Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study.

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study. Setting: Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019. Participants: Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registration: ClinicalTrials.gov NCT02035059.

Exposure to night-time light pollution and risk of prolonged duration of labor: A nationwide cohort study.

BACKGROUND: Light pollution (LP) is a ubiquitous environmental agent that affects more than 80% of the world's population. This large nationwide cohort study evaluates whether exposure to LP can influence obstetric outcomes. METHODS: We analyzed Austrian birth registry data on 717 113 cases between 2008 and 2016 and excluded cases involving day-time delivery, <23 + 0 gestational weeks, and/or birthweight <500 g, induction of labor, elective cesarean, or cases with missing data. The independent variable, that is, degree of night-time LP, was categorized as low (0.174 to <0.688 mcd/m2 ), medium (0.688 to <3 mcd/m2 ), or high (3 to <10 mcd/m2 ). Duration of labor and adverse neonatal outcomes served as outcome measures. RESULTS: Cases in regions with high LP (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57) and medium LP (OR, 1.22; 95% CI, 1.14-1.31) showed increased odds of prolonged labor (P < .0001 each). Newborns born in regions with high LP (OR, 1.12; 95% CI, 1.07-1.16) and medium LP (OR, 1.07; 95% CI, 1.04-1.10) showed increased odds of experiencing adverse outcomes (P < .0001 each). Preterm delivery <28 + 0 weeks was also associated with the degree of LP (P = .04). CONCLUSIONS: Night-time LP negatively interferes with obstetric outcomes. The perceived influence of LP as an environmental agent needs to be re-evaluated to minimize associated health risks.

Institutional guidelines on maternal care and investigations following antepartum stillbirth - a national survey.

BACKGROUND: Antepartum stillbirth, i.e., intrauterine fetal death (IUFD) above 24 weeks of gestation, occurs with a prevalence of 2.4-3.1 per 1000 live births in Central Europe. In order to ensure highest standards of treatment and identify causative and associated (risk) factors for fetal death, evidence-based guidelines on clinical practice in such events are recommended. Owing to a lack of a national guideline on maternal care and investigations following stillbirth, we, hereby, sought to assess the use of institutional guidelines and clinical practice after IUFD in Austrian maternity units. METHODS: A national survey with a paper-based 12-item questionnaire covering demographic variables, local facilities and practice, obstetrical care and routine post-mortem work-up following IUFD was performed among all Austrian secondary and tertiary referral hospitals with maternity units (n = 75) between January and July 2019. Statistical tests were conducted using Chi2 and Fisher's Exact test, respectively. Univariate logistic regression analyses were performed to calculate odds ratio (OR) with a 95% confidence interval (CI). RESULTS: 46 (61.3%) obstetrical departments [37 (80.4%) secondary; 9 (19.6%) tertiary referral hospitals] participated in this survey, of which 17 (37.0%) have implemented an institutional guideline. The three most common investigations always conducted following stillbirth are placental histology (20.9%), fetal autopsy (13.1%) and maternal antibody screen (11.5%). Availability of an institutional guideline was not significantly associated with type of hospital, on-site pathology department, or institutional annual live and stillbirth rates. Post-mortem consultations only in cases of abnormal investigations following stillbirth were associated with lower odds for presence of such guideline [OR 0.133 (95% CI 0.018-0.978); p = 0.047]. 26 (56.5%) departments consider a national guideline necessary. CONCLUSIONS: Less than half of the surveyed maternity units have implemented an institutional guideline on maternal care and investigations following antepartum stillbirth, independent of annual live and stillbirth rate or type of referral centre.

Performance of early risk assessment tools to predict the later development of gestational diabetes.

