Weight Standard Deviation Score Research Articles

The IGF system and longitudinal growth in preterm infants in relation to gestational age, birth weight and gender

ObjectiveGrowth factors in the blood of very preterm infants may reflect growth and contribute to the understanding of early development. We investigated postnatal levels of insulin-like growth factors (IGFs) in infants born very preterm and related them to early growth development. DesignBlood samples were analyzed weekly for IGF-I, IGF-II, IGF binding protein (BP)-1, IGFBP-3, and acid-label subunit (ALS). Methods73 children born very preterm (gestational age (GA) <32 weeks) were divided according to their gender-specific birth weight standard deviation score (SDS) into either appropriate for GA (AGA) or small for GA (SGA). Fifty-two (71%) and forty-three (59%) infants completed follow-up with anthropometry at approximately 3 years and at 5 years of age respectively. Thirty-six subjects (49%) had blood sampling for IGF-I and IGFBP-3 measurements up to 3 years of age. ResultsIGF-I, IGFBP-3, and ALS levels increased in all groups from week 31 to week 36, with generally lower levels in the SGAs, with a concomitant lower growth velocity. Postnatal ALS was strongly associated with IGF-I and IGFBP-3 in boys, girls and AGA infants. IGF-II was higher in earlier born preterms (GA < 27 weeks) at postmenstrual ages 27.5–29.9 weeks compared with SGAs and late GA (GA ≥ 27 weeks) preterms (p < .0001). IGF-II, in contrast to IGF-I, did not differ between SGAs and AGAs at weeks 31–36. Mean IGFBP-1 was highest in the SGAs compared to AGAs at mean week 28,5 and 31 (p = .001) and IGFBP-1 levels were elevated in relation to IGF-I in the SGAs at that period. At follow-up, the increase in IGF-I between week 31 and 33.5 was a significant positive determinant of height SDS at 3 and 5 years of age in forward multiple regression analysis, independent of target height. ConclusionThis is the first study to investigate postnatal ALS levels in preterm infants. In very preterm infants, IGF-II is less affected by size at birth during early postnatal weeks compared with IGF-I. Early elevated IGFBP-1 might protect the SGA infants from an intense metabolic rate. Our results indicate that anabolic and metabolic processes during weeks 31–36 predicts later height.

Development of a prediction model to target screening for high blood pressure in children

Targeted screening for childhood high blood pressure may be more feasible than routine blood pressure measurement in all children to avoid unnecessary harms, overdiagnosis or costs. Targeting maybe based e.g. on being overweight, but information on other predictors may also be useful. Therefore, we aimed to develop a multivariable diagnostic prediction model to select children aged 9–10 years for blood pressure measurement. Data from 5359 children in a population-based prospective cohort study were used. High blood pressure was defined as systolic or diastolic blood pressure ≥ 95th percentile for gender, age, and height. Logistic regression with backward selection was used to identify the strongest predictors related to pregnancy, child, and parent characteristics. Internal validation was performed using bootstrapping. 227 children (4.2%) had high blood pressure. The diagnostic model included maternal hypertensive disease during pregnancy, maternal BMI, maternal educational level, parental hypertension, parental smoking, child birth weight standard deviation score (SDS), child BMI SDS, and child ethnicity. The area under the ROC curve was 0.73, compared to 0.65 when using only child overweight. Using the model and a cut-off of 5% for predicted risk, sensitivity and specificity were 59% and 76%; using child overweight only, sensitivity and specificity were 47% and 84%. In conclusion, our diagnostic prediction model uses easily obtainable information to identify children at increased risk of high blood pressure, offering an opportunity for targeted screening. This model enables to detect a higher proportion of children with high blood pressure than a strategy based on child overweight only.

Visceral adipose tissue resides within the reference range in children with Prader-Willi syndrome receiving nutritional intervention on a regular basis.

Nutritional intervention for maintaining an appropriate body composition is central to the management of Prader-Willi syndrome (PWS). Despite evidence that visceral adipose tissue (VAT) is associated with increased metabolic risks, the effects of nutritional intervention on fat distribution have not been evaluated for PWS children. We herein investigated fat distribution in 20 genetically diagnosed PWS children (9 males and 11 females); 17 of which received nutritional intervention with or without growth hormone (GH) treatment [GH-treated group (n = 8), GH-untreated group (n = 9)]. GH treatment continued for median of 4.9 years. GH treatment significantly increased height standard deviation score (SDS) whereas body weight SDS and body mass index SDS were not affected in GH-treated group. In GH-untreated group, height SDS significantly decreased during approximately 5 years of follow-up. Fat distribution was evaluated at the median age of 6.93 years in GH-treated group and 7.01 years in GH-untreated group. VAT was maintained within the reference range in both groups. Subcutaneous adipose tissue (SAT) was elevated in GH-untreated groups compared to reference values whereas it was not in GH-treated group. The remaining three subjects, who had never received nutritional intervention or GH treatment, showed increased VAT and SAT. In conclusion, nutritional intervention is beneficial in maintaining VAT within the reference range during childhood, although excessive nutritional intervention may cause unfavorable effect on linear growth.

Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.

BackgroundMetformin treatment (1000–2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity.MethodsA pilot double-blind, placebo-controlled trial was conducted on 18 pre-puberal and early pubertal (Tanner stage I-II) children with obesity and risk markers for metabolic syndrome. Patients were randomly assigned (1:1) to receive metformin (850 mg/day) or placebo for 24 months. Clinical, biochemical (insulin, lipids, leptin, and high-sensitivity C-reactive protein [hsCRP]), and imaging (body composition [dual-energy X-ray absorptiometry and magnetic resonance imaging]) parameters as well as cIMT (ultrasonography) were assessed at baseline and at 6, 12, and 24 months.ResultsThe 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), BMI-SDS, leptin, leptin–to–high-molecular-weight (HMW) adiponectin ratio, hsCRP, cIMT, fat mass, and liver fat in metformin-treated children compared with placebo. The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment. No changes in insulin sensitivity (HOMA-IR) or adverse effects were detected.ConclusionIn this pilot study, metformin treatment in pre-puberal and early pubertal children with obesity seemed to improve body composition and inflammation markers. Our data encourage the development of future fully powered trials using 850 mg/day metformin in young children, highlighting its excellent tolerance and potential long-term benefits.

Cumulative live birth rates after weight reduction in obese women scheduled for IVF: follow-up of a randomized controlled trial.

STUDY QUESTIONDid weight reduction in obese women scheduled for IVF increase cumulative live birth rate (CLBR) after 2 years?SUMMARY ANSWERWeight loss prior to IVF did not increase CLBR.WHAT IS KNOWN ALREADYFew studies have investigated the effect of weight reduction in obese infertile women scheduled for IVF. In a recent randomized controlled trial (RCT), including one IVF cycle, we found no increase in live birth rate after weight reduction. Weight regain after obesity reduction treatment often occurs, and children born to obese women have a higher risk of childhood obesity.STUDY DESIGN, SIZE, DURATIONA 2-year follow-up of a multicenter, RCT running between 2012 and 2018 was performed. Out of 317 women randomized to weight reduction followed by IVF treatment or IVF treatment-only, 305 remained in the full analysis set. Of these women, 90.5% (276/305) participated in this study.PARTICIPANTS/MATERIALS, SETTING, METHODSNine infertility clinics in Sweden, Denmark and Iceland participated in the RCT. Obese women under 38 years of age having a BMI ≥30 and < 35 kg/m2 were randomized to weight reduction and IVF or IVF-only. In all, 160 patients were randomized to a low calorie diet for 12 weeks and 3–5 weeks of weight stabilization, before IVF and 157 patients to IVF-only. Two years after randomization, the patients filled in a questionnaire regarding current weight, live births and ongoing pregnancies.MAIN RESULTS AND THE ROLE OF CHANCE42 additional live births were achieved during the follow-up in the weight reduction and IVF group, and 40 additional live births in the IVF-only group, giving a CLBR, the main outcome of this study, of 57.2% (87/152) and 53.6% (82/153), respectively (P = 0.56; odds ratio (OR) 1.16, 95% CI: 0.74–1.52). Most of the women in the weight reduction and IVF group had regained their pre-study weight after 2 years. The mean weight gain over the 2 years was 8.6 kg, while women in the IVF-only group had a mean weight loss of 1.2 kg. At the 2-year follow-up, the weight standard deviation scores of the children born in the original RCT (index cycle) were 0.218 (1.329) (mean, SD) in the weight reduction and IVF group and − 0.055 (1.271) (mean, SD) in the IVF-only group (P = 0.25; mean difference between groups, 0.327; 95% CI: −0.272 to 0.932).LIMITATIONS, REASON FOR CAUTIONAll data presented in this follow-up study were self-reported by the participants, which could affect the results. A further limitation is in power for the main outcome. The study is a secondary analysis of a large RCT, where the original power calculation was based on live-birth rate after one cycle and not on CLBR.WIDER IMPLICATIONS OF THE FINDINGSThe follow-up indicates that for women with a BMI ≥30 and < 35 kg/m2 and scheduled for IVF, the weight reduction did not increase their chance of a live birth either in the index cycle or after 2 years. It also shows that even in this highly motivated group, a regain of pre-study weight occurred.STUDY FUNDING/COMPETING INTEREST(S)The 2-year follow-up was financed by grants from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-70940 and ALFGBG-77690), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Hjalmar Svensson Foundation. Ms Kluge has nothing to disclose. Dr Bergh has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Einarsson has been reimbursed for lectures for Merck and Ferring. Dr Thurin-Kjellberg reports grants from Merck, and reimbursement for lectures from Merck outside the submitted work. Dr Pinborg has been reimbursed for lectures and other informational activities (Ferring, MSD, Merck, Gedeon Richter). Dr Englund has nothing to disclose.TRIAL REGISTRATION NUMBER ClinicalTrials.gov number, NCT01566929.

