Abstract:

Non-invasive prenatal testing (NIPT) is a method that uses cell-free fetal DNA in maternal blood sample to detect common fetal chromosomal aneuploidies. It has been  recognized as the most clinically robust screening method and widely used worldwide. Although clinical validation and implementation of NIPT studies have consistently demonstrated high sensitivity and specificity for trisomy 21 (Down  syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) and sex chromosomes, evidence reflecting real-world implementation in Middle Eastern cohorts remains limited, especially in Jordan. This study aimed to evaluate the real world clinical implementation, distributions of fetal fractions, and screening outcomes of NIPT in a cohort of pregnancies in Jordan. A retrospective observational study was performed on 255 NIPT results obtained from a single diagnostic laboratory in Jordan. Collected variables included maternal age, gestational age at testing, fetal fraction, conception status [natural or in vitro fertilization (IVF)] , and final screening result. NIPT results were classified as low risk, high risk, or no result (inconclusive). Descriptive statistics were used, and comparisons between low-risk and high-risk groups were performed using Welch’s t-test and Fisher’s exact test for continuous and categorical variables, respectively. A two-sided P-value < 0.05 was considered statistically significant. Among 255 NIPT tests performed, 87.5% (n=223) generated reportable result and were included in the final analysis. The mean maternal age was 33.28 years, and the median gestational age at testing was 11 weeks. The overall screen-positive rate was 3.59% (8/223). Trisomy 21 was the most frequently detected aneuploidy (1.79%), followed by trisomy 13 (0.90%), trisomy 18 (0.45%), and 47, XXY [Klinefelter syndrome] (0.45%). Advanced maternal age (≥35 years) was not significantly associated with increased screen-positive rates (p=0.86). Notably, mean fetal fraction was significantly lower in screen-positive cases compared with low-risk cases (7.86% vs 9.91%; P = 0.008). In this real world Middle Eastern cohort, NIPT demonstrated screening outcome distributions consistent with established international data. Lower fetal fraction was significantly associated with screen-positive results. However, it was found no significant association between advanced maternal age and screen-positive status. The results presented in the current study support the effective integration of NIPT in routine prenatal care in Middle Eastern, particularly in Jordan and provide a critical region specific NIPT performance data.