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Bayley- III Scores of Children with Congenital Anomalies of the Kidney and Urinary Tract.

INTRODUCTION

Congenital anomalies of the kidney and urinary tract (CAKUT) include the kidneys, collecting system, or both, and arise as the result of factors affecting nephrogenesis, such as maternal, placental, fetal, environmental, and genetic factors. CAKUT constitute approximately between 20% and 30% of all anomalies determined in the antenatal period, and the overall rate of CAKUT in live and stillborn infants is 0.3 to 1.6 per 1000 (1,2). CAKUT usually progress to chronic renal disease, and they are the most common cause of renal replacement therapy for end-stage renal disease (ESRD) in childhood (3). The ESRD leads to growth failure and developmental delay, cognitive impairment, severe psycho-social adaptation problems, multi-system complications, and an increased mortality and morbidity (4).

One of the commonly used reliable tests for the evaluation of developmental delay in children aged between 1 and 42 months is "Bayley Scales of Infant and Toddler Development Screening Test, Third Edition" (Bayley-III). This test was first described in 1969, revised in 1993, and standardized in 2006 by Bayley (5). Bayley-III assesses the cognitive, language, and motor development of infants and children. The language scale is assessed as receptive and expressive communication, and the motor scale is assessed as gross motor and fine motor subscales.

The ESRD is a risk factor for a low lQ and academic unsuccess in a schoolchild, leading to a neurocognitive developmental delay in the pre-school period when rapid neurologic maturation occurs. Renal disease in early infant-hood is one of the risk factors for delayed developmental outcomes (6). Differently from literature, we aimed to evaluate the neurodevelopment of children who had CAKUT without ESRD by using the Bayley-III test.

MATERIALS and METHODS

Data of 30 patients with CAKUT aged between 1 and 41 months and 32 healthy children were included in the study. The exclusion criteria were the presence of acquired urinary system anomalies, chronic neuro-muscular diseases, epilepsy, dysmorphic findings or genetic syndromes, hypoxic and/or premature birth history, neonatal hyperbilirubinemia, hypoglycemia history, and surgery history. The Mersin University Ethics Committee approved the study (MEU 2016-113).

The height, weight, head circumference, and mid-arm circumference were measured with standard anthropometric techniques. The left-arm triceps skinfold thickness was measured by using standard Lange calipers and anthropometric measurements recorded from patients' files. We calculated standard deviation scores for each measurement by using the standardized measures for Turkish children (7). Complete blood count, serum ferritin, and urinary culture results were recorded from patients' files. Iron deficiency anemia was defined as the hemoglobin level <11 mg/dl and ferritin level <12 mcg/L, if these laboratory findings were not attributable to other causes (8). The urinary culture positivity [greater than or equal to]2 times was accepted as a recurrent urinary tract infection (UTI) in patients with CAKUT (9). The newborn hearing screening was recorded as normal in all cases.

Data of the cases whose cognitive, language, and motor scale scores had been evaluated with Bayley-III were studied retrospectively. The cognitive scale included thinking, learning, information processing, and problem-solving skills with plays and activities. The receptive communication subscale evaluated hearing, understanding, and responding abilities. The expressive communication sub-scale evaluated communication abilities using sounds, words, and body language. Coordination of motor skills, sensory and perceptual motor integration, and main locomotion stages were scored with fine and gross motor subtests. The composite test scores scaled as 40-160 were within the normal range of the Bayley-III, the mean value was identified as 100, and a standard deviation (SD) of 15. Infants who had cognitive, language, or global motor composite scores less than 85 were defined as developmentally delayed (5). An experienced specialist, blinded to the diagnosis (K.M.), performed the Bayley-III tests.

Statistical Analysis

In the statistical analysis of data, number (N) and percent (%) values were given as descriptive statistics for categorical sociodemographic variables. The association between the categorical variables was examined by the chi-square test. The normality distribution of continuous variables was tested by the Shapiro-Wilk test. The Student's t-test was used to test the difference between the averages. The analysis of variance was carried out in comparison of the mean values of independent groups. The results were considered to be statistically significant if P-values were less than 0.05.

