Adverse perinatal outcomes in gestational diabetes mellitus with and without SARS-CoV-2 infection during pregnancy: results from two nationwide registries in Germany.

INTRODUCTION: Pregnancy is a known independent risk factor for a severe course of COVID-19. The relationship of SARS-CoV-2 infection and gestational diabetes mellitus (GDM) on neonatal outcomes is unclear. Our aim was to determine if SARS-CoV-2 infection represents an independent risk factor for adverse perinatal outcomes in pregnancy with GDM. RESEARCH DESIGN AND METHODS: We compared data from two German registries including pregnant women with GDM, established during the SARS-CoV-2 pandemic (COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study) and already existing before the pandemic (German registry of pregnant women with GDM; GestDiab). In total, 409 participants with GDM and SARS-CoV-2 infection and 4598 participants with GDM, registered 2018-2019, were eligible for analyses. The primary fetal and neonatal outcomes were defined as: (1) combined: admission to neonatal intensive care unit, stillbirth, and/or neonatal death, and (2) preterm birth before 37+0 weeks of gestation. Large and small for gestational age, maternal insulin therapy, birth weight >4500 g and cesarean delivery were considered as secondary outcomes. RESULTS: Women with SARS-CoV-2 infection were younger (32 vs 33 years) and had a higher median body mass index (28 vs 27 kg/m²). In CRONOS, more neonates developed the primary outcome (adjusted OR (aOR) 1.48, 95% CI 1.11 to 1.97) and were born preterm (aOR 1.50, 95% CI 1.07 to 2.10). Fasting glucose was higher in women in CRONOS versus GestDiab (5.4 vs 5.3 mmol/L) considering each 0.1 mmol/L increase was independently associated with a 5% higher risk of preterm birth among women in CRONOS only (aOR 1.05, 95% CI 1.01 to 1.09). CONCLUSIONS: GDM with SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse fetal and neonatal outcomes as compared with GDM without SARS-CoV-2 infection.

COVID-19, Pregnancy, and Diabetes Mellitus.

During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women.

[Diabetes and Pregnancy]. / Diabetes mellitus und Schwangerschaft.

The quality of metabolic control at the beginning of pregnancy already determines the course and outcome of pregnanies with type 1 and type 2 diabetes mellitus. The preconceptional counseling and support provided by experienced teams is more important than modern technical equipment with insulin pumps and sensors for continuous glucose measurement. The incidence of congenital malformations is significantly reduced by a periconceptional HbA1c level < 6.5 % and folic acid supplementation started preconceptionally. To prevent preeclampsia, all women with type 1 and type 2 diabetes mellitus should be offered low-dose ASA, starting before 16 weeks of pregnancy. If the pregnant woman has a BMI < 25 kg/m² and persistently elevated fasting blood glucose levels, a GCK-MODY should be considered. For the diagnosis of asymptomatic gestational diabetes mellitus, all women in Germany with 24 + 0 to 27 + 6 weeks of pregnancy are offered a two-stage screening. Structured follow-up care is required after gestational diabetes mellitus, because these women have an increased risk of developing type 2 diabetes mellitus and cardiovascular complications. Pregnant women with COVID-19 and hyperglycemia have an increased risk of a severe course of the infection, which is further increased by obesity - they are an important target group for vaccination with an mRNA vaccine.

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.

[COVID-19 and pregnancy]. / COVID-19 und Schwangerschaft: Fallserie mit der Komorbidität Diabetes aus der Registerstudie "Covid-19 Related Obstetric and Neonatal Outcome Study" (CRONOS).

From March 3 to October 13, 2020, 27 cases with diabetes comorbidity have been recorded in the CRONOS registry (Covid-19 Related Obstetric and Neonatal Outcome Study in Germany) among 262 registered women with SARS-CoV­2 infection during their pregnancy. Of those, 21 presented with gestational diabetes, 5 with type 2 diabetes and 1 with type 1 diabetes. About half of the women were asymptomatic and were diagnosed via general screening at hospital admission. The most common symptoms were nasal congestion, cough, tiredness, malaise and changes in smell and taste. The majority of pregnant women showed a mild to moderate course, three women were admitted to the intensive care unit and none required invasive ventilation. In the type 2 diabetes group, there were two cases with late fetal death (37 and 40 weeks of gestation) and one with a malformation, an association with diabetes being most likely. Pregnant women with diabetes mellitus represent a special subgroup; 1 in 10 women in this small cohort required intensive care monitoring due to COVID-19. In addition, this case series underscores the need for unrestricted access to pregnancy care, especially in times of pandemic, for optimal perinatal outcome.

[Gestational diabetes - actual trends]. / Gestationsdiabetes ­ aktuelle Entwicklungen.

Gestational diabetes is asymptomatic. Screening in Germany has been part of the maternity guidelines since 2012. Uncovering the glucose tolerance disorder and intensive treatment reduce maternal and child risks. The aim of treatment for diabetic pregnant women is to align the results for mother and child with the results of metabolically healthy pregnant women. In addition to the diabetological therapy control through blood glucose measurements and weight control in the mother, a qualified sonographic growth control of the fetus can be used as a support. In 70-90 % of GDM cases, non-pharmacological basic therapy is sufficient; the gold standard in pharmacotherapy is insulin. Maternity clinics with a spatially connected children's clinic offer the best security for mother and child at birth. Breastfeeding should be recommended and encouraged because of its long-term protective effects.

Measurement and evaluation of fetal fat layer in the prediction of fetal macrosomia in pregnancies complicated by gestational diabetes.

