Preoperative anemia linked to postsurgical mortality in neonates

Neonates with preoperative anemia experienced a higher rate of in-hospital mortality after noncardiac surgery than neonates without anemia, according to retrospective study results.

The researchers identified a preoperative hematocrit level below 40% as an appropriate cutoff from predicting in-hospital mortality.

“Neonates have a high incidence of perioperative mortality worldwide,” Susan M. Goobie, MD, FRCPC, assistant professor of anesthesia at Harvard Medical School and associate in perioperative anesthesia at Boston Children’s Hospital, and colleagues wrote. “In a 2015 study, the incidences of 24-hour and 30-day mortality in children were 13.3 per 10,000 operations and 41.6 per 10,000 operations, respectively, [whereas] a higher 30-day postoperative mortality rate of 386.5 per 10,000 was reported in the neonatal population. ... To our knowledge, incidence of postoperative neonatal mortality in U.S. hospitals has never been reported.”

Goobie and colleagues identified 2,764 neonates (age range, 0-30 days) in the American College of Surgeons National Surgical Quality Improvement Program database with a preoperative hematocrit value reported. The entire database included 40,897 children with a hematocrit value.

The researchers compared demographic and postsurgical outcomes among neonates with and without preoperative anemia — defined as a hematocrit level below 40%.

Neonates included in the study had a median hematocrit value of 38% (interquartile range, 34-41). Most neonates were boys (64.5%), of non-Hispanic white race (66.3%), were full-term (greater than 36 weeks’ gestation, 69.9%) and weighed more than 2 kg (85%).

The in-hospital mortality rate after surgery was greater among neonates than among the collective age groups in the database (3.4% vs. 0.6%).

The researchers used the Youden J index to identify a preoperative hematocrit level less than 40% as the optimal cutoff for predicting mortality.

A receiver operating characteristic analysis found an association between preoperative hematocrit level and in-hospital mortality after surgery (area under the curve, 0.74; 95% CI, 0.68-0.8).

Thirty-one percent (n = 825) of neonate survivors had a hematocrit level of 40% or more, whereas 72% (n = 67) of neonates who died had a hematocrit level below 40%.

Multivariate analyses identified preoperative anemia as an independent predictive factor for in-hospital mortality (OR = 2.62; 95% CI, 1.51-4.57), with a significantly higher percentage of neonates with an anemia hematocrit level experiencing in-hospital death after surgery (7.5% vs. 1.4%; P < .001).

A validation cohort of 1,384 neonates confirmed the initial findings. Twenty-eight neonates died, which translated to a postsurgical mortality rate of 2% and a significant difference in median hematocrit levels between survivors and nonsurvivors (43.3% vs. 36.9%; P < .001).

A receiver operating characteristic analysis of the validation cohort confirmed the association (area under the curve, 0.7; 95% CI, 0.61-0.8).

The researchers acknowledged study limitations, including the potential for missing data, miscoding or inaccurate data collection associated with retrospective studies.

They further noted that because the database excludes many low-risk procedures, neonates included in the study may have been considered unusually high risk.

“To our knowledge, this is the first study to define the incidence of preoperative anemia in neonates, the incidence of postoperative in-hospital mortality in neonates, and the association between neonatal anemia and postoperative mortality in U.S. hospitals,” Goobie and colleagues wrote. “Timely diagnosis, prevention and appropriate treatment of preoperative anemia in neonates might improve outcomes and survival.”

These data should lead to further prospective research investigating the relationship between anemia and surgical outcomes among neonates, Rosemary D. Higgins, MD, neonatologist at Eunice Kennedy Shriver National Institute of Child Health and Human Development, Ravi Mangal Patel, MD, MSc, assistant professor of pediatrics at Emory University School of Medicine, and Cassandra D. Josephson, MD, professor of pathology and laboratory medicine at Emory University School of Medicine, wrote in an accompanying editorial.

“Because the authors did not control for type of surgery, the association between hematocrit and mortality may be confounded by surgical case mix between anemic and nonanemic groups,” Higgins, Patel and Josephson wrote. “If these critically ill neonates had an increase in their hematocrit prior to surgery, would their survival improve? The information provided by Goobie and colleagues is certainly thought-provoking. They are hypothesis-generating observational data that suggest optimizing preoperative hematocrit may improve postoperative survival, particularly in neonates who weigh less than 2 kg, are on mechanical ventilation prior to surgery, or are receiving inotropic medication prior to surgery.” – by Cameron Kelsall

Disclosures: The researchers report no relevant financial disclosures. Josephson reports a consultant role with Biomet Zimmer and Immocur. Higgins and Patel report no relevant financial disclosures.