A review of numerous studies of pregnant women with HIV has found that there are higher risks of various negative pregnancy outcomes associated with starting antiretroviral (ARV) treatment before rather than after conception. Such findings cannot establish, however, whether preconception treatment of HIV contributes to a raised risk of such outcomes as preterm birth or low birth weight.

Publishing their findings in The Lancet HIV, researchers conducted a systematic review of studies of HIV-positive pregnant women conducted in low-, middle- and high-income nations. They searched medical journal databases for randomized and quasi-randomized trials as well as prospective cohort studies conducted between January 1980 and June 2016 that included information on the timing of women’s initiation of ARV treatment.

The researchers ultimately reviewed 11 studies that included 19,189 pairs of mothers and infants. They found that compared with women who started ARVs after conception, women who started HIV treatment before conception were 20 percent more likely to deliver their babies preterm (between 34 and 37 weeks of gestation), 53 percent more likely to deliver very preterm (before 34 weeks of gestation) and 30 percent more likely to have low-birth-weight infants.

There were very little data available about infant death rates. The study authors did not see a significant difference between pre- or postconception ARV treatment initiation in the risk of very low birth weight, infants born small or severely small for their gestational age, stillbirth or birth defects.

The authors concluded: “The benefits of ART [antiretroviral treatment] for maternal health and prevention of perinatal transmission outweigh risks, but data for the extent and severity of these risks are scarce and of low quality. As use of ART before conception rapidly increases globally, monitoring for potential adverse pregnancy outcomes will be crucial.”

In an accompanying editorial in The Lancet, two French researchers write, “The association between ART and preterm birth is intriguing and elusive. Multicenter observational cohorts are a good way to study outcomes in large populations, but are not designed to inform whether starting ART before pregnancy has an effect on outcomes. An important treatment bias to remember is that, until recently, ART used to be reserved for people with advanced immune deficiency.”

In other words, the studies reviewed for the new paper may have seen more negative pregnancy outcomes among those women who started ARVs before conception because those women had worse health to begin with—which itself was a major driver of outcomes like low birth weight— and not because of the timing of HIV treatment initiation.

To read the study abstract, click here.