Premature infants of HIV-positive mothers may be at increased risk of rare bowel disorder

Premature infants of HIV-positive mothers may be more likely to develop a rare, but potentially fatal, bowel condition, according to French research published in the September 23^rd edition of AIDS. In a retrospective study the investigators found that having an HIV-positive mother was an independent risk factor for developing necrotising enterocolitis in babies born before the 37^th week of pregnancy. The investigators suggest that mitochondrial toxicity, resulting from the use of AZT to prevent mother-to-child transmission of HIV, is a possible cause. However, they caution that the small number involved in their study does not make it possible to draw firm conclusions.

Necrotising enterocolitis is a gastrointestinal disease which can affect premature infants and can result in destruction of the bowel. There have been case reports of bowel problems in the infants of HIV-positive mothers. The investigators, from neonatal services in Paris, hypothesised that there was a link between exposure to HIV in the womb and necrotising enterocolitis.

To test this hypothesis, the investigators conducted a retrospective study involving infants born before the 37^th week of gestation between 1995 and 2003.

Of the 30,000 infants born at the investigators’ unit, 4009 were premature. A total of 79 (2%) of these premature infants developed necrotising enterocolitis. The incidence of necrotising enterocolitis was 2% (72/3931) in the premature infants of HIV-negative mothers, but 9% (7/78) in the premature infants of HIV-positive mothers. None of the seven infants born to HIV-positive mothers were infected with HIV.

In multivariate analysis, the investigators established that having an HIV-positive mother was independently associated with necrotizing enterocolitis (odds ratio 6.63, p = 0.02), and was the single most significant factor. Other factors significantly associated with the condition were multiple pregnancy (odds ratio 2.29, p = 0.009), abnormal foetal heart rate (odds ratio 2.14, p = 0.04) and abnormal umbilical artery velocity (odds ratio 2.21, p = 0.03).

All seven infants with necrotising enterocolitis and an HIV-positive mother received doses of AZT to prevent mother-to-child transmission of HIV. Six of the seven mothers were also taking anti-HIV therapy; in two this consisted of AZT monotherapy, the other four women were taking a three-drug combination (AZT or ddI with 3TC and a protease inhibitor).

“This case-control study suggests a possible association between maternal HIV-positive status and the development of necrotising enterocolitis in premature infants. This association, which might be of clinical relevance, has not been previously reported”, comment the investigators.

The investigators suggest that mitrochondrial toxicity caused by AZT may be responsible for the condition. However, they emphasise the “enormous benefits resulting from the use of AZT” to prevent mother-to-child transmission of HIV.

The investigators also caution that the small number of cases in their study means that they were unable to establish a casual relationship between HIV status, prematurity and necrotising enterocolitis, and that larger studies will be needed to confirm “whether the suspected relationship really exists.” Nevertheless they conclude that “an awareness of a possible association between perinatal HIV exposure and an increased risk of necrotising enterocolitis in premature infants might help to improve the management of these infants.”