Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.

Risk of postneonatal mortality, hospitalisation and suboptimal breast feeding practices in low birthweight infants from rural Haryana, India: findings from a secondary data analysis.

OBJECTIVES: Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy. DESIGN: Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices. SETTING: Rural Haryana, North India. PARTICIPANTS: Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life. RESULTS: We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight <2000 g (RR 3.38; 95% CI 2.71 to 4.12). The risk of hospitalisation in the neonatal period and postneonatal period was (RR 1.86; 95% CI 1.64 to 2.11) and (RR 1.13; 95% CI 1.05 to 1.21), respectively. LBWs were at increased risk of breast feeding initiation 24 hours after birth (RR 1.64; 95% CI 1.45 to 1.81), no breast feeding at 6 months (RR 1.34; 95% CI 1.23 to 1.46) and at 12 months of age (RR 1.24; 95% CI 1.18 to 1.30). CONCLUSIONS: LBW babies, especially those with birth weight of <2000 g, were at increased risk of mortality, hospitalisation and suboptimal breast feeding practices during entire infancy and therefore require additional care beyond the first 28 days of life. TRIAL REGISTRATION NUMBER: NCT01138449.

Immunization practices in low birth weight infants from rural Haryana, India: Findings from secondary data analysis.

BACKGROUND: Low birth weight (LBW) infants constitute a vulnerable subset of infants with impaired immunity in early life. In India, there is scarcity of studies that focus on immunization practices in such infants. This analysis aimed to examine immunization practices in LBW infants with the intention to identify areas requiring intervention. METHODS: Data on immunization status of LBW infants enrolled in an individually randomized, double-masked, placebo-controlled trial of neonatal vitamin A supplementation were analysed. Study outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3. Multivariable logistic regression was performed to identify factors associated with the outcome(s). FINDINGS: Out of 10 644 LBW infants enrolled in trial, immunization data were available for 10 517 (98.8%). Less than one-third (29.7%) were fully immunized by one year of age. Lowest wealth quintile (adjusted odds ratio (AOR) 0.39, 95% confidence interval (CI) 0.32-0.47), Muslim religion (AOR 0.41, 95% CI 0.35-0.48) and age of mother <20 years (AOR 0.62, 95% CI 0.52-0.73) were associated with decreased odds of full immunization. Proportion of infants with delayed vaccination for DPT1 and DPT3 were 52% and 81% respectively. Lowest wealth quintiles (AOR 1.51, 95% CI 1.25-1.82), Muslim religion (AOR 1.41, 95% CI 1.21-1.65), mother aged <20 years (AOR 1.31, 95% CI 1.11-1.53) and birth weight <2000 g (AOR 1.20, 95% CI 1.03-1.40) were associated with higher odds of delayed vaccination for DPT-1. Maternal education (≥12 years of schooling) was associated with high odds of full immunization (AOR 2.39, 95% CI 1.97-2.91) and low odds of delayed vaccination for both DPT-1 (AOR 0.59, 95% CI 0.49-0.73) and DPT-3 (AOR 0.57, 95% CI 0.43-0.76). CONCLUSION: In this population, LBW infants are at a risk of delayed and incomplete immunization and therefore need attention. The risks are even higher in identified subgroups that should specifically be targeted.

Promotion of Weight Gain in Early Childhood Does Not Increase Metabolic Risk in Adolescents: A 15-Year Follow-Up of a Cluster-Randomized Controlled Trial.

BACKGROUND: A rapid gain in weight for length may put children at a higher risk of noncommunicable diseases later in life. OBJECTIVE: The objective of this study was to assess the long-term effects of nutrition counseling delivered in the first 2 y of life in Pelotas, a city in Southern Brazil. METHODS: The original cluster-randomized controlled trial was conducted in 1998. Nutrition counseling (breastfeeding promotion and increased intake of micronutrient-rich and energy-dense foods) was delivered to mothers of children aged 0-17.9 mo attending primary care. Six months later, weight gain was higher in the intervention group than in the control group for children ≥12 mo of age at enrollment. In 2013 (mean age 15 y), assessments included anthropometric measurements, body composition (air-displacement plethysmography), body shape (3-dimensional photonic scan), and plasma total, LDL, and HDL cholesterol, triglycerides, C-reactive protein, and glucose. RESULTS: A total of 363 of the 424 original participants were assessed. An a priori decision was made to prioritize analyses of subjects aged 12-17.9 mo at enrollment (51 from the intervention group and 45 from the control group). In this subgroup, boys in the intervention group were [mean (95% CI)] 3.4 (0.8, 6.0) cm taller than those in the control group. Systolic blood pressure tended to be 5.2 (-0.8, 11.1) mm Hg higher in male subjects from the intervention group than in those in the control group. Lipid profiles tended to be healthier in the intervention group. The plasma total cholesterol concentration was -17.8 (-29.8, -5.7) mg/dL lower in boys in the intervention group than in those in the control group. The total-to-HDL cholesterol ratio and triglyceride concentration in the girls in the intervention group were -0.4 (-0.6, -0.1) and -26.3 (-46.3, -6.3) mg/dL, respectively, lower than in the control group. There was no difference between the groups in terms of body composition. CONCLUSIONS: Promotion of weight gain in children between 12.0-17.9 mo of age was not associated with higher metabolic risk 15 y later. On the contrary, there was some evidence of reduced metabolic risk in the intervention group.

Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Supplementation of vitamin A in children aged 6-59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months). METHODS: We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants' families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055. FINDINGS: Between Aug 26, 2010, and March 3, 2013, 31,999 newborn babies were randomly assigned to receive vitamin A (n=15,995) or placebo (n=16,004; 15,428 and 15,464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95-1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90-1·29) and for girls was 1·12 (0·91-1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing. INTERPRETATION: Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation. FUNDING: Bill & Melinda Gates Foundation to WHO.

Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age. METHODS: We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220. FINDINGS: Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32]). INTERPRETATION: The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy. FUNDING: Bill & Melinda Gates Foundation to WHO.

Efficacy of early neonatal vitamin A supplementation in reducing mortality during infancy in Ghana, India and Tanzania: study protocol for a randomized controlled trial.

BACKGROUND: Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo. METHODS/DESIGN: The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation. DISCUSSION: The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.

Improvement of perinatal and newborn care in rural Pakistan through community-based strategies: a cluster-randomised effectiveness trial.

BACKGROUND: Newborn deaths account for 57% of deaths in children younger than 5 years in Pakistan. Although a large programme of trained lady health workers (LHWs) exists, the effectiveness of this training on newborn outcomes has not been studied. We aimed to evaluate the effectiveness of a community-based intervention package, principally delivered through LHWs working with traditional birth attendants and community health committees, for reduction of perinatal and neonatal mortality in a rural district of Pakistan. METHODS: We undertook a cluster randomised trial between February, 2006, and March, 2008, in Hala and Matiari subdistricts, Pakistan. Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters, which were allocated to intervention and control groups by restricted, stratified randomisation. The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education, use of clean delivery kits, facility births, immediate newborn care, identification of danger signs, and promotion of careseeking; control clusters received routine care. Independent data collectors undertook quarterly household surveillance to capture data for births, deaths, and household practices related to maternal and newborn care. Data collectors were masked to cluster allocation; those analysing data were not. The primary outcome was perinatal and all-cause neonatal mortality. Analysis was by intention to treat. This trial is registered, ISRCTN16247511. FINDINGS: 16 clusters were assigned to intervention (23,353 households, 12,391 total births) and control groups (23,768 households, 11,443 total births). LHWs in the intervention clusters were able to undertake 4428 (63%) of 7084 planned group sessions, but were only able to visit 2943 neonates (24%) of a total 12,028 livebirths in their catchment villages. Stillbirths were reduced in intervention clusters (39·1 stillbirths per 1000 total births) compared with control (48·7 per 1000; risk ratio [RR] 0·79, 95% CI 0·68-0·92; p=0·006). The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups (RR 0·85, 0·76-0·96; p=0·02). INTERPRETATION: Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential. FUNDING: WHO; Saving Newborn Lives Program of Save the Children USA, funded by the Bill & Melinda Gates Foundation.

Use of new World Health Organization child growth standards to assess how infant malnutrition relates to breastfeeding and mortality.

OBJECTIVE: To compare the estimated prevalence of malnutrition using the World Health Organization's (WHO) child growth standards versus the National Center for Health Statistics' (NCHS) growth reference, to examine the relationship between exclusive breastfeeding and malnutrition, and to determine the sensitivity and specificity of nutritional status indicators for predicting death during infancy. METHODS: A secondary analysis of data on 9424 mother-infant pairs in Ghana, India and Peru was conducted. Mothers and infants were enrolled in a trial of vitamin A supplementation during which the infants' weight, length and feeding practices were assessed regularly. Malnutrition indicators were determined using WHO and NCHS growth standards. FINDINGS: The prevalence of stunting, wasting and underweight in infants aged < 6 months was higher with WHO than NCHS standards. However, the prevalence of underweight in infants aged 6-12 months was much lower with WHO standards. The duration of exclusive breastfeeding was not associated with malnutrition in the first 6 months of life. In infants aged < 6 months, severe underweight at the first immunization visit as determined using WHO standards had the highest sensitivity (70.2%) and specificity (85.8%) for predicting mortality in India. No indicator was a good predictor in Ghana or Peru. In infants aged 6-12 months, underweight at 6 months had the highest sensitivity and specificity for predicting mortality in Ghana (37.0% and 82.2%, respectively) and Peru (33.3% and 97.9% respectively), while wasting was the best predictor in India (sensitivity: 54.6%; specificity: 85.5%). CONCLUSION: Malnutrition indicators determined using WHO standards were better predictors of mortality than those determined using NCHS standards. No association was found between breastfeeding duration and malnutrition at 6 months. Use of WHO child growth standards highlighted the importance of malnutrition in the first 6 months of life.

Implementing community-based perinatal care: results from a pilot study in rural Pakistan.

