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Background: Pregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes. Studies assessing interventions to improve maternal and infant outcomes have increased exponentially over recent years. Several outcomes in this field of maternal diabetes are rare, making it difficult to synthesise evidence. Objectives: To collect outcomes reported in studies assessing treatment interventions in pregnant women with PGDM. Search strategy: CENTRAL, Web of Science, Medline, CINAHL, Embase and ClinicalTrials.gov from their inception until 27 January 2020. Selection criteria: Any randomised controlled trial assessing treatment interventions in pregnant women with PGDM reported in English. Data collection and analysis: Two independent reviewers assessed the suitability of articles and retrieved the data. Outcomes extracted from the literature were broadly categorised into maternal, fetal/infant or other outcomes by the study advisory group. Main results: Sixty‐seven of the 1475 studies identified fulfilled the inclusion criteria. The median number of outcomes reported per study was 15 (range 1–46). The majority of studies were from North America and Europe. Insulin and metformin were the most commonly investigated pharmacological interventions. Glucose monitoring was the most assessed technological intervention. In all, 131 unique outcomes were extracted: maternal (n = 69), fetal/infant (n = 61) and other (n = 1). Conclusions: Outcome reporting in treatment interventions trials of pregnant women with PGDM is varied, making it difficult to synthesise evidence, especially for rare outcomes. Systems are needed to standardise outcome reporting in future clinical trials and so facilitate evidence synthesis in this area of maternal diabetes. Registration: The systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020173549). Outcome reporting is heterogeneous in intervention trials of pregnant women with diabetes existing before pregnancy. Outcome reporting is heterogeneous in intervention trials of pregnant women with diabetes existing before pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: This is a protocol for a Cochrane Review (prototype). The objectives are as follows: Main objective To assess the effects of alcohol consumption on the progression to symptomatic (stage C) heart failure in people at risk for heart failure (stage A) or in people with pre-heart failure (stage B). Secondary objectives To assess the effects of alcohol consumption on progression of left ventricular dysfunction in people with stage A or stage B heart failure. We will assess the effect of alcohol consumption on the development of heart failure with reduced ejection fraction, mildly reduced ejection fraction, and preserved ejection fraction. We also aim to evaluate the effects of alcohol consumption on the development of symptomatic (stage C) heart failure over the short, medium and long term., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain., Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38., Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria., Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care., Main Outcomes and Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38., Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7., Conclusion and Relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Aims: Gestational diabetes (GDM) is associated with the development of postpartum (PP) glucose intolerance. Plasma glycated CD59 (pGCD59) is an emerging biomarker for the detection of hyperglycaemia. The aim of this study was to assess the ability of PP pGCD59 to predict the development of PP GI as defined by the 2 h 75 g OGTT using the ADA criteria, in a cohort of women diagnosed with prior GDM in the index pregnancy using the 2 h 75 g OGTT at 24-28 weeks of gestation according to the World Health Organization (WHO) 2013 criteria., Methods: Of the 2017 pregnant women recruited prospectively 140 women with gestational diabetes had samples for pGCD59 taken PP at the time of the OGTT. The ability of pGCD59 to predict the results of the PP OGTT was assessed using nonparametric receiver operating characteristic (ROC) curves., Results: Women with PP glucose intolerance had significantly higher PP pGCD59 levels compared to women with normal glucose tolerance PP (3.8 vs. 2.7 SPU). PP pGCD59 identified women who developed glucose intolerance PP with an AUC of 0.80 (95% CI: 0.70-0.91). A PP pGCD59 cut-off value of 1.9 SPU generated a sensitivity of 100% (95% CI: 83.9-100), specificity of 16.9% (95% CI: 9.8-26.3), positive predictive value of 22.1% (95% CI: 21.0-22.6), and negative predictive value of 100% (95% CI: 87.4-100). PP fasting plasma glucose generated an AUC of 0.96 (95% CI: 0.89-0.99) for the identification of PP glucose intolerance., Conclusion: Our study found that PP pGCD9 may be a promising biomarker to identify women not requiring PP glucose intolerance screening using the traditional OGTT. While the diagnostic accuracy of pGCD59 is good, fasting plasma glucose remains a better test for the identification of PP glucose intolerance., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: Even though most pregnancies are uneventful, occasionally complications do occur. Gestational diabetes is linked to an increased risk of adverse pregnancy outcomes. Early identification of women at risk of