Current Selection Criteria and Perioperative Therapy Used for Fetal Myelomeningocele Surgery

Moise, Kenneth J.; Moldenhauer, Julie S.; Bennett, Kelly; Goodnight, William; Luks, François I.; Emery, Stephen P.; Tsao, KuoJen; Moon‐Grady, Anita; Moore, Robert C.; Treadwell, Marjorie C.; Vlastos, Emanuel; Wetjen, Nicholas M.

doi:10.1097/aog.0000000000001296

Cited by 43 publications

(42 citation statements)

References 6 publications

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“…3 Additionally, not all fetuses are candidates for fetal surgery, and there are considerable maternal and fetal risks. 3,4 Alternative and/or complementary medical approaches to treatment are warranted.…”

Section: Introductionmentioning

confidence: 99%

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Tarui

Kim

Flake

et al. 2017

American Journal of Obstetrics and Gynecology

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Background Cell-free (cf) RNA in amniotic fluid supernatant (AFS) reflects developmental changes in gene expression in the living fetus, including genes specific to the central nervous system (CNS). Although it has been previously shown that CNS-specific transcripts are present in AFS, it is not known whether changes in the AFS transcriptome reflect the specific pathophysiology of fetal CNS disorders. In myelomeningocele, there is open communication between the CNS and amniotic fluid. Objectives To identify molecular pathophysiologic changes and novel disease mechanisms specific to myelomeningocele by analyzing AFS cfRNA in fetuses with open myelomeningocele. Study Design AFS was collected from 10 pregnant women at the time of the open myelomeningocele repair in the second trimester (24.5+/−1.0 wks) and 10 archived AFS from sex and gestational age-matched euploid fetuses without myelomeningocele were used as controls (20.9+/−0.9 wks). Differentially regulated gene expression patterns were analyzed using Human Genome U133 Plus 2.0 arrays. Results Fetuses with myelomeningocele had 284 differentially-regulated genes (176 up- & 108 down-regulated) in AFS. Known genes associated with myelomeningocele (PRICKLE2, GLI3, RAB23, HES1, FOLR1) and novel dysregulated genes were identified in association with neurodevelopment and neuronal regeneration (up-regulated, GAP43 and ZEB1) or axonal growth and guidance (down-regulated, ACAP1). Pathway analysis demonstrated a significant contribution of inflammation to pathology and a broad influence of Wnt signaling pathways (Wnt1, Wnt5A, ITPR1). Conclusion(s) Transcriptomic analyses of living fetuses with myelomeningocele using AFS cfRNA demonstrated differential regulation of specific genes and molecular pathways relevant to this CNS disorder, resulting in a new understanding of pathophysiological changes. The data also suggested the importance of pathways involving secondary pathology, such as inflammation, in myelomeningocele. These newly identified pathways may lead to hypotheses that can test novel therapeutic targets as adjuncts to fetal surgical repair.

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Section: Introductionmentioning

confidence: 99%

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Tarui

Kim

Flake

et al. 2017

American Journal of Obstetrics and Gynecology

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“…Both currently vary considerably among institutions [5]. During open fetal surgery, fetal heart rate (FHR) monitoring is standard, but FHR changes are often a late sign of fetal distress.…”

Section: Introductionmentioning

confidence: 99%

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery

Sinskey¹,

Rollins

Whitlock³

et al. 2017

Fetal Diagn Ther

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Introduction: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery. Methods: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes. Results: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group. Discussion: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being.

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“…Some of these questions may be answered with the current outcomes data being collected through a multicenter fMMC outcomes registry conducted by the fMMC Consortium sponsored by NAFTNet [25]. Further investigations are still needed, however, to identify prenatal markers, biochemical or other, to optimally select patients that will recognize the greatest benefit of fMMC repair given the risks associated with this intervention.…”

Section: Discussionmentioning

confidence: 99%

Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele

Kim

Danzer²,

Moldenhauer³

et al. 2017

Fetal Diagn Ther

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Introduction: We investigated the correlation of amniotic fluid (AF) concentrations of glial fibrillary acidic protein (GFAP) with prenatal features of myelomeningocele (MMC) and neurodevelopmental outcome after fetal MMC (fMMC) surgery. Materials and Methods: AF was collected during fMMC surgery between December 2012 and November 2015. AF-GFAP concentration was determined by ELISA. Retrospective chart review identified the characteristics of the defect. Data regarding delivery and 1-year neurodevelopmental outcome was collected from The Children's Hospital of Philadelphia fMMC Registry. Results: Eighty-two AF samples were collected from fMMC surgeries. Perinatal data were obtained from 77 subjects, and 1-year follow-up data from 65 subjects. GFAP concentrations were significantly elevated in MMC compared to myeloschisis (24.1 ± 2.9 and 10.3 ± 1.5 ng/mL; p < 0.0001). A larger percentage of subjects with myeloschisis defects delivered before their scheduled due date (myeloschisis 88.5%; MMC 55.0%; p = 0.003) and delivered at an earlier mean gestational age (34.6 ± 0.4 weeks, n = 26) compared to those with MMC defects (35.2 ± 0.4 weeks, n = 51) (p = 0.04). Discussion: AF-GFAP levels differentiate between MMC and myeloschisis, and raise interesting questions regarding the clinical significance between the 2 types of defects.

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Current Selection Criteria and Perioperative Therapy Used for Fetal Myelomeningocele Surgery

Cited by 43 publications

References 6 publications

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery

Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele

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