Maternal glucose levels and future risk of developing cardiovascular disease: a systematic review and meta-analysis protocol.

INTRODUCTION: Hyperglycaemia during pregnancy has been considered as one of the risk factors for cardiovascular diseases (CVDs) among women. Although the evidence regarding the association between gestational diabetes mellitus (GDM) and subsequent CVD has been synthesised, there are no systematic reviews covering the evidence of the association among the non-GDM population. This systematic review and meta-analysis, therefore, aim to fill the gap by summarising existing evidence on the association between maternal glucose levels and the risk of future CVD in pregnant women with or without a diagnosis of GDM. METHODS AND ANALYSIS: This systematic review protocol was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. Comprehensive literature searches were performed in the following electronic databases: MEDLINE, EMBASE and CINAHL to identify relevant papers from inception to 31 December 2022. All observational studies (case-control studies, cohort studies and cross-sectional studies) will be included. Two reviewers will perform the abstract and full-text screening based on the eligibility criteria through Covidence. The Newcastle-Ottawa Scale will be used to assess the methodological quality of included studies. Statistical heterogeneity will be assessed by using the I2 test and Cochrane's Q test. If the included studies are found to be homogeneous, pooled estimates will be calculated and meta-analysis will be performed using Review Manager 5 (RevMan) software. Random effects will be used to determine weights for meta-analysis, if needed. Pre-specified subgroup analysis and sensitivity analysis will be performed, if needed. The study results will be presented in the sequence of main outcomes, secondary outcomes and important subgroup analysis for each type of glucose level separately. ETHICS AND DISSEMINATION: Given no original data will be collected, ethics approval is not applicable for this review. The results of this review will be disseminated by publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42022363037.

Indirect effects of the COVID-19 pandemic on risk of gestational diabetes and factors contributing to increased risk in a multiethnic population: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic has had indirect effects on pregnancy outcomes. There is limited data on the impact on gestational diabetes (GDM) in diverse populations and the possible underlying mediators. This study aimed to assess the risk of GDM pre-COVID-19 and in two distinct pandemic exposure periods, and to determine the potential factors contributing to increased risk in a multiethnic population. METHODS: A multicentre, retrospective cohort study was performed of women with singleton pregnancy receiving antenatal care at three hospitals two years pre-COVID-19 (January 2018 - January 2020), first year of COVID-19 with limited pandemic-mitigating restrictions (February 2020 - January 2021) and second year of COVID-19 with stringent restrictions (February 2021 - January 2022). Baseline maternal characteristics and gestational weight gain (GWG) were compared between cohorts. The primary outcome was GDM, assessed using univariate and multivariate generalised estimating equations models. RESULTS: 28,207 pregnancies met the inclusion criteria, 14,663 pregnancies two years pre-COVID-19, 6,890 in COVID-19 Year 1 and 6,654 in COVID-19 Year 2. Maternal age increased across exposure periods (30.7 ± 5.0 years pre-COVID-19 vs 31.0 ± 5.0 years COVID-19 Year 1 vs 31.3 ± 5 years COVID-19 Year 2; p < 0.001). There were increases in pre-pregnancy body mass index (BMI) (25.5 ± 5.7 kg/m2 vs 25.7 ± 5.6 kg/m2 vs 26.1 ± 5.7 kg/m2; p < 0.001), proportion who were obese (17.5% vs 18.1% vs 20.7%; p < 0.001) and proportion with other traditional risk factors for GDM including South Asian ethnicity and prior history of GDM. Rate of GWG and proportion exceeding recommended GWG increased with pandemic exposure (64.3% vs 66.0% vs 66.6%; p = 0.009). GDM diagnosis increased across exposure periods (21.2% vs 22.9% vs 24.8%; p < 0.001). Both pandemic exposure periods were associated with increased risk of GDM on univariate analysis, only COVID-19 Year 2 remaining significantly associated after adjusting for maternal baseline characteristics and GWG (OR 1.17 [1.06, 1.28], p = 0.01). CONCLUSIONS: Diagnosis of GDM increased with pandemic exposure. Progressive sociodemographic changes and greater GWG may have contributed to increased risk. However, exposure to the second year of COVID-19 remained independently associated with GDM after adjusting for shifts in maternal characteristics and GWG.

