Stillbirth in women with Type 1 Diabetes mellitus-still a current topic.

PURPOSE: Compared to the general stillbirth rate in Germany for term deliveries of 0.12% the risk in type 1 diabetes mellitus is reported to be up to ten times higher. The reasons for this excess risk of intrauterine demise are still not fully elucidated. Risk factors named in the literature include poor glycemic control before and during pregnancy and the occurrence of ketoacidosis. Additionally there might be a diabetes related type of placental dysfunction leading to organ failure in late pregnancy. Understanding the underlying causes is mandatory to develop strategies to reduce the incidences. The Purpose of this publication is to point out the difficulties in prediction of intrauterine death in pregnant type 1 diabetes patients and thus emphasizing the necessity of constant awareness to all caregivers. METHODS: We present a case series of four cases of stillbirth that occurred in patients with type 1 diabetes mellitus at our tertiary care obstetric unit during a five-year period. RESULTS: In all four presented cases the underlying cause of intrauterine demise was different and we could not find a common mechanism or risk profile. Furthermore, established monitoring tools did not become peculiar to raise awareness. We compared our cases to published data. Underlying causes of intrauterine death in type 1 diabetes are discussed in the light of the current literature. CONCLUSIONS: The main risk factors of stillbirth in diabetic pregnancies are high maternal blood glucose levels including pre-conceptional HbA1c and diabetic ketoacidosis. Late acute placental insufficiency are associated with intrauterine death in type 1 diabetes. Despite the elevated risk of near term intrauterine demise there are currently no guidelines on how to monitor pregnancies in type 1 diabetes for fetal distress during the third trimester. Established thresholds for fetal Doppler data indicating fetal distress in normal and growth restricted fetuses may not be applicable for overgrown fetuses. Future research on how to monitor the diabetic fetus needs to be initiated.

Design, rationale and protocol for Glycemic Observation and Metabolic Outcomes in Mothers and Offspring (GO MOMs): an observational cohort study.

INTRODUCTION: Given the increasing prevalence of both obesity and pre-diabetes in pregnant adults, there is growing interest in identifying hyperglycaemia in early pregnancy to optimise maternal and perinatal outcomes. Multiple organisations recommend first-trimester diabetes screening for individuals with risk factors; however, the benefits and drawbacks of detecting glucose abnormalities more mild than overt diabetes in early gestation and the best screening method to detect such abnormalities remain unclear. METHODS AND ANALYSIS: The goal of the Glycemic Observation and Metabolic Outcomes in Mothers and Offspring study (GO MOMs) is to evaluate how early pregnancy glycaemia, measured using continuous glucose monitoring and oral glucose tolerance testing, relates to the diagnosis of gestational diabetes (GDM) at 24-28 weeks' gestation (maternal primary outcome) and large-for-gestational-age birth weight (newborn primary outcome). Secondary objectives include relating early pregnancy glycaemia to other adverse pregnancy outcomes and comprehensively detailing longitudinal changes in glucose over the course of pregnancy. GO MOMs enrolment began in April 2021 and will continue for 3.5 years with a target sample size of 2150 participants. ETHICS AND DISSEMINATION: GO MOMs is centrally overseen by Vanderbilt University's Institutional Review Board and an Observational Study Monitoring Board appointed by National Institute of Diabetes and Digestive and Kidney Diseases. GO MOMs has potential to yield data that will improve understanding of hyperglycaemia in pregnancy, elucidate better approaches for early pregnancy GDM screening, and inform future clinical trials of early GDM treatment. TRIAL REGISTRATION NUMBER: NCT04860336.

Digital therapeutics-based lifestyle intervention for gestational diabetes mellitus prevention of high-risk pregnant women: a study protocol for a non-randomised controlled trial.

