HAART use in pregnancy and preterm delivery and low birth weight
Polly Clayden, HIV i-Base
An association between preterm delivery and use of HAART by HIV-positive mothers has been reported in some studies but not others.
A poster from Claire Townsend and co-workers showed findings from a comparison of three studies from the US, Europe and the UK and Ireland undertaken to investigate explanations for reported differences in preterm delivery with HAART use. The three studies were: Pediatric Spectrum of HIV Disease (PSD), a medical record-based cohort study (1990-2004) conducted at seven sites in the US between 1990-2004; European Collaborative Study (ECS), a consented cohort study conducted at 26 centres in nine European countries between1990-2006 and National Study of HIV in Pregnancy and Childhood (NSHPC), a national population-based surveillance study conducted at maternity units in the UK and Ireland between1990-2006.
This comparison included singleton infants born to HIV-positive women during the respective study periods and compared maternal characteristics, including ART and mode of delivery, and prematurity.
Strategies to treat mothers and/or prevent mother to child transmission varied over time in all three cohorts.
The investigators reported substantial variation in maternal and pregnancy characteristics.
They noted that prematurity rates were stable over time in both the PSD and NSHPC, but increased in the ECS (elective caesarean sections at <37 weeks were excluded).
Adjusting for history of injecting drug use, maternal ethnicity, maternal age (except PSD), HIV-related symptoms at delivery (except ECS) and child’s birth year, the investigators found the association between ART and prematurity compared to monotherapy across all three studies.
HAART use was associated with a significant increased risk of prematurity in ECS and NSHPC, but not in PSD. The investigators noted that there was evidence of interactions in the PSD between ART and ethnicity and ART and site of report, which they suggest require further analysis.
These data are interesting and it is very useful to have then analysed and presented so clearly. It is important to place the PTD rates into the context of the background rate of 6 – 8% in an HIV-negative UK population. The UK/Ireland data would seem to give a rate with AZT prophylaxis approaching this. This raises the question of the equivalent rate for North America.
The data would seem to suggest that the rate of PTD, even with AZT prophylaxis is very high, perhaps twice what we would see here.
An explanation of the data is that there are a number of factors that are associated with PTD and that where these are strong, leading to high background rates, then the effect of HAART on PTD is not seen, however where rates are lower, as in the UK with AZT prophylaxis, then an effect due to HAART can be detected.
One analysis that might be interesting is to compare the time on HAART during pregnancy in the three cohorts. Is it possible that HAART is started later in the PDS cohort?
Quite clearly, unless the impact of HAART is immediate, there is likely to be a lag between starting therapy and any associated PTD. HAART started after say 32 weeks will mean that no severe PTD will be associated and the data will be biased to exclude the background rate of PTD.
This will also be an important issue for resource limited settings as using HAART for prevention of mother to child transmission for women not indicated for treatment for their own health continues to be discussed.
Townsend CL, Schulte J, Thorne C et al. Differences in the association between ART in pregnancy and premature delivery: a comparison of three studies from the United States and Europe