Recent findings have examined a possible link between use of antiretroviral therapy during pregnancy and premature deilvery. These consist of three large cohort studies.

In a 14-year survey by the National Study of HIV in Pregnancy and Childhood (NSHPC), which follwed over 3800 pregnancies in HIV-positive mothers in the United Kingdom and Ireland, delivery before 37 weeks was found to be 47% more common in mothers taking combination antiretroviral therapy than those taking one antiretroviral drug. This has resulted in around 30% of HIV-positive mothers giving birth vaginally or having emergency Caesarian sections, despite having planned to deliver by Caesarian section in weeks 38 or 39. The study also found that the incidence of spontaneous abortion has increased over time as the use of antiretroviral therapy has increased, with 23% occurring between weeks 20 and 23 of gestation. Although a causative link cannot be proven, it is speculated that this may be an effect of the increased use of antiretroviral therapy in pregnant mothers. However, use of antiretroviral therapy was not associated with an increased risk of stillbirth or neonatal death (Tookey 2004).

A very similar report from the European Collaborative Cohort also suggests that combination therapy is associated with premature delivery. In this study, the proportion of premature births increased significantly with the use of antiretroviral therapy during pregnancy from 16% before 1989 to 25% in 2004. As in the NSHPC study, there was a trend for more emergency caesarean or vaginal deliveries to be performed over time. The investigators suggested that these findings should be considered when making therapeutic decisions for HIV-positive women of childbearing age whose clinical, immunological and virological status does not indicate a need for early initiation of antiretroviral therapy (Thorne 2004). Other risk factors included older age, injecting drug use and low CD4 cell counts during pregnancy.

In contrast, an analysis from the Women and Infants Transmission Study has reported improved outcomes and few toxicities associated with antiretroviral therapy. Data from 2543 HIV-infected women found an eightfold increase in premature deliveries only in women who began antiretroviral therapy that did not contain AZT late in pregnancy. The authors of this study concluded that the benefits of combination antiretroviral therapy in pregnancy continue to outweigh the observed risks.

These findings generally support those of observational studies suggesting a link between antiretroviral therapy, particularly involving protease inhibitors and an increased risk of premature delivery (Goldstein 1999; Wolf 1999; Cotter 2006). However, itis impossible to tell whether premature delivery was driven by protease inhibitor treatment, since the women in these studies who were receiving protease inhibitor treatment were more likely to have low CD4 cell counts, which may have some bearing on the risk of premature delivery (Beckerman 2004; Tuomala 2006). The problems caused by observational studies may be solved by the carrying out prospective, randomised controlled trials of the effects of protease inhibitors during pregnancy in women who do not need treatment for their own health. However, these may be difficult to carry out on ethical grounds.

A retrospective analysis of 233 pregnancies to women taking protease inhibitors found no evidence of an elevated risk of prematurity, with 22% of births occurring before 37 weeks. There was also no link between prematurity and individual protease inhibitors or the week when protease inhibitor treatment was started (Morris 2005). Further prospective studies are required to clarify this matter.

There is less evidence on the risks associated with antiretroviral therapy during pregnancy in the developing world. However, one observational study of 204 women in Ivory Coast found similar rates of prematurity between women on combination antiretroviral therapy and those receiving one- or two-drug short-course treatment to prevent HIV transmission. However, babies born to mothers taking combination antiretroviral therapy were more likely to have low birth weight (Toure 2005).