Biochemical Serum Markers Influencing Maternal Age Risk for Down's Syndrome in Quadruple Marker

Abstract

Objective: Maternal age is the primary risk factor associated with Down syndrome (DS) in the fetus. Biochemical serum markers in maternal screenings have improved DS detection rates in prenatal screenings. However, there is a dilemma regarding which age group should undergo preliminary noninvasive screening before undergoing invasive diagnostic procedures. Based on recommendations, all pregnancies are at risk of chromosomal abnormalities. While all women should be offered screenings, those over 35 are mainly offered an invasive diagnostic procedure, and serum screening tests are of little benefit for this age group. This study evaluated the maternal serum screening population and the significance of the final screen positivity rate in the risk group aged above 35 years. Method: An observational retrospective study was conducted on a cohort of pregnancies in the second trimester (14-20 weeks and 6 days of gestation) over a period of one year. The quadruple test consisted of serum alpha-fetoprotein (AFP), free beta hCG, unconjugated estriol e3 (Ue3), and inhibin-A. The risk for DS was calculated using software with corrections for ethnicity, smoking, weight, and age. We compared the age risk for DS with the biochemical risk. Statistical analysis was done using McNemar’s test to test the proportion of screen-positive (SP) cases between the two calculation methods, i.e., age alone versus final risk calculation with biomarkers. Results: The proportion of SP cases from age risk and final risk were 56.3% and 12.6%, respectively. The computed McNemar’s chi-square test statistic was 97.959 (p < 0.001), which showed a significant reduction in SP cases when biomarkers were added to screen for trisomy 21 women aged >35 years. Conclusion: The age risk of DS increased with increasing maternal age. Notably, the final biochemical risk in this population was significantly lower. Consequently, we proposed that a noninvasive serum screening be used to screen all age groups to rule out negative screen cases before subjecting them to invasive procedures.

Correlation of maternal age and combined assessments on risk of chromosomal anomaly during prenatal screening

“…This negates the belief that advanced maternal age is the only predisposing factor for the risk of Down Syndrome in a fetus. [14][15][16]18…”

Retrospective analysis of non-invasive prenatal testing results in 8237 pregnant women in Luohe District

“…In China, prenatal screening for fetal chromosomal disorders involves screening through serum biomarkers and prenatal diagnostic procedures. The former entails assessing biochemical markers in maternal serum such as alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin(free-β-hCG), unconjugated estriol(uE3), and inhibin A, combined with clinical information to evaluate the risk of fetal T21, T18, and open neural tube defects(ONTDs) [5]. This method, while convenient and cost-effective, has a detection rate of only 60-80% [6].…”