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CME / CE

What Can Be Learned From COVID-19--Related Perinatal Deaths?

  • Authors: News Author: Mary Chris Jaklevic; CME Author: Laurie Barclay, MD
  • CME / CE Released: 3/25/2022
  • Valid for credit through: 3/25/2023
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  • Credits Available

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

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

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

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    • Letter of Completion

Target Audience and Goal Statement

This activity is intended for obstetricians/gynecologists, infectious disease clinicians, primary care and internal medicine clinicians, nurses, pathologists and laboratory medicine practitioners, and other members of the healthcare team for pregnant women with SARS-CoV-2 infection who may be at risk for COVID-19--related perinatal deaths.

The goal of this activity is to describe the role of the placenta in causing stillbirth and neonatal death after maternal COVID-19 and confirmed placental positivity for SARS-CoV-2, according to a case-based retrospective clinico-pathological analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 493 neonatal deaths with placentas testing positive for SARS-CoV-2 after delivery.

Upon completion of this activity, participants will:

  • Describe the role of the placenta in causing stillbirth and neonatal death after maternal COVID-19 and confirmed placental positivity for SARS-CoV-2, according to a case-based retrospective clinico-pathological analysis
  • Determine clinical implications of the role of the placenta in causing stillbirth and neonatal death after maternal COVID-19 and confirmed placental positivity for SARS-CoV-2, according to a case-based retrospective clinico-pathological analysis
  • Outline implications for the healthcare team


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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

  • Mary Chris Jaklevic

    Freelance writer, Medscape

    Disclosures

    Disclosure: Mary Chris Jaklevic has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Stock, stock options, or bonds: AbbVie Inc. (former)

Editor/Nurse Planner

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

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

Compliance Reviewers

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Disclosure: Yaisanet Oyola, MD, has no relevant financial relationships.


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    For Nurses

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CME / CE

What Can Be Learned From COVID-19--Related Perinatal Deaths?

Authors: News Author: Mary Chris Jaklevic; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / CE Released: 3/25/2022

Valid for credit through: 3/25/2023

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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 COVID-19 vaccines may be provided in this activity 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

A CDC population-based study showed that pregnant women with COVID-19 had greater risk for stillbirth than uninfected women, particularly during Delta variant predominance. Most viral infections cause fetal death by transplacental passage and fetal infection, but the mechanism of fetal death from SARS-CoV-2 remains largely unknown. This led a global team of researchers to study COVID-19 infected placentas, which was published in February 2022 in the Archives of Pathology & Laboratory Medicine.[1] The results of this study also support the Centers for Disease Control and Prevention’s (CDC) report that maternal COVID-19 increases the risk of losing a pregnancy.[2] While additional studies will be needed, these current findings will help support members of the healthcare team to recommend vaccination against COVID-19 for women who are pregnant, recently pregnant, or planning to become pregnant.

Study Synopsis and Perspective

Recent evidence has shown women who contract COVID-19 during pregnancy are at increased risk for pregnancy loss and neonatal death. Now, an analysis of pathology data from dozens of perinatal deaths shows how.

Unlike numerous pathogens that kill the fetus by infecting it directly, SARS-CoV-2 causes "widespread and severe" destruction of the placenta that deprives the fetus of oxygen, a team of 44 researchers in 12 countries concluded after examining 64 stillbirths and 4 neonatal deaths in which the placentas were infected with the virus. They noted that such damage occurs in a small percentage of pregnant women with COVID-19, and that all the women in the study had not been vaccinated against the disease.

The findings were published online today in the Archives of Pathology & Laboratory Medicine.[1]

Nearly all placentas had each of 3 features that pathologists have dubbed "SARS-CoV-2 placentitis": large deposits of fibrin, a clotting protein that obstructs the flow of blood; death of cells in the trophoblast; and an unusual form of inflammation called "chronic histiocytic intervillositis." Some had other abnormalities that could have exacerbated the condition.

The researchers called the extent of damage "striking," affecting 77.7% of the placenta on average. The virus did not appear to harm fetal tissue, but placental damage "was extensive and highly destructive," they wrote. Notably, none of the women in the analysis was known to have severe COVID-19.

Virus Seen "Chewing Up the Placenta"

David Schwartz, MD, a pathologist in Atlanta, Georgia, and the lead author of the study, said COVID-19 appears to be unique in destroying the placenta.

"I don't know of any infection that does that to this degree or with this uniformity," Schwartz told Medscape Medical News. "The simple message is that this infection is chewing up the placenta and destroying its capability to oxygenate the fetus."

The CDC reported in November[2] that maternal COVID-19 increases the risk of losing a pregnancy. From March 2020 to September 2021, a total of 8154 stillbirths were reported, affecting 0.65% of births by women without COVID-19 and 1.26% of births by women with COVID-19, for an adjusted relative risk (aRR) of 1.9 (95% CI: 1.69, 2.15).

Delta, the variant that dominated in mid-2021, appears to have been particularly harmful. The CDC reported that the aRR for stillbirth for mothers with COVID-19 during that period increased to 4.04 (95% CI: 3.28, 4.97). Many cases in the new analysis coincided with Delta.

Schwartz and his colleagues said immunization, along with antiviral therapy, might reduce the chance of SARS-CoV-2 infecting the placenta.[1] None of the mothers in the analysis were vaccinated, and Schwartz said he is not aware of a single case in a vaccinated woman.