Longitudinal changes in bone mineral density in children with inflammatory bowel diseases.

Children with inflammatory bowel disease (IBD) are prone to low bone mineral density (BMD). Our aim was to assess longitudinal changes in BMD in this population. A retrospective longitudinal study of children with IBD, treated at two tertiary centres in Israel, who underwent two BMD measurements by dual-energy X-ray absorptiometry (DXA). Changes in lumbar spine BMD (∆L1-4 z-scores) were examined for correlations with clinical characteristics. The cohort included 41 patients (age at diagnosis 12.1±3.5years, 23 females).The mean interval between the scans was 3.4±2.0years. There was a trend towards improvement in L1-4 z-scores (-1.64±1.02 vs -1.45±0.83, P=.12). ∆L1-4 z-scores correlated positively with ∆weight-standard deviation scores (SDS), ∆height-SDS and ∆BMI-SDS, and with age at the second scan (R=.55, P<.01; R=.42, P<.01; R=.42, P=.01; R=.35, P=.02, respectively); and negatively with L1-4 z-scores at the first scan (R=-.63, P<.01). Stepwise linear regression analysis identified the first scan L1-4 z-scores and ∆weight-SDS as independent predictors of ∆L1-4 z-scores. An L1-4 z-score ≤-2 at the first DXA scan was associated with significant improvement at the second scan. Improvement in BMD was more pronounced in children who gained weight or whose BMD was low at the first scan.

Neonatal clinical blood sampling led to major blood loss and was associated with bronchopulmonary dysplasia.

AimStudies indicate that reduced foetal haemoglobin levels are related to increased neonatal morbidity rates. This study investigated the relationships between sampling‐related blood loss and adult blood transfusions administered during postnatal days 1‐14 and the development of severe neonatal morbidities in extremely preterm infants born before 28 weeks of gestation.MethodsThe medical files of 149 extremely preterm infants born at two university hospitals in Sweden from 2013 to 2018 were investigated.ResultsBlood sampling resulted in a 58% depletion of the endogenous blood volume postnatal days 1‐14 (median 40.4 mL/kg, interquartile range 23.9‐53.3 mL/kg) and correlated with the adult erythrocyte transfusion volume (rS = 0.870, P < .001). Sampling‐related blood loss on postnatal days 1‐7, adjusted for gestational age at birth and birth weight standard deviation score, was associated with the development of bronchopulmonary dysplasia (BPD) (odds ratio by a 10‐unit increase 2.4, 95% confidence interval 1.1‐5.4) (P = .03). No associations were found between blood sampling and intraventricular haemorrhage or necrotising enterocolitis in the full statistical model. The largest proportion of sampling‐related blood was used for blood gas analyses (48.7%).ConclusionDiagnostic blood sampling led to major endogenous blood loss replaced with adult blood components and was associated with the development of BPD.

Disease Severity and Genotype Affect Physical Growth in Children With Familial Mediterranean Fever.

This study aims to analyze the growth parameters in children with familial Mediterranean fever (FMF) according to disease characteristics including genotype and disease severity by a recently validated tool in relatively more patients. This retrospective study included 126 patients with FMF (70 males, 56 females; mean age 7.3±3.6 years; range, 4.1 to 18 years). MEditerranean FeVer (MEFV) gene analysis was performed with a molecular diagnostics tool by using a next-generation sequencing platform. Disease severity was determined for the first visit by the validated tool in children, international severity scoring system for FMF. Growth parameters including weight and height were investigated after standard deviation (SD) scores were calculated by anthropometric references in Turkish children. Median follow-up duration was 74.7 months (range, 7.5 to 169 months). Ninety-three patients (73.8%) had at least one M694V mutation in MEFV gene. Six patients (4.8%) had severe disease, 58 (46%) had intermediate severity, and 62 (49.2%) had mild disease. Mean height SD score was significantly lower at last visit than before colchicine treatment. Initial and last height and weight SD scores were lower in patients with at least one M694V mutation than those without. However, the difference was statistically significant for only initial height SD score. We also found statistically significant lower initial height, final height, and weight SD scores in patients with intermediate severity-severe disease activity than mild disease. We advise physicians to score disease severity prospectively and pay attention to patients with intermediate severity-severe disease to avoid growth disturbances.

