Auxological Data Research Articles

Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening

Objective The major objective of this study was to determine whether the embryo biopsy procedure might cause growth restriction or affect health outcome of children. Study design Auxological data and physical findings were compared at birth and age 2 for 102 children (70 singletons and 32 twins) born after PGD/PGS and 102 matched children born after intracytoplasmic sperm injection (ICSI) in a prospective study. Results No statistically significant differences regarding weight, height and head circumference standard deviation scores (SDS) at birth and at age two years were observed. At two years of age the mean BMI SDS tended to be lower in PGD/PGS children ( p = 0.058). PGD/PGS babies had been more often breastfed ( p = 0.013), but mostly during a shorter time. The prevalence of major as well as minor congenital anomalies, hospital admissions and surgical interventions was similar. Conclusion Children born after embryo biopsy applied in PGD/PGS present similar prenatal and postnatal growth and health outcome in the first two years of life compared to ICSI children. Up till now, PGD and PGS appear not to be associated with a higher risk for health problems.

New reference growth charts for Japanese girls with Turner syndrome

Currently used growth charts for Japanese girls with Turner syndrome (TS) were constructed with auxological data obtained before the secular trend in growth reached a plateau. These charts were published in 1992 and may no longer be valid for the evaluation of stature and growth in girls with TS in clinical settings. Thus, we need to establish new clinical growth charts. The samples for analysis were obtained by a retrospective cohort study. A total of 1867 Japanese girls with TS were registered between 1991 and 2004 for growth hormone (GH) treatment and their pretreatment anthropometric measurements were obtained. Reference growth charts were newly constructed using the LMS method from 1447 girls' cross-sectional data after exclusion of measurements derived from those with the presence of puberty, with previous growth-promoting treatment, or without cytogenetic evidence of TS. The new clinical reference growth charts differ from the old charts. Secular trends can be detected in both height and weight. Mean adult height on the new chart is 141.2 cm, 3.0 cm taller than the old data. This result seems attributable to the secular trend observed during the same period in Japanese women. The newly constructed clinical reference growth charts for Japanese girls with TS seem to be better for the evaluation of growth in girls with TS born after approximately 1970, although selection bias and some other limitations in the present study should be kept in mind.

Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease

Decreased bone mineral density has been reported in children with inflammatory bowel disease (IBD). We used peripheral quantitative computed tomography (pQCT) to assess bone mineralization, geometry, and muscle cross-sectional area (CSA) in pediatric IBD. In a cross-sectional study, pQCT of the forearm was applied in 143 IBD patients (mean age 13.9 +/- 3.5 years); 29% were newly diagnosed, 98 had Crohn's disease, and 45 had ulcerative colitis. Auxological data, cumulative glucocorticoid dose, disease activity indices, laboratory markers for inflammation, and bone metabolism were related to the results of pQCT. Patients were compromised in height (-0.82 +/- 1.1 SD), weight (-0.77 +/- 1.0 SD), muscle mass (-1.12 +/- 1.0 SD), and total bone cross-sectional area (-0.79 +/- 1.0 SD) compared to age- and sex-matched healthy controls (z-scores). In newly diagnosed patients, the ratio of bone mineral mass per muscle CSA was higher than in those with longer disease duration (1.00 versus 0.30, P = 0.007). Serum albumin level and disease activity correlated with muscle mass, accounting for 41.0% of variability in muscle mass (P < 0.01). The trabecular bone mineral density z-score was on average at the lower normal level (-0.40 +/- 1.3 SD, P < 0.05). Reduced bone geometry was explained only in part by reduced height. Bone disease in children with IBD seems to be secondary to muscle wasting, which is already present at diagnosis. With longer disease duration, bone adapts to the lower muscle CSA. Serum albumin concentration is a good marker for muscle wasting and abnormal bone development.

S1051 Faecal Calprotectin Home Test in Ulcerative Colitis - Is It Possible?

