Clinicopathological phenotypes of singleton stillbirth: A retrospective cohort study

INTRODUCTION: Interpreting the histopathology report after stillbirth and applying it to care in a subsequent pregnancy can be challenging. MATERIAL AND METHODS: A retrospective cohort study of singleton stillbirths in Iceland 1996-2021 (n = 338). Clinical information and description of placenta and umbilical cord were reviewed, and microscopic slides re-evaluated according to the Amsterdam Consensus. Clinical and histopathological findings, including major patterns of placental injury and umbilical cord at risk, were correlated and compared between gestational age groups: <28 weeks (n = 102), ≥28 but <37 weeks (n = 114), and ≥37 weeks (n = 122). RESULTS: Placental slides were reviewed for 96.4% (326/338) of singleton stillbirths and classified into major patterns of placental injury. Maternal vascular malperfusion (MVM) was diagnosed in 19.0% of placentas (62/326), fetal vascular malperfusion (FVM) in 31.6% (103/326), acute chorioamnionitis (ACA) in 32.2% (105/326), chronic villitis of unknown etiology (VUE) in 15.9% (52/326), and none of the major patterns in 27.9% (91/326). More than one pattern of placental injury was found in 7.7% of placentas (25/326), most often at term. A similar proportion of MVM was found irrespective of gestational age; FVM was more common after 28 weeks, ACA before 28 weeks, but VUE most frequent at term. A higher proportion of MVM was found in stillbirths with small for gestational age (SGA) infants than non-SGA (23.0 vs. 6.1%), as well as in stillbirths with maternal hypertensive disorder of pregnancy than in stillbirths with a normotensive mother (23.9 vs. 11.8%). The latter association was not seen with high-grade FVM nor VUE. The umbilical cord was at risk in 53.8% (175/326) of singleton stillbirths, increasing with gestational age to 71.7% (86/120) at term. Hypercoiled, excessive long, and wrapped cords were most common. Term stillbirths with cord at risk often also had placental MVM or VUE. CONCLUSIONS: Understanding major patterns of placental injury and their correlation with clinical phenotypes can help counseling after stillbirth. Stillbirths with placental MVM often had clinical signs suggesting a high-risk pregnancy. However, term stillbirths with placental VUE or FVM and umbilical cord at risk were commonly without recognized risk factors.