Aspects of abdominal surgery in children

Knowledge of long-term consequences following abdominal surgery in children and infants is crucial as the child will live and develop with possible risks and adverse effects for a lifetime. Children's postoperative development is challenging to predict as there is a complex interaction with several biological-, psychological- and social functions that can affect each other dynamically for a long time.

The overall aim of this doctoral thesis was to improve our understanding of long- term consequences following paediatric abdominal surgery. The studies focused on intra-abdominal adhesions, treatment of adhesive small bowel obstruction (ASBO) and long-term outcomes in the aspects of neuropsychiatric dysfunction. Finally psychiatric illness after childhood appendectomy and a possible link to the gut microbiome was explored.

In study I we conducted a retrospective study of 619 individuals with appendectomy before the age of 15. The occurrence of ASBO was compared after open appendectomy (OA) and laparoscopic appendectomy (LA) and risk factors for ASBO were identified. Age, sex and proportion of perforated appendicitis were comparable between the LA and OA groups. Median follow-up time was 11.4 years (2.6-18.4). The risk for ASBO was related to perforated appendicitis and postoperative intra-abdominal abscess and not to the surgical method. Perforation increased the risk for ASBO hazard ratio (HR) 9.03 (95% CI 2.44-33.34; p =< 0.001) and postoperative intraabdominal abscess HR 6.98 (95% CI 1.89-25.81; p=0.004).

In study II we conducted a retrospective study of 101 individuals who were hospitalized for a total of 137 episodes of ASBO before the age of 15. In 58.4% the first surgery was performed during the neonatal period. Median time to the first ASBO was 3.76 months and median follow-up was 11.3 (0.6-19) years. In the cohort 86.6% of the children required surgical treatment for ASBO and the rate of complications following surgery for ASBO was 52%, registered according to the Clavien Dindo Classification of Surgical Complications. A substantial cost was related to the treatment of ASBO.

In study III we compared a cohort of 485 individuals who were exposed to abdominal surgery during infancy to a cohort of 4835 unexposed controls matched by sex, age and gestational week in a population-based register study. Median gestational age was 38 weeks (24-44) and median age at surgery was seven days (0-365). Surgery was performed before 44 gestational weeks in 70%. Exposure to anaesthesia and abdominal surgery during infancy was not associated with cognitive dysfunction from the perspective of educational level, disposable income and ADHD in adolescent and adult individuals.

In study IV we compared a cohort of 752 individuals from study II who were exposed to appendectomy before 15 years of age to a cohort of individually- matched 3760 unexposed individuals in a population-based register study. Median follow-up time was 15.5 (6-21) years. We found that childhood appendectomy increased the risk of psychiatric illness, HR 1.19 (95% CI 1.04-1.37; p=0.013) in general and for affective disorders HR 1.20 (95% CI 1.01-1.42; p=0.038). The healthcare consumption was also significantly increased following childhood appendectomy.

In study V we added microbiome data from faecal samples to national population-based registers on 155 exposed individuals from study IV. A psychiatric diagnosis was found in 56 (36.1%) individuals. The microbiome was compared between individuals with psychiatric illness to individuals without. We identified significant changes in bacterial taxa within each diagnostic subgroup, with patterns of both up- and downregulation. Among these findings, we observed a downregulation of taxa associated with anti-inflammatory processes and an upregulation of taxa previously associated with pro-inflammatory processes. In addition, the microbial profile became less diverse as the number of psychiatric diagnoses increased in an individual.

In conclusion, the results of this thesis contributes to both novel and expanded knowledge in aspects of abdominal surgery in children. Highlighting the importance of having both short- and long-term perspectives in paediatric studies. Future studies are needed to develop safe management guidelines for the treatment of ASBO, appendicitis and infant abdominal surgery.

List of scientific papers

I. Adhesive small bowel obstruction after appendectomy in children - Laparoscopic versus open approach. Cecilia Arana Håkanson, Fanny Fredriksson, Helene Engstrand Lilja. Journal of Pediatric Surgery. 2020;55(11):2419-2424. https://doi.org/10.1016/j.jpedsurg.2020.02.024

II. Paediatric adhesive small bowel obstruction is associated with a substantial economic burden and high frequency of postoperative complications. Cecilia Arana Håkanson, Fanny Fredriksson, Helene Engstrand Lilja. Journal of Pediatric Surgery. 2023;58(11):2249-2254. https://doi.org/10.1016/j.jpedsurg.2023.05.017

III. Attention deficit hyperactivity disorder and educational level in adolescent and adult individuals after anesthesia and abdominal surgery during infancy. Cecilia Arana Håkanson, Fanny Fredriksson, Helene Engstrand Lilja. PLoS One. 2020;15(10):e0240891. https://doi.org/10.1371/journal.pone.0240891

IV. Childhood appendectomy and subsequent psychiatric illness. Cecilia Arana Håkanson, Fredrik Stiger, Nele Brusselaers, Helene Engstrand Lilja. PLOS Mental Health. 2025;2(1):e0000219. https://doi.org/10.1371/journal.pmen.0000219

V. Alterations in the gut microbiome following childhood appendectomy and subsequent psychiatric disease. Cecilia Arana Håkanson, Marcela Pereira, Marina Carrera-Dulsat, Fredrik Stiger, Ann-Marie Kassa, Lars Engstrand, Nele Brusselaers, Helene Engstrand Lilja. [Manuscript]