Published online July 3, 2006
PEDIATRICS Vol. 118 No. 1 July 2006, pp. 254-259 (doi:10.1542/peds.2005-2738)
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Breastfeeding During Infancy May Protect Against Bed-wetting During Childhood

Joseph G. Barone, MDa, Ranjith Ramasamy, BSa, Andrew Farkas, MD, PhDb, Emanuel Lerner, MDc, Eileen Creenan, RNd, Dawn Salmon, RNd, Jessica Tranchell, BAe and Dona Schneider, PhDe

a Urology
b Obstetrics and Gynecology
c Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey
d Robert Wood Johnson University Hospital, New Brunswick, New Jersey
e Edward J. Bloustein School of Planning and Public Policy, Rutgers, State University of New Jersey, New Brunswick, New Jersey


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. Our goal was to test the hypothesis that children who exhibit bed-wetting during childhood were less likely to be breastfed during infancy compared with normal controls.

METHODS. A case-control study was conducted in a pediatric continence center and a general pediatric practice. Cases (n = 55) were recruited from the continence center and defined as children 5 to 13 years of age who experienced lifetime involuntary voiding of urine during nighttime sleep at least 2 times a week in the absence of defects of the central nervous system or urinary tract. Age- and gender-matched controls (n = 117) who did not exhibit bed-wetting were enrolled from a general pediatric practice. Infant feeding practices were measured as breastfeeding (yes/no) and, for those who were breastfeed, by the duration of breastfeeding and the time of formula supplementation.

RESULTS. Among the case subjects, 45.5% were breastfed, whereas among the controls 81.2% were breastfed. The controls reported higher household incomes than the case subjects, and their mean family size (number of children) was slightly lower. After adjusting for race, income, and family size, the odds ratio was 0.283, indicating that case subjects were significantly less likely than controls to be breastfeed. Among all the study subjects who were breastfed, controls were breastfed for a significantly longer period than case subjects (an average of 3 months longer). Although breastfed controls were less likely to be supplemented with formula than breastfed case subjects, this difference was not statistically significant.

CONCLUSIONS. Breastfeeding longer than 3 months may protect against bed-wetting during childhood. Breast milk supplemented with formula did not make a difference in the rate of enuresis.

Key Words: bed-wetting • breastfeeding • enuresis

Abbreviations: OR—odds ratio • CI—confidence interval • CDC—Centers for Disease Control and Prevention

Bed-wetting is defined as the involuntary voiding of urine during nighttime sleep in the absence of defects of the central nervous system or urinary tract in a child aged 5 years or older.1 It is estimated that 6 million children wet the bed annually in the United States. The condition occurs in 15% of 5-year-olds, 5% of 10-year-olds, and 1% of 13-year-olds.2 Without treatment, ~15% of children stop bed-wetting annually. The prognosis for bed-wetting is usually spontaneous resolution; however, 1% of these cases are resistant to all treatment modalities.

Several etiologies have been proposed for bed-wetting, including developmental delay, immature sleep pattern, immature bladder function, and insufficient nocturnal antidiuretic hormone.3–5 All of these etiologies for bed-wetting are related to delayed development because they are seen normally in younger children.6

A constant observation that strongly supports the developmental delay theory for bed-wetting is the child’s natural tendency to outgrow bed-wetting. Bed-wetting is also considered normal in younger children and infants. The developmental theory for bed-wetting is supported further by clinical data that demonstrate more developmental delays in children with bed-wetting compared with controls.6–8 Therefore, there is strong and diverse clinical evidence that many cases of bed-wetting are a result of developmental delay.

Causes for bed-wetting that may not be developmental include psychosocial and familial factors. The effects of psychosocial factors such as stress are unclear but have been reported to be associated with bed-wetting. Also, familial causes for bed-wetting have been identified, indicating that some cases of bed-wetting tend to run in families.2

We examined the relationship between bed-wetting and breastfeeding because both have been reported to be strongly associated with childhood development. For example, since 1978, there has been increasing clinical and basic science evidence demonstrating that breastfeeding may provide visual, growth, and cognitive, neurodevelopmental advantages to children, compared with feeding with infant formula.9–12 It has been suggested that the developmental advantages seen in breastfed children are a result of higher n-3 and n-6 long-chain fatty acids found in breast milk compared with infant formula.13–15 These long-chain fatty acids are essential for the provision of rapid growth, fat-soluble vitamins, and essential fatty acids for the developing child.

