Higher fasting and higher post-load PG levels during 75-g oral glucose tolerance test (OGTT) were statistically significantly associated with increased risks of excess newborn birth weight and pre-term delivery. Compared with the HAPO study, the association of fasting PG level with excess newborn birth weight showed similar strength and dose-response pattern, contrasting with considerably weakened associations for post-load PG levels that involved glycemic control. Contrary risk associations were seen across GDM subtypes compared with non-GDM, isolated fasting GDM was associated with increased, whereas isolated post-load GDM was associated with decreased, risks of excess newborn birth weight and primary cesarean section. Limiting the analysis to non-GDM women and GDM women with low HbA1c (<6.0%) ≥30 days after interventions overall attenuated the risk associations. ConclusionsResidual risk associations exist between hyperglycemia and adverse pregnancy outcomes despite seemingly appropriate glycemic control.

Provider utilization of gestational diabetes screening methods – Have practices changed since the HAPO trial?

The 2008 Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study prompted an international change toward lowering the threshold for diagnosis and treatment of Gestational Diabetes Mellitus (GDM). However, it is unknown if this study changed practice patterns in the US. We assessed practice patterns in diagnosis and treatment of patients with GDM before and after the HAPO study.

941-P: Epiallopregnanolone Sulfate Is Reduced in Gestational Diabetes Mellitus and Induces Glucose-Stimulated Insulin Secretion

Introduction: Serum progesterone sulfate (P4S) concentrations increase in pregnancy and bind receptors that influence glucose homeostasis. We hypothesized that P4S modulate glucose homeostasis in pregnancy. Methods: Serum P4S were assayed using ultra-performance liquid chromatography- tandem mass spectrometry. Samples were studied in three separate patient groups: women with GDM (n=20) and matched healthy controls (n=38); participants (average 28 weeks’ gestation) from the upper (n=93) and lower (n=94) quartiles of fasting plasma glucose in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study; 11-13 week pregnant women with BMI≤25 or BMI≥35 who subsequently had uncomplicated pregnancies or developed GDM (n=50/group). Glucose-stimulated insulin secretion (GSIS) was quantified in isolated wild-type, Fxr-/- and Tgr5-/- mouse and human islets in the presence of P4S and TRPM3 inhibitor isosakuranetin (ISO). Intracellular calcium concentrations were measured after treatment with P4S in TRPM3 transfected HEK293. Computer modelling using Molecular Operating Environment generated 3D structures of TRPM3 and P4S binding. Results: Epiallopregnanolone sulfate (PM5S) concentrations were reduced in serum samples from the HAPO study participants with higher fasting plasma glucose (p&amp;lt;0.01), in women with GDM (p&amp;lt;0.05) and in early pregnancy samples from women with BMI ≥35 who subsequently developed GDM (P&amp;lt;0.05). In wild-type and human islets, 50μM PM5S increased GSIS by at least 2-fold at 20mM glucose concentrations (P&amp;lt;0.001). This effect was not abolished from islets obtained from Fxr-/- or Tgr-/- mice, however it was abolished by ISO. PM5S elicited Ca2+ influx in TRPM3-expressing HEK293 cells. Computer modelling and docking showed identical positioning of PM5S to cholesterol hemisuccinate in TRPM3. Conclusion: PM5S increases GSIS and concentrations are reduced in the serum of women with GDM. The increased GSIS is mediated by TRPM3. Disclosure H. Fan: None. F. Fraternali: None. K. F. Hunt: None. J. Bowe: None. C. Williamson: Consultant; Self; GlaxoSmithKline plc., Mirum Pharmaceuticals. A. Mitchell: None. M. Giorgi: None. P. M. Jones: None. D. R. Mccance: None. D. A. Andersson: None. S. Bevan: None. H. Marschall: None. I. Eberini: None. Funding Tommy’s; Guy’s and St Thomas’ Biomedical Research Centre; National Health Service

Gestational Diabetes Mellitus and Glucose Sample Handling.

