Birth Defects and Adverse Pregnancy Outcomes in Hospital-based Birth Surveillance in Eswatini

Background: The Botswana Tsepamo study identified an initial neural tube defect (NTD) safety signal with dolutegravir antiretroviral therapy (ART) exposure at conception. We conducted similar surveillance in 5 hospitals in Eswatini from September 2021 to September 2023 to evaluate the prevalence of birth defects and adverse pregnancy outcomes by maternal HIV status and ART regimen/timing. Methods: Routine pregnancy history and HIV/ART status were collected from clinic records. Women of live or stillborn infants with birth defects consented for interviews and photographs of defects. A medical geneticist reviewed blinded interview data and photographs. Results: Of 45,836 women with live-born or stillborn infants, 13,577 (29.6%) were living with HIV; 11,581 (86.0%) were receiving ART at conception (84.1% dolutegravir). Overall, birth defects were confirmed in 387 (0.8%) women. Comparing women with and without HIV, there were no significant differences in major defects (0.48% vs. 0.38%) or NTD (0.10% vs. 0.08%). In women with HIV, there were no significant differences between those on dolutegravir versus non-dolutegravir at conception for major defects (0.53% vs. 0.49%) or NTD (0.08% vs. 0.22%). Stillbirths were significantly higher in women with HIV than those without (2.6% vs. 1.9%, P < 0.001), as was low birthweight and preterm delivery (11.8% vs. 10.4%, P < 0.001; 12.5% vs. 10.7%, P < 0.001, respectively). There were no significant differences in outcomes by ART regimen. Conclusions: While these data from sub-Saharan Africa further strengthen the lack of a NTD safety signal in women with HIV on ART, there remained elevated adverse birth outcomes despite treatment compared to women without HIV.