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Retrospective Analysis of Correlation Between Fraction of Cell-Free Fetal DNA in Maternal Serum and Postpartum Pathological Analysis of Abnormal Placentation
Abstract Number: T5B-1
Abstract Type: Original Research
Cell free fetal DNA (cfDNA) is a test currently used to diagnose fetal chromosomal abnormalities by analyzing DNA from fetal cells identified in maternal serum. Provided in the results is the fraction of fetal cells (FF) present in the maternal circulation, which is not used clinically at this time. We hypothesize that the ratio may be affected by degree of interface between maternal and fetal circulations. Columbia University identified women with imaging studies suggestive of placenta accreta or previa, measured FF and compared them to age matched controls but found no significant differences1. This study suffered from small sample size and imaging diagnoses. A pathology team at our institution studied placental specimens to determine if extent of adherent basal plate myometrial fibers is a risk factor for development of subsequent placenta accreta2. We are uniquely positioned to use this bank of pathologic specimens to analyze possible relationships or patterns between specimens with abnormal placentation and FF. We hypothesize that in patients with abnormal placentation, FF may be an early predictor of degree of invasion.
All studied pathology specimens from 2012-early 2017 were designated as either 1) basal plate with attached myometrial fibers (BPMYO), 2) suspicious for accreta (degree of invasion was within 2 cell layers of myometrium) and 3) confirmed histologic accreta. We cross referenced the pathology results with FF from patients who also had cfDNA testing using the Sequenom Laboratory Materni21® test to more fully understand any possible relationships between the two. We looked at specimens within the three diagnoses and sub-analyzed based on patient use of in vitro fertilization (IVF), presence of preeclampsia at delivery and intrauterine growth restriction.
Initial analysis of the data revealed no difference between accreta and non-accreta groups. However, patients who underwent IVF had highly variable FF and therefore did not represent the normal population. In addition, patients found to have preeclampsia at time of delivery also had abnormally low values, thought to be due to placental pathophysiology that likely affected fetal cell crossover. We thus excluded them from the accreta evaluation group. Using age matched controls, the median FF was 12.63 and 8.65 (p 0.001) for the accreta and non-accreta groups, respectively. Analysis used Stata SE (Version 12 College Station, Tx).
Further evaluation of data will be required, as well as prospective observational studies, to identify all factors that play a role in the FF provided by cfDNA studies. However, based on initial evaluation of our current data, there appears to be a correlation between FF and specific disease states including, but not limited to, abnormal placentation.
Samuel A et al. Prenat Diagn. 2013 Nov;33(11):1050-3.
Linn R, Miller E, Lim G, Ernst L. Placenta. 2015 Dec;36(12):1419-24.