Placental pathology after sildenafil treatment in early-onset fetal growth restriction

Maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM) and villitis of unknown etiology (VUE) are placental lesions associated with early-onset fetal growth restriction (eoFGR). Recently, the Dutch STRIDER trial (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) revealed that the vasodilatory effects of sildenafil did not improve the perinatal outcomes of eoFGR. The effects of sildenafil on the placenta are, however, unknown. We aimed to describe placental histology in eoFGR after sildenafil treatment or placebo. The Dutch STRIDER study was a randomised controlled trial of sildenafil versus placebo in singleton pregnancies between 20+0 and 29+6 weeks of gestation with placental eoFGR. We analysed all available cases for placental pathology. Lesions were classified independently, following the international criteria as defined in the Amsterdam Placental Workshop Group Consensus Statement, by three perinatal pathologists blinded for clinical data. Disagreement was solved by consensus from joint evaluation. 158 cases were available, 81 treated with sildenafil and 77 with placebo. Baseline characteristics were similar. The presence of massive perivillous fibrin deposition (MPVFD) and chronic histiocytic intervillositis (CHIV) were lower in sildenafil compared to placebo (p = 0.026 and p = 0.043). Signs of fetal hypoxia (placental chorangiosis plus fetal nucleated red blood cells) were seen more in the placebo group (p = 0.040). There were no differences for occurrence of MVM, FVM and VUE. The equal distribution of MVM, FVM and VUE in eoFGR treated with sildenafil or placebo suggest that sildenafil had no effect on the most common placental pathology. The finding of a lower incidence of MPVFD and CHIV in the sildenafil group merits more research on the interaction between sildenafil and the maternal immune system, since these lesions are thought to originate from a maternal reaction to fetal antigens.