Clinicopathological phenotypes of singleton stillbirth: A retrospective cohort study

Interpreting the histopathology report after stillbirth and applying it to care in a subsequent pregnancy can be challenging.

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).

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.

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.