A Clinical Update on Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. GDM has long been associated with obstetric and neonatal complications primarily relating to higher infant birthweight and is increasingly recognized as a risk factor for future maternal and offspring cardiometabolic disease. The prevalence of GDM continues to rise internationally due to epidemiological factors including the increase in background rates of obesity in women of reproductive age and rising maternal age and the implementation of the revised International Association of the Diabetes and Pregnancy Study Groups' criteria and diagnostic procedures for GDM. The current lack of international consensus for the diagnosis of GDM reflects its complex historical evolution and pragmatic antenatal resource considerations given GDM is now 1 of the most common complications of pregnancy. Regardless, the contemporary clinical approach to GDM should be informed not only by its short-term complications but also by its longer term prognosis. Recent data demonstrate the effect of early in utero exposure to maternal hyperglycemia, with evidence for fetal overgrowth present prior to the traditional diagnosis of GDM from 24 weeks' gestation, as well as the durable adverse impact of maternal hyperglycemia on child and adolescent metabolism. The major contribution of GDM to the global epidemic of intergenerational cardiometabolic disease highlights the importance of identifying GDM as an early risk factor for type 2 diabetes and cardiovascular disease, broadening the prevailing clinical approach to address longer term maternal and offspring complications following a diagnosis of GDM.

Impact of COVID-19 mandatory lockdown on maternal gestational weight gain and neonatal macrosomia rate at an academic medical center in Israel.

BACKGROUND: In an effort to prevent the spread of coronavirus disease 2019 (COVID-19), governments restricted outdoor activities and imposed lockdown quarantine. This change in lifestyle probably affected individuals' eating habits and physical activity. OBJECTIVE: To examine the effect of lockdown due to the COVID-19 pandemic on maternal antenatal weight gain, neonatal macrosomia, and other maternal and neonatal outcomes of women delivering at an academic medical center in Israel. METHOD: A retrospective, two-period cohort study conducted at a university teaching medical center in Afula, Israel. The study period was between April and September 2020. This period signifies worsening in pandemic situations, during which citizens experienced strict prolonged lockdown measures. The parallel unexposed period (control period) was between April and September 2019. Singleton pregnancies delivered at >24 weeks were eligible. Primary outcome was incidence of macrosomia. Secondary outcomes included gestational weight gain, body mass index (BMI) at delivery, rates of gestational diabetes mellitus (GDM), mode of delivery, postpartum hemorrhage (PPH), and neonatal outcomes reflecting neonatal birth weight and condition at delivery. RESULTS: A total of 4,765 women were included, 2,442 in the study group and 2,323 in the control group. The incidence of macrosomia was significantly higher in 2020 (6.2%) than in 2019 (4.9%), (p = .048; OR: 1.29; 95% CI: 1.002- 1.65). Women gained significantly more weight (median 1 kg more), weighed more at delivery (median 1 kg), and had higher BMI at delivery in 2020 compared with those in 2019 (p < .01). The incidence of GDM was 9.5% and 8.5% in the study and control groups respectively (p = .26; OR: 1.12; 95% CI: 0.92-1.37). Greater percentage of women did not perform the glucose challenge test in 2020 (9.9%) compared with those in 2019 (7.5%) (p = .003, OR: 1.36; 95% CI: 1.11-1.67). The incidence of any hypertension related to pregnancy was significantly higher in 2020 compared to 2019 (5.8% vs 4.4% respectively, (p = .042; OR: 1.32; 95% CI: 1.02-1.71). The proportion of women who smoked during pregnancy was also significantly higher in 2020 than in 2019 (5.1% vs 3.7%, respectively, p = .02; OR: 1.40; 95% CI: 1.06-1.86). Delivery mode did not differ, while the incidence of PPH was significantly higher in 2020 than in 2019 (5.6% vs 3.4%, respectively, p = .001; OR: 1.65; 95% CI: 1.25-2.19). Neonatal condition at delivery was comparable. CONCLUSION: COVID-19-related lockdown was associated with the increased rate of macrosomic infants. This indirect effect of the pandemic is probably related to poorer maternal antenatal metabolic health status. Long-term consequences should be further examined.