The analysis comes on the heels of a study from the National Institutes of Health[3] linking severe to moderate COVID-19 to greater risk for other pregnancy complications: cesarean and preterm delivery, death during childbirth, postpartum hemorrhaging, and non--COVID-19.

Diana Bianchi, MD, director of the National Institute of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development, said those findings underscore the need for pregnant women to be vaccinated. (The shots have been shown to be safe for pregnant women.[4])

Denise Jamieson, MD, MPH, chair of the department of gynecology and obstetrics at Emory University, Atlanta, Georgia, who was not involved in the new analysis, said the findings may have important clinical implications. In addition to ensuring that pregnant patients are fully vaccinated, she said, "There may be opportunities to more closely monitor the placenta during pregnancy using imaging modalities such as ultrasound."

Even in the presence of severe abnormalities, a fetus that has reached a viable gestational age could potentially be delivered before stillbirth, Jamieson said. The 64 stillbirths in the analysis ranged from 15 to 39.2 weeks of gestation, with an average of 30 weeks.[1] Eight were delivered at full term.

Additional studies are needed to support monitoring of placental changes, she said, however, adding, "It is not ready for prime time now."

Christopher Zahn, MD, vice president of practice activities the American College of Obstetricians and Gynecologists (ACOG), cautioned that data on COVID-19 and pregnancy complications remain limited.

The findings in this analysis "do not prove the association between COVID-19 infection and neonatal outcomes," Zahn said. "While stillbirth could potentially be another adverse outcome for pregnant people who contract COVID-19, currently we don't have enough data to confirm that a COVID-19 infection at any point in pregnancy indicates increased risk of stillbirth."

He added that ACOG continues to strongly recommend vaccination against COVID-19 for women who are pregnant, recently pregnant, or planning to be pregnant.

Schwartz and Jamieson have disclosed no relevant financial relationships. One author reported receiving financial support from the Slovak Research and Development Agency. Another reported funding from the Belgian Fund for Scientific Research and the Fetus for Life charity.

Study Highlights

  • This study of placental and autopsy pathology findings from 12 countries included 64 stillborns and 493 neonatal deaths with placentas positive for SARS-CoV-2 after delivery to mothers with COVID-19.
  • None of the mothers were vaccinated or had severe COVID-19.
  • All 68 placentas had increased fibrin deposition and villous trophoblast necrosis, and 66 had chronic histiocytic intervillositis, which are the 3 findings of SARS-CoV-2 placentitis; 63 had massive perivillous fibrin deposition.
  • Severe destructive placental disease from SARS-CoV-98 placentitis averaged 77.7% tissue involvement.
  • Multiple intervillous thrombi occurred in 37% and chronic villitis in 32%.
  • In those placentas where the virus was localized using immunohistochemistry or RNA in situ hybridization, the syncytiotrophoblast was involved in all cases.
  • Among 30 autopsies, 63% had no significant fetal abnormalities except for intrauterine hypoxia and asphyxia; 4 had SARS-CoV-2 identified in internal organs.
  • The investigators concluded that SARS-CoV-2 placentitis pathology causes widespread, severe placental destruction, resulting in placental malperfusion and insufficiency.
  • The extent of placental damage (77.7%) far exceeded that seen with other viral TORCH agents and prevented placental function at the level needed to provide sufficient oxygen and nutrients to the fetus to sustain life.
  • Placental insufficiency and fetal hypoxic-ischemic injury likely caused intrauterine and perinatal death.
  • Fortunately, this sequence of events develops in only a small percentage of pregnant women with COVID-19.
  • Recent research suggests that the major pathology lesions -- fibrin deposition, trophoblast necrosis, and chronic histiocytic intervillositis -- can occur independent of maternal infection severity.
  • There was no evidence implicating fetal SARS-CoV-2 involvement in fetal deaths.
  • Unlike many other TORCH agents, SARS-CoV-2 virus did not cause mortality by inducing fetal somatic organ damage after placental infection and transplacental transmission.
  • Instead, tissue damage was confined to the placenta, where it was extensive and highly destructive, and might be detected by obstetrical ultrasound, which may be useful to screen pregnant women infected with SARS-CoV-2.
  • Doppler ultrasound including superb microvascular imaging and magnetic resonance imaging using T2-weighted rapid acquisition with relaxation enhancement may also be useful to image the placenta.
  • The investigators recommend that pregnant women with acute SARS-CoV-2 infection be closely monitored for the first 2 to 3 weeks for fetal well-being to help prevent intrauterine fetal death.
  • Reducing maternal SARS-CoV-2 viral burden through immunization and/or antiviral therapy may reduce risk of developing SARS-CoV-2 placentitis.
  • ACOG continues to strongly recommend vaccination against COVID-19 for women who are pregnant, recently pregnant, or planning to become pregnant.
  • Study limitations include retrospective design and protocols for clinical and laboratory evaluation varying by site.

Clinical Implications

  • SARS-CoV-2 placentitis pathology causes widespread, severe placental destruction, resulting in placental malperfusion and insufficiency.
  • Unlike many other TORCH agents, SARS-CoV-2 virus did not cause mortality by inducing fetal somatic organ damage after placental infection and transplacental transmission.
  • Implications for the Healthcare Team: ACOG continues to strongly recommend vaccination against COVID-19 for women who are pregnant, recently pregnant, or planning to become pregnant, since reducing maternal SARS-CoV-2 viral burden through immunization and/or antiviral therapy may reduce the risk of developing SARS-CoV-2 placentitis.

 

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