Small-for-gestational-age birth is linked to cardiovascular dysfunction in early childhood

The aim of this study was to assess clinical and echographic markers of cardiovascular dysfunction in infants born small for gestational age (SGA) compared to a control group of subjects born adequate for gestational age (AGA). This was a single-center cross-sectional case-control study. We recruited 20 SGA and 20 gestational age-matched AGA subjects at 24 months of age. The study population underwent anthropometric and Doppler 2-dimensional echocardiographic assessments, and carotid artery intima-media thickness (cIMT) and endothelium-dependent vasodilation evaluation (FMD). The pressure-volume curve during diastole was calculated using the algorithm for the elastance calculation on 1 single beat. SGA children showed lower stroke volume, lower left ventricle (LV) dimensions and volume, and greater LV thickness. Diastolic function was impaired in SGA with lower capacitance and higher elastance. Birth weight standard deviation score was positively associated with capacitance and negatively associated with E/E' ratio and elastance, and in SGA infants, the end-diastolic pressure-related volume curve was shifted to the left compared to AGA. cIMT and systemic vascular resistance were significantly higher, while FMD was lower, in SGA compared to AGA; birth weight standard deviation score was directly correlated with FMD and inversely correlated with cIMT. Finally, a longer breastfeeding duration was associated to a lower cIMT even after correction for confounding factors. This study shows that infants born SGA present an early and subtle cardiovascular dysfunction compared to AGA controls. These alterations are strongly related to weight at birth. Finally, breastfeeding exerts an important protective and beneficial cardiovascular effect.

Early or Late Transplantation in Congenital Nephrotic Syndrome: Which is Effective for Optimal Growth?

Congenital nephrotic syndrome (CNS) is a genetic disease that is present in the antenatal period or during the first 3 months of life. In this study, we aimed to compare growth parameters of patients with CNS who received kidney transplants and either (1) had a normal glomerular filtration rate (GFR) at the time of transplant or (2) chronic kidney disease (CKD) at the time of transplant. Patients with a diagnosis of CNS who had a minimum follow-up period of 6 months were evaluated retrospectively. Children at stages 4 or 5 CKD or patients receiving dialysis during the pretransplant period were defined as group 1; patients with normal GFR at the time of transplantation were classified as group 2. Short stature and low weight were defined as less than −2 standard deviation scores (SDS) for height and weight according to their age. A total of 17 patients were included in the study. Thirteen of 17 patients had NPHS1 gene mutations. Group 1 and group 2 consisted of 8 and 9 patients, respectively. Mean height SDS and mean weight SDS in group 2 were higher than group 1 in the pretransplant period (−4.34 ± 1.74 vs −2.84 ± 1.56; P = .011 and −3.54 ± 0.93 vs −1.83 ± 1.13; P = .008). In the post-transplant period, the significant difference in height SDS continued in favor of group 2 (−3.16 ± 1.11 vs −1.16 ± 0.87; P = .002). The short stature rate was 83% in group 1 and 72% in group 2 in the pretransplant period (P = .62), and 83% in group 1 and 27% in group 2 in the post-transplant period (P = .02). Early renal transplantation seems to be effective for optimal height gain in children with CNS.

Metabolic profile, cardiovascular risk factors and health-related quality of life in children, adolescents and young adults with congenital adrenal hyperplasia.

