The hearts of children whose mothers are infected with the human immunodeficiency virus (HIV) show subtle differences in cardiac structure and function by echocardiogram regardless of whether the children are born infected with HIV.

New results from a five-year, multicenter study indicate that, on average, these children are born with hearts that are larger than those of healthy children born to healthy mothers and that may not pump as effectively. The authors found the abnormalities to be initially mild and asymptomatic; they report that the changes appear to persist -- and, in some cases, even worsen -- in children born infected with HIV. The long-term cardiac consequences in uninfected children born to HIV-positive mothers are unknown.

The results are from a long-term pediatric AIDS study of more than 500 children -- the first of its size to examine cardiovascular structure and function -- supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Research Resources, both part of the National Institutes of Health.

"These results reinforce the importance of careful follow-up and the need to be alert to the possibility of cardiac complications when caring for children born to HIV-infected mothers," said NHLBI Director Dr. Claude Lenfant.

In 1998, between 6,000 and 7,000 births by HIV-infected women were reported in the United States, with approximately 380 children born infected with HIV, according to the Center for Medicare and Medicaid Services (CMS). Current guidelines from the U.S. Public Health Service (PHS) recommend long-term follow-up of all children born to mothers infected with HIV.

The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study assessed heart structure and function by echocardiogram in newborns of HIV-infected mothers, then monitored the children every four to six months for up to five years. Ninety-three children born with HIV and 463 children born uninfected comprised the two study groups. The groups had comparable proportions of girls to boys and of white, black, and Hispanic children, as well as of mothers who engaged in high-risk behaviors such as use of illicit drugs and cigarette smoking while pregnant.

"When they were born, the hearts of the babies who were not infected with HIV were similar to those who were infected. This suggests that HIV does not directly cause the cardiac abnormalities," said lead author Steven Lipshultz, M.D., chief of pediatric cardiology at Golisano Children's Hospital of the University of Rochester Medical Center.

The cause of the cardiac changes remains unclear, however. P2C2 scientists previously studied the effects of zidovudine (AZT) use by the mother during pregnancy or by the newborn. They found no association between use of the drug and the cardiac changes in the infants (September 14, 2000, "New England Journal of Medicine"). Approximately one-third of the P2C2 mothers received AZT during pregnancy to prevent transmission of HIV from mother to fetus.

"We believe that the intrauterine environment may play an important role in the development of these heart abnormalities, perhaps through factors such as maternal nutrition and the inflammatory process triggered by HIV," Lipshultz adds. "This research offers additional clues to how influences during fetal life might affect cardiovascular disease."

Both groups of children were born with left ventricles that, on average, had higher mass and lower contractility, or a diminished ability to pump. Between 4 and 30 months of age, the mass of the left ventricles of the HIV-infected children became significantly greater than those of the uninfected infants in the study. P2C2 investigators have previously shown that in HIV-infected children, these abnormalities can lead to an increased risk of heart failure and death within the first few years of life (September 26, 2000, "Circulation").

Furthermore, children born infected with HIV continued to have lower fractional shortening -- a measurement of the left ventricle's overall effectiveness during contractions -- for the first 20 months. Children who were uninfected, on the other hand, approached the functional level of healthy children born to healthy mothers by approximately 4 to 8 months. The researchers observed a trend toward normalization in the cardiac differences in the uninfected children, who remained asymptomatic.

Both groups of children in the study also had faster heart rates compared to healthy children born to HIV-negative mothers, starting at about 1 month of age. Throughout the study, HIV-infected children's heart rates were, on average, 13 beats per minute faster than healthy children of healthy mothers; heart rates of the uninfected children averaged only 3 beats per minute faster.

"The P2C2 study shows that differences in the heart's structure and function in uninfected children born to HIV-infected mothers were milder and tended to dissipate over time compared to changes found in HIV-infected children," noted Dr. George Sopko of the NHLBI Cardiovascular Medicine Research Group, and a coauthor of the paper. "We cannot determine at this time, however, whether uninfected children might be at increased risk for long-term effects on their cardiovascular health. More research is needed to help us better understand the effect of maternal HIV on the fetus and on the child's growth and development."

P2C2 investigators compared the two groups of study children with 195 infants who were born to HIV-negative mothers and who did not have cardiac abnormalities. This healthy external group, however, was limited in size and was not equally matched with the P2C2 children.

Nonetheless, the study results reinforce PHS recommendations to screen pregnant women for HIV and to take steps to prevent transmission from mother to infant. Since 1994, for example, federal guidelines have stated that healthcare providers should offer AZT to HIV-infected women during pregnancy and delivery, and to their newborns to prevent transmission from mother to child. AZT can reduce the risk of maternal transmission by two-thirds, according to CMS. Today, most HIV-infected pregnant women and their newborns in the U.S. receive AZT, often in combination with other antiretroviral drugs.