Early childhood psychological factors and risk for bedwetting at school age in a UK cohort

The sample comprised participants from the Avon Longitudinal Study of Parents and Children. Detailed information about ALSPAC is available on the study website (http://​www.​bristol.​ac.​uk/​alspac), which includes a fully searchable dictionary of available data (http://​www.​bris.​ac.​uk/​alspac/​researchers/​data-access/​data-dictionary). Pregnant women resident in the former Avon Health Authority in south-west England, having an estimated date of delivery between 1/4/91 and 31/12/92 were invited to take part, resulting in a cohort of 14,541 pregnancies and 13,973 singletons/twins (7217 boys and 6756 girls) alive at 12 months [19]. Ethical approval for the study was obtained from the ALSPAC Law and Ethics committee and local research ethics committees.

At ages 4¹/₂, 5¹/₂, 6¹/₂, 7¹/₂ and 9¹/₂ years (hereafter referred to as 4–9 years) parents were asked “How often usually does your child wet the bed?” and were given the options ‘never’; ‘less than once a week’; ‘about once a week’; ‘2–5 times a week’; ‘nearly every night’; ‘more than once a night’. Previously, we used these repeated measures data to identify trajectories of typical and atypical development of nighttime bladder control using longitudinal latent class analysis (LLCA) [18]. LLCA is a useful tool to examine developmental trajectories of disorders because it provides an empirical means of summarising large amounts of data and identifying clusters of individuals (latent classes) with typical and atypical courses of development. We derived an ordinal measure by collapsing the bedwetting frequency data into a three-level variable indicating no current bedwetting, infrequent bedwetting (less than once a week or about once a week) and frequent bedwetting (2–5 times a week, nearly every night or more than once a night). The latter category corresponds to the frequency of bedwetting required for a DSM-V diagnosis of nocturnal enuresis. LLCA examines response strings that describe each child’s longitudinal pattern of frequency of bedwetting (no bedwetting, 0; infrequent bedwetting, 1; frequent bedwetting, 2) from 4 to 9 years. For instance, the data for a child who attains nighttime bladder control at an early age may be “10,000”; a child who experiences delayed attainment (at around 6 years) might have the response “21,000” and the response pattern for a child with persistent and frequent bedwetting may be “22,221”. The model assumes that observed heterogeneity in responses is due to a latent (unobserved) grouping in the population.

The latent classes we derived describe typical and atypical development of nighttime bladder control: ‘normative development’ (71.5 % of the sample)—low probability of bedwetting at any time point; ‘infrequent delayed’ (14.3 %)—delayed attainment of nighttime bladder control (at around 6 years) and decreasing probability of infrequent bedwetting from 4 to 9 years; ‘infrequent persistent’ (8.6 %)—relatively high probability of infrequent bedwetting from 4 to 9 years; ‘frequent delayed’ (2.4 %)—high probability of frequent bedwetting at age 4 years, which decreased and became more infrequent at 6–9 years; ‘frequent persistent’ (3.2 %)—relatively high probability of bedwetting at least twice a week from 4 to 9 years.

Mothers completed the Toddler Temperament Scale (TTS) [20] when the study children were 24 months old. The TTS comprises statements describing specific behaviours and mothers were asked to rate how often their child behaves in that way on a scale ranging from 1 (almost never) to 6 (almost always). The scale comprises nine temperament traits, but we restricted our analysis to five traits that were associated with bedwetting in an earlier study [21]. These included activity—higher activity level e.g. fidgeting during quiet activities; adaptability—difficulties adjusting to changes in routines; intensity—high-energy responses e.g. screaming, stamping feet; mood—unpleasant and fussy disposition and tendency to show anxiety when learning new tasks; persistence—more easily frustrated and likely to give up activities e.g. routine tasks such as dressing and picking up toys.

The Emotionality Activity Sociability (EAS) Questionnaire [22] was administered when study children were 38 months. The questionnaire comprises 20 statements about behaviours and mothers rated the extent to which each statement describes their child on a scale ranging from 1 (not at all like) to 5 (exactly like). Scores on these items are combined to form four subscales (each comprising five items): emotionality (tendency to show distress, e.g. cries easily, reacts intensely when upset), activity level (preferred level of activity, e.g. is always on the go, is very energetic), shyness (tendency to be inhibited with unfamiliar people, e.g. tends to be shy, takes a long time to warm up to strangers), and sociability (tendency to prefer the company of others, e.g. likes to be with people, prefers playing with others to playing alone). The factor structure of the EAS has been demonstrated in this sample to correspond well to these four traits and to have good stability over time [23].