INTRODUCTION: Digital therapeutics have been approved as a treatment aid for various medical conditions and are increasingly prevalent. Despite numerous studies on the potential of digital therapeutic interventions in preventing gestational diabetes mellitus (GDM), there is a critical need for more high-quality, large-scale studies to validate their effectiveness. This need arises from the inconsistencies in results and variations in the quality of previous research. METHODS AND ANALYSIS: We propose a non-randomised controlled trial involving 800 high-risk pregnant women in 6 maternity and child health hospitals in Fujian, China. This study aims to investigate the role and effectiveness of digital therapeutics-based lifestyle intervention in managing the health of pregnant women at high risk for GDM. The study will compare the differences in GDM prevalence, pregnancy weight management and other pregnancy-related health outcomes between pregnant women who received digital therapeutics-based lifestyle intervention and those in the control group. The intervention includes dietary guidance, a personalised physical activity programme and lifestyle improvement strategies delivered through a smartphone app. Primary outcomes include the incidence of GDM at 24-28 weeks gestation and gestational weight gain (GWG). Secondary outcomes comprise improvements in individual lifestyle and risk factors, nutritional issues, implementation outcomes and other pregnancy-related outcomes. ETHICS AND DISSEMINATION SECTION: The trial was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital (approval number: 2023KY046), Jianyang Maternity and Child Health Hospital (approval number: A202401), Fuqing Maternity and Child Health Hospital (approval number: FY2024003), Changting Maternity and Child Health Hospital (approval number: 202401), Datian Maternity and Child Health Hospital (approval number: dtfy202401) and Quanzhou Maternity and Child Health Hospital (approval number: 2024(50)). We will disseminate our findings by publishing articles in leading peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300071496.

Supporting healthy lifestyles for First Nations women and communities through co-design: lessons and early findings from remote Northern Australia.

Background: The period before, during, and after pregnancy presents an opportunity to reduce diabetes-related risks, which in Australia disproportionately impact Aboriginal and Torres Strait Islander women. Collaboration with Aboriginal and Torres Strait Islander women/communities is essential to ensure acceptability and sustainability of lifestyle modifications. Using a novel co-design approach, we aimed to identify shared priorities and potential lifestyle strategies. We also reflected on learnings from this approach. Methods: We conducted 11 workshops and 8 interviews at two sites in Australia's Northern Territory (Central Australia and Top End), using experience-based co-design (EBCD) and incorporating principles of First Nations participatory research. Workshops/interviews explored participant' experiences and understanding of diabetes in pregnancy, contextual issues, and potential lifestyle strategies. Participants included three groups: 1) Aboriginal and Torres Strait Islander women of reproductive age (defined as aged 16-45 years); 2) Aboriginal and Torres Strait Islander community members; and 3) health/community services professionals. The study methodology sought to amplify the voices of Aboriginal women. Findings: Participants included 23 women between ages 16-45 years (9 with known lived experience of diabetes in pregnancy), 5 community members and 23 health professionals. Key findings related to identified priority issues, strategies to address priorities, and reflections on use of EBCD methodology. Priorities were largely consistent across study regions: access to healthy foods and physical activity; connection to traditional practices and culture; communication regarding diabetes and related risks; and the difficulty for women of prioritising their health among competing priorities. Strategies included implementation of a holistic women's program in Central Australia, while Top End participants expressed the desire to improve nutrition, peer support and community awareness of diabetes. EBCD provided a useful structure to explore participants' experiences and collectively determine priorities, while allowing for modifications to ensure co-design methods were contextually appropriate. Challenges included the resource-intensive nature of stakeholder engagement, and collaborating effectively with services and communities when researchers were "outsiders". Conclusions: A hybrid methodology using EBCD and First Nations participatory research principles enabled collaboration between Aboriginal women, communities and health services to identify shared priorities and solutions to reduce diabetes-related health risks. Genuine co-design processes support self-determination and enhance acceptability and sustainability of health strategies.

Antenatal Corticosteroids and Their Effects on Maternal Glycemic Status: A Prospective Observational Study From an Indian Tertiary Referral Center.

