Necrotizing enterocolitis (NEC) is a critical gastrointestinal (GI) medical complication that affects neonates (Springer & Annibale, 2007). NEC causes inflammations in the GI tissues and has been the reason for most new-born fatalities. In some cases, NEC leads to a perforation (a hole) in the baby’s intestine through which bacteria leak into the gut or the bloodstream (Springer & Annibale, 2007). The condition usually occurs within the first two to six weeks of birth. While it may be severe and life-threatening in most cases, NEC has been observed to only have mild effects on some infected infants. NEC causes serious damages to the intestinal tract, such as initial injuries to the mucosal or full-blow thickness necrosis and intestinal perforations. The image below, the Department of Pathology: Cornel University Medical College, shows two varying sections of the bowel. The image is a side-by-side comparison of a normal bowel section to a necrotized section of the bowel.
The symptoms of NEC are quite diverse. At times they can be confused with other bowel GI complications such as sepsis (Rich & Dolgin, 2017). In a systematic review performed by Neu and Walker (2013), NEC was suspected whenever symptoms such as abdominal distention were noticed. To ascertain NEC, a radiograph is usually recommended for the physician to confirm the presence of portal venous gas, pneumatosis intestinalis, or free intraperitoneal air (Neu & Walker, 2013). The infant might also begin experiencing feeding intolerance. In a case where there is not enough evidence to confirm NEC, the physician might confirm the diagnosis through clinical observation and treat with bowel decompression and a brief halting of feeding. The patient might also be considered for a short course of intravenous antibiotics. If there is definitive medical proof that there is NEC, from the aforementioned signs or other features such as dilated and fixed intestine loops and the lack of pathognomonic ileus patterns, the immediate action is to discontinue feeding enterally for at least a week. The platelet and white cell counts are then monitored closely and the patient's abdominal radiographs. The patient's blood is cultured, and they are placed under antibiotics for seven to ten days. In the worst-case scenario, NEC might require a surgical intervention. To ascertain the need for surgery, the patient's initial signs and symptoms have shown no significant improvement (Bell et al., 1978; Walsh & Kliegman, 1986). The abdominal distention and the ileus patterns have persisted, and their laboratory and clinical values such as platelet and neutrophil counts must have declined (Bell et al., 1978; Walsh & Kliegman, 1986). Here the surgical team could perform a laparotomy with resection (Bell et al., 1978; Walsh & Kliegman, 1986).
This systematic review was developed to look at the preventative and corrective measures of suspected or starting NEC rather than treatment measures. However, to understand the workings of supplementation in reducing NEC, it is necessary to understand the pathophysiology of the disease itself. Neu and Walker (2013) posit that the pathophysiology of NEC is not fully comprehended. However, their study further suggests the causes of NEC to be multifactorial. Starting from the point of genetic predisposition, the study weaves to factors such as immature intestines and an imbalanced microvascular tone (Neu & Walker, 2013). Abnormal microbial colonization in GI and prevalent immunoreactive intestinal mucosa further amalgamate these risk factors that predispose patients to NEC (Neu & Walker, 2013). In a separate and later study, Tanner et al. (2015) indicated that the pathophysiology of NEC is secondary to the infant's immunity responding to GI microbiota by the underdeveloped intestinal tract of the neonate. This, therefore, becomes the precursor to bowel inflammation. According to Kim et al. (2019), NEC's major histologic findings include haemorrhages, mucosal oedema, and bland transmural necrosis. Collection of gas in the ileus, secondary bacterial infections, and severe inflammation causes.
Up to this point, the consensus is that premature neonates have underdeveloped intestines just as other organs like the lungs. This immaturity means that they are weaker compared to full-term infants. As a result, premature babies do not have blood circulation or digestion of their food as properly as they should. Similar unfortunate characteristics might be experienced with very-low-birth-weight babies. When the birth weight is very low, their growth restriction and compromised development predispose them to NEC risks (Patel & Shah, 2012). Patel and Shah (2012) identify various risk factors that make premature and very low birth weight infants more susceptible to NEC. Their study outlines mechanical factors that lead to barrier integrity, such as decreased peristalsis, mucus layer deficiency, and composition of lipids which makes the premature bowel more permeable. Additionally, bacterial factors such as paucity of anaerobic bacteria and compromised colonization of bacteria suscept these very low birth weight infants to NEC (Patel & Shah, 2012). Other factors such as decreased levels of lactase, decreased production of gastric acid, and decreased bile acids all contribute to NEC in very low birth weight infants (Patel & Shah, 2012).
