Outcomes of Babies with Surgical Necrotizing Enterocolitis in the Children s Hospitals Neonatal Consortium

Transcription

1 Outcomes of Babies with Surgical Necrotizing Enterocolitis in the Children s Hospitals Neonatal Consortium Toby Debra Yanowitz, MD, MS Associate Professor of Pediatrics Division of Newborn Medicine University of Pittsburgh School of Medicine April 12, 2019 Disclosures I have nothing to disclose 1

2 Disclosures I have nothing to disclose. My only major expenses Outline What is Necrotizing Enterocolitis (NEC)? What is the Children s Hospitals Neonatal Database (CHND)? Why is CHND ideal for evaluating outcomes of babies with surgical NEC? Outcomes of babies with surgical NEC in CHND. 2

3 Necrotizing Enterocolitis (NEC) Leading cause of death from GI disease in the premature infant NEC affects nearly 10% of infants <1500 g Mortality rates of 50% or more depending on the severity of the disease Inflammatory condition of bowel whose etiology remains incompletely understood Prematurity 90% of cases are preterm babies More premature higher risk Intestinal malperfusion Congenital heart disease (esp. Left-sided obstructive lesions) In-utero hypoxia In-utero drug exposure PDA /treatment of PDA Necrotizing Enterocolitis: Gross Pathology Distension Edema Hemorrhage Necrosis Perforation Continuous or skip areas Most common sites: distal ileum proximal colon 6 3

4 Necrotizing Enterocolitis: Microscopic Pathology Presence of mucosal injury, patchy necrosis, and loss of villi Gangrene on the anti-mesenteric border Subserosal collections of gas on the mesenteric border Normal Intestine 7 Necrotizing Enterocolitis Necrotizing Enterocolitis: Microscopic Pathology Presence of mucosal injury, patchy necrosis, and loss of villi Gangrene on the anti-mesenteric border Subserosal collections of gas on the mesenteric border Normal Intestine Necrotizing Enterocolitis 8 4

5 Necrotizing Enterocolitis: Microscopic Pathology Presence of mucosal injury, patchy necrosis, and loss of villi Gangrene on the anti-mesenteric border Subserosal collections of gas on the mesenteric border Pneumatosis Intestinalis 9 Necrotizing Enterocolitis: Pneumatosis epithelium lamina propria muscularis mucosa linear submucosal pneumatosis submucosa serosa cystic submucosal pneumatosis linear subserosal pneumatosis 10 From: Das Narla, Hingsbergen and Bagwell. The spectrum of Pneumatosis Intestinalis in Children 5

6 Necrotizing Enterocolitis: Pathology Pneumatosis epithelium lamina propria muscularis mucosa linear submucosal pneumatosis submucosa serosa cystic submucosal pneumatosis linear subserosal pneumatosis 11 From: Das Narla, Hingsbergen and Bagwell. The spectrum of Pneumatosis Intestinalis in Children Necrotizing Enterocolitis: Pathology Pneumatosis epithelium lamina propria muscularis mucosa linear submucosal pneumatosis submucosa serosa cystic submucosal pneumatosis linear subserosal pneumatosis 12 From: Das Narla, Hingsbergen and Bagwell. The spectrum of Pneumatosis Intestinalis in Children 6

7 Necrotizing Enterocolitis: Pathology Pneumatosis epithelium lamina propria muscularis mucosa linear submucosal pneumatosis submucosa serosa cystic submucosal pneumatosis linear subserosal pneumatosis 13 From: Das Narla, Hingsbergen and Bagwell. The spectrum of Pneumatosis Intestinalis in Children Necrotizing Enterocolitis: Presentation Sudden onset of feeding intolerance Abdominal distension Bloody stools Bilious aspirates or emesis Peritonitis 7

8 Necrotizing Enterocolitis: Radiographic Findings Ileus Distension Thickened bowel walls 15 Necrotizing Enterocolitis: Radiographic Findings Pneumatosis Intestinalis Local 16 8

9 Necrotizing Enterocolitis: Radiographic Findings Pneumatosis Intestinalis Diffuse 17 Necrotizing Enterocolitis: Radiographic Findings Portal Venous Gas 18 9