BACKGROUND: Several prognostic models for gestational diabetes mellitus (GDM) are provided in the literature; however, their clinical significance has not been thoroughly evaluated, especially with regard to application at early gestation and in accordance with the most recent diagnostic criteria. This external validation study aimed to assess the predictive accuracy of published risk estimation models for the later development of GDM at early pregnancy. METHODS: In this cohort study, we prospectively included 1132 pregnant women. Risk evaluation was performed before 16 + 0 weeks of gestation including a routine laboratory examination. Study participants were followed-up until delivery to assess GDM status according to the IADPSG 2010 diagnostic criteria. Fifteen clinical prediction models were calculated according to the published literature. RESULTS: Gestational diabetes mellitus was diagnosed in 239 women, that is 21.1% of the study participants. Discrimination was assessed by the area under the ROC curve and ranged between 60.7% and 76.9%, corresponding to an acceptable accuracy. With some exceptions, calibration performance was poor as most models were developed based on older diagnostic criteria with lower prevalence and therefore tended to underestimate the risk of GDM. The highest variable importance scores were observed for history of GDM and routine laboratory parameters. CONCLUSIONS: Most prediction models showed acceptable accuracy in terms of discrimination but lacked in calibration, which was strongly dependent on study settings. Simple biochemical variables such as fasting glucose, HbA1c and triglycerides can improve risk prediction. One model consisting of clinical and laboratory parameters showed satisfactory accuracy and could be used for further investigations.

Cesarean Section Rate and Perinatal Outcome Analyses According to Robson's 10-Group Classification System.

OBJECTIVES: The cesarean delivery (CD) rate is increasing worldwide. An internationally recognized classification system had been required to analyse the trend and its possible consequences in a standardized manner. The goal of this study was to identify the main contributors to the CD rate at the Medical University of Vienna in an 11-year time period (2003-2013) and to analyse neonatal outcome parameters within the ten Robson categories. METHODS: This is a retrospective data-analysis of singleton and twin pregnancies in cephalic, breech and transverse presentation with a gestational age between 23 and 42 weeks. The cases were divided into ten classes based on the Robson criteria. CD rates and perinatal outcome parameters were analysed within each Robson class. The outcome parameters included: NICU-admission rate and 5 min Apgar score values < 7. RESULTS: The overall CD rate was at 44.2%. Within Robson class 5 the CD rate was the highest at 99.1%. Main contributors were Robson class 5 at 20.6%, followed by class 2 at 17.1% and class 8 at 15.0%. Neonatal outcome analyses revealed significant differences between the Robson classes. CONCLUSIONS: The main contributors to the CD rate were determined. We suggest reconsidering the frequently applied birth mode especially for Robson class 2, 4, 5 and 8. Lowering the CD rate could be achievable, if a careful delivery management and an individual risk evaluation is provided. It is important to reduce the CD rate in the individual Robson classes under consideration of perinatal outcome parameters, since a reduction should only take place where it is clinically useful and relevant.

Temporal changes in epidemiological profile and fetal indications for late termination of pregnancy: a retrospective single-center study.

PURPOSE: To explore whether epidemiological shifts regarding reproduction and pregnancy have influenced the spectrum of indications for late termination of singleton pregnancies (TOP) above 17 weeks of gestation and to evaluate temporal changes in maternal demographics and fetal indications over the last 16 years. METHODS: Retrospective single-center cohort study involving all late TOPs preceded by feticide between 1 January 2004 and 31 December 2019 at a tertiary referral hospital in Austria. Outcome variables were retrieved and a time trend assessed between two 8-year intervals (2004-2011 versus 2012-2019). RESULTS: Between January 2004 and December 2019, a total of 209 singleton pregnancies (50.7% male; 46.9% female fetuses, 2.4% no disclosed sex) were terminated medically at a median gestational age of 25+1 (17+3-37+1) weeks at our institution. Predominant conditions legally justifying the late medical abortion were abnormaltities of the brain/central nervous system (n = 83; 39.7%), chromosomal aberrations (n = 33; 15.8%), complex malformations (n = 31; 4.8%) and abnormaltities of the musculosceletal system including diaphragmatic hernias (n = 18; 8.6%), as reflected by the ICD-10-categories "Congenital malformation of the central nervous system", "Other congenital malformations" and "Chromosomal abnormalities". No changes were observed with regards to maternal age (30.1 ± 5.9 vs. 31.0 ± 6.0 years; p = 0.315) nor frequency of assisted reproductive technologies (7.0% vs. 8.5%; p = 0.550). Despite a 2.5-fold increase in incidence of late TOPs, no epidemiological changes in maternal or fetal characteristics were observed over the last 16 years. CONCLUSION: Population profile and indications for late TOPs followed by feticide remain unchanged over time.

Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study.

To describe the prevalence and spectrum of cardio-pathogenic variants in singleton fetuses after unexplained intrauterine fetal death (IUFD). DNA from post-mortem fibroblastic tissue samples of 16 fetuses after unexplained IUFD was retrieved at two tertiary university hospitals for clinical exome sequencing with subsequent filtering of 122 cardio-specific genes to elucidate underlying cardio-pathogenic variants. In total, we included 12 (75%) male and four (25%) female fetuses who were stillborn at a median gestational age of 34+6 (23+2-40+5) weeks. In two (12.5%) fetuses no cardio-pathogenic variants were found. In 14 (87.5%) fetuses, overall 33 variants were detected in 22 cardio-specific genes, involving 14 (63.63%) genes associated with cardiomyopathy, six (27.27%) arrhythmogenic susceptibility genes and two (9.09%) arrhythmia and cardiomyopathy associated genes. Among the 33 variants, five (15.2%) were classified as likely benign according to the American College of Medical Genetics and Genomics; 28 (84.8%) variants were considered as variants of uncertain significance. Compared to a cohort of explained IUFDs, the cases with and without fetal variants in cardiac genes differed not significantly regarding maternal age, previous history of stillbirth, time of stillbirth or fetal sex. Unexplained stillbirth may be caused by cardio-genetic pathologies, yet a high number of variants of uncertain significance merit a more detailed post-mortem examination including family segregation analysis.

Association between maternal triglycerides and disturbed glucose metabolism in pregnancy.

AIMS: Dyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy. METHODS: Sixty-seven pregnant women received a detailed metabolic characterization at 12+0-22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0-27+6 weeks of gestation. RESULTS: Elevated triglycerides in early gestation were associated with insulin resistance and ß-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03-1.34, p=0.022 for an increase of 10 mg/dl). CONCLUSIONS: Hypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and ß-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.

Maternal Overweight vs. Polycystic Ovary Syndrome: Disentangling Their Impact on Insulin Action in Pregnancy-A Prospective Study.

BACKGROUND: To investigate insulin sensitivity and glucose metabolism in pregnant lean and overweight polycystic ovary syndrome (PCOS) patients vs. lean and overweight controls without PCOS. METHODS: Prospective cohort study on 67 pregnant women (31 with PCOS and 36 controls, subdivided into overweight or obese and normal weight). All women underwent a 2h-OGTT including glucose, insulin, and C-peptide in early- and mid-gestation and were followed-up until delivery. RESULTS: Insulin sensitivity and glucometabolic parameters were comparable between PCOS patients and controls, whereas marked differences were observed between overweight/obese and lean mothers. Impaired whole-body insulin sensitivity at early pregnancy is mainly a consequence of higher BMI (body mass index; p < 0.001) compared to PCOS (p = 0.216), whereby no interaction between overweight/obesity and PCOS was observed (p = 0.194). Moreover, overweight was significantly associated with gestational diabetes (p = 0.0003), whereas there were no differences between women with and without PCOS (p = 0.51). Birth weight was inversely related to whole-body insulin sensitivity (rho = -0.33, p = 0.014) and positively associated with higher pregestational BMI (rho = 0.33, p = 0.012), whereas there was no association with PCOS. CONCLUSIONS: Impaired insulin action was mainly a consequence of overweight rather than PCOS. Our data suggest that overweight is more relevant than PCOS for the effects on insulin sensitivity and impaired glucose metabolism.