S1051 Faecal Calprotectin Home Test in Ulcerative Colitis - Is It Possible?

Health care of children living with their mother in prison compared with the general population

Italian law allows female prisoners in specific "nest areas" to keep their babies with them until the child reaches the age of 3 years. We describe health care of children living in the nest areas and we compare this condition with the general population. Our study was conducted in the female detention centre of Rome Rebibbia, Italy. Clinical diaries of all babies have been screened. The pediatrics ambulatory of A. Gemelli Hospital of Rome provided all data for comparison. We describe 391 children (150 in the prison group, G1; 150 children with Italian parents, G2, and 91 children with foreign parents, G3) with similar characteristics. There were statistical differences between-groups in respect of the auxological data, gestational age (lower in G1 vs G2, p < 0.0004, and lower in G1 vs G3, p < 0.03), time of weaning age earlier in G1 vs G2, (p < 0.035), number of respiratory infective disease (G1>G2, p < 0.0001, and G1>G3, p < 0.003). We also found inadequate immunisation status in children at their admission to prison. According to our observations children received good sanitary assistance inside the prison and the adjustment of their immunisation status when they stayed in prison for a long enough period. The significant information shown by our data suggest that children living in prison with their mothers represent a vulnerable group with particular healthcare needs.

Adequacy and tolerance to ass's milk in an Italian cohort of children with cow's milk allergy

BackgroundThe therapy for cow's milk proteins allergy (CMPA) consists in eliminating cow's milk proteins (CMP) from the child's diet. Ass's milk (AM) has been recently considered as substitute of CMP. This prospective study investigated tolerance and nutritional adequacy of AM in children with CMPA from Southern Italy.MethodsThirty children (aged 6 months to 11 years) with suspected CMPA were enrolled. They underwent skin prick tests and bouble-blind, placebo controlled food challenge to CMP. After confirming the diagnosis of CMPA, patients received fresh AM in a open challenge. Specific serum CMP and AM IgE, and biochemical parameters in blood were also assessed. Auxological evaluations were performed in all subjects at entry (T0) and after 4–6 months (T1) of AM intake.ResultsTwenty-five children resulted elegible for the study, and 24 out of 25 subjects (96%) tolerated AM at the food challenge. Auxological data resulted improved by the end of the study in all patients, while blood biochemical parameters did not vary during the follow-up.ConclusionOur data confirm the high rate of AM tolerability in children with moderate symptoms of CMPA. Moreover, we found that AM seems to have nutritional adequacy in subjects with a varied diet.

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: Magnetic Resonance Imaging and Magnetic Resonance Angiography protocol

BackgroundInfants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.MethodsThe study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease.Trial registrationCurrent Controlled Trials ISRCTN89493983

The exon 3-deleted/full-length Growth Hormone Receptor Polymorphism Does Not Influence the Effect of Puberty or Growth Hormone Therapy on Glucose Homeostasis in Short Non-Growth Hormone-Deficient Small-for-Gestational-Age Children: Results from a Two-Year Controlled Prospective Study

The exon 3-deleted/full-length (d3/fl) GH receptor polymorphism (d3/fl-GHR) has been associated with responsiveness to GH therapy in short small-for-gestational-age (SGA) patients, although consensus is lacking. However, its influence on glucose homeostasis, at baseline or under GH therapy, has not been investigated. Our objective was to evaluate whether the d3/fl-GHR genotypes influence insulin sensitivity in short SGA children before or after puberty onset or during GH therapy. We conducted a 2-yr prospective, controlled, randomized trial. Thirty Spanish hospitals participated. Auxological, GH secretion, and glucose homeostasis evaluation was hospital based, whereas molecular analyses and data computation were centralized. Patients included 219 short SGA children [body mass index sd score (SDS) < or = 2.0]; 159 were prepubertal (group 1), and 60 had entered puberty (group 2). Seventy-eight patients from group 1 were treated with GH (66 microg/kg.d) for 2 yr (group 3). Previous and 2-yr follow-up auxological and biochemical data were recorded, d3/fl-GHR genotypes determined, and data analyzed. In groups 1 and 2, fasting glucose, insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI) were similar in each d3/fl-GHR genotype. Group 2 glucose, insulin, and HOMA were significantly higher and QUICKI lower than in group 1. In group 3 GH-treated patients, height SDS, growth velocity SDS, fasting glucose, insulin, and HOMA significantly increased as did body mass index SDS at the end of the second year, and QUICKI decreased during the first and second years, with no differences among the d3/fl-GHR genotypes. In short SGA patients, the d3/fl-GHR genotypes do not seem to influence prepubertal or pubertal insulin sensitivity indexes or their changes over 2 yr of GH therapy (66 mug/kg.d).

