Low utility of serum folic acid blood tests in healthy children and adolescents, a nationwide cohort.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7603873 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1076 (Electronic) Linking ISSN: 03406199 NLM ISO Abbreviation: Eur J Pediatr Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer-Verlag.

Folic Acid*/blood ; Folic Acid Deficiency*/epidemiology ; Folic Acid Deficiency*/diagnosis ; Folic Acid Deficiency*/blood; Humans ; Male ; Female ; Child ; Cross-Sectional Studies ; Adolescent ; Child, Preschool ; Infant ; Infant, Newborn ; Retrospective Studies ; Risk Factors

This study aimed to evaluate the utility of serum folic acid testing in children and adolescents in a developed country without mandatory folic acid food fortification and to identify patients at risk for folic acid deficiency. In this cross-sectional study, records from primary care and hospitals were reviewed for patients aged 0-18 years who underwent serum folic acid testing. Data were retrieved from the Leumit-Health-Services database over a ten-year period (January 2008 to December 2018). Clinical and laboratory data were compared between patients with folic acid deficiency to those with normal levels. Among 20,411 pediatric patients tested, 884 (4.3%) had folic acid deficiency, of whom only 26.3% had anemia. Only two patients (0.2%) had megaloblastic anemia. Multivariate analysis showed that male gender (odds ratio(OR)1.6, 95% CI 1.22-2.12), older age (OR 1.32, 95% CI 1.26-1.39), higher BMI percentile (OR 1.01, 95% CI 1-1.01), antipsychotic treatment (OR 3.23, 95% CI 1.52-6.84), celiac (OR 2.97, 95% CI 1.66-5.34), and Attention-Deficit-and-Hyperactivity-Disease (ADHD) treated with psychostimulants (OR 2.21, 95% CI 1.56-3.12) were associated with folic acid deficiency(all p < 0.01). Lower hemoglobin levels were independently associated with increased OR of folic acid deficiency (OR 0.77, 95% CI 0.66-0.90, p = 0.001), but anemia as a diagnosis was not.
Conclusion: Pediatric folic acid deficiency rates were low in this nationwide cohort and not linked to megaloblastic anemia, likely due to concomitant iron deficiency anemia. Although retrospective, this might suggest low utility for routine serum folic acid testing in healthy children in developed countries, except in cases of celiac disease or specific medication use such psychostimulants or antipsychotics.
What Is Known: • Folic acid deficiency is common among children in developing countries, causing megaloblastic anemia, growth delays, and cognitive impairments. In developed countries, the prevalence is considered low.
What Is New: • Of 20,411 pediatric patients tested for serum folate, in a developed country, only 4.3% had folate deficiency. • Risk factors for deficiency included celiac, antipsychotics, and psychostimulant treatment for ADHD. • Routine folate testing in developed countries may have limited utility; Targeted screening is recommended.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gallagher PG (2022) Anemia in the pediatric patient. Blood 140:571–593. https://doi.org/10.1182/blood.2020006479. (PMID: 10.1182/blood.2020006479352136869373018)
Kliegman RM, Geme JWS (2020) Nelson textbook of pediatrics, 2-volume set. 21st Edition.
Haimi M, Lerner A (2014) Nutritional deficiencies in the pediatric age group in a multicultural developed country, Israel. World J Clin cases 2:120–5. https://doi.org/10.12998/wjcc.v2.i5.120. (PMID: 10.12998/wjcc.v2.i5.120248685104023304)
Socha DS, DeSouza SI, Flagg A et al (2020) Severe megaloblastic anemia: Vitamin deficiency and other causes. Cleve Clin J Med 87:153–164. https://doi.org/10.3949/ccjm.87a.19072. (PMID: 10.3949/ccjm.87a.1907232127439)
de Benoist B (2008) Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 29:S238–S244. https://doi.org/10.1177/15648265080292S129. (PMID: 10.1177/15648265080292S12918709899)
McLean E, de Benoist B, Allen LH (2008) Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull 29:S38-51. https://doi.org/10.1177/15648265080292S107. (PMID: 10.1177/15648265080292S10718709880)
Wong E, Molina-Cruz R, Rose C et al (2022) Prevalence and disparities in folate and vitamin B12 deficiency among preschool children in Guatemala. Matern Child Health J 26:156–167. https://doi.org/10.1007/s10995-021-03257-6. (PMID: 10.1007/s10995-021-03257-634637065)
Levy S, Rachmilewitz M, Grossowicz N et al (1975) Nutritional survey in an iron- and folate-deficient population. Am J Clin Nutr 28:1454–1457. https://doi.org/10.1093/ajcn/28.12.1454. (PMID: 10.1093/ajcn/28.12.1454803008)
Gómez-Bueno S, Vázquez-López MA, García-Escobar I et al (2021) Status of folate in healthy children in Almeria. Eur J Pediatr 180:1825–1832. https://doi.org/10.1007/s00431-020-03902-2. (PMID: 10.1007/s00431-020-03902-233517500)
Mattiello V, Schmugge M, Hengartner H et al (2020) Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group. Eur J Pediatr 179:527–545. https://doi.org/10.1007/s00431-020-03597-5. (PMID: 10.1007/s00431-020-03597-532020331)
(2024) Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. World Health Organization, Geneva. Licence: CC BY-NC-SA 3.0 IGO.
Hasle H (2010) Nathan and Oski’s hematology of infancy and childhood. Eur J Haematol 84:189–189. https://doi.org/10.1111/j.1600-0609.2009.01377.x. (PMID: 10.1111/j.1600-0609.2009.01377.x)
Morris JK, Addor M-C, Ballardini E et al (2021) Prevention of neural tube defects in Europe: a public health failure. Front Pediatr 9:647038. https://doi.org/10.3389/fped.2021.647038. (PMID: 10.3389/fped.2021.647038342498038264257)
Mahajan V, Siddiqui A, Tahlan A et al (2023) Spectrum of Anemia in Indian children with Nephrotic Syndrome: a prospective observational study. Eur J Pediatr 182:4723–4729. https://doi.org/10.1007/s00431-023-05150-6. (PMID: 10.1007/s00431-023-05150-637572146)
Winkels RM, Brouwer IA, Verhoef P et al (2008) Gender and body size affect the response of erythrocyte folate to folic acid treatment. J Nutr 138:1456–1461. https://doi.org/10.1093/jn/138.8.1456. (PMID: 10.1093/jn/138.8.145618641191)
Misiak B, Frydecka D, Łaczmański Ł et al (2014) Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients. Eur J Clin Pharmacol 70:1433–1441. https://doi.org/10.1007/s00228-014-1762-2. (PMID: 10.1007/s00228-014-1762-2252919924226930)
Vinker S, Krantman E, Shani M, Nakar S (2013) Low clinical utility of folate determinations in primary care setting. Am J Manag Care 19:e100–e105. (PMID: 23534944)

Keywords: ADHD; Anemia; Celiac disease; Folic-acid; Macrocytic anemia

935E97BOY8 (Folic Acid)

Date Created: 20240926 Date Completed: 20241031 Latest Revision: 20241104

20241104

10.1007/s00431-024-05798-8

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