Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing
polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included
flatulence,
abdominal pain,
nausea, diarrhoea and
headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with
lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional
laxative therapies. Eighteen per cent (27/154) of PEG patients required additional
therapies compared to 31% (47/150) of
lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea,
abdominal pain,
nausea,
vomiting and
pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of
magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of
magnesia over
lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing
liquid paraffin (
mineral oil) with
lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring
liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included
abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and
enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and
lactulose (1 study, 125 patients, P = 0.481), senna and
lactulose (1 study, 21 patients, P > 0.05),
lactitol and
lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed
guar gum and
lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and
liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95).
AUTHORS' CONCLUSIONS: The pooled analyses suggest that PEG preparations may be superior to placebo,
lactulose and milk of
magnesia for childhood
constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of
liquid paraffin (
mineral oil). There is no evidence to demonstrate the superiority of
lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood
constipation, as well as the role of
liquid paraffin. The optimal dose of PEG also warrants further investigation.