Gestational diabetes mellitus (GDM) continues to provide challenges in terms of both diagnosis and management. Recent scientific discussions around the preanalytical processing of glucose samples from the glucose tolerance test (GTT) have generated considerable interest and debate (1,2). For most women, the diagnosis of GDM is based on the measurement of plasma glucose after the GTT. The observational Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study (3) and the consensus agreement about diagnostic criteria by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) (4) provided glucose thresholds for the diagnosis of GDM. The HAPO study was meticulous in the preanalytical and analytical processing of glucose samples (3). Given that our current diagnostic criteria are based on the findings of the HAPO study, if results are to be comparable, the same meticulous processing must also be applied to glucose samples processed in routine clinical care. A major source of preanalytical error in measuring glucose is loss of glucose from blood samples …

Evaluation of the gestational diabetes mellitus diagnostic criteria recommended by the international association of diabetes and pregnancy study group for long-term maternal postpartum outcomes in mainland China.

The gestational diabetes mellitus (GDM) diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Group (IADPSG) were established based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and have been the most commonly used criteria for determining GDM worldwide. Although individuals from mainland China were not included in the HAPO study, the IADPSG criteria have been used in China since 2011. However, the appropriateness of the criteria for evaluating maternal postpartum outcomes in mainland China are unknown. We conducted this study to determine whether the IADPSG criteria are appropriate for Chinese patients for evaluating long-term maternal postpartum outcomes.Eighty-four patients who were diagnosed with hyperglycemia during pregnancy and had delivery in Peking University First Hospital from February 2007 to December 2009 were enrolled in the study. For patients in Group A, GDM was diagnosed using both the National Diabetes Data Group (NDDG) and the IADPSG criteria, while patients in Group B, gestational impaired glucose tolerance (GIGT) was diagnosed using the NDDG criteria while GDM was diagnosed based on the IADPSG criteria. Anthropometric data, glucose metabolism, lipid profiles, β cell function, and insulin resistance index were evaluated and compared to baseline after 5- to 6-year postpartum period.Patients in group A had significantly higher oral glucose tolerance test (OGTT) fasting, 2-hour and 3-hour plasma glucose levels compared to patients in group B at 24 to 28 weeks of gestation (P < .05). No significant differences were observed between the groups for anthropometric data, postpartum abnormal glucose metabolism (50.91% vs 44.83%, P = .596), type 2 diabetes mellitus (T2DM) (16.36% vs 3.45%, P = .167), lipid profiles, β cell function (homeostasis model assessment β-cell function index (HOMA-β) 1.04 vs 0.99, P = .935) and insulin resistance (homeostasis model assessment insulin resistance index (HOMA-IR) 2.01 vs 1.69, P = .583).Patients diagnosed with GDM using either the NDDG or IADPSG criteria had abnormal glucose levels and lipid metabolism after delivery. Patients with mild hyperglycemia had similar postpartum β-cell functional impairment and insulin resistance to those with moderate hyperglycemia during pregnancy. Hence, with respect to maternal long-term postpartum outcomes, the IADPSG diagnostic criteria for GDM could be appropriate for patients in mainland China.

Seasonality, temperature and pregnancy oral glucose tolerance test results in Australia

BackgroundThe oral glucose-tolerance test (OGTT) is currently the standard method for diagnosis of gestational diabetes (GDM). We conducted a post hoc analysis using the Australian Hyperglycemia and Adverse Pregnancy Outcome (HAPO) data to determine seasonal variations in OGTT results, the consequent prevalence of GDM, and association with select perinatal parameters.MethodWomen enrolled in the Australian HAPO study sites (Brisbane and Newcastle) from 2001 to 2006 were included if OGTT results between 24 to 32 weeks gestation were available (n = 2120). Fasting plasma glucose, 1-h plasma glucose, 2-h plasma glucose, HbA1c, HOMA-IR, and umbilical cord C-peptide and glucose values were categorized by season and correlated to monthly temperature records from the Australian Bureau of Meteorology for Brisbane and Newcastle. GDM was defined post hoc using the IADPSG/WHO criteria.ResultsSmall but significant (p < 0.01 on ANOVA) elevations in fasting glucose (+ 0.12 mM), HbA1c (+ 0.09%), and HOMA-IR (+ 0.88 units) were observed during the winter months. Conversely, higher 1-h (+ 0.19 mM) and 2-h (+ 0.33 mM) post-load glucose values (both p < 0.01) were observed during the summer months. The correlations between fasting glucose, 1-h glucose, 2-h glucose, and HbA1c with average monthly temperatures confirmed this trend, with positive Pearson’s correlations between 1-h and 2-h glucose with increasing average monthly temperatures, and negative correlations with fasting glucose and HbA1c. Further, umbilical cord C-peptide and glucose displayed negative Pearson’s correlation with average monthly temperature, aligned with trends seen in the fasting plasma glucose. Overall prevalence of GDM did not display significant seasonal variations due to the opposing trends seen in the fasting versus 1-h and 2-h post-load values.ConclusionA significant winter increase was observed for fasting plasma glucose, HbA1c, and HOMA-IR, which contrasted with changes in 1-h and 2-h post-load venous plasma glucose values. Interestingly, umbilical cord C-peptide and glucose displayed similar trends to that of the fasting plasma glucose. While overall prevalence of GDM did not vary significantly by seasons, this study illustrates that seasonality is indeed an additional factor when interpreting OGTT results for the diagnosis of GDM and provides new direction for future research into the seasonal adjustment of OGTT results.

