Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers

OBJECTIVE:  To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy-associated plasmaprotein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (freeβ-hCG) and to evaluate the influence of glycemic control on these parameters in the pregnant diabetic women.  DESIGN:  Retrospective study.  SETTING:  Data were extracted from electronic obstetric and laboratorydatabases at two Danish University Hospitals.  POPULATION:  Based on 36 415 pregnancies without T1DM (non-T1DM) and 331 pregnancies with T1DM; β-hCG and PAPP-A were obtained at 8+0 to 14+2 gestational weeks.  METHODS:  Medians for PAPP-A and free β-hCG were generated and multiple of the normal gestation-specific median (MoM) values were calculated for each separate pregnancy. After adjustment for maternal weight, ethnicity and smoking status, MoM values were compared across the T1DM and non-T1DM groups, respectively. Additionally, the relationship between PAPP-A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearman's rank correlation. MAIN OUTCOME MEASURES. Difference in biochemical marker levels between T1DM and non-T1DM.  RESULTS:  PAPP-A was 0.86 MoM in T1DM pregnancies and 1.01 MoM in non-T1DM pregnancies, p < 0.0001. Conversely, free β-hCG was not altered in T1DM pregnancies (T1DM 0.99 MoM, non-T1DM 0.98 MoM; p=0.14). There was a significant inverse correlation between HgbA1C and PAPP-A (rho=-0.12, p=0.02).  CONCLUSIONS:  In T1DM pregnancies, PAPP-A MoM values were lower than in non-T1DM pregnancies. This suggests that correction should be considered in first trimester biochemical screening for fetal aneuploidy in T1DM women.