In utero ventriculosubgaleal shunt placement in a fetal lamb model: Phase 1 technical insights

Progressive ventriculomegaly and the resulting irreversible brain damage may be mitigated through timely diversion prenatal intervention. While ventriculosubgaleal shunt (VSGS) is commonly performed postnatally in premature infants, in utero placement is unexplored.

We evaluated the feasibility of intrauterine placement of VSGS using a fetal lamb obstructive hydrocephalus model.

Hydrocephalus was induced in 14 fetal lambs by injecting 1-1.5 mL of BioGlueⓇ into the cisterna magna between Days 80 and 90 of gestation. Ten to 16 days later, ultrasound was performed to confirm hydrocephalus. Afterward, VSGS was surgically placed by creating a fetal subgaleal pocket, inserting a standard ventricular catheter, tunneling under the scalp, and securing with a silk suture, with the other end into a lateral ventricle. Near term, the ewes were sacrificed. Hysterotomy was performed to extract the lambs. Lambs were evaluated through gross inspection. Postmortem magnetic resonance imaging and pathology evaluations were performed. To assess the presence of activated microglia and astroglia, selected brain sections were immuno-stained with ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), respectively.

Ten ewes with 14 fetuses (four twins) underwent hydrocephalus induction (median 86 days) by maternal laparotomy and either hysterotomy (two out of 14) or transuterine (12 out of 14) methods. Two fetuses were found demised at the time of shunt placement; hydrocephalus was confirmed in 11/12 surviving fetuses (three severe, four moderates, and four mild). A VSGS was successfully placed in all 12 surviving fetuses (median 104 days) employing open uterus fetal surgery. After shunt placement, one case died immediately from severe hydrocephalus, three were aborted, and one intrauterine fetal demise was found during cesarean delivery. Of the remaining seven lambs, seven out of seven VSGS remained under the scalp without catheter migration, and all demonstrated full scalp healing. Pathologic analyses by gross and histological methods confirmed typical hydrocephalic changes, including altered and denuded ependyma. However, more than half of the catheters were macroscopically obstructed with tissue debris and fibrin (four out of seven).

Prenatal placement of the VSGS was technically successful in all cases, meaning the shunt could be inserted in 100% of fetuses. Survival to cesarean delivery was 58% (seven out of 12). Among survivors, no hardware migration or scalp breakdown occurred. Future studies should further explore the safety of the shunt.