Diagnosis of Gestational Diabetes Mellitus in China: Perspective, Progress and Prospects

Abstract Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy. Despite extensive research in the past 50 years, the universal approach to diagnose GDM continues to be debated around the world and clinical practices vary from country to country and unit to unit within the same country. As new evidence emerges, the diagnostic criteria of GDM has continuously evolved since the 1990s. In 2011, after the announcement of the landmark International Association of Diabetes and Pregnancy Study Groups diagnostic criteria, many international organizations have accepted and advocated its use. However, there are differences in glucose metabolism among different ethnic groups, and the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study lacked data from mainland China. Whether the criteria developed based on the HAPO study are applicable to China remains to be further validated. In this current review, we will discuss the evolution of GDM diagnostic criteria and guidelines in China, and compare them to that in western countries to figure out the proper recommendations on the diagnosis of GDM among Chinese women.

Much to HAPO FUS About: Increasing Maternal Glycemia in Pregnancy Is Associated With Worsening Childhood Glucose Metabolism.

The initial purpose of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was to examine the associations of increasing degrees of untreated maternal glycemia, less severe than overt diabetes, with adverse pregnancy and neonatal outcomes and bring a unified approach to the diagnosis of gestational diabetes mellitus (GDM). The HAPO study (1) demonstrated linear increases in the risk of the primary outcomes of neonatal birth weight, cord C-peptide >90th percentile, neonatal hypoglycemia, and primary cesarean delivery with increasing maternal glycemia on a one-step 75-g 2-h oral glucose tolerance test (OGTT). The secondary outcomes including neonatal skinfold thicknesses >90th percentile, preterm delivery, preeclampsia, and shoulder dystocia had similar associations. In two long-term offspring follow-up studies published in this issue of Diabetes Care (2,3), risks of adverse outcomes related to this continuum of maternal glycemia in pregnancy are now demonstrated to persist into early adolescence. The long-term risk of maternal hyperglycemia to the offspring exposed in utero has been an ongoing concern for decades. In 1954, Pedersen (4) proposed that excessive glucose in mothers with diabetes is available for trans-placental passage, resulting in fetal hyperinsulinemia and excess fat accretion. In his Banting lecture, Norbert Freinkel (5) proposed the concept that fetal exposures to altered levels of maternal fuels, after organogenesis, may result in long-range adverse anatomical and metabolic changes in the offspring, which he called “fuel-mediated teratogenesis.” A related “fetal programming” hypothesis proposed by Barker and Osmond (6) holds that nutritional (and other environmental) exposures during critical developmental windows may induce changes in tissue development and function that contribute to long-term chronic disease risk. Based on studies in animal models and in …

Maternal glucose levels during pregnancy and childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study.

Maternal type 2 diabetes during pregnancy and gestational diabetes are associated with childhood adiposity; however, associations of lower maternal glucose levels during pregnancy with childhood adiposity, independent of maternal BMI, remain less clear. The objective was to examine associations of maternal glucose levels during pregnancy with childhood adiposity in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Study was an observational epidemiological international multi-ethnic investigation that established strong associations of glucose levels during pregnancy with multiple adverse perinatal outcomes. The HAPO Follow-up Study (HAPO FUS) included 4832 children from ten HAPO centres whose mothers had a 75g OGTT at ~28weeks gestation 10-14years earlier, with glucose values blinded to participants and clinical caregivers. The primary outcome was child adiposity, including: (1) being overweight/obese according to sex- and age-specific cut-offs based on the International Obesity Task Force (IOTF) criteria; (2) IOTF-defined obesity only; and (3) measurements >85th percentile for sum of skinfolds, waist circumference and per cent body fat. Primary predictors were maternal OGTT and HbA1c values during pregnancy. Fully adjusted models that included maternal BMI at pregnancy OGTT indicated positive associations between maternal glucose predictors and child adiposity outcomes. For one SD difference in pregnancy glucose and HbA1c measures, ORs for each child adiposity outcome were in the range of 1.05-1.16 for maternal fasting glucose, 1.11-1.19 for 1h glucose, 1.09-1.21 for 2h glucose and 1.12-1.21 for HbA1c. Associations were significant, except for associations of maternal fasting glucose with offspring being overweight/obese or having waist circumference >85th percentile. Linearity was confirmed in all adjusted models. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls. Exposure to higher levels of glucose in utero is independently associated with childhood adiposity, including being overweight/obese, obesity, skinfold thickness, per cent body fat and waist circumference. Glucose levels less than those diagnostic of diabetes are associated with greater childhood adiposity; this may have implications for long-term metabolic health.

