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

INTERCOVID-2022 International Consortium

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Background: 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. Objective: 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. Study Design: 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. Results: 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. Conclusion: 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.

Original languageEnglish
JournalAmerican Journal of Obstetrics and Gynecology
Early online date16 Feb 2024
StateE-pub ahead of print - 16 Feb 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 The Authors


L.S. reports serving as a consultant and lecturer for Ferring Laboratories, GlaxoSmithKline, and Bayer, and as a lecturer for Norgine. A.T.P. was supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the National Institute for Health and Care Research (NIHR) Biomedical Research Centre funding scheme. The views expressed herein are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, or any of the other funders.

FundersFunder number
Oxford Partnership Comprehensive Biomedical Research Centre
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
National Institute for Health and Care Research


    • COVID-19
    • COVID-19 vaccination
    • SARS-CoV-2
    • SARS-CoV-2 exposure
    • morbidity
    • mortality
    • multicenter study
    • neonatal health
    • neonatal intensive care admission
    • neonatal outcomes
    • neurologic outcomes
    • newborn
    • perinatal practices
    • pregnancy
    • preterm birth
    • respiratory support
    • respiratory symptoms
    • skin-to-skin


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