56 research outputs found
Growth failure in children with renal disease : incidence, pathophysiology, new perspectives with growth hormone therapy
Stunted growth is a serious problem for children with chronic renal insufficiency (CRI).
Advances in the treatment of renal insufficiency, including dialysis and renal transplantation, have
greatly improved the survival rate for these patients. Consequently the failure to grow has become a
major issue. Unfortunately. despite intensive medical care, optimized nutrition. vitamin D and
mineral supplements, and dialysis, it has proved impossible to improve height velocity.' Growth
retardation tends to occur when the glomerular filtration rate drops below 20-30 ml/min/L73m'.
Infants with CRI secondary to congenital renal abnonnalities are particularly prone to growth failure
during the first years of life. When CRI is first diagnosed in a child, the child's height will often lie
below the third height percentile for age. It has been reported that nearly 40% of children that enter
dialysis have a height below the third height percentile
Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency
To assess the effects of long-term continuous GH treatment on body
composition, blood pressure (BP), and lipid metabolism in children with
short stature born small for gestational age (SGA), body mass index (BMI),
skinfold thickness measurements, systemic BP measurements, and levels of
blood lipids were evaluated in 79 children with a baseline age of 3-11 yr
with short stature (height SD-score, < -1.88) born SGA (birth length
SD-score, < -1.88). Twenty-two of the 79 children were GH deficient (GHD).
All children participated in a randomized, double-blind, dose-response
multicenter GH trial. Four- and 6-yr data were compared between two GH
dosage groups (3 vs. 6 IU/m2 body surface/day). Untreated children with
short stature born SGA are lean (mean BMI SD-score, -1.3; mean SD-score
skinfolds, -0.8), have a higher systolic BP (SD-score, 0.7) but normal
diastolic BP (SD-score, -0.1), and normal lipids (total cholesterol, 4.7
mmol/L; low-density lipoprotein, 2.9 mmol/L; high-density lipoprotein, 1.3
mmol/L) compared with healthy peers. During long-term continuous GH
treatment, the BMI normalized without overall changes in sc fat compared
with age-matched references, whereas the BP SD-score and the atherogenic
index decreased significantly. Although the mean 6-yr increase in height
SD-score was significantly higher in the children receiving GH treatment
with 6 IU/m2 x day (2.7) than in those receiving treatment with 3 IU/m2
day (2.2), no differences in the changes in BMI, skinfold measurements,
BP, and lipids were found between the GH dosage groups. The pretreatment
SD-scores for BMI, skinfold, and BP, as well as the lipid levels, were not
significantly different between GHD and non-GHD children, but after 6 yr
of GH treatment the skinfold SD-score and BP SD-score had decreased
significantly more in the GHD than in the non-GHD children. Our data
indicate that GH treatment has at least up to 6 yr positive instead of
negative effects on body composition, BP, and lipid metabolism. In view of
the reported higher risk of cardiovascular diseases in later life in
children born SGA, further research into adulthood remains warranted
Fatness and muscularity as risk indicators of child mortality in rural Congo
OBJECTIVES: To examine the relationship of anthropometrical indicators of
fatness and muscularity with mortality in children in a rural African
community. BACKGROUND: A prospective cohort study was carried out in the
rural health zone of Bwamanda, Northern Congo using a random cluster
sample of 5167 children, aged 0-5 years. MAIN OUTCOME MEASURES: Short- and
long-term mortality rates, being deaths within 3 months and deaths in
3-month periods observed 3-30 months after enrolment. Rates of all cause
mortality and of mortality from kwashiorkor or marasmus, by level of
baseline fatness and muscularity. Indicators of fatness and muscularity
were obtained by correcting anthropometric arm fat and arm muscle areas
for age, sex, weight and height. RESULTS: The relationship of both the
fatness and muscularity scores with short-term mortality was marked by a
clear threshold (-0.5 SDS) below which there was a significant rise in
mortality from all causes as well as from kwashiorkor and marasmus. These
excess mortalities were also found in normal weight children. Fatness and
muscularity scores remained significant determining factors of short-term
mortality in a multiple logistic regression analysis with sex, age, season
and weight-for-age. A ROC curve analysis showed that fat and muscularity
scores had better predictive abilities than weight-for-age. Low fat status
had a bad prognosis on the long-term in underweight children. CONCLUSIONS:
Measures of current nutritional status should not be based on weight
indices alone. Objective and/or clinical evaluation of fat and muscle
status (also in normal weight children) should be added in order to detect
a higher proportion of malnourished children and to more accurately
evaluate mortality risk
Validation and calibration of the Kabi Pharmacia International Growth Study prediction model for children with idiopathic growth hormone deficiency
In 1999 a model was published for prediction of growth in children with
idiopathic GH deficiency (IGHD) during GH therapy, derived using data from
the Kabi Pharmacia International Growth Study (KIGS) database (Pharmacia
\\|[amp ]\\| Upjohn, Inc., International Growth Database). We validated and
calibrated this KIGS model for growth in the first year of GH therapy
using data from 136 Dutch children with IGHD. Observed vs. predicted
outcomes were plotted, and the fitted regression line was significantly
different from the line of identity (P = 0.03). It appeared that the
predictions were too extreme: relatively low predictions were too low,
relatively high predictions were too high. This is a well known phenomenon
in the context of prediction models, called overoptimism. For valid
application to other data the KIGS predictions should be calibrated.
