Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study.

Villar J ，Ariff S ，Gunier RB ，Thiruvengadam R ，Rauch S ，Kholin A ，Roggero P ，Prefumo F ，do Vale MS ，Cardona-Perez JA ，Maiz N ，Cetin I ，Savasi V ，Deruelle P ，Easter SR ，Sichitiu J ，Soto Conti CP ，Ernawati E ，Mhatre M ，Teji JS ，Liu B ，Capelli C ，Oberto M ，Salazar L ，Gravett MG ，Cavoretto PI ，Nachinab VB ，Galadanci H ，Oros D ，Ayede AI ，Sentilhes L ，Bako B ，Savorani M ，Cena H ，García-May PK ，Etuk S ，Casale R ，Abd-Elsalam S ，Ikenoue S ，Aminu MB ，Vecciarelli C ，Duro EA ，Usman MA ，John-Akinola Y ，Nieto R ，Ferrazi E ，Bhutta ZA ，Langer A ，Kennedy SH ，Papageorghiou AT ... -  《-》

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed 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 and/or radiological pulmonary findings or ≥2 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. 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 delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.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 (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 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 neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery 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 were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

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 ，Usman MA ，Abd-Elsalam S ，Etuk S ，Napolitano R ，Liu B ，Prefumo F ，Savasi V ，Do Vale MS ，Baafi E ，Ariff S ，Maiz N ，Aminu MB ，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 ... -  《-》

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. None.

Villar J ，Soto Conti CP ，Gunier RB ，Ariff S ，Craik R ，Cavoretto PI ，Rauch S ，Gandino S ，Nieto R ，Winsey A ，Menis C ，Rodriguez GB ，Savasi V ，Tug N ，Deantoni S ，Fabre M ，Martinez de Tejada B ，Rodriguez-Sibaja MJ ，Livio S ，Napolitano R ，Maiz N ，Sobrero H ，Peterson A ，Deruelle P ，Giudice C ，Teji JS ，Casale RA ，Salomon LJ ，Prefumo F ，Cheikh Ismail L ，Gravett MG ，Vale M ，Hernández V ，Sentilhes L ，Easter SR ，Capelli C ，Marler E ，Cáceres DM ，Albornoz Crespo G ，Ernawati E ，Lipschuetz M ，Takahashi K ，Vecchiarelli C ，Hubka T ，Ikenoue S ，Tavchioska G ，Bako B ，Ayede AI ，Eskenazi B ，Thornton JG ，Bhutta ZA ，Kennedy SH ，Papageorghiou AT ，INTERCOVID-2022 International Consortium ... -  《-》

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Barros FC ，Gunier RB ，Rego A ，Sentilhes L ，Rauch S ，Gandino S ，Teji JS ，Thornton JG ，Kachikis AB ，Nieto R ，Craik R ，Cavoretto PI ，Winsey A ，Roggero P ，Rodriguez GB ，Savasi V ，Kalafat E ，Giuliani F ，Fabre M ，Benski AC ，Coronado-Zarco IA ，Livio S ，Ostrovska A ，Maiz N ，Castedo Camacho FR ，Peterson A ，Deruelle P ，Giudice C ，Casale RA ，Salomon LJ ，Soto Conti CP ，Prefumo F ，Mohamed Elbayoumy EZ ，Vale M ，Hernández V ，Chandler K ，Risso M ，Marler E ，Cáceres DM ，Crespo GA ，Ernawati E ，Lipschuetz M ，Ariff S ，Takahashi K ，Vecchiarelli C ，Hubka T ，Ikenoue S ，Tavchioska G ，Bako B ，Ayede AI ，Eskenazi B ，Bhutta ZA ，Kennedy SH ，Papageorghiou AT ，Villar J ，INTERCOVID-2022 International Consortium ... -  《-》

Clinical and epidemiological aspects of SARS-CoV-2 infection among pregnant and postpartum women in Mozambique: a prospective cohort study.

Although there is a significant increase of evidence regarding the prevalence and impact of COVID-19 on maternal and perinatal outcomes, data on the effects of the pandemic on the obstetric population in sub-Saharan African countries are still scarce. Therefore, the study aims were to assess the prevalence and impact of COVID-19 on maternal and neonatal outcomes in the obstetric population at Central Hospital of Maputo (HCM), Mozambique. Prospective cohort study conducted at teaching and referral maternity, HCM, from 20 October 2020 to 22 July 2021. We collected maternal and perinatal outcomes up to 6 weeks postpartum of eligible women (pregnant and postpartum women-up to the 14th day postpartum) screened for COVID-19 (individual test for symptomatic participants and pool testing for asymptomatic). The primary outcome was maternal death, Severe Acute Respiratory Syndrome (SARS) and Intensive Care Unit (ICU) admission. We estimated the COVID-19 prevalence and the unadjusted RR (95% CI) for maternal and perinatal outcomes. We used the chi-square or Fisher's exact test to compare categorical variables (two-sided p-value < 0.05 for statistical significance). We included 239 participants. The overall prevalence of COVID-19 was 9.2% (22/239) and in the symptomatic group was 32.4% (11/34). About 50% of the participants with COVID-19 were symptomatic. Moreover, the most frequent symptoms were dyspnoea (33.3%), cough (28.6%), anosmia (23.8%), and fever (19%). Not having a partner, being pregnant, and alcohol consumption were vulnerability factors for SARS-CoV-2 infection. The risk of adverse maternal and neonatal outcomes (abortion, foetal death, preterm birth, Apgar, and NICU admission) was not significantly increased with COVID-19. Moreover, we did not observe a significant difference in the primary outcomes (SARS, ICU admission and maternal death) between COVID-19 positive and COVID-19 negative groups. The prevalence of COVID-19 in the obstetric population is higher than in the general population, and fifty percent of pregnant and postpartum women with COVID-19 infection are asymptomatic. Not having a partner and alcohol consumption were factors of greatest vulnerability to SARS-COV-2 infection. Moreover, being pregnant versus postpartum was associated with increased vulnerability to COVID-19. Data suggest that pregnant women with COVID-19 may have a higher frequency of  COVID-19 infection, reinforcing the need for universal testing, adequate follow-up for this population, and increasing COVID-19 therapy facilities in Mozambique. Moreover, provide counselling during Antenatal care for COVID-19 preventive measures. However, more prospective and robust studies are needed to assess these findings.

Charles CM ，Osman NB ，Arijama D ，Matingane B ，Sitoé T ，Kenga D ，Lorenzoni C ，Luís E ，Pacagnella RC ，Sacarlal J ，Mozambique Study group of SARS-COV-2 ... -  《Reproductive Health》