The neuropathology of stillbirth — Correlation with apolipoprotein genotype in a Scottish population based study

• Published in: Early human development 2015-02, Vol.91 (2), p.139-148
• Main Authors: Bell, Jeanne Elisabeth, Becher, Julie-Clare, Keeling, Jean Winifred, McIntosh, Neil
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Amyloid beta-Protein Precursor - metabolism; Apolipoprotein E; Apolipoprotein E2 - genetics; Apolipoprotein E2 - metabolism; Brain - metabolism; Brain - pathology; Brain injury; Female; Fetus - metabolism; Fetus - pathology; Genotype; Humans; Neonatal and Perinatal Medicine; Neuropathology; Pregnancy; Scotland; Stillbirth; Stillbirth - genetics; β-Amyloid; β-Amyloid precursor protein
• ISSN: 0378-3782; 1872-6232
• DOI: 10.1016/j.earlhumdev.2014.12.008

Abstract Background The neuropathology of stillbirths has been widely studied but rarely on a population basis. Whether foetal apolipoprotein E (APOE) genotype exerts any influence has been little investigated, despite well known effects in adult brains. Aims To establish the neuropathology of a population cohort of stillbirths and compare with the APOE genotype. Study design and subjects The brains of 191 stillbirths (≥ 24 weeks of gestation) were recruited from a Scottish population cohort and grouped by clinical history. APOE genotype was available for 97%. Results and conclusions One or more neuropathological features, most appearing relatively recent, were found in 54% of 157 antepartum singletons, 44% of 9 abruption-associated stillbirths, 85% of 13 in multiple pregnancies but in only 19% of 12 intrapartum stillbirths. White matter injury (WMI) occurred in 36% of preterm and 21% mature stillbirths. Fresh petechial haemorrhages were common in all groups (29%) but germinal matrix haemorrhage (GMH) (7%) and periventricular leucomalacia (1%) were confined to preterm. GMH was significantly associated with WMI (p = 0.003). Placental inflammation was common in intrapartum stillbirths (50%), compared with antepartum (15%), multiple pregnancy (23%) and abruption (0%). β-Amyloid precursor protein (βAPP) positive axons (36% stillbirths overall) correlated closely with WMI (p < 0.0001), justifying future routine inclusion in foetal neuropathological investigation. This study highlights the paucity of brain damage in intrapartum stillbirths. While APOE2 was significantly overrepresented in stillbirths, there was no correlation between APOE genotype and neuropathological findings. We conclude that APOE does not influence neuropathological outcomes in stillbirths.