The incidence of NEC is not uncommon; thus, it is one to take note of. In the United States, the rate of NEC ranges from 1 per 1000 live births to 3 per 1000 live births (Kim et al., 2019). According to a systematic review and meta-analysis by Alsaied et al. (2020), 7 out of 100 of all very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU) are likely to develop NEC. These numbers add to the necessity of finding more, better, and improved therapeutic measures that give very low birth weight infants a fighting chance in the neonatal intensive care unit. Until recently, probiotic supplementation in reducing NEC has not been a common application. Probiotics are living microorganisms that confer health benefits to a host when administered in certain amounts (Patel & Shah, 2012). Probiotics add to the population of good bacteria in the digestive system. They have been presented in various therapeutic deliberations as an alternative for antibiotics, a statement that Patel and Shah (2012) posit in reference to reducing NEC as well. Sharif et al. (2020) conducted a meta-analysis to investigate the effect of supplemental probiotics on NEC risk factors in this same target population, but the trial designs of the included studies became a limiting factor. The review looked at 56 trials totalling 10,812, including infants. The findings of this meta-analysis did not include conclusive results regarding the effects of supplemental probiotics on NEC, death, and infection. However, from the ana analysis of 56 studies (10,812 infants involved), Sharif et al. (2020) still reported a risk ratio (RR) of 0.76, at a 95% Confidence Interval (CI) [0.65 to 0.89] for the reduction in mortality from NEC. Probiotics were also found to moderately reduce NEC risk: 0.54, 95% CI 0.45 to 0.65 (Sharif et al., 2020). The results of Sharif et al. (2020) did not cover the area aimed by this systematic review: how do supplemental probiotics reduce NEC?
Early agitations to the composition of gut microbiota heighten the risk of NEC. Modulating this microbiota has been an area of interest by various specialists. In a trial to investigate whether probiotic supplementation improves the growth and development of very-low-birth-weight infants, Al-Hosni et al. (2012) discovered that the velocity of growth in very-low-birth-weight infants increases with probiotic supplementation. Al-Hosni et al. (2012) tested 101 infants randomized into two groups probiotics-supplementation group (50) and the control group (51). After 34 weeks of observation, the probiotics-supplementation group had a growth velocity of 14.9g per day versus 12.6g per day in the control group (P = 0.05) (Al-Hosni et al., 2012). The study provided a further rationale for using probiotic supplementation in very-low-birth-weight infants to counter the effects of slowed growth and compromised development, but it also indicated the reliable safety levels of the intervention. In vitro tests conducted on human cell cultures and in vivo tests in mice revealed the reconstructive activities of probiotics in repairing inflamed guts. Strains of Lactobacillus acidophilus bacterium have been cited as necessary for the integrity restoration in an inflamed gut (Beghetti et al., 2021). All this evidence presents strong evidence that supports probiotics in preventing NEC in these low-birth-weight infants. Besides Lactobacillus acidophilus, Beghetti et al. (2021) state that Bifidobacterium lactis Bb-12/B94 had the ability to reduce the risk of NEC. In comparison, Lactobacillus acidophilus had better therapeutic results with an odds ratio of 0.03 at 95% credible intervals (CrIs) 0.00-0.21 (Bechetti et al., 2021). Evidence of effective results being achieved when treating with probiotics has been demonstrated in various other systematic reviews and metanalysis such as Patel & Underwood (2018), Underwood (2019), Neu (2014), among others.
While all these studies have been thorough in covering the effect of probiotics in effectively preventing the risk factors leading to NEC occurrence, there is enough emphasis placed on the general risks and benefits of using probiotics as a treatment option when dealing with NEC. In preparation for this systematic review, there are three target effects that were identified as barely reviewed. The effects of probiotics in preventing death, infection, and reducing NEC damage needed a more focused approach. This systematic review was carried out in the position that more support could be provided to warrant physicians using probiotics as treatment options in the place of antibiotics. The systematic review, therefore, sought to answer the PICO question; in very low birth weight infants (P), how can probiotic supplementation (I) reduce necrotizing enterocolitis (O)?