First trimester maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus.

OBJECTIVE: To investigate whether markers of first trimester screening for aneuploidies, including fetal nuchal translucency (NT), maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A), are altered in women with pre-existing type-1 and type-2 diabetes mellitus, and in women that subsequently develop gestational diabetes mellitus (GDM).

DESIGN: Retrospective analysis of prospective combined screening for aneuploidies in singleton pregnancies at 11(+0) -13(+6) weeks of gestation.

SETTING: Antenatal clinic.

POPULATION: Singleton pregnancies at 11(+0) -13(+6) weeks of gestation resulting in the delivery of phenotypically normal neonates. The study included 194 women with type-1 diabetes, 122 women with type-2 diabetes, 779 women who developed GDM and 41,007 non-diabetic controls.

METHODS: Maternal free β-hCG and PAPP-A levels were expressed as multiples of the respective normal median (MoM), and fetal NT was expressed as a difference from the expected median (Δ).

MAIN OUTCOME MEASURES: Comparison of median MoM maternal free β-hCG and PAPP-A, and fetal NT, in the four outcome groups.

RESULTS: There were no significant differences between the groups in median ΔNT and maternal free β-hCG MoM. Maternal median PAPP-A in type-2 diabetes, compared with the non-diabetic group, was reduced (0.75 MoM, IQR 0.50-1.09 MoM versus 1.00 MoM, IQR 0.68-1.42 MoM; P < 0.001), which resulted in doubling in the false-positive rate in the combined screening in this population. There were no significant differences in maternal PAPP-A between the other groups.

CONCLUSIONS: In women with type-2 diabetes, the estimation of accurate patient-specific risk in the first trimester combined screening for aneuploidies necessitates an adjustment of maternal serum PAPP-A.