A reassessment of biochemical marker distributions in trisomy 21-affected and unaffected twin pregnancies in the first trimester.

Objective: To estimate the difference between levels of the two biochemical markers pregnancy-associated plasma protein-A (PAPP-A) and maternal serum free β-human chorionic gonadotropin (free β-hCG) in twin pregnancies relative to singleton pregnancies and establish an improved screening procedure for chromosomal abnormalities such as trisomy 21 in twin pregnancies.

Methods: 4843 unaffected and 47 trisomy 21-affected twin pregnancies were included in the study. Chorionicity-specific medians were generated for PAPP-A and free β-hCG from gestational ages 8 to 14 weeks. Multiple of the median values for each of the biochemical markers were calculated. Detection rates and false-positive rates were estimated for screening tests incorporating nuchal translucency and maternal age, with and without biochemistry.

Results: Medians for the two biochemical markers for monochorionic and dichorionic twins in unaffected pregnancies show a gestational age-specific increase relative to singleton medians. Allowing for gestation and chorionicity, twin pregnancies affected with trisomy 21 had higher levels of free β-hCG and lower levels of PAPP-A. Adding biochemistry into the risk assessment using a fixed risk cut-off of 1 in 100 increased the detection rate for fetal trisomy 21 in dizygotic twin pregnancies from 78 to 90%, and decreased the false-positive rate from 8.0 to 5.9%.

Conclusions: Generation of chorionicity-specific medians for the biochemical markers and their use in risk assessment can improve the performance of first-trimester screening for chromosomal abnormalities in twins to a level comparable with that in singleton pregnancies.