A prospective, controlled study reported in the October edition of the journal Pediatrics shows that exposure to antiretrovirals in the womb did not affect the neurological development of children born to HIV-positive mothers, and that maternal use of substances such as cocaine and methadone may have a greater influence on neurological development.
Concerns have been raised about the possible harmful effects to infants of exposure to antiretroviral drugs during gestation or around the time of delivery. In particular, there are worries that antiretroviral drugs might affect neurological development, since brain development continues throughout pregnancy, and there have been reports of neural tube defects in a small number of children exposed to nucleoside analogues in the womb.
Researchers in Canada compared 39 children exposed to triple antiretroviral therapy in the womb with 24 children born to HIV-negative mothers with similar levels of substance abuse and hepatitis C infection as the HIV-positive mothers.
Children in the exposed group were identified through the British Columbia provincial care programme for HIV-positive women, and were followed for 18 to 36 months after birth. All children had been exposed to a combination of three antiretroviral drugs for at least one week in the womb and to AZT during delivery and the neonatal period, and were HIV-negative.
Children in the control group were born to a cohort of mothers identified through a British Columbia hepatitis C vertical transmission study, in order to match the background risk factors for impaired neurodevelopment that might be present in mothers with HIV in the province. Half of the HIV-negative mothers had a history of injecting drug use.
The majority of HIV-positive mothers took a nevirapine-based triple combination during pregnancy; 13 took a protease inhibitor-based combination. The median duration of ART exposure during pregnancy was 17 weeks.
An increased risk of premature delivery has been associated with exposure to antiretroviral therapy during pregnancy in some studies, and antiretroviral-exposed infants had a significantly lower birth weight and gestational age in this study.
Children in the exposed group had a mean gestational age of 37.7 weeks at birth compared to 39 weeks in the control group, and 25% were born between 34 and 37 weeks of pregnancy, but only one case of delivery prior to 34 weeks was reported in the exposed group. The mean birth weight was 3028 g versus 3410 g in the control group.
The researchers used a widely accepted neurodevelopment measure (BSID-II) to measure children’s mental development index and psychomotor development index. Communication and socialisation were measured using the Vineland Adaptive Behaviour scales.
A significant difference was found in the mental development index, which was found to be significantly lower in the exposed group (94 vs 85, p=0.041). A greater proportion of exposed children scored at least one standard deviation below average (54% vs 25%).
Exposed children also had a lower score on the Vineland daily living index, which measures the ability of the child to carry out tasks associated with normal daily life, such as feeding.
However, when the researchers controlled for maternal substance use, no differences between the exposed and control groups remained, leading the researchers to suggest that any analysis of developmental problems in children exposed to antiretrovirals during pregnancy needs to take more account of the mother’s drug and alcohol use during pregnancy.
One-third of children in the exposed group had narcotic withdrawal syndrome at birth, compared to none of the control group, and perinatal complications such as foetal distress and required resuscitation were reported in 25% of exposed infants, compared to only one of the control group.
The mean scores of exposed children without maternal substance use were substantially closer to those of the control group than to those of exposed children of substance-using mothers, the researchers reported. In addition, children of exposed mothers who were also exposed to methadone had significantly lower mental development scores when compared to exposed children without methadone exposure (p=0.039).
“Overall we found that maternal substance use was a stronger predictor of a poor neurodevelopmental outcome than HAART exposure,” the researchers conclude.
Also, they note: “One-third of the children in this study experienced a change in the family’s status (such as placement in foster care or separation from the father) in the preceding year. Home environment during the first years of life plays an important role in a child’s neurodevelopment.”
The researchers conclude that with antiretrovirals being made available to much larger numbers of pregnant women in developing countries, studies of potential toxicities are essential, but these need to take into account substance exposure and social factors as well as treatment history.