Evaluation of Nutritional and Developmental Consequences and Renal Function of Children who Recovered from Hypernatremia

Abstract

Hypernatremia (HN), defined as high sodium in the blood (≥145 μmol/L), is a serious complication of diarrheal diseases in children. However, clinical manifestations are usually observed in children in developing countries at the level of 150 μmol/L The primary cause of HN is excessive water loss relative to sodium loss. The resulting hyperosmolality can lead to neuronal cell shrinkage, causing brain injury, including widespread cerebral hemorrhage, thrombosis, subdural effusion, and permanent neurological deficits. Retrospective study conducted in icddr,b showed that 2.4-5.1% children with diarrhea had hypernatremia and case fatality ranges from 15-9%(Chisti et al., 2016).Deaths are often attributed to the severe effects of HN on the brain or to rapid rehydration, which can result in cerebral edema. A prospective observational study was conducted at Dhaka Hospital of icddr,b from August 2013 to October 2015. In total, 259 children under five years old were enrolled. After treatment, 224 children were successfully discharged. The death rate was 13.5%, with neurological sequelae in 29.9%, acute kidney injury in 32.4%, and severe malnutrition in 44% of the children. However, post hypernatremia impact in long term on morbidity, nutritional status, cognitive development, and renal function is largely unknown. Therefore, it is imperative to evaluate nutritional status, growth, cognitive development, and renal function in long term among children recovered from hypernatremia. vi Methodology: This Observational longitudinal study was conducted among children under five years of age who had hypernatremia and participated in the prospective observational study conducted from August 2013 to October 2015. The original study aimed to investigate neurologic complications and developmental consequences in children with hypernatremia. The sample size is based on 224 children who successfully recovered from the initial hypernatremia study. Accounting for a 25% attrition rate, the sample size was estimated to be 168. However, due to dropouts during follow-up, 143 children were successfully followed up in the present study. The study lasted from March 2016 to March 2017, and children were examined at the Dhaka Hospital of icddr, b. All children were brought to Dhaka Hospital inpatient ward for a complete physical, nutritional, neurological, and cognitive assessment. A spot urine analysis was also performed to evaluate their kidney function. Upon arrival, each child's weight, height, and mid-upper arm circumference (MUAC) were measured using standard procedures. Data were collected using pre-designed and pre-tested Case Report Forms (CRFs), which included the child’s medical records, exact address, socio-demographic information, family status, living conditions, history of illness, and immunization status. Cognitive, motor and neuropsychological development were assessed by a trained psychologist using standard procedures. Two different tools were used depending on the child's age. The Bayley Scales of Infant Development-III (BSID-III) was used for children under 36 months, while the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) was used for children older than 36 months. Motor function was assessed using the Movement Assessment Battery for Children-II (MABC-II). A spot urine sample was collected from each child for vii microscopic examination, and the protein-to-creatinine ratio was calculated to detect potential glomerular damage. Results: Of the 224 recovered hypernatremia children, 143 (64%) parents consented to participate in this study. The mean age of the children was 35 ± 8 months, and 59% were male. Mean± SD of weight and height of the study participants were 12.4 ±3.1 kg and 89.5 ±7.5 cm, respectively. Malnutrition was not significant in this study population. After stratified by two age groups, children aged up to 36 months and those older than 36 months, Median (IQR) of family income, 13000(10000,20000) vs. 11500 (8000,18000); maternal, 7(4,10) vs. 8(5,10); and paternal, 6(4, 9) vs. 8(1,10) education levels were comparable. Around 50% of the study children commonly presented with upper respiratory infections. After 12 months of recovering from hypernatremia, half of the children had an increased protein-to- creatinine ratio. Children with mild hypernatremia were more likely to have raised urinary Pr/Cr ratio, though none presented with any evidence of urinary problems or glomerular damage. Eighty-six percent (86%) of the children from better socioeconomic status were less likely to have a high Pr/Cr ratio in comparison with their poorest counterparts (p=<0.001). Children under 36 months are twice more likely to have raised urinary Pr/Cr compared to those more than 36 months; 2.31(1.06, 5.02); p-0.035. The mean cognitive score improved significantly at 12 months’ post-recovery (86.1± 16.3; p=0.002), as well as the motor and language composite score; 83. ±15.7, and 80.9± 13.8 respectively. These developmental scores were similar between male and female participants. viii However, 10% of the children showed poor cognitive performance (<69) after 12 months. After adjusting for age and weight-for-age Z-scores (WAZ), composite scores of cognitions and socioemotional domain of development showed a significant difference between baseline and end-line assessment (p=0.002 and p=0.013, respectively). On the other hand, after 12 months’ children mostly presented with average IQ. The mean Movement Assessment score indicated that children are at risk of movement difficulties during the post-hypernatremia recovery period. Conclusion: Long-term evaluation of children's nutritional status and renal function recovered from hypernatremia did not reveal any significant clinical abnormalities. However, developmental assessments indicated that most children exhibited average neurocognitive development and IQ. Further studies are required to validate the spot urine method against the gold standard 24-hour urine collection method for assessing proteinuria in post-hypernatremia children.