Effectiveness of real-time continuous glucose monitoring to improve glycaemic control and pregnancy outcome in patients with gestational diabetes mellitus: a study protocol for a randomised controlled trial.

INTRODUCTION: Real-time continuous glucose monitoring (rt-CGM) informs users about current interstitial glucose levels and allows early detection of glycaemic excursions and timely adaptation by behavioural change or pharmacological intervention. Randomised controlled studies adequately powered to evaluate the impact of long-term application of rt-CGM systems on the reduction of adverse obstetric outcomes in women with gestational diabetes (GDM) are missing. We aim to assess differences in the proportion of large for gestational age newborns in women using rt-CGM as compared with women with self-monitored blood glucose (primary outcome). Rates of neonatal hypoglycaemia, caesarean section and shoulder dystocia are secondary outcomes. A comparison of glucose metabolism and quality of life during and after pregnancy completes the scope of this study. METHODS AND ANALYSIS: Open-label multicentre randomised controlled trial with two parallel groups including 372 female patients with a recent diagnosis of GDM (between 24+0 until 31+6 weeks of gestation): 186 with rt-CGM (Dexcom G6) and 186 with self-monitored blood glucose (SMBG). Women with GDM will be consecutively recruited and randomised to rt-CGM or control (SMBG) group after a run-in period of 6-8 days. The third visit will be scheduled 8-10 days later and then every 2 weeks. At every visit, glucose measurements will be evaluated and all patients will be treated according to the standard care. The control group will receive a blinded CGM for 10 days between the second and third visit and between week 36+0 and 38+6. Cord blood will be sampled immediately after delivery. 48 hours after delivery neonatal biometry and maternal glycosylated haemoglobin A1c (HbA1c) will be assessed, and between weeks 8 and 16 after delivery all patients receive a re-examination of glucose metabolism including blinded CGM for 8-10 days. ETHICS AND DISSEMINATION: This study received ethical approval from the main ethic committee in Vienna. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03981328; Pre-results.

Novel Indices of Glucose Homeostasis Derived from Principal Component Analysis: Application for Metabolic Assessment in Pregnancy.

AIMS: This study is aimed at assessing the association of previously developed indices of glucose homeostasis derived from principal component analysis (PCA) with parameters of insulin action, secretion, and beta cell function during pregnancy. METHODS: In this prospective longitudinal study, an oral glucose tolerance test was performed in sixty-seven pregnant women at two prepartum (12+0 to 22+6 and 24+0 to 28+6) and one postpartum (2 to 11 months) visits. Three principal component scores (PCS) were calculated based on measurements of glucose, insulin, C-peptide, age, and BMI to assess their association with fasting and dynamic indices of insulin action, secretion, and ß-cell function. RESULTS: PCS1 was positively associated with fasting and dynamic parameters of insulin sensitivity (Matsuda index: r = 0.93, p < 0.001), whereas a strong negative association was observed for early, late, and total insulin response. PCS2 was associated with higher mean glucose but negatively related to parameters of insulin secretion. PCS3 was significantly associated with fasting indices of insulin sensitivity. PCS1 to 3 assessed at early pregnancy were also associated with development of GDM, whereby random forest analysis revealed the highest variable importance for PCS1. PCS1 to 3 were significantly related to the oral disposition index explaining 49.0% of its variance. CONCLUSIONS: PCS1 to 3 behaved similarly as compared to previous observations in nonpregnant women and were furthermore associated with the development of GDM. These findings support our hypothesis that PCS1 to 3 could be used as novel indices of glucose disposal during pregnancy.

Effects of gum chewing on glycaemic control in women with gestational diabetes mellitus: A randomized controlled trial. Impact of chewing on hyperglycaemia in women with GDM.

