Stem cell therapy in neonates with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

Apart from therapeutic hypothermia, no treatment is approved for neonates with hypoxic-ischemic encephalopathy (HIE). Stem cell therapy is a promising option, with a few studies conducted in recent years.

This systematic review assessed pooled 12-month survival and neurodevelopmental outcomes in neonates with HIE receiving stem cell therapy. Secondary outcomes included survival with favorable neurodevelopment, seizures during hospitalization, discharge on antiseizure medication (ASM), and 100% oral feeding. Both controlled and uncontrolled trials were included.

Four studies, including one quadruple-blinded randomized-controlled trial (RCT), met the inclusion criteria, comprising 153 neonates, with 52 in the stem cell therapy group and 101 in the standard care group. Among those receiving stem cell therapy, 46 neonates received umbilical cord blood-derived stem cells, while 6 received human cord tissue mesenchymal stem cells. The pooled 12-month survival rate in the stem cell group was 92% (95% CI: 82%-98%, I² = 0%), and survival with Bayley scores of 85 or more in all three domains was 76% (95% CI: 62%-87%, I² = 0%). Survival with favorable neurodevelopmental outcomes was significantly higher in the stem cell therapy group (RR = 1.89, 95% CI: 1.30-2.74, I² = 0%, p = 0.0008). However, overall survival at 12 months (RR = 1.09, 95% CI: 0.94-1.26, p = 0.25), seizures during hospitalization (RR = 0.76, 95% CI: 0.41-1.41, p = 0.38), discharge on ASM (RR = 0.83, 95% CI: 0.35-1.97, p = 0.67), and adverse events were comparable between groups.

Stem cell therapy appears safe and may improve neurodevelopmental outcomes in neonates with HIE. However, larger, more robust RCTs are needed before universal recommendations can be made.