Childhood appendicitis and future risk of inflammatory bowel disease - A nationwide cohort study in Sweden 1973-2017.

AIM: The aim of this study was to investigate the association between juvenile appendicitis, treated conservatively or with appendectomy, and adult risk of inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD). We used nationwide population data from more than 100,000 individuals followed for over four decades. METHOD: All Swedish patients discharged with a diagnosis of appendicitis before the age of 16 years between 1973 to 1996 were identified. Everyone diagnosed with appendicitis was matched to an individual in the general population without a history of juvenile appendicitis (unexposed) of similar age, sex and region of residence. The study population was retrospectively followed until 2017 for any development of UC or CD. Cox proportional-hazards models compared disease-free survival time between exposed and unexposed individuals, also analysing the impact of treatment (conservative treatment versus appendectomy). RESULTS: The final cohort consisted of 52,391 individuals exposed to appendicitis (1,674,629 person years) and 51,415 unexposed individuals (1,638,888 person years). Childhood appendicitis with appendectomy was associated with a significantly lower risk of adult IBD [adjusted hazard ratio (aHR) 0.48 (0.42-0.55)], UC [aHR 0.30 (0.25-0.36)] and CD [aHR 0.82 (0.68-0.97)]. Those treated conservatively had a lower risk of adult UC [aHR 0.29 (0.12-0.69)] but not CD [aHR 1.12 (0.61-2.06)] compared with unexposed individuals. CONCLUSION: Juvenile appendicitis treated with appendectomy was associated with a decreased risk of adult IBD, both UC and CD. Those treated conservatively instead of with surgery had a lower risk of UC only. Our findings warrant more research on the role of the appendix and gut microbiota in the pathogenesis of IBD.

Caesarean section and its relationship to offspring general cognitive ability: a registry-based cohort study of half a million young male adults.

BACKGROUND: A relationship between caesarean section and offspring cognitive ability has been described, but data are limited, and a large-scale study is needed. OBJECTIVE: To determine the relationship between mode of delivery and general cognitive ability. METHODS: A cohort of 579 244 singleton males, born between 1973 and 1987 who conscripted before 2006, were identified using the Swedish population-based registries. Their mode of delivery was obtained from the Swedish Medical Birth registry. The outcome measure was a normalised general cognitive test battery (mean 100, SD 15) performed at military conscription at around age 18. FINDINGS: Males born by caesarean section performed poorer compared with those born vaginally (mean score 99.3 vs 100.1; adjusted mean difference -0.84; 95% CI -0.97 to -0.72; p<0.001). Both those born by elective (99.3 vs 100.2; -0.92; 95% CI -1.24 to -0.60; p<0.001) and non-elective caesarean section (99.2 vs 100.2; -1.03; 95% CI -1.34 to -0.72; p=0.001), performed poorer than those born vaginally. In sibling analyses, the association was attenuated to the null (100.9 vs 100.8; 0.07; 95% CI -0.31 to 0.45; p=0.712). Similarly, neither elective nor non-elective caesarean section were associated with general cognitive ability in sibling analyses. CONCLUSION: Birth by caesarean section is weakly associated with a lower general cognitive ability in young adult males. However, the magnitude of this association is not clinically relevant and seems to be largely explained by familial factors shared between siblings. CLINICAL IMPLICATION: Clinicians and gravidas ought not to be concerned that the choice of mode of delivery will impact offspring cognitive ability.

The association between birth by cesarean section and adolescent cardiorespiratory fitness in a cohort of 339,451 Swedish males.

Birth by cesarean section is increasing worldwide and associates with offspring morbidities capable of adversely impacting cardiorespiratory fitness later in life. Whether birth by cesarean section associates with lower levels of cardiorespiratory fitness later in life is unknown and is of interest to public health. Four Swedish national registers were linked to follow 339,451 singleton males, born between 1973-1987 until December 31 2005, for Watt-maximum achieved on a cycle ergometer test at conscription into the Swedish military. Main exposure was birth by cesarean section which was compared to vaginal birth. A sub-population of 45,999 males born between 1982-1987 was identified to explore differentiated associations between elective and non-elective cesarean section with Watt-maximum. Within-family analyses of 34,252 families with 70,632 biological male siblings, who conscripted during the study period, were performed to explore the role of familial confounding on Watt-maximum. Swedish males born by cesarean section achieved lower mean Watt-maximum (- 2.32 W, 95%C.I. - 2.90 to - 1.75) and displayed excess odds of low cardiorespiratory fitness (aOR = 1.08, 95%C.I. 1.05 to 1.11) at conscription in the eighteenth life-year compared to males born vaginally after adjusting for birth characteristics, maternal morbidities and parental socioeconomic position. In the sub-population, males born 1982-1987, there was a greater negative association of elective cesarean section with cardiorespiratory fitness (- 4.42 W, 95%C.I. - 6.27 to - 2.57, p < 0.001) than non-elective cesarean sections (- 1.96 W, 95%C.I. - 3.77 to - 0.16, p = 0.033) as compared to vaginal births. No associations between modes of cesarean delivery and cardiorespiratory fitness levels persisted in the within-family analyses where biological male siblings were compared whilst controlling for factors shared within families. Males born by cesarean section had lower levels of cardiorespiratory fitness eighteen years later compared to males born vaginally. These findings appear to be largely explained by factors of familial confounding.

Childhood appendectomy and adult mental disorders: A population-based cohort study.

BACKGROUND: Recent studies suggest that disruption of the colonic microbiota homeostasis is associated with low-grade systemic inflammation and mental disorders. The cecal appendix may influence the homeostasis of the colonic microbiota. In this large population-based study, we investigated whether early removal of the appendix is associated with an increased risk of mental disorders later in life. MATERIALS AND METHODS: All Swedish individuals born between 1973 and 1992 (N = 1,937,488) were included and followed prospectively until December 31, 2016 for any psychiatric International Classification of Disease diagnosis from age 14 or later in life. The main exposure was defined as having a history of appendectomy before age 14 (N = 44,259); the second exposure, appendicitis before age 14 but without appendectomy (N = 1,542), and the third exposure studied was a history of hernia surgery before age 14 (N = 35,523). Control groups for each respective exposure were all unexposed individuals in the study population. RESULTS: Individuals exposed to appendectomy before age 14 had a 19% increased risk of depressive disorder (adjusted hazard ratio [aHR] = 1.19; 95% confidence interval [95% CI]: 1.15-1.23), 27% increased risk of bipolar affective disorder (aHR = 1.27; 95% CI: 1.17-1.37), and a 20% increased risk of an anxiety disorder (aHR = 1.20; 95% CI: 1.16-1.23) compared to individuals unexposed to childhood appendectomy. We found no association between appendectomy and increased risk of obsessive-compulsive disorder and schizophrenia and there was no association between appendicitis without appendectomy and mental disorders. The association between childhood hernia surgery and mental disorders later in life was small but significant. CONCLUSION: Childhood appendectomy, but not appendicitis without appendectomy, was associated with a significantly increased risk of mood and anxiety disorders in adulthood.