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Updated: Jun 4, 2025

Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Serum Folate Concentrations in Exclusively Breastfed Preterm Infants Who Received No Supplementary Oral Folic Acid
Isabel Iglesias-Platas1, Agata Sobczyńska-Malefora2,3, Vennila Ponnusamy4
1Neonatal Intensive Care Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.
Insights
Preterm infants showed adequate folate levels, with no deficiency observed. Concentrations were often high, particularly in those receiving folic acid supplements or specialized nutrition.
Area of Science:
- Neonatal Nutrition
- Pediatric Metabolism
- Folate Biochemistry
Background:
- Folate is crucial for preterm infant growth, yet evidence supporting current intake recommendations is limited.
- Assessing folate status in preterm infants is essential for optimizing developmental outcomes.
- Understanding folate exposure from various sources is key, especially for breastfed infants.
Purpose of the Study:
- To evaluate folate status in preterm infants near discharge and in early infancy.
- To correlate folate levels with dietary intake, including human milk and supplements.
- To investigate folate status in exclusively or predominantly breastfed preterm infants.
Main Methods:
- Prospective, multicenter observational cohort study of 45 preterm infants (<33 weeks GA).
- Serum folate levels measured at Neonatal Intensive Care Unit (NICU) discharge (T1) and 2-3 months corrected age (T2).
- Folate status categorized using World Health Organization (WHO) guidelines; nutritional intake data collected.
Main Results:
- No infant exhibited folate deficiency (<13.5 nmol/L) at either time point.
- A significant proportion of infants had elevated serum folate concentrations (>45.3 nmol/L): 31% at T1 and 42% at T2.
- High folate levels were associated with folic acid supplements, parenteral nutrition, and breast milk fortifiers.
Conclusions:
- Folate deficiency was not observed in this cohort of preterm infants.
- Elevated folate concentrations were common and comparable to those in healthy term infants.
- Further research is warranted to investigate the clinical implications of high folate levels in preterm infants.
Abstract:
Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
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