Background Antenatal corticosteroids prevent multiple fetal complications and improve overall neonatal survival but at the cost of adverse effects including maternal hyperglycemia. This study aimed to understand the effect of antenatal corticosteroids on maternal glycemic control. Methodology This prospective observational study included 93 pregnant women with singleton pregnancies between 32 and 37 weeks gestation admitted for potential preterm labor. We assessed their glucose tolerance and categorized 56 participants with normal glucose tolerance in group 1, while 37 who had diabetes mellitus (DM) were categorized in group 2. Of the women with DM, 30 had gestational diabetes mellitus and seven had pre-existing type 2 diabetes. Betamethasone was administered as per the standard of care, two doses of 12 mg each, 24 hours apart. To assess the effect of corticosteroids on maternal blood glucose control, we monitored capillary blood glucose levels at specific time intervals for three days following the steroid administration. Fasting and post-meal glucose levels were checked a week after the administration of the steroid therapy, and it was observed that participants from group 1 had developed steroid-related hyperglycemia. Blood glucose levels ≥140 mg/dL were considered significant hyperglycemia, while blood glucose levels ≥160 mg/dL were considered severe hyperglycemia. Following this observation, we documented any modifications in the diabetes management plan during or after the corticosteroid treatment, including medical nutrition therapy, addition of oral anti-diabetic medications, commencement of insulin, or increasing insulin dosage. Standard software programs such as Microsoft Excel and SPSS (IBM Corp., Armonk, NY, USA) were used to analyze the collected data, summarize the findings, and identify any statistically significant relationships between the variables descriptive and inferential statistics, respectively. Results Participants from both groups demonstrated worsening glycemia requiring treatment involving insulin, following corticosteroid administration. The percentages of significant hyperglycemic participants from groups 1 and 2 were 72% and 92%, respectively. Severe hyperglycemia was seen in 43% and 84% of the participants from groups 1 and 2, respectively. An intervention involving insulin administration was required by group 2 participants with pre-existing diabetes within six hours of steroid administration, followed by those with gestational diabetes requiring intervention within 12-24 hours, and by group 1 participants at 24-48 hours. One week after the administration of antenatal corticosteroids, hyperglycemia persisted in 20 (35.71%) of the 56 participants in group 1, of which six (30%) participants required insulin therapy. On the other hand, 18 (48.64%) participants from group 2 required additional insulin therapy after a week of administration of steroids when compared to pre-steroid administration status. Conclusions The findings of this study demonstrate that antenatal betamethasone therapy resulted in worsening hyperglycemia in most pregnant women, regardless of pre-existing glycemic status. These findings highlight the need for close monitoring of blood glucose levels and potential adjustments to medication regimens following antenatal betamethasone administration, irrespective of the pre-existing glycemic status.

Shoulder dystocia in babies born to Aboriginal mothers with diabetes: a population-based cohort study, 1998-2015.

BACKGROUND: Australian Aboriginal and Torres Strait Islander women with diabetes in pregnancy (DIP) are more likely to have glycaemic levels above the target range, and their babies are thus at higher risk of excessive fetal growth. Shoulder dystocia, defined by failure of spontaneous birth of fetal shoulder after birth of the head requiring obstetric maneuvers, is an obstetric emergency that is strongly associated with DIP and fetal size. The aim of this study was to investigate the epidemiology of shoulder dystocia in Aboriginal babies born to mothers with DIP. METHODS: Stratifying by Aboriginal status, characteristics of births complicated by shoulder dystocia in women with and without DIP were compared and incidence and time-trends of shoulder dystocia were described. Compliance with guidelines aiming at preventing shoulder dystocia in women with DIP were compared. Post-logistic regression estimation was used to calculate the population attributable fractions (PAFs) for shoulder dystocia associated with DIP and to estimate probabilities of shoulder dystocia in babies born to mothers with DIP at birthweights > 3 kg. RESULTS: Rates of shoulder dystocia from vaginal births in Aboriginal babies born to mothers with DIP were double that of their non-Aboriginal counterparts (6.3% vs 3.2%, p < 0.001), with no improvement over time. Aboriginal mothers with diabetes whose pregnancies were complicated by shoulder dystocia were more likely to have a history of shoulder dystocia (13.1% vs 6.3%, p = 0.032). Rates of guideline-recommended elective caesarean section in pregnancies with diabetes and birthweight > 4.5 kg were lower in the Aboriginal women (28.6% vs 43.1%, p = 0.004). PAFs indicated that 13.4% (95% CI: 9.7%-16.9%) of shoulder dystocia cases in Aboriginal (2.7% (95% CI: 2.1%-3.4%) in non-Aboriginal) women were attributable to DIP. Probability of shoulder dystocia among babies born to Aboriginal mothers with DIP was higher at birthweights > 3 kg. CONCLUSIONS: Aboriginal mothers with DIP had a higher risk of shoulder dystocia and a stronger association between birthweight and shoulder dystocia. Many cases were recurrent. These factors should be considered in clinical practice and when counselling women.

