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ObjeCtiveTo perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy. DesignExternal validation of all published prognostic models in large scale, prospective, multicentre cohort study. setting 31 independent midwifery practices and six hospitals in the Netherlands. PartiCiPantsWomen recruited in their first trimester (<14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded. Main OutCOMe MeasuresDiscrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots. results 3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated.The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit. COnClusiOnsIn this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact. IntroductionIn the field of obstetrics, the number of publications on prognostic models has more than tripled in the past decade, 1 which reflects an increasing interest in risk based medicine. Risk based medicine aims to provide the most appropriate care to each patient, often guided by outcome risk estimates based on individual patient characteristics, test results, or even genetic information. 2 As a result of the obesity pandemic, the incidence of gestational diabetes mellitus, notably occurring in the second or third trimester, is rising and is increasingly contributing to perinatal complications such as macrosomia, shoulder dystocia, caesarean section, and neonatal hypoglycaemia. 3 4 Moreover, long term sequelae of gestational diabetes mellitus are type 2 diabetes in mothers and obesity in their offspring. 5 6 Early diagnosis and treatment of gestational diabetes mellitus have been proven to improve pregnancy outcomes. 7 8 Some guidelines propose a population strategy for diagnosing the disorder [9][10][11][12] (that is, an oral glucose tolerance test) in all pregnant women, whereas others opt for a high ri...

After completion of this article, the reader should be able to summarize that there is still no worldwide consensus on the diagnosis, management, and adverse effects of Gestational Diabetes Mellitus (GDM); explain that all methods of screening vary in sensitivity and depend on very strict preparations for screening; state that there is no agreement on ideal levels of blood glucose to prevent untoward effects; and recall that there are two very large prospective studies that clarify the dark waters and that we should await their results.

BackgroundHypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.Methods/DesignThe proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis.DiscussionIn this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.Trial registration numberClinical Trials, protocol registration system: NCT00189007

NCT00189007, Dutch Trial Register NTR1383.