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First-Trimester Screening for Trisomy 21 with Adjustment for Biochemical Results of Previous Pregnancies

Objective: To investigate the effect of associations in serum free β-hCG and PAPP-A between successive pregnancies on the performance of screening for trisomy 21 at 11–13 weeks’ gestation. Methods: In 8,499 women with two consecutive pregnancies, including 49 women with fetal trisomy 21 in the second pregnancy, the correlation in serum free β-hCG multiples of the median (MoM) and PAPP-A MoM between pregnancies was determined, and the effects of correcting for the correlation on the performance of screening was estimated. Results: There were significant associations between pregnancies in free β-hCG MoM (r = 0.4435) and PAPP-A MoM (r = 0.4796). In screening by maternal age and biochemistry at a risk cutoff of 1 in 100, in the second pregnancies the false-positive rate was 35.5% for those with screen-positive results in the first pregnancy, and this was reduced to 17.1% after adjustment for the results of the first pregnancy. Similarly, in women with screen-negative results in the first pregnancy, adjustment for the results improved the detection rate in the second pregnancy from 66.7 to 81.2%. Conclusions: In screening for trisomy 21, adjustment for the biochemical findings in a previous pregnancy has major effects on individual patient-specific risks, increases the detection rate and reduces the false-positive rate.