Probiotics and the development of very low birthweight infants: follow-up study of a randomised trial

ABSTRACT: OBJECTIVE: To investigate the effect of Bifidobacterium bifidum OLB6378 on the development of very low birthweight (VLBW) infants at 18 months of corrected age. DESIGN: Long-term follow-up study of a cluster-randomised, placebo-controlled trial. PATIENTS: VLBW infants (birth weight <1500 g) born between January 2010 and March 2011 and managed at 19 neonatal intensive care unit facilities assigned to two groups to account for the effect of probiotic cross-contamination within facilities. INTERVENTIONS: For VLBW infants, administration of OLB6378 as a probiotic was started within 48 hours of birth and continued until the body weight reached 2000 g. MAIN OUTCOME MEASURES: At 18 months of corrected age, physical status and developmental quotient (DQ18) were assessed. The distribution of DQ18 scores was categorised into four levels of development: <70, significant developmental delay; 70–84, moderate developmental delay; 85–99, without developmental delay; ≥100, average development or better. RESULTS: Among 153 infants assigned to the OLB6378 administration group and 130 assigned to the placebo administration group, 102 and 105 infants, respectively, underwent the 18-month medical examination. The distribution of developmental levels (DQ18 scores <70, 70–84, 85–99 and ≥100) was significantly more favourable for OLB6378 administration (12, 12, 25 and 40 infants, respectively) than for placebo administration (15, 17, 23 and 24 infants, respectively) (ordered logistic regression analysis: partial correlation coefficient, 0.589; P value, 0.038). CONCLUSIONS: Although limited by assessment rates, result suggests that OLB6378 may have a beneficial effect on the psychological development in VLBW infants. CLINICAL TRIAL REGISTRATION: UMIN000002543.