10 Necrotizing Enterocolitis: Radiographic Findings Free air 19 Necrotizing Enterocolitis: Radiographic Findings Free air Central distribution Football Sign 20 10

11 Necrotizing Enterocolitis: Radiographic Findings Free air Lateral Decubitus 21 Necrotizing Enterocolitis: Radiographic Findings Free air X-table Lateral 22 11

12 Necrotizing Enterocolitis: Supportive Treatment NPO, TPN Replogle to suction for decompression Labs: Blood Culture, CBC, Gas, Lytes Broad spectrum antibiotics for 7-14 days Respiratory support as needed Vasopressors Slow re-introduction of feeds after 7-14 days of treatment Necrotizing Enterocolitis: Surgical Intervention Indications: Failure of medical management Pneumoperitoneum Abdominal wall cellulitis Signs of gangrenous intestine Ascites Fixed loop Persistent acidosis Persistent thrombocytopenia 12

13 Necrotizing Enterocolitis: Surgical Procedures Peritoneal Drain Usually placed after perforation Irrigation and drainage of peritoneal contents (succus entericus and inflammatory exudate) Sickest, unstable babies as stabilizing or temporizing procedure Maybe definitive procedure Exploratory laparotomy Resection of necrotic bowel with reanastomosis Resection of necrotic bowel with ostomy formation Options for NEC totalis (<25% viable gut) Exploratory laparotomy +/- resection of necrotic bowel, then close abdomen followed by comfort care Proximal stoma followed in later by bowel lengthening procedures Necrotizing Enterocolitis: Outcomes Reported in the literature Single site over many years Often from birth hospitals majority medical NEC Some may die acutely prior to transfer to Children's Hospital for surgical care Multiple sites as parts of trials for prevention/treatment of NEC Difficult to enroll in treatment studies given the urgency Children s Hospitals Neonatal Consortium s Database 13

14 Children s Hospitals Neonatal Consortium: Developed to Meet Challenges to Research and QI at Tertiary/Quaternary-Care Children s Hospitals Disease-specific populations are small, especially for any one center Complications of prematurity traditionally used for benchmarking (ROP, NEC, IVH, BPD) often pre-existing on admission to the tertiary center Medically complex, often undergo surgery (or, multiple surgeries) Have not had much benchmarking amongst centers Best care practices often extrapolated from other neonatal (or pediatric/adult) populations based on eminence not evidence Children s Hospitals Neonatal Consortium (CHNC): Mission Statement and Values Dedicated to improving care and outcomes for infants in children s hospitals NICU s through sharing of data and ideas for benchmarking and research development of safety and quality improvement initiatives Create environment of mutual respect integrity, trusting, and teamwork The focus on understanding and improving care for our complex patients is put above individual/self interest 14

15 Children s Hospitals Neonatal Consortium (CHNC) 1. Alfred I. dupont Hospital for Children, Wilmington, DE 26. Nationwide Children s Hospital, Columbus, OH* 2. All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL 27. Primary Children s Hospital, Salt Lake City, UT* 3. American Family Children s Hospital, Madison, WI 28. Rady Children s Hospital San Diego, CA* 4. Ann & Robert H. Lurie Children s Hospital of Chicago, Chicago, IL* 29. Riley Children s Hospital, Indianapolis, IN* 5. Arkansas Children s Hospital, Little Rock, AK 30. Seattle Children s Hospital, Seattle, WA 6. Boston Children s Hospital, Boston, MA* 31. St. Christopher Hospital for Children, Philadelphia, PA 7. Children s Healthcare of Atlanta at Egleston, Atlanta, GA* 32. St. Louis Children s Hospital, St. Louis, MO* 8. Children s Healthcare of Atlanta at Scottish Rite, Atlanta, GA 33. Texas Children s Hospital, Houston, TX 9. Children s Hospital and Medical Center, Omaha, NE 34. UCSF Benioff Children s Hospital Oakland, Oakland, CA* 10. Children s Hospital Colorado, Aurora, CO* 11. Children s Hospital of Pittsburgh of UPMC, Pittsburgh, PA* 12. Children s Hospital of Wisconsin, Milwaukee, WI 13. Children s Medical Center Dallas; Dallas, TX 14. Children s Mercy Hospitals and Clinics, Kansas City, MO 15. Children s National Medical Center, Washington, DC* 16. Children s of Alabama, Birmingham, AL* 17. Children's Hospital Los Angeles; Los Angeles, CA* 18. Children's Hospital of Michigan, Detroit, MI 19. Children s Hospital of Orange County 20. Children s Hospital of Philadelphia, Philadelphia, PA* 21. Cincinnati Children s Hospital, Cincinnati, OH* 22. Cook Children's Medical Center, Fort Worth, TX 23. Florida Hospital for Children, Orlando, FL 24. Hospital for Sick Children, Toronto, On Canada 25. Le Bonheur Children's Hospital, Memphis, TN Divisions of CHNC - Quality Improvement (CIQI) - Children s Hospitals Neonatal Database (CHND) Currently, >168,000 Records focusing on Regional NICU care/infants - Disease-specific Focus Groups Mortality Diaphragmatic Hernia Bronchopulmonary Dysplasia Hypoxic-Ischemic Encephalopathy 15