Adverse pregnancy outcomes in gestational diabetes mellitus: a systematic review and meta-analysis protocol.

INTRODUCTION: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, including adverse outcomes for both the mother and the fetus. Different diagnostic criteria are used for GDM, and it is not clear how these affect the reported prevalence of adverse pregnancy outcomes. This protocol is for a systematic review to describe and compare the prevalence of adverse pregnancy outcomes in GDM using the different diagnostic criteria applied in various countries/regions of the world. METHODS AND ANALYSIS: A systematic review and meta-analysis will be carried out. A comprehensive search of observational studies that report the outcomes of interest to this review from 2010 to 2021 will be conducted. We will search the major electronic databases such as PubMed, Scopus, CINHAL and Google Scholar, and screen references of included studies for additional studies. Meta-analyses will be performed, if there is low heterogeneity, and pooled estimates per outcome reported. We will use the bias-adjusted inverse variance heterogeneity model and random effects models, depending on the heterogeneity observed, to pool prevalence estimates and perform subgroup analyses by region, by age group, by diagnostic criteria and by GDM screening method if sufficient data are available. We will also compare the prevalence of adverse outcomes by diagnostic method and report prevalence ratios. We will report 95% confidence estimates for all estimates. ETHICS AND DISSEMINATION: Ethical approval is not required as the review uses published data. Findings will be published in peer-reviewed journals and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42020155061.

Protocol for cost-effectiveness analysis of a randomised trial of mHealth coaching (Bump2Baby and Me) compared with usual care for healthy gestational weight gain and postnatal outcomes in at-risk women and their offspring in the UK, Australia, Ireland and Spain.

INTRODUCTION: Gestational diabetes mellitus and overweight are associated with an increased likelihood of complications during birth and for the newborn baby. These complications lead to increased immediate and long-term healthcare costs as well as reduced health and well-being in women and infants. This protocol presents the health economic evaluation to investigate the cost-effectiveness of Bump2Baby and Me (B2B&Me), which is a health coaching intervention delivered via smartphone to women at risk of gestational diabetes. METHODS AND ANALYSIS: Using data from the B2B&Me randomised controlled trial, this economic evaluation compares costs and health effects between the intervention and control group as an incremental cost-effectiveness ratio. Direct healthcare costs, costs of pharmaceuticals and intervention costs will be included in the analysis, body weight and quality-adjusted life-years for the mother will serve as the effect outcomes. To investigate the long-term cost-effectiveness of the trial, a Markov model will be employed. Deterministic and probabilistic sensitivity analysis will be employed. ETHICS AND DISSEMINATION: The National Maternity Hospital Human Research and Ethics Committee was the primary approval site (EC18.2020) with approvals from University College Dublin HREC-Sciences (LS-E-20-150-OReilly), Junta de Andalucia CEIM/CEI Provincial de Granada (2087-M1-22), Monash Health HREC (RES-20-0000-892A) and National Health Service Health Research Authority and Health and Care Research Wales (HCRW) (21/WA/0022). The results from the analysis will be disseminated in scientific papers, through conference presentations and through different channels for communication within the project. TRIAL REGISTRATION NUMBER: ACTRN12620001240932.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) - a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health.

PURPOSE: Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health. PARTICIPANTS: Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols. FINDINGS TO DATE: We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight. FUTURE PLANS: Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.

Cost-effectiveness of a complex continuum of care intervention targeting women and children: protocol for an economic evaluation of the Bukhali trial in South Africa.

INTRODUCTION: As nearly two-thirds of women presenting at their first antenatal visit are either overweight or obese in urban South Africa, the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and non-communicable diseases. This protocol describes the planned economic evaluation of an individually randomised controlled trial of a complex continuum of care intervention targeting women and children in Soweto, South Africa (Bukhali trial). METHODS AND ANALYSIS: The economic evaluation of the Bukhali trial will be conducted as a within-trial analysis from both provider and societal perspectives. Incremental costs and health outcomes of the continuum of care intervention will be compared with standard care. The economic impact on implementing agencies (programme costs), healthcare providers, participants and their households will be estimated. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of child adiposity at age years averted. Additionally, ICERs will also be reported in terms of cost per quality-adjusted life year gained. If Bukhali demonstrates effectiveness, we will employ a decision analytical model to examine the cost-effectiveness of the intervention over a child's lifetime. A Markov model will be used to estimate long-term health benefits, healthcare costs and cost-effectiveness. Probabilistic sensitivity analyses will be conducted to explore uncertainty and ensure robust results. An analysis will be conducted to assess the equity impact of the intervention, by comparing intervention impact within quintiles of socioeconomic status. ETHICS AND DISSEMINATION: The Bukhali trial economic evaluation has ethical approval from the Human Ethics Research Committee of the University of the Witwatersrand, Johannesburg, South Africa (M240162). The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference. TRIAL REGISTRATION NUMBER: Pan African Clinical Trials Registry (PACTR201903750173871; https://pactr.samrc.ac.za).