Because breastfeeding and bed-wetting have both been associated with neurodevelopment, the objective of this study was to examine whether breastfeeding during infancy protects against bed-wetting during childhood by providing neurodevelopmental advantages to the child.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
We used a case-control study design because of the relatively long delay between the exposure (breastfeeding) and the outcome (bed-wetting). To examine the hypothesis that children who exhibit bed-wetting during childhood were less likely to be breastfed during infancy compared with normal controls, we needed 56 case subjects and 112 age- and gender-matched controls (total sample size of 164) to achieve a 90% power to detect a 25% difference in the rate of breastfeeding among the 2 groups using a 2-sided significance level of .05. We recruited 1 case subject per family from the Pediatric Continence Center at Robert Wood Johnson Medical School. Controls (age- and gender-matched) were selected from a large, general pediatric practice located nearby at the time of well-child visits. All children whose parents agreed to enroll had an initial medical screening that included a history and physical examination for all patients. We saw children and their parents when the children were between the ages of 5 and 13 years. Because supplementation of infant formula with docosahexaenoic acid (DHA) began in February 2002, even the youngest subjects in our study (age 5) would not have received formula fortified with DHA. Either parent of all subjects responded to the study questionnaires. The study protocol was approved by our medical school’s institutional review board.

Controls were defined as healthy children with typical development and no history of bed-wetting after the age of 4 years. Case subjects were children suffering from active bed-wetting, which was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, as the involuntary voiding of urine during nighttime sleep at least 2 times per week in the absence of defects of the central nervous system or urinary tract in a child aged 5 years or older.16 To meet the inclusion criteria, case subjects must have exhibited a lifelong history of bed-wetting and urine dipstick analysis must have shown normal glucose and protein levels and a specific gravity of ≥1.022.17 A single random urine dipstick was used to rule out a concentrating abnormality, because a concentrating deficit is unlikely if a random urine osmolarity is >1.022. We did not determine nocturnal urine concentrating ability between the 2 groups, because limiting fluid intake or using daytime diuretics to produce a relative dehydration and higher nocturnal urinary osmolarity have not been effective in the treatment of enuresis.18 This is because it is delayed maturation of all aspects of bladder development that affects nighttime urinary control.19 Patients with known anatomic malformations of the urinary tract, urinary tract infection, daytime urinary incontinence, diabetes, proteinuria, and patients with neurologic problems were excluded. In addition, case patients underwent urinalysis to rule out other medical problems that have nocturnal enuresis as a symptom. These problems included urinary tract infection, diabetes insipidus, psychogenic water intoxication, and diabetes mellitus.

Key Variables
The questionnaire elicited demographic variables (date of birth, gender, race/ethnicity, number of children in the household and their ages), socioeconomic variables (annual household income, educational levels of the parents), and family history of bed-wetting (mother, father, siblings, second-order relatives). Bed-wetting status was measured by 2 variables: a dichotomous variable (yes/no) and the frequency of bed-wetting (times per week). Breastfeeding history was measured by 2 variables: a dichotomous variable (yes/no) and duration of breastfeeding (in months). Parents were asked if they breastfed exclusively or if they supplemented feedings with formula. If supplementation was used, the month that supplementation was initiated was recorded.

Data Analysis
Nominal variables were described by proportions and evaluated by {chi}2 analyses. In instances of small cell sizes, Fisher’s exact test was used. Scale variables were evaluated by using Student’s t test and are presented with means and SDs. A crude odds ratio (OR) with a 95% confidence interval (CI) was calculated to evaluate the relationship of bed-wetting to breastfeeding. Adjusted ORs were calculated to examine the data for potential confounding variables, and the ORs were compared. All data were entered and analyzed by using SPSS 13.0 (SPSS, Inc, Chicago, IL).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Fifty-five case subjects and 117 controls were recruited. Among the case subjects 60% were male (n = 33), and among the controls 52% were male (n = 61). The case subjects and controls were similar for age and gender, the result of group matching in the study design. However, the case subjects and controls were not matched by race, and there are differences between the groups. Specifically, the case subjects were more likely to be white, whereas the controls were somewhat more likely to be Asian or Hispanic/Latino. The controls reported higher household incomes than case subjects, and their mean family size (number of children) was smaller (Table 1).


