Adverse birth outcome research case definitions associated with maternal HIV and antiretroviral drug use in pregnancy: a scoping review

Background: Adverse birth outcomes (preterm birth, low birth weight, small for gestational age, and stillbirth) seem to persist in infants born to people with HIV, even in the context of maternal antiretroviral therapy. However, findings have been disparate, inconclusive, and difficult to compare directly across settings, partly owing to variable outcome definitions. We aimed to collate, compare, and map existing adverse birth outcome definitions to inform a harmonized approach to universally measure these outcomes in studies including pregnant people with HIV.

Methods: We conducted a scoping review of studies that reported adverse birth outcomes associated with maternal HIV and antiretroviral use in pregnancy, specifically those that included definitions of 'preterm birth', 'low birth weight', 'small for gestational age', and 'stillbirth'. Five databases were searched from 01 January 2011 to 15 August 2022. Title, abstract and full-text screening was conducted independently in duplicate. A comparative quantitative analysis was conducted to compare study characteristics by period of study (< 2013; 2013-2015; > 2016) and country income group. A qualitative content analysis was conducted to compare and map deviations from the WHO definitions as a reference.

Results: Of the 294 articles that included at least one adverse birth outcome, 214 (73%) studies started before 2013, 268 (91%) were published as primary research articles, and 137 (47%) were conducted in Eastern and Southern Africa. Among the 283 studies included in the country income group analysis, 178 (63%) were conducted in low- and middle-income countries. Studies reporting low birth weight, preterm birth, small for gestational age and stillbirth deviated from the WHO definitions in n = 11/169 (7%), n = 93/246 (39%), n = 40/112 (36%) and n = 85/108 (79%) instances, respectively. The variations included the use of different thresholds and the addition of new terminology.

Conclusion: The current WHO definitions are valuable tools for population-level monitoring; however, through consensus, these definitions need to be optimized for research data collection, analysis, and presentation. In conjunction with good reporting, variation in adverse birth outcome definitions can be decreased to facilitate comparability of studies as well as pooling of data for enhanced evidence synthesis.