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CME / ABIM MOC / CE

Does Prenatal COVID-19 Exposure Affect Neurodevelopment?

  • Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 7/29/2022
  • Valid for credit through: 7/29/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for psychiatrists, internists, pediatricians, family medicine and primary care clinicians, physician assistants, obstetricians/gynecologists/women's health clinicians, neurologists, nurses, infectious disease clinicians, pharmacists, and other members of the healthcare team for pregnant women with COVID-19 and their offspring.

The goal of this activity is for learners to be better able to describe possible associations of in utero exposure to SARS-CoV-2 with risk for neurodevelopmental disorders in the first 12 months after birth.

Upon completion of this activity, participants will:

  • Describe possible association of in utero exposure to SARS-CoV-2 with risk for neurodevelopmental disorders in the first 12 months after birth, according to a retrospective cohort study of EHRs
  • Identify clinical implications of possible associations of in utero exposure to SARS-CoV-2 with risk for neurodevelopmental disorders in the first 12 months after birth, according to a retrospective cohort study of EHRs
  • Outline implications for the healthcare team


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated according to Medscape policies. Others involved in the planning of this activity have no relevant financial relationships.


News Author

  • Megan Brooks

    Freelance writer, Medscape

    Disclosures

    Megan Brooks has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie Inc.

Editor/Nurse Planner

  • Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

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    Medscape, LLC has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.25 AAPA Category 1 CME credits. Approval is valid until 7/29/2023. PAs should only claim credit commensurate with the extent of their participation.

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CME / ABIM MOC / CE

Does Prenatal COVID-19 Exposure Affect Neurodevelopment?

Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 7/29/2022

Valid for credit through: 7/29/2023

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Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to the approved COVID-19 vaccines are provided in this activity in an effort to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

During key developmental windows, maternal and placental inflammation and altered cytokine expression, as could be triggered by maternal COVID-19, may affect the developing fetal brain. Epidemiologic studies have shown that maternal infection in pregnancy is associated with adverse neurodevelopmental outcomes.

Some adults and children have neuropsychiatric symptoms and region-specific changes in brain morphology after COVID-19 persisting up to a year after acute illness. COVID-19 may be associated with preterm delivery and other birth complications, with greater infection severity linked to greater preterm risk.

Study Synopsis and Perspective

Infants exposed to SARS-CoV-2 in utero are at increased risk for neurodevelopmental disorders in the first year of life, new research suggests, but whether it is exposure to the pandemic or maternal exposure to the virus itself that may harm early childhood neurodevelopment is unclear, cautioned investigators, led by Roy Perlis, MD, MSc, with Massachusetts General Hospital, Boston, Massachusetts.

"In this analysis of 222 offspring of mothers infected with SARS-CoV-2, compared with the offspring of 7550 mothers in the control group (not infected) delivered during the same period, we observed neurodevelopmental diagnoses to be significantly more common among exposed offspring, particularly those exposed to third-trimester maternal infection," they wrote.

The study was published June 1 in JAMA Network Open.

Speech and Language Disorders

The study included 7772 mostly singleton live births across 6 hospitals in Massachusetts between March and September 2020, including 222 (2.9%) births to mothers with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) testing during pregnancy.

In all, 14 of 222 children born to SARS-CoV-2--infected mothers (6.3%) were diagnosed with a neurodevelopmental disorder in the first year of life vs 227 of 7550 unexposed offspring (3%) (unadjusted odds ratio [OR] 2.17 [95% CI: 1.24, 3.79]; P = .006).

In models adjusted for preterm delivery, as well as race, ethnicity, insurance status, child sex, and maternal age, COVID-exposed offspring were significantly more likely to receive a neurodevelopmental diagnosis in the first year of life (adjusted odds ratio [aOR 1.86 [95% CI: 1.03, 3.36]; P = .04).

The magnitude of the association with neurodevelopmental disorders was greater with third-trimester SARS-CoV-2 infection (aOR 2.34 [95% CI: 1.23, 4.44]; = .01).

The majority of these diagnoses reflected developmental disorders of motor function or speech and language.

The researchers noted the finding of an association between prenatal SARS-CoV-2 exposure and neurodevelopmental diagnoses at 12 months are in line with a "large body of literature" linking maternal viral infection and maternal immune activation with offspring neurodevelopmental disorders later in life.

They cautioned, however, that whether a definitive connection exists between prenatal SARS-CoV-2 exposure and adverse neurodevelopment in offspring is not yet known, in part because children born to women infected in the first wave of the pandemic have not reached their second birthday: a time when neurodevelopment disorders such as autism are typically diagnosed.

There is also the risk for ascertainment bias arising from greater concern for offspring of infected mothers who were ill during pregnancy. These parents may be more inclined to seek evaluation, and clinicians may be more inclined to diagnose or refer for evaluation, the researchers noted.

