Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial

Abstract

SummaryBackgroundEvidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation.MethodsIn this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31–33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149.FindingsBetween March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: −1·6 (SD 1·2) in the 4 month group versus −1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI −0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0–3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group.InterpretationAlthough there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation.FundingIndian Council of Medical Research supported the study until Nov 14, 2015. Subsequently, Shuchita Gupta's salary was supported for 2 months by an institute fellowship from All India Institute Of Medical Sciences, and a grant by Wellcome Trust thereafter.

The Timing of Initiating Complementary Feeding in Preterm Infants and Its Effect on Overweight: A Systematic Review

“…The primary outcome of Gupta et al [28] was weight for age Z-score at 12 months corrected age but also provided data on BMI for age Z-score at 12 months corrected age. Sun et al [24] also presented data in BMI Z-score at 1 year of age (corrected or uncorrected age).…”

“…The well-designed study of Gupta et al [28] randomized between initiating complementary feeding at 4 months or at 6 months corrected age. They found no significant difference in BMI Z-scores (mean –1.0, SD 1.0 in the 4 month group vs. –0.9, SD 1.1 in the 6 month group, p = 0.561); also, they did not find a significant difference in other growth parameters.…”

“…They found no significant difference in BMI Z-scores (mean –1.0, SD 1.0 in the 4 month group vs. –0.9, SD 1.1 in the 6 month group, p = 0.561); also, they did not find a significant difference in other growth parameters. Prominently, they found that 18% of the infants in the 4-month group required hospital admission during the study period, compared with 9% of the infants in the 6-month group (relative risk 1.9, 95% CI 1.1–3.3; p = 0.01) [28]. …”

“…Gupta et al [28] and Sun et al [24] found no significant difference in BMI Z-score at 1 year between early and late introduction of solid foods, using the same growth standards [29]. Spiegler et al [26] concluded that preterm infants may benefit from early introduction and Marriott et al [23] concluded that the early introduction of complementary feeding would lead to a significant greater mean rate of growth in length per week.…”

“…However, our outcome of interest, the start of complementary feeding, was not compared with that of the control group of term children. Sun et al [24] defined preterm infants as those born before 36 weeks of gestation and Gupta et al [28] randomized infants as those born in less than 34 weeks of gestation.…”