Fortification of breast milk in VLBW infants: metabolic acidosis is linked to the composition of fortifiers and alters weight gain and bone mineralization.

BACKGROUND & AIMS: Study objectives were to test (a) whether increased incidence of metabolic acidosis (MA) was caused by introduction of a new commercially available fortifier for breast milk, (b) if so, whether its modification would decrease the incidence of MA and (c) to analyze the impact of MA on growth. METHODS: Double-blind randomized design. Healthy breast-fed infants (≤34 gestational weeks). Primary outcome measure was incidence of MA (BE < -6.0 mmol/L). Secondary outcome measures were growth, bone mineral content (BMC), vital signs, treatment with sodium hydrogen carbonate and Ca and laboratory parameters (pH, pCO2, HCO3⁻, electrolytes). RESULTS: Part 1 (comparison of standard (SF) and new fortifier (NF)): Interim analysis showed MA in 1 out of 7 (SF) and 7 out of 8 (NF) infants, p = 0.01; therefore the study was interrupted; subsequently the fortifier was adapted by modifying mineral components. Part 2 (comparison of SF and reformulated fortifier (RF)): MA occurred in 3 out of 15 (SF) and 6 out of 19 (RF), p = 0.7. When data of all infants studied, those with MA had lower mean weight gain (median: 9 vs. 21 g/kg/d, p < 0.01) and lower BMC (1.6% vs. 1.9% BMC/lean, p = 0.04) at discharge. CONCLUSIONS: When fed fortified breast milk, mild MA spontaneously may develop in 20-30% of VLBW infants. A fortifier with an inappropriate composition may increase the severity and frequency of MA. Our data show that weight gain and BMC seem to be related to acid-base homeostasis. It may be speculated that inadequate growth of fully fed preterm infants is triggered more often by imbalances of acid-base status than previously expected.

Development of inflammatory bowel disease in patients with juvenile idiopathic arthritis treated with etanercept.

OBJECTIVE: With the increasing use of etanercept for juvenile idiopathic arthritis (JIA) new possible adverse events are reported including new autoimmune diseases. Our purpose was to examine if the incidence of inflammatory bowel disease (IBD) in patients with JIA using etanercept is higher than in the healthy age-matched population. We give the clinical characteristics of the IBD in patients with JIA using etanercept. METHODS: The national JIA registries for etanercept of The Netherlands, Germany, Finland, Denmark, and Italy were searched for patients with JIA and IBD. The total number of patient-years was used to calculate incidence. The physicians of the identified patients were asked to give clinical details. RESULTS: Thirteen cases of IBD in JIA patients were identified in the registries between 1999 and 2008. The IBD incidence in JIA patients while using etanercept was 362 per 100,000 patient-years under etanercept, about 43 times higher than in the general pediatric population. Clinical presentation of IBD in JIA patients using etanercept was similar to that in non-JIA patients. The median time between onset of JIA and onset of IBD was 6 years and 10 months. The time between the start of etanercept and the first appearance of IBD symptoms was between 9 days and 4.5 years. CONCLUSION: The incidence of IBD in JIA patients using etanercept seems to be markedly increased, analyzing data from European registries. This incidence of IBD in the etanercept registries cannot be compared to the incidence of IBD in JIA patients using other treatment without etanercept, because such registries do not exist yet in all European countries. These findings are in keeping with a report of 8 new IBD cases occurring in French children with JIA using etanercept. These findings illustrate the need for large international disease-specific registries focused on outcome and pharmacovigilance.