'Postnatal growth during the first five years of life in SGA and AGA neonates with reduced fetal growth'.

BACKGROUND: Even though a lot of research has been done on postnatal growth and the occurrence of catch-up growth in small-for-gestational age (SGA) neonates, this phenomenon has not been studied well in appropriate-for-gestational age (AGA) neonates. Postnatal catch-up growth may also occur in AGA neonates indicating a compensatory mechanism for undiagnosed intrauterine growth restriction, especially in AGA neonates with reduced fetal growth velocity. AIMS: To describe postnatal growth during the first 5 years of life in SGA and AGA neonates and evaluating the role of fetal growth velocity in catch-up growth. STUDY DESIGN: Retrospective study in a Dutch tertiary hospital. SUBJECTS: 740 singleton neonates, without congenital anomalies, with ultrasound fetal growth data from 20 weeks and 32 weeks of pregnancy. OUTCOME MEASURES: Postnatal growth measurements of height (cm) and weight (kg) from birth until five years of age. Postnatal catch-up growth defined as difference (delta) in both height and weight between 4 weeks and 3 years of age. RESULTS AND CONCLUSIONS: SGA neonates had a significantly lower height and weight compared to the AGA group for all available measurement moments till 3 years. The catch-up growth between the SGA and AGA groups from 4 weeks up to 3 years after birth was not different between the two groups. However, neonates with reduced fetal growth velocity had a significantly higher risk for catch-up growth in height during the first 3 years after birth. This suggests a role for fetal growth velocity measurement in predicting fetal and subsequent postnatal growth potential.

Characteristics of child health care practitioners in overweight prevention of children.

OBJECTIVES: To identify behavioral and personal characteristics of child health care (CHC) practitioners that influences the effect of early overweight prevention in children. METHODS: In total 216 questionnaires were filled out by CHC practitioners from four organizations in the Netherlands. RESULTS: There is a gap between awareness of the problem overweight in early childhood and actually discussing this with parents, as well as a gap between the existing recommendations and the perceived importance of early overweight prevention. Despite the fact that nurses have a more central task in life-style support than physicians, they reported to have less knowledge and skills than physicians. CONCLUSIONS: While both CHC physicians and nurses need support in improving their knowledge and skills, it is the nurses who need more support. A more structured and tailored implementation strategy with more emphasis on the needs of the nurses and physicians may improve early overweight management.

The growth of different body length dimensions is not predictive for the peak growth velocity of sitting height in the individual child.

The aim of this study was to determine whether the differences in timing of the peak growth velocity (PGV) between sitting height, total body height, subischial leg length, and foot length can be used to predict whether the individual patient with adolescent idiopathic scoliosis is before or past his or her PGV of sitting height. Furthermore, ratios of growth of different body parts were considered in order to determine their value in prediction of the PGV of sitting height in the individual patient. Ages of the PGV were determined for sitting height (n=360), total body height (n=432), subischial leg length (n=357), and foot length (n=263), and compared for the whole group and for the individual child in particular. Furthermore, the ages of the highest and lowest ratios between the body length dimensions were determined and compared to the age of the PGV of sitting height. The mean ages of the highest and lowest ratios were significantly different from the mean age of the PGV of sitting height in 3 out of 12 ratios in girls and 8 out of 12 ratios in boys. The variation over children was large and the ratios were too small, leading to a too large influence of measurement errors. The mean ages of the PGV all differed significantly from the mean age of the PGV of sitting height. However, the variation over individual children of the age differences in PGV between body dimensions was large, and the differences in timing of the PGV were not useful to predict whether the individual child is before or past his or her PGV of sitting height.

Sleep duration and body-weight development during puberty in a Dutch children cohort.

BACKGROUND: Short sleep duration is associated with obesity during childhood and adulthood. OBJECTIVE: The objective of our study was to investigate the relationship between sleep duration and body mass index (BMI) from Tanner stages 1 to 5 in a Dutch children cohort. DESIGN: In 98 children, anthropometric measurements and leptin concentrations were measured from age 7 to 16 years; body composition, physical activity (Baecke questionnaire), hours television viewing and self-reported sleep duration were measured yearly from age 12 to 16 years. Moreover, the polymorphisms of the FTO gene (rs9939609) and parental BMI's were determined. RESULTS: At Tanner stages 1-5 sex differences were observed in height, body weight, waist circumference, fat mass per squared meter height and leptin concentrations per kg fat mass. Inverse relationships were observed between the change in BMI (kg m(-2)) and the change in hours of sleep per night (h) from Tanner stages 1 to 4 (r=-0.68, P<0.001), from Tanner stages 2 to 5 (r=-0.35, P<0.05) and from Tanner stages 1 to 5 (r=-0.33, P<0.05). Univariate analysis of variance showed that with progressive Tanner stages, BMI increases and sleep duration decreases in an interrelated way independent of possible confounders (R(2)=0.38, P<0.02). CONCLUSION: Changes in BMI during puberty were inversely related to changes in sleep duration, independent of possible confounders.

