Necrotizing Enterocolitis: 21st Century Applications
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This document is a presentation on necrotizing enterocolitis (NEC) given by Dr. David Mendez. It discusses the epidemiology, risk factors, pathophysiology, clinical presentation, diagnosis, and management of NEC. The presentation covers topics such as the different populations that can develop NEC, intestinal immaturity in preterm infants that makes them susceptible, the role of abnormal bacterial colonization and an exaggerated inflammatory response, and the importance of enteral feedings as a risk factor. Radiologic images are included to demonstrate findings like pneumatosis intestinalis. Overall, the presentation provides a comprehensive overview of NEC from epidemiology to pathology.
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Necrotizing Enterocolitis: 21st Century Applications
- 1. Dr. David Mendez Miami Childrens Hospital Kidz Medical Serivces
- 2. NEC - 21st Century I have received no financial support for this presentation, but have liberally borrowed thoughts and ideas from people smarter than me 2
- 3. NEC - 21st Century OUTLINE 1. Epidemiology 2. Etiology and Risk Factors 3. Pathophysiology 4. Pathology 5. Clinical Characteristics 6. Diagnosis 3
- 4. NEC - 21st Century 7. Management 8. Prevention 9. Old Ideas 10. New Ideas 11. The Future OUTLINE 4
- 5. NEC - 21st Century EPIDEMIOLOGY All The Follwing Are True Term Babies Get NEC - Approx 5% of All NEC Developed Countries Have a Higher NEC Rate NEC Can Happen Any Time NEC Rates Have Not Changed NEC Clusters are Real NEC Hits Females and Males Equally 5
- 6. NEC - 21st Century EPIDEMIOLOGY NEC Is Often Seen as an Indicator of Survival and Medical Progress The More Skilled the NICU Is at Keeping Babies Alive, the More Higher the Rate of NEC 6
- 7. NEC - 21st Century Most NICU’s Have a NEC Rate Of 6-7% for their VLBW Population Mortality Rates Vary Between 12-30% Fatality Rates are Relatively Higher in Infants Requiring Surgical vs. Medical Management EPIDEMIOLOGY 7
- 8. NEC - 21st Century 3 POPULATIONS OF NEC Pre-term, Early Onset, Non-fed Pre-term, Fed, Later Onset Term 8
- 9. NEC - 21st Century PRE-TERM, EARLY ONSET, NON-FED Often appears in 1st few days of life “Spontaneous intestinal perforation” Have not been fed Associated with indomethacin use Associated with glucocorticoid exposure 9
- 10. NEC - 21st Century Occurs in the first week of birth Associated risk factors are present 1. Maternal drug exposure (cocaine) 2. Intestinal anomalies 3. Congenital heart disease 4. Perinatal stressors 5. IUGR 6. Hyperviscosity TERM NEONATES 10
- 11. NEC - 21st Century Prematurity- most important risk factor VLBW at highest risk 10% of all babies < 28 weeks 5% of all babies 28-32 weeks Exposure to enteral feeds Usually after the 1st week of life PRE-TERM, FED, LATER ONSET 11
- 12. NEC - 21st Century Umbilical lines – not causally associated TPN via UAC/UVC – does not increase risk of NEC Low Apgar scores – not associated Presence of a PDA – not causally associated Antenatal steroids – unclear PDA surgery and antenatal steroids-increase OTHER POSSIBLE RISK FACTORS 12
- 13. NEC - 21st Century Clinical Parameters Alone Cannot Adequately Predict the Outcome In NEC MOSS ET.AL JOURNAL OF PERINATOLOGY(2008) 28, 665-674DOL:10.1038/JP2008.119 13
- 14. NEC - 21st Century AS IT STANDS... NEC has a multifactorial cause; combining a genetic predisposition, intestinal immaturity, abnormal microbial colonization, abnormalities in microvascular tone and a highly immunoreactive intestinal mucosa leading to bacterial overgrowth, inflammation and ischemia of the bowel 14
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- 16. NEC - 21st Century 16 INTESTINAL IMMATURITY Motility Digestion Absorbtion Immune defense Barrier function Circulatory regulation