Background The present study was designed to evaluate the metabolic profile, cardiovascular risk factors and quality of life in children with congenital adrenal hyperplasia (CAH) and compare it with age- and sex-matched controls. Methods Fifty-two patients aged 3-21 years with classic CAH due to 21-hydroxylase deficiency were included in the study. Metabolic profiling was done for 36 cases and compared with 28 healthy age- and sex-matched controls. Quality of life was assessed in all 52 children and their parents using a validated Pediatric Quality of Life Inventory (PedsQL) questionnaire and was compared with normative data from the same population. Results The median age was 12 years with 14 (27%) males and 38 (73%) females. Out of the total 52 patients, 35 (67%) had salt wasting and 17 (33%) had simple virilising CAH. The median height standard deviation score (SDS) of cases was similar to that of controls (-0.72 vs. -0.64, p = 0.57) and 81% of females had normal pubertal status indicating a good control of the disease. Weight SDS, body mass index (BMI) SDS, mean diastolic blood pressure and insulin resistance were significantly higher in cases when compared to controls (0.31 vs. -0.3; 0.96 vs. 0.17; 67.8 ± 10.49 vs. 61 ± 8.49 and 2.1 vs. 0.95, respectively). The quality of life was significantly reduced in all domains as per parents' perspective, whereas the children reported reduced quality of social and school functioning. There was no significant correlation between quality of life and metabolic parameters. Conclusions Children with CAH despite a reasonably good control of the disease have a higher cardiovascular risk and reduced quality of life when compared to healthy controls.

Serum osteocalcin levels in overweight children.

PurposeBone plays a role in glucose metabolism through the release of uncarboxylated osteocalcin into the systemic circulation. The identified novel roles for osteocalcin include increasing insulin secretion and sensitivity, energy expenditure, reduction of fat mass, and mitochondrial proliferation and functional enhancement. This study aimed to determine serum osteocalcin levels in overweight children and to investigate the relationships of osteocalcin with glucose metabolism and insulin sensitivity.MethodsAfter overnight fasting, serum osteocalcin levels were measured in overweight (n=50) children between 6.0 and 12.9 years of age and nonoverweight controls (n=60). Height, weight, fasting serum glucose, insulin, alkaline phosphatase, total cholesterol, and 25 hydroxy vitamin D3 (25(OH)VitD3) were also measured in all subjects.ResultsThere were significant differences in serum osteocalcin levels between the overweight and control groups (64.00±20.44 vs. 89.56±28.63, P<0.001). Serum osteocalcin levels were inversely correlated with body mass index (BMI) (r=-0.283, P=0.003), weight standard deviation score (SDS) (r=-0.222, P=0.020), BMI SDS (r=-0.297, P=0.002), insulin (r=-0.313, P=0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) index (r=-0.268, P=0.005). In the subsequent multiple regression analyses, BMI, HOMA-IR, and age were determined to be independent predicting factors for serum osteocalcin.ConclusionsOur findings showed associations of serum osteocalcin with glucose metabolism and insulin sensitivity in overweight children, but we could not establish a causal relationship.

The Relationship between the Waist Circumference and Increased Carotid Intima Thickness in Obese Children.

Background: This study aimed to evaluate the cardiometabolic risk factors in normotensive obese and hypertensive obese (HT-obese) children by comparison of anthropomorphic measurements, fat distribution, carotid artery intima-media thickness (CIMT), and inflammatory markers. Methods: Fifty-three obese patients 10-18 years of age with a BMI-for-age/gender >95th percentile and 20 age- and gender-matched healthy volunteers enrolled in the study. Obese patients were divided into two groups according to the presence of hypertension (HT), as follows: HT-obese subgroup (n = 30) and nonhypertensive obese (non-HT-obese) subgroup (n = 23). Results: Weight standard deviation score (SDS), BMI-SDS, waist circumference (WC) SDS, and the fat tissue z-score were significantly higher (p < 0.001 for all) in the obese patients than the control groups. Obese patients had higher 24-hour systolic blood pressure (SBP) SDS and leptin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 levels. Furthermore, CIMT and CIMT-SDS were significantly higher in them. HT-obese patients (n = 30) had significantly higher WC-SDS and lower serum leptin and adiponectin levels than those of non-HT-obese group (n = 23). Finally, an association between increased CIMT-SDS and WC-SDS (β = 0.399, p = 0.002) and 24-hour SBP-SDS (β = 0.272, p = 0.009) was shown. Conclusions: Association between increased WC and HT implies the importance of central obesity in atherosclerosis. We concluded that WC measurement could be used to define risk groups since it is related to cardiometabolic complications.