experiencing adverse outcomes, ideally through a single blood test, would facilitate early intervention. Plasma glycated CD59 (pGCD59) is an emerging biomarker which has shown promise in identifying hyperglycaemia during pregnancy and has been associated with the risk of delivering an LGA infant. The aim of this study was to explore the ability of the first- and second-trimester pGCD59 to predict adverse pregnancy outcomes., Methods: This was a prospective study of 378 pregnant women. Samples for pGCD59 were taken at the first antenatal visit and at the time of the 2 h 75 g OGTT (24-28 weeks of gestation). Adjusted receiver operating characteristic curves were used to evaluate the ability of pGCD59 to predict maternal and neonatal outcomes., Results: First-trimester pGCD59 levels were higher in women with gestational diabetes who delivered a macrosomic infant (4.2 ± 0.7 vs. 3.5 ± 1.0 SPU, p < 0.01) or an LGA infant (4.3 ± 0.3 vs. 3.6 ± 1.0 SPU, p = 0.01) compared to women with GDM that did not experience these outcomes. Second-trimester pGCD59 levels were higher in women that developed polyhydramnios (2.9 ± 0.4 vs. 2.5 ± 1.1 SPU, p = 0.03). First- and second-trimester pGCD59 predicted pregnancy-induced hypertension with good accuracy (AUC:0.85, 95%CI:0.78-0.91; AUC: 0.80, 95%CI: 0.73-0.88, respectively) and neonatal hypoglycaemia with fair to good accuracy (AUC:0.77, 95%CI: 0.54-0.99, AUC:0.81, 95%CI:0.62-0.99)., Conclusions: This study has shown that pGCD59 has the potential to predict adverse pregnancy outcomes. Prospective studies with a larger number of cases are necessary to fully explore and validate the potential of this emerging biomarker in predicting adverse pregnancy outcomes., (© 2022. The Author(s).)

Context: Neonatal hypoglycaemia (NH) is the most common metabolic problem in infants born of mothers with gestational diabetes. Plasma glycated CD59 (pGCD59) is an emerging biomarker that has shown potential in identifying women at risk of developing gestational diabetes. The aim of this study was to assess the association between early maternal levels of pGCD59 and NH., Objective: The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycemia (NH)., Methods: This is an observational study of pregnant women with a prepregnancy body mass index (BMI) greater than or equal to 29 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59 were measured in fasting maternal samples taken at the time of a 75-g, 2-hour oral glucose tolerance test performed in early pregnancy (< 20 weeks). NH, the study outcome, was defined as a heel-prick capillary glucose level of less than 2.6 mmol/L within 48 hours of delivery., Results: We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy were positively associated with the prevalence of NH (one-way analysis of variance, P < .001). The odds of NH were higher in infants from mothers in tertile 3 of pGCD59 levels compared to those from mothers in tertile 1 (odds ratio [OR]: 2.41; 95% CI, 1.03-5.63). However, this was attenuated when adjusted for maternal BMI (OR: 2.28; 95% CI, 0.96-5.43). The cross-validated area under the curve (AUC) was 0.64 (95% CI, 0.54-0.74), and adjusted for maternal BMI, age, and ethnicity, the AUC was 0.70 (95% CI, 0.56-0.78)., Conclusion: Although pGCD59 levels in early pregnancy in women with BMI greater than or equal to 29 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Pregnancy induces physiological changes which affect biochemical and haematological parameters. As the significance of laboratory test results change throughout pregnancy, the reference interval (RI) or key result interpretive guide should be specific to pregnancy. This study sought to establish trimester-specific-RIs for routine biochemical and haematological tests in healthy white European women with singleton pregnancies with comparison to RIs for non-pregnant European adults., Methods: A retrospective analysis of a prospective longitudinal single-centre study of healthy pregnant women conducted between November 2018 and December 2020 in a tertiary academic hospital with approximately 3000 births annually. Inclusion criteria: signed informed consent, age ≥18 years, white European, body mass index (BMI) <25 kg/m2, blood pressure <140/90mmHg, non-smoker, no previous pathology or gestational diabetes. Trimester defined as T1: up to 13 weeks + 6 days, T2: 14-27 weeks + 6 days and T3: ≥28-41 weeks + 6 days. Baseline demographics, anthropometric and laboratory measurements were recorded. In total, 31 biochemical and 10 haematological ISO15189:2012 accredited tests were measured using Roche Cobas® and Sysmex XN-9100™ analysers, respectively. RIs were established according to the International Federation of Clinical Chemistry (IFCC) recommended method., Results: Apparently healthy pregnant women ( n = 124) with bio-banked serum samples in each trimester were recruited. At the booking visit, 49.2% ( n = 61) of participants were nulliparous, with median age of 34.4 (IQR: 31.3-37.3) years, gestational age of 89 (IQR: 84-93) days, BMI of 22.5 (IQR: 21.0-23.7) kg/m 2 and systolic and diastolic blood pressure of 116 (110-125) mmHg and 67 (61-75) mmHg, respectively., Conclusions: Normative trimester-specific biological intervals for routinely requested biochemical and haematological medical laboratory tests were established. These RIs will be invaluable to result interpretation and the management of pregnant women.