- 17. NEC - 21st Century INTESTINAL IMMATURITY After delivery the intestine undergo microbial colonization This results in modification of the cells immune response Fetal cell lines have an increased TLR4 response vs adult cell line Excessive TLR4 have been associated with extensive and inappropriate inflammatory response 17
- 18. NEC - 21st Century INTESTINAL IMMATURITY Gastric secretions are limited in pre-term babies Linked to increased risk of NEC Use of H2 blockers may further increase risk 18
- 19. NEC - 21st Century PREMATURITY Feeding Circulatory Regulation Barrier Function Immune Defenses Motility and Digestion NEC Abnormal microbial colonization Genetic predisposition 19
- 20. NEC - 21st Century INTESTINAL MOTILITY AND DIGESTION Motility develops in 2nd trimester, matures in 3rd Decreased and poorly organized motility can delay clearance, lead to bacterial overgrowth Decreased digestion from protease immaturity and increased ph impair this 1st line of defense against toxins and pathogens 20
- 21. NEC - 21st Century CIRCULATORY REGULATION Coagulation necrosis is the hallmark pathologic finding in NEC Attempts to explain this by cardiac output re-distribution after a period of asphyxia, the so called “diving reflex” Does not appear be causal to the development of NEC 21
- 22. NEC - 21st Century CIRCULATORY REGULATION Basal vascular resistance after birth Nitric Oxide Myogenic Response Endothelin ( Et-1) Anything that disrupts the balance can result in Intestinal Ischemia 22
- 23. NEC - 21st Century INTESTINAL BARRIER AND FUNCTION Barrier prevents invasion of microbes and resultant systemic inflammatory disease Preterms have higher intestinal permeability, the so-called “leaky gut” Components include: 1. Tight junction 2. Peristalsis 3. Mucus coat containing secretory IgA Breast Milk Contains IgA 23
- 24. NEC - 21st Century IMMUNE DEFENSES Antimicrobial peptides called defensins and cathelicidins produced by intestinal cells Attack wide range of microbes This in combination with iga effective barrier 24
- 25. NEC - 21st Century IMMUNE DEFENSES Factors include TLR4, TLR9, PAF, TNF, Interleukins Anti-inflammatory factors Pro-inflammatory factors 25
- 26. NEC - 21st Century Relates to polymorphisms in toll-like receptors (TLRs) TLRs appear to play a role in cell migration, proliferaton and inflammatory response within the intestine Two work in tandem TLR4 and TLR9 GENETIC PREDISPOSITION 26
- 27. NEC - 21st Century ABNORMAL BACTERIAL COLONIZATION Normal colonization is a natural barrier to pathogenic flora In pre-term babies that process is delayed and impaired Pathogenic bacterial overgrowth invades the intestine and spreads systemically 27
- 28. NEC - 21st Century MICROBIOLOGIC FLORA AND INFECTION Several organisms have been accused, but none has been proven to be causative: ̶ Enterobacteriaceae ̶ Enterobacter sakazakii ̶ Coagulase-negative staphylococci: SIP ̶ Closrtidium perfringens ̶ Candida species: SIP ̶ Cytomegalovirus ̶ Torovirus ̶ HIV ̶ Mucormycosis 28
- 29. NEC - 21st Century ABNORMAL BACTERIAL COLONIZATION Since most NEC occurs > week after birth, abnormal colonization has been thought a risk factor for NEC In the laboratory germ free intestines in lab animals don’t get NEC! 29
- 30. NEC - 21st Century A decrease in diveristy of microbes Presence of unusual microbial species (Often found in hospitals) An excessive inflammatory response in pre-term intestinal cells to normal and pathogenic flora ABNORMAL BACTERIAL COLONIZATION 30
- 31. NEC - 21st Century ABNORMAL BACTERIAL COLONIZATION The excessive immature inflammatory response associated with abnormal intestinal microbiota in considered a likely basis for the pathogenesis of NEC 31
- 32. NEC - 21st Century ENTERAL FEEDINGS Microbe colonization then followed by enteral feeds needed for NEC Too much enteral feeds or too late enteral feeds appears to increase NEC risk Breast milk fed babies at lower risk, but can still develop NEC 32
