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IS URINARY CREATININE ASSOCIATED WITH WASTING IN NEONATES

Results: There was no wasting neonates, WH z-score (WHZ) >-2 SD. The concentrations of absolute creatinine urine excretion were about 11.1–167.2 mmol/day, and creatinine urine excretion related to body weight was about 4.08–50.06 mmol/Kg/day. There were negative significant correlation between the absolute creatinine urine with WH (r=-0.357, p=0.035) and creatinine urine – body weight with WH (r=-0.482, p=0.003). Creatinine urine measurement is a sensitive biomarker of renal and total muscle mass that can be used as a child’s growth biomarker. Methods: The study was cross sectional by involving 35 healthy neonates aged 1–3 days that were born at Pekanbaru Andini Hospital, Indonesia, on August to September 2014. Body length gauges, digital weighing scale, family socioeconomic questionnaires, pediatrics urine collection bag, and creatinine urine were used to collect the data. We used two indicators (creatinine urine and weight/height [WH]) as a parameter in this study. Pearson correlation (significance p<0.05 and p<0.01) was applied for statistical analysis. Objective: To analyze the correlation between creatinine urine and wasting in neonates. Conclusion: The creatinine urine was associated with wasting in neonates therefore can be used as a growth biomarker.


INTRODUCTION
Wasting is a serious public health problem in Indonesia with 12.1% of prevalence [1]. Wasting describes a deficiency in weight for height due to a lack of tissue and fat mass. Children get wasted when they shed weight quickly, consequently of an infectious disease incidence and diets that do not cover nutritional needs. This carries an immediate increased risk of morbidity and mortality in short term and will be impeding children from achieving their full potential development and cognitive performance, for long-term effect will disrupt the country's productivity.
Wasted children have 5-20 times higher risk of dying than nourished children. World health organization (WHO) established wasting standards based on anthropometrics measurement with weight/ height z-score (WHZ-score) <−2 SD. Causes of wasting are insufficient access to health care, inadequate caring and feeding practice, lack of food security, and poor sanitary. Currently, some countries report a prevalence of wasting of more than 10% throughout the year, such as Nigeria (10%), Pakistan (15%), and India (20%). The prevalence of wasting in children under five about 6,8% and 5,3% severed wasting in Indonesia [2][3][4].
Wasting in infants aged under 6 months is often ruled out; particularly, wasting among neonates. Insufficiency of disease prevalence data is the main circumstance aggravating the challenges [5][6][7]. No certain method has been reported as an indicator. An anthropometric method in determining wasting less accurate because error possibility may occur during measuring such human error. Furthermore, it cannot predict nutrition status in short time and the other factor beyond nutrition.
Creatinine, the biochemical waste product that produced through the catabolism of phosphocreatine, is filtered mainly by the kidney. A high urinary creatinine level can mean a problem in the muscles, moreover, kidneys. The function of the kidney during early fetus in neonates was most affected by amniotic fluid and regulating fetal blood pressure. It will continue through the period after childbirth. The child's kidney perform important function for help the body to maintain the balance of nutrients and minerals, ability to use growth hormone, to correct levels of erythropoietin, to balance the proper levels of mineral and acid-bases in the blood.
Creatinine urine measurement is the most widely used to measure renal function [8], which is a sensitive biomarker of renal and total muscle mass. The aim of this study was to assess the correlation between creatinine urine and wasting in neonates therefore can be used as a growth biomarker.

Study design Subject and urine collection
It was a cross-sectional study conducted from January to December 2014. Of the 37 neonates that were selected, two individuals removed with missing values of urinary creatinine urine before the analysis. They were healthy neonates that were born at Andini Mothers and Children Hospital at Tuanku Tambusai

Data collection
All parents gave written informed consent. At the time of informed parental consent, neonates were stratified by gender (male and female), race (Indonesian and expatriate), and feeding (breastfeeding and formula). The 24-h urine was collected by using pediatrics urine collection bag, aliquot to 6 ml, and stored at −20°C until analysis.

Equipment and materials research
Body length gauges, weight scales digital baby, baby urine bags, household socioeconomic questionnaires baby (name, gender, age, race, height parents). The other materials were pediatrics urine collection bag, sanitizing wipe, diaper, urine jar were used in sampling babies wee.

Research procedure
Neonates' urine was collected by a nurse who was trained by researchers at the Andini Hospital. The mother was briefly explained about the implementation of the study and using of pediatrics urine collection bag. The urine is taken as 24-h samples and then stored in the refrigerator at a temperature of −20°C in Prodia Clinical Laboratory Pekanbaru until samples were fully collected. Urine of babies was packed by staff Prodia Pekanbaru and then it was sent to Prodia Centre in Jakarta for analysis. The analysis was carried out simultaneously.