Disorder in the serotonergic system due to tryptophan hydroxylation impairment: a cause of hypothalamic syndrome?

BACKGROUND: The hypothalamus regulates basic homeostasis such as appetite, circadian rhythm, autonomic and pituitary functions. Dysregulation in these functions results in the hypothalamic syndrome, a rare disorder of various origins. Since serotonin (5-HT) modulates most of the above-mentioned homeostasis, a defect in the serotonergic system can possibly participate in this syndrome. METHODS: We describe a girl suffering from hypothalamic syndrome with a decreased concentration of 5-hydroxytryptophan (5-HTP) and a normal level of tryptophan in the cerebrospinal fluid (CSF) suggesting a functional defect in tryptophan hydroxylase (TPH). TPH is a rate-limiting enzyme in the synthesis of the neurotransmitter 5-HT. RESULTS: Therapeutic intervention with 5-HTP, carbidopa and a specific serotonin reuptake inhibitor significantly improved her clinical symptoms and caused biochemical normalisation of neurotransmitters. CONCLUSION: The girl described had the typical symptoms of a hypothalamic disorder and a defective serotonergic metabolism, a relationship which has not been reported before. Therapeutic interventions to restore 5-HT metabolism resulted in clinical improvement. We suggest that investigation of 5-HT metabolism in CSF of patients with this rare disorder is included in the aetiological work-up.

Longitudinal growth during the first years of life: what is normal?

The anthropometric data of a longitudinal growth study on healthy infants, followed from birth until the age of 4 years and performed during 1995-1999 in The Netherlands, were used to analyze the general growth patterns in terms of height, weight and head circumference, based on z-scores, during the first 4 years of life. The well-known phenomenon where each infant or child tends to decelerate or accelerate its growth velocity depending on its starting position on the reference curve is obvious in this study too. This phenomenon, known as the regression to the mean, is a strong phenomenon especially during the first year. Regression to the mean is calculated for the different age groups as factor. With the given alpha, it is possible to estimate the individual expectation of growth.

Homozygous and heterozygous expression of a novel mutation of the acid-labile subunit.

CONTEXT: Acid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown. OBJECTIVE: To investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers. SUBJECTS: Three short Kurdish brothers and their relatives. RESULTS: The index cases presented with short stature, microcephaly, and low circulating IGF-I and IGF-binding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives. CONCLUSIONS: The clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect.

Physical activity as measured by accelerometry in children receiving growth hormone.

AIM: Parents of children treated with growth hormone (GH) frequently report to the paediatrician that their children have become more physically active. In the present study, activity patterns of GH-treated children were measured and compared to those of healthy controls. METHODS: Subjects were 25 children at the start of GH treatment (age 8.4 +/- 2.6 y) and 19 age- and gender-matched controls (age 8.8 +/- 3.2 y). Physical activity was assessed with a tri-axial accelerometer for movement registration over two separate 2-wk intervals, one before the start of GH treatment and one 2 wk after the start of treatment. GH-treated subjects were categorized as poor responders (change in height over 1 y <0.7 SDS, n = 15) or good responders (change in height over 1 y >0.7 SDS, n = 10). RESULTS: Before therapy, good responders showed a significantly lower physical activity compared to healthy controls, spending significantly less time on high-intensity activities. This difference disappeared 2 wk after the start of therapy. Physical activity in poor responders was not significantly different from controls before and after 2 wk of GH therapy. CONCLUSION: Children who respond well to GH therapy (change in height >0.7 SDS) showed a reduced amount of physical activity before therapy, which was normalized after 2 wk of GH therapy.

Providing physicians with feedback on how they supervise students during patient contacts.

