# Neurobehavioral Disorders after Appendectomy in Childhood

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $711,195

## Abstract

ABSTRACT
Concern about neurotoxicity following exposure to surgery and anesthesia in childhood has persisted for nearly
two decades, in part because there is no conclusive evidence to prove that it exists, nor is there adequate
evidence to prove that it does not. Large-scale observational studies evaluating neurobehavioral outcomes
after exposures to anesthesia and surgery have generated variable results, but none have demonstrated
actionable, un-confounded evidence suggesting increased risk. This proposal seeks to better define the
association between exposure to anesthesia and surgery and subsequent neurobehavioral disorders (defined
as behavioral disruptive disorders, mood disorders, and anxiety disorders) through a new analysis of existing
Medicaid data that has the potential to overcome limitations of previous studies. This study uses a new
approach for examining the question by: (1) using a natural experiment that reflects a stochastic exposure to
surgery (the near random event of appendectomy after controlling for age, sex and race) that is not associated
with lifestyle or disease-related treatments that may themselves be associated with long-term neurobehavioral
outcomes, and (2) through the use of multivariate matching techniques to account for potential observable
baseline differences in cohorts, we have the ability to compare an exposed cohort of approximately 68,000
pediatric appendectomy patients with 340,000 matched controls that are closely balanced for both observable
and potentially unobservable risk factors. This enables us to better study if there is a long-term association
between operative exposure with general anesthesia and subsequent adverse neurobehavioral outcomes in
children. Finally, (3) we will also examine a 68,000-patient medical control group with acute medical conditions
such as gastroenteritis, cellulitis and, community-acquired pneumonia to examine if neurobehavioral disorders
are elevated in this group not exposed to surgery or anesthesia. The study will examine outcomes of ADHD,
conduct disorders, anxiety, depression and bipolar disorder, to conduct a multivariate matched cohort study to
compare the hazard of study outcomes between exposed and unexposed children in Medicaid. We
hypothesize that patients with appendectomy will have an elevated hazard of these study outcomes as
compared to controls. We will identify all patients who underwent appendectomy from ages 3 to 15 years, and
match each patient to 5 controls who were the same age, omitting any exposed or control patient with a
baseline history of neurobehavioral disorders in the primary analysis or with evidence of complex chronic
disease, and perform a second 1:1 match between the appendectomy treated group and children who were
admitted for acute medical conditions. The results of this study will be generalizable beyond appendectomy
precisely because appendicitis occurs randomly (after matching on age, sex, and race) and should aid in
informing caregiv...

## Key facts

- **NIH application ID:** 10159944
- **Project number:** 5R01HD101415-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** JEFFREY H SILBER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $711,195
- **Award type:** 5
- **Project period:** 2020-05-06 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159944

## Citation

> US National Institutes of Health, RePORTER application 10159944, Neurobehavioral Disorders after Appendectomy in Childhood (5R01HD101415-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10159944. Licensed CC0.

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