Current Pediatric Research

Abstract

Background: Nocturnal enuresis (NE) is prevalent in patients with sickle cell disease. This has been attributed to a decreased ability to concentrate urine caused by sickling-induced nephropathy (hyposthenuria).Whether this is true in Sudanese children with sickle cell anemia is unknown.

Objective: To determine the frequency of NE in Sudanese children with sickle cell anemia and to see if hyposthenuria is the cause of NE in these patients. Method: A hospital based cross sectional descriptive study of 87 children with sickle cell anemia who met the study criteria and age sex matched 53 children with sickle cell trait and 50 children with normal hemoglobin genotype as control was conducted in the outpatient’s clinic of a major pediatric hospital in Khartoum. A questionnaire was used to collect relevant data; urine specific gravity was measured using urine dipsticks.

Results: NE is present in38%, 13% and 12% of children with sickle cell anemia, sickle cell trait and the control respectively. Hyposthenuria was not detected in children with or without enuresis.NE is common in siblings of enuretic children but not their parents.

Conclusion: NE is frequent in Sudanese children with homozygous sickle cell disease. The frequency is not increased in children with sickle cell trait. Hyposthenuria is not detected in these children. Familial tendency for NE is observed.

Keywords

Enuresis, Sickle cell, Children, Sudan

Introduction

Nocturnal Enuresis (NE) is defined according to DSM-IV as incontinence of urine at night after age 5 more than two times per week for at least 3 months [1]. It is usually divided clinically into primary (never being dry) and secondary (prior dry period) forms and monosymptomatic (absence of daytime symptoms) versus non-monosymptomatic (presence of daytime symptoms) enuresis [2].

The prevalence of NE in normal children seems to be the same throughout the world [1]. It has a prevalence of 7% for males and 3% for females at age five [3]. In Sudan, the prevalence rate vary from 6.5% to 33.5% depending on the definition of enuresis used [4-6].

Enuresis is frequent in children with sickle cell disease and its intensity is linked to severity of the disease [7]. In their review, Wolf et al. [8] reported the prevalence of NE in children and adolescent with SCD to range from 9-51%.

This was constructed based on 10 relevant studies reported in the literature. This variation in prevalence rate was attributed to inconsistent definitions of NE [8].

NE in SCD is commonly hypothesized to be due to an impairment of urine concentrating ability (hyposthenuria), leading to nocturia and polyuria [9]. However, no significant differences were seen in more recent studies comparing the maximum concentrating ability of children with homozygous SCD and enuresis with age and sex matched children without enuresis, although children with SCD and enuresis were more likely to have low maximum functional bladder capacity [3].

SCD is prevalent in Sudan but there are no reports of NE in these patients. The objective of this study was to identify the frequency of nocturnal enuresis among Sudanese children with SCD, to test the hypothesis of hyposthenuria as a cause of NE in sickle cell patient and to look at the previously suggested association between nocturnal enuresis and homozygous sickle cell disease.

Materials and Methods

Setting

Sickle cell clinic and general pediatrics outpatient clinics at Gaffer Ibn Ouf pediatrics Hospital. This is a specialized and central referral Hospital in Khartoum, Sudan.

Study Design, Period and Population

This is a Prospective, descriptive, hospital based study done during May 2012 to November 2012. The study group was children 5-16 years diagnosed as sickle cell anemia or sickle cell trait and confirmed by hemoglobin electrophoresis. Children attending general pediatric clinic who has no personal or family history to suggest sickle cell anemia and who have normal hemoglobin and hemoglobin electrophoresis were taken as control group (matching in sex and age). Children with constipation, snoring, mouth breathing, nasal congestion, diabetes mellitus, diabetes insipidus, chronic renal failure, nephritic syndrome, receiving diuretics and those with abnormal urine analysis were excluded from the study.

A Questionnaire for All Patient was filled by the Author (E), It Includes

History and physical examination: The history includes (personal data, past medical history (previous admissions, number of painful crisis and blood transfusion) family history and social history. The examination includes anthropometric measurements (weight, height and body mass index (BMI)) taken using standardized techniques and plotted on WHO standard charts. Children were examined for abdominal masses, abnormal neurological signs and anal tone. The spines were carefully inspected for evidence of spina bifida occulta. Urine analysis and urine specific gravity were done using urine dipsticks. Hemoglobin electrophoresis was obtained for all patients.

