Functional constipation in children: a systematic review on prognosis and predictive factors.

BACKGROUND AND AIM: Knowledge regarding prognosis and factors influencing the clinical course of functional constipation in children is important to enable general practitioners and paediatricians to give accurate patient information, to compare treatment strategies, and identify children with high risk for unfavourable outcome. The objective of the study was to investigate and summarize the quantity and quality of evidence on prognosis of childhood constipation with and without treatment and its predictive factors. METHODS: An extensive literature search in MEDLINE and Embase was performed to identify prospective follow-up studies evaluating the prognosis or prognostic determinants of functional constipation. Methodological quality was assessed using a standardised list. Results on prognosis of constipation were statistically pooled, and the influence of prognostic factors was summarised in a best evidence synthesis. RESULTS: The search strategy resulted in a total of 2882 abstracts. Only 14 publications met our inclusion criteria, of which 21% scored high methodological quality. Included studies showed large heterogeneity in study populations and outcome measures. Without regard to these differences, 49.3% +/- 11.8% of all of the children followed for 6 to 12 months were found to recover and taken off laxatives. The percentage of children who were free from complaints, regardless of laxative use, after 6 to 12 months was 60.6% +/- 19.2%. There is substantial evidence that defecation frequency and a positive family history are not associated with recovery from constipation. CONCLUSIONS: The few studies published on prognosis of childhood functional constipation and predictive factors showed large heterogeneity and poor methodological quality. Overall, 60.6% of children are found to be free from symptoms after 6 to 12 months. Recovery rate showed no relation with defecation frequency or positive family history. Based on the present literature, we are unable to identify a group of children with high risk for poor prognosis.

Currently recommended treatments of childhood constipation are not evidence based: a systematic literature review on the effect of laxative treatment and dietary measures.

INTRODUCTION: Constipation is a common complaint in children and early intervention with oral laxatives may improve complete resolution of functional constipation. However, most treatment guidelines are based on reviews of the literature that do not incorporate a quality assessment of the studies. OBJECTIVE: To investigate and summarise the quantity and quality of the current evidence for the effect of laxatives and dietary measures on functional childhood constipation. METHODS: The Medline and Embase databases were searched to identify studies evaluating the effect of a medicamentous treatment or dietary intervention on functional constipation. Methodological quality was assessed using a validated list of criteria. Data were statistically pooled, and in case of clinical heterogeneity results were summarised according to a best evidence synthesis. RESULTS: Of the 736 studies found, 28 met the inclusion criteria. In total 10 studies were of high quality. The included studies were clinically and statistically heterogeneous in design. Most laxatives were not compared to placebo. Compared to all other laxatives, polyethylene glycol (PEG) achieved more treatment success (pooled relative risk (RR): 1.47; 95% CI 1.23 to 1.76). Lactulose was less than or equally effective in increasing the defecation frequency compared to all other laxatives investigated. There was no difference in effect on defecation frequency between fibre and placebo (weighted standardised mean difference 0.35 bowel movements per week in favour of fibre, 95% CI -0.04 to 0.74). CONCLUSION: Insufficient evidence exists supporting that laxative treatment is better than placebo in children with constipation. Compared to all other laxatives, PEG achieved more treatment success, but results on defecation frequency were conflicting. Based on the results of this review, we can give no recommendations to support one laxative over the other for childhood constipation.

Functional characterization of two promoters in the human bone morphogenetic protein-4 gene.

Bone morphogenetic protein-4 (BMP-4) is a member of the BMP family, which consists of important regulators of bone formation and embryonic development. We have previously isolated the human BMP-4 encoding gene, which is associated with the heritable disorder Fibrodysplasia Ossificans Progressiva. In this study, we describe the molecular cloning and functional characterization of two promoters involved in the transcriptional regulation of the human BMP-4 gene, one upstream of exon 1, the second located in intron 1, upstream of exon 2. These two promoters give rise to different transcripts in a cell type- and differentiation-dependent manner. Mutational analysis showed cell type-specific regulation of both promoter activities. Gel mobility shift assays indicated the presence of cell type-specific transcription factor binding sites in promoter 1. In addition, evidence was found for a novel BMP-4 transcript. Since various human diseases can be linked directly to aberrant expression of BMP genes, the present findings are of great importance in attempts to develop strategies for therapeutic interference with such diseases.