Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease.

Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10 weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10 weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107 µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108 µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052).   Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: • Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. • Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

Early-Life Exposure to Antibiotics and Risk for Crohn's Disease: A Nationwide Danish Birth Cohort Study.

BACKGROUND: Early-life antibiotic use can alter the intestinal flora and modify the risk of developing Crohn disease (CD), but rigorous epidemiological evidence is limited, with inconsistent results. METHODS: We identified all children born in Denmark from 1995 to 2009 and followed them from birth until death, emigration, a diagnosis of CD, or January 1, 2013. Using Cox regression, we assessed the association between antibiotic exposure in the first year of life and subsequent risk for CD, adjusting for sex, degree of urbanization, birth order, birth year, route of delivery, gestational age, smoking during pregnancy, intake of nonsteroidal anti-inflammatory drugs in the first year of life, and family history of CD. RESULTS: During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children. Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4; 95% confidence interval [CI], 1.1-1.8), with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1; 95% CI, 2.0-8.5). A family history of CD did not modify these risk associations. The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16‰ (95% CI, 0.11‰-0.22‰) compared to 0.11‰ (95% CI, 0.08‰-0.15‰) for children unexposed to antibiotics in their first year of life. CONCLUSIONS: Antibiotic use in the first year of life is associated with a modestly increased risk for CD, although the absolute risk is very low.

An evaluation of phase angle, bioelectrical impedance vector analysis and impedance ratio for the assessment of disease status in children with nephrotic syndrome.

BACKGROUND: Oedema, characterized by accumulation of extracellular water (ECW), is one of the major clinical manifestations in children suffering from nephrotic syndrome (NS). The lack of a simple, inexpensive and harmless method for assessing ECW may be solved by the use of the bioelectrical impedance analysis (BIA) technique. The aims of this study were to examine whether phase angle (PA), bioelectrical impedance vector analysis (BIVA) and the impedance ratio (IR) reflect change in disease status in children with NS. METHODS: Eight children (age range: 2-10 years) with active NS (ANS group) were enrolled. In five of these (ANS* subgroup), impedance was also measured at remission (NSR group). Thirty-eight healthy children (age range: 2-10 years) were included as healthy controls (HC group). Whole-body impedance was measured with a bioimpedance spectroscopy device (Xitron 4200) with surface electrodes placed on the wrist and ankle. RESULTS: Values of PA, BIVA and IR were found to be significantly lower (p-value range < 0.001 to < 0.01) in the ANS patients compared to the HC and NSR groups. No significant differences were observed between the NSR and HC groups. CONCLUSION: The studied parameters can be used to assess change in disease status in NS patients. Data were consistent with NS being associated with expansion of ECW.

Bioimpedance Resistance Indices and Cell Membrane Capacitance Used to Assess Disease Status and Cell Membrane Integrity in Children with Nephrotic Syndrome.

BACKGROUND: Accumulation of extracellular water (ECW) is a major clinical manifestation of nephrotic syndrome (NS) in children. Bioimpedance spectroscopy (BIS) is a simple, noninvasive technique that reflects body water volumes. BIS can further measure cell membrane capacitance (CM), which may be altered in NS. The aims of the study were to explore how BIS measurements could reflect disease status in NS, while avoiding prediction equations which are often only validated in adult populations. METHODS: The study involved 8 children (2-10 years) with active NS (ANS group), 5 of which were also studied at NS remission (NSR group), as well as 38 healthy children of similar age (HC group). BIS measurements determined resistances RINF, RE, and RI (reflecting total body water, extracellular water, and intracellular water) and CM. Also resistance indices based on height (H) were considered, RI = H2/R. RESULTS: It was found that RE and RINF were significantly lower in the ANS group than in both NSR and HC groups (p < 0.001). Corresponding resistance indices were significantly higher in the ANS group than in the NSR (p < 0.01) and the HC (p < 0.05) groups, in accordance with elevated water volumes in NS patients. Indices of intracellular water were not significantly different between groups. CM was significantly lower in the ANS group than in NSR and HC groups (p < 0.05). CONCLUSION: BIS could distinguish children with active NS from well-treated and healthy children. Studies with more children are warranted.

Feasibility of salivary DNA collection in a population-based case-control study: a pilot study of pediatric Crohn's disease.

