The impact of prematurity on fetal haemoglobin and how it can bias measurement of glycated haemoglobin

Background: The extent to which fetal hemoglobin (HbF) concentrations are increased in premature infants at the age of six to eight months is only sporadically described. The influence of HbF on measurement of glycated haemoglobin (HbA_1c) has not been investigated in this population.

Methods: As part of a nutritional study on premature children, HbF and HbA_1c were measured in 46 premature infants at the age of six to eight months.

Results: Median HbF percentage was 10.3% (range 2.0 to 39.2%). In a multiple regression model only birth weight (P = 0.002) and post-conceptional age (P < 0.001) were significantly inverse correlated to HbF.  HbA_1c measurement could not be performed in 52% of the infants due to HbF concentrations > 10%, and only 13% of the HbA_1c results were reliable without corrections or validation of the chromatogram. Adjusted HbA_1c measurements (4.9±0.2%) differed significantly from unadjusted values (4.4±0.4%), (P < 0.0001) with bias for unadjusted values ranging from 1.9 to 33.3%.

Conclusions: The HbF concentration remains high in premature infants at six to eight months of age. The clinical implication of this work is a renewed attention on the prolonged HbF expression in premature infants and the hereof following complications in measuring different analytes, e.g. HbA_1c. The issue of HbA_1c measurement can be solved by awareness on the condition, while the reason for the prolonged HbF expression and the possible clinical implications of this warrants further investigations.