Growth Retardation In Patients Research Articles

Changes of GH-IGFs and its relationship with growth retardation in children with bronchial asthma

ObjectiveTo explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. Methods112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. ResultsGH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 μg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. ConclusionGH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

Fetal growth restriction in diabetic pregnancy: a retrospective single-center study

BACKGROUND: The high risk of adverse maternal and perinatal complications in patients with fetal growth restriction and diabetes mellitus requires a detailed assessment of the major risk factors and outcomes.&#x0D; AIM: The aim of this study was to determine the main risk factors for fetal growth retardation in pregnant women with pregestational and gestational diabetes mellitus, and to assess obstetric and perinatal outcomes in these patients.&#x0D; MATERIALS AND METHODS: We conducted a retrospective single-center cohort study at the premises of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Saint Petersburg, Russia. The study included 103 patients with type 1 diabetes mellitus, type 2 diabetes mellitus, or gestational diabetes mellitus with fetal growth retardation who delivered a singleton neonate from January 2017 to December 2021. Based on the antenatal diagnosis, the patients were divided into the following comparison groups: group I early fetal growth retardation (n = 29), group II late fetal growth retardation (n = 27), group III small for gestational age (n = 47). Relative risk calculations were used to assess the contribution of risk factors and the risk of developing secondary outcomes.&#x0D; RESULTS: Pregestational diabetes mellitus was the major risk factor for early fetal growth retardation development (relative risk 1.91; 95% confidence interval 1.043.50); especially type 1 diabetes mellitus (relative risk 1.64; 95% confidence interval 1.022.74) and more than 10 years of pregestational diabetes mellitus duration (relative risk 2.62; 95% confidence interval 1.126.17). Chronic hypertension increases the risk of early fetal growth retardation (relative risk 2.11; 95% confidence interval 2.213.68), while gestational hypertension was a significant risk factor for late fetal growth retardation development (relative risk 1.81; 95% confidence interval 1.013.70). Preeclampsia is associated with both early and late forms of fetal growth retardation. Maternal characteristics, such as age over 35 years, obesity, and in vitro fertilization pregnancy, increased the risk of early fetal growth retardation development. In turn, the presence of fetal growth retardation in patients with diabetes mellitus is associated with increased risk of cesarean section, prolonged stay of the newborn in the neonatal intensive care unit (5 days), low Apgar scores (7 at the 5th minute), and neonatal hypoglycemia. Early fetal growth retardation is a significant risk factor for preterm birth (relative risk 6.23; 95% confidence interval 2.8713.42) and fetal distress (relative risk 5.51; 95% confidence interval 2.2813.33).&#x0D; CONCLUSIONS: Being associated with a highly increased risk of adverse obstetric and perinatal outcomes, early fetal growth retardation in diabetic pregnancy is related to pregestational diabetes mellitus, especially type 1 diabetes mellitus, with a long history, as well as with hypertension in pregnancy.

Prevention of recurrent fetal growth retardation in patients with circulating antiphospholipid antibodies and genetic thrombophilia