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services.

OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN: This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING: Data were collected from the databases of six Teratology Information Services. PARTICIPANTS: This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS: Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS: This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes-a prospective cohort study in Shanghai.

OBJECTIVES: The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs). DESIGN: This was a prospective cohort study. SETTING: This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China. PRIMARY AND SECONDARY OUTCOME MEASURES: A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model. RESULTS: The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP. CONCLUSIONS: As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

Effectiveness of metformin to pregnant women with PCOS to reduce spontaneous abortion and gestational diabetes mellitus: a protocol for an overview of reviews.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a globally prevalent endocrinological disorder and has been associated with poor pregnancy outcomes, including a higher rate of gestational diabetes and miscarriage. Metformin is among the drugs investigated to improve the prognosis of pregnant women with PCOS. OBJECTIVE: To conduct an overview of systematic reviews examining the effects of metformin versus placebo or no intervention throughout pregnancy among pregnant women with a preconception PCOS diagnosis to reduce the incidence of miscarriage and gestational diabetes. METHODS AND ANALYSIS: We will perform an overview of systematic reviews by searching Embase, PubMed, Virtual Health Library, Cochrane Central Register of Controlled Trials, Trip Database, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature from inception to 17 August 2023. Language, publication status and year indexed or published filters will not be applied. Two reviewers will independently screen and select papers, assess their quality, evaluate their risk of bias and collect the data. The included reviews will be summarised narratively. The quality and risk of bias of the systematic review and meta-analysis studies included will be assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Second Version) and ROBIS (Risk of Bias in Systematic Reviews), respectively. ETHICS AND DISSEMINATION: This overview of reviews will analyse data from systematic reviews on the use of metformin for prepregnancy diagnosis of PCOS to reduce adverse outcomes. As there will be no primary data collection, a formal ethical analysis is unnecessary. The study outcomes will be submitted to a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42023441488.

Accuracy of intermittently scanned continuous glucose monitoring during caesarean delivery in pregnant women with insulin-treated diabetes.

AIM: Continuous Glucose Monitoring (CGM) systems are not currently recommended to guide intrapartum glucose and insulin infusion, due to insufficient data. In this study, intrapartum accuracy of intermittently scanned CGM (isCGM), compared to simultaneously measured capillary glucose (CG), was evaluated. METHODS: Paired isCGM (Freestyle Libre 2) - CG data during caesarean delivery in pregnant women with insulin-treated diabetes were prospectively collected. The isCGM accuracy was assessed by MARD and Clarke Error Grid analysis. Moreover, the impact on intrapartum management was evaluated. RESULTS: Sixty-eight paired isCGM-CG data of 19 women were evaluated. The overallMARD was 9.28 %. All values were in A and B zones of Clarke Error Grid. Forty-six (68 %) isCGM-CG pairs were in the same glycemic range, meaning the same intrapartum management. All discordant data were identified by checking CG in case of isCGM above 110 mg/dL or less than 70 mg/dL [chi-square 21.76, p < 0.001]. At ROC curve, isCGM above 110 mg/dL was associated with 100 % sensitivity to discordant result at CG (AUC 0.859, p < 0.001). CONCLUSION: The accuracy of isCGM during caesarean delivery was good, particularly for glucose values between 70 and 110 mg/dL, when CG confirmation could be safely avoided.

Case report: Glycaemic management and pregnancy outcomes in a woman with an insulin receptor mutation, p.Met1180Lys.

