Neuro-radiological changes developing in NHD still remain an under-researched area. Previous small studies have reported cerebral edema, brain hemorrhage, and cerebral venous sinus thrombosis in these neonates [4]. The exact incidence of brain lesions and patterns of injury are largely not known. This study was conducted to study magnetic resonance imaging (MRI) identified brain lesions, in the neonates admitted with hypernatremic dehydration.

This study was conducted in 30-bedded dedicated extramural neonatal intensive care unit (NICU) of a teaching hospital among 93 neonates consecutively seen between August, 2018 and July, 2019. Ethical approval was taken from the institutional ethics committee, and written informed consent was obtained from the caregivers of enrolled neonates.

Fully automated analyzer (EM360, ERBA Diagnostics Manheim GmBH) was used to measure serum sodium levels. For MRI brain, 1.5 Tesla MRI machine (Achieva 1.5 T, Philips) was used. T1, T2, fluid attenuated inversion recovery, diffusion weighted imaging, apparent diffusion coefficient map, and gradient echo sequences were taken in all the cases. MRI reporting was done for all neonates by a single senior radiologist. Standard treatment protocols were universally followed in all babies (Web Box I).

The study by Unal, et al. [5] has reported the incidence of neuroradiological changes among hypernatremic dehydrated infants to be around 10% (with some newborns having more than one change). Assuming an incidence of 10%, with 5% absolute precision and 95% confidence interval, the calculated sample size was 94 neonates. Assuming an attrition of　5% due to in-hospital deaths, the final sample size was calculated to be 100.

Statistical analysis: Data were collected in Microsoft Excel sheet and were analyzed using SPSS 20.0 software.

A total of 100 hypernatremic neonates were enrolled; out of which seven died during hospital stay due to decompensated shock and associated respiratory failure, and remaining 93 were analyzed. Decreased urine output was the most common presentation (n=90, 96.8%), followed by poor acceptance of feed (n=76, 81.7%), fever (n=74, 79.6%), seizures (n=39, 41.9%), and jaundice (n=21, 22.6%). On examination, 54 (58%) babies were lethargic and 15 (16.1%) were irritable; and neonatal reflexes (Moro’s, grasp, rooting and sucking reflexes) were depressed in 76 (81.7%) babies. Mean gestational age, birth weight and age at MRI scan were 39.61 (1.43) weeks, 2889 (0.48) grams and 11.81(1.03) days, respectively. Mean serum sodium, blood urea nitrogen and serum creatinine levels were 177.12 (11.90) mmol/L, 33.58 (19.7) mmol/L, and 309.47 (207.79) µmol/L, respectively. Most of the babies (n=46, 49.5%) had serum sodium levels exceeding 180 mmol/L, followed by 42 (45.2%) in 161-180 mmol/L category, and only 5 (5.4%) had mild hypernatremia.

Brain lesions were noted in 42 (45.2%) hypernatremic neonates with edema being the most common (n=37, 39.8%), followed by hemorrhage in 13 (13.9%), and thrombosis in 6 (6.4%) babies. Among the isolated lesions, cytoxic edema alone was noted in 24 (25.8%), and hemorrhage alone in 4 (4.3%) babies. None of the neonates developed isolated thrombosis, or both hemorrhage and thrombosis. Among combination of lesions, edema was associated with thrombosis in 4 (4.3%) babies, with hemorrhage in 7 (7.5%) babies, and with both thrombosis and hemorrhage in 2 (2.15%) babies. Cytotoxic edema predominantly affected juxtacortical/ subcortical white matter (n=21, 56.7%), followed by periventricular white matter and centrum semiovale (n=14, 37.8% each). Isolated white matter edema dominated the picture, it was observed in 21 (56.7%) brain edema patients (Table I). Fifteen hemorrhagic lesions were observed in 13 patients. Intraventricular hemorrhage (IVH) was the most common. Eight thrombotic lesions were observed in six patients. Superior saggital, transverse and straight sinuses were the most commonly affected site (Table II). Edema, hemorrhage and thrombosis were noted only when serum sodium levels exceeded 160, 170 and 180 mmol/L, respectively.

In the present hospital-based study conducted among 93 hypernatremic neonates; we observed brain lesions in 45.2% babies. The incidence of edema, hemorrhage, and thrombosis was 39.8%, 14%, and 6.4%, respectively. Cytotoxic edema affected both gray and white matter, but isolated involvement of white matter was more common. Brain edema, hemorrhage and thrombosis were noted only when serum sodium levels exceeded 160, 170 and 180 mmol/L, respectively.

The major limitations of our study are lack of a comparison group, and non-uniform timing of MRI brain scan. In our study MRI scan was carried out only after ensuring stability of the baby in the MRI suit. Lesions observed in our study cannot be purely ascribed to hypernatremic dehydration, as some of the complications might have evolved during rehydration therapy. However, for clinical purpose, outcome lesions (ultimate lesions at discharge) are more important than the initial insult.

