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Effect of Breastfeeding on Mortality Among HIV-1 Infected Women: A Randomized Trial

June 6, 2001

The authors completed a randomized clinical trial of breastfeeding and formula feeding among infants of 425 HIV-1- infected women in Nairobi, Kenya. Formula feeding is customary for HIV-1-infected women in the industrialized world, and is also recommended for infected women in less-developed countries who can use formula safely. Despite the risk of HIV-1 transmission, however, many seropositive women in less-developed countries continue to breastfeed because of financial constraints, little access to clean water and sanitation, fear of stigmatization, cultural practices or inadequate health care infrastructure.

Between November 6, 1992, and October 7, 1997, pregnant women who attended four Nairobi city council antenatal clinics were offered counseling and HIV testing. HIV-1 seropositive women were invited to participate in the study. At enrollment, participants were interviewed with a standardized questionnaire and were given a physical examination. Women were examined for STDs, and blood was drawn to assess T cell subsets, plasma viral load and HIV-1 subtype.

Women were randomly assigned to breastfeeding or formula feeding groups. All women were followed with an interim questionnaire and a brief physical examination every two weeks until 36 weeks' gestation, then every week until delivery. Researchers monitored mother-infant pairs monthly in the first year after delivery and quarterly in the second year until death, 2 years after delivery, or end of the study.

Of the 425 women in the study, 212 were randomly assigned to the breastfeeding group and 213 to the formula feeding group. "Of the 212 women in the breastfeeding group," reported the authors, "one died during pregnancy, eight were lost to follow- up before delivery, and six had no vital status information after delivery. Of the 213 women in the formula feed group, five were lost to follow-up before delivery and eight had no vital status information after delivery. Of the remaining 397 women, 24 died; 15 during the first year and nine during the second year of follow-up." The researchers' analysis dataset included only those women who were alive at the time of delivery and for whom information about vital status after delivery was available. "Thus, 197 women in the breastfeeding group and 200 in the formula group were included in the analysis of the relations between lactation and maternal death."

The researchers "noted that random assignment to the breastfeeding group was associated with a greater than three-fold increased mortality rate among HIV-1 infected mothers during 2 years of follow-up." They reported 18 deaths among mothers in the breastfeeding group, compared with six in the formula group, with respective cumulative probabilities of 10.5 percent and 3.5 percent. The mortality risk in infants increased eightfold if the mother died in the first two years after delivery. And the results confirmed that long-term breastfeeding roughly doubles the risk of HIV transmission to the infant, according to the authors.

The researchers offered two "potential mechanisms" for their findings. "First, the combined metabolic burdens of HIV-1 infections and breastfeeding in a population that has inadequate nutritional intake could result in substantial nutritional impairment," since "women in the breastfeeding group had greater weight loss postpartum than women in the formula feeding group," and since "weight loss was associated with maternal death. . . . Second, lactation might affect HIV-1 replication. . . . Mastisis is associated with raised viral load in breastmilk, but whether there is a concomitant rise in plasma viral load is unknown. Nor do we know whether other local factors associated with breastfeeding (e.g., nipple cracking or candida infection), or breastmilk production itself are associated with enhanced HIV-1 replication."

The researchers argued that more studies are needed to "further assess the association between breastfeeding and maternal death. . . ." They encouraged "promotion of the survival of the mother . . . in addition to the reduction of risk of HIV-1 infection to the infant." The researchers concluded by stating that the aim of public health workers "should be to ensure that all HIV-1 infected mothers are able to feed their infants in a way that keeps risk to a minimum for both mother and child."

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Excerpted from:
05.26.01; Vol 357: P 1651-55; Ruth Nduati; Barbra A Richardson; Grace John; Dorothy Mbori-Ngacha; Anthony Mwatha; Jeckoniah Ndinya-Achola; Job Bwayo; Francis E Onyango; Joan Kreiss

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