Hyperglycemia And Adverse Pregnancy Outcome Research Articles

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.

Maternal Exposure to Perfluorooctane Sulfonate (PFOS) Is Associated with Maternal Hyperglycaemia and Adverse Neonatal and Childhood Outcomes

Perfluorooctane sulfonate (PFOS) belongs to a class of endocrine-disrupting chemicals, perfluoroalkyl chemicals (PFCs), implicated in adiposity. Although supposedly phased out since 2002, its use remains widespread in Asia. We aim to examine the relationship between exposure to PFOS and maternal hyperglycaemia and metabolic outcomes in the offspring. We measured blood PFOS and other PFCs in archived samples taken at 24-32weeks gestation from mothers in the Hong Kong centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study between 2002-2004. All mothers underwent 75g OGTT and GDM was diagnosed according to the IADPSG/WHO 2013 criteria. Pregnancy outcomes, neonatal anthropometrics and childhood outcomes at 7 years were documented. PFCs were measured using high performance LC-MS-MS. We completed analysis of PFCs in 1,601 maternal samples, a subset of 99 cord blood samples, and 970 offspring at 7 years follow-up. There is strong correlation among PFOS and other PFCs in cord blood (ρ=0.51-0.74, p<0.001), as well as correlation with maternal levels (ρ=0.60, p<0.001). Ratio of cord blood to maternal PFOS was 0.60. Using regression analysis with adjustment for maternal age, BMI, and offspring gender, maternal PFOS showed association with maternal 1 hour glucose, 2 hour glucose, HbA1c, AUC during OGTT and GDM, though only the association with HbA1c remained significant using log-transformed PFOS (beta 0.0746 ± 0.0132, p=1.7x10-8). Log-transformed maternal PFOS was associated with higher birthweight, lower birth length, higher ponderal index and lower neonatal sum of skin fold thickness (beta -0.337 ± 0.085, p=7.1x 10-5), after adjustment for all covariates. Maternal PFOS during pregnancy was associated with lower height in offspring at age 7, but not offspring glycaemic parameters. Exposure to PFOS may be an important contributing factor to the epidemic of hyperglycaemia in pregnancy and childhood metabolic disorders in Asia. Disclosure R.C.W. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd.. C.H.T. Tam: None. G. Cheung: None. W. Lowe: None. B.E. Metzger: None. W.H. Tam: None. C.K. Wong: None.

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 …

Characteristics of different risk factors and fasting plasma glucose for identifying GDM when using IADPSG criteria: a cross-sectional study

BackgroundThe Swedish National Board of Health and Welfare (SNBHW) recommended the new diagnostic criteria for GDM based upon Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study thresholds. Due to limited knowledge base, no recommendations were made on GDM screening. The aim of this study is to evaluate test characteristics of risk factors and fasting blood glucose as screening tests for diagnosing GDM using diagnostic thresholds based upon HAPO study 1.75/2.0 (model I/II respectively) odds ratio for adverse pregnancy outcomes.MethodsThis cross-sectional, population-based study included all pregnant women who attended maternal health care in Örebro County, Sweden between the years 1994–96. A 75 g OGTT with capillary fasting and 2-h blood glucose was offered to all pregnant women at week 28–32. Risk factors and repeated random glucose samples were collected. Sensitivity, specificity and predictive values of blood glucose were calculated.ResultsPrevalence of GDM was 11.7% with model I and 7.2% with the model II criteria. Risk factors showed 28%, (95% CI 24–32) and 31%, (95% CI 25–37) sensitivity for model I and II respectively. A fasting cut off ≥4.8 mmol/l occurred in 24% of women with 91%, (95% CI 88–94) sensitivity and 85%, (95% CI 83–86) specificity using model I while a fasting cut off ≥5.0 mmol/l occurred in 14% with 91%, (95% CI 87–94) sensitivity and 92%, (95% CI 91–93) specificity using model II.ConclusionRisk factor screening for GDM was found to be poorly predictive of GDM but fasting glucose of 4.8–5.0 mmol/l showed good test characteristics irrespective of diagnostic model and results in a low rate of OGTTs.

Maternal vitamin D and markers of glycaemia during pregnancy in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome study.

To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and β-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

Gestational Diabetes Mellitus: Why the Controversy?

