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Risk Factors for and Timing of Infant Mortality among HIV-exposed Children: A Randomized Clinical Trial in Botswana
Shahin Lockman*1,2,3, L Smeaton3, R Shapiro2,3,4, I Thior2, C Wester2, J Makhema2, A Ogwu2, A Asmelash2, E van Widenfelt2, and M Essex2,3
1Brigham and Women`s Hosp, Boston, MA, US; 2Botswana Harvard Sch of Publ Hlth AIDS Initiative Partnership for HIV Res and Ed, Gaborone; 3Harvard Sch of Publ Hlth, Boston, MA, US; and 4Beth Israel Deaconess Med Ctr, Boston, MA, US
Background: Risk factors for infant mortality among
HIV-exposed infants are poorly understood, but may aformula feedect program
decisions regarding the prevention of mother-to-child HIV-1 transmission (MTCT)
and infant feeding.
Methods: In the Mashi study, 1200 HIV-infected pregnant
women in Botswana were randomized to breastfeed and give their infant
zidovudine (ZDV) prophylaxis for 6 months, or to formula feed with 1 month infant
ZDV. Short-course ZDV, single-dose nevirapine (NVP) or placebo, and HAART
(partway through the trial) were available, and mothers were counseled to
exclusively breastfeed. Results through 24 months are presented. Intent-to-treat
and as-practiced (feeding method) analyses were performed. Mortality was modeled
using Cox regression.
Results: Among 1179 live-born infants, by 24 months of age 49
(8.3%) of 588 in the breastfed arm vs 62 (10.5%) of 591 formula-fed arm had
died (with 30 of the total 111 deaths occurring in the 87 HIV-infected infants).
In the breastfed arm, 28.6% of mortality occurred in the first 3 months and
49.0% between 6 and 12 months (after weaning). In the formula-fed arm, 56.5% of
mortality occurred in the first 3 months. Gastroenteritis was the cause of
death in 36 (32.4%) of 111 infants, and pneumonia in 33 (29.7%); among
HIV-infected infants in the formula-fed arm, however, pneumonia accounted for
more (n = 9) deaths than diarrhea (n = 2). More diarrhea occurred
in December to January (the rainy season), and more pneumonia in July to August
(winter). Risk factors for mortality included infant HIV infection (HR 8.0, p
<0.0001), maternal delivery HIV-1 RNA (HR 1.4 for each log10 up; p
= 0.0003), maternal baseline CD4+ (HR 0.95 per 50 increase, p
= 0.02), maternal death (HR 10.2, p <0.0001), recent anemia (HR 3.2, p
<0.0001), having no latrine vs indoor toilet (HR 2.6, p = 0.04), no
solid foods by 5 months (HR 3.2, p <0.0001), and birth weight <2.5
kg (HR 2.9, p <0.0001) (but not randomized or as-practiced feeding
method, water source, or clinic). Multivariable risk factors (controlling for
assigned feeding) included infant HIV, low birth weight, and having no latrine.
Conclusions: In this randomized feeding trial, the first
period of life when breastfeeding did not occur was the time of greatest infant
mortality risk, particularly for HIV-infected children and families with no
toilet facilities. Knowing the populations and periods with greatest risk for infant
mortality will help guide PMTCT and infant health programs and related research
in resource-limited settings.
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