SUN-244 Birth and Perinatal Characteristics of Children with Congenital GH Deficiency (GHD) Due to Abnormal Pituitary Development: Data from a Prospective, Multinational Observational Study

Perinatal characteristics of children with non-acquired GHD are highly variable. Children with structural hypothalamic-pituitary abnormalities such as ectopic posterior pituitary (EPP) with/without pituitary stalk interruption syndrome, septo-optic dysplasia (SOD), or isolated anterior pituitary aplasia/hypoplasia (AP/HP) usually display more severe GHD than those with normal hypothalamic-pituitary magnetic resonance imaging (MRI) findings, and a higher prevalence of multiple pituitary hormone deficiencies (MPHD). Birth and perinatal characteristics in patients with structural hypothalamic-pituitary findings were assessed using data from the Genetics and Neuroendocrinology of Short Stature International study (GeNeSIS). Patients were grouped according to investigator-provided diagnoses: 1) EPP (N=396; including interrupted pituitary stalk; reported MPHD 57%); 2) SOD (N=202; MPHD 78%); 3) AP/HP (N=509; MPHD 36%); and 4) Other GHD (N=10470; non-acquired, non-pituitary abnormality associated; MPHD 9%). Birth/perinatal characteristics for EPP were compared to other diagnoses by ANOVA (all other diagnoses) and pairwise using Dunnett adjustment for continuous variables, and Chi-Square (all other diagnoses) and Fisher’s exact test (pairwise) for categorical variables. Gestation duration was ≈39 weeks for all diagnoses. Mean birth weight standard deviation scores (SDS) were 0.02 for EPP, -0.11 for SOD (p value for difference from EPP=0.651), -0.26 for AP/HP (p=0.020), and -0.38 for Other (p<0.001), while birth length SDS were -0.44, -0.17 (p=0.257), -0.60 (p=0.370) and -0.74 (p=0.003) respectively. Breech presentation was reported for 15% in the EPP group vs 3% SOD, 7% AP/HP and 5% Other (p<0.001 pairwise from EPP for all), with higher rates of reported Caesarean section for EPP (21%) vs SOD (17% [p=0.280]), AP/HP (17% [p=0.104]), and Other (14% [p<0.001]) or instrument assisted delivery (5%, 2% [p=0.167], 2% [p=0.033], and 2% [p=0.001] respectively). Perinatal asphyxia, then pregnancy, delivery, and neonatal complications were most prevalent for EPP and/or SOD, with values for EPP vs Other of 10% vs 3%, 18% vs 8%, 11% vs 4%, 35% vs 8%, respectively (p<0.001 for all) and 13% (p=0.027), 10% (p=0.911), 8% (p=0.249), 20% (p<0.001) respectively for AP/HP. In conclusion, among children with GHD, those with structural hypothalamic-pituitary abnormalities had delivery and perinatal complications more frequently than those without such MRI findings, but had birth weight and length SDS closer to the general population average. These findings from a large cohort of children with GHD reinforce previous smaller series suggesting that patients with congenital CNS midline defects and ultimately GHD or MPHD were more likely to have had complications during pregnancy and delivery, although causality is not established.

SAT-274 The Optimal Dosage of Vitamin D Supplement for Vitamin D Deficiency in Korean Children and Adolescents

Purpose: Vitamin D deficiency (VDD) is very common nowadays in children as well as in adults, probably due to decreased exposure to sunlight. In Korea, the prevalence of VDD was 47% in teenage boys and 65% in teenage girls. However, the optimal dosage regimen for correcting deficiency is unknown. We investigate the change of serum 25(OH) vitamin D concentration according to the treatment dosage and duration in VDD. Methods: Data was collected from 1797 children and adolescents aged 0 to 16 year between August in 2017 and July in 2018, retrospectively. They were divided to 3 groups (deficiency, insufficiency, sufficiency) according to their serum 25(OH) vitamin D concentrations (less than 20, between 20 and 30, more than 30 ng/mL, respectively). There were 3 subgroups (poor, moderate, good) according the daily increase (DI) of the serum 25(OH) vitamin D concentration (less than 0.3, between 0.3 and 0.6, more than 0.6 ng/mL/day, respectively) after 4 to 6 week oral administration of 25(OH) vitamin D in children and adolescents with vitamin D deficiency. Results: The serum 25(OH) vitamin D concentration showed the correlation with age (p=0.000), gender (p=0.000), weight standard deviation score (SDS) (p=0.008) and body mass index (BMI) SDS (p=0.000). And the serum 25(OH) vitamin D concentration showed seasonal variation in children over 2 years of age and adolescents (p=0.000). There was a significant correlation between serum 25(OH) vitamin D concentration and DI (p=0.021). In VDD patients treated with vitamin D, DI were not correlated with age, sex, weight SDS and BMI SDS. Conclusions: The prevalence of VDD increased in female, older age, overweight and winter in Korea and the response to treatment was higher in patient with lower serum 25(OH) D concentration. It may be appropriate to take an oral 25(OH) Vitamin D with 2000 IU/day for 6 weeks in Korean children and adolescents with VDD.

Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3M syndrome.