- 33. NEC - 21st Century Tolerated better Helps intestinal mucosa mature faster Presence of glutamate, nucleotides and growth factors Presence of inhibitors of proinflammatory cytokines such as PAF-AH 33 ENTERAL FEEDINGS Breast Milk
- 34. NEC - 21st Century 34 ENTERAL FEEDINGS When to start How much to give How quickly to advance
- 35. 35
- 36. NEC - 21st Century Study by Leaf et.al. Pediatrics 2012 Early group- 24-48hr after birth Late group- 120-144 hrs after birth Ave GA 31 weeks Smallest babies 11ml/kg/day Biggest babies 16ml/kg/day 36
- 37. NEC - 21st Century Study by Leaf et.al. Pediatrics 2012 No difference in the incidence of NEC 18% vs 15% 37
- 38. NEC - 21st Century Study by Money & Richardson (unpublished findings, 2010) Incidence of NEC with no feeding guidelines – 9% Incidence of NEC after feeding guidelines established – 2% 38
- 39. NEC - 21st Century TROPHIC FEEDS No standard definition Range from 1.5 ml/kg/day to 24 ml/kg/day No standard time line for trophic feeds No standard based on spec. birth weight/GA 39
- 40. NEC - 21st Century FULL ENTERAL FEEDS Can vary from 150 ml/kg/day to 180 ml/kg/day No standard how quickly to get there No standard based on BW/GA 40
- 41. NEC - 21st Century CLINICAL PRESENTATION 41
- 42. 42
- 43. NEC - 21st Century Pneumatosis intestinalis. Very obvious case. Tremendous amount of air in bowel walls Reference: Radiology Cases In Neonatology Copyright 1996, Loren Yamamoto DIAGNOSIS, RADIOLOGIC STUDIES 43
- 44. NEC - 21st Century Pneumatosis intestinalis. Note the air visible in the bowel wall. The air dissects the bowel wall giving it a double lined appearance (i.e., railroad tracks without the ties) Reference: Radiology Cases In Neonatology Copyright 1996, Loren Yamamoto DIAGNOSIS, RADIOLOGIC STUDIES 44
- 45. NEC - 21st Century Pneumatosis intestinalis DIAGNOSIS, RADIOLOGIC STUDIES 45
- 46. NEC - 21st Century Supine AXR, The bowel is mildly dilated with gas, mainly on the left side. The bubbly pattern of gas seen mainly in the right lower quadrant represents intramural gas. 30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285-305. DIAGNOSIS, RADIOLOGIC STUDIES 46
- 47. NEC - 21st Century Free intraperitoneal gas is present anteriorly (arrows) 30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285-305. DIAGNOSIS, RADIOLOGIC STUDIES 47
- 48. NEC - 21st Century DIAGNOSIS, RADIOLOGIC STUDIES NEC with perforation 48
- 49. 49
- 50. NEC - 21st Century Left lateral decubitus radiograph shows free air Reference: Necrotizing Enterocolitis, emidicine.com, Beverly P Wood, MD, MS, PhD DIAGNOSIS, RADIOLOGIC STUDIES 50
- 51. 51
- 52. NEC - 21st Century Closeup of intestine of infant showing necrosis and pneumatosis intestinalis. Autopsy PATHOLOGY 52
- 53. NEC - 21st Century 30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with pathologic correlation. RadioGraphics 2007; 27:285-305. Postmortem photograph of bowel involved with severe NEC. The arrows indicate areas of the bowel wall where there has been so much necrosis and sloughing of the mucosa, submucosa, and muscularis that only the serosa is intact. PATHOLOGY 53
- 54. NEC - 21st Century ENTEROCOLITIS NECROTIZANTE Necrosis y “burbujas” (neumatosis en serosa) 54
- 55. NEC - 21st Century NEC induced by an intravenous injection of PAF in a rat model PATHOLOGY 55
- 56. NEC - 21st Century BELL’S STAGING FOR NEC Dr. Martin Bell in 1978 devloped criteria based on radiologic and clinical findings Dr. Robert Kleigman in 1979 & 1986 helped to modify bells staging Modified bells staging current standard for NEC 56
- 57. NEC - 21st Century Stage IA Suspected Stage IIA Definite, mildly ill Stage IIIA Advanced, severely ill intact bowel Stage IB Suspected Stage IIB Definite, moderate ill Stage IIIB Advanced, severely ill perforated bowel BELL’S STAGING FOR NEC 57
