Use of Probiotics in Treatment of Neonatal Enterocolitis
Use of Probiotics in Treatment of Neonatal Enterocolitis
What is your opinion about the use of probiotics in the treatment of neonatal enterocolitis?
Necrotizing enterocolitis (NEC) is one of the most frustrating diseases we deal with in the neonatal intensive care unit. Since Santulli and colleagues' initial description of 64 cases of NEC published in 1975, there have been 2553 articles published on NEC (PubMed search July 11, 2004). Unfortunately, we still don't know the exact etiology of the disease or how to prevent it.
NEC is primarily a disease of premature infants, although up to 10% of cases present in term and near-term babies. Signs include abdominal distension, blood- or bile-stained emesis, bloody stools, and pneumatosis intestinalis, the pathognomic radiographic sign of the disease. Medical management is largely supportive; however, surgery is required for intestinal necrosis and mortality may approach 35%.
NEC is likely initiated with intestinal mucosal injury from any number of factors. Following this injury, bacteria in the gut proliferate with formula or breast milk as a substrate. The bacteria invade the damaged mucosa causing inflammation and, ultimately, necrosis of the infected area.
Because of the association of feeding and bacterial infection with NEC, prevention strategies have focused on manipulating the feeding of premature infants as well as trying to manipulate the bacterial environment of the intestine. Although some early trials showed a decreased incidence of NEC with slow advancement of feedings, recent randomized studies have shown no difference in the incidence of NEC with fast vs slow or early vs delayed feedings. In an attempt to modulate the immunologic milieu of the intestine, immunoglobulin (Ig)A and IgG have been given orally to infants. Unfortunately, a Cochrane analysis of these studies revealed that there was no significant difference in the incidence of NEC between those who received Ig and those who did not.
Recent interest has focused on giving probiotic bacteria to premature infants. Probiotic bacteria, such as Bifidobacteria and Lactobacillus, are live microbial supplements that colonize the intestines and provide benefit to the infant. The hope is to prevent the overgrowth of pathogenic organisms that have been associated with NEC. There have been a modest number of studies that primarily have looked at the safety of probiotics in newborns; and to date, it appears safe to administer these bacteria. A recent double-blind study from Italy randomized infants less than 33 weeks to receive either Lactobacillus or a placebo. The number of babies who developed either urinary tract infections, sepsis, or NEC was surprisingly low, and there was no significant difference between the probiotic and placebo groups. An open study from South America revealed a significant decrease in the incidence of NEC with the introduction of Lactobacillus enteral feeds, but this study used only historical controls.
In summary, although the use of probiotics to prevent NEC appears attractive, at this time it is too early to recommend their general use. Randomized trials of sufficient size are needed to determine whether probiotics decrease the incidence of NEC as well as to identify the possible side effects they may cause.
What is your opinion about the use of probiotics in the treatment of neonatal enterocolitis?
Necrotizing enterocolitis (NEC) is one of the most frustrating diseases we deal with in the neonatal intensive care unit. Since Santulli and colleagues' initial description of 64 cases of NEC published in 1975, there have been 2553 articles published on NEC (PubMed search July 11, 2004). Unfortunately, we still don't know the exact etiology of the disease or how to prevent it.
NEC is primarily a disease of premature infants, although up to 10% of cases present in term and near-term babies. Signs include abdominal distension, blood- or bile-stained emesis, bloody stools, and pneumatosis intestinalis, the pathognomic radiographic sign of the disease. Medical management is largely supportive; however, surgery is required for intestinal necrosis and mortality may approach 35%.
NEC is likely initiated with intestinal mucosal injury from any number of factors. Following this injury, bacteria in the gut proliferate with formula or breast milk as a substrate. The bacteria invade the damaged mucosa causing inflammation and, ultimately, necrosis of the infected area.
Because of the association of feeding and bacterial infection with NEC, prevention strategies have focused on manipulating the feeding of premature infants as well as trying to manipulate the bacterial environment of the intestine. Although some early trials showed a decreased incidence of NEC with slow advancement of feedings, recent randomized studies have shown no difference in the incidence of NEC with fast vs slow or early vs delayed feedings. In an attempt to modulate the immunologic milieu of the intestine, immunoglobulin (Ig)A and IgG have been given orally to infants. Unfortunately, a Cochrane analysis of these studies revealed that there was no significant difference in the incidence of NEC between those who received Ig and those who did not.
Recent interest has focused on giving probiotic bacteria to premature infants. Probiotic bacteria, such as Bifidobacteria and Lactobacillus, are live microbial supplements that colonize the intestines and provide benefit to the infant. The hope is to prevent the overgrowth of pathogenic organisms that have been associated with NEC. There have been a modest number of studies that primarily have looked at the safety of probiotics in newborns; and to date, it appears safe to administer these bacteria. A recent double-blind study from Italy randomized infants less than 33 weeks to receive either Lactobacillus or a placebo. The number of babies who developed either urinary tract infections, sepsis, or NEC was surprisingly low, and there was no significant difference between the probiotic and placebo groups. An open study from South America revealed a significant decrease in the incidence of NEC with the introduction of Lactobacillus enteral feeds, but this study used only historical controls.
In summary, although the use of probiotics to prevent NEC appears attractive, at this time it is too early to recommend their general use. Randomized trials of sufficient size are needed to determine whether probiotics decrease the incidence of NEC as well as to identify the possible side effects they may cause.
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