Fetal Central Nervous System Injury in Third Trimester Stillbirth: A Clinicopathologic Study of 63 Cases

Abstract

We report the neuropathologic findings and clinicopathologic associations in 63 3rd trimester singleton stillborn fetuses. All were ≥28 weeks estimated gestational age (EGA) with complete autopsies, including placental examination. Fetuses with chromosomal abnormalities, major congenital anomalies, and intrapartum demise were excluded. The cases were divided into those with abruption ( n = 12) and those with unexplained fetal demise ( n = 51). The latter group was then subdivided by gestational age with 3 subgroups (preterm 28 to <32 weeks EGA ( n = 16), preterm 32 to <37 weeks EGA ( n = 13), and term 37–41 weeks EGA ( n = 22). Each group was further subdivided as appropriate-for-gestational age/large-for-gestational age (AGA/LGA) or small-for-gestational age (SGA). Placental lesions were also evaluated and correlated with brain lesions. Established or recent injury involving gray or white matter was seen in 88% of the fetuses with unexplained demise versus 42% with abruption ( P = 0.001). The most common form of brain injury was established gray matter damage, seen in 65% of the fetuses with unexplained demise versus 25% with abruption ( P = 0.021), the most common pattern being established pontosubicular neuronal necrosis plus established neuronal necrosis in other sites. There was no significant difference in the frequency of brain injury between the SGA fetuses and AGA/LGA fetuses or between the unexplained stillbirth preterm and term subgroups, and there was no unequivocal correlation between placental lesions and brain lesions. Brain injury, most frequently established gray matter damage, is seen in the majority of stillborn infants with unexplained demise, indicating that the brain injury predates the period immediately before death.