BACKGROUND: Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls. SUBJECTS AND METHODS: Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs). RESULTS: A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate). A total of 126 controls were invited, and 54 contributed a saliva sample (44% response rate). As expected, demographic characteristics did not differ between cases and controls. DNA was successfully isolated from 93 of 94 samples. Genotyping was performed with only 2% undetermined genotypes. For five of six SNPs known to be associated with CD, risk allele frequencies were higher in cases than controls. CONCLUSION: This pilot study strongly supports the feasibility of augmenting traditional epidemiological data from Danish population-based registries with the de novo collection of genetic information from population-based cases and controls. This will facilitate rigorous studies of gene-environment interactions in complex chronic conditions such as CD.

Standardisation of bioelectrical impedance analysis for the estimation of body composition in healthy paediatric populations: a systematic review.

BACKGROUND: Bioelectrical impedance analysis (BIA) requires a high degree of standardisation in order to ensure valid and reproducible impedance measurements. The overall aim of this review was to study the degree to which BIA papers conducted in healthy paediatric populations (aged 0-17 years) were standardised. METHODS: Literature was identified on the basis of a systematic search of internationally-recognised electronic databases and hand searching of the reference lists of the included papers in order to identify additional relevant papers. The review was limited to lead-type BIA devices for whole-body, segmental- and focal impedance measurements. In total, 71 papers published between 1988 and 2016 were included. To evaluate the degree of standardisation of the papers, a recently published review detailing critical factors that may impact on BIA measurements in children was used as a model for structuring and extracting data. RESULTS: There was a general lack of BIA standardisation, or its reporting, in the papers under review, which hinders comparison of data between studies and could potentially lead to erroneous measurements. CONCLUSIONS: If the BIA technique should be accepted clinically for routine use in paediatric populations, there is a need for an increased focus on the importance of improved standardisation and its reporting in future studies. Consequently, this review contains recommendations for performing and reporting BIA measurements in a standardised manner.

Critical factors and their impact on bioelectrical impedance analysis in children: a review.

Several guidelines for bioelectrical impedance analysis (BIA) have been prepared for adults, but not for children. For that reason, there is a pressing need to develop a consensus set of guidelines to facilitate standardisation of BIA in this important group. This review provides an introduction to BIA, highlights critical factors that may impact on BIA and identifies areas where there is a need for further research in order to increase the quality of impedance measurements and prediction of body composition in children. Although the results of this review highlights a lack of studies in children to provide definitive BIA guidelines, the technique has, however, still proven valuable for body composition assessment in ill and healthy children. To fill the gaps in our knowledge, future studies should focus on methodological issues, particularly with regard to hydration, voiding, clothing, skin preparation and body position. The review may advantageously be used as a checklist in the planning of future studies. Finally, this review forms the basis for the development of guidelines for BIA assessment in this particular group; a task appropriately to be undertaken by scientific societies within the field.

Inappropriate arginine vasopressin levels and hyponatremia associated with cyclic vomiting syndrome.

We herein describe two children who presented with attacks of severe cyclic vomiting. The primary case was a 2.5-year-old girl with a history of several admissions with vomiting and altered mental status. She was diagnosed with cyclic vomiting syndrome (CVS). During her attacks she developed significant hyponatremia on several occasions, which prompted us to measure plasma arginine vasopressin (AVP) levels during attacks. We found inappropriately high AVP levels with concomitant hyponatremia. We also measured plasma AVP and plasma sodium in another child with CVS who did not develop manifest hyponatremia but showed inappropriately elevated plasma AVP levels. Since the standard treatment of CVS consists of fluids, high plasma AVP levels may lead to dilutional hyponatremia. We would therefore like to emphasize the importance of close assessment of electrolyte levels in patients with CVS to avoid water intoxication.

Does infliximab prevent colectomy in acute and chronic active ulcerative colitis?

OBJECTIVES: The aim of the study was to evaluate clinical response, use of colectomy, and adverse events related to infliximab (IFX) treatment in acute and chronic active ulcerative colitis (UC) in children. METHODS: Children from 3 centers, who had received IFX for UC, were identified, and patient charts were reviewed retrospectively. Data concerning symptoms, biochemistry, concomitant medical treatment, colectomy, and adverse events were registered. RESULTS: A total of 45 patients with UC (median age at diagnosis 12 years, interquartile range 10-14) were included, and studied for a median of 15 months (interquartile range 4.5-29) after first IFX infusion. The cumulative 1- and 2-year risks of colectomy were 21% and 26%, respectively. The cumulative 1- and 2-year risks of receiving a new course of systemic corticosteroids were 32% and 48%, respectively. Twenty-one patients (46%) experienced adverse events. Most common were mild infusion reactions, but 3 (7%) had serious adverse events. CONCLUSIONS: IFX was efficient in preventing colectomy in children with UC. The risk of receiving systemic corticosteroids was lower than that reported in other studies. Most adverse events were mild to moderate and self-limiting.

