A Folate Fallacy: Inappropriate Cut-off Resulting in An Epidemic of Folate Deficiency

From the 2018 HVPAA National Conference

Nivedita Arora (University of Texas Southwestern Medical Center, Dallas, TX;), Arjun Gupta (University of Texas Southwestern Medical Center, Dallas, TX;), Alagarraju Muthukumar (University of Texas Southwestern Medical Center, Dallas, TX;), Jyoti Balani (University of Texas Southwestern Medical Center, Dallas, TX;), Carol Croft (University of Texas Southwestern Medical Center, Dallas, TX;), Ellen Araj (University of Texas Southwestern Medical Center), Srikanth Nagalla (University of Texas Southwestern Medical Center, Dallas, TX;), Ravi Sarode (University of Texas Southwestern Medical Center, Dallas, TX;)

Background

Supplementation of grains with folate was mandated by the United States FDA in 1996. Since then, population based studies, and studies in the outpatient and inpatient setting have demonstrated that <1% of patients tested have low folate levels. We noted that rates of folate deficiency were higher at our institution.

Objectives

To study rates of low serum folate levels at our institution to compare and evaluate against other institutional and national rates.

Methods

We conducted a review of serum folate tests ordered at our institution (University of Texas Southwestern Medical Center) between January 1, 2015 to December 31, 2017. Both inpatients and outpatients were included. A distribution curve of folate levels versus percent ‘lower than cut-off for normal’ was constructed (Figure 1)

Results

: A total of 19,438 folate levels were ordered for 15,558 unique patients during this three-year period (mean 6,479 tests/ year). Of these, 52% were ordered in the inpatient and 48% in the outpatient setting. The rate of positive tests (serum folate less than the cut-off for normal) was noted to be 12.5%. On reviewing the cut-off, it emerged that we had been using a lower limit of normal of 8.4 ng/ml to define folate deficiency. The folate testing kit had recommended that the lower limit be adjusted between 4.5-8.4ng/ml based on the patient population. Utilizing a cut-off of 4.5 ng/ml would have resulted in 1.6% of tests being positive.

Conclusion

The rate of positive testing for folate deficiency at our institution was noted to be much higher than the national population data. We identified and fixed a rectifiable cause of this unexpectedly high rate of positive testing for folate deficiency. We found that the lower limit of the cut-off range suggested by the kit was more appropriate for our patient population. Based on these results, we proposed a change in the cut off for positive testing for low folate level from 8.4 ng/ml to 4.5 ng/ml. This would fix ‘mislabelling’ patients as folate deficient.

Implications for the Patient

Folate deficiency is rare in the post-fortification era. Institutions experiencing high rates of positive testing should review their testing methodology and cut-off values. These data are being used locally to educate providers about the rarity of folate deficiency, discouraging testing for folate, and promoting empiric folate supplementation for high risk.