Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype

OBJECTIVE: To assess the relation between maternal serum pregnancy associated plasma protein A (PAPP-A) in the first trimester and the outcome of pregnancy by karyotype. DESIGN: A retrospective study of PAPP-A levels in blood samples collected prior to chorionic villus sampling. SETTING: Milan, Italy. SUBJECTS: Five hundred twenty-two women aged 20 to 47, at 7 to 11 weeks gestation, prior to undergoing chorionic villus sampling. Four hundred forty-five women had a pregnancy with a normal karyotype; in 30 pregnancies the karyotype was abnormal (including 14 cases of Down's syndrome and 7 of trisomy 18). MAIN OUTCOME MEASURES: Normal or abnormal fetal karyotype. Serum PAPP-A at 6 to 11 weeks gestation measured by radioimmunoassay. RESULTS: The median value of PAPP-A in the abnormal group was 0.27 multiples of the normal median (MoM). This is significantly lower than the median value in the normal group (1.01 MoM) (95% CI for the difference 0.46-0.84 MoM; P < 0.00001 Mann-Whitney test). CONCLUSIONS: There is an association between low levels of PAPP-A in the first trimester with chromosome anomalies. Screening by measurement of PAPP-A might detect 60% of cases of Down's syndrome in the first trimester with a false positive rate of 5%.