Statistical package of social science (SPSS) version 15 software was used for data entering and coding. Microsoft word and Excel have been used to generate graphs and tables.

Results

There were 140 children in the study group, 87 as sickle cell anemia and 53 as sickle cell trait and 50 children in the control group. The control group matched the study group in age and sex (Table 1).

Table 1. Demographic and clinical characteristics of patients in the study group and control group

In children with sickle cell anemia in the study group 33 (37.9%) had NE. Out of these 33 children 28 (84.8%) had primary NE and 5 (15.2%) had secondary NE. NE was present in 7 children (13.2%) out of 53 children with sickle cell trait in the study group. Five of these 7 children had primary NE (71.4%) and 2 (28.6%) had secondary NE (Table 1, Figures 1 and 2).

Figure 1: Frequency of NE in the study and control group

Figure 2: Types of NE in the study and control group

In the Control group 6 children (12%) were enuretic 5 (83.3%) had primary NE and 1 child (16.7%) had secondary NE (Table 1).

Males predominate in enuretic children (64% in sickle cell anemia and 65% in sickle cell trait) P<0.001 in both groups.

Anthropometric measurement:

Sickle cell anemia group:

Weight: Table 2

Weight below 3^rd percentile was present in 58.8% of children with enuresis compared to 38.6% with no enuresis (P<0.05).

Table 2. Percentage (%) of patients with weight below third per centile in the study and control group

Height: Table 3

Height below 3^rd centile was present in 47.1% of children with enuresis compared to 29.5% in children without enuresis (P<0.05).

Table 3. Percentage (%) of patients with height below third per centile in the study and control

BMI: Table 4

BMI below 3rd centile was present in 50% with enuresis compared to 38% without enuresis (P<0.001).

Table 4. BMI in SS study group

Sickle cell trait:

BMI: Table 5

BMI below 3^rd centile was present in 85% of children with enuresis compared to 28% in those without enuresis (P<0.001).

Table 5. BMI in AS group

Control group:

BMI (Table 6): There was no significant difference between those with and without NE.

Table 6. BMI in the control group

Family size and education level of parent had no significant effect on the frequency of NE.

Low socioeconomic status was present in 70% of children with NE in SCD group compared to 52% in children with no NE in the same group (P<0.05).

In the study group a positive family history of NE was significantly higher in enuretic children with SCD compared to non-enuretic (76.5% vs. 4.5% P<0.001) All of them were siblings. 54% of these enuretic siblings had sickle cell anemia and 46% were normal (Table 1).

Urine specific gravity was within normal range in all patients (1.030-1.007). The mean USG was 1.025 in enuretic children with SCA compared to 1.027 in nonenuretic children with SCA (P 0.15).

Discussion

This study used DSM-IV to define NE. We had used this definition when we reported on NE in normal Sudanese children (4) and it was also used by 4 other studies reporting NE in children with SCA (8). This consistent definition will allow comparison with these studies.

The present study confirmed the previously suggested association between homozygous sickle cell disease and nocturnal enuresis [10,11]. The frequency of NE in SS group was at least thrice that found in control subjects. A similar association could not be shown for children with sickle cell trait since they had an almost similar rate as the control group. It is interesting to note that the frequency of NE in the control group is almost double the rate we reported before in normal children (12% vs. 6.5 % [4]. If we used our previously reported rate of NE then children with sickle cell trait in this study would have been considered to have high frequency of NE. There are no reports in the literature about the prevalence of NE in such patients.

The rate of NE reported in this study was higher than the rates reported in other three studies that used a similar definition [7,12,13]. These studies had included adult patients and it is known that the rate of NE declined with age [8]. A comparable prevalence rate of NE was reported by Ali and Chakraborty who used a similar definition and a similar age range like ours [14].

In the current study NE was common in boys with homozygous sickle cell disease and sickle cell trait. This had been reported previously in normal children as well as children with sickle cell anemia [3,4,7,15-19]. It is probable that factors contributing to enuresis in normal children like reduced responsiveness to toilet training and slower maturation in boys as well as the frequent developmental delay are also important in children with homozygous and heterozygous sickle cell disease [20,21]. However, there are no studies that determined the relative contribution of general pediatric and SCD in these factors [8].

