Introduction

Diarrhea in infants is defined as the passage of three or more abnormally loose or watery stools per day(1). Diarrhea is culprit for 18% of deaths in children age group which is estimated as 1.5milion deaths per year in the world and 5 million deaths per year in the developing countries.

The most common cause of acute diarrhea in all children is Rota-viruses. Chronic diarrhea, defined as diarrhea that lasts for more than two weeks, in developing countries is mostly due to intestinal infection(2) .

The risk of serious complications from chronic diarrhea depends on the cause of the diarrhea, age and general health status of the patient(3) .

The Infants have increased susceptibility to complications related to diarrhea due to immaturity of fluid homeostasis and immunologic responses(4) .

The list of diseases and mechanisms responsible for diarrhea in infants is large and higher compared to older children and Different approach is required for evaluating infants and young children with chronic Diarrhea.The most common cause of chronic diarrhea in infancy include: inclusion micro villi disease, food allergy, hirschsprung’s disease,malrotation,lymphangectasia,short bowel syndrome(2).

 We believe all these steps should be performed as a result of tight collaboration between the neonatologist, pediatric gastroenterologist, immunologist, geneticist, and nutritionist(5) . In the vast majority of cases appropriate therapy must be started immediately to prevent dehydration and long term, and sometimes life-threatening, complications(6) .

We performed this study to investigate chronic diarrhea, its etiologies, clinical features and outcomes in infancy.

Matherials and methods

Retrospective study investigating infants hospitalized in the gastroenterology department of Tehran tertiary care center from 2010 to 2012.Thirty six(36) infants under 3 months age, admitted  to tertiary care center complaining of chronic diarrhea, were entered the study.

Inclusion criteria were:

1-Infants below 3 months.

2- Diarrhea, defined on the basis of increased frequency and watery consistency of stools with dehydration according to definition employed in pediatric gastroenterology(7).

3-chronic diarrhea defined if duration of diarrhea was more than 14 days(1, 2).

Data was collected from patient’s medical files and was recorded in a specific questionnaire form. This study was approved by ethics committee of our institution.

Demographic data ,laboratory findings including: stool exam, and culture,  Characteristics of Diarrhea including Severity of dehydration, osmotic or secretory diarrhea and result of small or large  biopsy if had done, were elicited.

 osmotic or secretory diarrhea is defined by measuring stool osmotic gap that osmotic diarrhea has osmotic gap over 50 and secretory diarrhea has  below 50(6).

Possible correlation between variables including: gender, gestational age, birth weight,  weight percentile, severity of dehydration with etiology and type of diarrhea, were investigated by statistical analysis. data were analyzed in SPSS18 and a P-value

Results:

The medical files of admitted infants with chronic diarrhea during three years,  were reviewed and 36 cases were found to be suitable to enter the study. Median age of patients was 75 days (between 39-90 days)and median birth weight of patients was 4408/7 grams.

Different variables and  frequencies in the study population are shown in Table-1.

 Diagnosis of food allergy was reported in 15 cases (41/7%) which, diagnosis was confirmed by symptomatic improvement to extensively hydrolyzed formula(Aptamil pepti;Danone,Nutricia,schiphol,Netherland)  or the diet without cow's milk protein in lactating mother. Glucose /Galactose malabsorption reported in7 patients (19/4%) that confirmed by clinical manifestations and laboratory tests: Stool low PH, positive stool reducing substance , serum acidosis and improvement on glucose/galactose free formula.(Galactomin19;SHS company, Germany).Post gastroenteritis malabsorption was found in 4 cases (11/1%) which diagnosed with clinical manifestation  and response to lactose free formula(Isomil;Abbott laboratories,Abbott park,USA).

Three cases (8/3%) received diagnosis of sepsis that 2 of them had positive blood culture with pseudomonas spp.Two patients (5/6%) presented with Autoimmune Enteropathy based on duodenum and colon Biopsy and Response to corticosteroid treatment.Galactosemia was reported in one case (2/8%), which was diagnosed by serum Glucose chromatography, difference of oxidase glucose and Benedict test that confirmed by GALT test( Galactose 1 phosphate uridyl transferase test)and response to galactose free formula(Isomil formula;Abbott,Abbott laboratories, Abbott park, USA).One case (2/8%) with history of hirschsprung’disease that was admitted with complaint of chronic diarrhea had pseudomembranous colitis in colon Biopsy. For one case (2/8%) with chronic steatorrhea and sweat chloride>60meq/L final diagnosis of cystic fibrosis was achieved.

Intestinal malrotation reported in one case (2/8%).The diagnosis was confirmed with radiography. One case (2/8%) had congenital chloride diarrhea on the base of clinical manifestation, history of ployhydramniosis and laboratory results including:

Secretory diarrhea, Stool Chloride more than100 meq/lit and hypochloremic metabolic alkalosis.

Four patients (11.11%) had early onset of Diarrhea: one with congenital chloride  Diarrhea, one with glucose /Galactose malabsorption and one with cystic fibrosis presented in first day after birth and the other, Auto immune enteropathy  that presented second  day after birth.

In this study, food Allergy was the most common etiology(41/7%) and cystic Fibrosis, chloride diarrhea, pseudomembranous colitis,malrotation and galactosemia had the lowest prevalence(2/8%).