In this descriptive study an instrument is presented that has been developed to provide physicians with feedback about their strengths and weaknesses in facilitating student learning during patient contacts. The instrument is strongly theory based, i.e. it is based on current general theories of context-bound learning environments, and forms of facilitation promoting transfer of knowledge to actual professional practice. In addition, it has been developed in cooperation with physicians supervising students during patient contacts. The authors have shown how physicians can be provided with individualized feedback on their performance in supervising students during patient contacts.

Physical activity pattern of children assessed by triaxial accelerometry.

OBJECTIVES: Accelerometry was used to assess the relationship between the physical activity level (PAL) and time spent on activities of various intensities in children. DESIGN: A total of 20 children aged 8.6+/-3.3 y wore a triaxial accelerometer (Tracmor2) for 2 weeks. PAL was calculated with Tracmor2 output data. The fraction of time spent on activities with a given level of intensity (low, moderate, high) was calculated. The fractions of time spent on activities of different intensities were compared with previously obtained data for young adults and elderly persons. RESULTS: PAL showed an inverse relation with the percentage of time spent on low-intensity activities (r = -0.76; P < 0.0001) and a positive relation with the percentage of time spent on high-intensity activities (r = 0.93; P < 0.0001). The fraction of time spent on low-intensity activities was smaller in children than in young adults (P < 0.05) and elderly persons (P < 0.0001), while the fraction spent on high-intensity activities (P < 0.0001) was larger. CONCLUSIONS: The present data are important for a better understanding of physical activity in children, which is necessary for education and prevention about physical (in)activity in childhood. Our observations suggest that to obtain a higher PAL in children, they should be given the opportunities to perform high-intensity activities.

Growth velocity: a presentation of reference values in Dutch children.

Normal values are given for height velocity in a Dutch population. A construction of velocity curves is given and a comparison is made with other studies.

Physical activity levels in children and adolescents.

BACKGROUND: Reference data for physical activity level (PAL) and activity-related energy expenditure (AEE) are needed for a better understanding of the effect of activity on childhood health, growth and development OBJECTIVE: Data from 17 studies measuring TDEE (TDEE) with doubly labelled water DLW were combined to construct a reference line for PAL and AEE as a function of age. DESIGN: A total of 17 studies from the literature were analyzed; 17 on girls and 16 on boys. Children were aged 3-16 y and of Caucasian origin. Weighted least-squares regression was used to obtain reference lines for PAL and AEE as a function of age and gender. The relative numbers of children per study were used as a weighting factor. Basal metabolic rate (BMR) or nonfasted (NF) resting metabolic rate and sex were included in the analysis. RESULTS: Although there was no difference in PAL between boys and girls, a significant difference in AEE was found between the two sexes. PAL: 0.025 x age+1.40. AEE (MJ/day): boys 0.30 x age+0.025; girls 0.21 x age+0.33. If BMR is measured under NF conditions, the obtained value has to be reduced by 0.21 for PAL and 0.75 MJ/day for AEE. No relation was found between AEE/kg and age. CONCLUSIONS: PAL and AEE were found to increase with age, showing the importance of age-dependent recommendations. Recommendations for AEE need to be differentiated for sex. To compare PAL and AEE between studies, the measurement conditions of BMR have to be taken into account. The increase in PAL and AEE values can be attributed to an increase in weight, because there was no relation between AEE/kg and age.

Body composition and cardiorespiratory fitness indicators in prepubescent boys and girls.

Abstract. Relations between frequently used indicators of cardiorespiratory fitness, sex and body composition were studied in a birth-cohort based sample of young prepubescent children (age range: 6.8 - 8.2 years). The Bruce treadmill test was used to assess submaximal heart rate, endurance time (ET), calculated total work (W(total)) and maximal power output (P(max)) in 100 children (50 boys, 50 girls). Body composition was determined by skinfold measurements. In 17 children, maximal oxygen consumption was measured. Percent body fat was negatively associated with ET and relative oxygen uptake (ml x min(-1) x kg(-1)) and was positively related to submaximal heart rate at 6 minutes exercise (HR6). Fat-free mass was positively related to W(total), P(max) and absolute oxygen uptake (ml x min(-1)). Relative oxygen uptake (ml x min(-1) x kg(-1)) was related to ET. Absolute oxygen uptake (ml x min(-1)) was related to W(total) and P(max). The observed differences in indicators of cardiorespiratory fitness between boys and girls were largely attributable to a difference in body composition. The results further demonstrate that when oxygen uptake measurement is not feasible, W(total) or P(max) (expressed per kilogram fat-free mass) seem to provide better indicators of aerobic power than endurance time.