Effect of a 10-week weight loss camp on fatty liver disease and insulin sensitivity in obese Danish children.

BACKGROUND AND OBJECTIVE: Childhood nonalcoholic fatty liver disease (NAFLD) associated with insulin resistance and obesity is a growing problem and increases the risk of cirrhosis, type 2 diabetes mellitus, and cardiovascular complications. We examined the effects of a 10-week "weight loss camp" residency in obese children on the prevalence and degree of NAFLD and insulin sensitivity with 12-month follow-up. METHODS: At the camp, 117 obese white children (body mass index 28.0 ±â€Š3.6  kg/m, age 12.1 ±â€Š1.3 years) exercised moderately for 1 hour/day and restricted their energy intake to induce weight loss. NAFLD was diagnosed and graded using ultrasound and transaminasemia. Insulin sensitivity and glucose tolerance were assessed using homeostasis model assessment and oral glucose tolerance test. We performed anthropometric measurements and determined body composition using bioimpedance. Data were collected from 71 of 117 children at entry, after the 10 weeks at the camp, and 12 months after the camp ended. RESULTS: The children showed an average weight loss of 7.1 ±â€Š2.7  kg during the camp. At baseline, 43% had ultrasonographic liver steatosis, 50% elevated transaminases (>25  IU/L), and reduced insulin sensitivity. These abnormalities were mutually related and improved significantly during the camp (P ≤ 0.05). Liver fat improvement was sustained at 12 months. At the 12-month follow-up, 17 of 71 (24%) children maintained the body weight. CONCLUSIONS: This short-term diet and exercise program induced weight loss, markedly improved all aspects of the threatening condition of NAFLD, and reduced insulin sensitivity in childhood obesity; 24% of the children maintained weight loss at least until the 12-month follow-up.

Pediatric inflammatory bowel disease: increasing incidence, decreasing surgery rate, and compromised nutritional status: A prospective population-based cohort study 2007-2009.

BACKGROUND: The aim was to evaluate the incidence, treatment, surgery rate, and anthropometry at diagnosis of children with inflammatory bowel disease (IBD). METHODS: Patients diagnosed between January 1, 2007 to December 31, 2009 in Eastern Denmark, Funen, and Aarhus were included from a background population of 668,056 children <15 years of age. For evaluation of incidence, treatment, and surgery rate, a subcohort from Eastern Denmark was extracted for comparison with a previously published population-based cohort from the same geographical area (1998-2006). RESULTS: In all, 130 children with IBD: 65 with Crohn's disease (CD), 62 with ulcerative colitis (UC), and three with IBD unclassified (IBDU) were included. The mean incidence rates per 10(6) in 2007-2009 were: IBD: 6.4 (95% confidence interval [CI]: 5.4-7.7), CD: 3.2 (2.5-4.1), UC: 3.1 (2.4-4.0) and IBDU: 0.2 (0.05-0.5). Comparing the two cohorts from Eastern Denmark we found higher incidence rates for IBD (5.0 and 7.2 in 1998-2000 and 2007-2009, respectively, P = 0.02) and CD (2.3 versus 3.3, P = 0.04). Furthermore, we found a significant decrease in surgery rates (15.8/100 person-years versus 4.2, P = 0.02) and an increase in the rate of initiating immunomodulators (IM) within the first year (29.0/100 person-years versus 69.2, P < 0.001). IM use was associated with a trend towards a decreased surgery risk (relative risk [RR] 0.38; 0.15-1.0). Children with CD had poor nutritional status at diagnosis compared with the general pediatric population. CONCLUSIONS: Over the past 12 years we found an increase in the incidence of IBD in children, an increasing use of IM, and decreasing 1-year surgery rates. CD patients had poor nutritional status.

Age-dependency of galactose elimination capacity in healthy children and children with chronic liver disease.

