Background <p>Although vertical transmission of SARS-CoV-2 from mother to fetus is rare, the neurodevelopmental impact of in utero SARS-CoV-2 exposure on infants needs further elucidation.</p> Objective <p>To investigate the neurodevelopmental outcomes at 12 and 22 corrected age among infants who had exposure to confirmed maternal SARS-CoV-2 infection during pregnancy.</p> Design/Methods <p>We conducted a prospective cohort study of neonates born to women with SARS-CoV-2 infection in pregnancy, from March 2020 to December 2022 (COVID-19 waves 1–5). Infants were recruited from six (5 community and 1 tertiary) hospitals. Data were collected at birth and three subsequent time periods. A telephone call was made at one&#xa0;month to assess general health and wellness. A virtual neurodevelopmental assessment was conducted at 12 months using the Ages and Stages Questionnaire (ASQ) and the Communication and Symbolic Behavior Scales (CSBS). In-person neurodevelopmental assessment was conducted at 22 months using the Bayley Scales of Infant and Toddler Development-4th Edition (BSID-IV).</p> Results <p>A total of 142 infants were recruited and included in the study. Of those, a one-month assessment was completed in 141 (99%), a 12-month assessment completed in 63 (44%), and a 22-month assessment completed in 44 (31%) infants. At one&#xa0;month, most infants had no medical concerns; 11 infants were re-admitted to the hospital within the first month of life, predominantly for hyperbilirubinemia. At 12 months, median ASQ and CSBS scores were above standardized cut-offs for development across all developmental domains. At 22 months, while the median standard cognitive, language, and motor scores were within the average classification (25–37th percentile), twenty-three (52%) infants presented with developmental impairment (score &lt;85); 13 (30%) in motor, 17 (39%) in language, and 13 (30%) in cognitive domains. Nine (20%) infants were below cut-off for all three domains. Multivariable logistic modelling did not identify an independent relationship between trimester of SARS-CoV-2 acquisition or positive SARS-CoV-2 test at delivery and the&#xa0;presence of developmental delay on BSID-IV in any domain. No child had hearing impairment or blindness.</p> Conclusions <p>Developmental delay at 22 months may be identified among infants with in utero exposure to SARS-CoV-2, despite typical developmental progress at 12 months. These findings may be impacted by the loss to follow-up rate. Of those with developmental diversity, language delay was most common.</p>

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The association of in utero SARS-CoV-2 exposure on neurodevelopmental outcomes at 12 and 22 months

  • Ashraf Kharrat,
  • Erin Gleeson,
  • Vanessa Pippert,
  • Shaheen Doctor,
  • Douglas Campbell,
  • Catherine Taylor,
  • Simone Vaz,
  • Taslim Dawood,
  • Seungwoo Lee,
  • Jyotsna Shah,
  • Edmond Kelly,
  • Prakesh S. Shah

摘要

Background

Although vertical transmission of SARS-CoV-2 from mother to fetus is rare, the neurodevelopmental impact of in utero SARS-CoV-2 exposure on infants needs further elucidation.

Objective

To investigate the neurodevelopmental outcomes at 12 and 22 corrected age among infants who had exposure to confirmed maternal SARS-CoV-2 infection during pregnancy.

Design/Methods

We conducted a prospective cohort study of neonates born to women with SARS-CoV-2 infection in pregnancy, from March 2020 to December 2022 (COVID-19 waves 1–5). Infants were recruited from six (5 community and 1 tertiary) hospitals. Data were collected at birth and three subsequent time periods. A telephone call was made at one month to assess general health and wellness. A virtual neurodevelopmental assessment was conducted at 12 months using the Ages and Stages Questionnaire (ASQ) and the Communication and Symbolic Behavior Scales (CSBS). In-person neurodevelopmental assessment was conducted at 22 months using the Bayley Scales of Infant and Toddler Development-4th Edition (BSID-IV).

Results

A total of 142 infants were recruited and included in the study. Of those, a one-month assessment was completed in 141 (99%), a 12-month assessment completed in 63 (44%), and a 22-month assessment completed in 44 (31%) infants. At one month, most infants had no medical concerns; 11 infants were re-admitted to the hospital within the first month of life, predominantly for hyperbilirubinemia. At 12 months, median ASQ and CSBS scores were above standardized cut-offs for development across all developmental domains. At 22 months, while the median standard cognitive, language, and motor scores were within the average classification (25–37th percentile), twenty-three (52%) infants presented with developmental impairment (score <85); 13 (30%) in motor, 17 (39%) in language, and 13 (30%) in cognitive domains. Nine (20%) infants were below cut-off for all three domains. Multivariable logistic modelling did not identify an independent relationship between trimester of SARS-CoV-2 acquisition or positive SARS-CoV-2 test at delivery and the presence of developmental delay on BSID-IV in any domain. No child had hearing impairment or blindness.

Conclusions

Developmental delay at 22 months may be identified among infants with in utero exposure to SARS-CoV-2, despite typical developmental progress at 12 months. These findings may be impacted by the loss to follow-up rate. Of those with developmental diversity, language delay was most common.