Prenatal cell-free DNA screening for rare chromosome abnormalities and adverse pregnancy outcomes

  • Raymond, Yvette Christina (Primary Chief Investigator (PCI))
  • Lorber Rolnik, Daniel (Chief Investigator (CI))
  • Mol, Ben (Chief Investigator (CI))
  • Fernando, Shavi (Chief Investigator (CI))
  • Menezes, Melody Ann (Associate Investigator (AI))

Project: Research

Project Details

Project Description

CfDNA screening is a component of obstetric medicine which is plagued by a high degree of ambiguity. This is particularly true in relation to the introduction of genome-wide, as opposed to targeted, screening options, where the majority of screening results are revealed to involve a fetus unaffected by chromosomal anomaly.5 In current practise, when fetal anomaly is excluded by diagnostic investigations such as amniocentesis following a high-risk cfDNA result, women are no longer considered high-risk and generally return to low-risk obstetric care streams.

There is a considerably high probability that many of these inaccurate screening results were actually generated by chromosomal anomalies confined to the placenta.6 While many of these cases of placental mosaicism may be innocuous, some anomalies represent a significant risk of adverse pregnancy outcomes, such as Trisomy 16.3 For other chromosome anomalies, these risks have been poorly explored, largely because fetal genetic testing is generally prioritised over placental following high-risk screening results, and thus in many instances the genetic status of the placenta is unknown.

We propose that this research project may provide valuable information for guiding the management of pregnancies which screen falsely-positive, by indicating the likelihood of placental involvement depending on the chromosome anomaly, and furthermore the risk of complications associated.

Our other aim is to investigate for any association between adverse outcomes and fetal fraction values, which are currently considered more or less insignificant beyond aneuploidy screening. Should any associations be revealed, the impact of these findings could be of great clinical utility by transforming an existing measurement of no great clinical importance into a prognostic indicator.

By completion of these research projects, it is our aspiration that high-risk pregnancies which otherwise may have been overlooked can be monitored more closely for prevention and earlier interventions.
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Effective start/end date13/02/23 → …