Serum Folate Concentrations in Exclusively Breastfed Preterm Infants Who Received No Supplementary Oral Folic Acid After Discharge: A Prospective Cohort Study

<b>Background/Objectives:</b> Adequate folate intake is required in preterm infants for rapid growth and development, but there is little evidence to back recommendations. We aimed to assess folate status in preterm infants at discharge and in early infancy, according to exposure to folate sources, particularly in those exclusively/predominantly breastfed. <b>Methods:</b> A prospective, multicenter, observational cohort study was conducted in the UK, involving 45 preterm infants <33 weeks' gestational age (GA) exclusively/predominantly fed human milk when approaching NICU (Neonatal Intensive Care Unit) discharge. Serum folate levels were measured near NICU discharge (T1) and at 2-3 months corrected age (T2). Folate status was categorized per WHO (World Health Organization) guidelines: deficiency (<6.8 nmol/L), possible deficiency (6.8-13.4 nmol/L), normal (13.5-45.3 nmol/L), and elevated (>45.3 nmol/L). Nutritional information on feed and supplements was collected from hospital notes and maternal interviews. <b>Results:</b> Thirty-two infants (71%) received parenteral nutrition. Twelve infants (32%) remained exclusively breastfed at T2. No infant from the whole cohort had a serum folate concentration <13.5 nmol/L at either time point. A proportion of infants had serum folate concentrations >45.3 nmol/L: 14/45 (31%) at T1, 19/37 (42%) at T2, and 7/37 (16%) at both time points. Elevated concentrations were seen particularly in infants who received folic acid supplements or nutrition containing folic acid, such as parenteral nutrition and breastmilk fortifiers. <b>Conclusions:</b> Folate deficiency was not observed in this cohort; folate concentrations were high and in line with those observed in healthy term infants. Further research is needed to assess the high folate concentrations in premature babies and whether they may have any adverse clinical impact.