Address for Correspondence:


Girish C. Deshpande, Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, 374 Bagot Road, Subiaco, Perth, Western Australia 6008. E-mail: girish.deshpande@health.wa.gov.au

Development of intestinal microflora
It is important to understand the development of intestinal microflora in preterm and term neonates to appreciate the role of probiotics. Human gastrointestinal tract harbours a complex eco-system of microbes. Approximately 1014 microbes exist in the colon and intestines and consist of more than 500 species. ⁽¹⁵⁾ Microbial flora exists in symbiotic relationship with the host. A neonate is born with a sterile gut that is usually colonised within 12 to 24 hrs. Intestinal microbes from the mother are usually the first source of bacteria. Colonisation by anaerobes usually commences in next 2 or 3 days. Lactobacilli and bifidobacteria from breast milk colonise the gut subsequently. It is important to note that many other factors including mode of birth, surrounding environment and dietary factors also influence initial colonisation in a neonate.⁽¹⁶⁾ There are at least four different strains of lactobacilli and bifidobacteria isolated form human breast milk ^(17,18), which help to colonise newborn gut.

The microbial flora of the intestines of preterm neonates in neonatal intensive care units differs from that of normal term neonates. Very low birth weight (VLBW) preterm neonates usually acquire microbial flora mainly from intensive care environment rather than from their own mother. Few studies have demonstrated that there is delay in appearance of Bifidobacteria species in VLBW neonates until third week of life, even in those receiving only breast milk. ^(19,20) Stools of breastfed neonates have predominance of Bifidobacterium and Lactobacillus species, which compete with pathogens such as Bacteroides, Clostridia and Enterobacteriaceae species. ⁽²⁰⁾Unfortunately VLBW preterm neonates are at risk of gut colonisation with pathogens which can alter the permeability of intestines and promotes inflammatory cascade which facilitates NEC.^(21,22)

Probiotics for prevention of sepsis and NEC
NEC is the commonest neonatal gastrointestinal emergency. It is mainly associated with prematurity with full term neonates accounting for only 5-25% of all cases (23). The incidence of this potentially fatal illness is reported to be 5-10% in VLBW neonates (24). Extremely low birth weight (ELBW) neonates (birth weight < 1000 grams) with gestation under 28 weeks are most susceptible. (25) The mortality (20-40%) and morbidity including poor long term neurodevelopmental outcome after a diagnosis of definite NEC continue to be high, especially in ELBW neonates. (26) Despite decades of research the pathogenesis of NEC continues to be poorly understood. Prematurity however continues to be accepted as the single most important risk factor for the illness. Interplay of various risk factors including hypoxia, immaturity of intestinal tract, microbial colonisation with pathogenic organisms, formula feeding, sepsis and intestinal ischemia-reperfusion (I-R) injury against the background of a vulnerable gut is proposed to contribute to the inflammatory cascade that in some situations precipitates NEC. (27)

Probiotics may prevent NEC and sepsis by promoting colonisation with beneficial organisms (e.g. bifidobacteria species), preventing colonisation by pathogens (e.g. enterobacteria, clostridia, and staphylococcal species), improving the maturity and function of gut mucosal barrier in dealing with the flow of food and microbial antigens across it, and by modulating the immune system to the advantage of the host (1,28).