Body composition in Prader-Willi syndrome compared with nonsyndromal obesity: Relationship to physical activity and growth hormone function.

OBJECTIVE: To study the relationship of fat mass, extracellular-to-intracellular-water ratio, and bone mineral density with growth hormone function and physical activity in Prader-Willi syndrome. STUDY DESIGN: There were 17 patients with PWS (10 women, ages 7.5-19.8 years) and 17 obese control patients, matched for gender and bone age. FM and extracellular-to-intracellular-water ratio were measured by bromide-deuterium dilution, BMD by dual-energy x-ray absorptiometry, GH function by fasted serum insulin-like growth factor-I concentration, and physical activity by doubly-labeled water in combination with basal metabolic rate by a ventilated hood. RESULTS: The PWS group had a similar fat mass, but a lower fat-free mass, whereas the extracellular-to-intracellular-water ratio was higher compared with the control group (0.87 +/- 0.07 l/l and 0.80 +/- 0.06 l/l, respectively [P <.01]). Fat mass was inversely related with PA in the PWS group, whereas IGF-I was positively correlated with FFM, ICW, and BMD of the limbs. BMD tended to be lower in patients with PWS. CONCLUSIONS: In children and adolescents with PWS, adiposity is associated with a reduced fat-free mass and extracellular-to-intracellular-water ratio is increased. Both findings are related to GH function and physical activity. BMD, especially in the limbs, tends to be reduced in patients with PWS and is related to GH function.

Activity related energy expenditure in children and adolescents with Prader-Willi syndrome.

OBJECTIVE: To measure activity related energy expenditure in Prader-Willi syndrome (PWS) corrected for body size. SUBJECTS: 17 PWS subjects (10 females, seven males, age 7.5-19.8 y) and 17 obese controls, matched for gender and bone age. MEAUREMENTS: Basal metabolic rate (BMR) was measured by ventilated hood and average daily metabolic rate (ADMR) was measured with doubly labelled water. Activity induced energy expenditure (AEE) was calculated as 0.9ADMR -BMR. Activity related energy expenditure was corrected for body size using the following measures: AEE per kg body weight (AEE/kg), ADMR/BMR (PAL), and the residual of the regression of ADMR on BMR (rADMR). Group differences were analyzed by analysis of covariance adjusting for bone age, fat mass (FM) and gender. RESULTS: ADMR, AEE and PAL were lower (P < 0.01) in the PWS group compared with the control group (7.14 +/- 1.72, 1.07 +/- 0.69 and 1.33 +/- 0.15 MJ/day compared with 9.94 +/- 2.64, 2.56 +/- 1.03 and 1.55 +/- 0.12 MJ/day respectively). The variance of AEE/kg and PAL was significantly explained by gender and PWS, while AEE was additionally explained by FM. The variance of rADMR was explained by PWS and not by FM or gender. CONCLUSION: Activity related energy expenditure is decreased in PWS compared with controls adjusted for bone age, FM and gender.

Energy expenditure at rest and during sleep in children with Prader-Willi syndrome is explained by body composition.

BACKGROUND: Obesity in Prader-Willi syndrome (PWS) seems to be related to a low basal metabolic rate (BMR). In addition, abnormal sleep patterns reported in PWS might affect sleeping metabolic rate (SMR). OBJECTIVE: Our objective was to assess BMR and SMR adjusted for fat-free mass in young PWS patients. DESIGN: Subjects were 17 PWS patients (10 females and 7 males aged 7.5-19.8 y) and 17 obese control subjects matched for sex and bone age. SMR was measured in a respiratory chamber, BMR with a ventilated-hood system, and body composition by deuterium dilution. RESULTS: BMR and SMR were significantly lower in the PWS group than in the control group (5.36 +/- 1.18 and 4.62 +/- 1.08 MJ/d compared with 6.38 +/- 1.55 and 5.60 +/- 1.52 MJ/d, respectively; P < 0.05). When fat-free mass was included in the analysis, multiple regression showed no differences in BMR and SMR between groups. When weight was included in the analysis instead of fat-free mass, SMR was lower in the PWS group. Fat-free mass was lower in the PWS group both as an absolute value and when adjusted for height. CONCLUSION: BMR and SMR are low in young patients with PWS because of a low fat-free mass.

Effects of discontinuation of growth hormone treatment on body composition and metabolism.

