Investigation of Perinatal Loss, Molecular Genetic and Pathological Features

This review is a perinatal pathologist’s approach to the stillbirth with emphasis on the use of molecular techniques. Stillbirths are a heterogeneous group, with diverse aetiologies. The stillbirth investigation needs to be based on a good review of the history, antenatal scans, the autopsy, placental examination and ancillary investigations. Often a multidisciplinary team is required to identify and evaluate the factors. However an increasing understanding of the pathophysiology of stillbirths and the development of molecular techniques in both the diagnostic and research laboratories are introducing additional ways of identifying causal factors in stillbirths. The main areas where molecular techniques are currently useful in assessing a stillbirth are to identify or confirm: • Syndromes/genetic diseases from amniocentesis and foetal samples. • Infective aetiologies from amniocentesis and foetal tissues. • Maternal and foetal thrombophilia mutations which lead to an increased risk of stillbirth. However current research and probable future routine techniques includes the following areas; • The use of array technology instead of classical cytogenetics to identify chromosomal imbalances. • The identification of markers or polymorphisms related to intramniotic infection. • The use of foetal DNA in maternal blood for diagnosis. • Proteomic techniques to identify protein profiles in maternal serum or amniotic fluid to identify pregnancies at risk. • The identification of molecular markers of the interaction between the foetal and maternal immune systems at the placenta decidua/maternal blood interface. • Molecular techniques to understand the mechanisms of the foetal/developmental origins of adult disease. • The identification of the role of micro RNA in stillbirths and placental function. • Molecular techniques to refine poorly understood areas of placental maldevelopment.