The Effect of Probiotics Added to the Mother's Diet on the Occurrence of Necrotizing Enterocolitis and Sepsis and Other Parameters in Preterm Babies

Preterm birth is birth that occurs before the completion of the 37th week of pregnancy. It affects approximately 10% of pregnancies and is a leading cause of perinatal morbidity and mortality. Preterm infants are at high risk for necrotizing enterocolitis (NEC), sepsis, death, and lifelong neurodevelopmental and cognitive impairment.

The most important acquired disease of the gastrointestinal tract in preterm infants is NEC, which is characterized by intestinal necrosis of varying depths and locations and most commonly affects the terminal ileum and proximal colon. NEC is a devastating disease with multifactorial etiology that carries a great burden in terms of mortality, morbidity, and cost to society. It is seen with a frequency of 3-15% in neonatal intensive care units, and >90% of affected babies are preterm babies under 32 weeks of gestation . According to the data of the Turkish Neonatology Association, the incidence in very low birth weight (VLBW) babies is 9.1% . Although its etiology and pathogenesis are not fully understood, it is a condition characterized by inflammation-related ischemic necrosis of the intestinal mucosa. Despite early diagnosis and aggressive treatment, it causes 15-30% mortality and is an important cause of long-term morbidity, especially in VLBW babies. The inflammatory process initiated in the highly immunoreactive gut in NEC prolongs the effects of the disease systemically, affecting distant organs such as the brain and placing affected infants at significantly increased risk for neurodevelopmental delays . One hypothesis suggests that the main etiological factor for NEC is colonization of the neonatal intestine with an abnormal microbiota, specifically that NEC typically occurs 8-10 days after birth when anaerobic bacteria begin to colonize the intestine. In studies examining the effectiveness of probiotic supplementation in preventing NEC (Evidence Level 1+, Recommendation Level B/C), there was a significant reduction in overall mortality. concluded Neonatal sepsis is a clinical syndrome in which there are systemic signs and symptoms of infection in the first month of life and a specific agent is produced in blood culture. Despite the developments in the field of neonatology, it is still an important cause of morbidity and mortality. The incidence of neonatal sepsis varies between 1 and 8.1 per 1000 live births, although it is lower in developed countries. In our country, the incidence of late-onset sepsis has been reported as 6.4-14.1% and mortality as 0-75%. The incidence of sepsis is 3-10 times higher in preterm babies than in term babies. Disturbances in the establishment of normal intestinal microbiota and commensal microbes colonizing the digestive tract may increase the risk of sepsis through disruption of the mucosal barrier resulting in translocation of luminal contents. Although the correlation of disruptions in the intestinal microbiota with LOS is known, more microbiota-based studies are needed for early intervention to prevent LOS in high-risk infants.

The infant's gut microbiota is a highly dynamic community that is gradually and continuously shaped in the first days of life. Colonization of the infant microbiome begins at birth, when infants can acquire many different types of bacteria from the environment, from their mothers' vagina, skin, and intestines. The immature gut response and changes in the gut microbiota or abnormal colonization pattern in preterm infants predispose the intestines of newborns to inflammation and a range of pro-inflammatory and counter-inflammatory cytokine responses. Microbial translocation or increased permeability to microbial components can then initiate systemic inflammatory response syndrome (SIRS), LOS, NEC, and multisystem organ failure. Native gut microbes are an important source of maturation signals to the infant's developing immune system. Promoting the development of a healthy microbiota in preterm infants is important in preventing NEC and LOS , but the key question is whether natural colonization and succession of microbiota is possible in these infants.

Probiotics are defined as live microorganisms that benefit the host and are often administered enterally to colonize the gastrointestinal tract. Preterm infants are at risk for alterations in the normal protective microbiome due to increased rates of cesarean delivery, exposure to antibiotics, exposure to hospital-acquired pathogens, lack of skin contact with maternal flora, as well as conditions that preclude exposure to breast milk. Modifications of the neonatal microbiome can have long-term effects on health that can last into adulthood. Probiotics are used for various purposes, including preventing NEC and LOS in newborns and infants, reducing the risk of infectious and atopic diseases and treatment duration.

Multiple systematic reviews, meta-analyses, and network meta-analyses examining the results of randomized controlled trials involving more than 10,000 preterm infants have shown significant reductions in NEC and death with probiotic supplementation. When the literature is examined, there are many studies examining prophylactic probiotic supplementation. However, these studies were conducted by giving probiotics directly to babies. Although routine prophylactic probiotic supplementation in preterm infants is controversial, the safety of probiotic supplements is an important issue that should be emphasized. Although there are studies reporting neonatal lactobacillus sepsis,caution is recommended before using probiotics for prophylaxis in immunocompromised patients such as preterms.