Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing.

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. Design: This was an individual participant data meta-analysis of cohort studies. Setting: Source data from secondary and tertiary care. Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey. Primary outcomes: Early-onset (delivery at < 34 weeks’ gestation), late-onset (delivery at ≥ 34 weeks’ gestation) and any-onset pre-eclampsia. Analysis: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I ² and τ². A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. Results: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. Limitations: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. Conclusion: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. Future work: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. Study registration: This study is registered as PROSPERO CRD42015029349. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

Objective To compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome. Patients and methods Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease. Results A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank<0.05), whereas there was no difference between patients who received aspirin or aspirin-low-molecular weighted heparin combination. Conclusion Several non-criteria APL can be detected in patients with clinical APS features without any conventional APL, with various rates. The detection of non-criteria APL and thus the diagnosis of seronegative APS could discuss the therapeutic management similar to seropositive APS, but well-designed controlled studies are necessary.

BACKGROUND:Prenatal diagnosis of severe bone diseases is challenging and requires complete and precise analysis of fetal anomalies to guide genetic investigation and parental counselling. CASE REPORT:We report a rare case of Antley-Bixler syndrome prenatally diagnosed at 26 weeks’ gestation by ultrasound and computed tomography in a 28-year-old woman with a history of early termination of pregnancy for “malposition of the inferior limbs”. The prenatal ultrasound scan showed severe femoral bowing and frontal bossing. Taking into account the high probability of a recurrent severe skeletal disorder, a computed tomography (CT) scan was proposed. CT findings revealed bilateral femora deformation, craniosynostosis, severe midface hypoplasia, and radiohumeral synostosis. These anomalies strongly suggested Antley-Bixler syndrome. Sequencing of the POR gene in the fetus and the parents revealed compound heterozygous mutations in exon 9 and intron 7, both inherited from each parent, and this finding allowed genetic counseling. CONCLUSIONS:The first step in the proper prenatal diagnosis of fetal bone disorders is the precise analysis of ultrasonographic images. However, when a severe fetal inherited disorder is strongly suspected in late mid-trimester, CT may be discussed and usefully contribute to diagnosis and prognosis assessment.

Background: The debate surrounding the management of term breech presentation has excessively focused on the mode of delivery. Indeed, a steady decline in the rate of vaginal breech delivery has been observed over the last three decades, and the soundness of the vaginal route was seriously challenged at the beginning of the 2000s. However, associations between adverse perinatal outcomes and antenatal risk factors have been observed in foetuses that remain in the breech presentation in late gestation, confirming older data and raising the question of the role of these antenatal risk factors in adverse perinatal outcomes. Thus, aspects beyond the mode of delivery must be considered regarding the awareness and adequate management of such situations in term breech pregnancies. Main body: In the context of the most recent meta-analysis and with the publication of large-scale epidemiologic studies from medical birth registries in countries that have not abruptly altered their criteria for individual decision-making regarding the breech delivery mode, the currently available data provide essential clues to understanding the underlying maternal-foetal conditions beyond the delivery mode that play a role in perinatal outcomes, such as foetal growth restriction and gestational diabetes mellitus. In view of such data, an accurate evaluation of these underlying conditions is necessary in cases of persistent term breech presentation. Timely breech detection, estimated foetal weight/growth curves and foetal/maternal well-being should be considered along with these possible antenatal risk factors; a thorough analysis of foetal presentation and an evaluation of the possible benefit of external cephalic version and pelvic adequacy in each specific situation of persistent breech presentation should be performed. Conclusion: The adequate management of term breech pregnancies requires screening and the efficient identification of breech presentation at 36 weeks of gestation, followed by thorough evaluations of foetal weight, growth and mobility, while obstetric history, antenatal gestational disorders and pelvis size/conformation are considered. The management plan, including external cephalic version and follow-up based on the maternal/foetal condition and potentially associated disorders, should be organized on a case-by-case basis by a skilled team after the woman is informed and helped to make a reasoned decision regarding delivery route.