Psychological problems were assessed when the child was aged 42 months using the Revised Rutter Parent Scale for Preschool Children, which is an extension of the Rutter behaviour scale [24]. The questionnaire comprises 43 statements describing behaviours and mothers are asked to rate the extent to which each statement describes their child on a scale comprising the options 1 (certainly true), 2 (sometimes true) and 3 (not true). Responses were aggregated to create scores in four domains: emotional difficulties (e.g. appears miserable, unhappy, tearful or distressed), conduct difficulties (e.g. fights with other children), hyperactivity (e.g. has poor concentration or short attention span) and prosocial behaviour (e.g. considerate of other people’s feelings). High levels of psychological problems are indicated by high scores on emotional difficulties, conduct difficulties and hyperactivity and low scores on the prosocial behaviour scale.

We show correlations between the Rutter, TTS and EAS subscales in Online Resource Table A.

We considered a range of potential confounders including gender and a number of socio-demographic measures derived from responses to a questionnaire, completed by mothers during the antenatal period, containing items on socioeconomic position and adversity. Binary variables were generated from these questions and each item was scored as 1 if an adversity was present and 0 if not. The items included social class based on the lower of the mother or partner’s occupational social class using the 1991 British Office of Population and Census Statistics classification and dichotomized into non-manual (professional, managerial or skilled professions) and manual (partly or unskilled occupations); early parenthood (<19 years versus ≥19 years), housing adequacy (yes/no—comprising crowding, periods of homelessness, living conditions, major defects/infestation), maternal education (defined as none versus high school qualifications or greater), major financial difficulties (yes/no), family size (<3 children versus ≥3 children) and the presence of a social network (yes/no—comprising emotional support, practical/financial support).

In addition we included developmental level, which was assessed at 18 months using a questionnaire developed by ALSPAC including items from the Denver Developmental Screening Test [25] and comprising four domains of development (fine motor, gross motor, communication and social skills). Scores on each domain were adjusted for age in weeks, standardised (using a linear regression model and extracting the residuals) and reversed where appropriate so that high values on all scores reflected a lower level of development. We adjusted for a total development score derived from the sum of the scores on each domain.

Finally, models were also adjusted for maternal depression using the Edinburgh Postnatal Depression Scale (EPDS) [26]. The EPDS was dichotomized at the standard cut-off (score >12) used to indicate probable depressive disorder [27]. The analysis with the TTS was adjusted for maternal depression at 21 months and the analyses with the EAS and Rutter Scale were adjusted for maternal depression at 33 months.

We estimated the association between the risk factors and class membership using a series of univariable multinomial logistic regression models and employing the normative latent class as the baseline category for the outcome, before re-parameterizing to derive comparisons across the other outcome classes. Parameter estimates were obtained using the “Modal ML” 3-step method [28] implemented in Mplus. This has been shown to produce less-biased estimates than traditional three-step methods such as probability weighting, whilst avoiding the problem of covariates impacting on the measurement model itself [29]. Bias-adjusted estimates were obtained using the Mplus “auxiliary (r3step)” command. Models were adjusted for the confounders described above.

We show the distribution of confounding variables in each latent class in Online Resource Table B. There were a higher proportion of males in each of the atypical latent classes. The frequent persistent class had the highest proportion of manual social class, housing inadequacy and low maternal education. The frequent delayed and frequent persistent classes had the highest proportion from larger families.

Table 2 presents the results of the analysis examining the associations between the risk factors and latent class membership. Odds ratios for these analyses were derived in relation to the normative latent class of nighttime bladder control, which was used as the reference group in this analysis. The results show the increase in odds of membership to each latent class per one standard deviation (SD) increase in the score for each risk factor.

