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
... -
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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
... -
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Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection at the time of birth in England: national cohort study.
Some studies have suggested that women with SARS-CoV-2 infection during pregnancy are at increased risk of adverse pregnancy and neonatal outcomes, but these associations are still not clear.
This study aimed to determine the association between SARS-CoV-2 infection at the time of birth and maternal and perinatal outcomes.
This is a population-based cohort study in England. The inclusion criteria were women with a recorded singleton birth between May 29, 2020, and January 31, 2021, in a national database of hospital admissions. Maternal and perinatal outcomes were compared between pregnant women with a laboratory-confirmed SARS-CoV-2 infection recorded in the birth episode and those without. Study outcomes were fetal death at or beyond 24 weeks' gestation (stillbirth), preterm birth (<37 weeks' gestation), small for gestational age infant (small for gestational age; birthweight at the <tenth centile), preeclampsia or eclampsia, induction of labor, mode of birth, specialist neonatal care, composite neonatal adverse outcome indicator, maternal and neonatal length of hospital stay after birth (3 days or more), and 28-day neonatal and 42-day maternal hospital readmission. Adjusted odds ratios and their 95% confidence interval for the association between SARS-CoV-2 infection status and outcomes were calculated using logistic regression, adjusting for maternal age, ethnicity, parity, preexisting diabetes mellitus, preexisting hypertension, and socioeconomic deprivation measured using the Index of Multiple Deprivation 2019. Models were fitted with robust standard errors to account for hospital-level clustering. The analysis of the neonatal outcomes was repeated for those born at term (≥37 weeks' gestation) because preterm birth has been reported to be more common in pregnant women with SARS-CoV-2 infection.
The analysis included 342,080 women, of whom 3527 had laboratory-confirmed SARS-CoV-2 infection. Laboratory-confirmed SARS-CoV-2 infection was more common in women who were younger, of non-White ethnicity, primiparous, or residing in the most deprived areas or had comorbidities. Fetal death (adjusted odds ratio, 2.21; 95% confidence interval, 1.58-3.11; P<.001) and preterm birth (adjusted odds ratio, 2.17; 95% confidence interval, 1.96-2.42; P<.001) occurred more frequently in women with SARS-CoV-2 infection than those without. The risk of preeclampsia or eclampsia (adjusted odds ratio, 1.55; 95% confidence interval, 1.29-1.85; P<.001), birth by emergency cesarean delivery (adjusted odds ratio, 1.63; 95% confidence interval, 1.51-1.76; P<.001), and prolonged admission after birth (adjusted odds ratio, 1.57; 95% confidence interval, 1.44-1.72; P<.001) were significantly higher for women with SARS-CoV-2 infection than those without. There were no significant differences (P>.05) in the rate of other maternal outcomes. The risk of neonatal adverse outcome (adjusted odds ratio, 1.45; 95% confidence interval, 1.27-1.66; P<.001), need for specialist neonatal care (adjusted odds ratio, 1.24; 95% confidence interval, 1.02-1.51; P=.03), and prolonged neonatal admission after birth (adjusted odds ratio, 1.61; 95% confidence interval, 1.49-1.75; P<.001) were all significantly higher for infants with mothers with laboratory-confirmed SARS-CoV-2 infection. When the analysis was restricted to pregnancies delivered at term (≥37 weeks), there were no significant differences in neonatal adverse outcome (P=.78), need for specialist neonatal care after birth (P=.22), or neonatal readmission within 4 weeks of birth (P=.05). Neonates born at term to mothers with laboratory-confirmed SARS-CoV-2 infection were more likely to have prolonged admission after birth (21.1% compared with 14.6%; adjusted odds ratio, 1.61; 95% confidence interval, 1.49-1.75; P<.001).
SARS-CoV-2 infection at the time of birth is associated with higher rates of fetal death, preterm birth, preeclampsia, and emergency cesarean delivery. There were no additional adverse neonatal outcomes, other than those related to preterm delivery. Pregnant women should be counseled regarding risks of SARS-CoV-2 infection and should be considered a priority for vaccination.
Gurol-Urganci I
，Jardine JE
，Carroll F
，Draycott T
，Dunn G
，Fremeaux A
，Harris T
，Hawdon J
，Morris E
，Muller P
，Waite L
，Webster K
，van der Meulen J
，Khalil A
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