New hope after unexplained pregnancy loss

28 February 2023

Despite increased access to healthcare and advanced monitoring of pregnancies, eight pregnancies a day in Australia end in pregnancy loss or perinatal death, a figure that has not changed over the past two decades.

The Genomic Autopsy study, a partnership between SA Pathology, the Women’s and Children’s Hospital, the University of South Australia, and Australian Genomics, has explored the potential of using genomic testing to explain those cases of pregnancy loss and perinatal death that remain unexplained after standard investigation.

When standard autopsy failed to provide a diagnosis, couples were offered genomic testing to try and identify a genetic diagnosis for their foetal or newborn death. A total of 200 couples/families took part in the study.

Samples of DNA from the autopsy, and the parents, were collected and analysed using either whole exome or whole genome sequencing.

Whole exome sequencing is a simpler, cheaper but less comprehensive process that looks at specific sections of the genetic code that are most likely to hold genetic errors that cause diseases. Whole genome sequencing looks at the entire genetic code of an individual, providing a comprehensive analysis.

The study found that genomic testing could provide about half of the couples that participated with a definitive answer as to why their foetus or newborn had died. In addition, the analysis of the parental DNA could determine if the genetic lesion found was inherited.

Professor Hamish Scott, Head of Department Genetics and Molecular Pathology at SA Pathology and Head of Molecular Pathology Research Laboratory at the Centre for Cancer Biology – an SA Pathology and UniSA alliance - says the study has demonstrated the ability to give definitive answers about why families have lost pregnancies and prevent recurrence in twice as many cases compared to now.

Understanding if the genetic lesion was inherited informed couples of the risk of future pregnancies ending in loss. Risks ranged from a less than a one per cent chance of recurrence, when the lesion was not inherited, to as high as a one in two chance when inheritance was established. Knowing these risks gave parents the confidence to plan a family. Information from the genomic autopsy opened options to reduce the chance of future recurrence by using procedures like prenatal testing or in vitro fertilisation. For other family members, the information would determine their risk of carrying the same genetic problem in their DNA.

“Understanding the likelihood of inherited genetic disorders helps inform choices about future pregnancy pathways, including for extended family members who may be carriers of certain genetic conditions,” Professor Scott said.

Our researchers hope that the genomic autopsy, which offers short turnaround times and doubles the definite diagnoses compared to standard autopsy alone, can be rolled out widely as clinical standard-of-care, not only to give answers to families who have had losses, but to reduce the number of families who experience recurrent pregnancy loss.

The results and a commentary were published in the January issue of Nature Medicine, arguably one of the most prestigious and influential journals that plays a significant role in shaping the direction of medical research and clinical practice.