In the Italian population sexual dimorphism affects pre-natal thyroid migration but not biochemical severity of gland ectopia and pre-natal bone maturation

The aim of the present study was to retrospectively re-evaluate a population of selected infants with congenital hypothyroidism (CH), in order to investigate whether sexual dimorphism affects: a) CH etiology; b) its biochemical severity at the time of screening and recall; c) patients' biochemical response to replacement treatment during the 1st yr of life; d) their bone maturation (BM) at birth; e) their psychomotor status at 1 yr. This retrospective study covers 192 infants (116 females) with persistent CH who were selected from a larger population of CH patients identified during a 10-yr period (1990-1999) by the screening programs of 5 northern, central, and southern regions of Italy. Thirty boys (39.5%) and 66 girls (56.9%) were found to have ectopia, whereas the remaining 46 boys and 50 girls exhibited the other causes of CH. When compared with the prevalence of the remaining causes that of ectopia was significantly higher in girls than in boys (66/116 vs 30/76; chi2=5.57, p<0.025), and sex ratio in ectopia was significantly different also compared with the orthotopic gland group only (66/84 vs 30/51; chi2=6.02, p<0.025). No differences between males and females were detected in the groups with either athyreosis or orthotopic gland. In no groups were there differences between sexes for gestational age, birth auxological data, percentage of newborns with bone retardation or developmental quotient at 1 yr. Thyroid tests at birth, age at TSH normalization and average thyroid tests under L-T4 treatment during the 1st yr did not differ between sexes in any of the groups. a) in the Italian population sexual dimorphism affects pre-natal thyroid migration but neither biochemical severity of ectopia, nor pre-natal bone maturation and psychomotor development; b) girls with CH do not require higher doses of initial therapy in order to achieve TSH normalization; c) future developmental and molecular studies on ectopia etiology in CH need to take into account the effect of sexual dimorphism.

The Range of 2.2-3.3 mg/gCr of Pregnanetriol in the First Morning Urine Sample as an Index of Optimal Control in CYP21 Deficiency.

Auxological data are the gold standard indexes of the therapeutic conditions in patients with CYP21 deficiency over long-term periods, whereas urinary pregnanetriol (PT) for 24 h has been used as an index for short-term periods. We previously reported that the range of 1.2–2.1 mg/m2/day of PT for 24 h (24-h PT) could be used as an index of optimal control in patients with CYP21 deficiency. The purpose of this study was to analyze the range of PT in the first morning urine samples (morning PT) as an index of optimal control in patients with CYP21 deficiency. First, the therapeutic periods of 15 participants (aged 2 yr and 5 mo to 17 yr and 4 mo) were classified into excessive, good or poor control periods using auxological data and Cushing-like symptoms, and 24-h PT levels were analyzed in each period, retrospectively. The 95% confidence intervals for the means of 24-h PT levels in the excessive, good and poor control periods were 0.24–2.24 (n=25), 2.88–4.92 (n=114) and 13.26–21.28 (n=72) mg/gCr, respectively. Subsequently, 24-h PT and morning PT levels collected on the same day were analyzed for 14 participants (aged 9 mo to 29 yr and 8 mo). There was a significant correlation between the above two PT levels (n=25, p<0.0001). When the 24-h PT range of the good control period, 2.88–4.92 mg/gCr, was adjusted by the correlation, the ideal morning PT range became 2.15–3.34 mg/gCr. In conclusion, a morning PT in the range of 2.2–3.3 mg/gCr can be used as an index of optimal control in patients with CYP21 deficiency.

