COVID-19 Severity in Pregnancy Appears Lower Than H1N1

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MAY 18, 2020 -- Unlike past respiratory illnesses, pregnancy does not seem to put women at risk of worse outcomes from COVID-19, according to the first 6 weeks of births to women in the UK during the COVID-19 era.

"When we actually looked at our data in nonpregnant women of the same age, the outcomes look to be pretty similar for [mothers]" with COVID-19, study coauthor Marian Knight, MBChB, DPhil, professor of maternal and child health at the University of Oxford, United Kingdom, told Medscape Medical News.

The data, currently available on a pre-print database, also suggest that more severe outcomes are more likely in later pregnancy, which Knight said should support guidance that women in the third trimester be vigilant with physical distancing, masking, and hand hygiene to avoid acquiring SARS-CoV-2 in the first place. The paper has not been peer-reviewed and therefore the findings should be taken as preliminary until it is accepted.

The data may also temper concerns raised in early case reports on miscarriage and other poor outcomes.

"Most of the publications in pregnancy have been case series, and we've really had no idea how representative they are of all the women affected," she said. "These results can be reassuring" that poor outcomes may indeed be less common than the current literature suggests.

One, Two, 400 Cases

Back in 2012, Knight was doing surveillance on pregnancy during another pandemic: the H1N1 flu. It turned out to be vital for understanding that disease's spread. When that pandemic subsided, the UK National Institute of Health Research asked researchers to be prepared to conduct similar surveillance when the next pandemic arose. Knight and colleagues were among those who geared up for when the day came.

And then SARS-CoV-2 arrived in the UK. At the end of February, Knight got the call to start monitoring the UK's 194 obstetric units for COVID-19 hospitalizations and their outcomes.

"I was asked to start collecting data on the Friday and we started on the Monday," she said.

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Between March 1 and April 15, a total of 86,293 women gave birth. Only 427 of the births were to women with diagnosed COVID-19 that was serious enough for them to be hospitalized. The study does not include all women in the UK with SARS-CoV-2, as universal testing is unavailable, she said. Knight's results only look at hospitalized women with confirmed SARS-CoV-2 infection and serious disease.

These are likely not all the women in the UK who gave birth while positive for SARS-CoV-2, said Knight, so the data still represent a small slice of the overall infection rate.

"What we can't see is what potential impact a mild or indeed asymptomatic infection, if such a thing exists, has on the pregnancy," Knight said. "I cannot from this study give you an infection rate. But I can give you a 'hospitalized with infection' rate."

That rate is 4.9 per 1000 maternities. By comparison, the hospitalization rate — a marker of disease severity — of pregnant women with H1N1 was 8 per 1000 maternities.

This is notable and unexplained, said Christopher Zahn, MD, vice president of practice activities at the American College of Obstetricians and Gynecologists.

"It's interesting because looking back at some of the other infectious outbreaks, such as H1N1, where pregnant women were at increased risk," he told Medscape Medical News. "But with H1N1, pregnant women were at increased risk. But that's not been identified in COVID either in international data or the emerging US data."

Indeed, Lynne Mofenson, MD, senior HIV technical advisor to the Elizabeth Glaser Pediatric AIDS Foundation, saw Knight's data, and has been tracking all the current studies on COVID-19 and pregnancy; she's also been giving presentations on the current state of knowledge on the illness and pregnancy outcomes.

It's a subject close to Mofenson's heart. A former official at the Eunice Kennedy Shriver National Institute for Child Health and Human Development, Mofenson is best known for spearheading the government's effort to prevent mother-to-child transmission of HIV in the late 1980s and early '90s.

As of May 11, Mofenson found 100 papers — including Knight's — describing the experiences of 1308 pregnant women with COVID-19 hospitalized worldwide. Only 44 (3.3%) those 1308 cases were single-case reports of extreme experiences. Fifty papers "appear to be duplicate reports on the same patients," Mofenson wrote in a presentation she shared with Medscape Medical News.

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Over and over again, she pointed to studies that show a 2% hospitalization rate for pregnant women listed as their underlying condition requiring hospitalization.

"Given that about 2% of women in the US are pregnant on any day (3.3M/152M), pregnant women are not disproportionately represented among those with COVID-19 diagnosis," Mofenson explained in her presentation.

"In general, pregnant women appear to have mild disease as does the general population," she told Medscape Medical News. "There doesn't appear to be an increased risk of infection and potentially not increased risk of hospitalization."

But she added that most reports compare pregnant women with COVID-19 to nonpregnant women with COVID-19 — meaning they aren't necessarily comparing pregnant and nonpregnant women of the same age group, as Knight's paper does. So there are still questions to be answered.

"Pregnant women are in the 20- to 44-year-old age group, and that age group generally has more people with more mild disease and very low hospitalization or mortality," she said, while nonpregnant women with severe COVID-19 tend to be older. "So maybe we are comparing to the wrong group?"

Preterm Births

Indeed, among the pregnant women with SARS-CoV-2 infection in Knight’s study, 247 women gave birth during the study period. Four women experienced pregnancy loss, though it’s unclear if that was related to COVID-19. And 81% of them were in their last trimester (median 34 weeks completed gestation). Premature birth is generally before week 37.

Three quarters of births overall were at term, with 26% of them preterm births. By comparison, a 2010 surveillance report in the Journal of the American Medical Association found that 30.2% of pregnant women experienced preterm birth during the H1N1 pandemic in 2009. In 2018, the overall rate of preterm births in the US was 10% (black women, 14%; white women, 9%), according to the US Centers for Disease Control and Prevention.

But for UK residents with COVID-19 serious enough to be admitted to an intensive care unit, rates of preterm births flipped: For the 40 women admitted to an ICU, the preterm birth rates were 75%. The vast majority (79%) were medically indicated preterm births to protect the mother, the fetus, or for other obstetrical reasons.

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And even though 59% of women had cesarean deliveries, "the majority of cesarean births occurred for indications other than maternal compromise due to SARS-CoV-2 infections," Knight reports in the paper.

The 40 women admitted to the ICU represent 9% of the total cohort. Three out of four of those women gave birth during their hospitalization as a result of COVID-19 complications. At the end of the study period, 5 women died, or a rate of about 1%.

One in 10 of the mothers with COVID-19 required respiratory support, and nearly half of those were discharged by the time researchers began analyzing the data.

Of the births, 26% of the infants were admitted to a neonatal ICU. Most of these were preterm births (72%), with 1 neonatal encephalopathy diagnosis.

Twelve infants, representing 5% of the overall number, were positive for SARS-CoV-2 RNA — but it's unclear from the data whether any of the infants developed COVID-19. Six of those 12 were treated in the NICU.

In this surveillance study, no placenta samples or vaginal swabs were taken, so it's impossible to answer questions raised by some case reports, finding SARS-CoV-2 in the placenta.

Five babies died — three "definitely unrelated to SARS-CoV-2 infection," they write in the paper. In the other two, "it was unclear whether SARS-CoV-2 contributed to the death."

Comorbidities in Pregnant Women

Zahn said ACOG's COVID-19 practice advisory and its COVID-19 FAQs do not recommend changing practice based on case reports. Instead, he suggested that clinical practice include SARS-CoV-2 as an additional comorbidity for pregnant women — and that these women should be counseled accordingly.

"We certainly recognize that comorbidities put patients at higher risk" for severe COVID-19 outcomes, he said. "We assume — we don't actually have that data but we assume — that those same comorbidities in pregnant women could increase their risk."

But without comorbidities, he said, "the data would suggest so far that pregnant women are not at increased risk of either becoming infected or developing severe disease compared to nonpregnant patients."

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