White blood cell count affects fetal fraction and test failure rates in noninvasive prenatal screening

Abstract

ObjectiveTo investigate the effects of white blood cell (WBC) count on fetal fraction (FF), which is an essential quality control for obtaining reliable results, and on the rate of screen failures in noninvasive prenatal screening (NIPS).MethodsNoninvasive prenatal screening, serum lipid and liver enzyme level measurements, and WBC count were performed for 4,281 pregnancies with male fetuses. After adjusting for confounders, including the maternal characteristics and alanine aminotransferase (ALT) levels, the effect of WBC count on FF and test failure rate was measured by linear and logistic regression analyses.ResultsFetal fraction was negatively associated with BMI, ALT, IVF conceptions, and WBC count and positively correlated with gestational age in the multivariate linear regression model. Moreover, WBC count was the most important factor affecting FF after BMI according to the standardization coefficient analysis. In the 4,281 pregnancy samples with male fetuses, FF decreased with WBC count from 11.45% at ≤8 to 9.02% at >12, and FF markedly decreased to 7.40% in pregnancies with a higher WBC count (>12) and higher BMI (≥25 kg/m2). Meanwhile, the test failure rates were significantly higher in the WBC count > 12 group (4.29%) than in the WBC count ≤ 8 group (0.89%). Notably, when the BMI of pregnancies with a WBC count of >12 was >25, the rate reached 7.53%. Subsequently, multivariate logistic regression analysis further confirmed that an increased BMI and WBC count were independently and significantly associated with the test failure rates.ConclusionAn increased WBC count was associated with lower FF and higher test failure rates, suggesting that these important factors should be carefully considered during genetic counseling in pregnant women who decide to undergo blood collection or resampling.

What helps define outcomes in persistent uninterpretable non‐invasive prenatal testing: Maternal factors, fetal fraction or quality scores?

“…Even though many risk factors for low FF have been described, there was still a subset of patients in our study with no obvious reason for LFF. In search for other factors affecting FF, recent studies showed a negative correlation between FF and IVF‐conception, elevated triglyceride levels, alanine transaminase levels and increased white blood cells 53–55 . It should be further investigated if systematic evaluation of these parameters would be useful in NIPT‐failures and if this would help the decision to perform a redraw or not.…”

“…In search for other factors affecting FF, recent studies showed a negative correlation between FF and IVF-conception, elevated triglyceride levels, alanine transaminase levels and increased white blood cells. [53][54][55] It should be further investigated if systematic evaluation of these parameters would be useful in NIPTfailures and if this would help the decision to perform a redraw or not. We did not observe increased IVF rates, the other parameters were not investigated.…”

Cell-free DNA Screening for Aneuploidy

“…[27][28][29] FF has been associated with many other biological factors, including low molecular weight heparin use, aspirin use, hypertension, pregestational diabetes, autoimmune disease, race, multiple gestation, smoking, conception, and white blood cell count. [30][31][32][33] At present, there is no consensus regarding how to manage patients at risk for low FF, other than counseling regarding the possibility of a failed test due to inadequate FF.…”