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  		TABLE 1 Characteristics of Subjects

 
Case subjects were less likely to be breastfed than controls (P < .001). Among the case subjects, 45.5% were breastfed (n = 25), whereas among the controls 81.2% (n = 95) were breastfed. The crude OR of 0.193 (95% CI: 0.0954–0.3905) suggests that breastfeeding yields a protective effect for bed-wetting (P < .001). Stated in epidemiologic terms, case subjects were 81% less likely to be breastfed than controls. Figure 1 demonstrates the significant difference in the incidence of breastfeeding among case subjects and controls.


Figure 1
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  		FIGURE 1 Percentages of the control and study populations that were breastfed.

 
Because race, income, and number of children in the family were different between the case subjects and controls, we adjusted the data first for race (ORa: 0.252; 95% CI: 0.123–0.517) and then for income (ORb: 0.223; 95% CI: 0.108–0.461), race and income (ORab: 0.276; 95% CI: 0.130–0.590), the number of children in the family (ORc: 0.276; 95% CI: 0.130–0.590) and for all 3 covariates (ORabc: 0.283; 95% CI: 0.131–0.615). Although the adjusted ORs varied from the crude and from each other, they were not statistically significantly different. Thus, race, income, and family size may be confounders, but these factors did not significantly change our results.

Among the study subjects who were breastfed, controls were breastfed for a significantly longer period than case subjects (an average of 3 months longer). The number of case subjects and controls who were breastfed for various durations is provided in Table 2. We found no difference in the incidence of bed-wetting if the duration of breastfeeding was <3 months. However, there was a significant difference between the 2 groups if the children were breastfed for ≥3 months (Fig 2). Although breastfed controls were less likely to be supplemented with formula than breastfed case subjects, this difference was not statistically significant (P = .248).


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  		TABLE 2 Duration of Breastfeeding and Incidence of Bed-wetting

 

Figure 2
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  		FIGURE 2 Bed-wetting status in relation to duration of breastfeeding.

 
An exploration of the child’s place in the family yielded no additional information about bed-wetting status: case subjects were as likely to have older siblings as they were to have younger ones (data not shown). A family history of bed-wetting was more likely among the case subjects (n = 32) compared with controls (n = 18) (P < .001). Mothers were reported to have a history of bed-wetting 29.0% of the time by the case subjects (n = 9) and 22.2% of the time by the controls (n = 4) (P = .433, Fisher’s exact test). Fathers were reported by case subjects as having a history of bed-wetting 38.7% of the time (n = 12) vs 11.1% for controls (n = 2) (P = .038, Fisher’s exact test). Siblings were equally reported to have a history of bed-wetting among case subjects and controls, which may be because we failed to define bed-wetting for siblings as occurring after the age of 4 years. Responses for aunts, uncles, and cousins were too few to analyze.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
This is the first controlled study to develop preliminary data regarding the potential protective role that breastfeeding might have on bed-wetting. Only 2 studies have examined the effect of breastfeeding on enuresis. A cross-sectional study by Gumus et al20 examined different clinical factors associated with bed-wetting in children and found no difference between enuretics and nonenuretics with reference to breastfeeding rates in the "first 4 months of life." In our case-controlled study, there was no significant difference in the incidence of bed-wetting when breastfeeding duration was <3 months. These findings are consistent with reports that if breastfeeding is to have any positive effect on development, it must be continued beyond 4 months of age.21

Our study may have been limited by recall bias for breastfeeding practices (eg, number of months of breastfeeding) for both case and control families. In addition, recall may have been more difficult if there were more children in the household and case subjects had more children in the household than controls. Despite this limitation, we demonstrated a significant difference in the rate of bed-wetting when infants were breastfed for >3 months. Singh et al22 examined the relationship between bed-wetting and several diverse clinical characteristics observed in 100 children who wet the bed. Although their retrospective study lacked controls, the authors reported a higher rate of bed-wetting in bottle-fed infants compared with breastfed infants.

