Neurodevelopmental outcomes of infants secondary to in utero exposure to maternal SARS-CoV-2 infection: A national prospective study in Kuwait

Abstract

BackgroundAn increasing proportion of women are being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study is to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy.MethodsIn this prospective cohort study, the neurodevelopment status of infants (N=298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff score: ≤2 standard deviations (SDs) below the population mean) and no delay (score >2 SDs above the population mean).ResultsApproximately 10% of infants born to mothers with SARS-CoV-2 infections during pregnancy showed developmental delays. Two of 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infection during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P=0.039) and second trimesters (P=0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. Infants born at <31 weeks gestation were more prone to developmental delays than those born at >31 weeks gestation (10% versus 0.8%; P=0.002).ConclusionThe findings of the study highlight the need for long term neurodevelopmental assessment of infants born to mothers with SARS-CoV-2 infection.

COVID-19 in pregnancy: implications for fetal brain development

“…Early signals of adverse neurodevelopmental outcomes at 3-6 months, 1 year, and 1.5 years in infants and children exposed to SARS-CoV-2 in utero, and/or born during the COVID-19 pandemic are emerging [37][38][39][40][41]. A longitudinal cohort study of 57 infants with prenatal exposure to SARS-CoV-2 in China identified deficits in the social-emotional domain of neurodevelopmental testing at 3 months of age [40].…”

“…A longitudinal cohort study of 57 infants with prenatal exposure to SARS-CoV-2 in China identified deficits in the social-emotional domain of neurodevelopmental testing at 3 months of age [40]. A preliminary report of 298 infants born to women with SARS-CoV-2 infection during pregnancy found evidence of developmental delay in 10% of infants at 12 months of age, although neither study included a noninfected comparator group [41]. Another preliminary report of over 7000 infants born during the COVID-19 pandemic to both SARS-CoV-2 infected and noninfected mothers identified an association between maternal SARS-CoV-2 exposure and a neurodevelopmental diagnosis at 12 months [25].…”

COVID-19 Pandemic and Infant Neurodevelopmental Impairment

“…Fortunately, maternal-fetal vertical transmission of SARS-CoV-2 is rare, although the impact of maternal infection on fetal and postnatal neurodevelopment is still poorly understood. 12 Recently, a few cohort studies 13 , 14 , 15 , 16 on this clinically important issue have been published with controversial results. Shuffrey et al, 15 as one of the largest cohorts, assessed 255 infants born during the pandemic, and exposure to maternal SARS-CoV-2 infection was not associated with differences in neurodevelopmental screening scores at age 6 months, regardless of infection timing or severity.…”

Sex-specific neurodevelopmental outcomes in offspring of mothers with SARS-CoV-2 in pregnancy: an electronic health records cohort

“…Indeed, several studies demonstrated early signals (e.g. at 3-6 months, 12, and 18 months) of neurodevelopmental risk in offspring exposed to SARS-CoV-2 in utero 29,30(p19),31 , although those studies were limited by the absence of a contemporaneous non-infected control group. A preliminary report in a subset of the present cohort, including a non-infected contemporary control group, suggested that SARS-CoV-2 was associated with increased risk for neurodevelopmental diagnosis at 12 months of age, 19 but did not yet have sufficient neurodevelopmental diagnoses to examine the impact of fetal sex, as we have now been able to examine in this substantially larger cohort.…”