INTRODUCTION
MATERIALS AND METHODS
Search strategy and keywords
Eligibility criteria
(1) Population: Pregnant women living with HIV and/or children who were exposed to HIV or infected during pregnancy. Women at any gestational age were included, as the recent literature has suggested that focusing on congenital abnormalities only in the first trimester is outdated [15]. All countries and settings were eligible for inclusion.
(2) Interventions: All combinations and doses of ARTs. Standard combination antiretroviral therapy (cART) consists of a combination of antiretroviral drugs to maximally suppress HIV and stop the progression of disease. To be included, pregnant women should have taken ART for at least 1 month before delivery. Studies were not included if they examined ARTs that were directly administered to neonates, infants, or children; were pre-clinical animal studies; analyzed prophylaxis-only doses; or did not specify whether women were on ART.
(3) Comparators: Studies comparing antiretroviral medications administered to HIV-positive mothers to (i) HIV-negative women, (ii) HIV-positive women not receiving treatment, and (III) HIV-positive women taking another type of ART medication (medication classes as per the WHO 1a-1f category) were included. The last group was considered for a subgroup analysis to determine the effects of individual drugs on the occurrence of congenital anomalies.
(4) Outcomes: The presence or absence of congenital anomalies must have been stated and unambiguous. The primary safety outcome was major congenital malformations (overall and by specific type), as defined by the International Classification of Diseases, 10th revision [22], which includes congenital anomalies/birth defects in chapter XVII. Congenital anomalies were operationalized for this study as anatomical or functional defects, including metabolic ailments, which were present at birth [23].
(5) Study designs: Experimental (randomized clinical trials [RCTs] and non-RCTs), quasi-experimental (controlled before and after and time series), and observational (cohort, case-control, and drug registry) studies were included in the analysis. However, cross-sectional studies and case reports were excluded.
(6) Other limitations: No limitations were imposed on publication status, study site, and the duration of the study. However, non-English studies and those with a very small sample size (< 50) used to detect differences were excluded.