Aim: to evaluate the effectiveness of using low molecular weight heparin (LMWH) and low-dose acetylsalicylic acid (ASA) in preventing recurrence of early and late fetal growth retardation (FGR) in patients with antiphospholipid syndrome (APS) and/or genetic thrombophilia.Materials and Methods. A prospective randomized controlled study was conducted by examining 32 patients aged 23 to 43 years with a history of early and late II and III FGR as well as thrombophilia. Prevention protocol using LMWH and ASA was carried out from the pregravid period or early pregnancy. The control group included 35 women with uncomplicated pregnancy. Antiphospholipid antibodies (APA) were measured according to the Sydney antiphospholipid syndrome (APS) criteria by using enzyme immunoassay (ELISA): cardiolipin, β2-glycoprotein 1 and additionally antibodies to annexin V, prothrombin, etc. (IgG/IgM isotypes); lupus anticoagulant – by a three-stage method with Russell's viper venom; antithrombin III and protein C levels – by chromogenic method; prothrombin gene polymorphisms G20210A as well as factor V Leiden polymorphism – by chain reaction; homocysteine – by ELISA.Results. It was found that prevention protocol was effective in 78.1 % cases. FGR re-developed in 7 (21.9 %) pregnant women: in 2 (6.3 %) at 20 and 22 weeks, in 3 (9.4 %) at 30–32 weeks, in 2 (6.3 %) after 34 weeks of pregnancy. All these patients were found to have APA exceeding 40 U/ml with low dynamics of decline, 3 (9.4 %) were older than 35 years, 2 (6.3 %) had chronic kidney pathology and 1 (3.1 %) had a hypertension in the anamnesis.Conclusion. The use of LMWH and low-dose ASA starting from the pre-pregnancy period and early pregnancy as a part of complex therapy allows to effectively prevent re-development of FGR in patients with thrombophilia. In case of high APA titers, the use of LMWH and low-dose ASA may be ineffective, and alternative treatment methods in addition to anticoagulant therapy should be used to improve obstetric results.

Are COL4A1 and COL4A2 gene polymorphisms associated with cerebral palsy?

Objectives This study aims to investigate the association of COL4A1 and COL4A2 gene polymorphisms with susceptibility to risk of developing cerebral palsy (CP) and severity of CP. Patients and methods Between December 2016 and June 2017, a total of 176 patients with CP (101 males, 75 females; mean age 71.8±37.9 months; range, 24 to 184 months) and age-, sex-, and ethnically-matched 178 (90 males, 88 females; mean age 69.3±55.2 months; range, 24 to 214 months) controls were included. Two polymorphisms of COL4A1 (rs1961495) and COL4A2 (rs9521733) genes were typed from genomic deoxyribonucleic acid. Genotype distributions and allelic frequencies were compared between the patient and control groups. Gross Motor Function Classification System, the use of medical drugs, type of involvement, number of affected limbs, accompanying conditions, birth weight, gestational age, and magnetic resonance imaging (MRI) findings were used to evaluate the disease severity and their relationships with the COL4A1 and COL4A2 gene polymorphisms. Results There was no statistically significant difference between the groups in terms of genotype distribution and allele frequency of COL4A1 and COL4A2 gene polymorphisms (p>0.05). In addition, there was no relationship between severity of CP and two gene polymorphisms (p>0.05). A significant association was detected between the COL4A2 polymorphism and growth retardation in CP. The TT genotype (57.1%) and T allele (76.2%) were higher, compared to CC (4.8%) and CT genotypes (38.1%) and C allele (23.8%) in patients with CP with growth retardation (p=0.03 for genotype and p=0.01 for allele frequency). Conclusion These findings suggest that COL4A1 and COL4A2 gene polymorphisms are not associated with susceptibility to CP in a group of Turkish populations, although COL4A2 gene polymorphism may be associated with growth retardation in patients with CP.

Evaluation of parameters associated with growth retardation in children with coeliac disease.

Coeliac disease (CD) is an autoimmune disorder with a prevalence ≤2% that causes an immune reaction to gluten. Growth retardation (GR) generally accompanies CD due to gastrointestinal complications and should be treated as early as possible along with initiation of a gluten-free diet. The aim of this study was to determine the indicators of GR in patients with CD. This single-centre retrospective study included paediatric outpatients with CD. All patients were diagnosed with CD via serological analysis and upper gastrointestinal endoscopy if necessary. Patient records were obtained from Adana City Training and Research Hospital. Patients that were diagnosed with GR accompanying CD were given oral nutritional supplements and followed-up every 3-6months. Statistical relationships between demographics, and anthropometric measurements, duration of breastfeeding, gluten contact time, diet duration, presenting complaints and serological findings were evaluated. This study included 169 paediatric outpatients between ages 1 and 18. Longer symptom duration and shorter breastfeeding duration were significantly correlated with GR accompanying CD (P= 0.007 and P= 0.029, respectively). Vomiting was the only symptom that was correlated with the presence of GR (P= 0.010). Helicobacter pylori infection was not correlated with the presence of GR (P= 0.277). GR should be treated as early as possible to reduce the severity of CD and a 6months sole breastfeeding followed by solid foods accompanied by breastfeeding for 2 years is crucial for preventing GR. Moreover, vomiting as a presenting complaint in patients with CD might be indicative of the presence of GR.