RESULTS

Data of 62 children (30 patients, 32 controls) were included in the study. Characteristic features and anthropometric measurements were shown in Table 1. The patient and control groups were similar in regard to gender, age, birth weight, and maternal age (P>0.05). The mean values of the height, body weight, head circumference, body mass index (BMI, kg/[m.sup.2]), mid-arm circumference, and triceps skinfold thickness measurements were similar in both groups (P>0.05). Diagnoses of the patients and frequency of recurrent UTI are shown in Table 2. The mean cognitive, language, global motor scores, and mean receptive communication, expressive communication, fine motor, gross motor subscores are shown in Table 3. The mean cognitive score of the patient group was significantly lower than the control group's score (p=0.04). There was no significant difference between Bayley-III scores of the groups with or without iron deficiency anemia (Table 4). In the patient group, Bayley-III scores were statistically similar between the patients who had and did not have a recurrent UTI history. The mean cognitive score of patients with a recurrent UTI was lower than -1 SD value (Table 4). The educational level of mothers, classified as the primary school, secondary school, high school, and university was similar between the patient and control groups (P>0.05), and there was not a significant difference between the Bayley-III scores of groups with regard to educational level of mothers (P>0.05).

DISCUSSION

Congenital anomalies of the kidney and urinary tract (CAKUT) are the underlying reason of ESRD in 30%-50% of children diagnosed with it (3). Cognitive impairment and learning difficulties are common in children with ESRD compared to healthy peers. Attention deficit, memory and learning problems, and low IQ scores are observed particularly in dialysis patients. The onset of ESRD in childhood causes more occupational and marital problems in adulthood (10). Therefore, early management of CAKUT is important for preventing complications and unfavorable developmental outcomes.

Psychomotor development is affected by many genetic and environmental factors in childhood. We considered that recurrent UTIs, hospitalizations, or frequent outpatient clinic controls could cause the neuromotor retardation in children with CAKUT based on the influence of chronic diseases on neurocognitive development. In this retrospective study, we evaluated the neurodevelopment of normally growing children with CAKUT and without the onset of ESRD by using the Bayley-III test.

We found the Bayley-III scores to be similar in the language and motor scales. The mean cognitive score of children with CAKUT was significantly lower than the control groups' mean score. The mean cognitive score of patients with a recurrent UTI history was lower than -1 SD value. The febrile UTIs (UTI) incidence in children with CAKUT accompanied by severe hydronephrosis is the highest in the newborn period and the first months of life (11). This period is critical for neurodevelopment, so we consider that recurrent UTIs, frequent hospitalization, and parenteral treatments due to pyelonephritis could cause developmental delay, because hospitalizations change the environmental factors such as materials, settings, and social and physical needs that support child development. In this study, we found the highest frequency of recurrent UTIs in the collecting system anomaly group. We did not find a statistically significant difference between groups with or without recurrent UTI with regard to the Bayley-III scores. However, we think that neurodevelopment of children especially with VUR or UPJ obstruction must be evaluated with larger serried studies.

The study of Demirci et al. (12) which included 1514 Turkish children demonstrated significant associations between the maternal and paternal educational background, socio-economic status, consanguineous marriage, and developmental delay in children. The elementary school or a lower educational level, low socioeconomic status, and the presence of consanguineous marriage were associated with the high prevalence of developmental delay in children. Other studies also verify these findings (12-13). Not finding a significantly association between the Bayley-III scores and the maternal educational level could be explained with a small sample size in our study. The presence of consanguineous marriage, the paternal educational level, and the family's income level were not examined in our study due to a lack of data.

The presence of high quantities of iron in oligo-dendriocytes in a developing brain, the need for iron in the energy metabolism of glial cells, and the negative effect of iron deficiency anemia (IDA) on neuro-cognitive functions are known (14-15). Myelinization, dopamine and nor-epinephrine metabolism, neuronal energy metabolism, and there by child development are negatively affected by iron deficiency (16). In our study, IDA was found in 10 patients (33%) and 10 controls (31%), and a significant relationship was not found between IDA and low Bayley-III scores. The CAKUT and IDA comorbidity and the influence of the anemia on child development should be investigated with the studies including a larger series of patients.