Creatinine urine measurement and standardization
Creatinine measurements were performed with the use of Jaffe method and Spectrophotometer ADVIA 1800: ADVIA, Germany.

Statistical analysis
Statistical analysis and results are reported based on the complete data. Statistical outliers, defined as outside the 95% confidence, limits the normal probability plots. Determination of severely wasted, wasted, normal, and obese was performed according to the classification of WHO. Pearson correlation, with significance *p<0.05 and **p<0.01, was applied for statistical analysis. The analysis was performed by using IBM SPSS Statistics version 20 [9].

Familial socioeconomic characteristic of neonates
The familial socioeconomic characteristic of neonates are presented in Table 1. We met 35 individuals during the study period. Inclusion criteria are medically stable and receiving full enteral feeding (formula and breastfeeding), distribution characteristics (gender, ethnic, gestational age, body weight and body length at birth).
There were different neonates gender in our study population about 74.3% male and 25.7% female. The higher percentage of male neonates than female neonates, due to genital factor. Meanwhile, this was a coincidence that birth rate of male neonates was more than female neonates. Most of the neonates' ethnic were Malay (97.1%), only 2.9% was Chinese [10].

Nutritional status of neonates
The data of individuals' baseline characteristics are presented in Table 2. There was no wasting neonates (WHZ >−2 SD). WHZ of neonates is expected to be optimal. Study from Mgongo et al. [4] reported that 24.7% children, aged 0-36 months, were wasting in six districts of Kilimanjaro, Tanzania. In another study, Mahyar et al. from Qazvin, Iran indicated that 0.7% from 804 children aged 0-24 months were wasting.
The assessment of nutritional status based on birthweight and length is a manifestation of prenatal growth of the infant since individual prenatal growth occurs during the mother's pregnancy. The pattern of prenatal relied on genetic factors but also influenced by environmental factors such as energy and nutrition. The common method to determine nutritional status is the body mass index (BMI) measurement. The BMI is the determination of individual nutritional status by comparing body weight in kilograms (Kg) with height in meters (m) squared.
Mother's BMI before entering pregnancy is one indicator of nutritional status that needs to be considered. Assessment of mother's nutritional status through the calculation of BMI may indicate maternal nutritional quality in the past which may have an impact on maternal and fetal health during pregnancy and the quality of the baby to be born. Therefore, it is established that BMI of a mother before entering pregnancy should be sufficient which is in normal nutrient status category [12].
In our study, we found that mother's BMI of neonates about 65.625% normal, 18.75% underweight, 12.5% overweight, and 3.125% obese, it can be seen in Table 1. Mothers with normal and over nutritional status will affect the neonates' nutritional status not to wasting.
The measurement of daily creatinine excretion is used for the biochemical evaluation of the nutritional status of adults and children which is done by completeness check of 24-h urine collections. The result of measurement absolute creatinine urine excretion of the newborn was about 11.1-167.2 mmol/day, with a negative significant correlation between creatinine urine excretion and WH (r=−0.357, p=0.035), it was presented in (Fig. 1).
The investigation of creatinine urine in infancy is more complicated than other age groups. This is because, during the neonatal period, the renal system has a remarkable role in growth and development. The kidneys itself experience a maturation. Likewise, the condition of the musculoskeletal system at birth is not characterized by a lot of movement, personality, or activity; however, it will be directly affected by the dietary habits. Furthermore, limited references and studies about creatinine urine excretion in infancy give rise to difficulty in interpreting the level of urinary creatinine [8,6].
Several limitations of our study should be considered. First, we did not use a direct comparison to a standard of newborn creatinine urine. Second, we had no information on neonates' illness.
Urinary creatinine excretion related to body weight was about 4.08-50.06 mmol/Kg/day, with a negative significant correlation between creatinine urine-body weight to WH (r=−0.482, p=0.003), it can be seen in (Fig. 2). Based on international clinical reference, normal excretion of creatinine urine in newborns is about 0.11-1.78 mmol/Kg/ day [13]. Allegaert et al. [14] analyzed creatinine urine about 0.21-2.36 mmol/Kg/day in 84 neonates.
The amount of creatinine formed on a daily basis is related to muscle mass, which varies with diets, ethnicity, age, and gender. According to our study, creatinine urine excretion-body weight was 10-100 times higher