Repeated Dosing of Autologous Cord Blood Is Safe and Feasible in Babies with Congenital Hydrocephalus

Background:  Congenital hydrocephalus affects 0.3 to 1.5 per 1000 live births, is typically diagnosed in utero, and may occur in isolation or as a result of a genetic or other underlying cause.  Current standard therapy involves ventriculoperitoneal shunt placement shortly after birth to divert the flow of cerebrospinal fluid and decrease intracranial pressure.  However, survivors face the sequelae of brain injury resulting from the prolonged hydrocephalic state in utero.  Umbilical cord blood (CB) has been shown to lessen the clinical and radiographic impact of hypoxic brain injury and stroke in animal models.  Based on this data, we began to treat infants with congenital hydrocephalus with multiple autologous CB infusions during the first 1-2 years of life to determine the safety and feasibility of the procedure.

Methods:  Parents of children diagnosed with congenital hydrocephalus in utero elected to store their child’s CB in a private or public bank as a directed donor.  CB units were deemed eligible based on results of, cell count, sterility, potency and infectious disease screening.  On the day of infusion, CB units were thawed and washed in dextran-albumin and infused via peripheral IV in the outpatient clinic after premedication with acetaminophen, diphenhydramine, and methylprednisolone.  When possible, CB units were fractionated to allow for multiple doses over time. 

Results:  Since 2006, 70 patients with congenital hydrocephalus have been treated with 129 autologous CB infusions.  Most babies received repeated doses, for a total of 2 (N=24), 3 (N=12), or 4 (N=4) infusions.  Median age at the first infusion was 2 months (range 6 days – 4 years).  Median cell doses per infusion were TNC 2.0x10⁷/kg (range 0.1-13.3x10⁷/kg) and CD34 count 0.7 x10⁵/kg (range 0.04-6.4x10⁵/kg).  The infusions were well tolerated, with no acute or chronic adverse events.  Anecdotally, parents report that their children are making developmental gains after autologous CB infusion.

Conclusions:  Autologous CB infusion is safe and feasible in babies with congenital hydrocephalus.  Since the diagnosis is typically made in utero, there is sufficient time to plan for CB collection prior to delivery.  As the patients are so young and small at the time of treatment, a single CB unit can often be fractionated to permit a multiple dosing strategy.  While infants make developmental progress after the infusions, additional studies are necessary to determine if these gains are related to the CB treatment.