ABSTRACT
After an outbreak with Enterobacter cloacae we decided to routinely nurse all neonates in isolation who were transferred from a neonatal intensive care unit (NICU) to the neonatal unit of the Diakonessenhuis until cultures for MRSA and antibiotic-resistant gram-negative bacteria were negative. The goal of this study was to determine (1) the colonization patterns with (antibiotic-resistant) bacteria; (2) whether there is a trend in time and (3) to identify predictors for colonization. Neonates from 2001 till 2006 transferred from a NICU to our neonatal unit were included. Patients were monitored for infections. In total 287 neonates were included. The average birth weight was 1990 g and gestational age 33 weeks and 3 days. Only one patient was colonized with a highly resistant microorganism (HRMO) and no MRSA was isolated. A NICU-stay longer than one week was the only independent risk factor for bacterial colonization. Twenty-six percent of neonates were colonized with bacteria resistant to amoxicillin/clavulanate. Five neonates (1.7%) developed a bacterial infection after transfer, none of them caused by an antibiotic-resistant microorganism present at transfer. No significant trends in time were found. In conclusion, we found a low prevalence of HRMO and a low incidence of bacterial infections in neonates after transfer from a NICU. There was no significant increase in time in the prevalence of colonization with (resistant) bacteria. A NICU-stay longer than a week was an independent predictor for colonization with bacteria. Based on these observations we have ended standard culturing and nursing in isolation of these patients.
Subject(s)
Bacteria/growth & development , Bacterial Infections/prevention & control , Cross Infection/prevention & control , Disease Outbreaks , Drug Resistance, Microbial , Infection Control/methods , Intensive Care Units, Neonatal , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Birth Weight , Colony Count, Microbial , Cross Infection/drug therapy , Cross Infection/epidemiology , Enterobacter cloacae , Female , Gestational Age , Humans , Incidence , Infant, Newborn , Length of Stay , Male , Risk FactorsABSTRACT
Outbreaks with Enterobacter spp. have been described frequently in neonatal intensive care units (NICUs). This study investigated the factors that determine whether a neonate becomes colonised with Enterobacter spp., how long colonisation continues and whether the termination of isolation measures leads to spread of the organism. Neonates transferred from the NICUs of tertiary care hospitals were screened for the presence of Enterobacter spp. and any potential predictors for colonisation recorded. Those infected were monitored during their hospital stay and colonised neonates were screened every month for six months. Isolation infection control precautions were lifted and all neonates were screened for the presence of Enterobacter spp. six and 12 months later. Fifteen colonised neonates and 33 non-colonised controls were identified for study. Multivariate analysis showed that antibiotic therapy for more than three days and an Apgar score of <8 after 1 min were independently associated with Enterobacter spp. colonisation. Molecular typing using single-enzyme amplified-fragment length polymorphism (seAFLP) analysis revealed 22 different seAFLP genotypes. Three infants remained colonised with the same Enterobacter genotype after discharge; however, most neonates lost their strain or became colonised with another genotype. Lifting infection control measures for neonates colonised with Enterobacter spp. in a neonatal ward did not lead to increased incidence of colonisation and none of the infants became infected. Isolating neonates with susceptible Enterobacter spp. was not found to be necessary.
