Hormonal therapy for impaired growth due to pediatric-onset inflammatory bowel disease: a systematic review and meta-analysis with trial sequential analysis

INTRODUCTION: Inflammatory bowel diseases (IBDs) have an increasing incidence in the pediatric population. The dysabsorptive effects of this condition often lead to a decrease in linear growth. However, the effectiveness and safety of growth hormone (GH) therapy in this population is still a topic of debate, with studies showing conflicting results. CONTENT: MEDLINE, Embase, and Cochrane Library databases were systematically searched according to the PRISMA guidelines. All experimental studies featuring children with IBD receiving GH therapy were included. In addition, a trial sequential analysis (TSA) was conducted to determine the sample size required for each outcome. The prospective registry was carried out under protocol CRD42024563079. The total data set comprised eight studies involving 127 patients with IBD, 78 (61.41 %) of whom received GH therapy, with a mean follow-up duration of 1.3 years. A statistically significant effect of GH was found in increasing the height standard deviation score (HtSDS) of children with IBD (standardized mean difference - SMD=1.07; CI=0.58, 1.56; p<0.0001). When comparing children who received GH with controls, no significant improvement in HtSDS was observed (SMD=0.18; CI=-0.73, 1.08; p=0.70). However, meta-regression analysis indicated that a longer follow-up was associated with a greater improvement in the HtSDS (p=0.04). Regarding height velocity (HV), a significant increase was found when comparing measurements before and after the initiation of hormone therapy (mean difference - MD=4.09; CI=2.58, 5.60; p<0.0001). An increase in HV was also noted in children receiving GH compared to the control group (MD=4.47; CI=2.03, 6.90; p=0.0003). No significant changes in the Pediatric Crohn's Disease Activity Index (PCDAI) were detected, comparing values before and after the start of treatment (MD=-10.09; CI=-22.29, 2.10; p=0.10). The overall prevalence of any adverse effect was estimated at 15.51 % (95 % CI: 2.32-58.70 %). Most common reaction was itching at injection sites. TSA indicated a low risk of overestimating or underestimating the intervention's effect on the analyzed outcomes. SUMMARY: Our study points to the effectiveness and safety of GH therapy in children with IBD and growth impairment. OUTLOOK: Further randomized controlled trials (RCT) with standardized methodologies and extended follow-up periods are necessary to confirm these findings.