NE was observed to be associated with low socioeconomic status in this study. This is different from what had been reported from Jamaica and Nigeria but similar to previous studies that noted enuresis to be more in normal children from lower socio-economic status [3,19,22,23]. Rahim, et al. [16] in a large epidemiological study, reported a prevalence of 88% of NE in Sudanese children, 3-15 years, living in a suburban area in Khartoum. According to the same study, the prevalence of NE remained higher than the rate in European children after the age of 9 years [6]. This can be partly explained by the fact that Rahim et al. [16] study was conducted exclusively in an area of low socioeconomic status. Thus we can assume that low socioeconomic status is associated with an increased risk of NE in Sudanese children with or without sickle cell disease.

The association between NE and homozygous sickle cell (SS) disease has been attributed to poor urinary concentrating ability and obligatory high urinary volumes [1,4]. Urine specific gravity, found to be as good as measuring urine osmolarity in normal urine specimen, was measured in a random urine sample for all patients [12]. There was no significant difference in urine specific gravity between enuretic and non-enuretic patients. No significant differences were also demonstrated in studies from Jamaica comparing the maximum concentrating ability of children with homozygous sickle cell anemia and enuresis with age and sex matched children without enuresis [3]. In ten children with homozygous sickle cell anemia and NE treated by Figueroa et al. [3] with intranasal desmopressin acetate (DDAVP), four responded completely and another two had a partial response [3]. These findings support the concept that, although this population has an increased prevalence of nocturnal enuresis, the causes and treatment for this condition may be the same as children without a hemoglobinopathy.

Early and progressive inability to concentrate urine has been reported in sickle cell disorders including sickle cell trait. This persists and/or worsens with age [24]. Despite that not all children with SCD or sickle cell trait develop NE and those who develop it the rate of NE declines with age [8]. Therefore it is difficult to link NE in SCD to hypothenuria.

Sickle cell anemia and NE, as chronic illnesses, are known to be associated with poor growth [25-27]. Poor growth was also documented in Sudanese children with sickle cell anemia (personal unpublished data).Weight; height and BMI were significantly lower in enuretic children with sickle cell anemia compared to nonenuretic children. BMI is significantly lower in enuretic children with sickle cell trait as well. In two reports in the literature growth status was not affected in patients with sickle cell trait [28,29]. Therefore, we can say that apart from the effect of sickle cell anemia, NE is associated with poor growth in these children.

In normal children insufficient cerebral maturation, as an important factor in the pathogenesis of primary nocturnal enuresis, was suggested by previous studies. The indicators of brain immaturity in these studies were inferred from abnormal neurophysiological studies of the brain, significant lag in bone age and brain microstructure abnormalities in areas that are involved in micturition control network [30-34]. Children with sickle cell anemia had been described to have significant retarded bone age at 8 years of age [35]. Various brain injuries were also described in children with sickle cell anemia; cortical thinning was described with the largest regions of thinning in the precuneus and the posterior cingulate [36]. Another abnormality is reduced gray matter volume and that was mainly observed in the caudate, thalamus and cortex [37,38]. Ischemia and/or infarction especially of the thalamus and basal ganglia were also described [39,40]. We can see that some of the areas affected in patients with sickle cell anemia are part of the micturition control network making brain immaturity a possible explanation for NE in this population like normal children.

Low (but still within the normal reference value) serum vitamin B12 and folate level were reported in two studies in patients with primary NE when compared to the control group. This was suggested to have a role in the delay of CNS maturation as well [41,42]. More than half of sickle cell anemia patients had inadequate dietary folate intake. Despite adequate folate supplementation 15% of children with sickle cell anemia had low serum folate.B12 intake was adequate with only 3% had B12 deficiency [43]. Therefore low serum folate level might play a similar role in patients with sickle cell anemia and NE like that in enuretic normal children.

Neveus stated that NE is not only a nocturnal problem but also a disorder of sleep [44]. A systematic analysis of the literature from 1980 to 2010 identified nocturnal enuresis in 31% of children who had Sleep Disordered Breathing (SDB). After adenotonsillectomy the rate dropped to 16% [45]. Using polysomnography in children with sickle cell anemia the prevalence of Sleep Disordered Breathing (SDB), specifically habitual snoring and obstructive sleep apnea hypopnea syndrome, was 35% to 79% [46,47]. Using polysomnography Lehmann et al. demonstrated that habitual snoring and SDB with and without habitual snoring are associated with enuresis in children with SCA [48]. 23.5% of their cohort had SDB without habitual snoring. This means the absence of habitual snoring in a child with SCD and enuresis does not exclude SDB. In our study we had excluded children who were snoring or had history of snoring. We did not perform sleep studies to identify those with other sleep disorders like apnea and hypopnea which might be associated with NE.

