Pregnancy outcomes in women living with HIV and HIV‐negative women in South Africa: Cohort analysis based on bias‐corrected gestational age

Abstract

Background Antiretroviral therapy (ART) use during pregnancy may be associated with adverse outcomes, but findings have been inconsistent, at least in part due to unreliably estimated gestational age. Objective To quantify the association between HIV status, ART initiation timing and adverse birth outcomes, with reliably assessed gestational age at booking, in a public sector primary care facility in Cape Town, South Africa. Methods Pregnant women, HIV‐negative or living with HIV (WLHIV), were enrolled at first antenatal care visit and followed through delivery. Ultrasound‐assessed gestational age was deemed the gold standard. Based on quantitative bias analysis for outcome misclassification, gestational age by non‐ultrasound assessment was corrected using multiple overimputation, which deals with missing data and measurement error simultaneously. Using bias‐corrected gestational age, birth outcomes were compared between WLHIV and HIV‐negative women, and among WLHIV who initiated ART before versus during pregnancy, further divided into trimesters. Results Of 3952 women enrolled, 37% were WLHIV (mostly using tenofovir + emtricitabine + efavirenz). Last menstrual period (LMP)‐based gestational age was identified to be biased, and LMP measures were thus corrected using multiple overimputation. Comparing WLHIV and HIV‐negative women, adjusted risk ratio (aRR) of overall pregnancy loss was 1.26 (95% confidence interval [CI] 0.98, 1.61); aRR of preterm delivery was 1.02 (95% CI 0.88, 1.20); aRR of small for gestational age infants was 1.43 (95% CI 1.14, 1.80). Among WLHIV, outcomes were similar by ART initiation timing. Conclusions In this routine care cohort, risk of SGA, and possibly of pregnancy loss, was increased in WLHIV compared with HIV‐negative women, with no evidence of increased risk of preterm delivery. Further research is needed to improve mechanistic understanding of the contribution of ART to adverse birth outcomes to optimize treatment for pregnant WLHIV and ensure optimal maternal and infant outcomes.

Beyond COVID‐19: Equitable epidemiology for studying the impact of maternal infections on neonatal mortality and morbidity

“…Women in LMICs often attend their first antenatal visit in the second trimester which limits the access to early ultrasound examinations and makes accurate gestational age determination difficult. Malaba et al 4 highlighted this problem and used quantitative bias analysis to adjust for gestational age misclassification when estimated by last menstrual period or symphysis fundal height.…”

“…Malaba and colleagues 4 quantify the association between maternal HIV infection status, ART initiation timing, and adverse birth outcomes among a cohort of South African women. Using a bias‐corrected gestational age estimate, they found that women living with HIV compared with those without HIV had similar risks of overall pregnancy loss and of preterm delivery; the risk of delivering small for gestational age births was, however, higher among women living with HIV.…”

“…While this life-saving therapy remarkably improved the quality of life of people living with HIV, it means that many newborns are exposed to ART in utero, and the potential risks and benefits of this maternal treatment on birth outcomes and longer-term offspring health are still unclear. Three articles [4][5][6] in this special issue of Paediatric and Perinatal Epidemiology illustrate the importance of prospective studies from LMICs on infection during pregnancy, and on the impact of new strategies to improve birth outcomes and neonatal health.…”

Influence of different methods for calculating gestational age at birth on prematurity and small for gestational age proportions: a systematic review with meta-analysis

“…Regarding the target population, eleven were carried out with mothers from the general population, two in rural areas, and seven were associated with other screening programs conducted widely in the studied population, such as the study of the Alpha-Fetoprotein Screening Program (XAPF) [ 20 ]. One report comparing pregnancy outcomes between women living with HIV and HIV-negative had data extraction only from the control group [ 21 ].…”

Importance of considering infection during pregnancy: An underappreciated and preventable perinatal concern

“…In addition to the direct health implications of HIV infection, prevention of vertical transmission of HIV requires administration of antiretroviral therapy (ART), resulting in additional potentially harmful exposures during pregnancy. In a prospective cohort study, Malaba and colleagues 11 identified that among South African pregnant persons, HIV infection and ART use were associated with increased risk of small for gestational age birth and potentially pregnancy loss, but not preterm birth. In contrast to studies based in high‐resource settings, where ultrasound dating is readily available, self‐reported LMP may be the only method of measuring gestational age in LMIC‐based studies of maternal infection.…”