Exposure to Antiretroviral Therapy in Utero or Early Life: the Health of Uninfected Children Born to HIV-Infected Women

The risk of vertical HIV-1 transmission is significantly reduced by prophylactic ART before, during and after delivery. HIV-infected pregnant women are increasingly being treated with highly active antiretroviral therapy (HAART) for their own health and to reduce vertical transmission. However, medium- to long-term follow-up of the increasing number of children exposed to ART is important to elucidate the risk of adverse events.

Since 1985, infected and uninfected children born to HIV-infected women have been prospectively followed in the European Collaborative Study, which offers "a unique opportunity to assess the long-term health of uninfected children in the light of ART received by the mother and neonate," according to the study.

The researchers examined 2,414 uninfected children born to HIV-infected women enrolled in the ECS to December 2001. Median mother's age at delivery was 28, with a range from 14-44 years. Twenty percent of the women had used illicit drugs during pregnancy, a decline from 33 percent in 1990 to 4 percent in 2000. Eighty percent of the women were white, but there was an increase in black women from 9 percent in 1990 to 27 percent in 2000.

Of the 2,414 children, 687 (28 percent) were exposed to ART during the antenatal, intrapartum and neonatal periods. Eight percent (193) of the children were exposed to ART in two periods, and 5 percent (128) were exposed to ART during only one period. Of the total 1,008 infants exposed to any ART, 906 (90 percent) were exposed antenatally, 840 (83 percent) neonatally and 750 (74 percent) antenatally and neonatally. Fifty-eight percent of children, mostly born before 1994, were not exposed to ART. The proportion of children exposed to ART increased from 23 percent in 1994 to 78 percent in 1996 to 97 percent in 1998 to 100 percent in 2000.

Nearly two-thirds of the mothers had no ART during pregnancy. Twenty percent took monotherapy with zidovudine, and 18 percent were on combination therapy: 235 without a protease inhibitor, and 196 with a PI. Of the 235 mothers whose regimen did not include a PI, 121 were on double therapy and 114 were on three or more drugs.

Thirty-seven children had congenital abnormalities. Thirteen had been exposed to ART in utero. Congenital abnormalities in seven children exposed in the first trimester included Down syndrome (1), ventricular septal defect (2), hydronephrosis (1) and unspecified anomalies (3). An additional six children were exposed in a later stage of gestation. Their abnormalities included ventricular septal defect (1), Down syndrome (2), polyscystic kidney (1), polydactyly (1) and unspecified anomalies (1). The pattern and prevalence of abnormalities in infants exposed to ART (13/906) and those not exposed (24/1,508) were similar. However, women on combination therapy without a PI were nearly three times more likely to deliver prematurely than those on no therapy. Women on combination therapy with a PI were four times more likely to have a premature delivery.

"With the exceptions of a significantly increased risk of premature delivery and reversible anemia," the researchers wrote, "the data presented here do not show an adverse effect of ART exposure in uninfected children born to HIV-infected women in the short to medium term.... Although our data are reassuring, we cannot be complacent regarding any possible adverse health effects. When a pregnant woman is offered ART, there should be a discussion of the short- and long-term benefits and risks associated with such therapy."

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