Final Heights of Boys with Normal Growth Hormone Responses to Provocative Tests Following Priming

Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH deficiency is still debatable. We analyzed the auxological data of boys with growth retardation who had normal GH responses to stimulation tests only after priming to establish the validity of priming in the diagnosis of GH deficiency. We also analyzed the effect of different protocols for priming and their efficiency in the diagnosis of GH deficiency. Fifty boys with growth retardation who failed to respond to unprimed GH stimulation tests but responded normally to primed tests were included in the study. Thirty-one of 50 boys responded to GH stimulation tests after single low dose testosterone, 11/50 boys after single conventional dose, and 8/50 boys with multiple-dose testosterone. The study group was followed till final height; height velocity, final height and height SDS were compared to parental and mid-parental heights to determine whether or not the children achieved their height potential. Mean final height SDS of the study group (-1.27 +/- 0.72 SDS) was similar to mid-parental (-1.38 +/- 0.72 SDS) (p = 0.249) and maternal height SDS (-1.26 +/- 1.05 SDS) (p = 0.941), whereas it was greater than the paternal height SDS (-1.7 +/- 0.86) (p = 0.001). The final height SDS of the study group was correlated to maternal, paternal and mid-parental height SDS. Height velocity after the test was greater than the previous height velocity. Final height SDS of the boys who responded to the GH stimulation tests with different priming protocols were compared and found to be similar. Normal responders in primed GH tests grow normally to their target height, suggesting that priming might be a valuable method in the assessment of GH status. Use of priming in the GH stimulation tests of peripubertal boys with decreased growth rate may help avoid unnecessary GH therapy. Multiple-dose testing might exclude GHD in a patient population who failed to respond to a single dose of testosterone. This finding suggests that multiple-dose testosterone might be a more valuable method for priming in the differentiation of normal from abnormal GH secretion.

Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency

The objective of the study was to determine the degree of linear growth retardation of patients with vitamin D deficiency rickets at presentation and the magnitude of catch-up growth in relation to their calcium (Ca) homeostasis and hormones affecting it before and after treatment. This prospective study recorded the anthropometric data and measured the circulating 25-hydroxy vitamin D (25-OH-D), insulin-like growth factor I (IGF-I), parathyroid hormone, Ca, phosphate, and alkaline phosphatase concentrations in 46 infants and children with nutritional (vitamin D deficiency) rickets before and 6 months or more after treatment with one intramuscular injection of vitamin D3 megadose (300 000 IU). Forty normal age- and sex-matched children were included as controls for the auxological data. At presentation, patients' mean age = 13.1 ± 1.1 months, length standard deviation scores (LSDS) = −1.5 ± 0.2, and body mass index = 16.3 ± 0.85. They were significantly shorter and had markedly lower growth velocity standard deviation scores (GVSDS) compared with normal controls (LSDS = 0.25 ± 0.18 and 0.31 ± 0.22, respectively). Six months after treatment, the LSDS increased significantly in patients to −0.45 ± 0.13, with a significantly increased GVSDS (2.76 ± 0.45) and body mass index (16.9 ± 0.65). They were still shorter but with significantly higher GVSDS compared with normal controls. Serum Ca and phosphate concentrations increased from 2.07 ± 0.25 and 1.23 ± 0.24 mmol/L, respectively, before treatment to 2.44 ± 0.2 and 1.94 ± 0.2 mmol/L, respectively, after treatment. Serum alkaline phosphatase and parathyroid hormone concentrations decreased from 1183 ± 219 U/L and 294 ± 87 pg/mL, respectively, before treatment to 334 ± 75 U/L and 35.2 ± 15.2 pg/mL, respectively, after treatment. The 25-OH-D level increased from 4.5 ± 0.56 ng/mL before treatment to 44.5 ± 3.7 ng/mL after treatment. Circulating concentrations of IGF-I increased significantly after treatment (52.2 ± 18.9 ng/mL) vs before treatment (26.6 ± 12.8 ng/mL). The 25-OH-D concentrations were correlated significantly with the IGF-I levels before and after treatment ( r = 0.603 and r = 0.59, respectively; P < .001). The GVSDS after treatment was correlated with the increase of IGF-I and 25-OH-D levels ( r = 0.325 and r= 0.314, respectively; P < .01). These data denote that the accelerated linear growth after treatment of nutritional vitamin D deficiency is mediated through activation of the growth hormone/IGF-I system and suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and growth hormone/IGF-I secretion. Three different sequential stages of vitamin D deficiency can be recognized according to the clinical/radiological, biochemical, and hormonal data of patients at presentation.

