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

Abstract

ObjectiveTo estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.DesignNested case-control study.SettingAntenatal screening service.Population or Sample532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies.MethodsStored 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 MeasuresMedian PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa).ResultsFirst 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.ConclusionsFirst 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.

Evaluating first trimester maternal serum screening combinations for Down syndrome suitable for use with reflexive secondary screening via sequencing of cell free DNA: high detection with low rates of invasive procedures

“…The consensus found in these recent studies is nearly identical to the median of 0.79 MoM in 243 cases reported in a 1999 meta‐analysis . A review of PlGF and Down syndrome in the first trimester identified nine published studies . One set of results was identified as an outlier, with the lowest median MoM (0.610) reported along with the highest z‐score (1.72).…”

“…Important implementation considerations include what screening cut‐off should be used and how samples should be collected. Optimally, maternal plasma samples should be collected from all women at the time of first trimester serum screening, and the reflexive testing performed without informing each woman or the primary care provider of the preliminary results . In such a scenario, the proportion of initial tests considered positive would be mainly a function of the available funds for cf DNA testing.…”

First‐trimester Down syndrome screening using additional serum markers with and without nuchal translucency and cell‐free DNA

“…Wald et al . predicted a 1–7% increase in detection rate depending on the week of gestation and false‐positive rate . Donalson rate et al .…”

Angiogenic Gene Expression in Down Syndrome Fetal Hearts

“…Abnormal angiogenesis has also been related to other obstetric and fetal conditions such as peripartum cardiomyopathy and fetal cardiac defects, opening up new challenges for our understanding of angiogenic involvement in maternal cardiovascular function and fetal cardiac development [25]. Reduced maternal serum PlGF at 11-13 weeks has been reported in pregnancies that subsequently develop preeclampsia and intrauterine growth restriction [26,][27] and in those with fetal trisomy 21 [28,29]. In the case of preeclampsia, the low PlGF is accompanied by a low PAPP-A and a high uterine artery pulsatility index, and these findings are attributed to impaired trophoblastic invasion of the maternal spiral arteries, leading to reduced placental perfusion and function.…”