New Concerns about Children Born to HIV-Infected Mothers.

The last 15 years has seen dramatic progress globally in reducing mother-to-child transmission of HIV—from a rate of more than 25 percent, down to less than 5 percent.

But as one public health crisis has been addressed, another has emerged, according to a new study by School of Public Health researchers: Children exposed to HIV, but not infected, have a 70 percent increased risk of dying, often within the first two years of life.

The study in the journal AIDS raises concerns that a growing population of children born to HIV-infected mothers but who escaped infection are vulnerable to illness and death, for reasons not yet understood. The higher risk of death did not appear to change after 2002, when global implementation of antiretroviral therapy for all HIV-positive pregnant women became policy, the study found.

“We had thought that the children who were spared transmission might have dodged the bullet—but it seems, instead, that some portion of them are more susceptible to illness and death,” said senior study author Donald Thea, professor of global health. “We don’t really know why—and, given the serious health outcomes, we need to find out. The more success we have in preventing mother-to-child transmission, the larger this group of children will become. This could easily become one of the most prevalent medical-induced causes of death among children in the world.”

The research team, led by global health research scientist Alana Brennan, conducted the first-ever meta-analysis of more than 20 studies that have been done over the last 15 years on mortality among HIV-exposed children, many of them in sub-Saharan Africa. Nearly all of the studies showed a higher risk of mortality among young children born to HIV-infected mothers than among their non-exposed counterparts.

The researchers said that while the exact reasons for the elevated risk remain unknown, they may include a combination of biological and social factors. Among possible factors are: immune dysfunction in the child because of an abnormality passed on by an HIV-infected mother; poorer maternal health that impacts the quality of infant care; unrecognized non-HIV infections passed from the mother; side effects of HIV medicines given to the mother; and increased pre-term or low birth weight outcomes for HIV-positive women.

Although decreased trans-placental antibody transfer from HIV-infected mothers has been demonstrated, the researchers said, the fact that the increased risk of death for exposed children persists through two years of life “suggests that this cannot be the sole explanation” for the increased mortality risk.

The authors noted that there have been no studies on non-biological risk factors, such as social or environmental conditions.

“One possibility is that HIV-infected mothers may be sicker or more likely to be deceased, along with their male partner, than non-HIV infected mothers, and therefore may be less able to provide care” during the vulnerable infant period, the study says. “Such differences in maternal health status could also account for differences in breastfeeding practices between HIV-positive and HIV-negative mothers.” Breastfeeding is protective against all-cause mortality for all children, and is recommended even for mothers with HIV.

The authors urge further studies to determine which biological or environmental factors might be fueling the higher risk.

“Understanding the causes of increased mortality in HIV exposed, but uninfected, children will help countries strengthen the capacity to provide quality long term services for this population,” they wrote. “These efforts should ideally be complementary to national and international efforts to improve overall child survival, as (HIV-exposed) children are still at risk from major childhood diseases such as pneumonia, diarrhea, and malnutrition.”

Funding for the study came from the US Agency for International Development (USAID).

Co-authors from the Department of Global Health were: Matthew Fox, also a professor of epidemiology, Christopher Gill, Rachel Bonawitz, Mary Kleinman, Lindsey Garrison, Johanna Useem, Rachel Ceccarelli, and Chinenye Udoko. Lawrence Long, from the University of Witswatersrand in Johannesburg, South Africa, also contributed.

In a letter accompanying the study, a research team led by Kathleen Powis of the Harvard T.H. Chan School of Public Health agreed with the finding that HIV-exposed children “do not appear to be achieving equivalent health outcomes compared to children born to HIV-uninfected women within the same communities,” and called for research into those disparities.

“There is no mechanism to monitor health, neurodevelopment and survival outcomes of (HIV-exposed) children into adulthood,” Powis and co-authors said.

—Lisa Chedekel