Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined, Quadruple, Serum Integrated and Integrated Tests

OBJECTIVE To estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome. DESIGN Nested case-control study. SETTING Antenatal screening service. POPULATION OR SAMPLE 532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies. METHODS Stored maternal serum samples (-40°C) were assayed for PlGF. Monte Carlo simulation was used to estimate the screening performance of PlGF with the Combined, Quadruple, serum Integrated and Integrated tests. MAIN OUTCOME MEASURES Median PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa). RESULTS First trimester median PlGF was 15%, 28% and 39% lower in Down syndrome than unaffected pregnancies at 11, 12 and 13 completed weeks' gestation respectively (all p<0.001). Second trimester median PlGF was 31% lower at 14 weeks (p<0.001), and the difference decreased (6% lower at 17 weeks). At a 90% DR with first trimester markers measured at 13 weeks, adding PlGF decreased the FPR from 11.1 to 5.1% using the Combined test, 9.3% to 4.5% using the serum Integrated test, and 3.4% to 1.5% using the Integrated test (or 1.5 to 1.4% with first trimester markers measured at 11 weeks). Adding PlGF to the Quadruple test (measured at 15 weeks) decreased the FPR from 10.0% to 9.6% at a 90% DR. CONCLUSIONS First trimester PlGF measurements improve the performance of antenatal screening for Down syndrome using the Combined, serum Integrated and Integrated tests. Second trimester PlGF measurements are of limited value.