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Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.
Am J Obstet Gynecol. 2022 09; 227(3):488.e1-488.e17.AJ

Abstract

BACKGROUND

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.

OBJECTIVE

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.

STUDY DESIGN

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.

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 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.

CONCLUSION

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.

Authors+Show Affiliations

Neonatal Special Care Unit, Regina Margherita Children's Hospital, Turin, Italy. Electronic address: giuliani.pediatria@gmail.com.Aragon Institute of Health Research, Obstetrics Department, Hospital Clínico Universitario Lozano Blesa Zaragoza, Zaragoza, Spain.Center for Environmental Research and Community Health (CERCH), School of Public Health, University of California, Berkeley, CA.Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom; Neonatal Care Unit, School of Medicine, Department of Public Health and Pediatrics, University of Turin, Turin, Italy.Center for Environmental Research and Community Health (CERCH), School of Public Health, University of California, Berkeley, CA.Maternal and Child Department, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina.Division Neonatología, Hospital Materno Infantil Ramón Sarda, Buenos Aires, Argentina.Neonatal Unit of the University, City of Health and Science of Turin, Turin, Italy.Departamento de Pediatria, Faculdade Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.Departments of Obstetrics and Gynecology and of Global Health, University of Washington, Seattle, WA.Obstetrics and Gynaecology Department, IRCCS San Raffaele Hospital and University, Milan, Italy.Department of Obstetrics and Gynecology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.Hospital Regional Lic. Adolfo López Mateos ISSSTE, Mexico City, Mexico.Tufts Medical Center, Boston, MA.Department of Obstetrics and Gynaecology, Muhammad Abdullahi Wase Teaching Hospital, Kano State, Nigeria.Faculty of Medicine, Tropical Medicine and Infectious Diseases Department, Tanta University, Tanta, Egypt.University of Calabar Teaching Hospital, Calabar, Nigeria.Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, United Kingdom; Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London, United Kingdom.St George's University Hospitals NHS Foundation Trust, London, United Kingdom.Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.Ospedale Luigi Sacco University Hospital, Department of BioMedical and Clinical Sciences, University of Milan, Milan, Italy.Universidade Federal do Maranhão, São Luís, Brazil.Holy Family Hospital, Nkawkaw, Ghana.Department of Paediatrics & Child Health, The Aga Khan University Hospital, Karachi, Pakistan.Department of Obstetrics, Hospital Universitari Vall d'Hebron, Barcelona Hospital Campus, Barcelona, Spain.Department of Obstetrics and Gynaecology, Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria.Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City, Mexico.Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom.Department of Pediatrics, General Hospital Borka Taleski, Prilep, Republic of North Macedonia.Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, College of Medical Sciences, Gombe State University, Gombe, Nigeria.Hôpitaux Universitaires de Genève, Département de la Femme, de l'Enfant et de l'Adolescent, Geneva, Switzerland.Bayero University Kano, Nigeria; Aminu Kano Teaching Hospital, Kano State, Nigeria.Hospital de Moron, Moron, Buenos Aires, Argentina.Department of Obstetrics and Gynecology Bordeaux University Hospital, Bordeaux, France.Servicio de Neonatologia del Departamento Materno Infantil del Hospital Universitario Austral, Pilar, Buenos Aires, Argentina.Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan.Sanatorio Otamendi, Buenos Aires, Argentina.Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.Translational Health Science and Technology Institute, Faridabad, India.Division Neonatología, Hospital Materno Infantil Ramón Sarda, Buenos Aires, Argentina.Ospedale Vittore Buzzi Children's Hospital, Department of BioMedical and Clinical Sciences, University of Milan, Milan, Italy.Fr. Thomas Alan Rooney Memorial Hospital, Asankragwa, Ghana.Department of Obstetrics & Gynecology, Medical Faculty, Universitas Airlangga, Surabaya, Indonesia; Soetomo General Academic Hospital, Surabaya, Indonesia.Universidad de Buenos Aires, Buenos Aires, Argentina; Universidad de Moron, Moron, Argentina.National Medical Research Center for Obstetrics, Gynecology & Perinatology, Moscow, Russia.Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern Feinberg School of Medicine, Chicago, IL.Division of Maternal-Fetal Medicine and Division of Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, France.College of Medicine, University of Ibadan, Ibadan, Nigeria; University College Hospital, Ibadan, Nigeria.Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.Nuffield Department of Women's & Reproductive Health, Green Templeton College, University of Oxford, Oxford, United Kingdom.Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Department of Woman, Child and Neonate, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.Center for Environmental Research and Community Health (CERCH), School of Public Health, University of California, Berkeley, CA.Women and Health Initiative, Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA.Center for Global Child Health, Hospital for Sick Children, Toronto, Canada.Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom.Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom; St George's University Hospitals NHS Foundation Trust, London, United Kingdom.Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom; Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35452653

Citation

Giuliani, Francesca, et al. "Effects of Prenatal Exposure to Maternal COVID-19 and Perinatal Care On Neonatal Outcome: Results From the INTERCOVID Multinational Cohort Study." American Journal of Obstetrics and Gynecology, vol. 227, no. 3, 2022, pp. 488.e1-488.e17.
Giuliani F, Oros D, Gunier RB, et al. Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study. Am J Obstet Gynecol. 2022;227(3):488.e1-488.e17.
Giuliani, F., Oros, D., Gunier, R. B., Deantoni, S., Rauch, S., Casale, R., Nieto, R., Bertino, E., Rego, A., Menis, C., Gravett, M. G., Candiani, M., Deruelle, P., García-May, P. K., Mhatre, M., Usman, M. A., Abd-Elsalam, S., Etuk, S., Napolitano, R., ... Villar, J. (2022). Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study. American Journal of Obstetrics and Gynecology, 227(3), e1-e17. https://doi.org/10.1016/j.ajog.2022.04.019
Giuliani F, et al. Effects of Prenatal Exposure to Maternal COVID-19 and Perinatal Care On Neonatal Outcome: Results From the INTERCOVID Multinational Cohort Study. Am J Obstet Gynecol. 2022;227(3):488.e1-488.e17. PubMed PMID: 35452653.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study. AU - Giuliani,Francesca, AU - Oros,Daniel, AU - Gunier,Robert B, AU - Deantoni,Sonia, AU - Rauch,Stephen, AU - Casale,Roberto, AU - Nieto,Ricardo, AU - Bertino,Enrico, AU - Rego,Albertina, AU - Menis,Camilla, AU - Gravett,Michael G, AU - Candiani,Massimo, AU - Deruelle,Philippe, AU - García-May,Perla K, AU - Mhatre,Mohak, AU - Usman,Mustapha Ado, AU - Abd-Elsalam,Sherief, AU - Etuk,Saturday, AU - Napolitano,Raffaele, AU - Liu,Becky, AU - Prefumo,Federico, AU - Savasi,Valeria, AU - Do Vale,Marynéa Silva, AU - Baafi,Eric, AU - Ariff,Shabina, AU - Maiz,Nerea, AU - Aminu,Muhammad Baffah, AU - Cardona-Perez,Jorge Arturo, AU - Craik,Rachel, AU - Tavchioska,Gabriela, AU - Bako,Babagana, AU - Benski,Caroline, AU - Hassan-Hanga,Fatimah, AU - Savorani,Mónica, AU - Sentilhes,Loïc, AU - Carola Capelli,Maria, AU - Takahashi,Ken, AU - Vecchiarelli,Carmen, AU - Ikenoue,Satoru, AU - Thiruvengadam,Ramachandran, AU - Soto Conti,Constanza P, AU - Cetin,Irene, AU - Nachinab,Vincent Bizor, AU - Ernawati,Ernawati, AU - Duro,Eduardo A, AU - Kholin,Alexey, AU - Teji,Jagjit Singh, AU - Easter,Sarah Rae, AU - Salomon,Laurent J, AU - Ayede,Adejumoke Idowu, AU - Cerbo,Rosa Maria, AU - Agyeman-Duah,Josephine, AU - Roggero,Paola, AU - Eskenazi,Brenda, AU - Langer,Ana, AU - Bhutta,Zulfiqar A, AU - Kennedy,Stephen H, AU - Papageorghiou,Aris T, AU - Villar,Jose, Y1 - 2022/04/19/ PY - 2022/01/31/received PY - 2022/03/30/revised PY - 2022/04/13/accepted PY - 2022/4/23/pubmed PY - 2022/8/30/medline PY - 2022/4/22/entrez KW - COVID-19 KW - SARS-CoV-2 KW - SARS-CoV-2 exposure KW - birthweight KW - breastfeeding KW - cesarean delivery KW - cohort KW - feeding problems KW - hospital stay KW - infections KW - intrauterine growth restriction KW - morbidity KW - mortality KW - multicenter study KW - neonatal intensive care unit admission KW - neonatal outcomes KW - neonate KW - neurologic outcome KW - newborn KW - perinatal practices KW - preeclampsia KW - pregnancy KW - preterm birth KW - respiratory support KW - respiratory symptoms KW - risk ratio KW - rooming-in KW - skin-to-skin KW - small for gestational age SP - 488.e1 EP - 488.e17 JF - American journal of obstetrics and gynecology JO - Am J Obstet Gynecol VL - 227 IS - 3 N2 - BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. 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 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. CONCLUSION: 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. SN - 1097-6868 UR - https://www.unboundmedicine.com/medline/citation/35452653/Effects_of_prenatal_exposure_to_maternal_COVID_19_and_perinatal_care_on_neonatal_outcome:_results_from_the_INTERCOVID_Multinational_Cohort_Study_ DB - PRIME DP - Unbound Medicine ER -