BACKGROUND: Heterozygous insulin receptor mutations (INSR) are associated with insulin resistance, hyperglycaemia and hyperinsulinaemic hypoglycaemia in addition to hyperandrogenism and oligomenorrhoea in women. Numerous autosomal dominant heterozygous mutations involving the INSR ß-subunit tyrosine kinase domain resulting in type A insulin resistance have been previously described. We describe the phenotype, obstetric management and neonatal outcomes in a woman with type A insulin resistance caused by a mutation in the ß-subunit of the INSR. CASE PRESENTATION: We describe a woman with a p.Met1180Lys mutation who presents with hirsutism, oligomenorrhoea and diabetes at age 20. She has autoimmune thyroid disease, Coeliac disease and positive GAD antibodies. She is overweight with no features of acanthosis nigricans and is treated with metformin. She had 11 pregnancies treated with insulin monotherapy (n = 2) or combined metformin and insulin therapy (n = 9). The maximum insulin dose requirement was 134 units/day or 1.68 units/kg/day late in the second pregnancy. Mean birthweight was on the 37th centile in INSR positive offspring (n = 3) and the 94th centile in INSR negative offspring (n = 1). CONCLUSION: The p.Met1180Lys mutation results in a phenotype of diabetes, hirsutism and oligomenorrhoea. This woman had co-existent autoimmune disease. Her insulin dose requirements during pregnancy were similar to doses observed in women with type 2 diabetes. Metformin may be used to improve insulin sensitivity in women with this mutation. Offspring inheriting the mutation tended to be smaller for gestational age.

Insulin Sensitivity, Islet Cell Function, and Incretin Axis in Pregnant Women With and Without Gestational Diabetes Mellitus.

Introduction: The aim of this study was to compare insulin sensitivity, islet cell function, and incretin axes in pregnant subjects with GDM and normal healthy controls. Methods: Pregnant women at 24 to 28 weeks of gestation were subjected to a 75 g oral glucose tolerance test (OGTT). Samples for glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were collected at 0, 30, 60, and 120 min during the OGTT. The Matsuda index (MI) and insulin secretion and sensitivity index-2 (ISSI-2) were assessed. The glucagon suppression index (GSI) was calculated along with the area under the curve (AUC) for glucose, insulin, glucagon, GLP-1, and GIP. Results: A total of 48 pregnant women (25 GDM and 23 controls) were finally analysed. The MI and ISSI-2 were low in the GDM group [4.31 vs. 5.42; P = 0.04], [1.99 vs. 3.18, P ≤ 0.01] respectively). Total AUCglucagon was higher in the GDM group (7411.7 vs. 6320.1, P = 0.02). GSI30 was significantly lower in the GDM group (-62.6 vs. -24.7, P = 0.03). Fasting GLP-1 levels were low in GDM women (17.3 vs. 22.2, P = 0.04). The total AUCGLP-1 positively correlated with total GSI in the GDM group. Conclusion: Asian-Indian GDM women have high insulin insensitivity, islet cell dysfunction, and low fasting GLP-1. Incretin axis dysfunction plays a potential role in their islet cell dysfunction.