Gestational diabetes mellitus (GDM)6 has been defined as “any degree of glucose intolerance with onset or first recognition during pregnancy.” With the dramatic rise in the prevalence of type 2 diabetes, some organizations have advocated that hyperglycemia first detected in pregnancy should be classified as either diabetes mellitus in pregnancy or GDM. The rationale for identifying GDM is that it results in complications for both the fetus (e.g., large baby, neonatal hypoglycemia) and mother (e.g., preeclampsia, increased risk of cesarean delivery, and markedly increased likelihood of subsequent type 2 diabetes). Treatment of GDM reduces some of the adverse outcomes. Despite the 5 international workshops devoted to GDM since 1979, there is considerable controversy surrounding identification of GDM. Both the screening and diagnostic criteria vary among countries and commonly between obstetric and diabetes organizations in a single country. Recommendations for screening encompass “do not screen,” selective screening (high risk only), and universal. Moreover, the screening techniques vary; fasting glucose, random glucose, and oral glucose challenge are all used. The criteria for diagnosis are even more controversial. The major items of contention are the number of steps (1 or 2), the glucose load (75 g or 100 g), the duration of the test (2 h or 3 h), the glucose cutoff values, and whether 1 or 2 high glucose values are required. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was designed to determine the relationship between maternal blood glucose concentrations and adverse pregnancy outcomes. The prospective, randomized, multinational study included 23316 women who had a 75-g oral glucose tolerance test (OGTT) at 24–32 weeks of gestation. The study showed that the risk of adverse events increased continuously as a function of maternal glycemia. No convenient thresholds for increased risk were observed, and each of the 3 values (fasting, 1 h, …

Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry (n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms.

A cost-effectiveness comparison of the NICE 2015 and WHO 2013 diagnostic criteria for women with gestational diabetes with and without risk factors

ObjectivesTo compare the cost-effectiveness (CE) of the National Institute for Health and Care Excellence (NICE) 2015 and the WHO 2013 diagnostic thresholds for gestational diabetes mellitus (GDM).SettingThe analysis was from...

Maternal BMI and Glycemia Impact the Fetal Metabolome.

OBJECTIVEWe used targeted metabolomics to determine associations of maternal BMI and glucose levels with cord blood metabolites and associations of cord blood metabolites with newborn birth weight and adiposity in mother-offspring dyads.RESEARCH DESIGN AND METHODSTargeted metabolomic assays were performed on cord blood plasma samples from European ancestry, Afro-Caribbean, Thai, and Mexican American newborns (400 from each ancestry group) whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and who had anthropometric measurements at birth.RESULTSMeta-analysis across the four cohorts demonstrated significant correlation of all cord blood metabolites analyzed with maternal fasting levels of the same metabolites at ∼28 weeks’ gestation except for triglycerides, asparagine/aspartate, arginine, and the acylcarnitine C14-OH/C12-DC. Meta-analyses also demonstrated that maternal BMI with or without adjustment for maternal glucose was associated with cord blood metabolites including the branched-chain amino acids and their metabolites as well as phenylalanine. One-hour but not fasting glucose was associated with cord blood 3-hydroxybutyrate and its carnitine ester, a medium-chain acylcarnitine, and glycerol. A number of cord blood metabolites were associated with newborn birth weight and sum of skinfolds, including a negative association of triglycerides and positive association of 3-hydroxybutyrate, its carnitine ester, and serine with both newborn outcomes.CONCLUSIONSMaternal BMI and glycemia are associated with different components of the newborn metabolome, consistent with their independent effects on newborn size at birth. Maternal BMI is associated with a newborn metabolic signature characteristic of insulin resistance and risk of type 2 diabetes in adults.

Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups.

OBJECTIVEWe used targeted metabolomics in pregnant mothers to compare maternal metabolite associations with maternal BMI, glycemia, and insulin sensitivity.RESEARCH DESIGN AND METHODSTargeted metabolomic assays of clinical metabolites, amino acids, and acylcarnitines were performed on fasting and 1-h postglucose serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American mothers (400 from each ancestry group) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and underwent an oral glucose tolerance test at ∼28 weeks gestation.RESULTSK-means clustering, which identified patterns of metabolite levels across ancestry groups, demonstrated that, at both fasting and 1-h, levels of the majority of metabolites were similar across ancestry groups. Meta-analyses demonstrated association of a broad array of fasting and 1-h metabolites, including lipids and amino acids and their metabolites, with maternal BMI, glucose levels, and insulin sensitivity before and after adjustment for the different phenotypes. At fasting and 1 h, a mix of metabolites was identified that were common across phenotypes or associated with only one or two phenotypes. Partial correlation estimates, which allowed comparison of the strength of association of different metabolites with maternal phenotypes, demonstrated that metabolites most strongly associated with different phenotypes included some that were common across as well as unique to each phenotype.CONCLUSIONSMaternal BMI and glycemia have metabolic signatures that are both shared and unique to each phenotype. These signatures largely remain consistent across different ancestry groups and may contribute to the common and independent effects of these two phenotypes on adverse pregnancy outcomes.

