Critical Appraisl : Early Vs Late refeeding in Children with acute diarrhoea
Dr. Shubhra Prakash Paul MD (Ped.) Part IIBangladesh Institute of Child Health
TitleEarly versus DelayedRefeeding for Childrenwith Acute Diarrhoea(Intervention Review)
Article Particulars Gregorio GV, Dans Authors LF, Silvestre MA Evidence-based Child Health: a Cochrane Review Journal Journal 2012; 7:2: 721–757. DOI 10.1002/ebch.1835
Background Acute diarrhea is one of the principal causes of morbidity and mortality among children in developing countries. Oral rehydration therapy and dietary management is the cornerstone of treatment. There is a lack of data and studies on both the timing and type of feeding that should be adopted during the course of the illness.
ObjectiveTo compare the efficacy and safetyof early and late reintroduction offeeding in children with acutediarrhea.
MethodologyCriteria for considering studies forthis review I. Types of studies Randomized Controlled Trial (RCT) II. Types of participants Children less than 10 years old with acute diarrhea, including both breastfed and non-breastfed
MethodologyIII. Types of Intervention Intervention: Early Refeeding group Feeding was reintroduced within 12 hours from start of rehydration; continuous breastfeeding during rehydration was included in this group. Control: Late Refeeding group Feeding was reintroduced more than 12 hours after start of rehydration.
MethodologyIV. Types of Outcome Measure Primary Duration of diarrhea (hours) from admission until cessation of diarrhoea. Secondary • Total stool output (ml/kg) during the first 24 hours and 48 hours after start of rehydration. • Percentage weight gain 24 hours after start of rehydration and at resolution of diarrhea.
MethodologyIII. Types of Outcome Measure contd. Secondary contd. • Unscheduled intravenous (IV) fluid therapy. • Cases of vomiting Adverse events (all adverse effects including) • Hyponatraemia (low sodium; serum sodium level ≤130 mmol/L), • Hypokalaemia (low potassium; serum potassium level ≤3 mmol/L), and • Development of persistent diarrhoea
MethodologySearch Method Search Engine used • Cochrane Infectious Diseases Group Specialized Register (May 2011) • CENTRAL (The Cochrane Library 2011, Issue1) • MEDLINE (1966 to May 2011) • EMBASE (1974 to May 2011) • LILACS (1984 to May 1981) and • mRCT (metaRegister of Controlled Trial)
MethodologySearch Method Search terms used ‘diarrhoea’, ‘refeeding’, ‘breastfeeding’ and ‘feeding’
MethodologySearch Method Searched researcher and organizations • World Health Organization: • Child Health and Nutrition Research Initiative • International Clinical Epidemiology Network USAID; • Asian Development Bank; • World Bank • International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B)
Data collection and analysis Trial selection Trials are selected by the first two authors. Assessment of risk of bias Risk of bias of each trial is assessed using six components: Sequence generation, Allocation, Concealment, Blinding, Incomplete outcome data, Selective outcome reporting and other biases.
Data collection and analysis Assessment of risk of bias (contd.) Trials are classified into two groups high risk of bias (trials with unclear sequence generation or allocation or concealment and trials where less than 90% of randomized participants completed the trial) and low risk of bias. Studies with low risk of bias were included.
Data collection and analysisData extraction and managementFor continuous outcomes, authors extractedarithmetic means and standard deviations foreach treatment group and noted the numberof participants in each group. In trials withmultiple interventions (where two or moretypes of feeding were used as treatmentgroups), authors pooled the means andstandard deviations of the different feedinggroups across the treatment arms
Data collection and analysisData analysisThe authors• Analysed the data using Review Manager 5 and all results were presented with a 95% confidence interval (CI).• Combined trials that compared early versus late feeding using meta-analysis.• Analyzed data using an available case approach (i.e. all patients for whom an outcome was measured and reported are included in the analysis).
Data collection and analysisData analysis• Compared dichotomous data using risk ratio. The mean difference was used to combine continuous data summarized by arithmetic means and standard deviation.
