Wednesday, August 05, 2020

Pregnancy & COVID-19: Still More Questions Than Answers















#15,399

Historically, influenza pandemics have been particularly dangerous for pregnant women and their unborn children, and in 2016 we saw the tragic - and wholly unexpected - impacts of maternal Zika infection on developing fetuses (primarily) in South America (see CDC Vital Signs - Zika Virus Update).

In a Perspective written by 3 CDC physicians (Sonja A. Rasmussen, Denise J. Jamieson, Joseph S. Bresee) published in 2008 (see Pandemic Influenza and Pregnant Women) we get the following assessment of the historic impact of influenza on pregnant women.

Although appropriate nonpregnant control groups were generally not available, mortality rates among pregnant women in the pandemics of 1918 and 1957 appeared to be abnormally high (5,7). Among 1,350 reported cases of influenza among pregnant women during the pandemic of 1918, the proportion of deaths was reported to be 27% (5). 

Similarly, among a small case series of 86 pregnant women hospitalized in Chicago for influenza in 1918, 45% died (6). Among pregnancy-associated deaths in Minnesota during the 1957 pandemic, influenza was the leading cause of death, accounting for nearly 20% of deaths associated with pregnancy during the pandemic period; half of women of reproductive age who died were pregnant

The following year, the 2009 H1N1 pandemic virus emerged, and once again we saw numerous reports of a disproportionate impact on pregnant women, and their unborn child (see 2009's Pregnancy & Flu: A Bad Combination).
In 2011's  BMJ: Perinatal Outcomes After Maternal 2009 H1N1 Infection we saw a study showing women who were admitted to the hospital with maternal H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.
ABSTRACT: Severely ill women with 2009 H1N1 influenza during pregnancy were more likely to have adverse birth outcomes than women without influenza, providing more support for influenza vaccination during pregnancy.
Given this somber history, there are understandable concerns over the impact of SARS-CoV-2 infection on pregnant women and their child they carry.  Given how new COVID-19 is, we have limited data on which to rely.

But a couple of weeks ago, Nature Communications carried a report of a woman's infection in her 3rd trimester and the apparent infection of her child in utero. The child was born in March, and the neonate displayed temporary neurological manifestations, but has reportedly since recovered. 
Alexandre J. Vivanti, Christelle Vauloup-Fellous, Sophie Prevot, Veronique Zupan, Cecile Suffee, Jeremy Do Cao, Alexandra Benachi & Daniele De Luca 

Nature Communications volume 11, Article number: 3572 (2020) Cite this article

Abstract

SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. 

We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise.
The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.
          (SNIP)
In conclusion, we have demonstrated that the transplacental transmission of SARS-CoV-2 infection is possible during the last weeks of pregnancy. Transplacental transmission may cause placental inflammation and neonatal viremia. Neurological symptoms due to cerebral vasculitis may also be associated.

Another report, presented at a COVID-centric session of the 2020 virtual International AIDS Conference in July, described 31 pregnant women in Italy who were infected with the virus late in their 3rd trimester, with two of them giving birth to babies infected with SARS-CoV-2  (see MedPage Today  Report: COVID-19 Transmitted to Babies in Utero). 

While the evidence for in utero infection with SARS-COV-2 remains limited, as does proof of lasting harm to the unborn child, the evidence that COVID-19 is more dangerous for the mother than for non-pregnant women is a little more solid. 

In late June the CDC's MMWR reported:
Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020

Weekly / June 26, 2020 / 69(25);769–775

Sascha Ellington, PhD1; Penelope Strid, MPH1; Van T. Tong, MPH1; Kate Woodworth, MD1; Romeo R. Galang, MD1; Laura D. Zambrano, PhD1; John Nahabedian, MS1; Kayla Anderson, PhD1; Suzanne M. Gilboa, PhD1 (View author affiliations)View suggested citation

Summary

What is already known about this topic?

Limited information is available about SARS-CoV-2 infection in U.S. pregnant women.

What is added by this report?

Hispanic and non-Hispanic black pregnant women appear to be disproportionately affected by SARS-CoV-2 infection during pregnancy. Among reproductive-age women with SARS-CoV-2 infection, pregnancy was associated with hospitalization and increased risk for intensive care unit admission, and receipt of mechanical ventilation, but not with death.

What are the implications for public health practice?

Pregnant women might be at increased risk for severe COVID-19 illness. To reduce severe COVID-19–associated illness, pregnant women should be aware of their potential risk for severe COVID-19 illness. Prevention of COVID-19 should be emphasized for pregnant women and potential barriers to adherence to these measures need to be addressed.
          (Continue . . . )

The CDC maintains a Data on COVID-19 during Pregnancy website, but cautions that:
Because only about a quarter of case report forms include information on pregnancy status, these numbers likely do not include all pregnant women with COVID-19 in the United States and must be interpreted with caution. The completeness of this variable continues to improve each week.
The CDC's `living document' Evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from COVID-19, continues to list pregnancy as a 2nd tier (mixed evidence) risk group for severe illness due to COVID-19.  But their guidance for People with Certain Medical Conditions advises:
Pregnancy

Based on what we know at this time, pregnant people might be at an increased risk for severe illness from COVID-19 compared to non-pregnant people. Additionally, there may be an increased risk of adverse pregnancy outcomes, such as preterm birth, among pregnant people with COVID-19.

Actions to take
  • Do not skip your prenatal care appointments.
  • Make sure that you have at least a 30-day supply of your medicines.
  • Talk to your healthcare provider about how to stay healthy and take care of yourself during the COVID-19 pandemic.
  • If you don’t have a healthcare provider, contact your nearest community health centerexternal icon or health department.
  • Call your healthcare provider if you have any questions related to your health.
  • Seek care immediately if you have a medical emergency.
  • You may feel increased stress during this pandemic. Fear and anxiety can be overwhelming and cause strong emotions. Learn about stress and coping.

Admittedly, almost all of the guidance published so far are moderated by words like `might', and `may'.  While the data `may suggest' a heightened risk, it is too limited to base solid conclusions on. 

Frustratingly, we probably won't have a good handle on the actual risks to pregnant women - or their unborn child - for months to come.  And long-term sequelae (if any) make take years to assess. 

I would only add that practically every day we learn about more non-trivial complications from SARS-CoV-2 infection, and that until we know a lot more, avoiding infection if you can - particularly if you are in a high risk group - just makes sense.  

For now, you'll find the latest pregnancy-related guidance from the CDC below.