Metformin in pregnancy

Metformin in pregnancy

Population-Level Outcomes with a 2-Step Approach for Gestational Diabetes Screening and Diagnosis.

To examine outcomes associated with alternative glucose thresholds in a 2-step approach for screening and diagnosing gestational diabetes mellitus (GDM). We studied 178,527 pregnancies between 2008 and 2012 in Alberta, Canada. They were categorized retrospectively as normal 50 g screen (n=144,191); normal 75 g oral glucose tolerance test (OGTT) (n=21,248); abnormal at glucose thresholds suggested by the International Association of Diabetes and Pregnancy Group (IADPSG) (HAPO 1.75, n=4308); abnormal at glucose thresholds associated with an odds ratio of 2.0 for adverse events in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. This latter group, which would have been treated for GDM based on customary care, was further divided into those with 1 (HAPO 2-1 n=5528) or 2 or more abnormal glucose values (HAPO 2-2 n=3252). Main outcomes were large for gestational age (LGA), induced labour and Cesarean-section rates. LGA rates were 8.2%, 10.5%, 14.2%, 11.8% and 16.5% among normal 50 g, normal 75 g OGTT, HAPO 1.75, HAPO 2-1, and HAPO 2-2 groups, respectively. Labour induction and caesarean-section rates were 29.6% and 36.2% in the IADPSG, 38.2% and 36.8% in the HAPO 2-1 group, and 42.3% and 41.1% in the HAPO 2-2 groups, respectively. Excessive maternal weight (≥91 kg) was associated with a higher risk for all adverse outcomes. The 2-step approach effectively identifies pregnancies at low risk for adverse outcomes. Labelling influences induction practice. Any glucose intolerance increases risk for adverse outcomes, and pregnancies with highest (2 or higher) abnormal glucose values remain at greatest risk. Further research is needed to determine whether glycemic thresholds for GDM diagnosis should incorporate information about maternal weight.

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.

Gestational diabetes mellitus

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and offspring. Women detected to have diabetes early in pregnancy receive the diagnosis of overt, non-gestational, diabetes (glucose: fasting > 126 mg/dl, spontaneous > 200 mg/dl or HbA1c > 6.5 % before 20 weeks of gestation). GDM is diagnosed by an oral glucose tolerance test (OGTT) or fasting glucose concentrations (> 92 mg/dl). Screening for undiagnosed type 2 diabetes at the first prenatal visit (Evidence level B) is recommended in women at increased risk using standard diagnostic criteria (high risk: history of GDM or pre-diabetes (impaired fasting glucose or impaired glucose tolerance); malformation, stillbirth, successive abortions or birth weight > 4,500 g in previous pregnancies; obesity, metabolic syndrome, age > 45 years, vascular disease; clinical symptoms of diabetes (e. g. glucosuria)). Performance of the OGTT (120 min; 75 g glucose) may already be indicated in the first trimester in some women but is mandatory between 24 and 28 gestational weeks in all pregnant women with previous non-pathological glucose metabolism (Evidence level B). Based on the results of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study GDM is defined, if fasting venous plasma glucose exceeds 92 mg/dl or 1 h 180 mg/dl or 2 h 153 mg/dl after glucose loading (OGTT; international consensus criteria). In case of one pathological value a strict metabolic control is mandatory. This diagnostic approach was recently also recommended by the WHO. All women should receive nutritional counseling and be instructed in blood glucose self-monitoring and to increase physical activity to moderate intensity levels- if not contraindicated. If blood glucose levels cannot be maintained in the normal range (fasting < 95 mg/dl and 1 h after meals < 140 mg/dl) insulin therapy should be initiated as first choice. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g OGTT (WHO criteria) 6-12 weeks postpartum and every 2 years in case of normal glucose tolerance (Evidence level B). All women have to be instructed about their (sevenfold increased relative) risk of type 2 diabetes at follow-up and possibilities for diabetes prevention, in particular weight management and maintenance/increase of physical activity. Monitoring of the development of the offspring and recommendation of healthy lifestyle of the children and family is recommended.

Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants

ObjectiveObesity in pregnancy may be associated with reduced placental transfer of 25-hydroxyvitamin D (25-OHD). The objective of this study was to examine associations between maternal BMI and maternal and cord blood levels of 25-OHD in full term neonates born to a single racial cohort residing at similar latitude. Secondary objectives were to examine associations between maternal glucose tolerance with maternal levels of 25-OHD and the relationship between cord blood 25-OHD levels and neonatal size.MethodsThis study was conducted among participants of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study meeting the following criteria: residing at latitudes 41–43°, maternal white race, and gestational age 39–41 weeks. Healthy pregnant women underwent measures of height, weight, and a 75-g fasting oral glucose tolerance test (OGTT) at approximately 28 weeks gestation. Maternal and cord blood sera were analyzed for total 25-OHD by HPLC tandem mass spectrometry. Statistical analyses included ANOVA and linear regression models.ResultsMaternal and cord blood (N = 360) mean levels (sd) of 25-OHD were 37.2 (11.2) and 23.4 (9.2) ng/ml, respectively, and these levels were significantly different among the 3 field centers (ANOVA p< 0.001). Maternal serum 25-OHD was lower by 0.40 ng/ml for BMI higher by 1 kg/m2 (p<0.001) in an adjusted model. Maternal fasting plasma glucose, insulin sensitivity, and presence of GDM were not associated with maternal serum 25-OHD level when adjusted for maternal BMI. Cord blood 25-OHD was lower by 0.26 ng/ml for maternal BMI higher by 1 kg/m2 (p<0.004). With adjustment for maternal age, field center, birth season and maternal serum 25-OHD, the association of cord blood 25-OHD with maternal BMI was attenuated. Neither birth weight nor neonatal adiposity was significantly associated with cord blood 25-OHD levels.ConclusionThese results suggest that maternal levels of 25-OHD are associated with maternal BMI. The results also suggest that interpretation of neonatal 25-OHD levels may need to incorporate specific maternal factors in addition to season of birth and latitude.

Screening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand.

Gestational Diabetes Mellitus (GDM) is defined as any glucose intolerance with the onset or first recognition during pregnancy. This definition helps for diagnosis of unrecognized pre-existing Diabetes also. Hyperglycemia in pregnancy is associated with adverse maternal and prenatal outcome. It is important to screen, diagnose and treat Hyperglycemia in pregnancy to prevent an adverse outcome. There is no international consensus regarding timing of screening method and the optimal cut-off points for diagnosis and intervention of GDM. DIPSI recommends non-fasting Oral Glucose Tolerance Test (OGTT) with 75g of glucose with a cut-off of ≥ 140 mg/dl after 2-hours, whereas WHO (1999) recommends a fasting OGTT after 75g glucose with a cut-off plasma glucose of ≥ 140 mg/dl after 2-hour. The recommendations by ADA/IADPSG for screening women at risk of diabetes is as follows, for first and subsequent trimester at 24-28 weeks a criteria of diagnosis of GDM is made by 75 g OGTT and fasting 5.1mmol/l, 1 hour 10.0mmol/l, 2 hour 8.5mmol/l by universal glucose tolerance testing. Critics of these criteria state that it causes over diagnosis of GDM and unnecessary interventions, the controversy however continues. The ACOG still prefer a 2 step procedure, GCT with 50g glucose non-fasting if value > 7.8mmol/l followed by 3-hour OGTT for confirmation of diagnosis. In conclusion based on Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study as mild degree of dysglycemia are associated with adverse outcome and high prevalence of Type II DM to have international consensus It recommends IADPSG criteria, though controversy exists. The IADPSG criteria is the only outcome based criteria, it has the ability to diagnose and treat GDM earlier, thereby reducing the fetal and maternal complications associated with GDM. This one step method has an advantage of simplicity in execution, more patient friendly, accurate in diagnosis and close to international consensus. Keeping in the mind the diversity and variability of Indian population, judging international criteria may not be conclusive, thus further comparative studies are required on different diagnostic criteria in relation to adverse pregnancy outcomes.

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.

Diabetes in pregnancy

Diabetes in pregnancy is still considered a high-risk condition for both mother and baby. Even in the best centres, malformation and mortality rates are reportedly twofold to fivefold higher than in the background population, and pregnancy planning rates remain obstinately poor. Increasing global rates of type 2 diabetes are now extending into pregnancy, with similarly poor outcomes to type 1 diabetes, and excess maternal weight is adding to the complexity of management. Over the last 5-10 years, several randomised trials have offered new insight into the role of oral hypoglycaemic drugs and insulin analogues in pregnancy, while continuous subcutaneous insulin infusion (CSII) pumps and continuous glucose monitors (CGMs) are under scrutiny. The relevance of minor degrees of hyperglycaemia to adverse pregnancy outcome was clearly demonstrated by the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study, but translation of these data into clinical practice has proved challenging because of the continuum of risk. Long-term metabolic and cardiovascular implications of hyperglycaemia during pregnancy for mother and child are now generally recognised with major implications for public health.