Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.
Giuliani F., Oros D., Gunier RB., Deantoni S., Rauch S., Casale R., Nieto R., Bertino E., Rego A., Menis C., Gravett MG., Candiani M., Deruelle P., García-May PK., Mhatre M., Ado Usman M., Abd-Elsalam S., Etuk S., Napolitano R., Liu B., Prefumo F., Savasi V., Silva M., Baafi E., Ariff S., Maiz N., Baffah Aminu M., Cardona-Perez JA., Craik R., Tavchioska G., Bako B., Benski C., Hassan-Hanga F., Savorani M., Sentilhes L., Carola Capelli M., Takahashi K., Vecchiarelli C., Ikenoue S., Thiruvengadam R., Soto Conti CP., Cetin I., Nachinab VB., Ernawati E., Duro EA., Kholin A., Teji JS., Easter SR., Salomon LJ., Ayede AI., Cerbo RM., Agyeman-Duah J., Roggero P., Eskenazi B., Langer A., Bhutta ZA., Kennedy SH., Papageorghiou AT., Villar J.
BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes has been reported; however, a detailed understanding of the effect of maternal positivity, delivery mode and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of the mode of delivery, breastfeeding and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-exposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean section (52.8% compared to 38.5% for those without COVID-19 diagnosis, p<0.01) and pregnancy related complications such as hypertensive disorders of pregnancy and fetal distress, all with p-value < 0.001, compared to women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (p ≤0.001) and lower neonatal weight (p ≤0.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in-utero exposure was significantly correlated to the risk of the neonate testing positive (OR, 4.5; 95% CI 2.2-9.4 for length of in-utero exposure > 14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean section was a risk factor for them testing positive for COVID-19 (OR 2.4, 95% CI 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of Intensive Care Unit admission, fever, gastrointestinal and respiratory symptoms and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis, as well as hospital neonatal care practices including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSIONS: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean section was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother to child skin-to-skin contact, rooming-in and direct breastfeeding did not represent risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.