Introduction/Objectives: Gastroschisis has been associated with a characteristic type of amniocyte vacuolization. In this study, we determined the frequency and clinicoplacental correlates of this apparently unique alteration of the amniotic epithelium. Methods: We performed a retrospective clinicopathologic analysis of 74 consecutive cases of isolated gastroschisis. Placental membrane sections were reviewed for presence and extent of amniocyte vacuolization, and immunostained for adipophilin, a lipid droplet-associated protein. Controls included placentas from pregnancies complicated by omphalocele, meconium exposure or chorioamnionitis. Results: A distinct type of diffuse, fine and homogeneous amniocyte vacuolization was present in 15/74 (20%), absent in 41/74 (55%), and equivocal in 18/74 (24%) gastroschisis cases. Similar amniocyte vacuolization was seen in only 1/30 meconium-stained controls, and in none of the other non-gastroschisis controls. Adipophilin immunostaining enhanced the visualization of the cytoplasmic vacuoles and confirmed their lipid nature. Compared to gastroschisis cases without such vacuolization, cases with typical, extensive amniocyte vacuolization had a tendency to lower birth weight percentile (26% versus 40%; P < 0.08), a significantly lower fetal:placental weight ratio (4.72 versus 5.51; P < 0.01), and a significantly higher frequency of associated meconium exposure (14/15 versus 15/41, P < 0.001) and/or chorioamnionitis (8/15 versus 6/41; P < 0.01). The length of hospital stay was equivalent for infants with or without amniocyte vacuolization. Conclusion: Diffuse, fine and homogeneous lipid droplet accumulation in amniocytes is highly characteristic of gastroschisis, but only seen in about 20% of cases. The functional implications of excessive lipid accumulation, and the exact mechanisms underlying the strong association between amniocyte lipid accumulation and chorioamnionitis/meconium exposure in a subset of gastroschisis cases remain undetermined. (C) 2017 Elsevier Ltd. All rights reserved.