Association between prepregnancy body mass index or gestational weight gain and adverse pregnancy outcomes among Chinese women with gestational diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: The association between prepregnancy body mass index (BMI) or gestational weight gain (GWG) and adverse pregnancy outcomes among Chinese women with gestational diabetes mellitus (GDM) is unknown. This study aims to evaluate such association by synthesising the evidence. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Scopus, EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, Wangfang, and China Science and Technology Journal Database searched from inception to 11 August 2023. ELIGIBILITY CRITERIA: Prospective cohort studies, retrospective cohort studies and case-control studies estimating the relationship of abnormal prepregnancy BMI (including underweight, overweight or obesity) or inappropriate GWG (including excess GWG or insufficient GWG) with adverse pregnancy outcomes of interest were included. Outcomes included macrosomia, caesarean section, preterm birth, gestational hypertension, large for gestational age (LGA) and small for gestational age (SGA). DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies, extracted the data and assessed the risk of bias. OR estimate and its 95% CI were pooled using Stata software fixed-effect model. Subgroup analysis, meta-regression and sensitivity analysis were performed to ensure credibility of the results. RESULTS: Twenty-three studies (eighteen retrospective cohort studies, three prospective cohort studies and two case control studies) involving 57 013 Chinese women with GDM were identified. Meta-analysis results showed that compared with GDM women with normal weight, GDM women with underweight were at a higher risk of SGA (OR=1.79 (1.54 to 2.07), five studies involving 31 967 women); women with overweight had higher risks of macrosomia (OR=1.65 (1.49 to 1.82), eleven studies involving 41 683 women), caesarean section (OR=1.48 (1.38 to 1.59), ten studies involving 34 935 women), preterm birth (OR=1.27 (1.13 to 1.43), eight studies involving 38 295 women) and LGA (OR=1.73 (1.54 to 1.95), seven studies involving 31 342 women) and women with obesity had higher risks of macrosomia (OR=2.37 (2.04 to 2.76), eleven studies involving 41 683 women), caesarean section (OR=2.07 (1.84 to 2.32), nine studies involving 34 829 women), preterm birth (OR=1.31 (1.09 to 1.57), eight studies involving 38 295 women) and LGA (OR=2.63 (2.15 to 3.21), six studies involving 31 236 women). Regard to GWG, compared with Chinese GDM women with sufficient GWG, GDM women with excessive GWG had higher risks of macrosomia (OR=1.74 (1.58 to 1.92), twelve studies involving 40 966 women), caesarean section (OR=1.44 (1.36 to 1.53), nine studies involving 36 205 women) and LGA (OR=2.12 (1.96 to 2.29), twelve studies involving 42 342 women); women with insufficient GWG conversely had higher risks of preterm birth (OR=1.59 (1.45 to 1.74), nine studies involving 37 461 women) and SGA (OR=1.38 (1.27 to 1.51), ten studies involving 41 080 women). CONCLUSIONS: For Chinese women with GDM, abnormal prepregnancy BMI or inappropriate GWG were related to higher risks of many adverse pregnancy outcomes. Therefore, medical staff should pay more attention to the weight management of GDM women during pregnancy.

Manchester Intermittent Diet in Gestational Diabetes Acceptability Study (MIDDAS-GDM): a two-arm randomised feasibility protocol trial of an intermittent low-energy diet (ILED) in women with gestational diabetes and obesity in Greater Manchester.

INTRODUCTION: The prevalence of gestational diabetes mellitus (GDM) is rising in the UK and is associated with maternal and neonatal complications. National Institute for Health and Care Excellence guidance advises first-line management with healthy eating and physical activity which is only moderately effective for achieving glycaemic targets. Approximately 30% of women require medication with metformin and/or insulin. There is currently no strong evidence base for any particular dietary regimen to improve outcomes in GDM. Intermittent low-energy diets (ILEDs) are associated with improved glycaemic control and reduced insulin resistance in type 2 diabetes and could be a viable option in the management of GDM. This study aims to test the safety, feasibility and acceptability of an ILED intervention among women with GDM compared with best National Health Service (NHS) care. METHOD AND ANALYSIS: We aim to recruit 48 women with GDM diagnosed between 24 and 30 weeks gestation from antenatal clinics at Wythenshawe and St Mary's hospitals, Manchester Foundation Trust, over 13 months starting in November 2022. Participants will be randomised (1:1) to ILED (2 low-energy diet days/week of 1000 kcal and 5 days/week of the best NHS care healthy diet and physical activity advice) or best NHS care 7 days/week until delivery of their baby. Primary outcomes include uptake and retention of participants to the trial and adherence to both dietary interventions. Safety outcomes will include birth weight, gestational age at delivery, neonatal hypoglycaemic episodes requiring intervention, neonatal hyperbilirubinaemia, admission to special care baby unit or neonatal intensive care unit, stillbirths, the percentage of women with hypoglycaemic episodes requiring third-party assistance, and significant maternal ketonaemia (defined as ≥1.0 mmol/L). Secondary outcomes will assess the fidelity of delivery of the interventions, and qualitative analysis of participant and healthcare professionals' experiences of the diet. Exploratory outcomes include the number of women requiring metformin and/or insulin. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Cambridge East Research Ethics Committee (22/EE/0119). Findings will be disseminated via publication in peer-reviewed journals, conference presentations and shared with diabetes charitable bodies and organisations in the UK, such as Diabetes UK and the Association of British Clinical Diabetologists. TRIAL REGISTRATION NUMBER: NCT05344066.

Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study.

INTRODUCTION: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown. METHODS AND ANALYSIS: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT05124808.