Probiotics can stimulate initial head growth in premature infants

This issue of Acta Paediatrica contains a paper by Wejryd et al. 1 that addresses the importance of nutrition in extremely low birthweight (ELBW) infants. It produced key findings on the relevance of head circumference growth, which may have implications for later neurodevelopmental impairment. The authors carried out a prospective, double-blind, placebo-controlled, randomised study that focused on 134 ELBW infants who received the probiotic Lactobacillus reuteri DSM 17938 or a placebo. They showed that feeding tolerance and the time to full enteral feeds were similar in both groups. However, at 28 days of life the infants’ head circumferences had increased by a mean of 2.3 cm in the study group and 1.8 cm in the control group. According to the Food and Agriculture Organization of the United Nations and the World Health Organization, probiotics are live micro-organisms that can confer defined health benefits to the host. For example, after they have colonised the gastrointestinal tract, probiotics may protect against necrotising enterocolitis by several mechanisms, including up-regulation of immune responses and competition for nutrients. Al Faleh et al. 2 evaluated 24 trials on a total of 5500 infants born at less than 37 weeks and weighing under 2500 g. Their meta-analysis of 20 of those studies showed that the risk of necrotising enterocolitis (stages II-II) was significantly reduced in the probiotic group with a relative risk of 0.43 and a number needed to treat of 30. However, a significant result was only clear in six studies including two with high rates of necrotising enterocolitis of 14% and 16%. Similarly, only three of the 17 studies included in their meta-analysis, published in 2005, 2008 and 2009, showed that mortality was significantly reduced, with a relative risk of 0.65 and number needed to treat of 41. The type of probiotic, day of introduction and duration of treatment varied in all of these studies. In another prospective randomised phase three trials 3, performed on 1210 premature infants born at 23–30 weeks in 24 English hospitals, Bifidobacterium breve was started within 48 hours of birth and administered daily at a concentration of 8.3–8.8 log colony-forming units. There were no differences in the incidence of necrotising enterocolitis (9–10%) or sepsis (11–12%) in the probiotic and placebo groups, and mortality was similar (8–9%). In addition, the weight z-scores between birth and 36 weeks of corrected age were no different (−1.33 versus to 1.38). The literature reports various probiotics that have been evaluated in premature infants 4. The findings suggest that tolerance and safety seem to be good and they can also decrease mortality and protect against necrotising enterocolitis. The study by Wejryd et al. 1 is the first to report a positive effect on head circumference at 28 days of life, but the authors do point out that the difference was no longer significant at 36 weeks of corrected age. Since a high-fat diet, compared to a normal-fat diet, induces a gut microbial imbalance and an alteration in social behaviour 5, they suggest that modulation of the microbiota by the L. reuteri DSM 17938 could have been neuroprotective. An earlier study in 2017 had already stressed that adequate, even aggressive, nutrition in the neonatal period could prevent extra-uterine growth retardation and improve the weight gain of preterm infants 6. Many interventions were evaluated during this study: more proteins, more lipids, adequate amounts of essential fatty acids, medium-chain triglycerides and micro-nutrients, better fortification of human milk and personalised fortification of the mother's milk. But a positive effect on head circumference was rarely demonstrated 7. Post-natal growth, and in particular head circumference, has been associated with neurodevelopmental outcome. In the retrospective Canadian neonatal network study on infants born at less than 29 weeks, significantly more cognitive and motor delays were observed in the group with poor head growth 8. Similarly, in a population-based prospective cohort of preterm infants born at less than 35 weeks, head circumference at birth and catch-down head circumference growth were synergistically associated to neurodevelopmental impairment at two years of corrected age 9. Head circumference does not reflect the quality of brain development and an excess of extravascular space can artificially augment it. Beauport et al. 10 showed that increasing early energy and lipids intake was associated with a better magnetic resonance imaging score at term corrected age in premature infants born at less than 29 weeks, particularly for the grey matter component of the score. Future studies that investigate nutritional interventions in the neonatal period should take a number of factors into account: energy and lipids intake, the type and duration of probiotics, growth parameters at birth and changes in z-scores before discharge, magnetic resonance imaging results and any follow-up. The paper by Wejryd et al. provides a valuable contribution to our knowledge about probiotics, but more translational research is needed to clarify the mechanics of their positive and long-term protective effects. This paper did not receive any external funding. The author has no conflict of interests to declare.

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