Women living with HIV who tested positive for COVID-19 around childbirth were significantly more likely to experience adverse birth outcomes than other women with HIV, a study conducted in Botswana has found.
The study, which was presented Monday at Conference on Retroviruses and Opportunistic Infection (CROI 2022), also found that women who tested positive for COVID-19 around childbirth were more likely to experience adverse birth outcomes, such as preeclampsia, preterm birth, and stillbirth, regardless of HIV status.
Both COVID-19 and HIV have been associated with an increased risk of unwanted birth outcomes, but there is limited information on their combined effect in a high-prevalence environment of HIV among women of childbearing potential. A systematic review of 42 studies, published in April 2021 before the Delta variant wave, found that SARS-CoV-2 infection during pregnancy was associated with an increased risk of preeclampsia, stillbirth, and preterm birth in studies largely conducted in Europe, China, and North America.
However, these studies did not provide information on whether HIV increases the risk of unwanted birth outcomes in women with SARS-CoV-2. This question is particularly 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 unwanted birth outcomes in women living with HIV.
The study used the existing birth control monitoring system to capture the effects of HIV and antiretroviral treatment results 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 15 November 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 before birth and up to three days after birth.
During the study period, 11,483 women were tested for COVID-19, 4.7% tested positive (539), and of these, 144 lived with HIV (44% of the women giving birth at the study sites had not been tested for COVID-19 and symptomatic women may have been more likely to undergo screening due to a limited supply of test kits). Women with HIV were significantly more likely to test positive for COVID-19 at birth (5.6% vs. 4.3%, p <0.01). Women who tested positive for COVID-19 were slightly older, more likely to be at work and giving birth in a referral hospital.
COVID-19 cases peaked in July 2021, when the Delta variant wave led every tenth pregnant woman to test positive for COVID-19 at birth. Four percent of the women who tested positive died during the study period, and the incidence of death was higher after the emergence of the Delta variant (5%) from April 2021 than in the previous period (2%).
Undesirable birth outcomes occurred more frequently in women who tested positive for COVID-19 (31%) than those who did not (26%). After adjusting for age, the overall rate was 31% higher in women who tested positive. The incidence of preterm birth was 60% higher, the rate of very preterm birth 40% higher and the frequency of stillbirths 90% higher in those tested positive. The incidence of neonatal death, age too small-for-gestational age, and very small-for-gestational age did not differ significantly according to COVID-19 status.
The approximate doubling of the risk of stillbirth in women with COVID-19 is similar 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 U.S. Centers for Disease Control and Prevention estimated that approximately 30% of the women evaluated in this study had been vaccinated. The increased risk of stillbirth may be a consequence of disruption of blood flow and inflammation of the placenta due to SARS-CoV-2 infection, suggesting that prevention of severe COVID-19 disease may also reduce the risk of stillbirth.
Undesirable birth outcomes were significantly higher in women with HIV who tested positive for COVID-19 (43%) than in HIV-positive women without COVID-19 (30%). After adjusting for age, women with HIV and COVID-19 had a 78% higher risk of any unwanted birth outcome, a 65% higher risk of a serious birth outcome, twice the risk of premature birth or very preterm birth, and a 65% higher risk. to have an infant who is small in relation to the gestational age. COVID-19 status did not affect the risk of stillbirth or neonatal death.
Very few of the women who participated in this study had been vaccinated against COVID-19. Vaccination began in Botswana in late 2021 and prioritized individuals over 65 years of age. Population-level data on the effect of vaccination on adverse birth outcomes are limited; studies published to date have addressed concerns about the potential high risk of unwanted birth outcomes associated with vaccination (find none) instead of examining the equally pressing question of how lack of vaccine access contributes to an excessive risk of unwanted birth outcomes, especially in women with HIV.
Jackson-Gibson M et al. Impact of COVID-19 on adverse birth outcomes in Botswana by HIV status. Conference on Retroviruses and Opportunistic Infections, Abstract 29, 2022.