Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy

Abstract

ImportanceAssociations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding.ObjectiveTo assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months.Design, Setting, and ParticipantsThis cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants.ExposuresMaternal symptomatic or asymptomatic SARS-CoV-2 infection.Main Outcomes and MeasuresInfant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language.ResultsAmong 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (β = 0.31; 95% CI, −2.97 to 3.58), gross motor (β = 0.82; 95% CI, −1.34 to 2.99), fine motor (β = 0.36; 95% CI, −0.74 to 1.47), expressive language (β = −1.00; 95% CI, −4.02 to 2.02), or receptive language (β = 0.45; 95% CI, −2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores.Conclusions and RelevanceIn this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice

“…First, MIA is a classical pregnancy infection model of ASD [ 11 , 12 , 13 ], which differs from the genetic mutation model of ASD; its pathogenesis is not well understood. Second, with the COVID-19 pandemic, millions of pregnant women were infected, which may further increase the prevalence of ASD [ 14 , 15 , 16 ]. Coronavirus is an RNA virus, while the MIA model uses RNA virus analogue poly(I:C), and there is a certain similarity between the two pathogens.…”

“…The recent outbreak of COVID-19, an RNA virus that has infected millions of pregnant women worldwide, may further increase the incidence of ASD [ 14 , 15 , 16 ]. Since ASD is the leading psychiatric disabling disorder in children, it imposes a huge economic burden on families and society [ 17 ].…”

COVID-19 among infants: key clinical features and remaining controversies

“…Long-term assessments after neurological events are scarce [ 45 , 103 , 104 ]. One study of the neurodevelopmental score status at 6 months reported that those born during the pandemic had lower scores, whereas the variable of maternal infection at any time during pregnancy had no such association [ 104 ].…”

“…One study of the neurodevelopmental score status at 6 months reported that those born during the pandemic had lower scores, whereas the variable of maternal infection at any time during pregnancy had no such association [ 104 ]. The same authors did not find that maternal infection was associated with adverse long-term neurological outcomes [ 103 ].…”

Candidate Pathways Underlying Exposure to the COVID-19 Pandemic and Early Child Development—Risk and Resilience

“…Research on the COVID-19 pandemic and child neurodevelopment is predominantly represented by studies using one of two approaches. The first involves comparing developmental outcomes in children with vs without exposure to prenatal maternal SARS-CoV-2 infection . The second compares developmental outcomes in children born before vs during the COVID-19 pandemic .…”