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NEURODEVELOPMENTAL DELAY IN CHILDREN EXPOSED TO MATERNAL SARS‑COV‑2 IN‑UTERO
Author
Fajardo‑Martinez, Viviana
Ferreira, Fatima
Fuller, Trevon
Cambou, Mary Catherine
Kerin, Tara
Paiola, Sophia
Mok, Thalia
Rao, Rashmi
Mohole, Jyodi
Paravastu, Ramya
Zhang, Dajie
Marschik, Peter
Iyer, Sai
Kesavan, Kalpashri
Lopes, Maria da Conceição Borges
Britto, José Augusto A.
Moreira, Maria Elisabeth
Brasil, Patricia
Nielsen‑Saines, Karin
Ferreira, Fatima
Fuller, Trevon
Cambou, Mary Catherine
Kerin, Tara
Paiola, Sophia
Mok, Thalia
Rao, Rashmi
Mohole, Jyodi
Paravastu, Ramya
Zhang, Dajie
Marschik, Peter
Iyer, Sai
Kesavan, Kalpashri
Lopes, Maria da Conceição Borges
Britto, José Augusto A.
Moreira, Maria Elisabeth
Brasil, Patricia
Nielsen‑Saines, Karin
Affilliation
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Universidade do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
UCLA Institute for the Environment and Sustainability. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Heidelberg University. Center for Psychosocial Medicine. Department of Child and Adolescent Psychiatry. Heidelberg, Germany / University Medical Center Göttingen and Leibniz ScienceCampus Primate Cognition. Child and Adolescent Psychiatry and Psychotherapy. Göttingen, Germany / Medical University of Graz. Division of Phoniatrics. Interdisciplinary Developmental Neuroscience. Graz, Austria.
Heidelberg University. Center for Psychosocial Medicine. Department of Child and Adolescent Psychiatry. Heidelberg, Germany / University Medical Center Göttingen and Leibniz ScienceCampus Primate Cognition. Child and Adolescent Psychiatry and Psychotherapy. Göttingen, Germany / Medical University of Graz. Division of Phoniatrics. Interdisciplinary Developmental Neuroscience. Graz, Austria.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doenças Febris Agudas. Rio de Janeiro, RJ, Brasil.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Universidade do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.
UCLA Institute for the Environment and Sustainability. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Heidelberg University. Center for Psychosocial Medicine. Department of Child and Adolescent Psychiatry. Heidelberg, Germany / University Medical Center Göttingen and Leibniz ScienceCampus Primate Cognition. Child and Adolescent Psychiatry and Psychotherapy. Göttingen, Germany / Medical University of Graz. Division of Phoniatrics. Interdisciplinary Developmental Neuroscience. Graz, Austria.
Heidelberg University. Center for Psychosocial Medicine. Department of Child and Adolescent Psychiatry. Heidelberg, Germany / University Medical Center Göttingen and Leibniz ScienceCampus Primate Cognition. Child and Adolescent Psychiatry and Psychotherapy. Göttingen, Germany / Medical University of Graz. Division of Phoniatrics. Interdisciplinary Developmental Neuroscience. Graz, Austria.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doenças Febris Agudas. Rio de Janeiro, RJ, Brasil.
David Geffen. UCLA School of Medicine. Los Angeles, CA, USA.
Abstract
It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.
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