We found evidence that difficult temperament and behaviour problems in early childhood are risk factors for bedwetting at school age. Difficult temperament traits at 24 months, including problems adapting to change, high intensity and negative mood, were associated with bedwetting at 4–9 years. Behaviour problems including conduct problems, hyperactivity and low levels of prosocial behaviour at 42 months were also associated with subsequent bedwetting. We found less evidence that early emotional difficulties are linked to bedwetting. The ‘infrequent persistent’ bedwetting class was the only pattern of bedwetting that was linked to emotional difficulties. This could be because this pattern of intermittent wetting is closest to what is often referred to as secondary enuresis or relapse. Children who are prone to emotional difficulties may be more susceptible to increased life stress and this could contribute to relapses in bedwetting [16].

We found little evidence that bedwetting is associated with temperament ratings of high activity level, but higher scores on the hyperactivity scale of the Rutter were associated with bedwetting. This apparently contradictory result could be explained by evidence that inattentive symptoms of ADHD are more common in children with bedwetting than hyperactive-impulsive symptoms [30, 31]. Two of the four items on the Rutter Hyperactivity scale refer to inattention (“Has poor concentration, or short attention span”; “Is inattentive”) whilst the items of the TTS and EAS activity scales describe the child’s activity level e.g. fidgeting and inability to sit still (TTS); energetic, always on the go (EAS). A previous study with the ALSPAC cohort found that the EAS activity scale at 38 months was associated with the hyperactive–impulsive type of ADHD at 7 years, but not the inattentive type [32].

Our findings provide evidence that psychological factors in early childhood, including aspects of difficult temperament and behaviour problems, precede problems attaining nighttime bladder control. There are several potential explanations for this finding.

A major strength of our study is the prospective design with data available on difficult temperament and psychological problems before the age at which most children attain nighttime bladder control. This addresses potential biases inherent in cross-sectional studies and provides evidence that these early risk factors are associated with subsequent problems attaining nighttime bladder control.

A possible limitation of this study is the use of maternal reports for psychological factors. There is evidence to suggest that maternal depression results in a tendency view their child negatively and over-report problem behaviours [42]. Relying on maternal reports could have resulted in misclassification of difficult temperament or psychological problems in their young children. However, any such misclassification is likely to have been non-differential with respect to our outcome.

It has been argued that direct observations in a laboratory setting are more objective measures of child temperament than maternal reports [43]. A single observation from an artificial setting, however, could also have limitations by providing only a snapshot of the child’s current state. Parental reports of temperament traits are more likely to reflect more stable behavioural characteristics over multiple settings [33].

There was a relative lack of evidence for associations between the risk factors and the frequent delayed class. This might be due to this being the smallest class, leading to larger standard errors and hence, a lack of precision in our estimates of the effect of the risk factors on membership to this class.

There is evidence that children who suffer from frequent bedwetting are more likely to experience persistent incontinence than those with less frequent bedwetting. A previous study found a greater proportion of frequent, compared with infrequent, bedwetters among older children and adolescents [44]. Frequent bedwetting has been linked to persistent continence problems into adult life [45]. It would be particularly useful to be able to identify factors that might distinguish between children who are at risk of persistent bedwetting from those who are likely to experience a natural resolution of their bedwetting. This knowledge could improve the identification of children who should be prioritised for specialist services. We did not find evidence for distinct aetiologies for the latent classes. Our findings were mostly in agreement with a dose response relationship, in which increasing levels of difficult temperament and behaviour problems in early childhood are associated with increasing severity (frequency and persistence) of bedwetting. This could indicate that these risk factors are common to all types of atypical development of nighttime bladder control.

There is evidence that severe (frequent and persistent) bedwetting is often accompanied by daytime wetting [44] and, in agreement with this, we previously found the highest percentage of daytime wetting in the frequent persistent class [18]. It is possible that distinct risk factors would emerge if we further refined our bedwetting latent classes by incorporating additional symptom information such as concurrent daytime wetting and indicators of bladder dysfunction. For instance, psychological factors may be differentially associated with combined (day and night) wetting compared with bedwetting alone.

Many parents do not consider seeking treatment for bedwetting until it has started to have secondary impacts on their child’s quality of life and many are unaware that there are effective treatments available [46]. In the UK, evaluation and treatment for bedwetting is generally considered for children aged 5 and over. Parents should be encouraged to seek treatment for children who are still wetting the bed frequently at 5 years because timely intervention could help to reduce the risk of continence problems becoming persistent and lower the risk of secondary impacts.