In't Wuod et al. (17) studied maternal risk factors for the CAKUT spectrum. Maternal obesity was related to an increased risk of a double-collecting system and VUR, gestational diabetes mellitus was related to an increased risk of posterior urethral valve, and assisted reproductive techniques were related to an increased risk of CAKUT in general. Torabi et al. (18) showed a significant relationship between the developmental delay in children aged between 4 and 60 months and a high maternal BMI and gestational diabetes mellitus. When these results are evaluated together, we may suggest that our study should be supported by new studies that investigate the development of children with CAKUT and their maternal risk factors.

A normal cognitive development depends on acquiring language and motor skills. In a study investigating the interrelationships between motor, cognitive, and language development, the Bayley-III test was used in 77 children with developmental delay, and a strong correlation was shown between the motor, cognitive, and language scales when compared with results of 130 normally developing children. In conclusion, the importance of the early medical applications supporting one development area was emphasized, and it should be remembered that these applications would also contribute other development areas (19). We also started the applications that would support development in the early period of our patients' lives, in whom we detected cognitive delayed outcomes.

CONCLUSION

Our study contributes to the literature, to the best of our knowledge, as the first case-control study that applied the Bayley-III test in children with CAKUT, although it does not explain the direct effects of CAKUT on the neuromotor development. Neurologic maturation is a process affected by the environmental and genetic factors in pre-natal, peri-natal, and post-natal periods. CAKUT with recurrent UTIs may be one of the factors that negatively affects this process, and severe complications such as ESRD and dialysis may compromise developmental outcomes. Therefore, it would be right to prevent recurrent UTIs and follow up the neuromotor development of children with CAKUT by using developmental screening tests since early infanthood.

Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Mersin University (MEU 2016-113).

Informed Consent: Informed consent is not necessary due to the retrospective nature of this study.

Peer-review: Externally peer-reviewed.

Author Contributions: Conceived and designed the experiments or case: OT, KM. Performed the experiments or case: OT, KM. Analyzed the data: MT. Wrote the paper: OT, OH, AD. All authors have read and approved the final manuscript.

Conflict of Interest: The authors have no conflict of interest to declare.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES

(1.) Nicolaou N, Renkema KY, Bongers EM, Giles RH, Knoers NV. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat Rev Nephrol 2015; 11(12): 720-31. [CrossRef]

(2.) Andres-Jensen L, J0rgensen FS, Thorup J, Flachs J, Madsen JL, Maroun LL, et al. The outcome of antenatal ultrasound diagnosed anomalies of the kidney and urinary tract in a large Danish birth cohort. Arch Dis Child 2016; 101(9): 819-24. [CrossRef]

(3.) Soliman NA, Ali RI, Ghobrial EE, Habib EI, Ziada AM. Pattern of clinical presentation of congenital anomalies of the kidney and urinary tract among infants and children. Nephrology (Carlton) 2015; 20(6): 413-8. [CrossRef]

(4.) Groothoff JW. Long term outcomes of children with endstage renal disease. Pediatr Nephrol 2005; 20(7): 849-53. [CrossRef]

(5.) Bayley N. Bayley Scales of Infant and Toddler Development - Third Edition Screening Test Manual. San Antonio TX: The Psych Corp 2006.

(6.) Icard P, Hooper SR, Gipson DS, Ferris ME. Cognitive improvement in children with CKD after transplant. Pediatr Transplant 2010; 14(7): 887-90. [CrossRef]

(7.) Neyzi O, Gunoz H, Furman A, Bundak R, Gokcay G, Darendeliler F, et al. Turk cocuklarinda vucut agirligi, boy uzunlugu, bas cevresi ve vucut kitle indeksi referans degerleri. Cocuk Sagligi ve Hastaliklari Dergisi 2008; 51: 1-14.

(8.) Mcdonagh MS, Blazina I, Dana T, Cantor A, Bougatsos C. Screening and routine supplementation for iron deficiency anemia: a systematic review. Pediatrics 2015; 135(4): 723-33. [CrossRef]

(9.) Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011; 128(3): 595-610. [CrossRef]

(10.) O'Lone E, Connors M, Masson P, Wu S, Kelly PJ, Gillespie D, et al. Cognition in people with end-stage kidney disease treated with hemodialysis: a systematic review and meta-analysis. Am J Kidney Dis 2016; 67(6): 925-35. [CrossRef]

