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“Breastfeeding in HIV-1-positive Mothers”
(Published in Lancet – September 29, 2001)
A reply from Nduati and the other authors follows.
Sir–Ruth Nduati and colleagues (May 26, p 1651 [same issue of Lancet])1 claim to show that breastfeeding strikingly increases mortality among HIV-1-positive mothers. In her May 26 commentary, Marie-Louise Newell2 discusses some of the study’s limitations and compares it with research by Coutsoudis and co-workers3 that draws very different conclusions. We have concerns about some additional issues.
Balanced randomisation is essential in clinical trials. We believe Nduati and colleagues' randomisation was not successful. In a more detailed description of the trial,4 at birth only two of the babies in the formula-fed group were believed to be HIV-1 positive, compared with nine assigned breastfeeding. Obviously, method of feeding cannot have any impact on HIV-1 status at the time of birth, and these results suggest important differences between the mothers in the treatment groups that were not detected by the researchers nor balanced by randomisation.
The inability to mask feeding methods introduces a potential source of bias. In addition, the formula-feeding mothers might have had more extensive contact with researchers for education about the correct way to prepare formula.4 These women might have, if only indirectly, received more health-care interventions than those in the breastfeeding group.
Unlike Coutsoudis, Nduati and colleagues do not distinguish between partial and exclusive breastfeeding, and do not precisely define exclusive breastfeeding. 9% of mothers were exclusively breastfeeding by 6 months, which is a much higher proportion than the 3·5% at 4-5 months in the general population in Kenya.5 This difference might be due partly to the WHO definition of exclusive breastfeeding not being used by Nduati and colleagues. Adherence to exclusive formula feeding was only 71%, meaning that 29% of the mothers practised partial breastfeeding. Given that adherence was based on self-reporting, this proportion is probably an overestimate.
Because the analysis was done by intention to treat, differences between the two groups in actual feeding practices are unclear, since they both contained substantial proportions of mixed feeders. Some mothers in the formula-feeding group might have breastfed more than some mothers in the breastfeeding group.
Nduati and colleagues claim they have no reason to believe that dropouts (which were greater in number than deaths) differed between groups, but there is no reason to believe that they are the same. For example, a seriously ill woman might find formula preparation too great an effort and drop out. Conversely, some of the healthiest mothers with highest socioeconomic status in the breastfeeding group might have believed that their babies were at a disadvantage and left the trial to change to formula feeding.
We are concerned that policy may be based on this work, ignoring research by Coutsoudis and colleagues that claimed no risk to the health of mother (or child) from exclusive breastfeeding. An additional concern is the lack of written witnessed consent for participation. Surely, even if verbal information was given, women could still sign their names.
Policy decisions based on this information may seriously impact the lives of millions of mothers and children. We believe the raw data need reanalysis.
Phyll Buchanan, David Crowe, Ted Greiner, George Kent, Tessa Martyn, Valerie McClain, Pamela Morrison, Denise Parker, Magda Sachs, and Karen Zeretzke contributed to the writing of the letter.
Marian Tompson , AnotherLook, 1406 Hinman Avenue #1S, Evanston, IL 60201, USA
Sir--Randomisation in our trial was successful in that the two groups did not significantly differ for any enrolment, delivery, or neonatal characteristics.1 We have previously explained that the different HIV-1 infection rates at birth were probably an artefact of our definition of infant HIV-1 infection status rather than a failure of randomisation.1,2
Marian Tompson and colleagues raise the possibility that more contact with formula-feeding women might have resulted in improved health care. We would not judge such an outcome to bias the results, since it would be a component of the intervention, but it does suggest a mechanism for our observation. If true, more extensive contact with breastfeeders might lower their mortality risk.As we state in the discussion, the high non-adherence rate in the formula group would result in an underestimate of the true risk of maternal death associated with breastfeeding. If self-reported adherence in that group was inaccurate and true adherence was even lower, the underestimate would be even greater. Women were classified as exclusively breastfeeding if they reported that 100% of the infant feeds were from breastmilk. The median duration of breastfeeding among non-adherent women in the formula group was 13 months, compared with 17 months in the breastfeeding group.
Although loss to follow-up was a limitation, we found no correlation between that and any marker of HIV-1 disease status, including CD4-cell count or plasma viral load, which might have predicted mortality. The only distinctive feature of women lost to follow-up was lower socioeconomic status. Thus, we find no support for the scenarios suggested by Tompson and colleagues.
The effect of breastfeeding on health of HIV-1-infected women is an important issue and we encourage further research in this area. Unfortunately, the analysis of observational data by Coutsoudis and colleagues3 had inadequate power to address the issue of maternal death.
*Ruth Nduati, Barbra A Richardson, Grace John Stewart, Dorothy A Mbori-Ngacha, Joan Kreiss
*Department of Pediatrics, University of Nairobi, Nairobi, Kenya; and Departments of Biostatistics, Medicine, and Epidemiology, University of Washington, Seattle, WA, USA
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