Prevalence of hypoparathyroidism, growth retardation in patients of Beta-thalassemia major

Beta-Thalassemia is a genetic disorder which is associated with a lot of complications. Frequent blood transfusions result in increased iron deposition in various tissues leading to dysfunction of many vital organs. Endocrine disorders constitute a major part of such complications increasing the morbidity of thalassemia manifold in the affected patients. Early diagnosis of hypoparathyroidism (HPT) could prevent other severe disorders such as Tetany, seizures, osteopenia, and osteoporosis. Growth retardation can occur as complication of thalassemia as early as the 1st or 2nd year of life but these abnormalities more prominent after the 6 – 8 years of life.The aim of this study was carried out to determine; 1. The prevalence of Hypoparathyroidism (HPT) and Growth retardation in patients with beta thalassemia and to correlate them with serum ferritin, calcium, phosphorus and alkaline phosphatase levels; 2. The relationships of growth failure with certain variable including age, serum ferritin, mean hemoglobin level and gender of the patients. This is a descriptive cross sectional research study which was conducted on 200 subjects (100 cases and 100 controls) in the age group of 10-25 years who had visited the OPD/IPD of Subharti Medical College &amp; affiliated Hospitals, Meerut. The cases included were with confirmed diagnosis of beta thalassemia major, with regular blood transfusions and serum ferritin levels &amp;#62;2000 ng/ml irrespective of chelation therapy. Out of 100 patients, Hypoparathyroidism was diagnosed in 18% patients, Growth retardation/ Short stature 93% and Weight loss was found in 93% patients. The mean age at diagnosis was 12.6 years (range 11-16 years), mean serum calcium was 7.53 mg/dl (range7.58-9.04 mg/dl), mean serum ferritin was 5831.0 ng/ml (range 2000-8,064 ng/dl) and mean serum phosphate was 5.63 mg/dl (range 4.50-7.73 mg/dl). Serum parathyroid hormone (PTH) levels were low in most of the patients. Short stature was observed in most of the patients, while it was found normal in control subjects.Significant Hypoparathyroidism (HPT) observed along with growth retardation in beta thalassemia patients (p &amp;#60; 0.001). A significant decrease in serum calcium level was seen in cases when compared to controls, where as the levels of both serum phosphorus and alkaline phosphatase levels were found increased in cases as compared to control.

A broad range of symptoms in allgrove syndrome: single center experience in Southeast Anatolia.

Allgrove syndrome (OMIM 231550) is a rare autosomal recessive disease characterized by non-CAH primary adrenal insufficiency (non-CAH PAI), alacrima, and achalasia. It is caused by mutations in the AAAS gene. The syndrome is also associated with variable progressive neurological impairment and dermatological abnormalities. We diagnosed 23 patients from 14 families with Allgrove syndrome, based on the presence of at least two characteristic symptoms, usually adrenal insufficiency and alacrima, between 2008 and 2018. A previously described nonsense variant of AAAS was detected in 19 patients from 12 families at homozygous state. Another novel homozygous mutation (c.394-397delCTGT) in AAAS was detected in four patients from two families. Presenting symptoms were alacrima (23/23; 100%), adrenal insufficiency (18/23; 78%), achalasia (13/23; 57%), short stature/growth retardation (16/23; 70%), hyperreflexia (15/23; 65%), palmoplantar hyperkeratosis (13/23; 57%), hyperpigmentation of the skin (10/23; 43%), hypoglycemia-induced convulsion (7/23; 30%), swallowing difficulty and vomiting (6/23; 26%). Serum DHEAS concentrations were low in all patients (23/23; 100%). Clinical symptoms vary even among patients carrying the same mutation. Triple A syndrome should be considered in the etiology of non-CAH PAI in Arab populations and in Southeast Turkey. Any child with non-CAH PAI should be evaluated for the presence of alacrima and/or achalasia or family history of alacrima and/or achalasia. Children with alacrima and/or achalasia should also be investigated for adrenal insufficiency. Definitive molecular diagnosis is essential for early diagnosis and management of adrenal insufficiency, neurological symptoms, and growth retardation in patients and early diagnosis of as yet asymptomatic cases in the family, together with genetic counseling.

