Hemoglobin outcomes associated with supervised therapeutic iron or preventive multiple micronutrient powder supplementation in high-altitude Peruvian infants: A real-world natural experiment.
Vásquez-Velásquez C, Suchdev P, et al. • PloS one • 2026
Strict follow-up of iron and multiple micronutrient powder supplementation was associated with greater hemoglobin increases and lower altitude-adjusted anemia prevalence among high-altitude Peruvian infants, though residual anemia remained common after six months.
Key Findings
Results
Overall, only 14.8% of infants achieved an adequate hemoglobin response (increase ≥1 g/dL) across both follow-up groups.
Adequate Hb response was defined as an increase ≥1 g/dL
18.7% of infants in the strict follow-up group achieved adequate Hb response compared to 11.8% in the non-strict follow-up group
Among non-anemic infants at baseline, adequate Hb response was 8.3% under strict follow-up vs. 2.7% under non-strict follow-up
Study included 317 infants aged 6-12 months from Puno, Peru at 3,832 m altitude
Results
Strict follow-up was associated with significantly higher odds of achieving an adequate hemoglobin response in the primary adjusted model.
Primary adjusted odds ratio (aOR) for strict vs. non-strict follow-up: 3.53 (95% CI 1.40–8.84)
Crude (unadjusted) estimate: OR 2.45 (95% CI 1.30–4.63)
In sensitivity analyses incorporating additional socioeconomic, nutritional, and program-related covariates, the association was attenuated to aOR 2.18 (95% CI 0.53–8.99), crossing the null
Multivariable regression models were used to assess factors associated with hemoglobin response
Results
Strict follow-up was associated with a significantly greater mean increase in hemoglobin concentration as a continuous outcome.
Adjusted mean difference in hemoglobin increase: 0.74 g/dL (95% CI 0.23–1.25) in favor of strict follow-up
Hemoglobin was measured at baseline and at six-month follow-up
Hemoglobin values were adjusted for altitude using WHO 2024 criteria
Results
Altitude-adjusted anemia prevalence at six months was significantly lower in the strict follow-up group compared to the non-strict follow-up group.
Anemia prevalence at follow-up: 25.2% in strict follow-up group vs. 38.2% in non-strict follow-up group (p = 0.019)
Despite the improvement, residual anemia remained common after six months of supplementation in both groups
Supplements were provided monthly for six months per national guidelines
Results
Baseline anemia and older age were independently associated with larger hemoglobin gains over the six-month supplementation period.
These factors were identified through multivariable regression models
Anemic infants at baseline received therapeutic iron syrup (ferrous sulfate or iron polymaltose), while non-anemic infants received preventive multiple micronutrient powder (MNP)
The study population consisted of infants aged 6–12 months
Methods
This study used a policy-driven natural experiment design comparing two population-based cohorts evaluated before and after implementation of strict supplementation follow-up.
Randomized trials were precluded by Peru's legally mandated universal micronutrient supplementation policies
Two population-based cohorts totaling 317 infants were analyzed
The study was conducted in Puno, Peru (3,832 m altitude)
National guidelines dictated that anemic infants receive therapeutic iron syrup and non-anemic infants receive preventive MNP, with supplements provided monthly for six months
What This Means
This research examined whether more closely supervised iron or micronutrient supplement programs improve blood hemoglobin levels in babies living at high altitude in Peru. Because Peruvian law requires all infants to receive these supplements, researchers could not randomly assign infants to different groups. Instead, they took advantage of a natural policy change—comparing outcomes in 317 infants before and after stricter program follow-up was put in place. Babies with anemia received iron syrup, while babies without anemia received a powder containing multiple micronutrients, and both groups were followed for six months.
This research suggests that stricter program follow-up—meaning health workers more actively monitored whether families were giving supplements correctly—was associated with better hemoglobin outcomes. Infants in the strict follow-up group were about 3.5 times more likely to show a meaningful hemoglobin increase (of at least 1 g/dL) and had a 0.74 g/dL greater average hemoglobin increase compared to those under less strict follow-up. Anemia rates at six months were also lower in the strict follow-up group (25.2% vs. 38.2%). However, anemia remained very common even after six months of supplementation in both groups, and overall only about 1 in 7 infants achieved a meaningful hemoglobin improvement.
These findings matter because they suggest that simply providing supplements is not enough—the quality of program implementation and follow-up may play an important role in whether supplementation actually improves infant health. At the same time, the persistence of anemia in both groups points to additional factors beyond supplementation—possibly related to the challenges of living at high altitude, diet, infection, or other causes—that future research and public health programs will need to address.
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