Short-Term Effects of Blood Transfusions on Hepcidin in Preterm Infants.

BACKGROUND: Hepcidin, a key regulatory peptide hormone in iron homeostasis, may in future serve as a non-invasive iron status parameter for monitoring iron supplementation in preterm infants. For this, coexisting influencing factors should be taken into account. OBJECTIVES: To evaluate the short-term effects of red blood cell (RBC) transfusions on hepcidin concentrations in serum (HepS) and urine (HepU) of preterm infants. METHODS: This was a prospective, observational study conducted between May 2009 and September 2010 at a single neonatal unit (Tübingen University Hospital, Tübingen, Germany) in very preterm infants, i.e. with a gestational age (GA) of <32 weeks, who received clinically indicated RBC transfusions. The concentration of the mature, 25 amino-acid form of hepcidin was determined in serum und urine by competitive enzyme-linked immunosorbent assay together with cellular indices before and after transfusion. RESULTS: Twenty preterm infants born at a median GA of 26 + 0/7 (interquartile range: 24 + 6/7 to 27 + 3/7) weeks received 27 RBC transfusions at a median corrected age of 31 + 3/7 (29 + 6/7 to 34 + 5/7) weeks. When measured shortly after transfusion (mean time: 10 h), haematocrit values increased from a mean of 26.6% (SD 2.8) to 40.9% (SD 3.2); p < 0.0001. HepS also increased [geometric mean: 44.3 (95% confidence interval 30.8-63.8) ng/ml vs. 58.0 (35.7-94.3) ng/ml; p < 0.05] but HepU remained unaffected. CONCLUSION: The data indicate that HepS concentrations increase shortly after RBC transfusion in preterm infants. Long-term observational studies are needed to understand the dynamics of hepcidin regulation in preterm infants.

Publication bias in animal research: a systematic review protocol.

BACKGROUND: Systematic reviews and meta-analyses of pre-clinical studies, in vivo animal experiments in particular, can influence clinical care. Publication bias is one of the major threats of validity in systematic reviews and meta-analyses. Previous empirical studies suggested that systematic reviews and meta-analyses have become more prevalent until 2010 and found evidence for compromised methodological rigor with a trend towards improvement. We aim to comprehensively summarize and update the evidence base on systematic reviews and meta-analyses of animal studies, their methodological quality and assessment of publication bias in particular. METHODS/DESIGN: The objectives of this systematic review are as follows: •To investigate the epidemiology of published systematic reviews of animal studies until present. •To examine methodological features of systematic reviews and meta-analyses of animal studies with special attention to the assessment of publication bias. •To investigate the influence of systematic reviews of animal studies on clinical research by examining citations of the systematic reviews by clinical studies. Eligible studies for this systematic review constitute systematic reviews and meta-analyses that summarize in vivo animal experiments with the purpose of reviewing animal evidence to inform human health. We will exclude genome-wide association studies and animal experiments with the main purpose to learn more about fundamental biology, physical functioning or behavior. In addition to the inclusion of systematic reviews and meta-analyses identified by other empirical studies, we will systematically search Ovid Medline, Embase, ToxNet, and ScienceDirect from 2009 to January 2013 for further eligible studies without language restrictions. Two reviewers working independently will assess titles, abstracts, and full texts for eligibility and extract relevant data from included studies. Data reporting will involve a descriptive summary of meta-analyses and systematic reviews. DISCUSSION: Results are expected to be publicly available later in 2013 and may form the basis for recommendations to improve the quality of systematic reviews and meta-analyses of animal studies and their use with respect to clinical care.

Hepcidin concentrations in serum and urine correlate with iron homeostasis in preterm infants.

OBJECTIVES: To evaluate whether hepcidin concentrations in serum (Hep((S))) and urine (Hep((U))) correlate with iron metabolism, erythropoiesis, and inflammation in preterm infants. STUDY DESIGN: Thirty-one preterm infants (23-32 weeks gestational age) were included. The concentration of the mature, 25 amino-acid form of hepcidin was determined by enzyme-linked immunosorbent assay in serum, urine, blood counts, reticulocytes, and iron measurements. RESULTS: Median (IQR) Hep((S)) was 52.4 (27.9-91.9) ng/mL. The highest values were measured in patients with systemic inflammation. Hep((S)) and Hep((U)) correlated strongly (P = .0007). Hep((S)) and Hep((U)) also correlated positively with ferritin (P = .005 and P = .0002) and with reticulocyte hemoglobin content (P = .015 and P = .015). Hep((S)) and Hep((U)) correlated negatively with soluble transferrin receptor/ferritin-ratio (P = .005 and P = .003). Infants with lower hemoglobin concentrations and higher reticulocyte counts had lower Hep((S)) (P = .0016 and P = .0089). CONCLUSION: In sick preterm infants, iron status, erythropoiesis, anemia, and inflammation correlated with the mature 25 amino-acid form of hepcidin. Further evaluation of Hep((U)) for non-invasive monitoring of iron status in preterm infants appears justified.