Lactose avoidance for young children with acute diarrhea

For the current issue of the Journal, we asked Drs Natasha Saunders and Jeremy Friedman to comment on and put into context the recent Cochrane Review on avoiding or reducing intake of lactose-containing milk or milk products for reducing the duration and severity of acute diarrhea in children. Young children with acute diarrhea, typically due to infectious gastroenteritis, may temporarily stop producing lactase, the intestinal enzyme that digests lactose. Thus, they may not digest lactose, the main sugar in milk, and this may worsen or prolong the diarrheal illness. However, there is uncertainty regarding whether avoiding lactose-containing milk or milk products helps young children recover from acute diarrhea more quickly. The authors performed a search of the Cochrane Infectious Diseases Group Specialized Register (May 14, 2013), Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library (Issue 4, 2013), MEDLINE (1996 to May 14, 2013), EMBASE (1974 to May 14, 2013), LILACS (1982 to May 14, 2013) and the reference lists of potentially relevant trials and key conference proceedings, and wrote to individuals and organizations in the field. Randomized or quasi-randomized controlled trials that assessed the effects of avoiding or reducing exposure to lactose in young children <5 years of age with acute diarrhea. Data were extracted using the standard methods of the Cochrane Infectious Diseases Group, and two review authors independently evaluated trial quality and data extraction. Continuous outcomes were compared using mean difference (MD) and dichotomous outcomes were compared using the risk ratio (RR). All results are presented with 95% CIs; the quality of evidence was assessed using the GRADE approach. Thirty-three trials enrolling 2973 children with acute diarrhea were included. Twenty-nine trials were exclusively conducted on inpatients, all from high- or middle-income countries. Fifteen trials included children <12 months of age, and 22 excluded children who were being breastfed. Compared with lactose-containing milk, milk products or foodstuffs, lactose-free products may reduce the duration of diarrhea by a mean of approximately 18 h (MD −17.77 [95% CI −25.32 to −10.21]; 16 trials, 1467 participants, low-quality evidence). Lactose-free products likely also reduce treatment failure (defined variously as continued or worsening diarrhea or vomiting, the need for additional rehydration therapy or continuing weight loss) by approximately one-half (RR 0.52 [95% CI 0.39 to 0.68]; 18 trials, 1470 participants, moderate-quality evidence). Diluted lactose-containing milk has not been shown to reduce the duration of diarrhea compared with undiluted milk or milk products (five trials, 417 participants, low-quality evidence), but may reduce the risk of treatment failure (RR 0.65 [95% CI 0.45 to 0.94]; nine trials, 687 participants, low-quality evidence). In young children with acute diarrhea who are not predominantly breast-fed, a change to a lactose-free diet may result in earlier resolution of acute diarrhea and reduce treatment failure. Diluting lactose-containing formulas may also have some benefits; however, further trials are required to confirm this finding. There are no trials from low-income countries, where mortality for diarrhea is high and malnutrition is more common. The full text of the Cochrane Review is available in The Cochrane Library (1). Acute diarrhea is one of the most common illnesses experienced by children globally and contributes to widespread morbidity, mortality and health resource utilization (2). Current guidelines for treatment of diarrhea reflect the ultimate goal of replacing lost fluids and electrolytes. The Canadian Paediatric Society (CPS), American Academy of Pediatrics (AAP) and WHO recommend commercially prepared oral rehydration solutions (ORS) to replace losses for children with mild to moderate dehydration (2–4). ORS is widely available, easy to administer, well tolerated, contains appropriate concentrations of glucose and electrolytes, and is inexpensive. ORS is as effective as intravenous rehydration for the treatment of mild to moderate dehydration with lower costs and fewer adverse events (5). Breastfed infants should continue to breastfeed for both hydration and nutritional benefits (6). Once children have been rehydrated, current guidelines recommend early introduction of an unrestricted, age-appropriate diet, which can include lactose-containing milk products (3,4). Historic evidence has shown that this practice is safe in children with no or mild dehydration (7). Early feeding improves enterocyte regeneration and renews production of digestive enzymes, ultimately shortening the duration of diarrhea and improving nutrient absorption. Transient lactase deficiency from intestinal inflammation or injury following diarrhea is common and underlies the rationale behind some practitioners recommending avoidance of lactose-containing products during a diarrheal episode. This is believed to potentially reduce the duration and severity of diarrhea. Currently, for treatment of children with gastroenteritis, we generally follow the CPS/AAP recommendations as described above. We encourage caregivers to offer their child a regular diet if tolerated. We do not recommend diluting milk. In children with more prolonged diarrhea, usually lasting >1 week, or if milk feeds appear to trigger profuse diarrhea, we may empirically consider a trial of lactose avoidance. Use of pharmacological antimotility agents are not recommended for treatment of diarrhea in young children (8). More recently, good evidence has been published showing that probiotics shorten the duration of diarrhea, although implementation of this evidence is not yet part of routine practice (9). The current Cochrane Review (1) has several limitations. Most studies reviewed were based on hospitalized children whose severity of illness may be worse than children with diarrhea in the out-patient setting, and almost one-half were not from high-income countries, potentially reducing the generalizability of these findings. Many trials used either hydrolyzed or soy-based formulas; the change in protein content may confound the results and their interpretation. The majority of trials predated current treatment approaches and most lacked blinding, potentially impacting the results. Most trials involved cases of rotavirus infection. With the recent recommendations in favour of rotavirus vaccine in Canada, it is unclear how the changing etiology of infectious gastroenteritis will impact the findings from previous trials. The evidence that lactose avoidance may shorten the duration of diarrhea by an average of 18 h is of low quality (ie, we have limited confidence in the results) and reflects a wide range of duration of symptoms (29 h to 230 h), limiting clinical interpretability. While the evidence that lactose avoidance reduced ‘treatment failure’ by approximately one-half is rated as moderate quality (ie, we have reasonable confidence in the results), it is not easy to understand the clinical significance of this finding without a more rigorous definition of ‘treatment failure’ (10). In addition, there were only 8% fewer treatment failures, which begs the question of how practical and cost effective a change in formula for all children would be. In 11 trials, dilution of lactose-containing products did not significantly reduce the duration of diarrhea, and there is low-quality evidence that it reduced the odds of treatment failure. The quality of the evidence presented, combined with the limitations outlined above, are not sufficiently compelling for us to change our current practice as outlined in the CPS/AAP recommendations. Our personal practice of considering recommending a lactose-free formula in individual children with more persistent diarrhea appears to be appropriate based on the possibility that this may result in some reduction in ‘treatment failure’. Future studies using a large-scale randomized controlled trial design in a community setting with more clearly defined, clinically relevant outcomes may be required to allow for more robust recommendations.

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