BACKGROUND: The amount of chewing might be relevant in reducing hyperglycaemia in diabetic patients. The study assessed the impact of enhanced chewing on glycaemic control in women with gestational diabetes mellitus (GDM). METHODS: As an open-label, mono-centre randomized controlled trial, 59 women with recent diagnosis of GDM were included. They received either routine care or additional chewing gum intervention. SMBG was performed for five days. RESULTS: No significant impact on mean values of postprandial glucose levels were observed. The estimated mean differences (intervention vs. control group) were: 4.9 mg/dl, 98.4 %CI -7.2-17.1 (breakfast); -4.5 mg/dl, 98.4 %CI -15.1-6.0 (lunch); -3.8 mg/dl, 98.4 %CI -15.9 to 8.4 (dinner). OGTT levels at 60 and 120 min. were associated with glucose levels after breakfast. CONCLUSION: In conclusion, no significant differences in blood glucose levels were observed between the groups and therefore major effects of chewing on hyperglycaemia in women with GDM could be excluded. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03961542, Date of registration: 20.01.2019. Retrospectively registered.

Trajectories of Fetal Adipose Tissue Thickness in Pregnancies After Gastric Bypass Surgery.

PURPOSE: Recent studies showed that women after surgery are at higher risk of delivering small-for-gestational infants. Thus, this study aims to investigate longitudinal changes of fetal subcutaneous adipose tissue thickness (FSCTT) of fetuses conceived after gastric bypass surgery as compared to BMI-matched controls. METHODS: Retrospective cohort study measuring ultrasound-derived longitudinal trajectories of abdominal FSCTT in 41 singleton pregnancies after gastric bypass surgery compared to 41 BMI-matched controls and 64 obese mothers. RESULTS: FSCTT was significantly lower in fetuses of women after GB as compared to BMI-matched controls in the second (mean difference 1.38 mm, p < 0.001) and third trimester of gestation (mean difference 3.37 mm, p < 0.001). Longitudinal analysis revealed significant differences in mean FSCTT trajectories between offspring's in GB mothers, BMI-matched, or obese controls. The ratio of FSCTT and abdominal circumference remained constant in the BMI-matched control group whereas it significantly decreased in fetuses of women after GB. Despite remarkable differences were observed in longitudinally assessed FSCTT, further analyses in the GB subgroup revealed that FSCTT were not influenced by OGTT mean or 120 min glucose values, biochemically hypoglycemia, time since bariatric surgery, or weight loss since surgery. CONCLUSION: In fetuses of mothers with history of bariatric surgery, abdominal FSCTT was markedly reduced. While the underlying mechanisms are not fully understood, a multifactorial genesis including nutritional deficiencies and altered metabolism after bariatric surgery is assumed.

Intrauterine Fetal Growth Delay During Late Pregnancy After Maternal Gastric Bypass Surgery.

PURPOSE: To investigate intrauterine fetal growth development and birth anthropometry of fetuses conceived after maternal gastric bypass surgery. MATERIALS AND METHODS: Longitudinal cohort study describing longitudinal growth estimated by ultrasound on 43 singleton pregnancies after gastric bypass compared to 43 BMI-matched controls. RESULTS: In fetuses after maternal gastric bypass surgery, growth percentiles decreased markedly from the beginning of the second trimester until the end of the third trimester (decrease of 3.1 fetal abdomen circumference percentiles (95 %CI 0.9-5.3, p = 0.007) per four gestational weeks). While in the second trimester, fetal anthropometric measures did not differ between the groups, the mean abdomen circumference percentiles appeared significantly smaller during the third trimester in offspring of mothers after gastric bypass (mean difference 25.1 percentiles, p < 0.001). Similar tendencies have been observed in estimated fetal weight resulting in significantly more SGA offspring at delivery in the gastric bypass group. In children born after maternal gastric bypass surgery, weight percentiles (32.12th vs. 55.86th percentile, p < 0.001) as well as placental weight (525.2 g vs. 635.7 g, p < 0.001) were significantly reduced compared to controls. CONCLUSION: In fetuses conceived after maternal gastric bypass, intrauterine fetal growth distinctively declined in the second and third trimester, most prominently observed in fetal abdomen circumferences. Birth weight and placental weight at birth was significantly lower compared to BMI-matched controls, possibly due to altered maternal metabolic factors and comparable to mothers experiencing chronic hunger episodes.