- 58. NEC - 21st Century MODIFIED BELL’S STAGING FOR NEC Temperature instability, apnea,bradycardia, lethargy Gastric retention, abdominal distension, emesis, heme + stool Stage IA Clinical Findings 58
- 59. NEC - 21st Century MODIFIED BELL’S STAGING FOR NEC Normal or intestinal dilatation Mild ileus Stage IA Radiographic Findings 59
- 60. NEC - 21st Century Temperature instability, apnea,bradycardia, lethargy Gastric retention, abdominal distension, emesis, heme + stool Stage IB Clinical Findings Only difference – grossly bloody stools MODIFIED BELL’S STAGING FOR NEC 60
- 61. NEC - 21st Century Normal or intestinal dilatation Mild ileus Stage IB Radiographic Findings Same as Stage IA MODIFIED BELL’S STAGING FOR NEC 61
- 62. NEC - 21st Century Temp. instability, apnea, bradycardia, lethargy Gastric retention, abd. distension, heme + stool or grossly blood stool In addition Absent bowel sounds, +/- abdominal tenderness Stage IIA Clinical Findings MODIFIED BELL’S STAGING FOR NEC 62
- 63. NEC - 21st Century Intestinal dilatation, ileus Pneumatosis intestinalis Stage IIA Radiographic Findings MODIFIED BELL’S STAGING FOR NEC 63
- 64. NEC - 21st Century Temp.Instability, apnea, bradycardia, lethargy Gastric retention, abd. Distension, heme + stool or grossly blood stool Absent bowel sounds, abdominal tenderness In addition Mild met. acidosis, thrombocytopenia, +/- abdominal cellulitis , +/- RLQ mass Stage IIB Clinical Findings MODIFIED BELL’S STAGING FOR NEC 64
- 65. NEC - 21st Century Intestinal dilatation, ileus Pneumatosis intestinalis In addition Asicites Stage IIB Radiographic Findings 65 MODIFIED BELL’S STAGING FOR NEC
- 66. NEC - 21st Century All of IIB plus: Hypotension, bradycardia, severe apnea, combined resp. and metabloic acidosis, DIC and neutropenia Signs of peritonitis, marked tenderness, abdominal distension Stage IIIA Clinical Findings MODIFIED BELL’S STAGING FOR NEC 66
- 67. NEC - 21st Century Intestinal dilatation, ileus Pneumatosis intestinalis Ascites Stage IIIA Radiographic Findings MODIFIED BELL’S STAGING FOR NEC 67
- 68. NEC - 21st Century All of IIB plus: Hypotension, bradycardia, severe apnea, combined resp. and metabloic acidosis, DIC and neutropenia Signs of peritonitis, marked tenderness, abdominal distension Stage IIIB Clinical Findings (Same as IIIA) MODIFIED BELL’S STAGING FOR NEC 68
- 69. NEC - 21st Century Intestinal dilatation, ileus Pneumatosis intestinalis Ascites In addition Pneumoperitoneum Stage IIIB Radiologic Findings (Same as IIIA) MODIFIED BELL’S STAGING FOR NEC 69
- 70. NEC - 21st Century “Acquired Neonatal Intestinal Disease” (ANID) 70 DIFFERENTIAL DIAGNOSIS
- 71. NEC - 21st Century *J AM Coli Surg. 2002 Dec; 195(6):796-803. Spontaneous localized intestinal perforation in very-low-birth weight infants: a distinct clinical entity different from necrotizing enterocolitis SPONTANEOUS INTESTINAL PERFORATION Isolated perforation of newborn Typically at terminal ileum Separate clinical entity from NEC* Differentiation is important as there are managment considerations 71
- 72. NEC - 21st Century EPIDEMIOLOGY Commonly found in VLBW, ELBW Risk ~ 2-3% in VLBW, 5% in ELBW Median gestational age 25-27 weeks Median BW 670-973g More frequent in male infants 72
- 73. NEC - 21st Century *Maternal factors in extremely low birth weight infants who develop spontaneous intestinal perforation. Ragouilliaux CJ; Keeney SE; Hawkins HK; Rowen JL Pediatrics 2007. @Focal small bowel perforation: an adverse effect of early postnatal dexamethasone therapy in extremely low birthweight infants. Gordon PV; Young ML; Marshal DD; J Perinatol. 2001 Apr-May;21(3) New insights into spontaneous intestinal perforation using a national data set Attridge JT; Clark R; Gordon PV J Perinatol. 2006 Nov;26(11):667-70. Epub 2006 Oct 5. 1. Prematurity 2. Antenatal 3. Severe placental chorioamnionitis* 4. ? Glucocorticoids/NSAIDS 5. Postnatal 6. Early postnatal glucocorticoids@ 7. ? Indocid 73 RISK FACTORS
