Neurodevelopment of Very Preterm Infants Who Participated in a Randomised Trial of Live Versus Heat-Inactivated Probiotics: A Long-Term Follow-Up Study

Background and Objective: Our previously reported randomised trial (ProPara) showed that supplementation with a live probiotic (P) compared with heat-inactivated probiotic (HP) was safe and had comparable intestinal anti-inflammatory effect in very preterm (VP) infants < 32 weeks. Assessing the long-term neurodevelopment of preterm infants exposed to HP in early postnatal life is important. We aimed to compare long-term neurodevelopmental outcomes among ProPara trial participants. Methods: Data on long-term outcomes, including composite disability, cerebral palsy (CP), and autism spectrum disorder, were obtained from unit database. Neurodevelopment was assessed using age-appropriate standardised tools at corrected age one, two, and three years and chronological age five years, including the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition (WPPSI-IV). Results: Of the surviving children enrolled in the trial, follow-up data were available for 61 participants. Fifty-nine children completed at least one formal neurodevelopmental assessment during childhood, and 30 underwent school-age assessment at approximately five years chronological age. Rates of composite disability, CP, sensory impairment and median WPPSI-IV full-scale IQ scores at five years (P: 102; HP: 99; p = 0.599) were comparable between groups. Severe autism occurred in three P group infants. Developmental scores across all domains were comparable between groups. Conclusions: Neurodevelopmental outcomes through early childhood and at five years were broadly comparable between VP infants receiving early-life HP supplementation and those receiving live probiotics. Given the small sample size and incomplete follow-up, larger adequately powered randomised controlled trials are needed to confirm long-term safety.