Maternal Serum Placental Growth Factor In First Trimester Screening For Down Syndrome

BackgroundDown syndrome,also know as21-trisomy,is one of the most common unusualchromosome disease.There was a opportunity get Down syndrome per600-800livebirths or per150pregnancies,most of the fetus affected by Down syndrome abortionin the first trimester,survivors will occur metal retardation,growth retardation andmutiple malformations.So chidren born with Down syndrome would take tremedousburden to social and family.Down syndrome is one of the major birth defects thatneeds prevent and control in our Country,there was many categories of screening forDown syndrome,for example,the Combined test,the Integrated test,the Quadruple testat second trimester and so on.Case-control studies in other contries have reported thatmaternal serum PLGF in nomal pregnancies is significantly different from the fetaltrisomy-21. Literatures published abroad show that if PLGF is applied to thescreening for Down syndrome in the first trimester will increase its screeningperformance,but this conclusion is still controversial.At present,there was no literaturereport the value of PLGF in screening for Down syndrome.So establish the median ofPLGF concentration of Chinese population in normal pregnancy and investigate theclinical value of maternal serum PLGF in screening fetal trisomy21at11-13+6weeks’ gestation would play important role in Obstetric field. ObjectivesThis article aims to explore the correlation between maternal serum PLGF andmaternal age,gestational age,maternal weight,storage time of samples and establishthe median of PLGF concentration of Chinese population in normal pregnancy andexplore the value of maternal serum PLGF in screening of21-trisomy at11-13+6weeks’ gestation.Methods1. A total of600pregnancies performed combined screening for Down syndrome at11-13+6weeks in Guangzhou Woman and Children’s Medical Center betweenJanuary2011and november2013were included in the study. Study subjects weredivided into three groups,the first group of pregnant women gave birth to childrenwith Down syndrome(case group),the second group was the control group,thethird group was used to establish the median of maternal serum concentrations ofPLGF in normal pregnancy.2. The concentration of maternal serum PAPP-A and Free β-hCG were measured byfluorescence immunoassay.Using time-resolved fluorescence assay to detect theconcentration of maternal serum PLGF.Ultrasound was used to detect fetal NT.PAPP-A, Free β-hCG, PLGF, NT are adjusted for maternal weight and gestationalage,all of the values were expressed in MoM then,which was used to do statisticalanalysis.3. Mutiple linear regression was applied to assess the correlation between maternalserum PAPP-A,Free β-hCG,PLGF,NT and maternal age,gestational age,storagetime of samples.Using Spearman rank correlation to find out if the fourparameters have revelance to each other.Defferences of serum markers and NTMoM between affected group and unaffected group was analyzed using Wilcoxonrank sum test. T test was used to identify the differences of the four markers levelbetween the two groups after transforming the value of the markers tologarithm.Using the Monte Carlo method to obtain false positive rate anddetection rate.A P value less than0.05was considered(correlation analysis between the four markers taking P<0.01indicates significant difference).Results1. The basical information of study population.The difference of pre-production age between cases and controls was statisticallysignificant (P=0.011).However,the difference of gestational age,weight,crown-rumpdiameter,sample storage time between the two groups were not statisticallysignificant(P>0.05).2. The correlation between the four research indicators and maternalcharacteristics, sample storage time at11-13+6weeks.1) In the unaffected pregnancies,there was no correlation between maternalserum concentration of PLGF and maternal age（β=0.058，P=0.331）.Theconcentration of PLGF increased significantly with gestational ag（eβ=0.297，P<0.0001） and sample storage time （β=0.140， P=0.021）, decreasedsignificantly with maternal weight（β=-0.188，P=0.021）.The Log10PLGF inChinese shows4.9%higher than Caucasian populations.2) In the unaffected pregnancies,there was no correlation between maternalserum concetration of PAPP-A and maternal age（β=0.959,P=0.339）.Theconcentration of PAPP-A increased significantly with gestational age（β=0.458，P<0.0001） and decreased significantly with maternal weight（β=0.331，P<0.0001）.3) In the unaffected pregnancies,there was no correlation between maternalserum concentration of Free β-hCG and maternal age （β=-0.042,P=0.467）.The concentration of Free β-hCG decreased significantly withgestational age（β=-0.287，P<0.0001） and maternal weight (β=-0.184，P=0.002).4) In the unaffected pregnancies,there was no correlation between fetal NT andmaternal age (β=-0.061，P=0.271) and maternal weigh（tβ=0.047，P=0.398）.The value of fetal NT increased significantly with gestational age（β=0.512，P<0.0001）. 3. The MoM value of markes’concentration at11-13+6weeks.The median concentration of PAPP-A MoM, Free β-hCG MoM, NT MoM,PLGF MoM at11-13+6weeks was1.00,1.04,1.03,1.00,were not exceed1±10%.4. The correlation between the four markers.1) Affected group:The concentration level of maternal serum PAPP-A and Freeβ-hCG was positively correlated in cases(r=0.363,P<0.01).2) Control group:The concentration level of maternal serum PLGF and Freeβ-hCG was positively correlated(r=0.308,P<0.01). The concentration level ofmaternal serum PAPP-A and Free β-hCG was positively correlated incases(r=0.209,P<0.01).5. Comparison median of the four research marks MoM value between nomalpregnancy goup and abnormal pregnancy group.The median PLGF MoM was1.00in control group,significantly lower valueswere observed in pregnancies with21-trisomy(0.62MoM). The median PAPP-AMoM was1.05in control group,significantly lower values were observed inpregnancies with21-trisomy(0.53MoM). The median Free β-hCG MoM was1.04incontrol group,significantly higher values were observed in pregnancies with21-trisomy(1.98MoM). The median NT MoM was1.04in control group,significantlyhigher values were observed in pregnancies with21-trisomy(2.10MoM).6. Maternal serum PLGF in first trimester screening for Down syndrome.Adding PLGF to first maternal combined screening increased the detection rateof1.9%,2.1%,1,8%as the FPR was1%,3%,5%.Combining PLGF and combinedscreening for Down syndrome reduced the false-positive rate of0.5%,0.4,1.8%as theDR was70%,80%,90%.Conclusions1. There was no correlation between maternal serum concentration of PLGF andmaternal age.The concentration of PLGF increased significantly with gestationalage and sample storage time, decreased significantly with maternal weight.TheLog10PLGF in Chinese showed4.9%higher than Caucasian populations. 2. The concentration of PLGF was significantly lower in21-trisomy at11-13+6gestational weeks.3. Adding PLGF to first maternal combined screening increased the detection rateand reduced the false-positive rate.4. Pregnancies gave birth to children with Down syndrome have defect in placentalangiogenesis.