OBJECTIVES: To explore the predictive power of measuring the abdominal fetal fat layer (FFL) as a soft tissue marker at 31, 34, and 37 weeks' gestation to improve the detection of fetal macrosomia in pregnant women with GDM, in addition to the biometric values with close monitoring of maternal blood sugar level and BMI changes. METHODS: We conducted a prospective observational study at the Department of Obstetrics, University Hospitals, Campus Kiel, Germany, in collaboration with diabetic clinic staff. Participants underwent a third-trimester scan and extra FFL measurements were performed at 31, 34, and 37 weeks of gestation. The clinical outcomes of pregnancy and birth weight were collected from the obstetric record. All of the enrolled women had an early pregnancy ultrasound scan to confirm gestational age. RESULTS: The FFL at 34 and 37 weeks, with respective cutoff values of >0.48 cm and >0.59 cm, showed a very good sensitivity of 60% for both gestational points, and specificity of 89.3 and 90.6%, respectively. The probability of fetal macrosomia could be more than doubled if the FFL at 34 weeks was more than 0.48 cm. However, the probability of macrosomia dropped to 16% if the FFL was ≤0.48 cm. The median FFLs of macrosomic fetuses at 34 and 37 weeks were 0.50 (IQR 0.10) and 0.60 (IQR 0.25) cm, respectively. The mean age of the study population (n = 80) was 32.26 (SD = 5.06) years. In our study population, ten newborns were born with birth weight >4000 g. The body mass index (BMI) for the mothers of later-onset macrosomic newborns showed higher median values of 30 (IQR 8), 32 (IQR 5), and 33 (IQR 9) at 31, 34, and 37 weeks, respectively, in comparison to mothers of non-macrosomic newborn. However, the BMI did not show any statistically significant difference from those with normal-weight newborn and did not show any specific sensitivity for predicting macrosomia. CONCLUSION: Measuring the FFL at 34 and 37 weeks of gestation, in addition to the standard measurement, might be useful for predicting macrosomia and is worth further evaluation.

[Diabetes in Pregnancy - Type 1/Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus]. / Diabetes in der Schwangerschaft.

In Germany in 5.5% of all births diabetes is registered. In patients with type 1 and type 2 diabetes planning pregnancy, preconception counseling, diabetologic care with optimized periconceptional metabolic control and folic acid supplementation are essential for good pregnancy outcome. Gestational diabetes (GDM) should be diagnosed timely and managed according to existing guidelines. GDM is treated with insulin in approximately 20%. In 1-2% of GDM cases a glucokinase gene mutation is present (MODY 2). Pregnancies after bariatric-metabolic surgery are increasing and show high risks.

German gynecologists' experience with a universal screening for gestational diabetes mellitus in daily practice: A qualitative study.

OBJECTIVE: In March 2012, a universal screening for gestational diabetes mellitus (GDM) was implemented in Germany. Despite international recommendations, a two-step approach was introduced [step 1: 50-g glucose challenge test (GCT); if GCT is suspicious, step 2 follows: 75-g oral glucose tolerance test with (OGTT)]. This qualitative study aimed at examining how gynecologists administer the screening for GDM in daily practice, whether they perceive any difficulties, and whether they have suggestions for improvement. MATERIAL AND METHODS: Seventeen resident gynecologists were interviewed face-to-face in semi-structured interviews. The interviews were recorded, transcribed verbatim, coded, and analyzed using qualitative content techniques. RESULTS: We revealed differences in the screening administration. Three gynecologists directly offered the second step of the two-step screening (OGTT) instead of completing the first step before offering the second step. These gynecologists only conducted GCT if the woman (with statutory health insurance) was not willing to pay for OGTT. Critique concerns the late introduction of billing codes, lack of information from official institutions, unavailability of readymade syrup with 50-g glucose, and lack of information material for pregnant women. CONCLUSION: Our results reflect that not all gynecologists appear to conduct the screening conforming to the maternity directive. However, this has to be validated in larger quantitative surveys. That some gynecologists directly conducted OGTT may fuel the discussion regarding the screening procedure. The two-step approach was already highly controversial at the time of introducing the screening because national and international organizations recommend a one-step approach. Therefore, our results are also relevant for other countries who have implemented a two-step screening and for countries planning to implement a screening.

Screening for gestational diabetes mellitus in Germany: A qualitative study on pregnant women's attitudes, experiences, and suggestions.

OBJECTIVE: to explore pregnant women's experiences with the recently implemented screening for gestational diabetes mellitus (GDM). DESIGN: qualitative study. SETTING: Rhine-Neckar Metropolitan region, Germany. PARTICIPANTS: 20 pregnant women aged 27-41 years (mean: 32.6 years) who were at least in gestational week 29, i.e., those who should have already been screened for GDM. MEASUREMENTS AND FINDINGS: semi-structured interviews with open-ended questions were conducted via telephone between November 2013 and February 2014. All interviews were audiotaped, transcribed verbatim and subsequently analyzed using qualitative content analysis according to Mayring. The screening was seen as an important instrument to detect GDM and thus to prevent possible health problems in both mother and child. Some deviations from the recommended screening procedure were reported in the interviews, e.g., collecting capillary blood instead of venous blood during an oral glucose tolerance test (OGTT); offering an OGTT without a prior glucose challenge test (GCT); conducting a GCT after an overnight fast. Two women had to actively ask for the screening to be done. One woman reported that her gynaecologist advised her against the screening. CONCLUSION AND IMPLICATION FOR PRACTICE: this qualitative study reflects the women's experiences with the new screening for GDM. Our findings show that two years after the introduction of universal GDM screening in Germany the screening procedure does not always seem to meet the standards of the German maternity guidelines.