There were 23,662 live-born infants during the study period and a total of 759 neonatal deaths (neonatal mortality rate = 32.1/1000 live births). Many (409, 53.9%) of the neonatal deaths occurred in the first 48 h and were excluded from the analysis. Among 23,235 infants surviving to 48 h, there were 71 for whom breast-feeding data were not available (53 of these infants subsequently died). There were a total of 23,164 (99.7%) infants for whom we could confirm that breast-feeding was ever initiated and the actual time to breast-feeding was estimable for 22,838 (98.6%) infants (). The median time to breast-feeding was 18.4 h and the mean was 22.7 ± 22.1 h. Only 771 infants (3.4%) were breast-fed within the first hour after birth, but breast-feeding within the first 24 (56.6%) or first 48 (83.1%) h was more common. Breast-feeding was established within 72 h for 97.2% of breast-fed infants.
Flowchart of infants with defined breast-feeding initiation time and included in the analysis.
Partial breast-feeding (i.e. combined breast-feeding with other milk-based fluids and/or solids) was the most common established breast-feeding pattern in this setting (72.6% of infants). Goat and/or buffalo milk are often provided to the newborn infant in Sarlahi, especially during the first 24-48 h after birth. Partially breast-fed infants were at substantially higher mortality risk than those who were exclusively breast-fed (relative risk [RR] = 1.77 [95% CI = 1.32, 2.39]). Infants who were breast-fed in the first 24 h were more likely to be exclusively breast-fed (42.3%) than late initiators (8.0%, OR = 8.47 [95% CI 7.81, 9.18]).
Both the pattern of breast-feeding (exclusive vs. partial) and initiation time varied substantially between the 2 major ethnic groups. Infants of pahadi households (those originating from the hills region of Nepal, 28.8% of households) were more likely to be breast-fed exclusively (58.4 vs. 14.8%; OR = 8.09 [95% CI = 7.57, 8.64]) and be early initiators (92.9 vs. 41.9%; OR = 18.2 [95% CI = 16.4, 20.1]) than those from madeshi households (those originating from the plains region of Nepal). Similarly, mothers of pahadi infants were more likely to report feeding their infant(s) colostrum (90.9 vs. 78.1%; OR = 2.86 [95% CI = 2.61 - 3.13]).
Among the 22,838 infants included in the analysis, there were 297 deaths after 48 h and prior to 28 d. There was a trend toward significantly higher risk of mortality among infants who were breast-fed later compared with those who received breast milk within the first hour of life (; ). Compared with those fed within the first hour after birth, mortality risk was 2.80, 4.08, and 4.19 times higher among infants first breast-fed after d 1, 2, or 3 of life, respectively. Mortality risk was 2.56 (95% CI = 0.96, 6.85) times higher comparing all those fed after vs. before 1 h after birth. Late initiators (≥24 h) were 1.74 (95% CI = 1.39, 2.19) times more likely to die during the neonatal period than early initiators (<24 h).
Mortality risk by breast-feeding initiation time (BI time) among breast-fed infants surviving to 48 h1
Risk of mortality of infants in Nepal by time of breast-feeding initiation (Kaplan-Meier survival curves).
Given the substantial differences in pattern and timing of breast-feeding between pahadi and madeshi households, estimates of mortality risk comparing early vs. late initiators is also shown separately by ethnic status. The interaction term for ethnic group status was marginally significant (P = 0.06).
The relationship between mortality risk and breast-feeding initiation time was adjusted for multiple covariates, including low birth weight (LBW, <2500 g) status, prematurity (<37 wk), cord and skin cleansing treatment allocation in the parent trial, maternal literacy, sex, maternal hand-washing, previous death of a sibling, ethnicity, parity, and maternal report of fever in the 7 d prior to delivery (). The most important confounders of the main relationship were birth weight and prematurity; after adjustment for these variables, the relationship between initiation time and mortality was not significant for any individual category, although there was a trend (P = 0.03) toward increasing risk with delayed initiation time. Furthermore, when comparing early to late initiators, adjusted risk of mortality was 1.41 (95% CI = 1.08, 1.86) times higher among those initiating after the first day of life. Sex of the newborn, maternal literacy, and treatment allocation in the parent trial, parity, and maternal report of fever in the 7 d prior to delivery did not confound this association.
Adjusted mortality risk by breast-feeding initiation time (BI time) among breast-fed infants surviving to 48 h1
The adjusted model was estimated separately by ethnic status (). There was little change from the ethnic group-specific, nonadjusted estimates from , suggesting that after the effect modification of ethnic group was taken into account, the relationship between mortality and initiation time was not confounded by LBW or preterm birth. For pahadi newborns, the adjusted risk of mortality was 3.00 [95% CI = 1.50-5.98] times higher among late initiators compared with early initiators. Among madeshi newborns, the magnitude of the relationship and the statistical strength of evidence was lower, but late initiators in this subgroup remained 1.32 [95% CI = 1.00-1.74] times more likely to die than early initiators.
Adjusted mortality risk by breast-feeding initiation time (BI time) among breast-fed infants surviving to 48 h by ethnic group1
Infant illness status was defined only for infants for whom daily morbidity data were available within 48 h of life (82.3%). In analyses restricted to this subset of infants, the multivariate model was further adjusted by this variable and there was little evidence for confounding; after adjustment, the RR estimate for mortality comparing early vs. late initiators increased only slightly from 1.41 to 1.44 (95% CI = 1.08-1.92). Whereas infants who were ill prior to 48 h after birth (n = 741, 4.0%) were more likely to die (RR = 1.76 [95% CI =1.07-2.91]), removing them from the analysis led to no substantial change in the association of early vs. late breast-feeding initiation on neonatal mortality (1.35 [95% CI = 1.02-1.78]). This suggests that any residual reverse-causation bias in this analysis is likely to be minimal.