History of Management of Fetal Myelomeningocele

Understanding of Disease

• 1995 — Two-hit hypothesis: Autopsy studies in stillborn neonates with myelomeningocele suggest a progressive in-sequence set of injuries that culminate in the myelomeningocele phenotype. An immediate neurologic injury occurs when primary neurulation fails. Progressive neurologic dysfunction observed in the fetus suggests that additional insults are incurred with an open NTD during gestation. It is hypothesized, then, that prenatal closure of the spinal defect may halt or even reverse neurologic deterioration (9).
• 1996–early 2000s — Rationale for in utero repair: Research using both animal models and human fetuses demonstrated not only that closure of the exposed defect midgestation minimized damage to the developing nervous system, but also that disease reversal was possible: hindbrain herniation reversed following fetal closure of the open NTD in sheep and humans (10,11,12).
• 2011 — MOMS trial: Modifications to the open fetal technique improved preliminary outcomes for humans and led to the MOMS trial, which for the first time demonstrated a benefit to intrauterine closure, including significantly reduced rates of postnatal hydrocephalus (1).
• 2018 — Improved motor function: Review of the 30-month outcomes from the MOMS cohort demonstrated that the fetal repair cohort experienced higher rates of independent ambulation and a functional level at least two levels better than expected based on the anatomic lesion level (13).

Technological Development

• 1970s — Fetal ultrasonography: Routine use of more advanced ultrasonographic technology allowed earlier diagnosis and counseling for parents of a fetus diagnosed with an open NTD. Robust imaging obtained from modern prenatal ultrasonography allows correlation with additional cranial and ventricular measurements, along with identification of concomitant congenital defects that may preclude fetal repair (14).
• 1980s-2010s — Dural substitutes: The development of patch-facilitated dural closure was important for fetal repair, both to save valuable operative time and to accommodate otherwise thin dura that does not tolerate circumferential suturing. Many patches are available and include those derived from nonhuman (bovine and porcine) and human (dermal matrix, collagen, amnion) tissue, as well as purely synthetic substances (silica, Teflon, and polyester). Consensus on which substitute provides the best outcome does not exist, and many patches likely behave similarly in vivo (15).
• 1997-2015 — Evolution of endoscopy: The field has witnessed a regression and reemergence of endoscopy for myelomeningocele treatment. The earliest operations in a human fetus were performed using an endoscope, a technology that was quickly abandoned following poor outcomes. Open fetal surgery then gained acceptance and ultimately became the standard following the favorable results demonstrated in the MOMS trial. As the field researches strategies that may reduce maternal morbidity from fetal myelomeningocele repair, fetoscopic closure is undergoing modifications and regaining attention (16,17,18).

Surgical Technique

• 1997-2003 — Early endoscopic closure: Recognizing potential morbidity with open hysterotomy, several early series trialed patching the open NTD via an endoscopic route. The results were discouraging, with high rates of mortality, need for wound revision, and VP shunting — all ultimately leading to an abandonment of this approach (19,20).
• Early 2000s — Open hysterotomy fetal closure: Better exposure of the spinal defect allowed for more precise and durable dural patching. After favorable preliminary obstetric and neonatal (including hydrocephalus rates) results, the open hysterotomy became the standard for fetal closure that persists through the 2020s (21).
• Mid-2010s — Fetoscopic closure: In an effort to minimize obstetric complications, the endoscopic approach was revisited as a viable alternative to open hysterotomy (17). After roughly a decade of technique development and refinement, technical variations exist across centers but preliminary results suggest the fetoscopic approach could carry relative benefits to both the fetus and mother (18,22).