Continuous glucose monitor use in type 2 diabetes mellitus in pregnancy and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess whether continuous glucose monitor use in type 2 diabetes mellitus in pregnancy is associated with improved perinatal outcomes. DATA SOURCES: We searched Ovid MEDLINE, Scopus, ClinicalTrials.gov, and Cochrane library from inception through May 9, 2022. STUDY ELIGIBILITY CRITERIA: We included all studies that compared continuous glucose monitor use with fingerstick glucose monitoring in women with type 2 diabetes mellitus. METHODS: The initial search yielded 2463 unique citations that were screened in Covidence by 2 independent reviewers. Study types included randomized controlled trials, cohort studies, and cross-sectional studies. Our outcomes of interest were macrosomia or large-for-gestational-age infants, hemoglobin A1c, cesarean delivery, hypertensive disorders of pregnancy including preeclampsia, gestational age at delivery, and neonatal hypoglycemia. RESULTS: Three randomized controlled trials met the inclusion criteria. We performed random-effects meta-analyses of estimates from 2 studies without risk of significant bias and reported summary adjusted odds ratios and 95% confidence intervals. Meta-analysis of 56 women with continuous glucose monitor use and 53 control women without continuous glucose monitor use showed that there was no difference in the incidence of large-for-gestational-age infants between continuous glucose monitor users and standard-of-care controls (odds ratio, 0.78; 95% confidence interval, 0.34-1.78) with an I2 of 0%. In addition, there was no difference in the development of preeclampsia between continuous glucose monitor users and standard-of-care controls (odds ratio, 1.63; 95% confidence interval, 0.34-7.22) with an I2 of 0%. CONCLUSION: Continuous glucose monitor use was not associated with improved perinatal outcomes as assessed by large-for-gestational-age infants and preeclampsia. This review is limited by the small amount of data available for this population, and further research is needed.

Comparison of the clinical characteristics, glycemic control, and pregnancy outcomes between women with gestational diabetes mellitus in waves I and III of the COVID-19 pandemic: a reference center report.

OBJECTIVES: The medical care of patients with gestational diabetes mellitus (GDM) during the COVID-19 pandemic was influenced by changing epidemiological conditions and government regulations. Aim - To compare the clinical pregnancy data of GDM women between waves I and III of the pandemic. MATERIAL AND METHODS: We performed a retrospective analysis of medical records from the GDM clinic and compared the periods of March-May 2020 (wave I) and March-May 2021 (wave III). RESULTS: Women with GDM during wave I (n = 119) compared to wave III (n = 116) were older (33.0 ± 4.7 vs 32.1 ± 4.8 years; p = 0.07), booked later (21.8 ± 8.4 vs 20.3 ± 8.5 weeks; p = 0.17), and had their last appointment earlier (35.5 ± 2.0 vs 35.7 ± 3.2 weeks; p < 0.01). Telemedicine consultations were used more frequently during wave I (46.8% vs 24.1%; p < 0.01), while insulin therapy was used less often (64.7% vs 80.2%; p < 0.01). Mean fasting self-measured glucose did not differ (4.8 ± 0.3 vs 4.8 ± 0.3 mmol/L; p = 0.49), but higher postprandial glucose was reported during wave I (6.6 ± 0.9 vs 6.3 ± 0.6 mmol/l; p < 0.01). Pregnancy outcome data were available for 77 wave I pregnancies and 75 wave III pregnancies. The groups were similar in terms of gestational week of delivery (38.3 ± 1.4 vs 38.1 ± 1.6 weeks), cesarean sections (58.4% vs 61.3%), APGAR scores (9.7 ± 1.0 vs 9.7 ± 1.0 pts), and birth weights (3306.6 ± 457.6 g vs 3243.9 ± 496.8 g) (p = NS for all). The mean wave I neonate length was slightly higher (54.3 ± 2.6 cm vs 53.3 ± 2.6 cm; p = 0.04). CONCLUSIONS: We identified differences between wave I and wave III pregnancies for several clinical characteristics. However, nearly all pregnancy outcomes were found to be similar.

Effects of COVID-19 home quarantine on pregnancy outcomes of patients with gestational diabetes mellitus: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the effects of the home quarantine on pregnancy outcomes of gestational diabetes mellitus (GDM) patients during the COVID-19 outbreak. METHODS: The complete electronic medical records of patients with GDM with home quarantine history were collected and classified into the home quarantine group from 24 February 2020 to 24 November 2020. The same period of patients with GDM without home quarantine history were included in the control group from 2018 to 2019. The pregnant outcomes of the home quarantine and control groups were systematically compared, such as neonatal weight, head circumference, body length, one-minute Apgar score, fetal macrosomia, and pre-term delivery. RESULTS: A total of 1358 patients with GDM were included in the analysis, including 484 in 2018, 468 in 2019, and 406 in 2020. Patients with GDM with home quarantine in 2020 had higher glycemic levels and adverse pregnancy outcomes than in 2018 and 2019, including higher cesarean section rates, lower Apgar scores, and higher incidence of macrosomia and umbilical cord around the neck. More importantly, the second trimester of home quarantine had brought a broader impact on pregnant women and fetuses. CONCLUSION: Home quarantine has aggravated the condition of GDM pregnant women and brought more adverse pregnancy outcomes during the COVID-19 outbreak. Therefore, we suggested governments and hospitals strengthen lifestyle guidance, glucose management, and antenatal care for patients with GDM with home quarantine during public health emergencies.