Maternal vitamin D and neonatal anthropometrics and markers of neonatal glycaemia: Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks' gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks' gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

Gestational Diabetes Mellitus: Is It Time to Reconsider the Diagnostic Criteria?

It has been 10 years since results from the landmark Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study were published (1) and 8 years since the recommendations of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) appeared in this journal (2). The HAPO study demonstrated a continuous relationship between glucose levels on a 75-g oral glucose tolerance test (GTT) and the risks for selected fetal outcomes. Potential diagnostic criteria for gestational diabetes mellitus (GDM) were considered by a Consensus Panel of the IADPSG, which, after a close vote, decided to select an odds ratio (OR) of 1.75, relative to the mean, for selected outcomes. This corresponded to glucose levels of ≥5.1 mmol/L at fasting, ≥10.0 mmol/L at 1 h, and ≥8.5 mmol/L at 2 h on a 75-g GTT. Although the prevalence of GDM varied markedly between the 15 study centers when applying these criteria, the relationship between glucose and outcomes was consistent, and therefore it was considered appropriate for these criteria to be applied globally (3). The IADPSG recommendations were initially generally greeted with enthusiasm. Finally, diagnostic criteria based on fetal outcomes were available and would replace criteria in the U.S., for example, that were derived from the prediction of subsequent maternal diabetes. Furthermore, given the ethnic diversity of the HAPO participating centers, there was a realistic prospect that their universal adoption was both feasible and practical. However, in the same issue of Diabetes Care that the IADPSG recommendations appeared in there was also a commentary (4) that asked whether the new criteria represented a “problem solved or a …

Will the Use of Lyophilized Citrate Tubes Lead to the Over-Diagnosis of Diabetes in Pregnancy?

The International Association of Diabetes and Pregnancy Study Group (IADSPG)1 plasma glucose concentration thresholds used for diagnosing gestational diabetes mellitus (GDM) (1) are based on the risk of an adverse fetal outcome according to the landmark Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The HAPO study used research-grade methodology to minimize preanalytical glucose loss after an oral glucose tolerance test (OGTT); thus, samples were cooled and plasma separated shortly after phlebotomy (1). This sample processing is the gold standard for GDM-related studies of plasma glucose. A diagnosis of GDM using IADSPG criteria has been shown to be sensitive to bias in plasma glucose measurement; for …

Laboratory diagnosis of gestational diabetes: An in silico investigation into the effects of pre-analytical processing on the diagnostic sensitivity and specificity of the oral glucose tolerance test

IntroductionDelayed separation of red cells from plasma causes pre analytical glucose loss, which in turn results in an under-diagnosis of GDM (gestational diabetes) based on the OGTT (oral glucose tolerance test). In silico investigations may help laboratory decision making, when exploring pragmatic improvements to sample processing. MethodsLate pregnancy 0, 1 and 2h 75g OGTT values were obtained from two distinct populations of pregnant women: 1. Values derived from the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) Study and 2. New Zealand women identified as at higher risk of GDM by their caregivers, undergoing OGTT during routine antenatal care. In both populations studied, in silico modelling focussed on the effects of pre-analytical delays in plasma separation, when using fluoride collection tubes. ResultsUsing a model that ‘batched’ samples from the three OGTT collection times, diagnostic sensitivity was estimated as follows: 66.1% for HAPO research population and 48.4% for the 1305 women receiving routine antenatal care. If samples were not batched, but processed shortly after each blood sample was collected, then sensitivity increased to 81%. ConclusionExploration of a range of clinical and laboratory scenarios using in silico modelling, showed that delaying the processing of pregnancy OGTT samples, using batched sample collection into fluoride tubes, causes unacceptable loss of GDM diagnostic sensitivity across two distinct population groups. This modelling approach will hopefully provide information that helps with final decision making around improved laboratory processing techniques.

