Significant gender difference in serum levels of fibroblast growth factor 21 in Danish children and adolescents

INTRODUCTION: Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor with effect on glucose and lipid metabolism, and shown to be elevated in diseases related to metabolic syndrome. Due to the increasing frequency of metabolic syndrome in the pediatric population, and as FGF21 studies in children are limited, we investigated baseline serum levels of FGF21 in healthy children during an oral glucose tolerance test. METHODS: A total of 179 children and adolescents from the COPENHAGEN Puberty Study were included. An OGTT with glucose and insulin measurements, a dual energy X-ray absorptiometry (DXA) scan and a clinical examination including pubertal staging were done on all subjects. Serum levels of FGF21, adiponectin, and leptin were determined by immunoassays at baseline. RESULTS: The girls had significantly higher levels of FGF21 compared with boys (155 pg/mL vs. 105 pg/mL, P = 0.04). 38 children (21%) had levels below detection limit of assay. Baseline levels of FGF21 showed positive correlation with triglycerides, but no significant correlations were found between FGF21-concentration and body mass index (BMI), DXA-derived fat percentage, LDL- HDL- and non-HDL cholesterol, leptin or adiponectin levels, respectively. Neither was any correlation found between baseline FGF21-levels and the dynamic changes in glucose and insulin levels during the OGTT. CONCLUSION: FGF21 is independent of adiposity in children, and the significant metabolic effect seems to be limited to pathological conditions associated with insulin resistance. The higher levels of triglycerides in the girls may explain the significantly higher levels of FGF21 in girls compared with boys. SYSTEMATIC REVIEW REGISTRATION: The COPENHAGEN Puberty Study was registered in ClinicalTrials.gov (identifier NCT01411527), and approved by the local ethics committee (reference no. KF 01 282214 and KF 11 2006–2033)

Altered Response to A(H1N1)pnd09 Vaccination in Pregnant Women: A Single Blinded Randomized Controlled Trial

<div><p>Background</p><p>Pregnant women were suspected to be at particular risk when H1N1pnd09 influenza became pandemic in 2009. Our primary objective was to compare the immune responses conferred by MF59®-adjuvanted vaccine (Focetria®) in H1N1pnd09-naïve pregnant and non-pregnant women. The secondary aims were to compare influences of dose and adjuvant on the immune response.</p><p>Methods</p><p>The study was nested in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC₂₀₁₀) pregnancy cohort in 2009-2010 and conducted as a single-blinded block-randomised [1∶1∶1] controlled clinical trial in pregnant women after gestational week 20: (1) 7.5 µg H1N1pnd09 antigen with MF59-adjuvant (Pa7.5 µg); (2) 3.75 µg antigen half MF59-adjuvanted (Pa3.75 µg); (3) 15 µg antigen unadjuvanted (P15 µg); and in non-pregnant women receiving (4) 7.5 µg antigen full adjuvanted (NPa7.5 µg). Blood samples were collected at baseline, 3 weeks, 3 and 10 months after vaccination, adverse events were recorded prospectively.</p><p>Results</p><p>58 pregnant women were allocated to Pa7.5 µg and 149 non-pregnant women were recruited to NPa7.5 µg. The sero-conversion rate was significantly increased in non-pregnant (NPa7.5 µg) compared with pregnant (Pa7.5 µg) women (OR = 2.48 [1.03–5.95], p = 0.04) and geometric mean titers trended towards being higher, but this difference was not statistically significant (ratio 1.27 [0.85–1.93], p = 0.23). The significant titer increase rate showed no difference between pregnant (Pa7.5 µg) and non-pregnant (NPa7.5 µg) groups (OR = 0.49 [0.13–1.85], p = 0.29).</p><p>Conclusion</p><p>Our study suggests the immune response to the 7.5 µg MF59-adjuvanted Focetria® <i>H1N1pnd09</i> vaccine in pregnant women may be diminished compared with non-pregnant women.</p><p>Trial Registration</p><p>ClinicalTrials.gov<a href="http://www.clinicaltrials.gov/ct2/show/NCT01012557?term=NCT01012557&rank=1" target="_blank"> NCT01012557</a>.</p></div

Study group flowchart.

<p>Study group flowchart.</p

Antibody responses according to vaccine groups.

<p>P: Pregnant.</p><p>NP: Non-pregnant.</p><p>GMT: Geometric mean titer.</p><p>GMR: Geometric mean ratio.</p><p>CI: Confidence interval.</p><p>Sero-protection: Titer ≥40.</p><p>Sero-conversion: Pre titer<10, Post titer ≥40.</p><p>Significant increase: Pre titer ≥10, Post titer 4 fold Pre titer.</p><p>Sero-conversion or significant increase: Percentage of total number of women in each vaccine group.</p>†<p>At day 0 GMT were the same in all groups (ANOVA, p = 0.51).</p>‡<p>The number of women with sero-protection did not differ in any of the groups compared over time (GEE).</p>*<p>GMT at 3 weeks, 3 months and 10 months were adjusted for baseline titer.</p

Evolution of sero-conversion rate (as percentage) in women in the four vaccine groups over time.

<p>The trends over time for the number of women sero-converted were not significantly different. The number of non-pregnant women (NPa7.5 µg) who sero-converted was 2.48-fold higher than among pregnant (Pa7.5 µg) women using general estimating equations.</p