An Evaluation of Virtual Care for Gestational Diabetes Using the Quadruple Aim Framework: Assessment of Patient and Provider Experience, Cost, and Clinical Outcomes.

OBJECTIVE: Our aim in this study was to evaluate the impact of virtual care for gestational diabetes mellitus (GDM) in the context of the COVID-19 pandemic. METHODS: This multiple methods program evaluation used the Quadruple Aim Framework. The impact on patient experience, cost, and provider satisfaction was assessed using surveys and interviews. Chi-square and Poisson statistics were used to compare clinical outcomes before (April 2019 to February 2020) and after (May 2020 to March 2021) the shift to virtual care. RESULTS: Patient experience surveys were completed by 85 women. Most of them rated their virtual care experience as good or excellent (93%), with a preference for continued virtual visits in the future (84%). Most respondents felt virtual care saved them money (93%) and time (98%). Six health-care providers at the Diabetes in Pregnancy Clinic were interviewed and all believed the switch to virtual care was largely positive. Overall, interview transcripts revealed that health-care providers were happy with the transition, although nurses initially perceived an increased workload. There were no significant differences in rates of cesarean section procedures, macrosomia, neonatal intensive care unit admissions or the proportion of appointments at which insulin was initiated between in-person and virtual care patient outcomes. There was a decreased proportion of missed appointments after the switch to virtual care (6.15% vs 1.21%, p<0.0001). CONCLUSIONS: There has been high patient and provider satisfaction with virtual GDM care, with no difference in clinical outcomes and fewer missed appointments. Virtual GDM care should remain an option in the future.

SARS-CoV-2 Seroconversion and Pregnancy Outcomes in a Population of Pregnant Women Recruited in Milan, Italy, between April 2020 and October 2020.

The possible link between SARS-CoV-2 infection and adverse pregnancy outcomes has so far demonstrated heterogeneous results in terms of maternal, fetal, and neonatal complications. We aim to investigate the correlation between SARS-CoV-2 seroconversion and/or neutralization titer and pregnancy outcomes. We analyzed a population of 528 pregnant women followed up from the first trimester of gestation until delivery. For each woman, we collected a first blood sample between 11 and 13 weeks of gestation and a second sample in the perinatal period (between peripartum and puerperium) to assess the presence of SARS-CoV-2 antibodies and/or microneutralization titer (MN titer). Data on pregnancy outcomes (gestational age at delivery, preterm birth before 34 weeks, hypertensive disorders, gestational diabetes, and abnormal fetal growth) were collected. We observed that serologic status per se is not associated with major pregnancy complications. On the contrary, the MN titer was associated with increased odds of gestational diabetes. Although we mainly reported asymptomatic SARS-CoV-2 infections and the absence of severe maternal and neonatal adverse outcomes, SARS-CoV-2 infection might challenge the maternal immune system and explain the moderate increase in adverse outcome odds.

The Effect of Online Supervised Exercise throughout Pregnancy on the Prevention of Gestational Diabetes in Healthy Pregnant Women during COVID-19 Pandemic: A Randomized Clinical Trial.

(1) Background: to examine the effect of an online supervised exercise program during pregnancy on the prevention of GDM, and on maternal and childbirth outcomes. (2) Methods: we conducted a randomized clinical trial (NCT04563065) in 260 pregnant women without obstetric contraindications who were randomized into two study groups: intervention group (IG, N = 130) or control group (CG, N = 130). An online supervised exercise program was conducted from 8-10 to 38-39 weeks of pregnancy. (3) Results: no significant differences were found at baseline in maternal characteristics; nevertheless, certain outcomes showed a favorable trend towards the IG. A lower number and percentage of GDM cases were found in the IG compared to the CG (N = 5/4.9% vs. N = 17/16.8%, p = 0.006). Similarly, fewer cases of excessive maternal weight gain (N = 12/11.8% vs. N = 31/30.7%, p = 0.001) were found in the IG, and a lower percentage of instrumental deliveries (N = 8/11.3% vs. N = 13/15.1%) and c-sections (N = 7/9.9% vs. N = 20/23.3%, p = 0.046). (4) Conclusions: an online supervised exercise program can be a preventative tool for GDM in healthy pregnant women.

