Hemoglobin Bart hydrops fetalis: A model for studying vascular changes in placental hypoxia

Placental ischemia can be pre-placental (maternal), placental or post-placental (fetal), with corresponding changes in villous vasculature. Hydrops fetalis (HF) resulting from hemoglobin (Hb) Bart disease can serve as a model for intrauterine hypoxia, and placentas from such cases show a distinctive peripheral villous stromal myofibroblastic hypercellularity (PVSH). We hypothesized that Hb Bart disease, which results in profound fetal hypoxia, would lead to placental hypoxia on a post-placental basis.

We assessed villous vasculature using computerized morphometry, comparing placentas in 14 Hb Bart HF cases to 18 non-Hb Bart HF cases. Morphometric parameters were matched as closely as possible to those reported in the literature for comparison purposes.

Villous vessels of Hb Bart HF showed significantly increased numbers of vessels (p = 0.001), longer vascular perimeter (p = 0.002), thickening of vascular endothelial layer (p = 0.038) and higher shape coefficient (p = 0.042) indicating a more branching pattern of vessels. In addition, placental villi of Hb Bart HF containing PVSH showed a longer vascular perimeter (p = 0.008) and narrower lumen (p = 0.002), with a higher shape coefficient (p = 0.03), in comparison to villi lacking PVSH.

Contrary to expectations, the overall pattern of vascular changes in Hb Bart HF suggested multifactorial hypoxia: pre-placental, on the basis of the marked placentomegaly, compromising blood flow from uterine distention; placental, from hydropic villi causing a generalized diminished intervillous space; and post-placental from the greatly reduced capacity of Hb Bart to extract oxygen from the intervillous space. Standardized vascular morphometry will facilitate comparison between different conditions, for a better understanding of placental hypoxia.