Calibrated predictions are obtained using Y(cal) = Y(orig) + (2.153 -
0.192 x Y(orig)), where Y(cal) is the calibrated prediction, and Y(orig)
is the KIGS prediction. The calibrated prediction will be higher than the
original KIGS prediction when the original prediction is less than 11.2
cm/yr and will be lower otherwise. The variability of the prediction
errors of the calibrated predictions was positively related to the value
of the prediction (P < 0.001), described by the equation SD(pred err) =
-1.017 + 0.286 x Y(cal). Our calibrated model will give better predictions
for children with IGHD fulfilling the same criteria
Puberty in growth hormone-treated children born small for gestational age (SGA)
Seventy-five small for gestational age (SGA) children were studied in a
randomized, double-blind, dose-response GH trial with either 1 or 2 mg
GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data
were compared with Dutch reference data. In SGA boys, mean (SD) age at
onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was
10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d,
respectively. SGA boys treated with the lower GH dose started puberty
later than the appropriate for gestational age (AGA) controls; for the
other GH-dosage groups there was no significant difference in age at onset
of puberty compared to AGA controls. The age at menarche and the interval
between breast stage M2 and menarche were not significantly different for
GH-treated SGA girls compared to their peers. The duration of puberty and
pubertal height gain of GH-treated SGA boys and girls were not
significantly different between the two GH-dosage groups and were
comparable with untreated short children born SGA. In conclusion,
long-term GH therapy in short SGA children has no influence on the age at
onset and progression of puberty compared to AGA controls, regardless of
treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and
pubertal height gain were not significantly different between the
GH-dosage groups
Serum dehydroepiandrosterone sulfate levels and pubarche in short children born small for gestational age before and during growth hormone treatment
It has been suggested that the programming of the endocrine axes occurs
during critical phases of fetal development and will be affected by
intrauterine growth retardation. As a result, children born small for
gestational age (SGA) might have several hormonal disturbances. In later
life, one of the questions that might arise is: Do short children born SGA
have higher serum dehydroepiandrosterone sulfate (DHEAS) levels than their
peers? Therefore, we compared serum DHEAS levels of 181 short prepubertal
children aged 3-9 yr born SGA [birth length (SD score) below -2 for
gestational age] with a control group of 170 prepubertal age-matched,
normal-statured children born appropriate for gestational age (birth
length between -2 and +2 SD score). Because relatively high serum DHEAS
levels at a young age might result in a premature pubarche, we
investigated the incidence of premature pubarche. We also investigated the
association between serum DHEAS levels and bone maturation. In addition,
we analyzed whether 1 yr of GH treatment with 1 and 2 mg/m(2).d (
approximately 0.035 and 0.070 mg/kg.d, respectively) had an effect on
serum DHEAS levels of prepubertal short SGA children. Serum DHEAS levels
of the SGA group were comparable with those of age-matched appropriate for
gestational age controls. The incidence of premature pubarche was
comparable with that of the normal population. There was a weak negative
correlation between serum DHEAS levels and bone maturation after the age
of 7 yr. After 1 yr of GH treatment, the increase of serum DHEAS levels
was the same for both GH dosage groups and the untreated group. In
conclusion, this study shows that small size at birth, which might be a
feature of fetal growth restriction, has no effect on serum DHEAS levels
before the age of 9 yr. The incidence of premature pubarche is comparable
with the normal population. Finally, 1 yr of GH treatment has no effect on
serum DHEAS levels
Reduced cortical complexity in children with prader-willi syndrome and its association with cognitive impairment and developmental delay
Background: Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group.Methods: High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite.Results: Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ.Conclusions: These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development
Longitudinal Study on Metabolic Health in Adults SGA During 5 Years After GH With or Without 2 Years of GnRHa Treatment
BACKGROUND: In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH. METHODS: A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and Ξ²-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans. FINDINGS: In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group. INTERPRETATION: This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood. CLINICAL TRIAL REGISTRATION: ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389
Effects of size at birth, childhood growth patterns and growth hormone treatment on leukocyte telomere length
__Background__ Small size at birth and rapid growth in early life are associated with increased risk of cardiovascular disease in later life. Short children born small for gestational age (SGA) are treated with growth hormone (GH), inducing catch-up in length. Leukocyte telomere length (LTL) is a marker of biological age and shorter LTL is associated with increased risk of cardiovascular disease.
__Objectives__ To investigate whether LTL is influenced by birth size, childhood growth and long-term GH treatment.
__Methods__ We analyzed LTL in 545 young adults with differences in birth size and childhood growth patterns. Previously GH-treated young adults born SGA (SGA-GH) were compared to untreated short SGA (SGA-S), SGA with spontaneous catch-up to a normal body size (SGA-CU), and appropriate for gestational age with a normal body size (AGA-NS). LTL was measured using a quantitative PCR assay.
__Results__ We found a positive association between birth length and LTL (p = 0.04), and a trend towards a positive association between birth weight and LTL (p = 0.08), after adjustments for gender, age, gestational age and adult body size. Weight gain during infancy and childhood and fat mass percentage were not as
Methylphenidate and the Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age
Background: Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory. Objective: To explore the effects of MP treatment on growth in GH-treated short SGA children Methods: Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis. Results: The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (Β±0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (-1.9 SDS and -1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups. Conclusion: MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected
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