(11.) Walsh TJ, Hsieh S, Grady R, Mueller BA. Antenatal hydronephrosis and the risk of pyelonephritis hospitalization during the first year of life. Urology 2007; 69(5): 970-4 [CrossRef]

(12.) Demirci A, Kartal M. The prevalence of developmental delay among children aged 3-60 months in Izmir, Turkey. Child Care Health Dev 2016; 42(2): 213-9. [CrossRef]

(13.) Rai NK, Tiwari T. Parental factors influencing the development of early childhood caries in developing nations: a systematic review. Front Public Health 2018; 6: 64. [CrossRef]

(14.) Mccann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr 2007; 85(4): 931-45. [CrossRef]

(15.) Beard JL, Felt B, Schallert T, Burhans M, Connor JR, Georgieff MK. Moderate iron deficiency in infancy: biology and behavior in young rats. Behav Brain Res 2006; 170(2): 224-32. [CrossRef]

(16.) Black MM, Quigg AM, Hurley KM, Pepper MR. Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential. Nutrition Reviews 2011; 69: 64-70. [CrossRef]

(17.) Groen ln 't Woud S, Renkema KY, Schreuder MF, Wijers CH, van der Zanden LF, Knoers NV, et al. Maternal risk factors involved in spesific congenital anomalies of the kidney and urinary tract: a case-control study. Birth Defects Res A Clin Mol Teratol 2016; 106(7): 596-603. [CrossRef]

(18.) Torabi F, Akbari SAA, Amiri S, Soleimani F, Majd HA. Correlation between high-risk pregnancy and developmental delayin children aged 4-60 months. Libyan J Med 2012; 7: 18811-7. [CrossRef]

(19.) Houwen S, Visser L, Van Der Putten A, Vlaskamp C. The interrelationships between motor, cognitive, and language development in children with and without intellectual and developmental disabilities. Res Dev Disabil 2016; 53-54: 19-31. [CrossRef]

Ozlem Tezol (1), Khatuna Makharoblidze (1), Olgu Hallioglu (1), Ali Delibaj (2), Merve Turkegun (3)

(1) Department of Pediatrics, Mersin University Faculty of Medicine, Mersin, Turkey

(2) Division of Pediatric Nephrology, Department of Pediatrics, Mersin University Faculty of Medicine, Mersin, Turkey

(3) Department of Biostatistics, Mersin University Faculty of Medicine, Mersin, Turkey

Correspondence

Ozlem Tezol Department of Pediatrics, Mersin University Faculty of Medicine, Mersin, Turkey

Phone: +90 3242410000

e.mail: ozlemtezol@hotmail.com

Cite this article as: Tezol O, Makharoblidze K, Hallioglu O, Delibas, A, Turkegun M. Bayley- III Scores of Children with Congenital Anomalies of the Kidney and Urinary Tract. Erciyes Med J 2018; 40(3): 120-4.

Submitted

12.02.2018

Accepted

15.05.2018

Available Online Date

03.09.2018

DOI: 10.5152/etd.2018.0034
Table 1. Characteristics and anthropometric measurements of patients
and controls

                  Patient               Control               p
                  (n=30)                (n=32)

Gender
Female (%)          16 (53)               14 (43)            0.488
Age (month)         27.58[+ or -]9.30     22.96[+ or -]9.59  0.087
Birth weight (g)  3301.6[+ or -]514.9   3211.5[+ or -]371.5  0.476
Mother's age        30.8[+ or -]5.3       31.6[+ or -]5.6    0.638
(years)
Weight (SDS)        -0.03[+ or -]1.13     -0.11[+ or -]0.79  0.775
Height (SDS)         0.03[+ or -]1.11      0.07[+ or -]0.71  0.881
HC (SDS)            -0.14[+ or -]0.79     -0.02[+ or -]0.81  0.592
BMI (SDS)           -0.04 [+ or -]1.08     0.07[+ or -]0.79  0.655
MAC (SDS)           -0.50 [+ or -]0.69    -0.48[+ or -]0.67  0.910
TSF (SDS)           -0.17[+ or -]0.5      -0.02[+ or -]0.53  0.349

HC; head circumference, BMI; body mass index, MAC; mid-arm
circumference, TSF; triceps skinfold thickness, SDS; standard deviation
score