- 74. NEC - 21st Century Single isolated perforation Typically in terminal ileum, but also reported in jejunum, colon Focal hemorrhagic necrosis with well defined margins seen (in contrast to ischemic, coagulative necrosis in NEC) Bowel proximal and distal to perforation normal PATHOLOGY AND PATHOGENESIS 74
- 75. NEC - 21st Century SIP NEC First week of life, median age 7 (0-15) Abdominal distention, bluish discoloration (groin, scrotum) Hypotension Pneumoperitoneum, gasless abdomen Associated sepsis due to CONS, fungemia Leukocytosis, raised ALP, bilirubin, decreased patelet, hct After first week, median age 15 Abdominal distention Abdominal erythema Crepitus, induration Pneumatosis intestinalis, portal venous gas, transient thickening of intestinal wall, fixed dilated SB loops, pneumoperitoneum CLINICAL PRESENTATION 75
- 76. NEC - 21st Century Septicemia with ileus Neonatal pseudomembranous colitis Meconium plug/fetal peritonitis Viral enteritis Milk protein allergy DIFFERENTIAL DIAGNOSIS (cont.) 76
- 77. NEC - 21st Century MANAGEMENT AND WORK UP NPO GI Decompression IVF KUB 77
- 78. NEC - 21st Century MANAGEMENT AND WORK UP Laboratory studies- definite CBC with PLT, blood C/S, electrolytes blood gas 78
- 79. NEC - 21st Century MANAGEMENT AND WORK UP Laboratory studies - probably Urine, stool c/s crp, pt/ptt Spinal tap, full DIC work up, abdominal U/S, LFT’s are not standard but can be considered 79
- 80. NEC - 21st Century MANAGEMENT AND WORK UP Surgical vs Medical 80
- 81. NEC - 21st Century SURGICAL MANAGEMENT Laparotomy vs Peritoneal Drainage 81
- 82. NEC - 21st Century Peritoneal Drainage vs Laparotomy for NEC and Intestinal Perforation: A Meta-Analysis 82 SURGICAL MANAGEMENT Dr. Juan E Sola, Et.al Jour. of Surgical Research 161, 95-100 (2010)
- 83. NEC - 21st Century PD vs LAP PD used as alternative to lap, even definitive therapy Sola reviewed all comparative studies from 2000-2008 Of the 12 studies done during this time 5 were selected for analysis ( 3 were prospective, 2 were RCT) 273 babies received PD vs 250 babies for LAP 83
- 84. NEC - 21st Century PD vs LAP Mortality for the PD group 35-54% Mortality for the LAP group 15-43% The combined estimate of all studies noted a 55% increase in mortality with the PD group 84
- 85. NEC - 21st Century PD vs LAP PD patients were on average younger (by .78 weeks) and smaller ( by 67 grams) Of the 3 trials that were prospective, non- randomized trials , PD associated with an 89% increase in mortality Of these babies they were 1.16 wks younger and 100 grams lighter 85
- 86. NEC - 21st Century PD vs LAP Hypothesis that PD is superior to LAP was based on retrospective data Results of studies by Rees et.al went as far to recommend early LAP and questioned the safety of PD in patients with perforated NEC and SIP 86
- 87. NEC - 21st Century PD vs LAP There are limitations to meta-analysis papers Survival data is subject to the design flaws of each individual study There were differences in inclusion data (i.e. BW < 1000gm vs < 1500gm ) 87
- 88. NEC - 21st Century PD vs LAP An editorial by pierro et.al echoed the opinion that PD may not have a role in the surgical treatment of NEC In 2012, a cochcrane search noted that only 2 RCTs met eligibilily criteria and no significant difference in PD vs LAP were noted 88
- 89. NEC - 21st Century PD vs LAP At present, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Is recruiting participants in the following study: Laparotomy vs. Drainage for infants with necrotizing enterocolitis (NEST) 89
- 90. NEC - 21st Century PREVENTION At present, there is no clinical approach to prevent the occurance of NEC in any Neonatal Unit in the world 90
- 91. 91
