Median Standard Deviation Score Research Articles

Pediatric Crohn’s disease from onset to adulthood: granulomas are associated with an early need for immunomodulation

Objective. Childhood onset Crohn’s disease (CD) is considered more aggressive than adult onset disease. Epithelioid cell granulomas in intestinal biopsies are one, non-obligate, criterion of CD. We investigated granulomas as markers of CD severity in children followed to adulthood. Material and methods. Forty-five individuals with childhood onset CD were studied from diagnosis until attainment of final height, with data on disease location, medical and surgical management and with detailed growth data analyses. A blinded review of diagnostic biopsies was also performed. Results. We found granulomas in 22/45 (49%) children at diagnosis, altogether in 28/45 (62%) patients during the disease course (median overall follow-up – 12.3 years, range 9.3–18). Granulomas were found in 9/11 (82%) with upper gastrointestinal involvement (cumulatively 17/20, 85%) (p = 0.017 and p = 0.006, respectively). The time from diagnosis to initiating immune modulating treatment (median 4.5 months, range 0–75) was shorter in the granuloma-positive group (16/22) compared to the granuloma-negative group (18/23) (median 33 months, range 2–105; p = 0.01). The median standard deviation score height at diagnosis and final adult height (both adjusted for target height) did not correlate to findings of granulomas. Conclusions. Epithelioid cell granulomas were associated with a shorter time to initiating immune modulating drugs, as a possible sign of more severe disease, but growth was not affected.

Sequential Measurement of Bone Mineral Density Identifies Ongoing Recovery of Detrimental Bone Mass in Very Long Term Adult Survivors of Childhood Cancer

AbstractAbstract 4296 BackgroundAim of this study was to investigate status and longitudinal evolvement of BMD in long-term adult survivors. Patients and methodsA single-center cohort of 410 adult long-term survivors (171 females) was included in this retrospective study. Age at diagnosis was 6.6 years (0.0–16.8 yrs), and at follow up 24.5 years (18.0–49.3 yrs). Median follow-up time was 15.2 years (5.1–39.8 yrs).BMD of the lumbar spine (BMDLS) and total body (BMDTB) were measured. Results were compared with healthy age matched controls. ResultsOverall BMDTB and BMDLS were low in long-term survivors (median standard deviation score (SDS) −0.60, P < 0.001 and median SDS −0.40, P < 0.001 respectively). In ALL survivors both BMDTB (median SDS −0.65, P < 0.001) and BMDLS (median SDS −0.48, P < 0.001) were low. Backwards elimination of the multivariate linear regression analysis showed that both cranial irradiated and/or total body irradiated survivors were at significant risk for low BMDTB. BM(A)DLS was not different between survivors and controls and no risk factors were identified for low BM(A)DLS. In general, a slight but significant improvement of BMDTB and BMDLS was found in our sequential measurement. This BMD improvement was not found for ALL survivors alone. ConclusionsOur study shows low BMD in childhood cancer survivors treated with cranial or total body irradiation. However, sequential DXA analysis shows ongoing recovery of bone mass, which suggests a potential for reaching peak bone mass later in life. Disclosures:No relevant conflicts of interest to declare.

Obstetric Outcomes in Women With Turner Karyotype

There is concern over the high risk of cardiovascular complications, hypertensive disorders, and other adverse obstetric outcomes among pregnant women with Turner syndrome (TS). A diagnosis of TS is made in some women late in life or not at all. Spontaneous pregnancies are rare in women with TS and are associated with a high rate of complications, especially miscarriage. The use of assisted reproductive techniques is an option for these women; pregnancy and implantation rates after oocyte donation in women with TS seem to be comparable with those without TS who need this treatment. Few data are available on obstetric outcome in pregnant women with TS. The aim of this retrospective population-based cohort study was to compare maternal and neonatal outcomes among singleton pregnancies of women with and without TS. Data on births occurring between 1973 and 2007 from the Swedish Genetic Turner Register and the Swedish Medical Birth Register were cross-linked. Obstetric outcome in infants born to women with TS was compared with a reference group of 56,000 women from the general population. Mean gestational age and birth weight were adjusted for maternal age. Outcome in TS women with twins was described separately. A total of 115 women with TS gave birth to 208 children (202 singletons and 3 sets of twins) during the study period. The TS diagnosis was unknown in 52% of the women before the first delivery. Women in the TS group were older at the first delivery than women in the reference group; median age was 30 years and 26 years, respectively (P < 0.0001). There was a trend toward more women with TS having preeclampsia during their first pregnancy (6.3 vs. 3.0%; P = 0.07). One woman suffered from an aortic dissection during her second spontaneous pregnancy. Compared with the reference group, the median gestational age was shorter in children in the TS group (-6.4 days, P = 0.0067), and median birth weight was lower (-208 g, P = 0.001); however, no significant difference was found in median standard deviation scores for weight and length at birth. The rate of cesarean delivery was higher in the TS group than in the reference group (35.6% vs. 11.8%, respectively, P < 0.0001). There was no significant difference in birth defects between groups. These findings show that women with a TS karyotype have mostly favorable obstetric outcomes. Singletons of women with TS have a shorter gestational age but a similar size at birth. The data also show no difference in birth defects between women with and without TS.

Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia

Imatinib mesylate, a tyrosine kinase inhibitor, is used in the treatment of chronic myelogeneous leukemia (CML). Given its ease of administration and manageable side effects in adults, imatinib mesylate was introduced as therapy for pediatric CML. Recently published case reports describe growth deceleration in children treated with imatinib. This study details the growth phenotype of seven pediatric patients maintained in remission on imatnib mesylate over an extended period of time. This study is a retrospective chart review of pediatric patients with CML at Oregon Health & Science University treated with imatinib. Height, weight, and body mass index (BMI) measurements were collected before and during treatment. Median standard deviation scores (SDS) were analyzed by Wilcoxon Rank-Sum test and Wilcoxon signed rank cohort analysis. Individual patient analysis demonstrated five of seven subjects with a statistically significant decrease in height SDS pre versus during treatment. The whole group analysis showed a trend to significance for difference in median height SDS pre and during treatment (P = 0.078). Bone age was delayed in all four patients in whom bone ages were obtained. IGF-1, IGFBP-3, and thyroid levels during treatment were normal. Four patients experienced an improvement in height SDS during puberty. However, three patients approaching near final adult height failed to achieve genetic height potential determined by mid-parental target height. Growth in children with CML appears to be adversely impacted by imatinib therapy. BMI and IGF-1/IGFBP-3 are maintained during treatment, suggesting a direct effect of imatinib on the growth plate.

Overweight children with type 1 diabetes have a more favourable lipid profile than overweight non-diabetic children

In the present article, we aimed to compare the cardiometabolic risk between overweight children with and without type 1 diabetes (T1DM). Therefore, data with regard to cardiometabolic risk parameters of 44 overweight Caucasian children (3–18 years) with T1DM were matched with 44 overweight peers without T1DM for sex, ethnicity, age and standard deviation score of BMI (Z-BMI). Detailed history was taken, information regarding anthropometrics and family history were collected and blood pressure was measured. Blood samples were collected for evaluation of lipid profiles (fasting in controls, non-fasting in T1DM children), alanine aminotransferase and HbA1c (in children with T1DM). It was found that overweight children with T1DM had lower median standard deviation score of waist circumference (Z-WC) as compared to the overweight control group [median, 2.0 (interquartile range, IQR, 1.5–2.3) vs. 2.6 (IQR, 2.0–2.9), P < 0.001]. After adjustment for Z-WC, in children with T1DM, median high-density lipoprotein cholesterol levels were significantly higher and median low-density lipoprotein cholesterol lower in T1DM children, as compared to their peers without T1DM [1.40 (IQR, 1.2–1.5) vs. 1.2 (IQR, 1.0–1.3) and 2.7 (IQR, 2.5–3.2) vs. 3.0 (IQR, 2.5–3.4), respectively, all P < 0.01]. When dividing children according to glycaemic status, children with suboptimal glycaemic control had higher values of triglycerides as compared to well-controlled children [1.3 (IQR, 1.0–1.8) vs. 0.96 (IQR, 0.80–1.2), P = 0.036]. In conclusion, overweight children with T1DM have a more favourable lipid profile, as compared to non-diabetic overweight controls, in spite of a higher frequency of a positive family history of CVD, T2DM and hypertension. Still, paediatricians should give extra attention to cardiometabolic risk factors within this vulnerable group, taking into account the already high cardiometabolic risk.

Growth Hormone Treatment in Prepubertal Children With Celiac Disease and Growth Hormone Deficiency

To evaluate the growth response to growth hormone (GH) replacement therapy during a gluten-free diet in patients with celiac disease (CD) associated with GH deficiency (GHD). A total of 14 prepubertal children affected by CD and GHD with no catch-up growth after >/=12 months of gluten-free diet and a reversion to seronegativity for antiendomysium antibodies and 10 age-matched prepubertal children with idiopathic GHD (IGHD) entered the study. All of the patients were treated with the same GH dosage (0.25 mg/kg subcutaneously each week). Height, growth rate, and body mass index were measured at the time of diagnosis of CD, at the time of endocrinological evaluation, and after the first, second, and third year of GH replacement therapy. Growth rate strikingly increased (P < 0.005) during the first year of therapy in a similar way in subjects with CD/GHD and IGHD (from a median standard deviation score [SDS] of -2.34 to an SDS of 3.25 and from an SDS of -1.29 to an SDS of 2.79, respectively). During the second and third years of GH treatment, the growth rate tended to decrease but the values at the third year were always positive (CD/GHD, median SDS, 1.10; IGHD, median SDS, 0.11), indicating continued catch-up growth. In patients with CD with GH deficiency confirmed after >/=12 months of gluten-free diet, GH replacement therapy should be started to allow complete catch-up growth in children. In addition, the effect of GH treatment in patients who comply with a gluten-free diet seems to be comparable to that observed in children with IGHD.