There is an anatomic evidence for an association between 25-hydroxy vitamin D (25(OH) D) and sleep patterns. Vitamin D receptors are present in the same areas that are thought to play important roles in the initiation and maintenance of sleep [49]. Moreover, clinical studies suggested that vitamin D supplementation for patients with sleep disorders may contribute to significant improvements in sleep quality [50-52]. Low 25(OH) D was reported to be associated with an increased risk of NE in normal children aged five to seven years [53]. Vitamin D deficiency in children and adolescents with sickle-cell disease is prevalent and was associated with painful crisis [54]. Low vitamin D level was detected in 63% of Sudanese children with SCA compared to 38% in the control (personal unpublished data). It is plausible to assume that low vitamin D might contribute to NE in patients with SCA through its effect on sleep or by increasing pain episodes that will add to sleep disturbance.

The existence of familial history of nocturnal enuresis in enuretic children with and without sickle cell anemia had been documented [4,55-60]. This had been shown also in this study as well further supporting the genetic predisposition to enuresis. Few gene loci associated with nocturnal enuresis in normal children had been identified [61], but no such work had been done in enuretic children with SCA.

Limitations of the Study

This study did not differentiate between monosymptomatic and nonmonosymptomatic enuresis. The exclusion of those with snoring had possibly leaded to a lower prevalence rate of NE than it should be.

Conclusion

Sudanese children with SCD are at higher risk to develop NE than normal children. We reported for the first time on the prevalence NE in children with sickle cell trait which is similar to that in normal children. WE had also shown the significant adverse effect of NE on the BMI of enuretic children with sickle cell trait. We found no association between NE and hypothenuria. Further research is needed to look at vitamin D level as a possible modifiable cause of enuresis in children with sickle cell anemia.