- 92. NEC - 21st Century PREBIOTICS AND PROBIOTICS In theory, by pre-populating the small intestine with appropriate non-pathogenic flora( prebiotic) or by altering a possibly pathogenic flora (probiotic) we lower the incidence of NEC 92
- 93. NEC - 21st Century PREVENTION CW WOODS et.al, Journal of Perinatology (2012) 32, 150-152 93 Development of NEC in preterm infants receiving thickened feeds of ‘simplythick’
- 94. NEC - 21st Century PREBIOTICS A nondigestible food ingredient that benefits the host by selectively stimulates the favorable growth and/or activity of one or more indigenous probiotic bacteria 94
- 95. NEC - 21st Century 95 PREBIOTICS Oligosaccharides Indigestible Selectively enhances proliferation of probiotic bacteria Especially bifodbacteria species
- 96. NEC - 21st Century PREBIOTICS Examples of oligosaccarides ̶ Inulin ̶ Fructo-oligosaccarides ̶ Galacto-oligosaccarides ̶ Soybean oligosaccarides 96
- 97. NEC - 21st Century 97 PREBIOTICS Human milk contains over 100 specific types of oligosaccarides that appear to bind to specific organisms and actively provide host defense Studies note that presence of human milk promotes gut colonization of a more bifidogenic flora
- 98. NEC - 21st Century 98 PROBIOTICS An oral supplement or a food product that contains a sufficient number of viable microorganisms to alter the microflora of the host and has potential health benefits
- 99. NEC - 21st Century PROBIOTICS 1960’s and 70’s artificial colonization of infants in nurseries by less pathogenic strains of s.aureus was shown to prevent colonization by more pathogenic strains In 1994-95 hoyos administered probiotics to all newborns admitted to the NICU in columbia and noted a drop in the incidence of NEC from 6.6% to 2.9% 99
- 100. NEC - 21st Century 100 PROBIOTICS 1999- 2003 lin et.al. In a double-blind control trial of 367 infants < 1500 gms received breast milk with and w/o probiotics when enterally fed, clinically stable and > 7 days of life Demonstrated a reduction of NEC from 5.3% in the controls vs 1.1% in the probiotic-fed babies As of 2011 there are 9 published trials that favor the use of probiotics to reduce the risk of NEC
- 101. NEC - 21st Century PROBIOTIC Lactobacillus acidophilus Bifidobacterium infantis Bifidobacterium bifidis Streptococcus thermophilus 101
- 102. NEC - 21st Century PROBIOTICS The published studies differed significantly in the types of probiotics used Dosing of the probiotics differed Some studies used a combination of probiotics and those studies appeared to be more effective Studies also used different strains of the same probiotic 102
- 103. NEC - 21st Century PROBIOTICS The studies didn’t stratify patients based on formula vs breast milk feeds There are studies that did not demonstrate a difference in the incidence of NEC In two of the studies, the NEC rate was 15-16% well above the usual incidence rate ( 6-7%) 103
- 104. NEC - 21st Century PROBIOTICS Tarnow-mordi, et.al in pediatrics, 2009 “All infants who meet eligibility criteria,those parents should be offered probiotics.” “ Knowing what we know now, do we have a right to deny parents that option?” 104
- 105. NEC - 21st Century 105 PROBIOTICS Lack of available, quality-controlled, highly reliable product- most are over the counter food additives By FDA guidelines they are “gras” The one most widely available probiotics “lactobacillus gg” when evaluated in a multi-center randomized trial, failed to show a difference
- 106. NEC - 21st Century A relatively new concept that implicates a causal association between the use of PRBC transfusions and the onset of NEC 106
- 107. NEC - 21st Century Transfusion associated NEC (TANEC) Transfusion related acute gut injury (TRAGI) 107
- 108. NEC - 21st Century TRANSFUSIONS AND NEC Case report in 2004 of the association of an intrauterine transfusions and NEC Initial reports from 2005- 2006 saw a temporal association between PRBC transfusions and NEC Compared to NEC unrelated to transfusions these cases tended to be more severe, most requiring surgery and a higher mortality 108