Selective late steroid withdrawal after renal transplantation

Steroid withdrawal (SW) after paediatric renal transplantation (RTPL) is controversial. Selective late SW has been performed in our unit since 1995. The safety and effects of SW were analysed retrospectively in 47 patients undergoing RTPL between 1995 and 2004. Initial immunosuppression consisted of cyclosporine A, azathioprine or mycophenolate mofetil and steroids. Criteria for SW were: (1) stable renal function, (2) time interval after RTPL > or = 1 year, (3) no rejection or time interval after last rejection > or = 1 year and (4) good compliance. SW was performed in 30 patients at an age of 13.5 years (range 4.5-18.5) and 2.2 years (range 1-6.6) after RTPL. After SW, one patient experienced a steroid-sensitive rejection. Follow-up after SW (1.3 year; range 0.25-7.5) showed maintained renal function: glomerular filtration rate at SW and currently was 82 (65-128) and 82 (42-115) ml/min per 1.73 m(2), respectively. The number of patients on antihypertensive treatment did not significantly change (at SW: n = 15; currently: n = 11). Height and body mass index (BMI) remained stable: Median standard deviation score (SDS) for height/BMI at SW and currently was -1.1/0.2 and -0.8/0.1, respectively. Selective late SW was safe regarding renal function and had no significant effect on blood pressure and growth.

Chronic hemodialysis in infants and children under 2 years of age.

Over the past 16 years, 18 children under 2 years of age received chronic hemodialysis (HD) at our center. Five children were anuric at the start of HD and 6 had significant co-morbidity. The most common underlying diagnosis was posterior urethral valves. The median age at the start of HD was 12.2 months. A total of 39 episodes (defined as a discrete time period during which HD was the principle form of renal replacement therapy) of HD were performed, with a median duration of 7 months and 91.3 dialysis sessions per episode. Problems with vascular access were very common, with a revision ratio of 40%. Twenty-two line revisions were required for 36 episodes of line infection, with a median rate of line infection of 2.7 infections/patient years. The most commonly encountered organism was coagulase-negative Staphylococcus (69%). Twenty-three lines needed revision due to poor line function, despite the routine use of heparin. The effectiveness of HD was assessed in 11 patients who received HD for a continuous period of 3 or more months. The median urea reduction rate was 72%, while the parathyroid hormone levels improved to within twice the upper limit of the reference range in 69%. While there was no significant change in the median weight and height standard deviation score (SDS), the median SDS for head circumference showed significant improvement ( P=0.04). Both growth and developmental outcomes were strongly influenced by existing co-morbidity. Sixteen (89%) children were transplanted. Four (22%) children died, 3 after successful transplants. None of the deaths occurred on HD or resulted from its complications. In conclusion, HD in infants and small children is an effective and safe form of renal replacement therapy, but problems with vascular access limit its long-term use.

Analysis of growth in children after orthotopic liver transplantation.

Growth after pediatric liver transplantation is an important factor in determining the quality of life. We collected data on height, skeletal age, and liver function of 45 consecutive pediatric transplant recipients and assessed the influence of primary diagnosis, liver function, and immunosuppressive regimen on their growth. Height and skeletal age were plotted as median standard deviation scores versus years post-transplantation. Growth, in terms of both height and skeletal age, were continuous without catch-up growth. Primary diagnosis was found to have no influence on height and poor liver function had a negative effect on both height and skeletal growth. A higher alternate day prednisolone maintenance dose also had negative effect on skeletal growth. Thus, it can be concluded that a pretransplant lack of growth will not be restored and is an indication for early transplantation in end-stage liver disease, especially in younger children.

Analysis of growth in children after orthotopic liver transplantation

Abstract Growth after pediatric liver transplantation is an important factor in determining the quality of life. We collected data on height, skeletal age, and liver function of 45 consecutive pediatric transplant recipients and assessed the influence of primary diagnosis, liver function, and immunosuppressive regimen on their growth. Height and skeletal age were plotted as median standard deviation scores versus years post-transplantation. Growth, in terms of both height and skeletal age, were continuous without catch-up growth. Primary diagnosis was found to have no influence on height and poor liver function had a negative effect on both height and skeletal growth. A higher alternate day prednisolone maintenance dose also had a negative effect on skeletal growth. Thus, it can be concluded that a pretransplant lack of growth will not be restored and is an indication for early transplantation in end-stage liver disease, especially in younger children.

Focal intestinal perforation in preterm infants is an emerging disease

In order to elicit the pathogenesis of focal intestinal perforation in preterm infants we contrasted 8 infants who developed this disease with 16 gestation-matched controls. The cases were found to have lower birthweights for gestation (median standard deviation score of -1.02 in cases versus -0.08 in controls), and more frequently had pre-existing patent ductus arteriosus and intraventricular haemorrhage (88 and 63% in cases versus 25 and 6% in controls, respectively). There were similar rates of other perinatal variables in the two groups, including indomethacin and umbilical arterial catheter use. Conditions associated with fetal or neonatal hypoxia are important antecedents for this emerging distinct clinical entity.