Purpose To explore the placental pathological changes in fetuses with congenital heart disease(CHD)and the presence of hypoxia and mitochondrial-related protein abnormali-ties in CHD placenta.Methods Clinical data and placental tissues from 52 fetuses undergoing induction of labor for CHD were collected.Placental sections from the CHD group and con-trol group(fetuses with isolated cleft lip and palate without other malformations)were stained with routine HE staining for mor-phological observation under a microscope.Immunohistochemis-try with EnVision method was used to detect the expression of hypoxia-related factor HIF-1α and mitochondrial-related factors COX Ⅰ and COX Ⅳ in placental trophoblastic cells.Its clinical characteristics and placental pathological changes were also ana-lyzed.Results Approximately 84.6%(44/52)of the CHD group were accompanied by morphological changes,including stem villous inclusion bodies(38.5%,20/52),stem villous mesenchymal dysplasia(23.1%,12/52),and stem villous cal-cification(19.2%,10/52),chorioamnionitis(32.7%,17/52).Compared to the control group,the CHD group had a sta-tistically significant difference in the occurrence of villous inclu-sion bodies and chorioamnionitis(P<0.05).Among the four CHD subgroups,the incidence of villous dysplasia was higher in the complex cardiac malformation subgroup(P<0.05).Com-pared to the control group,the CHD group showed significantly increased expression of HIF-1α protein(P<0.05)and de-creased expression of mitochondrial-related factors COX Ⅰ and COX Ⅳ(P<0.05),with statistically significant differences.Conclusion There are some changes in placenta pathology in fetuses with CHD,including villous inclusion bodies,villous dysplasia,villous calcification,and chorioamnionitis.Placental hypoxia affects trophoblast mitochondrial function and ATP ener-gy supply,which may have certain effects on fetal cardiac devel-opment during the fetal-heart-placenta symbiotic stage.