P2C334: Zinc Supplementation Improves Linear Growth in Premature and Very Low Birth Weight Infants

Background: Zinc deficiency is associated with prematurity, intrauterine growth restriction, and growth failure with stunting. Since most of zinc accretion in the fetus occurs in the second and last trimesters, extremely low gestational age newborns (ELGANs) are at risk for zinc deficiency. A review of randomized controlled trials in preterm infants showed that zinc supplementation improved weight gain and possibly slightly improved linear growth. In a prior study at this site, among infants < 33 weeks gestational age (GA) or birthweight < 1500 g fed their own mother's milk and/or donor breast milk, zinc level was measured in those with insufficient growth; 14% were diagnosed with zinc deficiency (serum zinc level < 0.74 mcg/ml) (Sanchez-Rosado 2023).

We hypothesized that routine enteral zinc supplementation would positively impact growth parameters, such as weight, length, and fronto-occipital circumference (FOC), in infants born < 33 weeks GA or birthweight < 1500 g.

Methods: In Epoch-1, zinc supplementation in total parenteral nutrition (TPN) was 450 mcg/kg/day and enteral supplementation was provided only to those with documented zinc deficiency. In Epoch-2, zinc was provided as recommended by ESPGHAN with 500 mcg/kg/day in TPN and routine enteral supplementation (to achieve 2.5 and later 3 mg/kg/day [Koletzko 2022]) until 36 weeks postmenstrual age or discharge. In Epoch-2 serial zinc levels were obtained at birth, when at 140 ml/kg/day of feeds, and one month after the second level. Growth was assessed by change in z-scores from birth to discharge in accurate measurements of length (Δlengthz), weight, and FOC, adjusted for GA, sex, and length of stay (LOS).

Results: The study included 530 infants in Epoch-1 and 327 in Epoch-2. Birth characteristics were similar in both epochs (Table 1). Adjusted Δlengthz improved by 10% in Epoch-2 compared to Epoch-1 (Table 2). However, there was no significant change in z-scores of weight and FOC. In Epoch-2, 91% of infants had at least one serum zinc level obtained before discharge. A low serum zinc level was observed in 42/295 (14.2%) neonates within the first 48 hours postnatally and 144/296 (48.6%) at any time before discharge. In both epochs, Δlengthz was lower among infants whose lowest serum zinc level was < 0.8 mcg/ml than among those with higher levels [-1.24±0.69 (n=128) vs -0.94±0.62 (n=29), P=0.03], respectively.

Conclusion: In this study, routine enteral zinc supplementation in preterm or VLBW infants improved linear growth by 10%. Low serum zinc levels, suggesting zinc deficiency, occurred frequently despite zinc intake as currently recommended.