COVID-19 in Schwangerschaft, Geburt und Wochenbett

Coronavirus disease 2019 (COVID-19) is an infectious disease that can lead to severe respiratory symptoms. Pregnant women have an increased risk for a severe course. Therefore, the Association of the Scientific Medical Societies in Germany (AWMF) Guidelines 015/092 "SARS-CoV-2 in pregnancy, childbirth, and the puerperium" were established to standardize care in the COVID-19 pandemic. The guideline group used data from the "COVID-19 related obstetrics and neonatal outcome study" (CRONOS) to generate evidence-based recommendations for action. CRONOS collects data from more than 130 affiliated maternity hospitals nationwide in Germany. According to the study, pregnant women positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are often asymptomatic;however, in 1 out of 25 detected infections there is a severe course requiring intensive medical treatment. Thromboembolism occurs in 1 out of 30 women hospitalized for COVID-19. An infection of the neonate of a mother infected peripartum is occasionally detected (about 1 out of 20 infants) and usually remains without consequence in the short-term outcome. Many other questions have been answered using CRONOS data. The registry is still open and recruiting and will also provide more in-depth information on different virus variants and vaccination in the future with more than 6000 cases. CRONOS is exemplary for an unprecedented cooperation of gynecologists during the pandemic.

COVID-19 in Schwangerschaft, Geburt und Wochenbett : Das CRONOS-Register COVID-19 in pregnancy, childbirth and puerperiumThe CRONOS registry

COVID(„coronavirus disease“)-19 ist eine Infektionserkrankung, die zu schweren respiratorischen Symptomen führen kann. Schwangere haben ein erhöhtes Risiko für einen schweren Verlauf. Für eine gute Betreuung in der COVID-19-Pandemie wurde daher die AWMF(Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften)-Leitlinie 015/092 „SARS-CoV‑2 in Schwangerschaft, Geburt und Wochenbett“ erstellt. Die Leitliniengruppe nutzte zur Erstellung von evidenzbasierten Handlungsempfehlungen die Daten der „Covid-19 Related Obstetrics and Neonatal Outcome Study“ (CRONOS). CRONOS sammelt deutschlandweit Daten aus mehr als 130 angeschlossenen Geburtenkliniken. SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-positive Schwangere sind demnach häufig asymptomatisch. Bei 1 von 25 erkannten Infektionen kommt es jedoch zu einem schweren Verlauf mit intensivmedizinischer Behandlung. Bei 1 von 30 stationär wegen COVID-19 behandelten Frauen kommt es zu einer Thromboembolie. Eine Infektion des Neugeborenen einer peripartal infizierten Mutter wird gelegentlich (etwa 1 von 20 Kindern) nachgewiesen und bleibt in der Regel ohne Konsequenz im Kurzzeit-Outcome. Viele weitere Fragestellungen wurden mithilfe von CRONOS beantwortet. Das weiter aktiv rekrutierende Register wird zukünftig mit mehr als 6000 Fällen auch tiefere Informationen zu verschiedenen Virusvarianten und zum Impfen liefern. CRONOS steht vorbildlich für eine beispiellose Kooperation von Ärztinnen und Ärzten der Frauenheilkunde in der Pandemie.

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.

Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study.

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 - 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 - 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 - 21.3) to 76.4% (95% CI 72.2 - 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week; umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042; p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare; however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.

Maternal and neonatal outcomes of pregnancies with COVID-19 after medically assisted reproduction: results from the prospective COVID-19-Related Obstetrical and Neonatal Outcome Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 infections in pregnancy have been associated with maternal morbidity, admission to intensive care, and adverse perinatal outcomes such as preterm birth, stillbirth, and hypertensive disorders of pregnancy. It is unclear whether medically assisted reproduction additionally affects maternal and neonatal outcomes in women with COVID-19. OBJECTIVE: To evaluate the effect of medically assisted reproduction on maternal and neonatal outcomes in women with COVID-19 in pregnancy. STUDY DESIGN: A total of 1485 women with COVID-19 registered in the COVID-19 Related Obstetric and Neonatal Outcome Study (a multicentric, prospective, observational cohort study) were included. The maternal and neonatal outcomes in 65 pregnancies achieved with medically assisted reproduction and in 1420 spontaneously conceived pregnancies were compared. We used univariate und multivariate (multinomial) logistic regressions to estimate the (un)adjusted odds ratios and 95% confidence intervals for adverse outcomes. RESULTS: The incidence of COVID-19-associated adverse outcomes (eg, pneumonia, admission to intensive care, and death) was not different in women after conceptions with COVID-19 than in women after medically assisted reproduction pregnancies. Yet, the risk of obstetrical and neonatal complications was higher in pregnancies achieved through medically assisted reproduction. However, medically assisted reproduction was not the primary risk factor for adverse maternal and neonatal outcomes including pregnancy-related hypertensive disorders, gestational diabetes mellitus, cervical insufficiency, peripartum hemorrhage, cesarean delivery, preterm birth, or admission to neonatal intensive care. Maternal age, multiple pregnancies, nulliparity, body mass index >30 (before pregnancy) and multiple gestation contributed differently to the increased risks of adverse pregnancy outcomes in women with COVID-19 independent of medically assisted reproduction. CONCLUSION: Although women with COVID-19 who conceived through fertility treatment experienced a higher incidence of adverse obstetrical and neonatal complications than women with spontaneous conceptions, medically assisted reproduction was not the primary risk factor.

Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study Immunantwort und Antikörper-Transfer zwischen Mutter und Kind bei schwangeren Frauen mit SARS-CoV-2-Infektion: eine multizentrische Beobachtungsstudie

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 – 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 – 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 – 21.3) to 76.4% (95% CI 72.2 – 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week;umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042;p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare;however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.