Quresh Zehratul, Dharavath Chinni
Clinical Biochemistry, Apollo Diagnostics, Hyderabad, IND.
Cureus. 2022 Mar 27;14(3):e23555. doi: 10.7759/cureus.23555. eCollection 2022 Mar.
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.
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.
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.
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.
孕妇年龄是与胎儿唐氏综合征（DS）相关的主要风险因素。母体筛查中的生化血清标志物提高了产前筛查中DS的检出率。然而，对于哪个年龄组应在接受侵入性诊断程序之前进行初步无创筛查存在困境。根据建议，所有妊娠都有染色体异常的风险。虽然应向所有女性提供筛查，但35岁以上的女性主要接受侵入性诊断程序，血清筛查试验对该年龄组益处不大。本研究评估了35岁以上风险组的母体血清筛查人群及最终筛查阳性率的意义。
对一组孕中期（妊娠14 - 20周6天）的孕妇进行了为期一年的观察性回顾性研究。四联检测包括血清甲胎蛋白（AFP）、游离β - 人绒毛膜促性腺激素（β - hCG）、非结合雌三醇（Ue3）和抑制素A。使用针对种族、吸烟、体重和年龄进行校正的软件计算DS风险。我们将DS的年龄风险与生化风险进行了比较。采用McNemar检验进行统计分析，以检验两种计算方法（即仅年龄法与使用生物标志物的最终风险计算法）之间筛查阳性（SP）病例的比例。
年龄风险和最终风险的SP病例比例分别为56.3%和12.6%。计算得到的McNemar卡方检验统计量为97.959（p < 0.001），这表明在对35岁以上的21三体综合征女性进行筛查时，添加生物标志物后SP病例显著减少。
DS的年龄风险随孕妇年龄增加而升高。值得注意的是，该人群的最终生化风险显著更低。因此，我们建议使用无创血清筛查对所有年龄组进行筛查，以在进行侵入性检查之前排除筛查阴性的病例。