3M syndrome is characterized by severe pre- and postnatal growth retardation, typical facial features, and normal intelligence. Homozygous or compound heterozygous mutations in either CUL7, OBSL1, or CCDC8 have been identified in the etiology so far. Clinical and molecular features of 24 patients (23 patients and a fetus) from 19 unrelated families with a clinical diagnosis of 3M syndrome were evaluated and genotype-phenotype correlations were investigated with the use of DNA sequencing, chromosomal microarray, and whole exome sequencing accordingly. A genetic etiology could be established in 20 patients (n = 20/24, 83%). Eleven distinct CUL7 or OBSL1 mutations, among which eight was novel, were identified in 18 patients (n = 18/24, 75%). Ten patients had CUL7 (n = 10/18, 56%) while eight had OBSL1 (n = 8/18, 44%) mutations. Birth weight and height standard deviation scores at admission were significantly (p < 0.05) lower in patients with CUL7 mutation compared to that of patients with OBSL1 mutation. Two patients with a similar phenotype had a de novo 20p13p deletion involving BMP2. No genetic etiology could be established in four patients (n = 4/28, 17%). This study yet represents the largest cohort of 3M syndrome patients from a single center in Turkey. Microdeletions involving BMP2 may cause a phenotype similar to 3M syndrome with some distinctive features. Larger cohort of patients are required to establish genotype-phenotype correlations in 3M syndrome.

Growth Pattern in Chinese Children With 5α-Reductase Type 2 Deficiency: A Retrospective Multicenter Study.

Background5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD).ObjectiveTo study the growth pattern in Chinese pediatric patients with 5αRD.SubjectsData were obtained from 141 patients with 5αRD (age: 0–16 years old) who visited eight pediatric endocrine centers from January 2010 to December 2017.MethodsIn this retrospective cohort study, height, weight, and other relevant data were collected from the multicenter hospital registration database. Baseline luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) after human chorionic gonadotropin (HCG) stimulation test were measured by enzyme enhanced chemiluminescence assay. Bone age (BA) was assessed using the Greulich-Pyle (G-P) atlas. Growth curve was constructed based on λ-median-coefficient of variation method (LMS).ResultsThe height standard deviation scores (HtSDS) and weight standard deviation scores (WtSDS) in 5αRD children were in the normal range as compared to normal boys. Significantly higher HtSDS was observed in patients with 5αRD who were <1 year old (t = 3.658, 2.103, P = 0.002, 0.048, respectively), and higher WtSDS in those <6 months old (t = 2.756, P = 0.012). Then HtSDS and WtSDS decreased gradually and fluctuated near the median of the same age until 13 years. WtSDS in 5αRD children from northern China were significantly higher than those from the south (Z = -2.670, P = 0.008). The variation tendency of HtSDS in Chinese 5αRDs was consistent with the trend of stimulating T. HtSDS and stimulating T in the external masculinization score (EMS) <7 group were slightly higher than those in EMS ≥ 7 group without significant difference. Additionally, the ratio of BA over chronological age (BA/CA) was significantly <1 in children with 5αRD.ConclusionChildren with 5αRD had a special growth pattern that was affected by high levels of T, while DHT played a very small role in it. Their growth accelerated at age <1 year, followed by slowing growth and fluctuating height near normal median boys’ height. The BA was delayed in 5αRD children. Androgen treatment, which may be considered anyway for male 5αRD patients with a micropenis, may also be beneficial for growth.