- 109. NEC - 21st Century TRANSFUSIONS AND NEC Harsono et al in 2011 reported that PRBC transfusions were protective against late onset NEC in VLBW infants HARSONO M, TALATI A, DHANIREDDY R, ELABIAD MT. ARE PACKED RED BLOODCELL TRANSFUSIONS PROTECTIVE AGAINST LATE ONSET NECROTIZING ENTEROCOLITIS IN THE VERY LOW BIRTH WEIGHT INFANTS? E-PAS; 2011;509 109
- 110. NEC - 21st Century TRANSFUSIONS AND NEC CHRISTENSEN RD, ET.AL TRANSFUSION, 2010; 50 1106-1112 In 2010, christensen et.al studied cases where baies with NEC confirmed by laparotomy and diagnosis was confirmed by the surgeon and pathologist They then did a three-part study 1. NEC within 48 hrs of a PRBC transfusion 2. A case-control study of transfusion HX 3. Age of the blood transfused & feeding HX 110
- 111. NEC - 21st Century TRANSFUSIONS AND NEC Chirstensens study found the following: The odds of tanec increased in babies who got PRBC The age of the blood was not different Neonates who developed tanec had been givn large volumes of milk in the 24 hours before and during transfusions. Furthermore, those given a boving milk product developed NEC 2x as many as those given human milk 111
- 112. NEC - 21st Century TRANSFUSIONS AND NEC Chirstensens study found the following: The babies that got NEC: Lower bw Earlier gestation Later onset Than babies who did not get NEC 112
- 113. NEC - 21st Century TRANSFUSIONS AND NEC Meta-analysis of Tanec in 2012 MOHAMED A, SHAH PS, P ; PEDIATRICS 2012; 129;529 Exposure to transfusions increase risk of NEC Babies were younger by GA, smaller, most likely ventilated and with the presence of a PDA Mortality was higher for this group vs non–tanec In this meta-analysis the role of feeding was not able to be anaylzed for significance 113
- 114. 114
- 115. NEC - 21st Century OLD IDEAS Delay, delay, delay enteral feeds Rapid feeding of babies Formula vs human milk Thickeners of breast milk Aggressive and random transfusion practices Antibiotics always, a lot, for a long time 115
- 116. NEC - 21st Century 116 NEW IDEAS Initiate early, trophic feeds (10-30ml/kg/day) within the 1st week of life Advance to full feeds over 13-16 days Human milk whenever possible Consider pasteurized donor breast milk Hold feeds before and during transfusions
- 117. NEC - 21st Century NEW IDEAS Evaluate NICU-specific NEC rate as benchmark Standardized feeding practices Standardize transfusion practices Participation in a registry (i.e. tragi registry) 117
- 118. 118
- 119. NEC - 21st Century A baby is born premature We have screened the genetic code for the balance of pro-inflammatory vs anti-inflammatory cytokine We are aware of the normal microbicrobial flora for this baby in our population The use of prebiotic and probiotic supplements are given to properly adjust the flora Breast milk is given at a specified time, amount and advancement rate 119
- 120. NEC - 21st Century We continue to monitor the intestinal microflora for changes in composition and biodiversity Aware of the genetic predispostion for an inflammatory reaction- we adjust the iga levels as well as the various tlr, interleukins, paf, tnf by increasing or decreasingthere signal to keep the balance between the two forces While holding feeds for transfusions we monitor the nitric oxide receptors and endothelin levels and make sure they are balanced to prevent ischemia to the intestinal wall Our mesenteric circulation in continually monitored to detect decreases in flow 120
- 121. NEC - 21st Century Having thus eliminated NEC and thus the need for surgical intervention, pediatric surgeons and neonatologists achieve a harmony of medical and surgical sprituality that transcends medicine and becomes the beacon of light that causes all branches of medicine to unite 121
- 122. 122