Two Factors Affecting the Success Rate of the Second Non-Invasive Prenatal Screening After Initial No-Call Result: Experience from a Single Tertiary Center in China
Non-invasive prenatal screening (NIPS), based on cell-free DNA (cfDNA) sequencing, has become a widely adopted method for fetal aneuploidy screening over the past decade. Compared to traditional screening methods, which rely on serum biochemical assays and fetal nuchal translucency measurements, NIPS offers a significantly lower false-positive rate and a higher positive predictive value. This has led to a reduction in unnecessary invasive procedures, making NIPS a preferred choice for many healthcare providers and pregnant women. However, one of the inevitable shortcomings of NIPS is the occurrence of uninterpretable or “no-call” results, which are primarily caused by an insufficient fetal fraction. This study aims to investigate the factors associated with a successful second NIPS after an initial no-call result and to determine the optimal management strategy for women in this situation.
The study was conducted at the Women’s Hospital of Nanjing Medical University, a tertiary center in China, and retrospectively analyzed data from women who underwent NIPS between 2017 and 2019. Among the 33,684 women who underwent NIPS during this period, 244 (0.72%) received no-call results. Of these, 142 (0.42%) were due to an insufficient fetal fraction, while the remaining 102 (0.30%) were attributed to other causes such as sampling failure, experimental failure, or bioinformatics failure. Out of the 142 women with insufficient fetal fraction, 137 (96.48%) agreed to undergo a second NIPS test, and their data were included in the analysis.
The primary focus of the study was to compare the maternal and pregnancy characteristics of women who achieved a successful second NIPS result with those who did not. The results showed that 87 out of 137 women (63.50%) obtained an informative result after the second test, while the remaining 50 women (36.50%) still received a no-call result due to an insufficient fetal fraction. The analysis revealed that the initial fetal fraction and maternal body mass index (BMI) were the two most significant factors influencing the success rate of the second NIPS.
The initial fetal fraction was found to be significantly higher in women who achieved a successful retest compared to those who did not (3.13% vs. 2.72%, respectively). Furthermore, the fetal fraction gain (the change in fetal fraction between the first and second tests) was also significantly different between the two groups (1.59% vs. -0.10%, respectively). These findings suggest that the initial fetal fraction is a critical determinant of the likelihood of a successful second NIPS. In particular, the study found that when the initial fetal fraction was less than 2.00%, the chance of a successful retest was virtually nonexistent. This indicates that for women with an initial fetal fraction below this threshold, a second NIPS may not be beneficial, and alternative diagnostic methods should be considered.
Maternal BMI was another significant factor affecting the success rate of the second NIPS. Women who achieved a successful retest had a significantly lower BMI compared to those who did not (25.39 kg/m² vs. 27.24 kg/m²). The study classified women into three BMI categories based on the World Health Organization obesity classification system: normal weight (<25.00 kg/m²), overweight (25.00–29.99 kg/m²), and obese (≥30.00 kg/m²). The success rates in these categories were 76.40%, 53.80%, and 56.70%, respectively, indicating a negative correlation between maternal BMI and the likelihood of a successful retest. This finding aligns with previous studies that have highlighted the association between obesity and NIPS test failure, likely due to the dilution effect of higher maternal blood volume on fetal cfDNA.
Interestingly, other factors such as maternal age, gestational age at the time of the first blood draw, the time interval between the two blood draws, parity, method of conception, and history of heparin use did not show significant differences between the successful and unsuccessful retest groups. This contrasts with some previous studies that suggested a positive correlation between the time interval between blood draws and the success rate of a second NIPS. The discrepancy may be attributed to the fact that most women in this study underwent their first NIPS in the second trimester, whereas previous studies often included women who were tested in the first trimester.
The study also conducted a multivariate logistic regression analysis to further evaluate the factors affecting the success rate of the second NIPS. The results confirmed that the initial fetal fraction was significantly associated with the likelihood of a successful retest, while the association between maternal BMI and retest success was marginal. This underscores the importance of the initial fetal fraction as the primary determinant of retest success and suggests that maternal BMI, while relevant, may have a less pronounced impact.
To provide a more detailed understanding of the relationship between the initial fetal fraction and retest success, the study classified women into four groups based on their initial fetal fraction: <2.00%, 2.00–2.49%, 2.50–2.99%, and ≥3.00%. The success rates in these groups were 0%, 47.40%, 56.10%, and 80.90%, respectively. This clear positive correlation highlights the critical role of the initial fetal fraction in predicting retest success. Notably, the success rate was significantly higher in women with an initial fetal fraction of ≥3.00% compared to those with lower fractions, further emphasizing the importance of this factor.
In terms of clinical implications, the study suggests that a second NIPS may be beneficial for women with an initial fetal fraction greater than 2.00%, particularly if their BMI is within the normal range. However, for women with an initial fetal fraction below this threshold, the likelihood of a successful retest is minimal, and alternative diagnostic methods such as invasive testing should be considered. This tailored approach can help optimize the management of women with initial no-call results, ensuring that they receive appropriate care while minimizing unnecessary procedures.
The study also highlights the need for specialized management strategies for women with initial no-call results, taking into account the specific factors that influence retest success. For instance, women with a higher BMI may require additional counseling regarding the potential limitations of a second NIPS and the possible need for alternative diagnostic methods. Similarly, healthcare providers should be aware of the critical role of the initial fetal fraction in determining the likelihood of retest success and use this information to guide their recommendations.
In conclusion, this study provides valuable insights into the factors affecting the success rate of a second NIPS after an initial no-call result, with a particular focus on the initial fetal fraction and maternal BMI. The findings underscore the importance of these factors in predicting retest success and suggest the need for a tailored management strategy for women in this situation. By considering the initial fetal fraction and maternal BMI, healthcare providers can optimize the management of women with initial no-call results, ensuring that they receive appropriate care while minimizing unnecessary procedures.
doi.org/10.1097/CM9.0000000000001531
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