Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study - 08/03/24

Doi : 10.1016/j.ajog.2024.02.008

Fernando C. Barros, PhD ^a, Robert B. Gunier, PhD ^b, Albertina Rego, PhD ^c, Loïc Sentilhes, PhD ^d, Stephen Rauch, MPH ^b, Serena Gandino, MD ^e,^f, Jagjit S. Teji, MD ^g, Jim G. Thornton, MD ^h, Alisa B. Kachikis, MD ⁱ, Ricardo Nieto, MD ^j, Rachel Craik, BSc ^e, Paolo I. Cavoretto, PhD ^k, Adele Winsey, PhD ^e, Paola Roggero, MD ^l, Gabriel B. Rodriguez, PhD ^e, Valeria Savasi, MD ^m,ⁿ, Erkan Kalafat, MD ^o, Francesca Giuliani, PhD ^p, Marta Fabre, MD ^q, Anne Caroline Benski, MD ^r, Irma Alejandra Coronado-Zarco, MD ^s, Stefania Livio, MD ^t, Adela Ostrovska, MD ^u, Nerea Maiz, PhD ^v, Fabiola R. Castedo Camacho, MD ^w, Ashley Peterson, MD ^x, Philippe Deruelle, PhD ^y, Carolina Giudice, MD ^z, Roberto A. Casale, PhD ^aa, Laurent J. Salomon, PhD ^ab, Constanza P. Soto Conti, MD ^j, Federico Prefumo, PhD ^ac, Ehab Zakaria Mohamed Elbayoumy, MD ^ad, Marynéa Vale, MSc ^ae, Valeria Hernández, MD ^af, Katherine Chandler, MD ^ag, Milagros Risso, MD ^ah, Emily Marler, BSc ^ai, Daniela M. Cáceres, MD ^aj, Guadalupe Albornoz Crespo, MD ^ak, Ernawati Ernawati, PhD ^al, Michal Lipschuetz, PhD ^am, Shabina Ariff, MBBS ^an, Ken Takahashi, MD ^ao, Carmen Vecchiarelli, MD ^ap, Teresa Hubka, MD ^aq, Satoru Ikenoue, MD ^ar, Gabriela Tavchioska, MD ^as, Babagana Bako, MD ^at, Adejumoke I. Ayede, MBBS ^au, Brenda Eskenazi, PhD ^b, Zulfiqar A. Bhutta, PhD ^av, Stephen H. Kennedy, MD ^e,^f, Aris T. Papageorghiou, MD ^e,^f,^ai,^⁎ , Jose Villar, MD ^e,^f
On behalf of the
INTERCOVID-2022 International Consortium
^a Post Graduate Program in Health in the Life Cycle, Universidade Católica de Pelotas, Pelotas, Brazil
^b School of Public Health, University of California, Berkeley, CA
^c Departamento de Pediatria, Faculdade Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
^d Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France
^e Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom
^f Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom
^g Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
^h University of Nottingham Medical School, Nottingham, United Kingdom
ⁱ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA
^j Division Neonatología, Hospital Materno Infantil Ramón Sarda, Buenos Aires, Argentina
^k Department of Obstetrics and Gynecology, IRCCS San Raffaele Hospital and University, Milan, Italy
^l Department of Woman, Child and Neonate, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
^m Unit of Obstetrics and Gynecology, L- Sacco Hospital ASST Fatebenefratelli Sacco, Milan, Italy
ⁿ Department of Biological and Clinical Sciences, University of Milan, Milan, Italy
^o Department of Obstetrics and Gynecology, Koc University Hospital, Istanbul, Turkey
^p Neonatal Special Care Unit, Regina Margherita Children’s Hospital, Turin, Italy
^q Instituto de Investigación Sanitario de Aragón (IIS Aragon), Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
^r Hôpitaux Universitaires de Genève, Geneva, Switzerland
^s Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico
^t Hospital Buzzi, ASST Fatebenefratelli Sacco, Milan, Italy
^u Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London, United Kingdom
^v Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Vall d’Hebron, Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Barcelona, Spain
^w Unidad Académica de Neonatología, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
^x Tufts Medical Center, Boston, MA
^y Department of Obstetrics and Gynecology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
^z Servicio de Neonatologia, Hospital Italiano de Buenos Aires, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina
^aa Maternal and Child Department, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
^ab Hôpital Universitaire Necker-Enfants Malades, Paris, France
^ac Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
^ad Obstetrics and Gynecology Specialized Hospital in Port Said, Port Said, Egypt
^ae Hospital Universitário da Universidade Federal do Maranhão, São Luís, Brazil
^af Universidad Nacional de Córdoba, Córdoba, Argentina
^ag Brigham and Women's Hospital, Harvard Medical School, Boston, MA
^ah Servicio de Neonatología del Departamento Materno Infantil, Hospital Universitario Austral, Buenos Aires, Argentina
^ai St George's University Hospitals NHS Foundation Trust, London, United Kingdom
^aj Hospital Julio C. Perrando, Resistencia, Chaco, Argentina
^ak Clínica y Maternidad Suizo Argentina, Buenos Aires, Argentina
^al Medical Faculty Universitas Airlangga - Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
^am Obstetrics and Gynecology Division, Hadassah Medical Center Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
^an Department of Paediatrics & Child Health, The Aga Khan University Hospital, Karachi, Pakistan
^ao Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
^ap Sanatorio Otamendi, Buenos Aires, Argentina
^aq AMITA Health Resurrection Medical Center, Chicago, IL
^ar Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
^as General Hospital Borka Taleski, Prilep, North Macedonia
^at Department of Obstetrics and Gynaecology, College of Medical Sciences, Gombe State University, Gombe, Nigeria
^au University College Hospital, Ibadan, Nigeria
^av Center for Global Child Health, Hospital for Sick Children, Toronto, Canada

^∗Corresponding author: Aris T. Papageorghiou, MD.

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Abstract

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.

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

Plan

Introduction

Materials and Methods

Study design and participants

Neonatal outcomes for mothers diagnosed and not diagnosed with COVID-19

Neonatal outcomes of mothers diagnosed with COVID-19 by vaccination status

Comment

Principal findings

Results in the context of what is known and clinical implications

Strengths and limitations

Conclusion

CRediT authorship contribution statement

	A.T.P. and J.V. contributed equally.
	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.
	This study did not receive any funding.
	Cite this article as: Barros FC, Gunier RB, Rego A, et al. Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study. Am J Obstet Gynecol 2024;XX:x.ex–x.ex.