IMPORTANCEAssociations 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 PARTICIPANTSA 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 MEASURESOutcomes 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. RESULTSOf 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

The intrauterine environment strongly influences development. Neurodevelopmental effects of in utero exposure to maternal SARS-CoV-2 infection are widely speculated but currently unknown. The COVID-19 Mother Baby Outcomes (COMBO) initiative was established at Columbia University Irving Medical Center (CUIMC) in New York City to prospectively study the health and wellbeing of infants with and without in utero exposure to maternal SARS-CoV-2 infection. We report findings on 6-month neurodevelopmental outcomes using the parental-report Ages & Stages Questionnaire, 3rd Edition (ASQ-3), from 107 in utero exposed and 131 unexposed full-term infants born between March and December, 2020. We compare these infants to a historical cohort comprised of 62 infants born at CUIMC at least two months prior to the onset of the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with differences on any ASQ-3 subdomain regardless of infection timing or severity, however, infants born during the pandemic had significantly lower scores on gross motor, fine motor, and personal-social subdomains when compared to the historical cohort. Infants born to women who were in the first trimester of pregnancy during the peak of the pandemic in NYC had the lowest personal-social scores. Birth during the pandemic, but not maternal SARS-CoV-2 infection, was associated with differences in neurodevelopmental outcomes at 6-months. These early findings suggest significantly higher public health impact for the generation born during the COVID-19 pandemic than previously anticipated.

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.

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Importance: In 2021, the American Academy of Pediatrics published a policy statement seeking to create a paradigm shift away from a focus on childhood toxic stress and toward the emphasis on early relational health (ERH) as a buffer for childhood adversity and promoter of life-course resilience. A comprehensive appraisal of the efficacy of contemporary parent/caregiver-child interventions in — primarily — improving ERH, and — secondarily — enhancing child wellbeing and neurodevelopment is needed to guide widespread implementation and policy. Objective: Determine the effectiveness of contemporary early dyadic parent/caregiver-infant interventions on ERH, child socio-emotional functioning and development, and parent/caregiver mental health. Data Sources: PubMed, Medline, Cinhal, ERIC, and PsycInfo were searched on April 28, 2022. Additional sources: clinical trial registries (clinicaltrials.gov, ISRCTN Registry, EU Clinical Trials Register, Australian New Zealand Clinical Trials Registry), contacting authors of unpublished/ongoing studies, backward/forward reference-searching. Study Selection: Studies targeting parent/caregiver-infant dyads and evaluating effectiveness of a dyadic intervention were eligible. Study selection was performed in duplicate, using Covidence. Data Extraction and Synthesis: Cochrane methodological guidance presented per PRISMA guidelines. Data extraction and risk of bias assessment were completed in duplicate with consensuses by first author. Data were pooled using inverse-variance random effects models. Main Outcomes and Measures: The primary outcome domain was ERH. Secondary outcome domains were child socio-emotional functioning and development, and parent/caregiver mental health, and were only considered in studies where at least one ERH outcome was also measured. The association between dose of intervention and effect estimates was explored. Results: 93 studies (14,993 parent/caregiver-infant dyads) met inclusion criteria. Based on very low to moderate quality of evidence, we found significant non-dose-dependent intervention effects on several measures of ERH, including bonding, parent/caregiver sensitivity, attachment, and dyadic interactions, and a significant effect on parent/caregiver anxiety, but no significant effects on other child outcomes. Conclusion: Current evidence does not support the notion that promoting ERH through early dyadic interventions ensures optimal child development, despite effectively promoting ERH outcomes. Given the lack of an association with dose of intervention, the field is ripe for novel, innovative, cost-effective, potent ERH intervention strategies that effectively and equitably improve meaningful long-term child outcomes.