References

1. American Psychiatric Task Force on DSMIV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association; Washington, DC, USA 2000.
2. Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children's Continence Society. J Urol 2010; 183: 441.
3. Readett DRJ, Morris J, Serjeant GR. Determinants of nocturnal enuresis in homozygous sickle cell disease Arch Dis Child 1990; 65: 615-618.
4. Salih K, Ahmed FE, Omer YI, et al. Characteristics and etiological factors of nocturnal enuresis in Sudanese Children. Am J Med Den Sci 2013; 1: 40-45.
5. Mahgoub, Magdi AH. Nocturnal enuresis in Sudan. Australasian Aust Med J 2010.
6. Rahim SI, Cederblad M. Epidemiology of nocturnal enuresis in a part of Khartoum, Sudan. I. The extensive study. Acta Paediatr Scand 1986; 75: 1017-1020.
7. Barakat LP, Smith-Whitley K, Schulman S, et al. Nocturnal enuresis in pediatric sickle cell disease. J Dev Behav Pediatr 2001; 22: 300-305.
8. Wolf RB, Kassim AA, Goodpaster RL, et al. Nocturnal enuresis in sickle cell disease. Expert Rev Hematol 2014; 7: 245-254.
9. Akinyanju O, Agbato O, Ogunmekan AO, et al. Enuresis in sickle cell disease. I. Prevalence studies. J Trop Pediatr 1989; 35: 24-26.
10. Hatch FE, Culbertson JW, Diggs LW. Nature of the renal concentrating defect in sickle cell disease. J Clin Invest 1967; 46: 336-345.
11. Pham PT, Pham PC, Wilkinson AH, et al. Renal abnormalities in sickle cell disease. Kidney Int 2000; 57: 1-8.
12. Ekinci O, Celik T, Ünal S, et al. Nocturnal enuresis in sickle cell disease and thalassemia major: associated factors in a clinical sample. Int J Hematol 2013; 98: 430-436.
13. Jordan SS, Hilker KA, Stoppelbein L, et al. Nocturnal enuresis and psychosocial problems in pediatric sickle cell disease and sibling controls. J Dev Behav Pediatr 2005; 26: 404-411.
14. Ali M, Chakravorty S. Prevalence of nocturnal enuresis and proteinuria in children with sickle cell disease and its relation to severity of painful crises. Arch Dis Child 2014; 99: A101-A102.
15. Oge O, Kocak I, Gemalmaz H. Enuresis: Point prevalence and associated factors among: Turkish children. Turk J Pediatr 2001; 43: 38-43.
16. Gόmόώ B, Vurgun N, Lekili M, et al. Prevalence  of  nocturnal enuresis and accompanying factors in children aged 7-11 years  in Turkey. Acta Paediatr 1999; 88: 1369-1372.
17. Cher TW, Lin GJ, Hsu KH. Prevalence of nocturnal enuresis and associated familial factors in primary school children in Taiwan. J Urol 2002; 168: 1142-1150.
18. Mithani S, Zaidi Z. Bed wetting in school children of Karachi. J Pak Med Assoc 2005; 55: 2-5.
19. Eneh CI, Okafor HU, Ikefuna AN, et al. Nocturnal enuresis: Prevalence and risk factors among school-aged children with sickle-cell anemia in a South-east Nigerian city. Ital J Pediatr 2015; 41: 66.
20. Golding J, Tassier G. Soiling and wetting. In: Butler NR, Golding J, editors. From birth to five. Oxford: Pergamon press 1986: 64–79.
21. Garfinkel BO. The elimination disorders. In: Garfinkel BO, Carlson GA, Weller EB, editors. Psychiatric disorders in childhood and adolescents. 2nd ed. Philadelphia: WB Saunders (Publ); 2000: 326-336.
22. Gunes A, Gunes G, Acik Y, et al. The epidemiology and factors associated with nocturnal enuresis among boarding and daytime school children in southeast of Turkey: A cross sectional study. BMC Public Health 2009; 9: 357.
23. Chiozza ML, Bernadi L, Cainone P, et al. An Italian epidemiological multicenter study of nocturnal enuresis. Br J Urol 1988; 81: 86-89.
24. Sesso R, Almeida MA, Figueiredo MS, et al. Renal dysfunction in patients with sickle cell anemia or sickle cell trait. Braz J Med Biol Res 1998; 31: 1257-1262.
25. Al-Saqladi AW, Bin-Gadeen HA, Brabin BJ. Growth in children and adolescents with sickle cell disease in Yemen. Ann Trop Paediatr 2010; 30: 287-298.
26. Bennett EL. Understanding growth failure in children with homozygous sickle-cell disease. J Pediatr Oncol Nurs 2011; 28: 67-74.
27. Power C, Manor O. Asthma, enuresis and chronic illness: long‐term impact on height. Arch Dis Child 1995; 73: 298‐304.
28. Rehan N. Growth status of children with and without sickle cell trait. ClinPediatr (Phila) 1981; 20: 705-709.
29. Kramer MS, Rooks Y, Pearson HA. Growth and development in children with sickle-cell trait. A prospective study of matched pairs. N Engl J Med 1978; 299: 686-689
30. Hallioğlu O, Ozge A, Comelekoglu U, et al. Evaluation of cerebral maturation by visual and quantitative analysis of resting. J Child Neurol 2001; 16: 714-718.
31. Electroencephalography in children with primary nocturnal enuresis. J Child Neurol 2001; 16: 714.
32. Freitag CM, Röhling D, Seifen S, et al. Neurophysiology of nocturnal enuresis: Evoked potentials and prepulse inhibition of the startle reflex. Dev Med Child Neurol 2006; 48: 78-84.
