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.

Sudheer Gupta ,Reena Kuriakose,Arun Kumar Gupta,Lalit Gupta,Pawan Kumar Popli,Chandra Kumar Natarajan,Mari Jeeva Sankar,Kailash Chandra Aggarwal,Ramesh Agarwal,Kanaklata Gupta,Sukhram Babu,Anil Duggal,Pratibha Gupta,Brijesh Kumar,Vishnubhatla Sreenivas,Vikas Yadav,Sunita Bhatia,Garima Dhankar,Chander Prakash Yadav,Ramesh Sharma,Vandana Jain,Harish Chellani,Somi Suresh,Faizan Mujeeb,Sant Lal,Sugandha Arya,Anne Therasa,Nisha Rani,Ajay Pratap Singh ,Vinod K Paul ,Farah Aziz Khan ,Ashok K Deorari ,Meenakshi

doi:10.1016/s2214-109x(17)30074-8

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.

Highlights

Exclusive breastfeeding for 6 months followed by complementary feeding for term infants is a standard recommendation by WHO, widely endorsed and accepted by the global community
Between March 20, 2013, and April 24, 2015, we identified 2135 livebirths at less than 34 weeks gestation. 412 were eligible at 4 months corrected age, nine of whom refused consent, and 403 were randomly assigned—206 infants to the 4 month group and 197 infants to the 6 month group
A total of 22 infants in the 4 month group and eight infants in the 6 month group were excluded from the analysis of the primary outcome

Summary

Introduction

Exclusive breastfeeding for 6 months followed by complementary feeding for term infants is a standard recommendation by WHO, widely endorsed and accepted by the global community. None of the organisations including WHO,[1] the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN),[2] or the American Academy of Pediatrics[3] provide evidence-based guidelines with respect to the optimal time of initiation of complementary feeding in preterm infants who are at a much higher risk of postnatal growth restriction than full-term infants.[4,5] The only available guidelines are from the UK, and are based on a single, non-systematic review of primarily physiological studies. Extrapolating the recommendation for full-term infants to initiate complementary feeding at 6 months of age to preterm infants is dependent on two major questions: what does 6 months refer to in a preterm infant—chronological (postnatal) age or corrected age? We searched the reference list of all these 50 studies to identify any other relevant studies

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Conclusion