Reference intervals for hemoglobin A1c in pregnant women: data from an Italian multicenter study.

BACKGROUND The reference intervals for hemoglobin A1c (Hb A1c) in pregnant women without diabetes are not well defined, and few examples of reference intervals established by networks of different laboratories are available. METHODS Five Italian Diabetic Care Units were involved in the study. Data were collected from 445 pregnant women without diabetes, selected on the basis of glucose challenge test results, and from 384 nonpregnant control women. The Hb A1c measurements were performed with HPLC systems aligned to the Diabetes Control and Complications Trial. Plasma glucose measurements were also performed locally. Both Hb A1c and glucose measurements were harmonized by running appropriate external quality assessment schemes. The reference intervals were calculated in terms of nonparametric 2.5th to 97.5th percentiles with 0.90 confidence intervals. RESULTS The Hb A1c measurements were reproducible (CV = 2.0%) and accurate [mean (SE) difference from the target values, -0.10 (0.06)%]. Glucose measurements were also reproducible (mean CV = 3.2%) and accurate [difference from the target values, -0.01 (0.04) mmol/L]. To calculate common reference intervals, we merged the data collected in the different centers. The Hb A1c reference intervals were 4.0%-5.5% for pregnant nondiabetic women and 4.8%-6.2% for nonpregnant controls. CONCLUSIONS Healthy pregnant women have lower Hb A1c concentrations than nonpregnant women. The reference intervals for Hb A1c in pregnant women should therefore be lower than those currently in use.