Subject(s)
Cross Infection/epidemiology , Cross Infection/microbiology , Enterobacter/isolation & purification , Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae Infections/microbiology , Gastrointestinal Tract/microbiology , Anti-Bacterial Agents/therapeutic use , Apgar Score , Bacterial Typing Techniques , DNA Fingerprinting , DNA, Bacterial/genetics , Enterobacter/classification , Enterobacter/genetics , Female , Genotype , Humans , Infant, Newborn , Male , Molecular Epidemiology/methods , Multivariate Analysis , Patient Isolation , Polymorphism, Restriction Fragment Length , Risk Factors , Time FactorsABSTRACT
Several studies have demonstrated an association between low birth weight and impaired insulin sensitivity or even type 2 diabetes mellitus (DM2) in later life. Growth hormone (GH) is known to increase fasting and postprandial insulin levels. For that reason concern has been expressed regarding possible detrimental effects of GH therapy in children born SGA. In a Dutch trial the possible side effects of GH therapy on carbohydrate metabolism were assessed in short children born SGA after 6 years and at 6 months after discontinuation of GH therapy. This study included 79 prepubertal short children born SGA, participating in a multicenter double-blind, randomized, dose-response GH trial. Inclusion criteria were: 1) birth length SDS below -1.88, 2) age 3-11 years in boys and 3-9 years in girls, 3) height SDS < -1.88, 4) no spontaneous catch-up growth, and 5) an uncomplicated neonatal period. Mean (SD) value for age was 7.3 (2.1) years, birth length SDS -3.6, height SDS -3.0 (0.7) and BMI SDS -1.2 (1.3). All children were randomly assigned to either group A (n = 41) using 1 mg GH/m2/day or group B (n = 38) using 2 mg/m2/ d/ay (approximately 0.1 or 0.2 IU/kg/d, respectively). Standard oral glucose tolerance tests (OGTTs) were performed before and during 6 years of GH therapy and 6 months after discontinuation of GH therapy. Before GH therapy 8% of the children had impaired glucose tolerance (IGT) according to criteria of the WHO. After 6 years of GH therapy, IGT was found in 4% and after stopping GH in 10%. Mean fasting glucose increased significantly with 0.5 mMol/l after 1 year of GH therapy, without a further increase thereafter. GH therapy induced considerably higher fasting and glucose-stimulated insulin levels. None of the observed changes were different between the GH dosage groups. Children who remained prepubertal had similar glucose and insulin levels compared to children who entered puberty. HbA1c levels were always in the normal range and none of the children developed diabetes mellitus. After discontinuation of GH therapy the mean serum glucose levels remained normal and the mean serum insulin levels decreased significantly, to normal age reference values. Before the start of GH the mean systolic blood pressure was significantly higher compared to age-matched peers, whereas during GH therapy a significant decline in mean systolic blood pressure occurred, which remained similar after discontinuation of GH treatment. In conclusion, continuous, long-term GH therapy in short children born SGA has no adverse effects on glucose levels, even with GH dosages up to 2 mg/m2/day. However, as has been reported in other patient groups, GH induced higher fasting and glucose-stimulated insulin levels, indicating insulin resistance. After discontinuation of GH, serum insulin levels declined to normal age-matched reference levels. Since impaired insulin sensitivity and DM2 have been demonstrated in relatively young patients born SGA, long-term follow-up of children born SGA is advised, also after discontinuation of GH therapy.
Subject(s)
Endocrine Glands/metabolism , Human Growth Hormone/therapeutic use , Infant, Small for Gestational Age/metabolism , Blood Pressure/drug effects , Blood Pressure/physiology , Child , Child, Preschool , Double-Blind Method , Endocrine Glands/drug effects , Female , Follow-Up Studies , Glucose Intolerance/diagnosis , Glucose Tolerance Test/methods , Glycated Hemoglobin/chemistry , Human Growth Hormone/administration & dosage , Humans , Infant, Newborn , Injections , Insulin/blood , Male , Patient Selection , Time FactorsSubject(s)
Body Height/drug effects , Bone Development/drug effects , Estradiol/pharmacology , Testosterone/pharmacology , Age Factors , Body Height/genetics , Body Height/physiology , Bone Development/genetics , Estradiol/adverse effects , Estradiol/therapeutic use , Female , Follow-Up Studies , Forecasting , Growth Hormone/metabolism , Growth Substances/metabolism , Humans , Male , Pregnancy , Reproducibility of Results , Testosterone/adverse effects , Testosterone/therapeutic use , Thyroid Hormones/metabolism , Vitamin D/metabolismABSTRACT
Children of constitutionally tall stature may experience serious problems related to their height. Treatment with high dose sex steroids may be considered in order to limit final adult height. Prediction of adult height plays a central part in the management of children of tall stature. Various aspects of height prediction in children of tall stature are discussed. The height reducing effect varies between studies from 2 to 10 cm. Recently, in a large Dutch study the mean effects of therapy were 0.7 and 2.4 cm for boys and girls respectively. The effect depended on the bone age at start of treatment. Beyond a critical bone age of about 14 years treatment had no effect. Minimal age for intervention is 9.5-10 year for boys and 9.0-9.5 year for girls. Recommended treatment for boys is 250 mg testosterone esters i.m. per week and for girls ethinyloestradiol orally 200 micrograms per day in combination with medroxyprogesterone or dydrogesterone (both 5-10 mg per day) during the first 12-14 days of the cycle. Treatment has to be continued until complete closure of the epiphyses. While side effects during hormonal therapy are frequent, they are mostly temporary and mild and seldom lead to cessation of therapy. So far there have been no indications of adverse effects on, for instance, gonadal function.
