Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Diabetes risk after a normal oral glucose tolerance test during pregnancy.

INTRODUCTION: Our aim was to conduct a follow-up of a cohort of women screened for GDM with a normal oral glucose tolerance test (OGTT) during pregnancy to investigate the incidence and time of diagnosis of manifest diabetes mellitus and identify risk factors for subsequent development of diabetes. METHODS: This was a follow-up study of a cohort with normal and borderline OGTT in 1991/1992. Among the original 352 women, only five were lost to follow-up. RESULTS: In total, 64 women (18%) had manifest diabetes. Their median age was 57 years after 28 years of follow-up. This amounts to three times the expected rate compared with the background population. The rate of manifest diabetes rises 10-20 years after pregnancy and after the age of 40 years. A normal fasting glucose and also a borderline fasting glucose at OGTT during pregnancy were associated with an increased risk of manifest diabetes (p less-than 0.001), also after adjustment for age, Body Mass Index, non-Danish origin and smoking during pregnancy (p less-than 0.002). CONCLUSION: The incidence of diabetes is higher in women with various risk factors for DM and a previously normal OGTT in pregnancy than in the background population. Our results are useful in identifying the time during which women may benefit from effective implementation of evidence-based treatment to postpone and avert manifest DM, even though they had a normal OGTT during pregnancy. FUNDING: none. TRIAL REGISTRATION: The trial was registered with the the Regional Ethics Committee and the Data Protection Agency, nos. 2014-41-3433, 1-16-02-824-17 (under running permission no. 621549), 1-16-02-825-17, and 1-16-02-180-17, all under the cover of data handling agreement no. 509 with the Danish Health Authority.

Metabolic syndrome in women with previous gestational diabetes.

To evaluate the incidence and timing of the diagnosis of metabolic syndrome in a cohort of Danish women after a pregnancy with gestational diabetes (GDM) to estimate the optimum time for preventative actions in relation to metabolic syndrome (MetS). In this follow-up study, 435 women were included from a consecutive cohort with prior history of GDM. Data on dyslipidemia, hypertension and other cardiovascular disorders (CVD) were extracted from the electronic patient journal. Any antidiabetic, cardiovascular and cholesterol-lowering medicine was ascertained in the national prescription database. Similarly, any blood test taken was evaluated. We defined a patient having MetS if the criteria of the WHO based definition of diabetes or impaired glucose regulation were met. Further, we added as alternative for glucose intolerance, a glycosylated hemoglobin (HbA1c) > 44 mmol/mol or the former level ≥ 6.5%. Further, dyslipidemia, lipid lowering medications, BMI > 30 kg/m2 or antihypertensive treatment were used. For MetS outcome, diagnosis or medication for CVD was registered. All women were followed for median 5.7 years (range 0; 9). The incidence of MetS was 28%. Thirteen percent of these qualified already within one year after pregnancy for the diagnosis of MetS. Postpartum MetS was detected after a median of 3 years (range 0; 7 years); further, 36 (8%) had been diagnosed with manifest diabetes after pregnancy. The diagnosis of postpartum MetS was strongly associated with the prevalence of manifest diabetes. Six years after pregnancy the rate of metabolic syndrome was more than tripled (25 vs. 89%, no DM vs manifest DM, RR: 6.7; 95% CI 2.7-17, p < 0.001). At 40 years the MetS rate nearly tripled if manifest DM was diagnosed (26 vs. 78%, no DM vs. manifest DM, RR: 3.3, 95% CI 1.8-6, p < 0.001). We found that GDM and later on manifest DM in women increase the risk of metabolic syndrome. There seems to be a window of opportunity before the early thirties where it would be especially beneficial to begin preventive efforts in women with GDM.