Evaluation of serum Resistin in children with chronic renal failure undergoing hemodialysis.

IntroductionHigh serum resistin levels are associated with the incidence of chronic kidney disease (CKD). The objectives of this study were to determine the serum concentrations of resistin in children that present with chronic renal failure (CRF) and end stage renal disease (ESRD), in order to examine the impact of hemodialysis (HD) on serum resistin levels, and to determine if a correlation exists between resistin and growth retardation in patients with CRF.MethodsThis case control study was undertaken in the pediatric hemodialysis unit of the Benha and Menoufia University hospitals from April 2014 to March 2015. The case group consisted of 50 patients with CRF aged from 6–18 years (25 of them under HD and 25 of them under conservative treatment) and 30 healthy children who constituted the control group. Urea, creatinine, and serum resistin were measured before and after the HD session for patients with CRF who are already under HD.ResultsA highly significant difference was found between the resistin levels in the two groups with mean level of 20.2 ± 7.58 ng/ml in the patient case group as compared to 4.9 ± 1.72 ng/ml in the control group. This highly significant difference found in the resistin level differed according to the Chronic Kidney Disease (CKD) stage of progression as patients on regular HD had resistin levels with a mean of 24.6 ± 7.28 ng/ml while the CKD patients under conservative treatment have resistin level mean of 15.6 ± 4.72 ng/ml. there was a highly significant difference in resistin levels before HD (mean = 24.6 ± 7.28) and after hemodialysis (mean = 14.7 ± 5.2).ConclusionPatients with CRF experienced higher than normal resistin levels as compared to the case control group and it was found that patients on HD had more elevated levels of resistin than did those patients who were on conservative treatment. HD treatments were found to be capable of lowering a patient’s resistin levels. A highly significant negative correlation was found between serum resistin levels and the two contributing factors of total body weight and body mass index (BMI) as well as demonstrating a significant negative correlation between serum resistin levels and height percentiles.

P-29: Growth Retardation in Patients with Esophageal Atresia

P-29: Growth Retardation in Patients with Esophageal Atresia

A retrospective analysis of synthetic protein prescription in Irish children with phenylketonuria

