Effect of zinc supplementation on morbidity and growth in hospital-born, low-birth-weight infants.

Randomized, placebo-controlled trial in hospital-born term low-birth-weight infants in urban New Delhi, India. In the zinc arm, 1026 infants were randomized in a 1:1 zinc:placebo design after enrollment at 2-4 weeks of age and followed with monthly dispensing and repeated morbidity and growth assessments to 12 months.

Oral elemental zinc as zinc sulfate was given daily at 5 mg/d from enrollment (age 2-4 weeks) through 6 months, then 10 mg/d from >6 months through 12 months. Tablets were dissolved in expressed breast milk or water and compared with placebo.

Daily zinc supplementation did not meaningfully reduce diarrhea, acute lower respiratory infections, or improve weight and length outcomes over 12 months. The clearest effect was biochemical: 12-month plasma zinc was 100.2 6 41.9 vs 73.3 6 22.5 lg/dL, a difference of 26.9 lg/dL (95% CI 19.6 to 34.2), and zinc deficiency decreased to 12.6% vs 24.4% (difference -11.8%; 95% CI -20 to -3.4; P < 0.005). Care-seeking for illness was lower at 9 months (difference -5.7%; 95% CI -9.9 to -1.4), but deaths were similar (21 vs 19). The authors concluded that RDA-level zinc did not confer substantial clinical benefit in this setting.

The trial was limited to mostly breastfed, hospital-born term low-birth-weight infants from one urban Indian setting, which limits generalizability. Clinical morbidity and growth outcomes were largely null despite a clear biomarker response, so the findings may not translate to better health outcomes in other populations, contexts, or dosing strategies.