The Effect of Elevated Alanine Transaminase on Non-invasive Prenatal Screening Failures

ObjectiveTo determine the effects of alanine transaminase (ALT) levels on the screening failure rates or "no calls" due to low fetal fraction (FF) to obtain a result in non-invasive prenatal screening (NIPS). MethodsNIPS by sequencing and liver enzyme measurements were performed in 7,910 pregnancies at 12-26 weeks of gestation. Univariate and multivariable regression models were used to evaluate the significant predictors of screening failure rates among maternal characteristics and relevant laboratory parameters. ResultsOf the 7,910 pregnancies that met the inclusion criteria, 134 (1.69%) had "no calls." Multiple logistic regression analysis demonstrated that increased body mass index, ALT, prealbumin, albumin levels, and in vitro fertilization (IVF) conception rates were independently associated with screening failures. The test failure rate was higher (4.34 vs. 1.41%; P < 0.001) in IVF pregnancies relative to those with spontaneous conceptions. Meanwhile, the screening failure rates increased with increasing ALT levels from 1.05% at <= 10 U/L to 3.73% at >40 U/L. In particular, IVF pregnancies with an ALT level of >40 U/L had a higher test failure rate (9.52%). Compared with that for an ALT level of <= 10 U/L, the adjusted odds ratio of "no calls" for ALT levels of 10-20, 21-40, and >40 U/L was 1.204 [95% confidence interval (CI), 0.709-2.045], 1.529 (95% CI, 0.865-2.702), and 2.764 (95% CI, 1.500-5.093) (P-trend < 0.001), respectively. ConclusionsIncreased ALT and IVF conceptions were associated with a higher screening failure rates in NIPS. Therefore, a feasible strategy to adjust these factors to reduce the probability of "no calls" due to low FF would be of great clinical significance.