Background: Phenylketonuria (PKU) is an inherited inborn error of metabolism resulting in the inability of the patient to metabolise the essential amino acid (AA) phenylalanine (Phe) and convert it to tyrosine. Untreated, a build-up of Phe occurs that damages the brain and leads to mental retardation (Williams et al., 2008). Management guidelines for the treatment of the disorder by the Medical Research Council (MRC) make recommendations on the quantity of AA substitute to be provided and the desired ranges for Phe levels. The aim of this study was to address the hypothesis that children consuming less than recommendation for synthetic AA intake can grow normally and achieve good biochemical control. Methods: Patients with moderate to classical hyperphenylalaninaemia born between the 1 January 1998 and December 2008 were retrospectively identified from the patient database of the National Centre for Inherited Metabolic Disorders for inclusion in the study. Anthropometric data and protein intake data were collected from medical records of 121 patients from birth to the age of 2 years, at six specific time-points. From these data, exact weight/height centiles and change in centile z-scores were calculated. Intakes (g kg−1) of synthetic AAs and natural protein were calculated at each time-point based on protein intake reported by parents and noted in dietetic notes. The cohort was split into groups based on synthetic AA intake: ≥ 3g kg−1day−1, representing those meeting the MRC guidelines, 1.5–1.99 g kg−1 day−1 and 2–2.5 g kg−1 day−1. These groups were then statistically compared in terms of growth parameters and biochemical control using Student's t-tests and Mann–Whitney U-tests depending on data distribution. Results: At 2 years, subjects in the groups achieving lower than the recommended synthetic AA intake displayed a significantly smaller decrease in the change in z-score for height (P = 0.001 for 2–2.5 g kg−1 group, P = 0.034 for 1.5–1.99g kg−1 group compared to ≥3 g kg−1 day−1) and weight (P = 0.006 for 2–2.5 g kg−1 group compared to ≥3 g kg−1 day−1), indicating that they had less of a growth deficit compared to those meeting the AA intake guideline. Mean blood Phe levels over the time-points investigated were also significantly lower in the groups consuming less than the MRC guideline. Discussion: This study has shown that the growth deficit is less in patients consuming decreased amounts of synthetic protein. Schaefer et al. (1994) found no correlation between Phe intake and the rates of growth, although they did not analyse the effect of synthetic protein intake on these parameters. In the current study, significant negative correlations were found between change in weight and height centile z-scores and synthetic AA intake at 2 years. This negative correlation was upheld, even when the confounding effect of natural protein intake was controlled for. These results are contrary to previously published studies showing no correlation between protein intake and growth retardation (Weglage et al., 1994; Dobbelaere et al., 2003). As with the study by Schaefer et al. (1994), these studies did not analyse the two separate fractions of protein that PKU patients consume (i.e. natural and synthetic). These results support the hypothesis that children can achieve adequate growth and biochemical control at synthetic AA intakes below the MRC recommendation. Conclusions: This study provides a base upon which prospective studies should be designed to determine a more appropriate synthetic AA intake recommendation for children with PKU.

Risk Factors to Growth Retardation in Major Thalassemia

The increasing in the life span of patients with major thalassemia should be followed by increased quality of life. There are factors which can affect growth retardation in these patients. The aim of this study was to find out the risk factors for growth retardation in patients with major thalassemia. An analytical study with cross-sectional design was conducted at Pediatric Thalassemia Clinics of Dr.Hasan Sadikin Hospital, Bandung, in June to July 2006. The subjects of this study were patients with major thalassemia. Inclusion criteria’s were age under 14 years old, had no chronic diseases like tuberculosis, cerebral palsy with complete medical records. Risk factors were the timing of diagnosis, initial and dose of deferoxamine, volume of transfused blood, mean pretransfusion hemoglobin level, family income, and age. Antropometric measurement indices were used to assess the growth which expressed in Z score. Growth evaluated based on height/age (H/A) and growth retardation if H/A

Somatomedin-C/IGF-I, insulin and prolactin levels in Ullrich-Turner's syndrome.

To clarify the pathogenesis of growth retardation in patients with Ullrich-Turner's syndrome (TS) we have investigated basal SmC/IGF-I, insulin and prolactin concentrations. Compared with 56 age matched healthy controls basal SmC/IGF-I concentration in 51 patients with TS older than 9-11 years was significantly lower (age group 13-14 years; TS 273 +/- 47 and controls 479 +/- 114 ng/ml). Mean basal prolactin level in 43 patients with TS (406 +/- 211 microU/ml) was significantly higher (p less than 0.01) than in 192 female controls (age 3-11 years; 264 +/- 176 microU/ml). Basal insulin concentration in 28 TS patients in comparison to 20 healthy children of a control group was significant higher (TS 18 +/- 8 microU/ml; controls 9 +/- 4 microU/ml; p less than 0.01). It seems that neither insulin nor prolactin are relevant stimulators of Smc/IGF-I in man, especially in patients with gonadal dysgenesis. Considering these results we speculate that despite higher prolactin and higher insulin levels in TS, the lower SmC/IGF-I concentrations may be predominantly related to the abnormal sex steroid secretion.

