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%. CONCLUSION 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.