Gestational diabetes mellitus in the COVID-19 pandemic: A retrospective study from Hangzhou, China.

AIMS: Our study aimed to investigate changes in the prevalence of gestational diabetes mellitus (GDM) in the COVID-19 pandemic and postpandemic era and the risk of adverse pregnancy outcomes in pregnant women diagnosed with GDM during the blockade period. METHODS: First, we investigated changes in the prevalence of GDM and the population undergoing oral glucose tolerance tests (OGTT) after the COVID-19 pandemic. We then collected clinical information from pregnant women diagnosed with GDM to explore the risk of adverse pregnancy outcomes in pregnant women with GDM during the COVID-19 pandemic. RESULTS: After the COVID-19 pandemic, the proportion of pregnant women in the total number of outpatient OGTT tests decreased yearly. The ratio was 81.30%, 79.71%, and 75.48% from 2019 to 2021, respectively, with the highest proportion of pregnant women in February 2020 (92.03%). The prevalence of GDM was higher in March 2020 compared to the same period in 2019. However, from 2019 to 2021, the prevalence decreased year by year with 21.46%, 19.81%, and 18.48%, respectively. The risk of adverse pregnancy outcomes for pregnant women diagnosed with GDM during the most severe period of the COVID-19 pandemic did not differ from before the COVID-19 pandemic. CONCLUSIONS: After the COVID-19 pandemic, the prevalence of GDM increased during the most severe period of the epidemic, but the overall prevalence of GDM decreased year by year. In addition, the pandemic did not change the risk of adverse pregnancy outcomes in pregnant women with GDM.

A global view of hypertensive disorders and diabetes mellitus during pregnancy.

Two important maternal cardiometabolic disorders (CMDs), hypertensive disorders in pregnancy (HDP) (including pre-eclampsia) and gestational diabetes mellitus (GDM), result in a large disease burden for pregnant individuals worldwide. A global consensus has not been reached about the diagnostic criteria for HDP and GDM, making it challenging to assess differences in their disease burden between countries and areas. However, both diseases show an unevenly distributed disease burden for regions with a low income or middle income, or low-income and middle-income countries (LMICs), or regions with lower sociodemographic and human development indexes. In addition to many common clinical, demographic and behavioural risk factors, the development and clinical consequences of maternal CMDs are substantially influenced by the social determinants of health, such as systemic marginalization. Although progress has been occurring in the early screening and management of HDP and GDM, the accuracy and long-term effects of such screening and management programmes are still under investigation. In addition to pharmacological therapies and lifestyle modifications at the individual level, a multilevel approach in conjunction with multisector partnership should be adopted to tackle the public health issues and health inequity resulting from maternal CMDs. The current COVID-19 pandemic has disrupted health service delivery, with women with maternal CMDs being particularly vulnerable to this public health crisis.

Maternal Early-Life Risk Factors and Later Gestational Diabetes Mellitus: A Cross-Sectional Analysis of the UAE Healthy Future Study (UAEHFS).

Limited studies have focused on maternal early-life risk factors and the later development of gestational diabetes mellitus (GDM). We aimed to estimate the GDM prevalence and examine the associations of maternal early-life risk factors, namely: maternal birthweight, parental smoking at birth, childhood urbanicity, ever-breastfed, parental education attainment, parental history of diabetes, childhood overall health, childhood body size, and childhood height, with later GDM. This was a retrospective cross-sectional study using the UAE Healthy Future Study (UAEHFS) baseline data (February 2016 to April 2022) on 702 ever-married women aged 18 to 67 years. We fitted a Poisson regression to estimate the risk ratio (RR) for later GDM and its 95% confidence interval (CI). The GDM prevalence was 5.1%. In the fully adjusted model, females with low birthweight were four times more likely (RR 4.04, 95% CI 1.36-12.0) and females with a parental history of diabetes were nearly three times more likely (RR 2.86, 95% CI 1.10-7.43) to report later GDM. In conclusion, maternal birthweight and parental history of diabetes were significantly associated with later GDM. Close glucose monitoring during pregnancy among females with either a low birth weight and/or parental history of diabetes might help to prevent GDM among this high-risk group.