Testicular function in boys previously treated with recombinant-human growth hormone for non-growth hormone-deficient short stature

Data on the effects of recombinant human GH (hGH) therapy during male puberty on future testis function are still inconclusive. The aim of this study was to investigate the long-term effects of recombinant hGH treatment on reproductive function in non-GH-deficient short stature boys. Eight boys with non-GH-deficient short stature, affected by constitutional delay of puberty or idiopathic short stature, were retrospectively studied after recombinant-hGH treatment to verify gonadal development, hormone production and semen quality. Auxological data, endocrinological/ andrological parameters and laboratory evaluation (GH, IGF-I, FSH, LH, testosterone, inhibin B) were assessed before treatment; after completion of pubertal development, the same parameters plus SHBG levels were evaluated and a seminal fluid examination was conducted (ejaculate volume, pH, sperm concentration, total sperm count, forward and total motility, morphology). All patients showed normal testicular volume at the final pubertal stage, with regular androgenization. Hormonal levels were within the normal adult range in all boys. Considering the immature reproductive system of these patients in comparison with adults, semen parameters (sperm count, motility, and morphology) were within almost normal limits, except in one patient. Although patients showed the wide fluctuation of semen values frequently observed at the end of puberty, the hypophysis-gonadal axis hormones were in the normal range in all adolescents. Pathological measurements of some seminal parameters were found in one patient only. This study suggests that recombinant hGH treatment has no detrimental effects on the development and maturation of male gonadal function in non- GH deficient short stature young patients.

Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age

BackgroundMathematical models can be used to predict individual growth responses to growth hormone (GH) therapy. The aim of this study was to construct and validate high-precision models to predict the growth response to GH treatment of short children, independent of their GH status, birth size and gestational age. As the GH doses are included, these models can be used to individualize treatment.MethodsGrowth data from 415 short prepubertal children were used to construct models for predicting the growth response during the first years of GH therapy. The performance of the models was validated with data from a separate cohort of 112 children using the same inclusion criteria.ResultsUsing only auxological data, the model had a standard error of the residuals (SDres), of 0.23 SDS. The model was improved when endocrine data (GHmax profile, IGF-I and leptin) collected before starting GH treatment were included. Inclusion of these data resulted in a decrease of the SDres to 0.15 SDS (corresponding to 1.1 cm in a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a separate cohort, showed similar SDres for both types of models. Preterm children were not included in the Model group, but predictions for this group were within the expected range.ConclusionThese prediction models can with high accuracy be used to identify short children who will benefit from GH treatment. They are clinically useful as they are constructed using data from short children with a broad range of GH secretory status, birth size and gestational age.

