Studies Shed New Light on Mother-to-Infant HIV Transmission
HIV-infected women who give birth more than four hours after rupture of the fetal membranes are nearly twice as likely to transmit the virus to their infants, compared to women who deliver within four hours of membrane rupture, according to a study funded by the National Institutes of Health (NIH) and reported in the June 20, 1996 issue of The New England Journal of Medicine.
Rupture of the fetal membranes, the protective sac that surrounds the fetus in the womb, is what occurs when a woman's "water breaks." Maternal drug use during pregnancy, low prenatal CD4 lymphocyte count and low infant birth weight also were independently associated with increased risk for mother-to-infant HIV transmission.
These findings will help us develop better strategies for caring for HIV-infected women and preventing HIV infection in their babies. They complement earlier NIH studies that showed that many cases of HIV infection in infants can be prevented with prenatal and perinatal drug therapy," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID).
Approximately 7,000 HIV-infected women give birth in the United States each year. Without treatment, about one-fourth of them transmit the virus to their children. In 1994, an NIH-supported clinical trial, ACTG 076, proved that the anti-HIV drug zidovudine (AZT), given to HIV-infected pregnant women before and during childbirth and to their infants after childbirth, reduces HIV transmission by as much as two-thirds. Treatment with AZT is now the standard of care in this country for preventing HIV infection in infants, although scientists believe factors other than the virus itself also contribute to infants' risk of infection.
In the current study, researchers assessed the role that various childbirth conditions and maternal factors play in perinatal transmission. The investigators collected detailed medical information from 525 HIV-infected women enrolled in the Women and Infants Transmission Study (WITS), a long-term research project funded by NIAID, the National Institute of Child Health and Human Development (NICHD) and the National Institute on Drug Abuse (NIDA). Study sites included several hospitals in Massachusetts as well as in New York City, Chicago and San Juan, Puerto Rico. Women in the study received standard medical care throughout their pregnancies. Approximately 20 percent of the women received AZT prior to delivery: some were co-enrolled in ACTG 076, others were prescribed the drug to combat their HIV infection. Infants were tested for HIV at regular intervals until they were 18 months old.
HIV infection occurred in 25 percent of babies born to women whose fetal membranes ruptured more than four hours before delivery. In contrast, HIV was transmitted to only 14 percent of babies whose mothers gave birth less than four hours after membrane rupture occurred. Researchers say the findings have clear implications for the care of pregnant women.
This observation could lead to precautions as simple as not intentionally rupturing the fetal membranes in order to induce or accelerate labor," says the study's lead author, Sheldon H. Landesman, M.D., of the State University of New York Health Science Center at Brooklyn.
In an editorial accompanying the report, NIAID grantee Richard L. Sweet, M.D., and Daniel V. Landers, M.D., both of the Magee-Women's Hospital in Pittsburgh, urge obstetricians caring for HIV-infected women to take note of the findings.
We strongly believe that every effort should be made to shorten the time between the rupture of membranes and delivery," they write, "but this does not mean using interventions that could increase morbidity for the mother or her infant."
Dr. Landesman and his co-authors add that obstetricians should consider caesarean section delivery for women who have not used AZT or who show evidence of resistance to AZT, if the duration of ruptured membranes appears likely to exceed four hours. They caution, however, that the effectiveness of caesarean delivery in preventing perinatal transmission has not been demonstrated in prospective clinical trials. They also warn that the procedure may be associated with an increased risk of infectious and other complications in severely immunocompromised HIV-infected women.
"The obstetrician and the patient must balance the known risks of caesarean section against its probable but as yet unproven benefits in decreasing the transmission of HIV to infants," says Dr. Landesman.
In a related clinical trial conducted by the National Cancer Institute (NCI) with support from NIAID, and published in the June 15, 1996 issue of The Lancet, researchers studied nearly 7,000 women giving birth at a hospital in the southern African nation of Malawi to determine whether simple cleansing of the birth canal during labor could reduce HIV-infection rates.
Thirty percent of the women in the study were infected with HIV. Women in the control group delivered their infants using standard practices while, in the intervention group, birth canals were cleansed during labor with a mild soap solution containing chlorhexidine, a compound that has been shown to neutralize HIV in laboratory experiments.
In general, birth canal washing did not reduce perinatal HIV transmission--slightly more than one-fourth of the infants born to women in each group tested positive for HIV. However, the intervention did appear to make a difference for women who delivered more than four hours after their fetal membranes ruptured. Among controls in this subgroup, 39 percent transmitted HIV to their infants, compared to 25 percent in the intervention group. Nearly 25 percent of women in the control group who delivered less than four hours after membrane rupture also transmitted HIV to their infants.
"As performed in this study, birth canal cleansing cannot be recommended as an effective public health approach," says NIAID's Paolo Miotti, M.D., M.P.H., one of the study's co-authors. "However, the encouraging results of the intervention among women who delivered more than four hours after membrane rupture points to a need for further testing of this approach by modifying the way the antiseptic is applied or by increasing its concentration." Dr. Miotti was at the Johns Hopkins School of Hygiene and Public Health when this study was conducted.
Dr. Landesman adds that the increased rate of perinatal transmission observed among women in the Malawi study whose membranes ruptured more than four hours before delivery reinforces his group's findings. The apparent association between birth canal washing and reduction in perinatal transmission in these women warrants further study, he says.
NIAID, NICHD, NIDA and NCI are components of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.