Subject(s)
Dydrogesterone/administration & dosage , Ethinyl Estradiol/administration & dosage , Growth Disorders/therapy , Medroxyprogesterone/administration & dosage , Progesterone Congeners/administration & dosage , Testosterone/administration & dosage , Administration, Oral , Adolescent , Body Height/drug effects , Child , Drug Therapy, Combination , Female , Growth Disorders/psychology , Humans , Injections, Intramuscular , MaleABSTRACT
In order to develop new height prediction models for children with constitutionally tall stature, 55 such boys and 88 girls were recalled for measurement of adult final height (FH). Data on height (H), age (CA), and target height (TH) were collected from the hospital charts and radiographs of the left hand and wrist were retrieved and used for bone age (BA) determination [BA according to the methods of Greulich and Pyle (BAGP) and Tanner and Whitehouse (BARUS)]. Standard multiple regression techniques were used to develop prediction equations for FH. In addition to test the validity of the new equations, FH was measured in a second group of constitutionally tall children (n = 32) and compared with the predicted FH according to our models. In addition, a comparison was made with other prediction methods. Mean (SD) FH was 196.0 (4.9) cm in boys and 180.5 (3.8) cm in girls. The ultimate regression equation was FH (cm) = 216.07 + 0.75 x H + 0.25 x TH -11.09 BAGP + 0.74 x (CA x BAGP) for boys and FH = 161.42 + 0.73 x H + 0.15 x TH - 8.41 x CA -8.83 x BARUS -2.45 x M + 0.55 x (CA x BARUS) for girls. The models showed satisfying accuracy: the mean (SD) errors were -1.4(3.2) cm for boys and -0.5(3.1) cm for girls with corresponding mean (SD) absolute errors of 2.7 (2.2) cm and 2.0 (2.4) cm, respectively. Compared with the current prediction methods, the new models were quite promising. Their clinical validity has to be ascertained in larger groups of tall children.
Subject(s)
Body Height , Models, Statistical , Adult , Child , Female , Follow-Up Studies , Humans , Male , Regression Analysis , Reproducibility of Results , Sex FactorsABSTRACT
Height reduction by means of treatment with high doses of sex steroids in constitutionally tall stature (CTS) is a well known, though still controversial, therapy. The establishment of the effect of such therapy is dependent on the height prediction method applied. We evaluated the reliability of various prediction methods together with the subjective clinician's judgment in 143 untreated children (55 boys and 88 girls) with CTS and the effect of height-reductive therapy in 249 tall children (60 boys and 159 girls) treated with high doses of sex hormones (cases). For this purpose, we compared the predicted adult height with the attained height at a mean adult age of 25 yr and adjusted the therapeutic effect for differences in bone age (BA), chronological age (CA), and height prediction between untreated and treated children. At the time of the height prediction, controls were significantly shorter, had more advanced estimated BAs (except for the BA according to Greulich and Pyle in boys), had lower target heights, and had smaller adult height predictions compared with the CTS patients (P < 0.05). At the time of the follow-up, CTS patients were significantly taller than controls for both boys and girls (P < 0.02). In controls, a large variability was found for the errors of prediction of the various prediction methods and in relation to CA. The prediction according to Bailey and Pinneau systematically overestimated adult height in CTS children, whereas the other prediction methods (Tanner-Whitehouse prediction and index of potential height) systematically underestimated final height. The mean (SD) absolute errors of the prediction methods varied from 2.3 (1.8) to 5.3 (4.3) cm in boys and from 2.0 (1.9) to 3.7 (3.5) cm in girls. They were significantly negatively correlated with CA (r = [minus 0.27 to -0.65; P < 0.05), except for the Tanner-Whitehouse prediction in boys, indicating that height prognosis is more reliable with increasing CA. In addition, experienced clinicians gave accurate height predictions by evaluating the growth chart of the child while taking into account various clinical