Treating growth faltering in infants under six months: Critical research gaps

Growth faltering, or a slower gain in weight, length, or head circumference than expected for a child’s age and sex, increases the risk of mortality and morbidity. For many children, growth faltering is present at birth or develops within the first 6 months of life. Evidence is lacking on effective growth interventions for infants aged under 6 months (u6m).

This systematic review and meta-analysis was commissioned by the World Health Organization (WHO) to identify and evaluate interventions that included provision of supplemental milks to address growth faltering among infants u6m. The review was conducted according to the US National Academies of Sciences, Engineering, and Medicine guidelines. Of 7,390 deduplicated articles identified, 227 full texts were assessed for eligibility. Two randomised controlled trials were included, of which only 1 was published in a peer-reviewed journal.

The first study was a three-armed randomised controlled trial conducted in Bangladesh (2012–2015) in the context of infant rehabilitation from severe wasting. A total of 153 infants u6m admitted with diarrheal illness and weight-for-length z-score (WLZ) <-3 and/or bipedal oedema were provided with F-100, diluted F-100 (DF-100), or standard infant formula after stabilisation. While breastfeeding mothers were encouraged to continue, only about half of infants were breastfed upon trial entry and only a small proportion of their feeds were from breastmilk. Infants were offered water in between feeds, which runs counter to the WHO guidelines. Infants were discharged when they gained 15% of their weight or had oedema-free WLZ ≥-2.

The second study compared DF-100 and standard infant formula provided to infants u6m in the Democratic Republic of Congo (DRC) (2007–2008). Infants were included in the study if they were free of oedema and their mother reported breastfeeding failure or their child’s lack of weight gain at home. All infants were either being breastfed or their mothers were receiving relactation support. Supplementation was halved when infants were gaining 20 g/day and stopped when infants maintained a weight gain of 10g/day for 3 consecutive days. Infants were discharged when they maintained weight gain for 3–5 days.

The Bangladesh study showed significantly higher rates of weight gain in infants receiving F-100 (mean difference 4.6 g/kg/day; p=0.004) and DF-100 (mean difference 3.1 g/kg/day; p=0.015) than those receiving infant formula. In the DRC trial, no difference in weight gain was observed for infants receiving F-100 compared to infant formula within a broader context of lactation support. The meta-analysis also showed no difference in weight gain between infants receiving DF-100 and infant formula.

The main limitation of this review was the dearth of high-quality evidence on interventions for nutritional management of infants u6m with growth faltering. The 2 included studies differed in their inclusion criteria and methods, had few shared outcomes, small sample sizes, and high attrition rates, thus limiting comparability between studies and the generalisability of study findings. Both interventions focused on providing supplemental milk, with no or limited support for breastfeeding or relactation – a misalignment with WHO guidance for exclusive breastfeeding to six months.

The authors recommend a paradigm shift to reorient research around supporting and restoring breastfeeding, rather than on supplementation. They propose a new framework to guide future research to inform development of an evidence-based decision tree to ascertain if, when, and for how long a malnourished child should receive supplemental milk and, if so, what form this should take.