Body composition and cardiometabolic health of pediatric patients with X-linked hypophosphatemia (XLH) under burosumab therapy

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The Natural History of Metabolic Comorbidities in Turner Syndrome from Childhood to Early Adulthood: Comparison between 45,X Monosomy and Other Karyotypes

ObjectivePatients with Turner syndrome (TS) are at increased risk for metabolic disorders. We aimed to delineate the occurrence and evolution of metabolic comorbidities in TS patients and to determine whether these differ in 45,X monosomy and other karyotypes.MethodsA longitudinal and cross-sectional retrospective cohort study was conducted in a tertiary pediatric endocrine unit during 1980–2016. Ninety-eight TS patients, 30 with 45,X monosomy were followed from childhood to early adulthood. Outcome measures included weight status, blood pressure (BP), glucose metabolism, and lipid profile.ResultsLongitudinal analysis showed a significant change in body mass index (BMI) percentiles over time [F(3,115) = 4.8, P = 0.003]. Age was associated with evolution of elevated BP [systolic BP: odds ratio (OR) = 0.91, P = 0.003; diastolic BP: OR = 0.93, P = 0.023], impaired glucose metabolism (HbA1c: OR = 1.08, P = 0.029; impaired glucose tolerance: OR = 1.12, P = 0.029), and abnormal lipid profile (cholesterol: OR = 1.06, P = 0.01; low-density lipoprotein cholesterol: OR = 1.07, P = 0.041; high-density lipoprotein cholesterol: OR = 1.07, P = 0.033). The occurrence of metabolic comorbidities was similar in 45,X monosomy and other karyotypes. Coexistence of multiple metabolic comorbidities was significantly higher in 45,X monosomy [F(1,72) = 4.81, P = 0.032]. BMI percentiles were positively correlated with metabolic comorbidities (occurrence and number) in each patient (r = 0.35, P = 0.002 and r = 0.383, P = 0.001, respectively).ConclusionOur longitudinal study provides unique insights into the evolution of weight gain and metabolic disorders from childhood to early adulthood in TS patients. Since overweight and increasing age aggravate the risk for metabolic comorbidities, careful surveillance is warranted to prevent and control obesity already from childhood. The more prominent clustering of metabolic comorbidities in 45,X monosomy underscores the importance of a more vigorous intervention in this group

Midkine and Pleiotrophin Concentrations in Amniotic Fluid in Healthy and Complicated Pregnancies

<div><p>Background</p><p>Midkine (MDK) and pleiotrophin (PTN) are heparin-binding growth factors that, in rodents, are highly expressed in early life and decrease to undetectable levels by adulthood. The potential roles of MDK and PTN in human growth and development are not completely elucidated.</p><p>Method and Findings</p><p>To delineate the role of MDK and PTN in human development, we developed high sensitivity assays to measure their concentrations in amniotic fluid (AF) at various gestational ages in both healthy and complicated pregnancies. We found that both of these growth factors could be readily measured in AF and that the concentrations were higher than most cytokines previously reported in AF.</p><p>Conclusion</p><p>The concentration of MDK but not that of PTN declined with gestational age. Both MDK and PTN concentrations were found to be lower in pregnancies that were complicated by chorioamnionitis at term, raising the possibility that these growth factors might be useful as markers for infection.</p></div

Plasma MDK concentrations during pregnancy and in non-pregnant healthy female controls.

<p>Plasma MDK concentrations were similar among non-pregnant healthy women, normal preterm pregnancies in the absence of labor, preterm in labor, PPROM, term not in labor, and term in labor. Data are presented as mean ± SEM.</p

Amniotic fluid PTN concentrations.

<p>Panel A: AF PTN concentrations (n = 170) did not vary significantly with gestational age (Panel A). Panel B: AF PTN concentrations were similar between the absence and presence of labor in healthy term pregnancies, and also similar between pregnancies complicated by PPROM and by premature labor. MDK was lower in term pregnancies complicated by chorioamnionitis than in term pregnancies without infection (P = 0.01). Data are presented as mean ± SE. Panel A: Black triangle (mid-gestation), x (preterm labor), blue circle (premature preterm rupture of membranes), black diamond (term not in labor), green square (term in labor), orange triangle (term chorioamnionitis).</p

Amniotic fluid MDK concentrations.

<p>Panel A: AF MDK concentrations (n = 202) declined with gestational age. Panel B: AF MDK concentrations were not significantly different between healthy term pregnancies in the absence of labor and during labor or between pregnancies complicated by PPROM and premature labor. MDK was lower in term pregnancies complicated by chorioamnionitis than in term pregnancies without infection (P = 0.015). Data are presented as mean ± SEM. Panel A: Black triangle (mid-gestation), x (preterm labor), blue circle (premature preterm rupture of membranes), black diamond (term not in labor), green square (term in labor), orange triangle (term chorioamnionitis).</p

Flowchart of samples evaluated for plasma midkine (1A), amniotic fluid midkine (1B), and amniotic fluid pleiotrophin (1C).

<p>PPROM, preterm premature rupture of membranes; n, number of samples; gestational age represents the median (range) age at which sample was obtained.</p