Aims: To evaluate the ability of first trimester plasma glycated CD59 (pGCD59) to predict gestational diabetes mellitus (GDM) at 24-28 weeks of gestation., Methods: Prospectively, in 378 pregnant women, GDM was diagnosed using the one step 2 h 75 g oral glucose tolerance test adjudicated by the World Health Organisation (WHO) 2013 criteria. The ability of pGCD59 to predict GDM was assessed using receiver operating characteristic (ROC) curves adjusted for maternal age, body mass index (BMI), maternal ethnicity, parity, previous GDM, family history of diabetes mellitus and week of gestation at time of pGCD59 sampling., Results: pGCD59 generated an adjusted area under the curve (AUC) of (a) 0.63 (95 %CI:0.56-0.70, p < 0.001) for predicting GDM, and (b) 0.71 (95 %CI:0.62-0.79, p < 0.001 for GDM diagnosed with a fasting plasma glucose (FPG) ≥ 5.1 mmol/L. Sensitivity analysis of BMI subgroups showed that pGCD59 generated the highest AUC in the 35 kg/m 2  ≤ BMI < 40 kg/m 2 (AUC:0.85, 95 %CI:0.70-0.98) and BMI ≥ 40 kg/m 2 (AUC:0.88, 95 %CI:0.63-0.99) categories., Conclusions: Early in pregnancy, pGCD59 may be a good predictor of GDM in women with a high BMI and a fair predictor of GDM diagnosed by an elevated FPG independent of BMI., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JAH has a financial interest in Mellitus LLC. Mellitus has licensed intellectual property for the technology used in this research and in developing diagnostic tools for diabetes. The interests of J.A.H. are reviewed and are managed by Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. Reagents and laboratory analysis for pGCD59 were provided by Prof Jose Halperin., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the ability of second trimester plasma glycated CD59 (pGCD59), a novel biomarker, to predict the results of the 2 h 75 g oral glucose tolerance test at 24−28 weeks of gestation, employing the 2013 World Health Organisation criteria. This was a prospective study of 378 pregnant women. The ability of pGCD59 to predict gestational diabetes (GDM) was assessed using adjusted ROC curves for maternal age, BMI, maternal ethnicity, parity, previous GDM, and family history of diabetes. The pGCD59 levels were significantly higher in women with GDM compared to women with normal glucose tolerance (p = 0.003). The pGCD59 generated an adjusted AUC for identifying GDM cases of 0.65 (95%CI: 0.58−0.71, p < 0.001). The pGCD59 predicted GDM status diagnosed by a fasting glucose value of 5.1 mmol/L with an adjusted AUC of 0.74 (95%CI: 0.65−0.81, p < 0.001). Analysis of BMI subgroups determined that pGCD59 generated the highest AUC in the 35 kg/m2 ≤ BMI < 40 kg/m2 (AUC: 0.84 95%CI: 0.69−0.98) and BMI ≥ 40 kg/m2 (AUC: 0.96 95%CI: 0.86−0.99) categories. This study found that second trimester pGCD59 is a fair predictor of GDM status diagnosed by elevated fasting glucose independent of BMI and an excellent predictor of GDM in subjects with a very high BMI.

Introduction: Diabetes mellitus is the most common metabolic complication of pregnancy and its prevalence worldwide is rising. The number of randomised controlled trials (RCTs) being conducted in people with diabetes is also increasing. Many studies preferentially publish findings on clinical endpoints and do not report patient-reported outcomes (PROs). In studies that do include PROs, PRO reporting is often of poor quality., Methods: We will conduct this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using a combination of medical subject headings and keywords (combined using Boolean operators), we will search web-based databases (PubMed, Cochrane and EMBASE) for RCTs published in English between 2013 and 2021. Two reviewers will review titles and abstracts. We will review the full texts of any relevant abstracts and extract the following data: date of publication or recruitment period, journal of publication, country of study, multicentre or single centre, population and number of participants, type of intervention, frequency of PRO assessment and type of PRO (or PRO measurement) used. We will also record if the PRO was a primary, secondary or exploratory outcome. We will exclude reviews, observational studies, unpublished data for example, conference abstracts and trial protocols. Any published RCT that includes data on a PRO as a primary or secondary outcome will then be compared against the Consolidated Standards of Reporting Trials-Patient-Reported Outcome extension checklist, a structured and approved framework for the publication of results of PROs., Ethics and Dissemination: Ethical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 24 March 2021 (CA 2592). We aim to publish our findings in a peer-reviewed journal and present our findings at national and international conferences., Systematic Review Registration: This systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42021234917., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)