COVID-19 raises the risk of adverse birth outcomes, especially in women with HIV

Maya Jackson-Gibson at CROI 2022.
Maya Jackson-Gibson at CROI 2022.

Women living with HIV who tested positive for COVID-19 around the time of giving birth were significantly more likely to experience adverse birth outcomes than other women with HIV, a study carried out in Botswana has found.

The study, presented on Monday at the Conference on Retroviruses and Opportunistic Infection (CROI 2022), also found that women who tested positive for COVID-19 around the time of delivery were more likely to experience adverse birth outcomes, such as pre-eclampsia, premature delivery and stillbirth, regardless of HIV status.

Both COVID-19 and HIV have been linked to an increased risk of adverse birth outcomes but there is limited information about their combined impact in settings with a high prevalence of HIV among women of child-bearing age. A systematic review of 42 studies, published in April 2021 prior to the Delta variant wave, found that SARS-CoV-2 infection during pregnancy was associated with increased risks of pre-eclampsia, stillbirth and pre-term birth in studies largely carried out in Europe, China and North America.

Glossary

systematic review

A review of the findings of all studies which relate to a particular research question and which conform to pre-determined selection criteria. 

symptomatic

Having symptoms.

 

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

inflammation

The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.

referral

A healthcare professional’s recommendation that a person sees another medical specialist or service.

But these studies did not provide information on whether HIV increases the risk of adverse birth outcomes in women with SARS-CoV-2. This question is especially relevant for women living with HIV in sub-Saharan Africa, where HIV prevalence is high and access to SARS-CoV-2 vaccination remains limited.

Maya Jackson-Gibson of Northwestern University and colleagues conducted a study to investigate whether COVID-19 increased the risk of adverse birth outcomes in women living with HIV.

The study used the birth outcomes surveillance system already in place to capture the effects of HIV and antiretroviral treatment outcomes in Botswana, the Tsepamo study. Data on COVID-19 status at the time of delivery began to be collected at participating hospitals during 2020-2021.

This analysis looked at birth outcomes at 13 Tsepamo sites from September 2020 to November 15 2021, which is before the spread of the Omicron variant in Botswana.

Women were included in the study if they had a known HIV status, gave birth to a single infant and had undergone COVID-19 testing between 14 days prior to delivery and up to three days after delivery.

During the study period 11,483 women were tested for COVID-19, 4.7% tested positive (539) and of these, 144 were living with HIV (44% of women giving birth at study sites had not been tested for COVID-19 and symptomatic women may have been more likely to undergo screening owing to a limited supply of test kits). Women with HIV were significantly more likely to test positive for COVID-19 at delivery (5.6% vs 4.3%, p<0.01). Women who tested positive for COVID-19 were slightly older, more likely to be in work and to deliver at a referral hospital.

COVID-19 cases peaked in July 2021, when the Delta variant wave led to one in ten pregnant women testing positive for COVID-19 at delivery. Four per cent of women who tested positive died during the study period, and the incidence of deaths was higher after the emergence of the Delta variant (5%) from April 2021 than in the previous period (2%).

Adverse birth outcomes occurred more frequently in women who tested positive for COVID-19 (31%) than those who did not (26%). After adjustment for age, the overall rate was 31% higher in women who tested positive. The rate of pre-term delivery was 60% higher, the rate of very pre-term delivery 40% higher and the rate of stillbirth 90% higher in those who tested positive. The rates of neonatal death, small-for-gestational age and very small-for-gestational age did not differ significantly according to COVID-19 status.

The approximate doubling in the risk of stillbirth in women with COVID-19 is similar to the increased risk of stillbirth associated with COVID-19 observed in a study of 1.2 million women who gave birth in the United States between March 2020 and September 2021. The US Centers for Disease Control and Prevention investigators estimated that approximately 30% of women evaluated in that study had been vaccinated. The increased risk of stillbirth may be a consequence of disruption of blood flow and inflammation in the placenta due to SARS-CoV-2 infection, suggesting that prevention of severe COVID-19 illness might also reduce the risk of stillbirth.

Adverse birth outcomes were substantially higher in women with HIV who tested positive for COVID-19 (43%) than HIV-positive women without COVID-19 (30%). After adjustment for age, women with HIV and COVID-19 had a 78% higher risk of any adverse birth outcome, a 65% higher risk of a severe birth outcome, twice the risk of pre-term delivery or very pre-term delivery and a 65% higher risk of having a small-for-gestational age infant. COVID-19 status did not affect the risk of stillbirth or neonatal death.

Very few of the women who took part in this study had been vaccinated against COVID-19. Vaccination began in Botswana in late 2021 and prioritised people over 65 years old. Population-level data on the impact of vaccination on adverse birth outcomes are limited; studies published to date have addressed concerns about the potential excess risk of adverse birth outcomes associated with vaccination (finding none) rather than exploring the equally pressing question of how lack of vaccine access contributes to an excess risk of adverse birth outcomes, especially in women with HIV.

References

Jackson-Gibson M et al. The impact of COVID-19 on adverse birth outcomes in Botswana by HIV status. Conference on Retroviruses and Opportunistic Infections, abstract 29, 2022.

View the abstract on the conference website.