16 Necrotizing Enterocolitis (NEC): CHND definition Infant must meet at least one of the following criteria: Necrotizing Enterocolitis (NEC) diagnosed at surgery, or NEC diagnosed at postmortem examination, or NEC diagnosed clinically and radiographically using the following criteria: a. One or more of the following clinical signs present: 1. Bilious gastric aspirate or emesis 2. Abdominal distention 3. Occult or gross blood in stool with no apparent rectal fissure AND b. One or more of the following radiographic findings present: 1. Pneumatosis intestinalis 2. Hepato-biliary gas 3. Pneumoperitoneum Note: Infants who satisfy the definition of Necrotizing Enterocolitis but are found at surgery or postmortem examination for that episode to have a Focal Gastrointestinal Perforation are coded as having focal gastrointestinal perforation, not as having NEC. Spontaneous Perforation: A separate entity defined in CHND. Spontaneous Intestinal Perforation: Yes, No or Presumed Yes Focal Intestinal Perforation not associated with (NEC). Dx made by visual inspection of the bowel at the time of surgery or autopsy A single focal perforation, with the remainder of the bowel appearing normal. NOTE: gastric perforation is also a separate diagnosis in CHND No the infant did not have a Focal Intestinal Perforation as defined above. Presumed Spontaneous Perforation Infant did not have NEC clinically or radiographically Pneumoperitoneum Drain placed without a laparotomy (thus, no visual inspection of bowel) Patient care team identified an isolated (Ileal) perforation as a diagnosis. OR.the infant died and did not have an autopsy to confirm the hole in the bowel. 16

17 The Surgical NEC population within the Children s Hospitals Neonatal Database (CHND) Total Cohort (January 2010 July 2013) 55, 581 Surgical NEC Cases <37 weeks % of CHND population had Surgical NEC Total Cohort (January 2010 February 2015) 86, 975 Surgical NEC cases % of CHND population had Surgical NEC Surgical NEC Cases <32 weeks and <1000 gm 528 CHNC Surgical NEC Focus Group Projects Short-term Outcomes of Babies with NEC Infant GA 36 6/7 weeks Laparotomy vs. Peritoneal Drain as Initial Surgery for NEC Infant GA 31 6/7 weeks and BW <1000gm Effect on short term outcomes Predictors on length of stay Antibiotic Use Among Babies with Medical NEC and With Surgical NEC Variability among centers Relationship to time to full feeds 17

18 CHNC Surgical NEC Focus Group Projects Short-term Outcomes of Babies with NEC Infant GA 36 6/7 weeks Laparotomy vs. Peritoneal Drain as Initial Surgery for NEC Infant GA 31 6/7 weeks and BW <1000gm Effect on short term outcomes Predictors on length of stay Antibiotic Use Among Babies with Medical NEC and With Surgical NEC Variability among centers Relationship to time to full feeds CHNC Surgical NEC Focus Group Projects Short-term Outcomes of Babies with NEC Infant GA 36 6/7 weeks Laparotomy vs. Peritoneal Drain as Initial Surgery for NEC Infant GA 31 6/7 weeks and BW <1000gm Effect on short term outcomes Predictors on length of stay Antibiotic Use Among Babies with Medical NEC and With Surgical NEC Variability among centers Relationship to time to full feeds 18

19 Short-Term Outcomes Paper: Population 19

20 Short-Term Outcomes: Preexisting Conditions Babies <28 weeks were more likely to have IVH and PDA prior to or at time of referral Babies < 28 weeks were more likely to have sepsis present at time of referral Babies <28 weeks were less likely to have NEC at time of referral Short-Term Outcomes: Mortality and Morbidity Short Bowel Syndrome/Intestinal Failure (SBS/IF) Definition: >90 days of parenteral nutrition, with or without major intestinal resection Major Resection: <75 cm or <50% bowel length remaining after resection 20

21 Short-Term Outcomes: Mortality and Morbidity by GA Short-Term Outcomes: Mortality and Morbidity by GA 21

22 Short-Term Outcomes: Mortality and Morbidity by GA Short-Term Outcomes: NEC Totalis 84 Infants (11%) had NEC Totalis 6/86 infants with NEC Totalis (7%) survived 22

23 Short-Term Outcomes: Select Morbidities Short-Term Outcomes: Summary Surgical NEC has high mortality Surgical NEC is associated with prolonged LOS and Neonatal Morbidity Not only is surgical NEC more common in lower GA babies, morbidities associated with Surgical NEC are more prevalent in lower GA babies. 23

24 Objectives OVERALL OBJECTIVE: Quantify short-term outcomes associated with initial surgery [laparotomy (LAP) vs. peritoneal drain (PD)] for NEC in Extremely-low-birth-weight (ELBW) infants. PRIMARY AIM: Test the null hypothesis that the composite outcome of Death/Short Bowel Syndrome occurred at similar rates between infants in CHND born at <1kg who develop snec and whose first operative procedure was a LAP versus a PD. SECONDARY AIM Identify specific clinical and demographic characteristics that contribute to both mortality and length of stay in this population. 24

25 Inclusion Criteria and Time frame Inclusion <1000 gm BW and <32 weeks GA. Surgical treatment for NEC at any of 27 regional NICUs participating in Children s Hospital Neonatal Consortium. January Feb the Exclusion Open database records. Spontaneous intestinal perforation, NEC totalis, volvulus, abdominal wall defects, congenital heart disease and other major anomalies. Initial surgery for NEC occurred prior to referral. 49 Distribution by site Site Code N LAP (n=369) DRAIN (n=169) K W Q F B U I O M R T L Z A P S D V G H C J N CC

26 Distribution by site Site Code N LAP (n=369) DRAIN (n=169) K W Q F B U I O M R T L Z A P S D V G H C J N CC ~1/3 drain ~1/3 drain ~1/3 drain 1/4-1/2 drain 51 Distribution by site Site Code N LAP (n=369) DRAIN (n=169) K W Q F B U I O M R T L Z A P S D V G H C J N CC Drain slightly > lap 52 26

27 Distribution by site Site Code N LAP (n=369) DRAIN (n=169) K W Q F B U I O M R T L Z A P S D V G H C J N CC drain >>> lap 53 Distribution by site Site Code N LAP (n=369) DRAIN (n=169) K W Q F B U I O M R T L Z A P S D V G H C J N CC Laps >>> drain 27

28 Distribution over time Total n Lap n Drain % Lap % Drain There may have been a slight trend towards more drains in the latter years, but this trend is NS (p=0.0592) 55 Baseline characteristics Variable {median [IQR] or n (%)} All (n=528) LAP (n=359) Drain (n=169) p-value Gestational age (weeks) 25 [24, 26] 25 [24, 26] 24 [23, 25] < PMA at admission to CHNC hospital (weeks) 28 [25, 30] 28 [26, 30] 26 [25, 28] < Birth weight (grams) 710 [600, 810] 720 [620, 825] 665 [560, 770] < Weight on admission to CHNC hospital (grams) 835 [700, 1090] 910 [740, 1140] 735 [615, 910] < Antenatal glucocorticoids received 259 (49) 177 (49) 82 (49) Apgar <5 at 5 minutes 147 (28) 91 (25) 56 (33)

29 Baseline characteristics Variable {median [IQR] or n (%)} All (n=528) LAP (n=359) Drain (n=169) p-value Severe IVH before admission 66 (13) 36 (10) 30 (18) PDA treated medically before admission 213 (40) 130 (36) 83 (49) Age of onset of NEC (days) 19 [9, 34] 21 [12, 36] 12 [7, 30] <0.001 Age at surgery (days) 21 [10, 36] 24 [14, 38] 13 [8, 27] < Time to surgery after admission (days) 0 [0, 5] 1 [0, 6] 0 [0, 3] Baseline characteristics Variable {median [IQR] or n (%)} All (n=528) LAP (n=359) Drain (n=169) p-value Perforation associated with the NEC 383 (73) 283 (66) 145 (86) < Sepsis on admission to CHNC hospital 80 (15) 51 (14) 29 (17) Hypotension requiring vasopressors at or shortly after admission 160 (30) 102 (28) 58 (34) Pre-operative ph* 7.3 [7.2, 7.3] 7.3 [7.2, 7.3] 7.2 [7.1, 7.3] Pre-operative PCO2 (mmhg)* 50 [41, 59] 50 [41, 58] 51 [40, 61] *Data available for 442/528 babies (306/359 in laparotomy group and 136/169 in drain group) 58 29

30 Non-GI clinical characteristics Variable {median [IQR] or n (%)} All (n=528) LAP (n=359) PD (n=169) p-value PDA treated medically at CHNC hospital 44 (8.33) 31 (8.64) 13 (7.69) PDA ligation at CHNC hospital 90 (17.05) 51 (14.21) 39 (23.08) Ventilator days 28.5 (10,52) 27 (9,49) 35 (10,55) BPD* 61 (11.55) 40 (11.14) 21 (12.43) Severe BPD 181 (34.28) 117 (32.59) 64 (37.87) PVL or encephalomalacia 59 (11.17) 34 (9.47) 25 (14.79) ROP stage 3 or tx with Surgery/Avastin 130 (24.62) 88 (24.51) 42 (24.85) * BPD = any O2 at 36 weeks PMA Severe BPD = On PPV or NC>2L or O2>30% at 36 weeks 59 Primary Outcome: Bivariate Analysis Death or SBS & Component Parts Variable [n (%)] All (n=528) LAP (n=359) Drain (n=169) p-value Death or SBS 233 (44) 155 (43) 78 (46) Death 173 (33) 104 (29) 69 (41) SBS 60 (17) 51 (14) 9 (5)

31 Primary Outcome : Bivariate Analysis Death or SBS & Component Parts Variable [n (%)] All (n=528) LAP (n=359) Drain (n=169) p-value Death or SBS 233 (44) 155 (43) 78 (46) Death 173 (33) 104 (29) 69 (41) SBS 60 (17) 51 (14) 9 (5) Primary Outcome : Bivariate Analysis Death or SBS & Component Parts Variable [n (%)] All (n=528) LAP (n=359) Drain (n=169) p-value Death or SBS 233 (44) 155 (43) 78 (46) Death 173 (33) 104 (29) 69 (41) SBS 60 (17) 51 (14) 9 (5)

32 Multivariable analysis Outcome: Death and/or Short Bowel Syndrome Predictors: Lap vs drain Age at Admission (days) Birth Weight SGA (< 10th%ile) Male Gender Sepsis present on admission [(+) blood culture)] Hypotension present on admission PDA treated medically before admission ph prior to surgery pco 2 prior to surgery Severe BPD Ventilator days 63 Multivariable Analysis Death or Short Bowel Syndrome Variable OR 95% CI p-value Laparotomy versus Drain Age at Admission (days) ph prior to surgery < Hypotension requiring vasopressors at or shortly after admission Interpretation of logistic regression for Death/SBS: Open laparotomy and drain peritoneal drain placement as initial surgery for NEC had similar rates of Death or SBS. Irrespective of the initial procedure for surgical NEC, Age at admission, pre-operative ph and hypotension increased the risk. Death or SBS increased by 2% for each day older a baby was upon admission Death or SBS increased by 40% for each 0.1 unit decrease in ph. 64 Death or SBS increased by 93% when the infant had hypotension requiring vasopressors. 32

33 Multivariable Analysis: Death Variable OR 95% CI p-value Laparotomy versus Drain ph prior to surgery < Hypotension requiring vasopressors at or shortly after admission Interpretation of the logistic regression model for Death: Open laparotomy and drain peritoneal drain placement as initial surgery for NEC had similar rates of Death. Irrespective of the initial procedure for surgical NEC, pre-operative ph and hypotension were associated with an increased risk of death. Death increased by 42% for each 0.1 unit decrease in ph. Death increased by 74% when the infant had hypotension requiring vasopressors. Note: Neither BW nor Age at Admission were significant in this model. 65 Multivariable Analysis: Short Bowel Syndrome Variable OR 95% CI p-value Laparotomy versus Drain Hypotension requiring vasopressors at or shortly after admission Age at Admission (days) Interpretation of the logistic regression model for Short Gut Syndrome: Babies who had Laparotomy as initial surgery for NEC were 2.25 fold more likely to develop SBS than babies who had a Drain Pre-operative hypotension was also associated with a 2.25-fold increased risk of SGS The risk of SBS increases by 2% for each day older at admission

34 Univariate Analysis: LOS Among Survivors: Variable (median [IQR]) All (n=355) LAP (n=255) Drain (n=100) p-value LOS in Hospital 125 [95, 169] 119 [92, 166] 140 [105, 185.5] LOS in NICU 118 [90, 163] 114 [86, 157] [102.5, 181] Multivariable analysis Outcome: Length of Hospital Stay Among Survivors Predictors: Lap vs drain Antenatal Steroids Gestational Age or Birthweight Age at Surgery (days) Sepsis present on admission ph prior to surgery Days to full feeds Number of surgeries Stricture CLABSI Surgical ligation of PDA ROP surgery Severe BPD 68 34

35 Multivariable Analysis: Hospital LOS Among Survivors Variable Estimate Standard Error p-value Laparotomy versus Drain Gestational Age (weeks) ph prior to surgery Stricture CLABSI < Severe BPD PDA ligation ROP requiring laser surgery or Avastin Interaction of PDA ligation and ROP requiring laser surgery or Avastin Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]

36 Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]. LOS increases by 5% for each 0.1 unit decrease in ph [exp( )=0.95]. 71 Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]. LOS increases by 5% for each 0.1 unit decrease in ph [exp( )=0.95]. LOS increases by 16% for infants that develop a stricture compared to infants with no stricture [exp(0.1563)=1.16]

37 Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]. LOS increases by 5% for each 0.1 unit decrease in ph [exp( )=0.95]. LOS increases by 16% for infants that develop a stricture compare to infants with no stricture [exp(0.1563)=1.16]. LOS increases by 28% for infants with a CLABSI compared to no CLABSI [exp(0.2505)=1.28]. 73 Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]. LOS increases by 5% for each 0.1 unit decrease in ph [exp( )=0.95]. LOS increases by 16% for infants that develop a stricture compare to infants with no stricture [exp(0.1563)=1.16]. LOS increases by 28% for infants with a CLABSI compare to no CLABSI [exp(0.2505)=1.28]. LOS increases by 20% for infants that develop severe BPD compared to no/mild/moderate BPD [exp(0.1838)=1.20]

38 Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]. LOS increases by 5% for each 0.1 unit decrease in ph [exp( )=0.95]. LOS increases by 16% for infants that develop a stricture compare to infants with no stricture [exp(0.1563)=1.16]. LOS increases by 28% for infants with a CLABSI compare to no CLABSI [exp(0.2505)=1.28]. LOS increases by 20% for infants that develop severe BPD compared to no/mild/moderate BPD [exp(0.1838)=1.20]. LOS increases by 30% for infants that undergo both PDA ligation & treatment for severe ROP compared to neither procedure or either alone [exp(0.2692)=1.30]. 75 Multivariable Analysis: Hospital LOS Among Survivors Interpretation of the model estimates: LOS increases by 6% for each one week decrease in gestational age [exp( )=1.06]. LOS increases by 5% for each 0.1 unit decrease in ph [exp( )=0.95]. LOS increases by 16% for infants that develop a stricture compare to infants with no stricture [exp(0.1563)=1.16]. LOS increases by 28% for infants with a CLABSI compare to no CLABSI [exp(0.2505)=1.28]. LOS increases by 20% for infants that develop severe BPD compared to no/mild/moderate BPD [exp(0.1838)=1.20]. LOS increases by 30% for infants that undergo both PDA ligation & treatment for severe ROP compared to neither or either alone [exp(0.2692)=1.30]. Hospital LOS is not affected by initial surgical procedure when the above factors 76 are taken into account. 38

39 Secondary outcomes Variable { median [IQR] or n (%) } All (n=528) LAP (n=359) Drain (n=169) p-value Central Line Days 63 [20, 108.5] 65 [23, 107] 55 [17, 114] Days TPN 64 [35, 109] 66 [34.5, 111.5] 63 [35, 104] CLABSI Rate* < Reached 100 kcal/kg/day 305 (58) 208 (58) 97 (57) Days to full feedings 66 [39, 100] 62.5 [36.5, 93] 71 [46, 107] * CLABSI rate = (# Central Line Associated Blood Stream Infections / # central line days) x Secondary outcomes Variable [n (%)] All (n=528) LAP (n=359) Drain (n=169) p-value Stricture 57 (10.8) 31 (8.6) 26 (15.4) Enterocutaneous fistula 25 (4.73) 13 (3.62) 12 (7.1) Evisceration 9 (1.7) 6 (1.67) 3 (1.78) Late ischemia 13 (2.46) 8 (2.23) 5 (2.96) Wound infection 33 (6.25) 22 (6.13) 11 (6.51)

40 Secondary outcomes Variable (median, [IQR]) All (n=528) LAP (n=359) Drain (n=169) p-value Total times baby went for surgery 2 [1, 3] 2 [1, 3] 2 [1, 3] Total surgical TF that involved an abdominal surgery 2 [1, 3] 2 [1, 3] 2 [1, 3] Secondary outcomes Variable All (n=528) LAP (n=359) Drain (n=169) p-value Breast Milk at 100 kcal/kg/day 164/305 (54) 109/208 (52) 55/97 (57) Breast Milk at discharge 61/291 (21) 45/212 (21) 16/79 (20) Home with ostomy or colostomy 80/291 (27) 56/212 (26) 24/79 (30) Home on tube feeds 110/291 (38) 77/212 (36) 33/79 (42) Home on TPN 14/291 (5) 13/212 (6) 1/79 (1) or more outpatient referrals at discharge 13/291 (46) 92/212 (43) 41/49 (52) All Data: [n/eligible (% of eligible)] 80 40

41 Summary Babies with surgical NEC and BW <1000 gm who received a peritoneal drain as the first surgical procedure were younger (both by GA and DOL) and lighter than babies who received a laparotomy as the first surgery. In multivariable analysis: There was no difference in the rate of the composite outcome Death or SBS between babies who received LAP and those that received a PD as the initial surgical procedure. Predictors of death included lower pre-operative ph and the presence of significant hypotension around the time of admission, but neither initial surgical procedure nor age. Survivors in the LAP group were 2.25 times more likely to develop structural or functional short bowel syndrome than survivors in the PD group. Other predictors of SBS include hypotension and older age at admission Summary (continued) In multivariable analysis, there was no difference in the Hospital LOS between babies who received LAP and those that received a PD as the initial surgical procedure for necrotizing enterocolitis. The following factors were identified as increasing hospital length of stay among babies <1000gm who survive surgical NEC: Lower GA at Birth (6% increase in LOS for each 1 week decrease in GA) Lower pre-operative ph (5% increase in LOS for each 0.1 unit decrease in ph) Stricture (16% increase in LOS) CLABSI (28% increase in LOS) Severe BPD (20% increase in LOS) PDA Ligation+Treatment for Severe ROP (30% increase in LOS) 41

42 Conclusion Surgical NEC is a rare but devastating disorder among premature infants High mortality rate Significant morbidities and increased LOS among survivors Initial surgical approach does little to alter outcomes Given the small number of babies in individual NICUs with Surgical NEC, The Children s Hospitals Neonatal Database is an ideal platform for evaluating outcomes of babies affected by this disease. Acknowledgements The Children s Hospitals Neonatal Consortium, its member institutions and all the babies/families cared for at CHNC centers. Statistician: Isabella Zaniletti Surgical NEC focus group members: Irfan Ahmad Beverly Brozanski Bob DiGeronimo Levi Fuches Karna Murthy Pritha Nayak Mike Padula Anthony Piazza Kristina Reber Jessica Roberts Joti Sharma Rajan Wadhawan 42

43 Thank You Questions? 43