Table 2. Diagnosis of the patients and the frequency of recurrent UTIs

Diagnosis                  n (%)   Recurrent UTI n (%)

Renal parenchymal          6 (20)    2 (16)
malformations
  Polycystic kidney        1 (3)     -
  disease
  Multicystic              1 (3)     -
  dysplasia
  Renal agenesis           4 (13)    2 (16)
Anomalies of renal         5 (16)    1 (8)
embryonic migration
  Renal ectopia            3 (10)    -
  Horseshoe kidney         2 (6)     1 (8)
Anomalies of the          19 (63)    9 (75)
collecting system
  Vesicoureteral reflux    6 (20)    4(33)
  Ureteropelvic junction  11 (36)    4(33)
  obstruction
  Double collecting        2 (6)     1 (8)
  systems

UTI; urinary tract infection

Table 3. Mean scores of Bayley-III in patients and controls

               Patient            Control               p
               (n=30)             (n=32)

Cognitive      83.60[+ or -]8.38  100.00[+ or -]11.61  0.04
Language       99.92[+ or -]8.88  106.00[+ or -]13.91  0.07
Receptive      11.80[+ or -]1.60   12.23[+ or -]2.58   0.18
communication
Expressive      9.08[+ or -]1.73    9.73[+ or -]2.70   0.31
communication
Global motor   98.36[+ or -]8.73  103.46[+ or -]13.17  0.11
Gross motor     9.08[+ or -]1.68    9.69[+ or -]2.63   0.33
Fine motor     10.32[+ or -]1.97   11.53[+ or -]2.51   0.06

Bayley III, Bayley Scales of Infant and Toddler Development Screening
Test, Third Edition

Table 4. Bayley-III scores with and without iron deficiency anemia and
recurrent UTIs

                        Cognitive            Language

Controls  With IDA      102.50[+ or -]15.58  102.38[+ or -]13.08
(n=32)    (n=10, %31)
          Without IDA    99.16[+ or -]9.73   107.61[+ or -]14.32
          (n=22.%68)
          p               0.51                 0.38
Patients  With IDA       83.66[+ or -]9.35    99.22[+ or -]8.25
(n=30)    (n=10, %33)
          Without IDA    83.56[+ or -]8.10   100.31[+ or -]9.45
          (n=20,%66)
          p               0.97                 0.77
          With RUTI      82.15[+ or -]10.83  100.38[+ or -]7.92
          (n=12, %40)
          Without RUTI   85.05[+ or -]7.30    99.70[+ or -]9.52
          (n=18, %60)
          p               0.09                 0.86

          Receptive          Expressive         Global
          Communication      Communication      Motor

Controls  11.75[+ or -]3.19   9.12[+ or -]1.80  104.25[+ or -]18.01
(n=32)
          12.44[+ or -]2.33  10.00[+ or -]3.02  103.11[+ or -]11.00
           0.53               0.45                0.84
Patients  11.00[+ or -]1.65   8.66[+ or -]1.87   96.11[+ or -]7.67
(n=30)
          10.68[+ or -]1.62   9.31[+ or -]1.66   99.62[+ or -]9.26
           0.65               0.38                0.34
          11.25[+ or -]1.16   8.87[+ or -]1.95  101.38[+ or -]9.36
          10.58[+ or -]1.76   9.17[+ or -]1.66   96.94[+ or -]8.32
           0.34               0.69                0.24

          Gross             Fine
          Motor             Motor

Controls  9.87[+ or -]3.48  12.00[+ or -]2.72
(n=32)
          9.61[+ or -]2.27  11.33[+ or -]2.47
          0.81               0.54
Patients  9.00[+ or -]1.00   9.66[+ or -]2.12
(n=30)
          9.12[+ or -]1.99  10.68[+ or -]1.85
          0.86               0.22
          9.50[+ or -]1.51  10.87[+ or -]2.23
          8.88[+ or -]1.76  10.05[+ or -]1.85
          0.40               0.34

IDA; iron deficiency anemia, RUTI; recurrent urinary tract infection
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Title Annotation:ORIGINAL ARTICLE
Author:Tezol, Ozlem; Makharoblidze, Khatuna; Hallioglu, Olgu; Delibaj, Ali; Turkegun, Merve
Publication:Erciyes Medical Journal
Date:Sep 1, 2018
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