OBJECTIVE: Galactose elimination capacity (GEC) is used as a quantitative measure of liver metabolic function with prognostic value in adults with acute and chronic liver failure. Almost no data are available regarding GEC in children, however. This study thus aims to meet the previously unmet clinical need for age-related data on GEC in children. MATERIAL AND METHODS: We studied galactose elimination in 10 healthy children (median age 10.7 years; range 7 months to 16 years) and 30 children with chronic liver disease (median age 8.6 years; range 3 months to 16 years). GEC was estimated from the linear decrease in concentration of galactose in arterialized capillary blood from the ear following intravenous infusion of galactose. RESULTS: In both groups of children, GEC (µmol/min/kg body weight) was highest in the youngest children and decreased with age, although at a significantly lower level in the children with liver disease (p = 0.05). GEC was significantly higher in healthy children than in healthy adults, diminishing to the adult level by the age of 16 years. CONCLUSIONS: GEC was found to be higher in children than in adults until the age of 16 years. Moreover, GEC was significantly lower in children with chronic liver disease than in healthy children, underlining that GEC testing also has potential clinical usefulness as a quantitative measure of liver metabolic function in children.

[Lactose intolerance. Genotyping simplifies and improves diagnosis]. / Laktoseintolerans. Gentest forenkler og forbedrer diagnostikken.

The molecular genetics of adult-type hypolactasia is reviewed. Genotyping for the LCT-13910C>T polymorphism as a standard first-stage diagnostic approach for the diagnosis of adult-type hypolactasia and a replacement of the lactose tolerance test is suggested.

[The role of hepatobiliary scintigraphy in neonates with persistant jaundice]. / Betydningen af galdevejsskintigrafi hos neonatale med prolongeret ikterus.

Hepatobiliary scintigraphy of infants being examined for persistant neonatal jaundice is best carried out using mebrofenin, a 99m Tc-labeled IDA derivative. This article summarizes the most frequently occurring etiologies of persisting neonatal jaundice and the diagnostic work-up of this condition. Perinatal obliteration of extrahepatic bile ducts requires immediate surgery, whereas other causes of persisting jaundice may be treated medically and/or conservatively.

Gastric dysrhythmia in infants with gastrointestinal diseases measured by epigastric impedance.

BACKGROUND: Gastrointestinal symptoms have been reported in association with myoelectrical dysrhythmia, where different types of gastric electrical activity have been described. These types of gastric myoelectrical activity and dysrhythmia can be measured by electrogastrography using cutaneous electrodes. Epigastric impedance is a non-invasive method used to study gastric emptying time and gastric phasic activity. At present no study of gastric dysrhythmia, measured with epigastric impedance, has been presented, and the purpose of the present study was to investigate gastric rhythms by means of impedance gastrography in control infants, compared to infants with different gastrointestinal diseases, before and after treatment of their disease. METHOD: 21 patients (age 0-2 months) and 40 healthy infants (age 0-2 months) were investigated. The patients suffered from partial or total intestinal obstruction, necrotizing enterocolitis or pyloric stenosis.All infants were fasting and studied during periods of at least one hour. The patients were examined in the acute state and after treatment when possible. RESULTS: A pathologic result was found in 90% of the patients. A persistent phasic activity pattern was found in 19 of the 21 patients, high frequency phasic activity in 11 of the 21 patients. Short-term phasic activity was only found in 13 out of 40 of the normal infants (32.5%). CONCLUSION: Using epigastric impedance we found that infants with partial or total intestinal obstruction had gastric phasic activity, which was not found in the control infants. The origin of the gastric phasic activity patterns is unknown, but they may be related to electrical control activity.

The need for pain relief in uncomplicated deliveries in an alternative birth center compared to an obstetric delivery ward.

The need for pain relief during uncomplicated labour and delivery was studied in 125 women attending an Alternative Birth Center (ABC) and 170 women attending an obstetrical ward. The ABC was staffed only with midwives and assistant nurses who took care of all deliveries. In case of complications the doctor on duty at the obstetrical ward could come in a few minutes and the patient was transferred to the obstetrical ward. At the ABC the delivery room was next to the sleeping rooms and the living room and the woman in labour could have a chat with the women, who had given birth. At the obstetrical ward this was not possible. The delivery rooms were on one floor, and after giving birth the woman was moved to another floor. Women at the ABC were older and had a higher social status than women at the obstetrical ward. Twenty four of the 170 women had initially planned to give birth at the ABC but gave birth at the obstetrical ward due to accommodation restrictions at the ABC. Women refused by the ABC resembled women giving birth at the ABC but their need for pain relief was identical with the other women giving birth at the obstetrical ward. Pain relief with pethidine was 4 times more frequent among women giving birth at the obstetrical ward (18%) than at the ABC (4.8%). Pethidine was predominantly administered to young women and primiparas at the obstetrical ward and to women with prolonged labour at both birthplaces.