Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death

Nat Med. 2023 Jan;29(1):180-189. doi: 10.1038/s41591-022-02142-1. Epub 2023 Jan 19.

Abstract

Pregnancy loss and perinatal death are devastating events for families. We assessed 'genomic autopsy' as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a definitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifies novel phenotypes and disease genes. Inheritance of 42% of definitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous* / genetics
  • Autopsy
  • Female
  • Genomics
  • Humans
  • Perinatal Death* / etiology
  • Pregnancy
  • Prenatal Diagnosis