Crown-rump length in aneuploid fetuses: implications for first-trimester biochemical screening for aneuploidies

This study examined the effect of estimation of gestational age from the menstrual history compared with that from crown-rump length (CRL) measurement on the detection rate of screening for aneuploidies in the first trimester. Pregnancy-associated plasma protein A (PAPP-A) was assayed in blood collected prior to chorionic villus sampling in 356 women with unaffected pregnancies and 28 women with an aneuploid pregnancy. There were 14 Down's syndrome (DS) pregnancies. All pregnancies were dated from menstrual history and CRL measurement. The average CRL gestation in the aneuploid population was 2.5 days less than that derived from the LMP (95 per cent confidence interval (CI) for LMP-CRL gestation: using the algorithm based on unaffected pregnancies 0-3.5 days; using the matched case-control approach 1-4.5 days). The average CRL gestation in the DS population was 2 days less but this did not reach statistical significance (95 per cent CI for LMP-CRL gestation: using the algorithm -1 to 4.5 days; using the matched case-control approach 0 to 5.5 days). The detection rate of aneuploidies in the first trimester using maternal serum PAPP-A was reduced by 7 per cent (and by 3 per cent for DS) for a 5 per cent false-positive rate when using CRL rather than LMP to date the pregnancy. This phenomenon is a consequence of an apparent reduction of gestational age when estimated by CRL in the aneuploid population. Further studies are required to evaluate whether CRL is an unbiased estimate of gestation for Down's syndrome pregnancies.