Growth retardation in patients with juvenile idiopathic arthritis and growth hormone therapy

Methods Study cohort was presented by 170 JIA patients (47 boys, 123 girls, mean age 12.1, disease duration 5.1 yrs). Annual growth parameters were studied in relation with premorbid and disease related factors. 30 prepubertal patients, having the most significant delay of growing were randomized in 2 groups. 15 patients were received recombinant GH 0,05–0,07 mg/kg within 4–18 months; other 15 patients were as control.

Crecimiento en niños con artritis idiopática juvenil

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that often requires steroid therapy. Growth retardation can be a serious complication in some of these patients. To study linear growth in patients with JIA and evaluate the factors involved in its disturbance. We studied 91 patients with JIA with a follow-up of at least one year. A cross sectional study, a longitudinal retrospective study, and a longitudinal prospective study were performed. Height in the first consultation, in the cross sectional study, and one year previously was evaluated. Height velocity (HV) was calculated. Several parameters related to disease activity, corticosteroid therapy, nutritional and hormonal status, and bone mineral density (BMD) were analyzed. A correlation study and multivariate regression analysis were carried out. Height was < or = -2 SD in 14.3 % of the series and in 55.6 % of the systemic group. Variables independently associated with height were total corticosteroid dose, functional class, nutritional index, BMD, and age at onset of the disease. HV was < or = 2 SD in 25.3 % of the series and in 61 % of the systemic group. Variables independently associated with HV were corticosteroid dose and the number of swollen joints. Growth retardation in patients with JIA was associated with factors related to the disease, corticosteroid therapy, nutritional status, BMD, and earlier onset of the disease.

Intractable diarrhea after liver transplantation for Byler's disease: successful treatment with bile adsorptive resin.

Intractable diarrhea and prolonged growth retardation after liver transplantation for Byler's disease are serious complications limiting the ultimate outcome of liver transplantation for this disease. However, details of these complications have not been documented thoroughly. Six patients with Byler's disease developed intractable diarrhea after living donor liver transplantation. Because of high bile acid concentrations in stool, four patients were treated with bile acid adsorptive resin for bile acid diarrhea, and all showed improved bowel movements. Four of these patients who were followed up for 1 year registered a significant height gain. Also, the cause of postoperative diarrhea and growth retardation in patients with Byler's disease after liver transplantation is discussed.

Does treatment of asthmatic children with inhaled corticosteroids affect their adult height?

In this retrospective study, adult height was assessed in young adult asthmatics who were treated with inhaled corticosteroids (ICs) during childhood (n = 42; 26 boys) and compared to those obtained in asthmatic patients who were never treated with ICs during childhood (n = 43; 23 boys). Standing height of all subjects and their parents was measured. Height data were analyzed using actual length and target height in centimeters, standard deviation scores (SDS), and difference between adult height of the patients and their target height (adult height minus target height). Mean adult height was the same in subjects who took ICs during childhood as compared to those who had never received ICs (boys: 179.3cm+/-6.8 vs. 180.4 cm+/-5.6; girls: 165.8 cm+/-7.5 vs. 167.7 cm+/-7.2). SDS of adult height was also not different between the two groups: in subjects who did not take ICs it was 0.89+/-1.00, while in those who took ICs it was 0.66+/-1.10 (P = 0.31). SDS of target height was also not different between the two groups: in subjects not taking ICs it was 0.95+/-0.86, while in those who took ICs it was 0.28+/-0.76 (P = 0.30). However, subjects who took ICs during childhood showed a statistically significant lower value of adult height minus target height than those who never took ICs (whole group: -0.003+/-5.9 vs. 2.54 +/-4.8, P = 0.03 ; boys: 0.004+/-5.8 vs. 3.09+/-4.5, P = 0.04 ; girls: -0.075+/-6.3 vs. 1.91+/-5.2, P = 0.31). Patients on ICs during childhood who had ever been hospitalized for asthma showed a lower value for adult height minus target height than those who took ICs but were never hospitalized (-3.08+/-7.8 vs. 1.06+/-4.8, P = 0.046). A logistic regression analysis predicting growth impairment showed that the best-fitting model was one that used only ICs as a dependent variable (crude odds ratio, 3.3; 95% CI, 1.3-8.4). Patients who were treated with ICs in combination with intranasal corticosteroids (treatment for rhinitis) tended to have a lower value of adult height minus target height than the other children, but the difference was not statistically significant (P = 0.07). We conclude that although adult height was the same in young adults who were treated with ICs during childhood compared to those who were not treated with ICs during childhood, there was a statistically significant difference between the two groups for adult height minus target height, suggesting mild growth retardation in patients who took ICs during childhood. These findings may be explained by the use of ICs, but it seems more likely that a difference in asthma severity between both groups was responsible for it.