Nonetheless, as reported by Medscape Medical News, the study results support those of research released at the European Psychiatric Association (EPA) 2022 Congress[2]; those results also showed an association between maternal SARS-CoV-2 infection and impaired neurodevelopment in 6-week-old infants.

Hypothesis-Generating

In an accompanying commentary,[3] Torri D. Metz, MD, MS, with University of Utah Health, Salt Lake City, Utah, said the preliminary findings of Perlis and colleagues are "critically important, yet many questions remain.

"Essentially all of what we know now about the effects of in utero exposure to maternal SARS-CoV-2 infection is from children who were exposed to the early and Alpha variants of SARS-CoV-2, as those are the only children now old enough to undergo rigorous neurodevelopmental assessments," Metz pointed out.

Ultimately, Metz said it is not surprising that the pandemic and in utero exposure to maternal SARS-CoV-2 infection may adversely affect neurodevelopmental outcomes in young children.

Yet, as a retrospective cohort study, the study can only demonstrate associations, not causality.

"This type of work is intended to be hypothesis-generating, and that goal has been accomplished as these preliminary findings generate numerous additional research questions to explore," Metz wrote.

Among them: Are there genetic predispositions to adverse outcomes? Will we observe differential effects by SARS-CoV-2 variant, by severity of infection, and by trimester of infection? Is it the virus itself or all of the societal changes that occurred during this period, including differences in how those changes were experienced among those with and without SARS-CoV-2?

"Perhaps the most important question is how do we intervene to help mitigate the adverse effects of the pandemic on young children," Metz noted.

"Prospective studies to validate these findings, tease out some of the nuance, and identify those at highest risk will help health care practitioners appropriately dedicate resources to improve outcomes as we follow the life course of this generation of children born during the COVID-19 pandemic," she added.

The study was supported by the National Institute of Mental Health and the National Institute of Child Health and Human Development. Metz reported receiving personal fees and grants from Pfizer Inc. and grants from GestVision.

Study Highlights

  • The retrospective cohort included live offspring of all mothers who delivered between March and September 2020 (7772 live births; 7466 pregnancies, 96% singleton, 222 to SARS-CoV-2--positive mothers) at 6 Massachusetts hospitals across 2 health systems.
  • International Classification of Disease, 10th revision diagnostic codes for neurodevelopmental disorders over the first 12 months of life and sociodemographic and clinical features of mothers and offspring were determined from EHR review.
  • Mean maternal age was 32.9 ± 5 years; offspring were 9.9% Asian, 8.4% Black, 69.9% White, and 15.1% were Hispanic.
  • Mothers with SARS-CoV-2 infection (confirmed by PCR test) during pregnancy were more likely to have preterm delivery (14.4% vs 8.7%; P = .003).
  • Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (OR 2.17 [95% CI: 1.24, 3.79]; P = .006) and in models adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (aOR 1.86 [95% CI: 1.03, 3.36]; P = .04).
  • Third-trimester infection was associated with larger effects (aOR 2.34 [95% CI: 1.23, 4.44]; P = .01).
  • Most developmental disorders affected motor function or speech and language.
  • Median time to diagnosis was earlier among exposed (214 [interquartile range (IQR), 183-316] days) vs unexposed offspring (275 [IQR, 253-346]) days.
  • The investigators concluded that their study found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring, even after accounting for preterm delivery.
  • The finding that directionality and magnitude of effect are maintained among term deliveries warrants follow-up in larger, adequately powered studies.
  • Prospective studies with longer follow-up of large, representative cohorts are needed to confirm these associations and exclude confounding and to more precisely estimate the risk for, and potential nature of, neurodevelopmental sequelae of prenatal SARS-CoV-2 exposure.
  • The analysis also indicates the feasibility of using EHR data for a retrospective cohort study allowing detection of risk signals before such large-scale, prospective follow-up studies are available.
  • This approach, using coded clinical data extracted from the EHR, could be scaled across multiple US and international health systems.
  • Study limitations include ascertainment bias arising from greater concern for offspring of mothers who were ill during pregnancy, and limited duration of follow-up, as the offspring analyzed are younger than the age at which neurodevelopmental disorders such as autism are typically diagnosed.
  • An accompanying commentary noted that these preliminary findings were only from children with prenatal exposure to early and Alpha SARS-CoV-2 variants, as only they are now old enough to undergo rigorous neurodevelopmental testing.
  • The retrospective design precludes causal inferences.
  • Still unanswered questions include genetic predispositions to adverse outcomes; differing effects by SARS-CoV-2 variant, infection severity, and trimester; possible confounding effects of societal changes during the pandemic; and possible interventions to lessen the pandemic’s adverse effects on young children.

Clinical Implications

  • Maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring, even after accounting for preterm delivery.
  • The preliminary findings need confirmation in larger, prospective, adequately powered studies with longer follow-up.
  • Implications for the Healthcare Team: While further studies are needed, members of the healthcare team should continue to provide education on evidence-based mitigation strategies as COVID-19 may be associated with preterm delivery and other birth complications.

 

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