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

Importance: Associations 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. Objective: To 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 Participants: This 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. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant 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. Results: Among 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 (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 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 Relevance: In 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.

Pandemic beyond the virus: maternal COVID-related postnatal stress is associated with infant temperament.

BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.

Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection.

Importance: Associations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown. Objective: To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months. Design, Setting, and Participants: A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses. Exposures: Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic. Main Outcomes and Measures: Outcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months. Results: Of 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models. Conclusions and Relevance: In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic.