1. Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Preoperative Anemia and Postoperative Mortality in Neonates Goobie SM, Faraoni D, Zurakowski D, DiNardo JA. Association of preoperative anemia with postoperative mortality in neonates. JAMA Pediatr. Published online July 18, 2016. doi:10.1001/jamapediatrics.2016.1032.

2. Copyright restrictions may apply Background –Neonates undergoing noncardiac surgery are at risk for adverse outcomes. Preoperative anemia is a strong independent risk factor for postoperative mortality in adults. This association has not been investigated in the neonatal population. Study Objective –To assess the association between preoperative anemia and postoperative mortality in neonates undergoing noncardiac surgery in a large sample of US hospitals. Introduction

3. Copyright restrictions may apply Study Design –Retrospective study using data from the 2012 and 2013 pediatric databases of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Setting –Neonates (0-30 days old) undergoing noncardiac surgery in US hospitals. Patients –All neonates (0-30 days old) with a recorded preoperative hematocrit value who were undergoing noncardiac surgery were included. –Exclusion criteria were children who had a preoperative transfusion and neonates with congenital heart disease. Methods

4. Copyright restrictions may apply Outcomes –Owing to the lack of a universally accepted definition of anemia in neonates and also because of the wide reference range of acceptable hematocrit values for this age group, preoperative hematocrit was used as a continuous variable in receiver operating characteristic curve analysis to assess the relationship between preoperative hematocrit and mortality and for determining the optimal cutoff (Youden J Index) to define anemia in the neonatal population. –Demographic and postoperative outcomes variables were compared between anemic and nonanemic neonates. –Univariate and multivariable logistic regression analyses were used to determine factors associated with postoperative neonatal mortality. –An external validation was performed using the 2014 ACS NSQIP database. Methods

5. Copyright restrictions may apply Methods Limitations –This study included only neonates from hospitals in the NSQIP database (typically larger academic centers); therefore, the findings may not be generalizable to all hospitals caring for neonates in the United States such as smaller community hospitals. –Because the NSQIP data collection excludes herniorraphy, myringotomy tube placement, and other low-risk procedures, it is a selective sample of disproportionately high-risk procedures. Consequently, there is likely undersampling of the lowest-risk patients and selective sample bias. –Confounding by indication may also be a factor influencing these results because anemic patients may well be the sicker, higher-risk patients. However, no increased incidence of mortality was found when stratified for surgical type or complexity. Furthermore, the study controlled for this using multivariate analysis and a robust receiver operating characteristic curve; a hematocrit level <40% held as an independent risk factor for increased mortality.

6. Copyright restrictions may apply Results Neonates accounted for 2764 children (7%) with a recorded preoperative hematocrit level in the 2012-2013 ACS NSQIP databases. Neonates undergoing noncardiac surgery in US hospitals had a higher (3.4%) postoperative in-hospital mortality rate than older children, in whom the postoperative mortality rate was 0.6%. The incidence of preoperative neonatal anemia, defined as a hematocrit level <40%, was 32% (892 of 2764). Multivariable regression analysis demonstrated that preoperative anemia was an independent risk factor for mortality (odds ratio = 2.62; 95% CI, 1.51-4.57) in neonates undergoing noncardiac surgery in US hospitals. The prevalence of postoperative in-hospital mortality was significantly higher in neonates with a preoperative hematocrit level <40%, being 7.5% (95% CI, 1%-10%) vs 1.4% (95% CI, 0%-4%) for preoperative hematocrit levels ≥40%. The relationship between anemia and in-hospital mortality was confirmed in the validation cohort (NSQIP 2014).

7. Copyright restrictions may apply Results Comparison of Anemic and Nonanemic Neonates

8. Copyright restrictions may apply Results Multivariable Analysis of Factors Associated With Postoperative In-Hospital Mortality (N = 2764)

9. Copyright restrictions may apply Probability of In-Hospital Mortality Based on Multivariable Predictors a Results

10. Copyright restrictions may apply Comment This is the first report to define the incidence of preoperative anemia in neonates (32%), the incidence of postoperative in-hospital mortality in neonates (3.4%), and the association between preoperative anemia and postoperative mortality in neonates undergoing noncardiac surgery in US hospitals. This is the first report of a strong association between preoperative anemia and postoperative mortality in neonates undergoing noncardiac surgery. The incidence of preoperative neonatal anemia in this database, defined as a hematocrit level <40%, was 32% (892 of 2764). More than 70% of neonates who died had a hematocrit level <40%, compared with 31% of survivors who had a preoperative hematocrit level <40%. Postoperative in-hospital mortality was higher in neonates with preoperative anemia (hematocrit level <40%) when controlling for the other independent risks factors: American Society of Anesthesiologists class, body weight, preoperative inotropic support, or preoperative mechanical ventilation. This association held despite the study’s liberal definition of neonatal anemia as a hematocrit level <40%, which is considered mild or, at most, moderate anemia.

11. Copyright restrictions may apply This study’s results call into question the current trend of using a restrictive hematocrit strategy vs a liberal hematocrit strategy in neonatal blood management. Given that mild to moderate anemia in neonates has a strong independent association with mortality, consideration may be given to a target hematocrit level ≥40% in high-risk infants (American Society of Anesthesiologists classification of 3-5, weight ≤2 kg, preoperative mechanical ventilation, and inotropic support) to possibly minimize mortality associated with anemia. However, while this study has identified a strong independent association between preoperative anemia and postoperative neonatal mortality, no causative conclusions can be drawn. Timely diagnosis, prevention, and appropriate treatment of preoperative anemia in neonates might improve postoperative outcomes and survival. Comment

12. Copyright restrictions may apply If you have questions, please contact the corresponding author: –Susan M. Goobie, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (susan.goobie@childrens.harvard.edu). Funding/Support This work was supported by the Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts. Conflict of Interest Disclosures None reported. Contact Information