The breastfeeding rates in our study were similar to the rates reported by the Centers for Disease Control (CDC) for New Jersey (non-Newark). In New Jersey, the rates for "ever breast fed," "breastfeeding at 6 months," and "breastfeeding at 12 months" were 72%, 38%, and 18%, respectively.23–25 In our study, case subjects had a lower incidence of breastfeeding compared with those in the CDC report; the rates for "ever breast fed," "breastfeeding at 6 months," and "breastfeeding at 12 months" were 45%, 21%, and 5% respectively. Hence, the breastfeeding rates of our study group were slightly lower than those reported by the CDC. In contrast, our control group demonstrated slightly higher breastfeeding rates than those reported by the CDC. The rates for "ever breast fed," "breastfeeding at 6 months," and "breastfeeding at 12 months" were 81%, 51%, and 18%, respectively.

In our study, groups were well matched for age and gender. This matching was essential, because bed-wetting occurs more often in boys and in younger children.2 Our sampling framework yielded more Asian and Hispanic children in the control group and more white children in the case-subjects group. Although a literature search revealed no definitive evidence to suggest that bed-wetting incidence varies significantly between racial or ethnic groups, we did gather the variable and tested it for confounding. Our results show that although race may be a confounder, it did not change our results significantly. Indeed, a study that was performed in Scotland and England found somewhat similar results, with bed-wetting more frequent in Afro-Caribbean children compared with white children.26 Also, although breastfeeding has been shown to be less common among black and non-Hispanic children compared with white and Hispanic children, the reason for this is unclear and is more likely related to socioeconomic status rather than differences in health beliefs and parenting attitudes between the races.27

Although frank psychological illness has not been shown to be associated with nocturnal enuresis,28 psychosocial factors may be a predisposing factor for this problem. Therefore, potential confounding variables in our study included the differences in household income and number of children in household between case subjects and controls (Table 1). In particular, it has been reported that women of higher socioeconomic status are more likely to breastfeed compared with those of lower socioeconomic status. Parity has been shown to have minimal effects on breastfeeding rates.27 In our study, controls reported a higher average household income than case subjects and fewer children per family. To ensure that socioeconomic status or family size did not explain the observed differences, adjusted ORs were calculated, and the results demonstrated that although family size and income level may be confounders, they did not significantly change our findings.

Any child will suffer from nocturnal enuresis if more urine is produced than can be contained in the bladder or if the child is not awakened by a nocturnal detrusor contraction. Detrusor function is governed by the autonomic nervous system, which under ideal conditions is under central nervous control. Neurodevelopment maturation is essential to impede the development of nocturnal enuresis. For example, cystometric studies have demonstrated that urinary bladder instability (latent uninhibited bladder contractions) is more frequently seen in enuretics than controls.6 Over time, bladder stability and striated urinary sphincter control is achieved through neurodevelopment and maturation.

Several studies have reported that breastfeeding has beneficial effects on neurodevelopment in children.9–12 Breastfeeding has been suggested to not only provide overall developmental and psychological advantages to the child but also enhance neuronal development. Vestergaard et al12 showed that the proportion of infants who mastered the specific milestones for motor skills and early language development was higher with increasing duration of breastfeeding. Also, studies have reported that formula-fed preterm infants score lower on visual and developmental tests relative to breastfed preterm infants.29,30

The mechanism that aligns improved development with breastfeeding has been related to the role that long-chain fatty acids have in brain development. In infants who were exclusively breastfed for >3 months, red blood cell levels of long-chain fatty acids were related to improved visual acuity and cognitive development.31 These findings are consistent with our hypothesis that breastfeeding during infancy protects against childhood nocturnal enuresis by providing neurodevelopmental advantages to the child.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Nocturnal enuresis has a multifactorial etiology, but clinical evidence strongly suggests that many cases result from delayed neurodevelopment. There is biological plausibility in inferring that breastfeeding protects against bed-wetting, and our results show a strong statistical association between the 2 variables. Despite this, causation cannot be directly inferred. We can state that our case-control study supports the hypothesis that breastfeeding during infancy protects against the development of nocturnal enuresis in childhood. If a prospective cohort study further supports this hypothesis, breastfeeding could be viewed as the first true preventative approach toward bed-wetting.


   FOOTNOTES
 
Accepted Jan 20, 2006.

Address correspondence to Joseph G. Barone, MD, Department of Urology, 1 Robert Wood Johnson Place, MEB 588E, New Brunswick, NJ 08901. E-mail: baronejg{at}umdnj.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Norgaard JP. Pathophysiology of nocturnal enuresis. Scand J Urol Nephrol Suppl. 1991;140 :1 –35[Medline]
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics



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