Altered placental phenotype and increased risk of placental pathology in fetal spina bifida: A matched case-control study

Introduction

Spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies.

Methods

Placental pathology and transcriptome were evaluated for fetuses with isolated open SB born preterm (cases; n = 12) and control fetuses without congenital anomalies (n = 22) born at full term (FT) or preterm (PT). We evaluated associations between study group and placental histopathology, and between placental histopathology and gene expression.

Results

Placental weight was lower in cases than PT controls (median [IQR]: 263 g [175, 370] vs. 455 g [378, 560], p = 0.001). Placental villi structural phenotype was different in cases, where proportion of immature intermediate villi was higher in cases than PT controls (32.5 % [6.3, 56.3] vs. 10 % [5, 13.8], p = 0.01), but cases and FT controls had similar proportions of mature intermediate (10 % [5, 10] vs. 10 % [8.75, 11.25]) and terminal villi (22.5 % [11.3, 43.8] vs. 30 % [20, 36.3]), and similar odds of having many syncytial knots (adjusted odds ratio [aOR] = 6 [0.2, 369]). Case placentae also had higher odds of having many Hofbauer cells (aOR = 16.2 [1.4, 580], p = 0.02) and a thick syncytial membrane (aOR = 146 [3, 3.46e5], p = 0.007). Gene expression in immune/inflammatory processes, spinal cord injury, and Hedgehog and Wnt signaling pathways were associated with placental maturity in cases.

Discussion

Improved knowledge on placental phenotypes in SB increases our understanding of mechanisms that may drive comorbidities, and may ultimately inform efforts to reduce offspring morbidity and mortality.