Effects of intrauterine exposure to SARS-CoV-2 on infants’ development: a rapid review and meta-analysis

Pinheiro, Gabriela Soutto Mayor Assumpção; Souza, Rayany Cristina de; Azevedo, Vívian Mara Gonçalves de Oliveira; Guimarães, Nathália Sernizon; Pires, Laura Gregório; Lemos, Stela Maris Aguiar; Alves, Cláudia Regina Lindgren

doi:10.1007/s00431-023-04910-8

Cited by 16 publications

(12 citation statements)

References 58 publications

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“…(6, 7). Similarly, authors of a prospective cohort study of 127 children in Brazil found an increased risk of neurodevelopmental delay with in utero SARS-CoV-2 exposure during pregnancy (8), and a recent meta-analysis of smaller studies identified additional evidence of neurodevelopmental sequelae – including reductions in fine motor and problem-solving skills – in infants with in utero SARS-CoV-2 exposure compared to unexposed and pre-pandemic cohorts (9). If these early signals foreshadow an increased risk of neurodevelopmental disorders in childhood and adulthood, the public health implications could be profound, given the significant number of pregnancies exposed to SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

Shook,

Batorsky,

De Guzman

et al. 2023

Preprint

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The SARS-CoV-2 virus activates maternal and placental immune responses, which in the setting of other infections occurring during pregnancy are known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. Here, we assessed the impact of maternal SARS-CoV-2 on HBCs isolated from term placentas using single-cell RNA-sequencing. We demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells, with altered morphology and impaired synaptic pruning behavior compared to HBC models from negative controls. These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.

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Section: Introductionmentioning

confidence: 99%

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

Shook,

Batorsky,

De Guzman

et al. 2023

Preprint

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“…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 .…”

mentioning

confidence: 98%

“…Similarly, other studies have compared developmental outcomes between children assessed before vs during the pandemic, but these have not taken into account potential in utero effects. 5 The findings of Finegold et al 2 highlight the differential associations between postnatal exposure to the COVID-19 pandemic and early child developmental outcomes in a homogeneous, sociodemographically advantaged population. The study authors implemented a study of preschool children assessed at ages 24 and 54 months, all of whom were born before the COVID-19 pandemic began.…”

mentioning

confidence: 99%

“…The first involves comparing developmental outcomes in children with vs without exposure to prenatal maternal SARS-CoV-2 infection. [3][4][5] The second compares developmental outcomes in children born before vs during the COVID-19 pandemic. 6 The interpretation of these findings is limited in that the children born during the pandemic inherently had a different in utero experience than the comparison cohort of children born before the pandemic.…”

mentioning

confidence: 99%

“…The interpretation of these findings is limited in that the children born during the pandemic inherently had a different in utero experience than the comparison cohort of children born before the pandemic. Similarly, other studies have compared developmental outcomes between children assessed before vs during the pandemic, but these have not taken into account potential in utero effects …”

mentioning

confidence: 99%

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

Firestein,

Shuffrey

2023

JAMA Netw Open

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Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic

Firestein,

Manessis,

Warmingham

et al. 2024

JAMA Netw Open

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ImportanceStress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown.ObjectiveTo examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings.Design, Setting, and ParticipantsData for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024.ExposuresPrenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection.Main Outcomes and MeasuresThe primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed.ResultsThe COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07).Conclusions and RelevanceIn this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

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Effects of intrauterine exposure to SARS-CoV-2 on infants’ development: a rapid review and meta-analysis

Cited by 16 publications

References 58 publications

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

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

Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic

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