Working-hour phenomenon in obstetrics is an attainable target to improve neonatal outcomes.

BACKGROUND: Giving birth in a health care facility does not guarantee high-quality care or favorable outcomes. The working-hour phenomenon describes adverse outcomes of institutional births outside regular working hours. OBJECTIVES: The objectives of the study were to evaluate whether the time of birth is associated with adverse neonatal outcomes and to identify the riskiest time periods for obstetrical care. STUDY DESIGN: This nationwide retrospective cohort study analyzed data from 2008 to 2016 from all 82 obstetric departments in Austria. Births at ≥ 23+0 gestational weeks with ≥500 g birthweight were included. Independent variables were categorized by the time of day vs night as core time (morning, day) and off hours (evening, nighttime periods 1-4). The composite primary outcome was adverse neonatal outcome, defined as arterial umbilical cord blood pH <7.2, 5 minute Apgar score <7, and/or admission to the neonatal intensive care unit. Multivariate logistic regression was used to develop a model to predict these adverse neonatal outcomes. RESULTS: Of 462,947 births, 227,672 (49.2%) occurred during off hours and had a comparable distribution in all maternity units, regardless of volume (<500 births per year: 50.3% during core time vs 49.7% during off hours; ≥500 births per year: 50.7% core time vs 49.3% off hours; perinatal tertiary center: 51.2% core time vs 48.8% off hours). Furthermore, most women (35.8-35.9%) gave birth between 2:00 and 5:59 am (night periods 3 and 4). After adjustment for covariates, we found that adverse neonatal outcomes also occurred more frequently during these night periods 3 and 4, in addition to the early morning period (night 3: odds ratio, 1.05; 95% confidence interval, 1.03-1.08; P < .001; night 4: odds ratio, 1.08; 95% confidence interval, 1.05-1.10; P < .001; early morning period: odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P < .001). The adjusted odds for adverse outcomes were lowest for births between 6:00 and 7:59 pm (odds ratio, 0.96; 95% confidence interval, 0.93-0.99; P = .006). CONCLUSION: There is an increased risk of adverse neonatal outcomes when giving birth between 2:00 and 7:59 am. The so-called working-hour phenomenon is an attainable target to improve neonatal outcomes. Health care providers should ensure an optimal organizational framework during this time period.

Fetal weight estimation at term - ultrasound versus clinical examination with Leopold's manoeuvres: a prospective blinded observational study.

BACKGROUND: Fetal weight estimation is of key importance in the decision-making process for obstetric planning and management. The literature is inconsistent on the accuracy of measurements with either ultrasound or clinical examination, known as Leopold's manoeuvres, shortly before term. Maternal BMI is a confounding factor because it is associated with both the fetal weight and the accuracy of fetal weight estimation. The aim of our study was to compare the accuracy of fetal weight estimation performed with ultrasound and with clinical examination with respect to BMI. METHODS: In this prospective blinded observational study we investigated the accuracy of clinical examination as compared to ultrasound measurement in fetal weight estimation, taking the actual birth weight as the gold standard. In a cohort of all consecutive patients who presented in our department from January 2016 to May 2017 to register for delivery at ≥37 weeks, examination was done by ultrasound and Leopold's manoeuvres to estimate fetal weight. All examiners (midwives and physicians) had about the same level of professional experience. The primary aim was to compare overall absolute error, overall absolute percent error, absolute percent error > 10% and absolute percent error > 20% for weight estimation by ultrasound and by means of Leopold's manoeuvres versus the actual birth weight as the given gold standard, namely separately for normal weight and for overweight pregnant women. RESULTS: Five hundred forty-three patients were included in the data analysis. The accuracy of fetal weight estimation was significantly better with ultrasound than with Leopold's manoeuvres in all absolute error calculations made in overweight pregnant women. For all error calculations performed in normal weight pregnant women, no statistically significant difference was seen in the accuracy of fetal weight estimation between ultrasound and Leopold's manoeuvres. CONCLUSIONS: Data from our prospective blinded observational study show a significantly better accuracy of ultrasound for fetal weight estimation in overweight pregnant women only as compared to Leopold's manoeuvres with a significant difference in absolute error. We did not observe significantly better accuracy of ultrasound as compared to Leopold's manoeuvres in normal weight women. Further research is needed to analyse the situation in normal weight women.

Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction?

BACKGROUND: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication. METHODS: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15⁺6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery. RESULTS: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%). CONCLUSION: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.

Value of increased nuchal translucency in the era of noninvasive prenatal testing with cell-free DNA.

OBJECTIVE: To assess the value of increased nuchal translucency (NT) at first-trimester screening (FTS) despite the superiority of noninvasive prenatal testing with cell-free DNA (cfDNA) for the detection of fetal aneuploidies. METHODS: Retrospective analysis of all FTS data from 2005 to 2015 in our department. Only cases with increased NT and euploid karyotype were considered eligible for inclusion. Abnormal findings, diagnostic work-up, and perinatal outcomes were assessed. RESULTS: Of 18 084 FTS results, 460 (2.5%) showed increased fetal NT, of which 242 (52.6%) underwent invasive karyotyping and 179 (74.0%) had an aneuploidy. Of the remaining 63 cases, 61 (96.8%) showed an additional sonographic finding at FTS and25 (78.1%) had a major anomaly at the second trimester organ scan. The outcome was termination of pregnancy in 28 (44.4%) cases, fetal demise in 5 (7.9%), delivery of an infant with malformation in 21 (33.3%), and delivery of a healthy infant in 7 (11.1%) cases. CONCLUSION: All cases with increased NT would have been detected by cfDNA or by a major sonographic anomaly not later than the second trimester. Routine use of cfDNA, a basic sonogram, and an organ scan could reduce unnecessary work-up and anxiety.

Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of Roux-en-Y gastric bypass operation.

BACKGROUND: The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB. METHODS: In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using 1H-magnetic resonance spectroscopy (1H-MRS). RESULTS: RYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ±â€¯1.1% vs. 0.1 ±â€¯0.2% in the OB and vs. 0.8 ±â€¯0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ±â€¯5.22% vs.5.68 ±â€¯4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group. CONCLUSION: GLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved.

Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome.

Bariatric surgery (BS) is regarded to be the most effective treatment of obesity with long lasting beneficial effects including weight loss and improvement of metabolic disorders. A considerable number of women undergoing BS are at childbearing age.Although the surgery mediated weight loss has a positive effect on pregnancy outcome, the procedures might be associated with adverse outcomes as well, for example micronutrient deficiencies, iron or B12 deficiency anemia, dumping syndrome, surgical complications such as internal hernias, and small for gestational age (SGA) offspring, possibly due to maternal undernutrition. Also, there is no international consensus concerning the ideal time to conception after BS. Hence, the present narrative review intents to summarize the available literature concerning the most common challenges which arise before and during pregnancy after BS, such as fertility related considerations, vitamin and nutritional deficiencies and their adequate compensation through supplementation, altered glucose metabolism and its implications for gestational diabetes screening, the symptoms and treatment of dumping syndrome, surgical complications and the impact of BS on pregnancy outcome. The impact of different bariatric procedures on pregnancy and fetal outcome will also be discussed, as well as general considerations concerning the monitoring and management of pregnancies after BS.Whereas BS leads to the mitigation of many obesity-related pregnancy complications, such as gestational diabetes mellitus (GDM), pregnancy induced hypertension and fetal macrosomia; those procedures pose new risks which might lead to adverse outcomes for mothers and offspring, for example nutritional deficiencies, anemia, altered maternal glucose metabolism and small for gestational age children.