As compared to previously available retrospective data [5], the incidence of brain edema, hemorrhage and thrombosis are approximately 5-10 times higher in the present study. Lack of neuroimaging in all cases, predominant use of ultrasonography and computerized tomography (CT) scan for brain imaging, and less severe hypernatremia might explain the lower incidence of brain lesions in the previous study. The most common type of lesion and/or combination of lesions has not been defined in previous studies [2,4,6,7], as these were based on few case reports/small case series or retrospective analyses. The most common site of lesions also remained inconclusive in the past except for thromboses, which in most case reports showed predominant involvement of sagittal, straight and transverse sinuses [8-11], similar to our findings. These findings are in contrast to adults with hypernatremia, in whom osmotic demyelination syndrome has been noticed as the most common neuroradiological lesion; extra pontine myelinolysis (EPM) being more common than central pontine myelinolysis (CPM) [12,13].

In our population besides hypernatremia, associated presence of uremia and metabolic acidosis might also have contributed to the neurological insults. Uremia predominantly affects the basal ganglia followed by cortical/subcortical regions and white matter. This pattern of injury has an important bearing on neurodevelopment, as reversibility is less and outcome is poor [12, 14]. Most of our babies had isolated white matter edema which usually carries a good prognosis. Associated involvement of basal ganglia and cortical/subcortical white matter might have been contributed by uremia and acidosis.

Our center caters to a wide spread of population of the Thar desert. Some of the settlements are located more than 300 km away from our center. Long travel probably further aggravates the dehydration in the neonates coming from far-flung areas. As almost half (49.5%) of our babies had serum sodium levels higher than 180 mmol/L, the present findings may not be generalizable to the predominantly mild hypernatremia group.

MRI brain should be advocated in all neonates admitted with hypernatremic dehydration, especially in severe hypernatremia (serum sodium levels exceeding 160 mmol/L). Further multi-centric research is required to focus on neuroradiological and neurodevelopmental outcomes of this high risk population. As brain edema, which was the most common lesion in our study, usually evolves during rehydration therapy, choice of rehydrating fluid and its rate of infusion also needs exploration.

Note: Additional material related to this study is available with the online version at www.indianpediatrics.net

Ethics clearance: Institutional Ethics Committee, Dr SN Medical College, Jodhpur. No. SNMC/IEC/2019/55 dated March 16, 2019.

Contributors: AM: data acquisition, and initial manuscript; AS: conception, design and manuscript revision; VKG: conception, design and intellectual content; NG: data analysis and manuscript revision; VP: conception, data interpretation, initial manuscript; KC: data interpretation, initial manuscript. All authors approved the final manuscript.

Funding: None; Competing interest: None stated.

1. Mujawar NS, Jaiswal AN. Hypernatremia in the neonate: Neonatal hypernatremia and hypernatremic dehydration in neonates receiving exclusive breastfeeding.　Indian J Crit Care Med. 2017;21:30-33.

2. Musapasaoglu H, Muhtesem Agildere A, Teksam M, et al. Hypernatraemic dehydration in a neonate: Brain MRI findings. Br J Radiol. 2008;81:e57-60.

3. Boskabadi H, Akhondian J, Afarideh M, et al. Long-term neurodevelopmental outcome of neonates with hyper-natremic dehydration. Breastfeed Med. 2017;12:163-68.　

4. Lavagno C, Camozzi P, Renzi S, et al. Breastfeeding-associated hypernatremia: A systematic review of the literature.　J Hum Lact. 2016;32:67-74.

5. Unal S, Arhan E, Kara N, et al. Breastfeeding-associated hypernatremia: retrospective analysis of 169 term newborns. Pediatr Int. 2008;50:29-34.

6. Mocharla R, Schexnayder SM, Glasier CM. Fatal cerebral edema and intracranial hemorrhage associated with hyper-natremic dehydration.　Pediatr Radiol. 1997;27:785-787.

7. Han BK, Lee M, Yoon HK. Cranial ultrasound and CT findings in infants with hypernatremic dehydration.　Pediatr Radiol. 1997;27:739-742.

8. van Amerongen RH, Moretta AC, Gaeta TJ. Severe hypernatremic dehydration and death in a breast-fed infant.　Pediatr Emerg Care. 2001;17:175-80.　

9. Caglar MK, Ozer I, Altugan FS. Risk factors for excess weight loss and hypernatremia in exclusively breast-fed infants.　Braz J Med Biol Res. 2006;39:539-544

10. Gebara BM, Everett KO. Dural sinus thrombosis complicating hypernatremic dehydration in a breastfed neonate.　Clin Pediatr (Phila). 2001;40:45-48.

11. Hilliard TN, Marsh MJ, Malcolm P, et al. Sagittal sinus thrombosis in hypernatremic dehydration.　Arch Pediatr Adolesc Med. 1998;152:1147-48.

12. Ismail FY, Szóllics A, Szólics M, et al. Clinical semiology and neuroradiologic correlates of acute hypernatremic osmotic challenge in adults: A literature review.　Am J Neuroradiol. 2013;34:2225-32.　

13. Han MJ, Kim DH, Kim YH, et al. A case of osmotic demyelination presenting with severe hypernatre-mia.　Electrolyte Blood Press. 2015;13:30-36.

14. de Oliveira AM, Paulino MV, Vieira APF, et al. Imaging patterns of toxic and metabolic brain disorders. Radio-graphics. 2019;39:1672-95.