SAN FRANCISCO – The 10-year follow-up of neonates treated for posthemorrhagic ventricular dilatation (PHVD) has demonstrated the long-term success of drainage, irrigation, and fibrinolytic therapy (DRIFT), with a cognitive advantage in the now school-age children evident, compared with those neonates who had not received the therapy.
“Children in the DRIFT group had a 23-point cognitive quotient advantage and were nine times more likely to be alive without severe cognitive disability at 10 years,” presenter and DRIFT investigator Karen Luyt, MBChB, PhD, of the University of Bristol and St. Michael’s Hospital, Bristol, England, said at the Pediatric Academic Societies meeting.
PHVD carries a high risk of disabilities in cognition and movement. DRIFT was developed as a way to wash out the ventricles in the brain to clear the effects of bleeding, with the goal of reducing neurodevelopmental disability. In the technique, catheters are inserted into the affected ventricles and are used to deliver an anti-clotting agent (alteplase) and to drain the bloody fluid. The catheters remain in place for a time as a conduit for artificial cerebrospinal fluid (CSF) containing antibiotics.
In the DRIFT trial, 77 preterm infants were randomized to DRIFT (n = 39) or the standard treatment of siphoning off cerebrospinal fluid to restrict brain expansion (n = 38). At 2 years, the DRIFT group displayed fewer cases of severe disability and cognitive disability, and death ( ).
Dr. Luyt summarized the final 10-year data from 52 school-age children (28 treated using DRIFT and 24 treated in the standard manner). The primary outcomes in the school-age children were cognitive quotient (CQ) and survival without severe cognitive disability. Secondary outcomes included visual function, sensory and motor disabilities, and emotional or behavior problems.
The age at the time of treatment randomization was 19 days in the DRIFT group and 19 days in the standard group. The DRIFT group was composed of more males (79% vs. 63%) and newborns with lower birth weight (336 vs. 535 grams). The gestational age and the prevalence of grade 4 intraventricular hemorrhage were similar between the groups.
DRIFT increased cognitive ability at 10 years (P = .096). Adjustment for gender, birth weight, and grade of intraventricular hemorrhage strengthened this association, with the DRIFT group having an average advantage in CQ score of 23.5 points (P = .009), which translated to a 2.5-year advantage in cognitive ability. When the data was further adjusted by ruling out the three children (two in the DRIFT group and one in the standard treatment group) who died between the 2- and 10-year follow-ups, the CQ score advantage remained (20 points; P = .029).
The other primary outcome of survival without severe cognitive disability also favored DRIFT, with an unadjusted odds ratio (OR) of 3.3 (95% confidence interval [CI] 1.1-10.4 (P = .037) and adjusted (as above) OR of 8.9 (95% CI, 1.9-42.3; P = .006). Fewer children in the DRIFT group were attending schools with an expertise in special needs (OR, 0.27; 95% CI, 0.07-1.05; P = .059). No differences between the groups were evident for the secondary outcomes.
The number needed to treat to prevent death or severe cognitive disability was four.
Dr. Luyt’s recommendation that DRIFT become the standard of care for neonatal intraventricular hemorrhage comes with the caveat of increased secondary bleeding, which caused the trial to be halted after a planned external safety monitoring review. Children who already had been treated were followed up, with no further recruitment. In her response to a question from the audience regarding her endorsement of DRIFT despite the trial’s halt, Dr. Luyt pointed to the comparable safety profiles of the two groups, the superior outcomes in the DRIFT group, and the knowledge that modifications made to the technique in the intervening years have reduced the possibility of secondary bleeds.
The sponsor of study was Dr. Birgit Whitman of the University of Bristol. The study was funded by the National Institute of Health’s Health Technology Assessment Programme. Dr. Luyt disclosed the off-label use of alteplase.