Is Folic Acid Supplementation Really Necessary in Preterm Infants ≤32 Weeks of Gestation?

Objectives: The aim of this study was to define whether there was folate deficiency in hospitalized preterm infants, and, second, to define the effect of feeding modalities on serum folate levels. Methods: Infants born ≤32 weeks of gestation were included in the study. Blood samples for the determination of serum folate levels were obtained on days 14 and 28 postnatally, as well as 36 weeks postconceptionally (or just before discharge if patients are discharged <36 weeks)—samples A, B, and C, respectively. Infants were divided into 3 groups based on mode of feeding; human breast milk (HBM), fortified HBM (fHBM), or preterm formula (PF). Results: A total of 162 preterm infants were enrolled: 17 (10.5%) of whom received HBM alone, 94 (58%) received fHBM, and 51 (31.5%) were fed with PF. None of the preterm infants developed folate deficiency during the study period. Preterm infants in the fHBM and PF groups had significant higher serum folate levels in samples C when compared with those receiving HBM alone ( P < 0.001 for both). Multivariate analysis to evaluate the effects of maternal supplementation, smoking habit, gestational age, birth weight, and cumulative folic acid intake in samples A, B, and C suggested that maternal smoking and maternal folic acid supplementation had significant effects on serum folate levels in sample A and B. Conclusions: Preterm infants receiving parenteral nutrition with high folic acid content have no risk of folate deficiency during the 2 months of age; however, preterm infants fed orally from birth with HBM or PF with a low folic acid content could be at risk for folate deficiency, especially when mothers are smokers and/or do not receive folic acid supplementation during pregnancy.