The Study Of Serum Marker Inhibin-A Used For Prenatal Screening Of Down Syndrome

Down Syndorme, also called trisomy21, is the most commonautosomal chromosomes abnormal. There are10percent of children withmental retardation can be explianted by the Down syndrome. Theincidence of Down syndrome is between1/800and1/600in the neonatus,and increases with the maternal age. So, it is necessary to perform a testto screen the women with high risk and then clarify a diagnosis. Thedetection rate of prenatal screening of Down syndrome is improvedgradually, with the increasing number of serum biochemical markers wasfound one after the other. Inhibin-A is a new marker which already addedto the existing second trimester screening protocol in the Ulited States.Several studies reported that the detection rate increased by5-10percentafter the addition of inhibin-A. However, there are no reports about the efficacy of inhibin-A used in the second trimester screening amongChinese people. Our current study retrospectively assessed the screeningefficacy of inhibin-A used in the second trimester triple screening amongwomen in the GuangDong province, and discussed the value of inhibin-Ain the prenatal screening of Down syndrome.Objective1. To establish the distribution of inhibin-A in the second-trimestermaternal serum concentration in Guangdong province, and assess theefficacy of inhibin-A and quadruple test used for Down syndromescreening.2. To investigate the correlation between the second-trimester seruminhibin-A level and other markers，such as AFP, uE3and hCG, andinfluencing factors including vaginal bleeding, Gestational DiabetesMellitus and fetal gender.Methods1. A total of2802singleton pregnancies performed triple test in thesecond trimester in Guangzhou women and children’s medical centerbetween March2008and December2010were included in the study.There were12cases affected with Down syndrome. The follow-upinformation of these women was obtained by medical records and telephone interview, including pregnancy complications or adverseoutcomes, delivery time, fetal gender and birth weight.2. Inhibin-A was measured by automatic enzyme linked immunosorbentchemiluminescence assay. The concentration of inhibin-A wasexpressed in multiple of median (MOM), and adjusted for maternalweight and gestational age.3. Parameters of SURUSS were used to recalculate the risk of Downsyndrome. The efficacy of single marker and combination wereevaluated via receiver operating characteristic (ROC) curve and thearea under the curve.4. Student T test was used to determine whether there is significantdifference among gestation weeks from15to20weeks. Correlationtest was used to assess the association between inhibin-A and otherfactors, such as serum markers of AFP, CG, E3, fetal gender, maternalvaginal bleeding or gestational diabetes mellitus (GDM).Results1. In the unaffected pregnancy, the median concentration of inhibin-Abetween15week0day and20week6days was286.60,267.10,249.10,243.40,242.30and256.60pg/ml, respectively. There isrelatively stable distribution between gestational weeks. The meanconcentration and median MOM value of maternal serum inhibin-A in affected pregnancy were significantly higher than non-affectedpregnancy [(852.83±370.04) pg/ml vs (293.28±149.46) pg/ml(t=5.37，P<0.05),2.82vs1, respectively].2. The detection rate was83.3%(10/12) by using the quadruple test atfalse positive rate of5.8%. When detection rate was kept at83.3%,the quadruple test would approximately reduce the false positive ratefrom7.7%using the triple test to5.8%. The receiver operatingcharacteristic curve showed that the relative area of inhibin-A, AFP,fβ-hCG and uE3was63.7%,20.5%,46.1%and4.8%, respectively, atfalse positive rate of5%. Accordingly, the relative area of routinetriple test and quadruple test was46%and63%, respectively.3. In the unaffected pregnancy, there is significant relationship betweeninhibin-A and free β-hCG, AFP (P<0.01), but not uE3(P>0.05). In theaffected pregnancy, there is no significant relationship betweeninhibin-A and free β-hCG, AFP and uE3(P>0.05). There is nodifference between inhibin-A level in women with vaginal bleeding orgestational diabetes mellitus and women with no complications(P>0.05). Serum inhibin-A levels was negatively correlated withmaternal weight (r=-0.101, P<0.01). There is significant difference ofinhibin-A level between women with female and male fetus (P<0.01).Conclusions 1. The level of inhibin-A is relatively stable in the second trimester.Unlike other markers, the efficacy of inhibin-A used in the secondtrimester screening is less affected by the inaccuracy of gestationweeks.2. Inhibin-A is the most effective marker used for second-trimesterscreening, can improve the second trimester Down syndromescreening in Chinese population when combined with existingmarkers.3. There is significant correlation between serum inhibin-A level and freeβ-hCG, maternal weight and fetal gender, but not with maternalvaginal bleeding or gestational diabetes mellitus.