Correlation between the components of the insulin-like growth factor I system, nutritional status and visceral leishmaniasis

The role of the insulin-like growth factor I (IGF-I) system and nutritional status was studied in 241 children from a Brazilian area endemic for visceral leishmaniasis (VL). Thirty-nine children had the active form, 20 were oligosymptomatic, 38 were asymptomatic and 144 were not infected. Serum concentrations of growth hormone (GH), total and free IGF-I and IGF binding-protein 3 (IGFBP3) were measured by radioimmunoassay. Nutritional status was evaluated by anthropometric indicators and biochemical measurements. Total and free IGF-I and IGFBP3 were significantly reduced in the active form. Z scores for total and free IGF-I and for IGFBP3 were found to be significantly lower for active VL and oligosymptomatic individuals than for asymptomatic individuals, but never reached values <or=2 SD. Median values of weight-for-age Z and height-for-age Z (HAZ) scores and albumin concentration were significantly different in the active VL group compared with the other groups. Multiple discriminant analysis selected albumin and HAZ score as predictors of active and oligosymptomatic VL. The lack of correlation between auxological data and serum concentrations of the GH/IGF axis components suggested that the primary cause of retarded growth in children with active VL is not dependent on IGF-I or IGFBP3, but rather on VL intrinsic factors that might secondarily involve the GH/IGF axis.

Bone mass, biochemical markers and growth in children with chronic kidney disease: a 1‐year prospective study

This study was designed to investigate bone mineral density (BMD), growth parameters and biochemical markers in children with chronic kidney disease (CKD). Sixteen patients, 4-18 years, with CKD were prospectively followed for 1 year. Auxological data, body composition, BMD by dual-energy X-ray absorptiometry, bone age, bone turnover markers, vitamin D, parathyroid hormone (PTH), leptin, osteoprotegerin, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were measured. A questionnaire regarding bone health and diet was also performed. Delayed bone age was observed (n = 11) and the BMD Z-scores for total body were below zero in seven patients. However, total body BMD (TBBMD) increased in 12 patients. Most patients had increased osteocalcin and carboxy-terminal telopeptide of type I collagen, but normal alkaline phosphatase, type I procollagen intact amino-terminal propeptide and tartrate-resistant acid phosphatase 5b. Ten patients had increased PTH. Most children had normal levels of leptin, osteoprotegerin, IGF-I and IGFBP-3. Leptin, at baseline, correlated with differences in TBBMD over 1 year. Only seven (44%) had negative Z-scores and TBBMD increased over 1 year. Bone markers at baseline did not predict the longitudinal changes in BMD.

Metabolic parameters and adipokine profile during GH replacement therapy in children with GH deficiency

GH replacement therapy in children with GH deficiency (GHD) mainly promotes linear growth. Not only have very few studies fully analyzed the metabolic consequences of GH therapy, but also the question as to whether GH may affect adipokine secretion has been insufficiently investigated. Our aim was to study the effects of GH replacement therapy on auxological data, lipid and glycemic profiles, insulin homeostasis (HOMA-IR) and serum adipokines in children. This was a 1-year prospective study. Thirty-four GHD children (11.6 +/- 2.6 years) and thirty healthy matched controls were enrolled. Children affected by GHD were studied both before beginning continuous GH replacement therapy and again at 12 months. At the beginning of the study, total and LDL cholesterol were higher in GHD children than in controls (P<0.001), whereas HDL cholesterol, triglycerides, insulin, HOMA-IR, leptin, and adiponectin were similar. At 12 months of continuous GH replacement therapy in the GHD group, there was a significant increase in both auxological data and IGF-I (P<0.001); total cholesterol (P<0.001), LDL (P<0.001), triglycerides (P<0.005), and leptin (P<0.001) decreased significantly; HDL (P<0.003), insulin (P<0.001), HOMA-IR (P<0.001) increased while adiponectin was unmodified. Furthermore, IGF-IDelta showed an inverse correlation with leptin Delta (rho = -0.398, P = 0.02). In GHD children, the evaluation of metabolic parameters proves to be a useful tool for the evaluation of auxological parameters during GH replacement therapy. In our study, GH replacement therapy in GHD children improved final height, restored IGF-I levels, reduced leptin levels, and improved the lipid profile, without producing any unfavorable effects on glucose metabolism.

