Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial

Sonja Y Hess, K Ryan Wessells, Guy-Marino Hinnouho, Maxwell A Barffour, Kanokwan Sanchaisuriya, Charles D Arnold, Kenneth H Brown, Charles P Larson, Supan Fucharoen, Sengchanh Kounnavong, Sonja Y Hess, K Ryan Wessells, Guy-Marino Hinnouho, Maxwell A Barffour, Kanokwan Sanchaisuriya, Charles D Arnold, Kenneth H Brown, Charles P Larson, Supan Fucharoen, Sengchanh Kounnavong

Abstract

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6-23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (-1·93 (95 % CI -1·88, -1·97)) v. placebo (-1·88 (95 % CI -1·83, -1·92)), and the opposite occurred among initially anaemic children (final mean LAZ -1·90 (95 % CI -1·86, -1·94) in MNP v. -1·92 (95 % CI -1·88, -1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

Trial registration: ClinicalTrials.gov NCT02428647.

Keywords: Anaemia; Diarrhoea; Growth; Inherited Hb disorder; Iron status; Micronutrient powder; Young children.

Figures

Fig. 1
Fig. 1
Flow chart of study participants. * The main trial included four intervention groups; only two of these are included in the present analysis, for which details are shown here. MNP, micronutrient powder; IHbD, inherited Hb disorders.
Fig. 2
Fig. 2
Effect modification of baseline anaemia and iron status on Hb and iron status at end line among young children who received either a low-iron-, high-zinc-containing micronutrient powder (▪) or a placebo powder (◻). Only selected significant or marginally significant effect modifications are shown; a complete overview of effect modifications is included in Table 4. Iron status indicators adjusted for inflammation. Continuous outcomes log transformed for analysis. sTfR, soluble transferrin receptor. Values are means, with standard deviations represented by vertical bars.
Fig. 3
Fig. 3
Effect modification of inherited Hb disorder (IHbD) on final iron status among young children who received either a low-iron, high-zinc micronutrient powder (◻) or a placebo powder (◻). Only significant or marginally significant effect modifications are shown; a complete overview of effect modifications is included in Table 4. Iron status indicators adjusted for inflammation. Continuous outcomes log transformed for analysis. All IHbD were combined into one category and compared against all cases without clinically significant IHbD. sTfR, soluble transferrin receptor. Values are means, with standard deviations represented by vertical bars.
Fig. 4
Fig. 4
Effect modification of inherited Hb disorder (IHbD) and baseline anaemia on selected growth outcomes among young children who received either a low-iron-, high-zinc-containing micronutrient powder (◻) or a placebo powder (◻). Only selected significant or marginally significant effect modifications are shown; a complete overview of effect modifications is included in Table 4. All IHbD were combined into one category (i.e. α- or β-thalassaemia or Hb E) and compared against all cases without clinically significant IHbD. WLZ, weight-for-length z score; LAZ, length-for-age z score; MUAC, mid-upper arm circumference; MUACZ, mid-upper arm circumference z score. Values are means, with standard deviations represented by vertical bars.

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