Data collection and analysis Subgroup analysis and investigation of heterogeneity• The presence of statistical heterogeneity among the interventions was evaluated by inspecting the forest plot and by performing a 2 test for heterogeneity using a p value of 0.10 to determine statistical significance.• Subgroup analysis is used to investigate the effect of age , nutritional status (normal and mild malnutrition versus moderate and severe malnutrition),
Data collection and analysisSubgroup analysis andinvestigation of heterogeneitybreastfeeding (breastfed and non-breastfedinfants) and type of food reintroduced (dilutedversus full-strength milk formula, lactose-freeversus lactose containing)
Result Result of the search 22 relevant trials are assessed • 12 trials are selected • 10 trials are excluded 5 Trials do not satisfy the definition of early or late refeeding used in this review 3 Trials were unclear about when the refeeding started 2 Trials were not randomized controlled trials
Result Total 1283 patients in 12 trials are included (757 for early refeeding and 526 for late refeeding) Drop out 1226 patients were used in the final analysis Early Late refeeding refeeding ( 502 ) (724 )
Result Location 12 Trials were conducted in 16 countries • 1 Multicentre study including 11 European countries • Each 2 trials from UK, USA, Burma and Israel • Each 1 trial from Egypt, Pakistan and Peru Among these 12 • 10 trials conducted in hospital setting • 2 trials enrolled patients from out patient clinic
Result ParticipantsAll trials included children with acute diarrheaof 14 days or less in duration. • 6 trials ---- duration of diarrhoea 5 – 7 days • 4 trials ---- duration of diarrhoea < 72 hours AgeAll trials included children less than five yearsold.Only two trials considered the nutritional status of theparticipants. • 6 trials ---- Age of children < 2 years of age • 2 trials ---- Age of children 3 months to 3
Result Type and timing of refeedingEarly feeding group• Half- or full-strength cow’s milk formula - 4 trials• Boiled rice or the child’s usual diet –3 trials• Soy-based milk formula - 2 trials• Breast milk or cow’s milk formula - 1 trial• Another trial allocated patients to receive either oral rehydration solution and breastfeeding during the rehydration phase or oral rehydration alone for 24 hours
Result Type and timing of refeedingLate feeding group • Feeding after start of rehydration was allowed either after 24 hours – 7 trials • 48 hours – 2 trials • 20 hours – 1 trial • between 24 and 48 hours – 1 trial • One trial allowed feeding only after the diarrhea had stopped
ResultDuration of Follow up TrialsUntil resolution of diarrhoea 6Two weeks after hospital discharge 5Once full strength milk formula could 1be tolerated
ResultOutcome reportedOverall mean duration of diarrhea from 7admission to resolutionThe number who required unscheduled use of IV 6fluidsTotal stool output in the first 24 hours 3Oral intake in the form of ORS, formula or rice 6between 24 and 48 hoursMean percentage weight gain at the 24th hour 3after start of rehydrationMean percentage weight gain at the resolution of 3diarrhoea
Forest plot of early versus laterefeeding in the outcome ofunscheduled use of intravenous fluidsThere was no significant difference in both groups in thenumber of participants who needed IV fluids (RR 0.87, 95% CI0.48 to - 1.59; 813 participants, 6 trials
ResultOutcome reported contd.The number of participants with vomiting 4The development of persistent diarrhea 4The length of hospital stay 2Monitored patients for development of 3hyponatraemia or hypokalaemia
ResultEffects of interventionI. Duration of diarrhea (hours) from admission until cessation of diarrhoea • Shorter Duration Early feeding group 2 trial Late feeding group 1 trial • Similar outcome on both group 4 trial
ResultEffects of interventionII. Total stool output (ml/kg) during the first 24 and 48 hours after start of rehydration After rehydration total stool output in The first 24 hours 3 trials 48 hours 3 trials Less stool output 24 hours (early refeeding) 1 trial 48 hours (Late refeeding) 1 trial
ResultEffects of intervention III. Percentage weight gain at the 24th hour after start of rehydration and at resolution of diarrhea No difference was observed in the mean percentage weight gain at the 24th hour after start of rehydration and atresolution of illnessIV. Cases of vomiting No significant difference between thetwo groups in the number of patientswith episodes of vomiting (RR 1.16, 95% CI 0.72 to 1.86; 456 participants, five
ResultEffects of interventionV. Adverse events: development ofpersistent diarrhea There was no significant difference in the number of patients who developed persistent diarrhea (RR 0.57, 95% CI0.18 to 1.85; 522 participants, four trials)
Discussion Some physicians still recommend variable periods of fasting during acute diarrhea to allow ’bowel rest’ followed by gradual reintroduction of food. The proponents of this practice contend that early refeeding may increase the stool output and lead to more complications, such as unscheduled use of IV fluids, episodes of vomiting, and persistent diarrhea. Present meta-analysis did not provide evidence that early refeeding increases unscheduled use of IV fluids, episodes of vomiting, and development of persistent
Discussion The results support existing practice of early refeeding during or after start of rehydration of patients The review clearly shows that early refeeding does not adversely affect the secondary outcome measures: stool output, weight gain at the end of treatment (which ) likely reflects rehydration, the unpredicted need for intravenous fluids, onset of vomiting, persistence of diarrhea, hyponatremia or length of hospital stay.
Limitation of the study • 7 of the 12 trials (with 1283 participants) included in this review came from high – income countries limiting the applicability for low-income countries. • Quality assurance is difficult because 8 trials were published in or before 1990, when the methods rarely included details about randomization, allocation, concealment or blinding • Heterogeneity regarding participants, interventions and outcome measures
Limitation of the study • No data were provided on the aetiology of acute diarrhoea, but different organisms have varying influence on a child’s symptoms, severity of dehydration, tolerance of food and thus rate of recovery • No consideration was given to use of adjuvant treatment such as zinc, probiotics.
RecommendationFurther trials with more homogenouspopulations (particularly children at highrisk from recurrent diarrhea andmalnutrition with diarrhea of knownetiology) is recommended
Message There is little additional risk of unscheduled use of IV fluids, persistent diarrhea, vomiting or longer hospital stays for children who were re-fed early. So there is no need to keep the bowel at rest during the episode of acute watery diarrhea.