Results of Growth Factor Therapy in Children with Short Bowel Syndrome
A.M. Nucci, PhD, RD; D. Finegold, MD; J.A. Yaworski, MSN, RN; L. Kowalski, MS, RD, CNSD; and E.M. Barksdale Jr., MD. The Intestinal Care Center, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pa.
Purpose: In addition to the structural, ultrastructural and functional changes that occur after extensive enterectomy or in utero bowel loss that results in short bowel syndrome (SBS), a complex array of humoral responses take place that also may affect adaptation of the remaining small intestine as well as nutritional status and/or growth. These include alterations in the levels of circulating hormones and trophic substances such as growth hormone (GH) and insulin-like growth factors (IGF-1 and IGFBP-3). The purpose of this investigation is to report on the management/treatment of three children with SBS (>four years in duration) and growth failure.
Methods: Serum measures of growth factors and response to GH stimulation following an arginine insulin tolerance test (AITT) were determined. Weight and height z-scores as well as linear growth velocity were calculated annually pre- and post-initiation of medication therapy.
Results: Patient #1 (male, 8.5 years old, midgut volvulus, 36 cm bowel) was found to be GH deficient while patients #2 (female, 12.5 years old, gastroschisis, 70 cm bowel) and #3 (male, 13 years old, jejunal atresia, 21 cm bowel) were found to have limited GH responsiveness. Subsequently, treatment with GH [#1] and growth releasing factor (GRF) [#2 & 3] was prescribed. Z scores for both weight and height improved over time. Positive linear growth velocity was observed from initiation of therapy (<0.5 cm/year for all) to over three years of treatment [mean #1: 4.7 cm/year, #2: 9.0 cm/year, #3: 5.0 cm/yr (normals >4.5, >8.5 and >4.9 cm/year, respectively)]. All patients received a regular diet with oral supplements while two received parenteral nutrition support for ~one year.
Conclusion: In children with medically refractory SBS, it is not only important to offer trophic factors but also essential that sufficient nutrient substrate be provided to achieve adequate growth.
Presented at the 34th Annual Meeting of the American Pediatric Surgical Association, Fort Lauderdale, Fla., May 25-28, 2003.
Insulin-like Growth Factor 1 and Insulin-like Growth Factor 3: Indices of Intestinal Failure in Children
E.M. Barksdale Jr., MD; A.N. Koehler, PhD, RD; J.A. Yaworski, MSN, RN; M. Gardner, RN; and J. Reyes, MD. The Intestinal Care Center, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pa.
Purpose: A number of pediatric patients with short bowel syndrome (SBS) manifest growth failure despite aggressive nutritional support. Exogenous growth hormone (GH) therapy in children with SBS has proved disappointing.
The purpose of this study was to determine if there were characteristic patterns of GH, IGF-1 or IGFBP-3 levels in pediatric SBS patients with profound growth failure in an effort to elucidate an early strategic approach to management of SBS in the subpopulation.
Methods: Forty patients (29 boys, 11 girls; mean age 5.3 years; range, 0.5 to 18.6 years) with SBS (<30% total bowel length) who received intensive nutrition support and follow-up underwent serological tests for GH, IGF-1, IGFBP-3, and thyroid function. Height (HT), weight (WT), and bone age were assessed relative to age-appropriate percentiles. Growth failure was defined as a HT and WT at less than the fifth percentile and bone age >two standard deviations below actual age. Residual small bowel length was determined by review of pathological and operative reports. Comparisons between the growth factors, bowel length and anthropometric data were analyzed by X2.
Results: Two distinct subgroups of patients emerged from our study. Thirty-eight percent of patients (n=11) had growth failure by anthropometry that was associated significantly with low IGF-1 independently and with both IGF-1 and IGFBP-3 levels (p<0.05). There were no significant associations with GH level, thyroid function, small bowel length or the amount of parenteral versus enteral intake in either subgroup of these patients. Low IGF-1 and IGFBP-3 but not GH levels may be indices of intestinal failure in pediatric SBS. Growth in the subpopulation is refractory to aggressive standard approaches to nutritional support and may require early interventions.
Conclusion: Exogenous IGF-1 and IGFBP-3, not GH, may be beneficial to treat this subpopulation.
Published in the Journal of Pediatric Surgery, Vol. 34(5):655-662, May 1999.
