Placental pathology in pregnancies complicated by fetal growth restriction: recurrence vs. new onset

Objective: In an attempt to shed new light on the pathogenesis of fetal growth restriction (FGR), we aimed to study pregnancy characteristics, neonatal outcomes, and placental histopathological lesions of FGR pregnancies in two different subgroups: when developed after appropriate for gestational age (AGA) pregnancy and when developed after previous pregnancy with FGR. Study design: Pregnancy and placental reports of all singleton pregnancies complicated by FGR (defined as actual birthweight below the 10th percentile according to local birthweight nomograms) between 2008 and 2018 were reviewed. Included were only cases with previous delivery. Maternal background, neonatal outcomes, and placental histopathology were compared between FGR that occurred after FGR (recurrent FGR group) and FGR that occurred after an AGA pregnancy (FGR after AGA group). Placental lesions were classified according to the current “Amsterdam” criteria. Continuous variables were compared using the Student’s t test or the Mann–Whitney test as appropriate. Categorical variables were compared using Chi-square or Fisher’s exact test as appropriate. Results: A total of 334 FGR cases with a previous delivery were included in the study. Of them, 111 cases constituted the recurrent FGR group and 223 constituted the FGR after AGA group. The recurrent FGR group was characterized by higher rates of maternal diabetes during pregnancy and hypertensive diseases (9% versus 2.7%, p = 0.01 and 19.8% versus 11.6%, p = 0.04). The FGR after AGA group was characterized by a higher rate of fetal vascular malperfusion (FVM) lesions (29.6% versus 18.0%, p = 0.02), and by lower mean birthweight (1842 ± 424.9 versus 1977.4 ± 412.2, p = 0.005), as compared to the recurrent FGR group. Conclusion: Recurrent FGR was associated with maternal background morbidities during pregnancy which represents a chronic repeated insult, while “new” FGR cases (those followed an AGA pregnancy) were characterized by a higher rate of FVM lesions and lower birthweight which probably represent an “accident” in placentation. These findings may suggest that different mechanisms of placental dysfunction exist in the two subgroups of FGR.