COVID-19 and Gestational Diabetes: The Role of Nutrition and Pharmacological Intervention in Preventing Adverse Outcomes.

Pregnant women with GDM affected by COVID-19 seem to be at higher risk of adverse maternal and neonatal outcomes, especially those with overweight or obesity. Good glycemic control seems to be the most effective measure in reducing the risk of GDM and severe COVID-19. For such purposes, the Mediterranean diet, micronutrient supplementation, and physical activity are considered the first line of treatment. Failure to achieve glycemic control leads to the use of insulin, and this clinical scenario has been shown to be associated with an increased risk of adverse maternal and neonatal outcomes. In this review, we explore the current evidence pertaining to the pathogenesis of SARS-CoV-2 leading to the main complications caused by COVID-19 in patients with GDM. We also discuss the incidence of complications caused by COVID-19 in pregnant women with GDM according to their treatment.

Fasting Glucose for the Diagnosis of Gestational Diabetes Mellitus (GDM) during the COVID-19 Pandemic.

BACKGROUND: During the COVID-19 pandemic, different non-validated tests were proposed to simplify the diagnosis of gestational diabetes (GDM). AIM: To analyse the effects of replacing the two-step approach for Early-GDM and GDM diagnosis, with a fasting plasma glucose test. MATERIAL AND METHODS: This is a cohort study consisting of 3200 pregnant women: 400 with Early-GDM, 800 with GDM and 2000 with Non-GDM diagnosed using the two-step approach. Using fasting plasma glucose for Early-GDM and GDM diagnosis, according to the recommendations of Spain, Australia, Italy and the UK during the pandemic, the rates of missed and new Early-GDM and GDM were calculated and perinatal outcomes were analysed. RESULTS: Using fasting plasma glucose in the first trimester >100 mg/dL for Early-GDM diagnosis, the rates of post-COVID missed and new Early-GDM were 79.5% and 3.2%, respectively. Using fasting plasma glucose at 24-28 weeks <84 or >92, 95 or 100 mg/dL for GDM diagnosis, the rates of missed GDM were 50.4%, 78%, 82.6% and 92.4%, respectively, and 8.6%, 5.6% and 2.3% women with Non-GDM were diagnosed with new GDM. CONCLUSION: Fasting plasma glucose is not a good test for the diagnosis of GDM either in the first trimester or at 24-28 weeks.

Study protocol on risk factors for the diagnosis of gestational diabetes mellitus in different trimesters and their relation to maternal and neonatal outcomes (GDM-RIDMAN).

INTRODUCTION: Gestational diabetes mellitus (GDM) is often associated with adverse pregnancy outcomes. However, the association of risk factors with GDM diagnosis, maternal and neonatal health outcomes is less established when compared with women without GDM. We aim to examine the diagnostic accuracy of the conventional and novel risk factors for a GDM diagnosis and their impact on maternal and neonatal health outcomes. METHODS AND ANALYSIS: This retrospective cohort and nested case-control study at six public health clinics is based on medical records and questionnaire survey of women between 2 and 12 months postpartum. The estimated required sample size is 876 complete records (292 cases, 584 control, at a ratio of 1:2). Oral glucose tolerance test results will be used to identify glucose dysregulation, and maternal and neonatal outcomes include maternal weight gain, pre-eclampsia, polyhydramnios, mode of delivery, preterm or postdate birth, complications in labour, birth weight, gestational age at birth, Apgar score, congenital anomaly, congenital hypothyroidism, neonatal death or stillbirth, hypoglycaemia and hyperbilirubinaemia. Psychosocial measures include the WHO Quality of Life: brief, mother-infant bonding (14-item Postpartum Bonding Questionnaire and 19-item Maternal Postnatal Attachment Scale), anxiety (7-item Generalised Anxiety Disorder), depression (9-item Patient Health Questionnaire) and stress (Perceived Stress Scale symptoms) questionnaires. The comparative incidences of maternal and neonatal health outcomes, the comparative prevalence of the psychosocial outcomes between women with GDM and without GDM, specificity, sensitivity, positive and negative predictive values of the risk factors, separately and combined, will be reported. All GDM risk factors and outcomes will be modelled using multivariable regression analysis and the receiver operating characteristics curve will be reported. ETHICS AND DISSEMINATION: This study was approved by the Malaysia Research and Ethics Committee, Ministry of Health Malaysia. Informed consent will be obtained from all participants. Findings will be submitted for publications in scientific journals.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.