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BJOG. 2012 Mar;119(4):410-6. doi: 10.1111/j.1471-0528.2011.03253.x.

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

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Academic Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, UK.



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).


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


Antenatal clinic.


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.


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).


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


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.


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.

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