Fetal surgery is not associated with increased inflammatory placental pathology

Abstract

Objective: Fetal surgery has improved neonatal outcomes; however, it is unknown if the intervention contributes to the developmental of inflammatory pathologies in the placenta. Here, an association between fetal surgery and placental pathology was examined.

Method: This case-control study compared pregnancies with fetal surgery (n = 22), pregnancies with an indication for fetal surgery but without an intervention being done (n = 13), and gestational-age and fetus-number matched controls (n = 36). Data on maternal, infant, and placental outcomes were abstracted. Additionally, immunohistochemistry identified expression of lymphoid and myeloid cells in the placenta on a subset of cases. Comparisons were performed using Kruskal-Wallis or Pearson's chi-squared tests.

Results: Maternal characteristics were comparable between groups. Most fetal interventions were for diaphragmatic hernia, spina bifida, or twin-to-twin transfusion syndrome. Fetuses who were operated on before birth were more likely to be born preterm (p = 0.02). There was no increase in the rate of observed placental pathologies or immune cell infiltration in fetal surgery cases compared to controls.

Conclusion: The data suggest that fetal surgery is not associated with increased inflammatory or morphologic pathology in the placenta. This observation supports the growing field of fetal surgery.

Figure 1:

Flow diagram of the overall study population and outcomes reported from each group.

Figure 2:. Representative images of pathologies commonly encountered in both the control and fetal intervention cohorts.

A) Intervention (200x, H&E) and control (400x, H&E) demonstrate low-grade chronic villitis; B) Surgery (200x, H&E) and control (400x, H&E) show basal chronic villitis; C) Intervention and control (200x, H&E) display features of fetal vascular malperfusion, with a thrombosed stem vessel and avascular villi, respectively; D) Intervention (100x, H&E) with an intervillous thrombus and control (200x, acute chorioamnionitis), which were found in both cohorts.

Figure 3:. Representative images of immunohistochemical staining of immune cells in the intervention and control cohorts, demonstrating similar staining patterns.

Row 1) H&E stain displaying lymphocytic infiltrate with patchy perivillous fibrin; Row 2) CD4+ T-cells, histiocytes, or monocytes are faintly positive; Row 3) CD8+ T cytotoxic cells are strongly positive; Row 4) CD56+ NK cells show absent staining; Row 5) CD163+ histiocytes are strongly positive, with areas of perivillous fibrin also staining positive; Row 6) CD138+ plasma cells and trophoblast cell membranes are strongly positive in the trophoblastic lining, but negative in focus of chronic villitis.

Figure 4:. Quantification of immune cell staining intensity in placentae from fetal surgery and control cohorts.

Median pixel intensity between groups for A) CD4+ helper T cells; B) CD8+ cytotoxic T cells; C) CD56+ NK cells; D) CD138+ plasma and trophoblast cells and E) CD163+ histocytes. Results displayed as medians with interquartile ranges (n=5–11/group). Significance determined by Mann-Whitney testing.