Failure to increase insulin-like growth factor-I synthesis is involved in the mechanisms of growth retardation of children with inherited liver disorders.

Growth retardation is a prominent secondary feature of chronic liver disease. We investigated the hypothalamic-pituitary-liver axis in six patients with inherited liver disease and growth failure. The objectives were to determine (1) whether there were any abnormalities in the GH/IGF-I/IGFBPs/GH binding protein (GHBP) axis, (2) whether any abnormalities were nutrition-dependent, and (3) whether recombinant human (rh) GH could be efficaciously and safely administered. The evaluation included two standard GH provocative tests, GHRH test, night-time GH secretion, GHBP; and IGF-I, IGFBP-3 and IGFBP-1 before and after 0.1 and 0.3 U/kg/day of rhGH given i.m., for 4 days. Two patients were enrolled for rhGH treatment. Quantitative nutritional assessment showed the patients' calorie and protein intake to be compatible with the recommended daily allowance in liver disease. The mean baseline GH level was higher in patients than in controls (8.4 +/- 3.8 vs 2.6 +/- 2.0 mU/l, P < 0.005) and the GH response to stimuli was normal; spontaneous GH secretion was apparently normal. The mean baseline IGF-I value in the patients was significantly below the mean of controls (31.6 +/- 16.4 vs 260 +/- 35.2 micrograms/l, P = 0.00001) and similar to that of children with GH-deficiency (40.8 +/- 18.4 micrograms/l). The mean peak IGF-I response after 0.1 U/kg/day of rhGH increased (84.9 +/- 28.2 micrograms/l, P = 0.009) but remained lower than the mean IGF-I response in GH-deficient patients and in controls (P = 0.00001). The mean peak IGF-I response after 0.3 U/kg/day (113.3 +/- 52.3 micrograms/l) was significantly higher than that after 0.1 U/kg/day (P = 0.002). The mean standard deviation score (SDS) peak for IGF-I response to 0.1 and 0.3 U/kg/day of rhGH decreased significantly from -1.7 to -1.0 (P = 0.02) and from -1.9 to -0.9 (P = 0.005), respectively. There was no difference between patients and controls in serum GHBP activity or in mean baseline IGFBP-3 and IGFBP-1 levels. IGFBP-3 levels did not change significantly in response to rhGH at either 0.1 or 0.3 U/kg/day, while IGFBP-1 significantly decreased after 0.3 U/kg/day (56.3 +/- 35.6 vs 45.9 +/- 33.1 micrograms/l, P = 0.04). A significant positive correlation was present between albumin and peak IGF-I responses to rhGH at the dose of 0.1 and 0.3 U/kg/day (R = 0.83, P = 0.03; R = 0.78, P = 0.03 respectively), as well as between height SDS and baseline or stimulated IGF-I after rhGH 0.1 U/kg/day (R = 0.81, P = 0.04; R = 0.88, P = 0.01 respectively). In the two patients treated with rhGH at 22-25 U/m2/week, the growth rate doubled in one and trebled in the other during the first year of treatment, and in both was maintained in the second year without acceleration of bone maturation or evidence of adverse effects. The underlying cause of growth retardation in patients with inherited liver disease seems to be a progressive failure to increase IGF-I synthesis (at the conventional rhGH dose) and the consequent lack of its growth-promoting effect. The moderate increase in baseline GH values, the greater IGF-I response to the higher rhGH dose and the improvement in growth rate following rhGH administration suggest at least a degree of sensitivity to rhGH which could be of therapeutic value.

