Risk factors for adverse pregnancy outcomes in Botswana
Polly Clayden, HIV i-Base
It is unclear whether the use of highly active antiretroviral treatment (HAART) in pregnancy is associated with adverse outcomes and data from resource-limited settings are particularly lacking.
A poster authored by Jennifer Chen, Roger Shapiro, and co-workers from Botswana and the USA showed results from a prospective review of obstetrical records of women who delivered at 20 weeks or greater in four facilities in Botswana between October 19, 2007 and June 30, 2008.
This study particularly evaluated stillbirths, preterm delivery (<37 weeks gestation) (PTD), low birth weight (<2500g) (LBW), small for gestational age (SGA) and neonatal death.
The investigators found 5676 recorded birth outcomes, of which 5327 (94%) women had a documented HIV test. Among those with an HIV test, 1629 (30.6%) had a positive result.
The investigators observed high overall rates of: still birth, 2.7% and 3.6%; PTD, 20.6% and 27.3%; LBW, 13.5% and 20.4%; SGA, 19.4% and 23.8% and neonatal death, 1.9% and 2.7% in HIV negative and positive women respectively.
Of the HIV positive group, 146 women received no antiretrovirals (ARV); 471 received AZT; 112 initiated HAART and 127 continued HAART from prior to the current pregnancy. Median CD4 counts were 283 cells/mm3 for those receiving no ARV and 417 cells/mm3, 266 cells/mm3 and 378 cells/mm3 for women who initiated AZT, initiated HAART, and continued HAART from prior to the current pregnancy respectively.
The majority of women initiated on HAART or AZT did so at 28 weeks gestation, so the investigators noted that they were unable to capture early pregnancy outcomes comparing these groups.
CD4 cell count was lower among women who received HAART (p<0.0001).
The investigators found in multivariate analysis, HAART was associated with SGA and possibly with stillbirths, and this association remained after adjustment for CD4 cell count (See table 1).
Table 1. Multivariate analylses of HIV positive women
|Risk factor||Still birth AOR (95% CI)||PTD AOR (95% CI)||SGA AOR (95% CI)|
|HAART continued vs all others*||2.0 (0.9, 4.4)||1.2 (0.8, 1.9)||1.8 (1.2, 2.8)|
|HAART initiated vs AZT initiated by 30 weeks||3.7 (0.9, 15.6)||1.2 (0.6, 2.7)||2.8 (1.4, 5.7)|
|HAART continued vs HAART initiated**||—||—||0.7 (0.4, 1.2)|
* All others includes HIV-positive women on no ARV intervention and those who later initiated ARVs. ** Multivariate analyses that compared women who continued HAART with those who initiated HAART were not performed for the outcomes stillbirth and preterm delivery, since women who continued HAART had more opportunities for events in pregnancy.
The investigators also found anaemia to be associated with PTD (p=0.0001) in HIV positive women, but anaemia was not associated with HAART use. However, they reported hypertensive complication at delivery was more common among women receiving HAART from prior to the current pregnancy (p=0.02) and was a risk factor for stillbirth, OR 7.2 (95% CI 3.8, 13.7), PTD, OR 1.7 (95%CI 1.3,2.4) and SGA, OR 2.1 (95% CI 1.4, 3.0). They suggest that this may be a potential explanation for some associations between HAART and adverse outcomes.
They wrote, High risk obstetrical and neonatal care need to be prioritised in Botswana to address the large number of HIV-infected pregnant women with increasing access to HAART for treatment and PMTCT.
These data add to the accumulating evidence that HAART in pregnancy may be associated with adverse outcomes and re-emphasise the importance of Phase 4 studies. Importantly they come from the region of the world where ARVs will be most widely prescribbed in pregnancy. Understanding the mechanisms and determining whether these events are substance-specific or part of the spectrum of immune reconstitution will help policy makers and healthcare workers to make decisions about therapy.
Botswana is planning a pilot of universal HAART for 50,000 HIV-positive pregnant women, which is expected to generate important large-scale outcome data.
Chen J et al. A et al. Risk Factors for Adverse Pregnancy Outcomes among HIV-infected Women in Gaborone, Botswana. 16th CROI, Montreal, 2009. Abstract 949.