Long-term growth in children with posterior urethral valves

Posterior urethral valves (PUVs) are one of the leading causes of pediatric chronic kidney disease (CKD). Growth impairment is prevalent in pediatric CKD, and children with PUVs are at high risk for growth retardation. The objective of this study was to describe growth profiles in PUVs and to identify risk factors for stunting, defined as age-specific height standard deviation score (SDS) below -2. Medical records of 65 patients with PUVs and a minimum follow-up of two years were retrospectively reviewed. Chronic kidney disease stage 1-3 was considered mild CKD, whereas CKD stage 4-5 was considered advanced CKD. Age-specific height, weight, and body mass index (BMI) SDS were determined. Seven potential risk factors for stunting, namely timing of diagnosis, renal dysplasia, timing of surgery, requirement of urinary diversion, nadir serum creatinine after surgery, recurrent febrile urinary tract infection (UTI), and severity of CKD, were analyzed. Median age at diagnosis, at surgery, and at last follow-up was 0.51, 0.75, and 7.53 years, respectively. All patients underwent valve ablation, and 33.8% required urinary diversion. Median nadir serum creatinine after surgery was 0.40mg/dL and was higher in patients who underwent urinary diversion (P<0.001). Growth profiles by CKD stage are displayed in Fig.1. Median height SDS was -0.40 and was lower in patients with advanced CKD (P=0.03). Stunting was diagnosed in 15.4%. Advanced CKD was an independent risk factor for stunting, with the odds ratio of 12.7. Urinary diversion and nadir creatinine more than 0.80mg/dL were weakly associated with stunting but not significant. Timing of diagnosis and surgery, unilateral renal dysplasia, and recurrent febrile UTI were not associated with stunting. Median SDS of weight and BMI was -0.64 and -0.19, respectively. Patients who were thin, of normal weight, overweight, and obese comprised 26.2%, 58.5%, 10.8%, and 4.6%, respectively. There was no significant difference of SDS of weight and BMI across CKD stages (Fig.1). Deterioration in height began early in the course of disease and was worsening in relation to the decline of renal function. The impact of timing of diagnosis or surgery on height was controversial. Patients who underwent urinary diversion had high nadir creatinine and were likely to have severe PUVs. Although patients with severe baseline renal dysfunction may require urinary diversion, nadir serum creatinine and urinary diversion are not associated with stunting. Delaying progression of CKD could maximize linear growth potential in PUVs. A substantial proportion of patients were overweight or obese. Sufficient caloric intakes may be maintained in patients with PUVs.

Long-Term Effectiveness of Antireflux Surgery in Esophageal Atresia Patients.

Gastroesophageal reflux disease (GERD) is a common morbidity after esophageal atresia (EA) repair, and the antireflux procedure (ARP) is a way of treating GERD symptoms. The aim of this study was to evaluate whether reflux index (Ri) and growth were improved by ARP. Ninety-nine individuals with EA treated at the Queen Silvia Children's Hospital in Gothenburg, Sweden, between 1997 and 2010 were followed prospectively according to a structured care program. Twenty-four-hour pH-metry (Ri) and growth were studied at birth, then at 1, 7, and 15 years of age. All the patients included had reached 7 years of age. Preoperatively, Ri was significantly higher (32%) in the ARP than the non-ARP group (10%). Postoperatively, no difference was seen between the groups. However, at 7 and 15 years of age, Ri was significantly higher in the ARP group than in the non-ARP group. Weight (standard deviation scores) was significantly lower in the ARP group at 1 and 7 years of age when compared with the non-ARP group, but these differences were not seen at birth and at 15 years of age. In a multivariate analysis, only birth weight remained a significant factor for low weight at 7 years of age. At 15 years of age, no risk factors for low body weight were found. In the long term, ARP is not effective in reducing GERD as measured as Ri in EA patients. The ARP group had significantly lower weight at 1 and 7 years of age than the non-ARP group, but this was not the case at the age of 15.

Association between hemoglobin levels and diabetic retinopathy risk in type 2 diabetes mellitus

Objective To investigate the independent association of the body mass index(BMI) with serum uric acid among shorter children and adolescent. Methods A cross-sectional study was conducted to collect general clinical data of 922 subjects with shorter statures. In each case, their information about height, weight, insulin-like growth factor-Ⅰ(IGF-Ⅰ), growth hormone peak, uric acid, and blood lipids were collected, and their BMI and BMI standard deviations score(SDS) were calculated. Smooth curve fitting and multiple piecewise linear regression were used to analyze the relationship between BMI SDS and uric acid. Results Univariate analysis found that serum uric acid was positively correlated with age, height standard deviation score, body weight standard deviation score, BMI SDS, IGF-Ⅰ standard deviation score, growth hormone peak, triglyceride, and creatinine(P<0.05), while negatively correlated with high-density lipoprotein-cholesterol(P<0.01). Female had significantly lower serum uric acid levels than male(P=0.003). The serum uric acid level was significantly increased after puberty(P<0.01). After adjusting for potential confounders, the smooth curve fitting revealed a U-shaped relationship between BMI SDS and uric acid, with a BMI SDS inflection point of -0.7. In the population of BMI SDS<-0.7, for every unit increase of BMI SDS, serum uric acid decreased by 11.78 μmol/L(P=0.030). In the population of BMI SDS≥-0.7, uric acid increased by 11.79 μmol/L(P<0.01) for every unit increase of BMI SDS. Conclusion Serum uric acid levels seem to be affected by BMI, and increased in population with thin or obesity. We should pay attention to the measurement of serum uric acid in both thin and obese children. Key words: Body mass index; Uric acid; Children and adolescents; Cross-sectional study