Abstract

Background Assessments of the efficacy of interventions to improve child growth are often based on differences in mean height-for-age z-scores (HAZ) and stunting (HAZ<-2) in randomized controlled trials (RCTs). However, this approach does not account for children’s starting skeletal age and does not enable assessment of the extent to which interventions optimized linear growth.

Objective To develop and apply a new method using height-age to express linear growth effects in RCTs.

Methods Longitudinal individual participant data (IPD) from a Bangladeshi trial cohort were used to compare height-age estimates derived from individual-level heights, mean raw height, or mean HAZ. Then, using average height-age as a proxy for skeletal age, we developed the ‘proportion of maximal benefit’ (PMB) metric to quantify intervention effects relative to optimal growth for children’s starting skeletal age. Optimal growth occurs when height-age increases in parallel with chronological age (i.e., PMB=100%) whereas no effect (versus control) corresponds to a PMB of 0%. Linear growth outcomes in 4 published RCTs of nutrition-specific interventions were re-expressed as mean height-age and PMB, and compared to effects conventionally expressed as intervention-versus-control mean differences (MD) in HAZ.

Results Mean height-age could be derived from any published estimate of mean raw height or mean HAZ; however, to calculate the PMB, height or HAZ data were required at both the beginning and end of the observation period. Interpretations of intervention effects were consistent when expressed as either the height-age MD or HAZ MD. In contrast, the PMB does not have a corresponding metric on the HAZ scale, and therefore provided a new way to quantify intervention efficacy.

Conclusion Height-age can be used as an alternative to HAZ to express intervention effects. The PMB has the advantage of conveying the extent to which an intervention improved average linear growth in relation to a biologically-defined benchmark.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Kelly Watson was funded by the Canadian Institutes of Health Research (CIHR), through the Canadian Graduate Scholarship – Masters (CGS-M) and a project grant (#169133). The CIHR had no involvement in this study and does not restrict works for publication.

Author Declarations

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The research ethics board (REB) of The Hospital for Sick Children (SickKids) gave ethical approval for this work (SickKids REB #1000079659).

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AbbreviationsBONUSKidsBONe and mUScle health in KidsCIconfidence intervalDIVIDSDelhi Infant Vitamin D SupplementationHAZheight-for-age z-scoreIPDindividual participant dataLAZlength-for-age z-scoreLMICslow– and middle-income countriesLMSlambda-mu-sigmaMDmean differenceMDIGMaternal vitamin D for Infant GrowthPMBproportion of maximal benefitRCTrandomized controlled trialREBresearch ethics boardSDstandard deviationSEstandard errorSickKidsThe Hospital for Sick ChildrenWHO-GSWHO growth standards