The Role of a Multi-strain Probiotic in Very Low Birth Weight Premature Infants

Prematurity leads to the birth of a neonate who is not developmentally ready to enter the outside world. The neonate’s immature organs still need to develop fully to survive outside the protective environment of the womb. Immaturity can increase the risk of short-term morbidity [e.g. hospital-acquired bloodstream infection (HA-BSI), necrotising enterocolitis (NEC), and failure to grow]. It can also increase the risk of long-term neurodevelopmental and/or metabolic disorders (as seen in metabolic syndrome) and mortality. This thesis focused on the role that a multi-strain probiotic can play in preventing common short-term morbidities in very and extremely low birth weight preterm neonates. In Chapter 1, a review of the literature provided a background of what is known with respect to the premature neonate’s immature gut, the development and function of the microbiome, factors affecting the microbiome, consequences of dysbiosis and the possible role probiotics can play in reducing short-term morbidities in the preterm neonate. Chapter 2 provided a brief overview of the study methodology. Chapter 3 explored preterm neonates’ vulnerability to dysbiosis, as peri-rectal swab colonisation with drug-resistant Gram-negative bacteria (DR-GNB) was already present shortly after birth. Encouragingly, we found that probiotics can effectively reduce the peri-rectal colonisation of pathogenic DR-GNB by day 7, with an even more pronounced effect by day 14. On the day of enrolment 15% of the neonates showed peri-rectal colonisation with DR-GNB, indicating probable maternal-to-neonate (vertical) bacterial transmission or environmental acquisition at time of delivery, with no difference between the probiotic and placebo groups. By day 7 (corresponding to early gut colonisation), neonates in the probiotic group were 57% less likely to have peri-rectal DR-GNB colonisation and by day 14 (corresponding to late gut colonisation), neonates in the probiotic group were 93% less likely to have peri-rectal DR-GNB colonisation. The protective effect against a positive extended-spectrum beta-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae (CRE) swab was particularly apparent in the 26–32 weeks gestational age group. Chapter 4 presented the results of the effect of a multi-strain probiotic on HA-BSI. It was shown that the incidence of HA-BSI and the combined outcome (sepsis/death) was lower in the probiotic group than in the placebo group. These findings could lead to a significant reduction in HA-BSI-associated morbidity and mortality outcomes. In Chapter 5, the incidence of NEC was examined, showing that the multi-strain probiotic was effective in reducing the incidence and severity of NEC. In addition, feeding intolerance was significantly reduced (number of days of emesis and emesis incidents observed, and days with abdominal distention), as well as the amount of nil per os days in the probiotic group. This reduction was especially apparent among the neonates in the below 33 gestational weeks age group. In Chapter 6, we investigated the effect of the multi-strain probiotic on feeding and growth. The administration of the probiotic led to improved feeding tolerance and earlier full feeds, resulting in neonates regaining their birthweight earlier than the placebo group. The probiotic intervention had a more positive effect on the mean Z-score change in weight over the 28-day trial period than the placebo intervention. Thus, the use of a multi-strain probiotic may be a key to preventing the growth restriction often seen in premature neonates. The findings of the trial provide a cost-effective, low-risk opportunity to improve the short-term outcomes of preterm neonates, which show promise in positively influencing survival rates and long-term outcomes.