33. Dündaröz MR, Sarici SU, Denli M, et al. Bone age in children with nocturnal enuresis. Int Urol Nephrol 2001; 32: 389-391.
34. Mimouni M, Shuper A, Mimouni F, et al. Retarded skeletal maturation in children with primary enuresis. Eur J Pediatr 1885; 144: 234-235.
35. Lei D, Ma J, Shen X, et al. Changes in the brain microstructure of children with primary monosymptomatic nocturnal enuresis: a diffusion tensor imaging study. PLoS One 2012; 7: e31023.
36. Stevens MC, Maude GH, Cupidore L, et al. Prepubertal growth and skeletal maturation in children with sickle cell disease. Pediatrics 1986; 78: 124-132.
37. Kirk GR, Haynes MR, Palasis S, et al. Regionally specific cortical thinning in children with sickle cell disease. Cereb Cortex 2009; 19: 1549-1556.
38. Steen RG, Langston JW, Ogg RJ, et al. Diffuse T1 reduction in gray matter of sickle cell disease patients: Evidence of selective vulnerability to damage? Magn Reson Imaging 1999; 17: 503-515.
39. Steen RG, Langston JW, Reddick WE, et al. Quantitative MR imaging of children with sickle cell disease: striking T1 elevation in the thalamus. J Magn Reson Imaging 1996; 6: 226-234.
40. Moser FG, Miller ST, Bello JA, et al. The spectrum of brain MR abnormalities in sickle-cell disease: A report from the Cooperative Study of Sickle Cell Disease. AJNR Am J Neuroradiol 1996; 17: 965-972.
41. Kwiatkowski JL, Zimmerman RA, Pollock AN, et al. Silent infarcts in young children with sickle cell disease. Br J Haematol 2009; 146: 300-305.
42. Albayrak S, Zengin K, Tanik S, et al. Vitamin B12, folate and iron levels in primary nocturnal enuresis. Pak J Med Sci 2015; 31: 87-90.
43. Altunoluk B, Davutoglu M, Garipardic M, et al. Decreased vitamin B12 levels in children with nocturnal enuresis. ISRN Urol 2012; 2012: 789706.
44. Kennedy TS, Fung EB, Kawchak DA, et al. Red blood cell folate and serum vitamin B12 status in children with sickle cell disease. J Pediatr Hematol Oncol 2001; 23: 165-169.
45. Nevéus T. Enuretic sleep: Deep, disturbed or just wet? Pediatr Nephrol 2008; 23: 1201-1202.
46. Jeyakumar A, Rahman SI, Armbrecht ES, et al. The association between sleep-disordered breathing and enuresis in children. Laryngoscope 2012; 122: 1873-1877.
47. Kaleyias J, Mostofi N, Grant M, et al. Severity of obstructive sleep apnea in children with sickle cell disease. J Pediatr Hematol Oncol 2008; 30: 659.
48. Spivey JF, Uong EC, Strunk R, et al. Low daytime pulse oximetry reading is associated with nocturnal desaturation and obstructive sleep apnea in children with sickle cell anemia. Pediatr Blood Cancer 2008; 50: 359.
49. Lehmann GC, Bell TR, Kirkham FJ, et al. Enuresis associated with sleep disordered breathing in children with sickle cell anemia. J Urol 2012; 188: 1572-1576.
50. Eyles DW, Smith S, Kinobe R, et al. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005; 29: 21-30.
51. Gominak SC, Stumpf WE. The world epidemic of sleep disorders is linked to vitamin D deficiency. Med Hypotheses 2012; 79: 132-135.
52. Huang W, Shah S, Long Q, et al. Improvement of pain, sleep and quality of life in chronic pain patients with vitamin D supplementation. Clin J Pain 2013; 29: 341-347.
53. McCarty DE. Resolution of hypersomnia following identification and treatment of vitamin D deficiency. J Clin Sleep Med 2010; 6: 605-608.
54. Li L, Zhou H, Yang X, et al. Relationships between 25-hydroxyvitamin D and nocturnal enuresis in five to seven year old children. PLoS One 2014; 9: e99316.
55. de Oliveira JF, Vicente NG, Santos JP, et al. Vitamin D in children and adolescents with sickle cell disease: an integrative review. Rev Paul Pediatr 2015; 33: 350-355.
56. Ekinci O, Celik T, Ünal Ş, et al. Nocturnal enuresis in sickle cell disease and thalassemia major: Associated factors in a clinical sample. Int J Hematol 2013; 98: 430-436.
57. Eneh CI, Okafor HU, Ikefuna AN, et al. Nocturnal enuresis: Prevalence and risk factors among school-aged children with sickle-cell anemia in a South-east Nigerian city. Ital J Pediatr 2015; 41: 66.
58. Bakhtiar K, Pournia Y, Ebrahimzadeh F, et al. Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of Khorramabad in 2013. Int J Pediatr 2014; 2014: 120686.
59. Kalo BB, Bella H. Enuresis: Prevalence and associated factors among primary school children in Saudi Arabia, Acta Paediatrica 1996; 85: 1217–1222.
60. Gümüş B, Vurgun N, Lekili M, et al. Prevalence of nocturnal enuresis and accompanying factors in children aged 7-11 years in Turkey. Acta Paediatr 1999; 88: 1369-1372.
61. Kanaheswari Y. Epidemiology of childhood nocturnal enuresis in Malaysia. J Paediatr Child Health 2003; 39: 118-123.
62. Von Gontard A, Schaumburg H, Hollmann E, et al. The genetics of enuresis: A review. J Urol 2001; 66: 2438-2443.