Long term outcome following NEC

Myron Yaster MD, Michael E. Nemergut MD PhD, and Stephen J. Gleich MD

In the middle of the night when providing anesthesia for an emergency exploratory laparotomy for necrotizing enterocolitis (NEC), I always wondered what was the long term outcome of NEC on these extremely low birth weight infants?  Was the surgery futile? Were these children developmentally normal?  How did the disease and loss of bowel affect their growth and quality of life? I’m pretty sure many of you have had similar thoughts and questions.  Today’s PAAD provides several answers.  Because I am neither expert nor particularly knowledgeable about the tools used in neurodevelopmental assessment, I asked Drs. Mike Nemergut and Steve Gleich of the Mayo clinic, who do have this expertise and are frequent contributors to the PAAD to help. Myron Yaster MD  

PS: Welcome back from Thanksgiving! I hope you all enjoyed it as much as I did

Original article

Ruben Vaidya, Joe X Yi, T Michael O'Shea, Elizabeth T Jensen, Robert M Joseph, Jeffrey Shenberger, Semsa Gogcu, Kathryn Wagner, Michael E Msall, Amanda L Thompson, Jean A Frazier, Rebecca Fry, Rachana Singh, ELGAN-ECHO Study Investigators.  Long-Term Outcome of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation. Pediatrics. 2022 Nov 1;150(5):e2022056445  PMID: 36200375

“Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are gastrointestinal complications in preterm infants associated with high morbidity and mortality in extremely low birth weight (ELBW) infants.  NEC is characterized by ischemic necrosis of the intestinal mucosa, severe inflammation, invasion by enteric gas-forming organisms, and dissection of gas into the bowel wall and portal venous system.  Pathophysiology of SIP is distinct from NEC and typically presents as a focal intestinal perforation at the terminal ileum.  Among ELBW infants, the incidence of NEC is ∼7%, whereas the incidence of SIP is 3% to 8%.”1 In this study, Vaidya et al. compared anthropometric and neurodevelopmental (ND) outcomes, at 10 and 15 years, for children born at 23-27 weeks’ gestational age with medical NEC, surgical NEC, SIP, and neither NEC nor SIP.

Many of the strengths of this study include use of  validated tools by examiners who were masked to the children’s neonatal histories, utilization of several individually administered tests of achievement, and inclusion of a wide array of standardized testing in motor function, cognitive outcomes, IQ, neuropsychological function and ADHD.   

First the reassuring news:  There were no differences in long-term neurodevelopmental outcomes when comparing infants with surgical or medical NEC or SIP to controls without NEC/SIP in this study population. 

However, there was growth impairment that persisted throughout late childhood.  “Children with medical NEC had similar weight, BMI, height, and head circumference compared with controls at both 10 and 15 years. At 15 years, children with surgical NEC had lower weight z-score (adjusted β: −0.75, 95% confidence interval [CI]: −1.25 to −0.25), lower BMI z-score (adjusted β: −0.55, 95% CI: −1.09 to −0.01), and lower height z-score (adjusted β: −0.65, 95% CI: −1.16 to −0.14). Children with SIP had lower weight and height z-scores at age 10 years when adjusted for sample attrition, but these differences were not significant when adjusted for confounders.”1

As many of you who are frequent readers of the PAAD know, I (MY) am extremely skeptical about the effects of general anesthesia on neuroapoptosis and neuro development.  One of the limitations of the study is the “lack of detailed information about exposure to anesthesia and pain medications, and the occurrence of short gut syndrome, factors that have been shown to negatively influence neurodevelopmental outcomes in multiple studies.”1  Additionally, perturbations in physiologic parameters, such as hypotension, are not reported.  While these details would be interesting to see, do they matter in this study? 

Many patients with surgical NEC arrive to the operating room in extremis.  Further, many likely had several operations to address NEC.  Consequently, in this study of the sickest of the sick, in a group of babies at high risk of neurodevelopmental insult, patients who underwent surgical exploration (presumably with general anesthesia) had neurodevelopmental outcomes that were no different than premature infants who did not undergo surgery for NEC.   These data suggest that, even if one assumes an impact of anesthetics on ND development (MY-dubious!), it is not additive to the impact of extreme prematurity.

Indeed, “Overall, these findings should offer encouragement to parents and clinicians caring for extremely premature low birth weight infants who encounter the devastating short-term effects of NEC or SIP, while acknowledging that there are multiple factors after discharge from hospital that can potentially impact these outcomes and it may not be possible to adjust for all cofounders in any study.”1

From our perspective, this is another nail in the neuroapoptosis coffin.

References

1.           Vaidya R, Yi JX, O’Shea TM, et al. Long-Term Outcome of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation. Pediatrics. 2022;150(5):e2022056445. doi:10.1542/peds.2022-056445