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.

To 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. This 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. Among 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. Women 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.

Untreated Mild Hyperglycemia During Pregnancy and Anthropometric Measures of Obesity in Offspring at Age 5-7 Years.

OBJECTIVEObesity in the offspring of women with hyperglycemia during pregnancy has been reported, but the results are conflicting. This study examined the association of hyperglycemia during pregnancy and anthropometry in 5- to 7-year-old offspring whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study at the Belfast Centre.RESEARCH DESIGN AND METHODSWomen in the HAPO study underwent a 75-g oral glucose tolerance test (OGTT) at approximately 28 weeks of gestation. Mothers and caregivers remained blinded to the results unless the fasting plasma glucose (FPG) concentration was >5.8 mmol/L or the 2-h plasma glucose (2hPG) concentration was >11.1 mmol/L. Offspring weight, height, and skinfold thicknesses (triceps, subscapular, and suprailiac) were measured at age 5–7 years. Overweight, obesity, and extreme obesity were defined as a BMI z score ≥85th, ≥95th, and ≥99th percentile, respectively, based on the 1990 British Growth Standard.RESULTSBelfast HAPO offspring (n = 1,320, 82%) aged 5–7 years attended for follow-up. With use of multiple regression, maternal FPG, 1h PG, and 2hPG did not show any relation to offspring BMI z score or offspring skinfold sum independent of maternal BMI at OGTT and offspring birth weight z score. This lack of association with maternal glycemia persisted with the offspring BMI z score expressed as ≥85th, ≥95th, or 99th percentile and the sum of skinfolds expressed as ≥90th percentile specific for sex. The initially significant relation between FPG and all offspring adiposity measures was explained by maternal BMI at the OGTT.CONCLUSIONSAfter adjustment for maternal BMI at the OGTT, higher maternal FPG concentration during pregnancy (short of diabetes) is no longer a risk factor for obesity, as reflected by BMI and the sum of skinfolds in offspring aged 5–7 years.

NICE's latest guidelines on diabetes in pregnancy: getting the balance right

<scp>NICE</scp>'s latest guidelines on diabetes in pregnancy: getting the balance right

Diabetic pregnancy: an overview of current guidelines and clinical practice.

We review the recent changes in diagnostic criteria of gestational diabetes mellitus (GDM), describe problems with maintaining and monitoring adequate blood glucose, especially in type 1 diabetes, and provide a brief overview of the currently approved glucose-lowering therapies in pregnancy. After the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, the definition of GDM was revised under the auspices of the International Association of Diabetes and Pregnancy Study Groups. The guidelines, with minor modifications, were endorsed by WHO in 2013. Intensive debate continues, focused on the expected large increase in prevalence of GDM and shortage of experimental evidence of clinical benefits from the new diagnostic criteria. Despite a very good glycaemic control, the prevalence of macrosomia remains high. This indicates a serious deficiency in current monitoring tools and the available therapies. So far, the only glucose-lowering medications approved for use during pregnancy are insulins. The HAPO study provides a very suggestive evidence for a strong, continuous association of maternal glucose levels with an increased risk of excessive foetal weight gain. The new definition of GDM results in higher healthcare expenditure, but remains cost-effective. The current therapeutic goals require careful revision to further reduce the risk of adverse outcomes. New glucose-monitoring strategies and markers, and approval of new pharmacotherapies are needed.

The interplay between maternal obesity and gestational diabetes mellitus.

There is a strong epidemiological association between maternal obesity and gestational diabetes mellitus (GDM). Since the publication of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study on women with mild hyperglycemia in 2008, new criteria have been introduced in maternity services internationally for the diagnosis of GDM. As a result, the diagnosis of GDM may be made in one-third of obese women (n=68). The aim of this review was to examine the interplay between maternal obesity and GDM in light of the HAPO study and the subsequent revised diagnostic criteria. Obesity and GDM are important obstetric risk factors because they both are potentially modifiable. However, the new international criteria for the diagnosis of GDM have serious resource implications for maternity services provided to the large number of women attending for care in developed countries. Further consideration needs to be given as to whether obese women with mild hyperglycemia need to be referred to a multidisciplinary team antenatally if they do not require insulin treatment.