OBJECTIVE: This pilot study investigated the feasibility of delivering a package of community-based interventions for improving perinatal care using lady health workers (LHWs) and traditional birth attendants (Dais) in rural Pakistan. METHODS: The intervention was implemented in four of eight village clusters (315 villages, total population 138,600), while four served as a comparison group. The LHWs in intervention clusters received additional training focused on essential maternal and newborn care, conducted community education group sessions, and were encouraged to link up with local Dais. The intervention was delivered within the regular government LHW programme and was supported by the creation of voluntary community health committees. FINDINGS: In intervention villages, there were significant reductions from baseline in stillbirth (from 65.9 to 43.1 per 1000 births, P < 0.001) and neonatal mortality rates (from 57.3 to 41.3 per 1000 live births, P < 0.001). The proportion of deliveries conducted by skilled attendants at public sector facilities also increased, from 18% at baseline to 30%, while the proportion of home births decreased from 79% to 65%. A household survey indicated a higher frequency of key behaviours (e.g. early and exclusive breastfeeding, delayed bathing and cord care) in intervention villages. CONCLUSION: The improved stillbirth and neonatal mortality rates observed indicate that community health workers (i.e. LHWs and Dais) can be effective in implementing a community and outreach package that leads to improved home care practices by families, increased care-seeking behaviour and greater utilization of skilled care providers. These preliminary observations require confirmation in an adequately powered trial.

Integrated care of childhood disease in Brazil: mothers' response to the recommendations of health workers.

AIM: To describe the process of follow-up in primary care facilities where the Integrated Management of Childhood Illness (IMCI) strategy was implemented. IMCI was developed by WHO and UNICEF as an integrated approach to manage sick children under 5 y of age and aims to reduce mortality and morbidity. METHODS: From August 2001 to February 2002, 229 sick children who had a health condition included in the IMCI case management guidelines were seen in six family healthcare facilities in Brazil. We analysed the care provided to 153 children who were recommended for a 2- or 5-d follow-up visit. Children who did not return were visited and assessed at home. RESULTS: Only 87 children (56.9%) timely returned for follow-up: 70 had improved, eight presented the same health conditions, five were worse and four had a new problem. The main reasons given for not returning for follow-up were: the child had improved (35.1%) and other family priorities (47.4%). Home visits showed that, although most children had improved (n=49), some had a new health problem and one child was sick enough to be referred. Prescription of antibiotics was associated with increased probability of returning for a follow-up visit (RR =1.64 [1.22-2.20], p=0.001). CONCLUSION: Adherence to follow-up was just over 50%, mostly because the condition had already resolved, but some children were still sick and needed intervention. Training on counselling on the recognition of danger signs and when to return for a follow-up visit must be reinforced.

Use of multiple opportunities for improving feeding practices in under-twos within child health programmes.

OBJECTIVES: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities. METHODS: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization. FINDINGS: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p<0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation. CONCLUSIONS: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvement.

Infant feeding patterns and risks of death and hospitalization in the first half of infancy: multicentre cohort study.

OBJECTIVE: To determine the association of different feeding patterns for infants (exclusive breastfeeding, predominant breastfeeding, partial breastfeeding and no breastfeeding) with mortality and hospital admissions during the first half of infancy. METHODS: This paper is based on a secondary analysis of data from a multicentre randomized controlled trial on immunization-linked vitamin A supplementation. Altogether, 9424 infants and their mothers (2919 in Ghana, 4000 in India and 2505 in Peru) were enrolled when infants were 18-42 days old in two urban slums in New Delhi, India, a periurban shanty town in Lima, Peru, and 37 villages in the Kintampo district of Ghana. Mother-infant pairs were visited at home every 4 weeks from the time the infant received the first dose of oral polio vaccine and diphtheria-pertussis-tetanus at the age of 6 weeks in Ghana and India and at the age of 10 weeks in Peru. At each visit, mothers were queried about what they had offered their infant to eat or drink during the past week. Information was also collected on hospital admissions and deaths occurring between the ages of 6 weeks and 6 months. The main outcome measures were all-cause mortality, diarrhoea-specific mortality, mortality caused by acute lower respiratory infections, and hospital admissions. FINDINGS: There was no significant difference in the risk of death between children who were exclusively breastfed and those who were predominantly breastfed (adjusted hazard ratio (HR) = 1.46; 95% confidence interval (CI) = 0.75-2.86). Non-breastfed infants had a higher risk of dying when compared with those who had been predominantly breastfed (HR = 10.5; 95% CI = 5.0-22.0; P < 0.001) as did partially breastfed infants (HR = 2.46; 95% CI = 1.44-4.18; P = 0.001). CONCLUSION: There are two major implications of these findings. First, the extremely high risks of infant mortality associated with not being breastfed need to be taken into account when informing HIV-infected mothers about options for feeding their infants. Second, our finding that the risks of death are similar for infants who are predominantly breastfed and those who are exclusively breastfed suggests that in settings where rates of predominant breastfeeding are already high, promotion efforts should focus on sustaining these high rates rather than on attempting to achieve a shift from predominant breastfeeding to exclusive breastfeeding.