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

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.