Non-invasive prenatal testing (NIPT) for fetal aneuploidies by massively parallel sequencing has emerged as a powerful tool in the management of high-risk pregnancies. It is vital that patients receive pre-test counseling about limitations of the test. Here we note a correlation between low molecular weight heparin, (LMWH), and non-reportable NIPT results.METHODS:
Maternal blood samples submitted to Sequenom Laboratories for MaterniT21® PLUS testing were subjected to DNA extraction, library preparation, and whole genome massively parallel sequencing as described by Jensen et al (2013).RESULTS:
During the routine follow up of these 23 non-reportable results, feedback from clinicians revealed that the patients were taking LMWH. Analysis of two independent aliquots revealed very low fetal fraction, library preparation failure or total sequencing count failure. In most cases, another specimen draw had been requested and obtained, the results of which mimicked the original results. Heparin is a known inhibitor of PCR. Samples from only one patient had library preparation failure that relies on PCR amplification. For 21 patients, the sample failed for insufficient fetal DNA. For 5 other known patients on LMWH, all quality metrics passed and a result was issued.CONCLUSION:
Although it is unclear how LMWH use, or the underlying biological condition itself, is impacting NIPT results, it is important that providers are educated about confounding maternal conditions and therapeutic agents that can affect results. LMWH in itself is not a contraindication to NIPT.