This study was directed to the investigation of two different aspects of growth hormone: What are the metabolic consequences following the discontinuation of treatment and are these metabolic effects correlated with the growth-promoting effects seen in the first year of treatment? The study was performed on 12 growth hormone-deficient (GHD) patients who reached their final height. Each patient was matched with a non-GHD person of the same sex and about the same age. Immediately after the discontinuation of treatment, and 6 weeks and 6 months later, the following anthropometric variables were assessed: height, weight, skinfold thicknesses (biceps, triceps, subscapular and suprailiacal), body volume (underwater weighing) and total body water (deuterium dilution). To describe energy metabolism, basal metabolic rate assessed by ventilated hood, and sleep metabolic rate assessed by respiration chamber, were studied. Body composition was calculated from weight, volume and total body water. Clear metabolic effects were found after the discontinuation of treatment in GHD children: there was a decrease in fat free mass and sleep metabolic rate. Also, a strong correlation between the above-mentioned effects and the growth-promoting effects of human growth hormone at the beginning of the treatment was observed. The fact that this correlation exists poses the interesting question of whether the results from a test treatment lasting some weeks could be used to predict the long-term effects of hGH.

Body proportions during 6 years of GH treatment in children with short stature born small for gestational age participating in a randomised, double-blind, dose-response trial.

The aim of this study was to assess body proportions in children with short stature born small for gestational age (SGA) before and during 6 years of growth hormone (GH) treatment. A prospective randomised double-blind dose-response study comparing the effects of 3 vs. 6 IU GH/m2/day. Seventy-nine children with short stature (height SD-score < -1.88) born small for gestational age (birth length SD-score < -1.88). Before and during GH treatment, height, sitting height (SH), hand (Hand) and foot length (Foot), biacromial (Biac) and biiliacal diameter (Biil) were measured. All results were adjusted for age and sex, and expressed as SD-scores (SDS) using reference values for healthy Dutch children. To describe the size of SH, Hand, Foot, Biac, and Biil in relation to height, these values were adjusted for the SDS of height. At baseline, these short children had small hands and feet and narrow shoulders and pelvis compared to healthy peers. Height and SH, were, however, even more affected. Consequently, on average, these children had relatively large hands and feet, and relatively broad shoulders and pelvis compared to their height, but a normal sitting height in proportion to height. In most of the individuals, the values for body proportions were, however, within the normal range. During 6 years of GH treatment the SD-scores of all measurements increased significantly towards values more close to zero. The mean size of Hand, Foot, and Biil decreased in proportion to height. The mean SH increased relatively more than height, however, to values well within the normal range. The mean Biac in relation to height had not changed after 6 years of GH treatment. No differences in the 6-year changes in body proportions were found between the two GH dosage groups. Untreated short children born small for gestational age have, on average, relatively large hands and feet, and broad shoulders and pelvis, but a normal sitting height compared to height. The increase in height during 6 years of GH treatment is accompanied by an improvement of the proportions of the size of hands, feet, and biiliacal diameter, in relation to height. The increase in height appeared to be the result of the increase in sitting height as well as leg length, but the sitting height SD-score increased slightly more than that of leg length. The changes in body proportion during GH treatment were dose-independent. Thus, 6-year continuous GH treatment with either 3 or 6 IU/m2/day in children with short stature born small for gestational age does not negatively influence body proportions.

Growth until puberty after in utero exposure to coumarins.

Anticoagulation with coumarins is an effective therapy during pregnancy. Fetal exposure to coumarin derivatives during the first trimester, however, is associated with skeletal anomalies (warfarin or coumarin embryopathy). Information about long-term effects of prenatal coumarin exposure on the skeletal development is not available. We investigated growth and body proportions at school age of children exposed to coumarins in utero. A blind population-based cohort study was conducted on 307 exposed children and 267 non-exposed controls ages 8-15 years. The exposed cohort was based on a prospective registry of coumarin-treated pregnant women. Anthropometric data included height, weight, head circumference, and measurements to evaluate body proportions. The mean height of exposed children did not differ from that of the non-exposed children (mean difference 0.01 SD). In addition, no differences were found for the proportional measures. As a group, children exposed in the first trimester showed no evidence of growth impairment. Two children in this group, however, were born with signs of coumarin embryopathy and one of these displayed a deficit in height at school age. Long-term growth was not affected by a high cumulative dosage or exposure after the first trimester. We conclude that, when exposure during the first trimester is avoided, coumarin therapy during pregnancy has no demonstrable risk for the child's skeletal development.