In this study it was no statistical difference between type of diarrhea and sex, gestational Age, severity of dehydration, birth weight and nutrition. In this study 58/3%of cases with osmotic diarrhea and 63/6%with secretory diarrhea had weight percentile at admission below3%that There was statistical difference between type of diarrhea and weight percentile at admission (p<0.03).In infants with food allergy,33/3% had  more than 5 white blood cell ( WBC) ,13/9% had less than 5 WBC and 50% no WBC in stool exam and in this group 13/9%of infants had more than 5 Red Blood Cell( RBC), 19/4%  had less than 5  RBCand 63/9%no RBC in stool exam.

 Prevalence of food Allergy in non-exclusive breastfed infants were 3/5times greater than exclusive Breast fed infants, but the difference was not statistically significant. (P=0.243)

Risk of allergy and sepsis were higher in preterm infants compared with term infants, but the difference was not statistically significant (P=0/4).

60% of infants with gestational age below 37 weeks, had 10% dehydration but 62/96% of infants with gestational age over 37weeks had 5% dehydration, which was a significant statistical difference between gestational age and severity of dehydration  (P=0.044).

Intestinal biopsy was done in 7 (20%) of patients. One case had diagnosis of  glucose /Galactose malabsorption with normal biopsy results. One case had sepsis in which biopsy had done to rule out other diagnoses, one had changes suggestive of auto immune enteropathy in biopsy and four cases had pathological changes, suggesting allergy. Positive stool culture was found in none of the cases. Four (11/1%) deaths were reported among 36 patients: one due to cystic fibrosis, two due to sepsis and one in Glucose/Galactose malabsorption patient.

Discussion

The results of study showed that in this particular age group; diarrhea is a relatively uncommon but critical condition underlying abroad spectrum of diseases. Several diseases responsible for infantile Diarrhea and number of etiologies are higher compared to older patients.The most common etiology in this study was food Allergy(41/7%).

 In a retrospective study by Passariello et al, evaluating infants hospitalized in Neonatal Intensive Care Unite (NICU) in Italy, from 5801 infants in NICU, 39 cases had diarrhea, which was acute in 92.3% and chronic in 7.7% of cases. The most common cause of diarrhea in these infants was food allergy (20.5%)and  hirschsprung’s disease, hospital diarrhea ,metabolic errors , and cystic fibrosis had the lowest incidence. (2.5%)(5) .This implies the variation in different studies are.

  Recently, international study of Asthma and Allergy in childhood reported an increase in Allergic Disease prevalence in the younger pediatric age group (8). In this study, food allergy was the most common cause of diarrhea in non-Exclusive breastfed infants. It is presumed that breast feeding has an allergy preventive  effect compared with cows’ milk formula feeding, but the extent of the preventive effect remains controversial (9).

In a recent Finnish study of non-selected newborns followed up to 17 years of age, breast feeding was associated with lower rates of eczema and food allergy at 1 and 3 years, as well as a lower score of respiratory allergy up to 17 years of age, compared with cows’ milk formula fed individuals (10).It is presumed that exclusive breast Feeding or combination with avoidance of Supplementary foods, in high risk infants with atopic disease in at least one first degree relative, has preventive effect on allergy in infants less than 4 months (3).

in the study by Victora in Brazil, infants who received powdered milk or cow's milk in addition to breast milk, were at 4.2 times higher risk of death from diarrhea compared with infants who did not receive artificial milk; while the risk for infants who didn't receive any breast milk was 14.2 times higher (11).but in this study there was no correlation between nutrition and mortality rate.  In this study 60% of infants with chronic diarrhea has weight percentile under 3% that Demonstrates that  malnutrition prolongs the duration of diarrhea and Increases its mortality rate.

The interaction between malnutrition and diarrheal disease is bi-directional. Increases in immunization coverage, better health care access, improvements in water and electrolyte replacement, and other socioeconomic changes affect both mortality from diarrhea, and childhood nutrition status (12). The majority of patients with osmotic (58/3%) and secretory diarrhea(63/6%),had weight percentile below3%; which shows malnutrition as a risk factor for both types of diarrhea. In a study done by Nichols et al on Infants with chronic diarrhea and malnutrition, maltase and lactase enzyme wasn’t found in intestinal villi, which caused osmotic diarrhea (13). Our study demonstrates that infants with gestational age  below 37weeks had more severe dehydration than infants  over 37 weeks of gestation(20% vs. 3/8%, p<0.04); which can be  explained by prematurity of hemodynamic regulatory systems in preterm  infants.

In this study the most common cause of death 2(50%) was sepsis  that both of them had positive blood culture .In a study by Chisti on infants hospitalized due to diarrhea in Bangladesh, the case-fatality rate was significantly higher among bacteremic infants compared with those without bacteremia. (33% vs. 6%, p < .01) (14). Bacteremia appears to be an important link between diarrheal illness and death. In children with diarrhea who are suspected of being septic, early implementation of anti-microbial therapy against the broad spectrum of pathogens appears to be indicate(15) .

Conclusion

This study demonstrates that Chronic diarrhea of infancy, includes several diseases with different etiologies .Early diagnosis and timely treatment are both crucial in prognosis of infantile diarrhea.  This study demonstrated  that food allergy is the most common etiology that the suspicion  importance of food allergy in infants presenting with diarrhea has highlighted .The  further clinical and epidemiologic studies, are needed for improving  diagnostic approach for infantile diarrhea.

Acknowledgments

We thank, department of pediatric gastroenterology of children medical center(Tehran university, Iran)for clinical data collection.

Conflict of interests: None

 Table-1 Different variables and their frequencies in the study population.