Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

Abstract

To improve outcomes of fetuses with spina bifida (SB), better knowledge is needed on the molecular drivers of SB and its comorbidities. We have recently shown in historical data that SB often associates with reduced fetal growth. We here use placental transcriptome sequencing and a novel nutrient-focused analysis pipeline to determine whether this association is due to placental dysfunction. We show that fetuses with SB have dysregulation in placental gene networks that play a role in nutrient transport, branching angiogenesis, and immune/inflammatory processes. Several of these networks are sensitive to multiple micronutrients, other than the well-known folic acid, and this deserves further investigation. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with SB and its comorbidities, and reveal new targets to improve fetal outcomes in this population.

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

“…In utero fetal spina bifida closure was performed for six cases. GA at delivery was similar between cases and PT controls, and shorter in both groups compared to SB controls (17). 1C and S1, Supplementary Table S1).…”

“…Maternal clinical data and medical history, and a 24-hour dietary recall (Automated Self-Administered 24-hour Recall™, specific to the Canadian population [ASA24-Canada-2016] (18)) were collected at recruitment for cases and SB controls. Methods used to analyse the maternal dietary recall data for this cohort have been previously described (17), and included calculations of estimated average requirements (EARs) (19), Healthy Eating Index (HEI)-2015 (20) scores, and dietary inflammatory index (DII) scores (21).…”

“…This case-control study has been previously described in detail (17). In brief, we prospectively recruited patients carrying a fetus with open SB (cases) early in the third trimester of pregnancy through the Fetal Medicine Unit at Mount Sinai Hospital, Toronto.…”

“…1, Sigma-Aldrich) and eosin (Eosin Y-Solution, Sigma-Aldrich; H&E), following standard protocols (23). Placental biopsies were also snap frozen in liquid nitrogen and stored at -80°C for whole transcriptome profiling (17).…”

“…Baseline characteristics have been described elsewhere (17). In brief, maternal demographic and clinical characteristics did not differ between cases, PT controls and SB controls.…”