Post-COVID in women after SARS-CoV-2 infection during pregnancy - a pilot study with follow-up data from the COVID-19-related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Pregnant women are at an increased risk of severe COVID-19 and adverse pregnancy outcomes; data on maternal long-term outcome is scarce. We analyzed long-term follow-ups on women who experienced a SARS-CoV-2 infection during pregnancy to evaluate post-COVID symptoms, particularly fatigue, and their association with quality of life (QoL). METHODS: 773 women who enrolled in the CRONOS registry between April 2020 and August 2021 were contacted for follow-up from December 2022 to April 2023. Data was gathered through a web-based questionnaire. Subsequently, study coordinators matched the follow-up data with the existing CRONOS data. RESULTS: 110/773 (14%) women provided data. 20.9% experienced only acute symptoms during their SARS-CoV-2 infection in pregnancy, while 2.7% women experienced symptoms lasting longer than 4 weeks (long COVID). Symptoms lasting longer than 12 weeks (post-COVID) were reported by 63.6% women and occurred more often after severe COVID-19. Fatigue was the most frequently reported symptom (88%), with 55% of women still experiencing it more than one year after initial infection. 76% of women rated their QoL as "good" or "very good". Women experiencing post-COVID reported a significantly lower QoL. CONCLUSION: This is the first German long-term data on women after SARS-CoV-2 infection during pregnancy, showing a high rate of post-COVID, a persistence of fatigue, and the impact on QoL. Continuous monitoring of pregnant women with COVID-19 is needed to develop comprehensive management strategies.

Long-Term Outcome of Neonates and Infants whose Mothers Tested Positive for SARS-CoV-2 during Pregnancy - a Pilot of the Post-CRONOS Project.

OBJECTIVE: Long-term effects on infants of mothers with SARS-CoV-2 infection during pregnancy are increasingly discussed in the literature. Besides potential neurodevelopment impairments after intrauterine SARS-CoV-2 exposure, there might be differences in the postnatal pediatric care of those children, like the timing of preventive medical examinations (PME) or vaccinations. In this first national long-term follow-up study of women included in the CRONOS registry, we describe maternal impressions of their child´s development and the prevalence of regulatory disorders, and we analyze the timing of PMEs and vaccinations. METHODS: 773 women who were enrolled between April 3, 2020, and August 24, 2021, in the CRONOS registry were eligible to be contacted by the study coordinators and asked to fill out a web-based questionnaire. RESULTS: 110/773 (14%) women completed the questionnaire. Their children were between the ages of 12 and 31 months (median 20 months). All mothers were satisfied with their child´s development, milestones were achieved in a timely fashion. The reported prevalence for excessive crying, sleeping, and feeding disorders was 11%, 18-32%, and 7%, respectively. PMEs were mostly not delayed, but only 54% of infants received their first vaccination within their first 60 days of life. DISCUSSION: In summary, our exploratory findings suggest that developmental milestones in infancy are reached in time after maternal SARS-CoV-2 infection during pregnancy. However, there are effects on the implementation of PMEs and vaccinations. EINFüHRUNG: In der Literatur werden zunehmend potenzielle Langzeitfolgen für Säuglinge nach intrauteriner SARS-CoV-2-Exposition diskutiert. Neben möglichen Beeinträchtigungen der neurologischen Entwicklung können Unterschiede in der pädiatrischen postnatalen Betreuung bei diesen Kindern z. B. bei der Durchführung von Vorsorgeuntersuchungen (sog. U´s) oder Impfungen bestehen. In dieser ersten nationalen Langzeit-Follow-up-Studie aus dem CRONOS-Register beschreiben wir mütterliche Eindrücke zur Entwicklung ihres Kindes, sowie die Prävalenz von Regulationsstörungen. Wir analysieren den Zeitpunkt von U´s und Impfungen. METHODEN: 773 Frauen, die zwischen dem 03.04.2020 und dem 24.08.2021 in CRONOS aufgenommen wurden, wurden von den Studienkoordinatoren kontaktiert und gebeten, einen webbasierten Fragebogen auszufüllen. ERGEBNISSE: 110/773 (14%) Frauen füllten den Fragebogen aus, ihre Kinder waren zwischen 12 und 31 Monate alt (Median 20 Monate). Alle Mütter waren mit der Entwicklung ihres Kindes zufrieden, Meilensteine der Entwicklung wurden zeitgerecht erreicht. Die berichtete Prävalenz für exzessives Schreien, Schlaf- und Fütterstörungen betrug 11%, 18-32% bzw. 7%. U´s wurden meist zeitgerecht durchgeführt, aber nur 54% der Säuglinge erhielten ihre erste Impfung innerhalb der ersten 60 Lebenstage. DISKUSSION: Zusammenfassend deuten unsere explorativen Ergebnisse darauf hin, dass Entwicklungsmeilensteine im Säuglingsalter nach mütterlicher SARS-CoV-2-Infektion in der Schwangerschaft rechtzeitig erreicht werden. Es zeigen sich jedoch Auswirkungen auf die Durchführung von Vorsorgen und Impfungen.

Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

Introduction: Studies have shown that pregnant women with COVID-19 have a higher risk of intensive care unit admission and invasive mechanical ventilation support than non-pregnant women. Pregnancy-associated physiological changes in respiratory function may contribute to the elevated risk. Alteration in lung volumes and capacities are attributed to the mechanical impediment caused by the growing fetus. Multiple pregnancies may therefore compromise functional lung capacity earlier than singleton pregnancies and contribute to severe respiratory symptoms of COVID-19. Materials and Methods: A total of 5514 women with a symptomatic SARS-CoV-2 infection during pregnancy registered in the COVID-19 Related Obstetric and Neonatal Outcome Study were included. The COVID-19-related adverse maternal outcomes were compared in 165 multiple versus 5349 singleton pregnancies. Combined adverse maternal outcome was defined as presence of COVID-19-related hospitalization and/or pneumonia and/or oxygen administration and/or transfer to ICU and/or death. Multivariate logistic regression was used to estimate the odds ratios and 95% confidence intervals were calculated. Results: The frequency of dyspnea, likelihood of developing dyspnea in a defined pregnancy week and duration of the symptomatic phase of the COVID-19 infection did not differ between the two groups. On average, COVID-19-related combined adverse outcome occurred earlier during pregnancy in women expecting more than one child than in singleton pregnancies. The overall incidence of singular and combined COVID-19-associated adverse maternal outcomes was not significantly different between groups. However, regression analysis revealed that multiple gestation, preconceptional BMI > 30 kg/m 2 and gestational age correlated significantly with an increased risk of combined adverse maternal outcome. Conversely, maternal age and medically assisted reproduction were not significant risk factors for combined adverse maternal outcome. Conclusion: Our data show that multiple gestation alone is a risk factor for COVID-19-associated combined adverse maternal outcome. Moreover, severe courses of COVID-19 in women expecting more than one child are observed earlier in pregnancy than in singleton pregnancies.

Correction: Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

[This corrects the article DOI: 10.1055/a-2196-6224.].

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.

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.

Therapeutic implications of tumor free margins in head and neck squamous cell carcinoma.

OBJECTIVES: The resection status is one of the most important prognostic factors for patients with head and neck squamous cell carcinoma (HNSCC) concerning overall survival (OS) and recurrence free interval (RFI). To assess whether therapy concepts changed depending on different resection margins and extracapsular extension, OS and RFI data were set into clinical context. METHODS: All HNSCC patients who underwent head and neck surgery with/without adjuvant therapy (n=534) were selected over a ten-year period (2001-2011). Clinical parameters and survival data were collected retrospectively and histopathological analysis of tumor free margins and extracapsular extension were done. RESULTS: Patients with microscopic in-sano resection showed mean OS/RFI of 95/96 months. OS/RFI decreased in microscopic non-in-sano and macroscopic non-in-sano (56/58 and 35/39 months) as well as in unclear resection margins (63/60 months). Patients with extracapsular extension, microscopic non-in-sano resection as well as patients with in-sano resection after follow up resection demonstrated therapy escalation by adjuvant (chemo-) radiation. CONCLUSIONS: Insufficient surgical margins and extracapsular extension are main risks for a reduced overall and recurrence free survival. Although there is no measure to prevent positive extracapsular extension, clear margins at first pass protect patients from adjuvant therapy escalation.