Does impaired growth of PKU patients correlate with the strictness of dietary treatment? National Dutch PKU Steering Committee.

To assess whether growth retardation in patients with phenylketonuria (PKU) is related to the strictness of their dietary treatment, the relationship between Z scores for height up to 3 y of age and different indices of dietary control in 103 early treated Dutch PKU patients was studied. As indices of dietary control, the mean phenylalanine (Phe) concentration, the frequency of plasma Phe concentrations < 200 and < 120 micromol/l, and the standard deviation of the individual plasma Phe concentrations were studied. These measures of the dietary control were divided into quartiles. The mean Z score of the studied patients showed a decrease of 0.18/y (SD 0.36). No statistically significant difference between any of the quartiles of the studied indices with growth retardation was found. None of the used indices of dietary control based on plasma Phe concentrations showed a relationship between different degrees of the strictness of dietary treatment with growth retardation in Dutch PKU patients.

Quantification of Orbital and Mid-facial Growth Retardation after Megavoltage External Beam Irradiation in Children with Retinoblastoma

The late side effects of external beam irradiation in patients with retinoblastoma such as orbital bony growth retardation, are a serious problem in adolescence. Therefore, a quantitative study was performed to investigate the late effects of irradiation on orbital growth in patients with retinoblastoma. The orbits of 68 patients with retinoblastoma, 52 bilateral and 16 unilateral, were divided into two treatment groups: radiotherapy alone, 77 orbits; and radiotherapy + enucleation, 43 orbits. Follow-up time was 12 to 240 months (mean, 95 months) in group 1 and 27 to 216 months (mean, 97 months) in group 2. These groups were subdivided further into age groups at which radiotherapy was given. The morphometric measurements of these groups were compared. The authors showed that irradiation causes a significant growth retardation when compared with the growth of nonirradiated orbits (P<0.001). They also demonstrated that radiotherapy in children younger than 6 months of age is more damaging to the orbital growth than at an older age (P<0.01). Finally, the authors showed that secondary enucleation does not have an additive growth-retarding effect. Orbital growth retardation in patients with retinoblastoma after radiotherapy is influenced mainly by the age at which irradiation is given and is defined at 6 months. Theoretically, it would be desirable to postpone irradiation in children until they are older than 6 months of age if possible. The irradiation effect on these orbits is not enhanced by enucleation.

Uterine Doppler wave form and the prediction of the recurrence of pre-eclampsia and intra-uterine growth retardation in patients treated with low-dose aspirin

Objective: To examine if early uterine Doppler remains a predictor of vascular complications in pregnant women treated with low-dose aspirin for a poor previous obstetrical history. Design: A study of the uterine diastolic index and the uterine notch with a continuous wave Doppler ultrasound. Setting: The maternity Hospital Port-Royal Baudelocque Paris, France. Subjects: All pregnant women between 1991–1992 ( n = 48) early treated with 100 mg daily of aspirin (15.9 (S.D. = 1) weeks) for a poor previous obstetrical history. Methods: The 48 patients underwent a uterine Doppler examination at 23.8 (S.D. = 2.6) weeks. A diastolic index was calculated and the presence of diastolic notch was noted. Main outcome measures: Vascular complications (pre-eclampsia, intra-uterine growth retardation), birth weight. Results: Twenty six patients (54.2%) had an abnormal early uterine Doppler. Nine patients (18.7%) had a vascular complication, which occurred more frequently in pregnant patients with an abnormal uterine Doppler ( 8 26 vs. 1 22 ; P < 0.05). The mean birth weight was lower in patients with a pathological uterine Doppler (2419 (S.D. = 679) vs. 2841 (S.D. = 482) g; P < 0.05). Conclusions: In pregnant, early treated with low-dose aspirin for poor previous pregnancies, early uterine Doppler predicted patients with a high-risk of recurrence of vascular complications.