Growth parameters in maternal uniparental disomy 7 and 14

Growth retardation has been reported in most cases of maternal uniparental disomy (UPD) 7 and 14, but has never been evaluated in a systematic approach. In this study, an analysis is presented of the auxological data from the literature at birth and on the occasion of the last evaluation of 34 cases with maternal UPD 7 (21 heterodisomy, 13 isodisomy) and 29 cases with maternal UPD 14 (22 heterodisomy, 7 isodisomy). For maternal UPD 7, statistical analysis revealed that length and weight at birth as well as on the occasion of the last evaluation were strongly below average (-2.94 SD and -2.62 SD, and -3.39 SD and -3.11 SD, respectively), whereas at both evaluations occipitofrontal head circumference (OFC) was only slightly below the average (-1.00 SD and -0.85 SD). For maternal UPD 14 at birth, growth retardation is rather concordant for length, weight, and OFC (-2.78 SD, -2.84 SD, and -1.69 SD). Later in life body mass index (BMI) is above average (1.06 SD) and continuously increasing before and after puberty (-0.58 SD and 2.07 SD). Growth retardation and relative macrocephaly are of prenatal onset and still present in adults with maternal UPD 7. For patients with maternal UPD 14, growth curves for height, BMI and OFC differ strongly. Genomic imprinting might be a major causative factor, but it seems to function differently for maternal UPD 7 and maternal UPD 14.

Pregnanetriol in the Range of 1.2-2.1 mg/m(2)/day as an Index of Optimal Control in CYP21A2 Deficiency.

Auxological data is the gold standard index of the therapeutic condition in CYP21A2 deficiency over a long-range period, whereas urinary pregnanetriol for 24 h (PT) is variable for a shorter-range period. Ideal PT levels in comparison with auxological data have not been reported. The main purpose of this study was to analyze ideal PT values as an index of optimal control for CYP21A2 deficiency. First, inter-daily fluctuation of PT was analyzed in one participant. PT levels were distributed over a wide range of 0.44–14.7 mg/day (n=42) in this participant, suggesting that the therapeutic condition should be judged by multiple PT samples. Second, the therapeutic periods of 15 participants with CYP21A2 deficiency were classified using auxological data and Cushing-like symptoms, and the PT levels were analyzed in each period retrospectively. The 95% confidence intervals for the means of the PT levels in the excessive, good and poor control periods were 0.03–1.25 (n=26), 1.23–2.09 (n=116), and 5.35–8.37 (n=72) mg/m2/day, respectively. In conclusion, 1.2–2.1 mg/m2/day of PT values can be used as an index of optimal control in CYP21A2 deficiency.

Exon 3-Deleted/Full-Length Growth Hormone Receptor Polymorphism Genotype Frequencies in Spanish Short Small-for-Gestational-Age (SGA) Children and Adolescents (n = 247) and in an Adult Control Population (n = 289) Show Increasedfl/flin Short SGA

A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy. The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations. An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected. Thirty Spanish hospitals participated in the selection of the short non-GH-deficient SGA children in the setting of a controlled, randomized trial, and one of these hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine adult subjects of both sexes constituted the ACPNH and 247 children and adolescents of both sexes the short SGA patients. Heights and weights were recorded in the ACPNH, and auxologic and biochemical data were recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were determined and data analyzed in a single hospital. In short SGA patients, d3/fl-GHR genotype frequencies were significantly different from those in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a trend toward diminished d3/d3 genotype frequency was observed in the shortest height group (height <or=-1 SDS and >or=-2 SDS, n = 60). Our data showed significant differences in the frequency distribution of the d3/fl-GHR genotypes between a normally distributed adult height population and short SGA children, with the biologically less active fl/fl genotype being almost twice as frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism might be considered among the factors that contribute to the phenotypic expression of growth.