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How much evidence is needed to prove the association between a condition and a comorbidity?

Several studies have looked into the possible influence of obesity and the incidence of bedwetting, nocturnal enuresis and the chance of success of treatment [1–3].

A statistics teacher once told me that if you choose the correct statistical tool, you can prove any association between two things.  So let us look at these studies with a critical view.

Warner et al. have interviewed more than 4,000 first-grade Danish children and almost 3,000 adolescents from the seventh to ninth grade during a school nurse visit and asked specifically about incontinence, nocturia and nocturnal enuresis [1]. It seems that “some form of incontinence” is quite common in first-grade children, with daytime incontinence in 22% and nocturnal enuresis in 17%. In these children, the prevalence of symptomatic obese children was not different from the non-symptomatic children.  In the adolescent age group, daytime incontinence was still 4.5% and nocturnal enuresis was 1%. However, the prevalence of obese symptomatic children was higher as well as in the daytime incontinence as in the nocturnal enuresis group. The authors conclude a two-fold increased risk for nocturnal enuresis or nocturia in the adolescent-age group. However, they have correctly analysed that there is no direct association between obesity and a specific incontinence type.  

Ma et al. have looked retrospectively into their patient population, from a clinic in a large hospital in Beijing, China, diagnosed with nocturnal enuresis [2]. 666 patients have been seen in their clinic with nocturnal enuresis over a period of 1.5 years. It was interesting to see that there was a 50/50 distribution between girls and boys, whereas we usually expect to see more boys with nocturnal enuresis. In addition, only 30% of the children had a positive family history.  

The authors describe overweight children as children with a BMI between 85th and 94th percentile and obese children with a BMI higher than their 95th percentile. Although this is not an ICCS terminology, the authors have additional categorized their patients in mild-moderate and severe nocturnal enuresis. They have found a (10%) higher incidence of obese children in the “severe” enuresis patients.  

The authors have also looked into the obesity as comorbidity factor and effect of treatment. However, their treatment strategy is, what they call “behavioural treatment”. Behavioural treatment involves suggestion for voiding pattern, limiting fluid intake, carrying the child to the toilet at night, providing motivation and exercises aiming to increase voided volumes and treating constipation if present. The authors have found that the (complete) success rate of “the behavioural treatment” was lower in children with obesity. It must be emphasized that none of the children have received treatment with desmopressine nor the alarm treatment.  

Zhang et al. have performed a questionnaire study in 8 Chinese cities and included almost 24,000 primary school children [3]. The authors emphasized the fact that they only include prepubertal children in this study. The questionnaire included sociodemographic characteristics, sleeping patterns and behaviour of the child, as well as, quality of life and emotions. The authors have found a statistical significant relationship between nocturnal enuresis and the following factors: Obesity, snoring, ADHD, depressive moods, asthma, large housing, large families in one home, and a higher income of the parents. This study includes a lot and several different statistical analyses, however any logic hypothesis to explain any of the correlations lack any scientific evidence.  

In summary, do we have to inform our patients that obesity is one of the causes of their nocturnal enuresis, and that their success of treatment will be lower? At present, I think that it is too early to do so. More good evidence is needed.

[1] Warner TC, Baandrup U, Jacobsen R, Bøggild H, Aunsholt Østergaard PS, Hagstrøm S. Prevalence of nocturia and fecal and urinary incontinence and the association to childhood obesity: a study of 6803 Danish school children. J Pediatr Urol 2019;15:225.e1-225.e8. doi:10.1016/j.jpurol.2019.02.004.
[2] Ma Y, Shen Y, Liu X. Association between enuresis and obesity in children with primary monosymptomatic nocturnal enuresis. Int Braz J Urol 2019;45:790–7. doi:10.1590/S1677-5538.IBJU.2018.0603.
[3] Zhang A, Li S, Zhang Y, Jiang F, Jin X, Ma J. Nocturnal enuresis in obese children: a nation-wide epidemiological study from China. Sci Rep 2019;9:1–8. doi:10.1038/s41598-019-44532-5.