parameters, such as CA, BA, and pubertal stage. The effect of sex hormone therapy was assessed by means of multiple regression analysis while adjusting for differences in height prediction, CA, and BA at the start of therapy between treated and untreated children. The mean (SD) adjusted effect varied from -0.5 (2.4) to 0.3 (1.4) cm in boys and from -0.6 (2.1) to 2.4 (1.4) cm in girls. The adjusted height reduction was dependent on the BA at the time of start of sex hormone therapy and was more pronounced when treatment was started at a younger BA. In boys, the treatment effect was significantly negative at BAs exceeding 14-15 yr. After cessation of therapy, additional mean (SD) growth of 2.4 (1.2) and 2.7 (1.1) cm was observed for boys and girls, respectively. The mean (SD) BA according to Greulich and Pyle at that time was 17.1 (0.7) yr for boys and 15.2 (0.6) yr for girls. These data demonstrate that height prediction in children with CTS is inaccurate in boys, but clinically acceptable in girls. With increasing age, height prognosis became more accurate. Overall, the height-reducing effect of high doses of sex hormones in children with CTS was limited, especially in boys. However, a significant effect of treatment was observed when treatment was started at BAs less than 14-15 yr, depending on the method of BA assessment. In boys, treatment appeared to be contraindicated at BAs older than 14-15 yr, because androgen administration caused extra growth instead of growth inhibition. It is recommended that referral should take place early, preferably before puberty, for careful monitoring of growth and height prediction. Moreover, it is recommended not to discontinue therapy before complete closure of the epiphyses of the hand has occurred to avoid considerable posttreatment growth.
Subject(s)
Body Height , Gonadal Steroid Hormones/therapeutic use , Growth Disorders/drug therapy , Adolescent , Adult , Aging , Bone Development , Evaluation Studies as Topic , Female , Forecasting/methods , Humans , Male , Sex Characteristics , Treatment OutcomeABSTRACT
The objective of this study was to assess self-concept in children with short stature after intrauterine growth retardation (IUGR), before and after 2 years of growth hormone (hGH) treatment. We assessed 25 children before treatment, and 40 children after a 2-year treatment period. Seventeen of the 25 children of whom we had pretreatment data, were reassessed after 2 years of hGH treatment. All children had a birth length below the 3rd percentile, and did not show catch-up growth (current height < P3). We compared the self-concept measures (Self-Perception Profile for Children; SPPC) of the IUGR group with similar measures of a Dutch school sample. Four of the six SPPC mean scale scores of the IUGR group prior to treatment were significantly lower than mean scores of the school sample. Mean-scale scores of the group children, assessed after 2 years of hGH treatment, did not differ significantly from those of the school sample. In the group of 17 children who were assessed before as well as after 2 years of treatment, the mean scale scores of 'social acceptance' and 'general self-worth' were significantly higher at the second assessment (t = -5.93, p < 0.001 and t = -4.36, p < 0.001, respectively). From the present study we can hypothesize that short stature after IUGR and a low self-concept are related.
Subject(s)
Fetal Growth Retardation/psychology , Human Growth Hormone/therapeutic use , Self Concept , Child , Cohort Studies , Double-Blind Method , Female , Fetal Growth Retardation/drug therapy , Follow-Up Studies , Human Growth Hormone/administration & dosage , Humans , Male , Time FactorsABSTRACT
AIM: To evaluate possible long term side effects of high doses of sex steroids in the management of constitutionally tall stature, with special attention to hypothalamic-gonadal function. METHODS: Sixty four tall adult men and 180 tall adult women, who received supraphysiological doses of sex hormones during puberty, were interviewed in a standardised way at a mean follow up period of 10 years after cessation of treatment. Sixty one untreated tall adult men and 94 untreated tall adult women served as controls. RESULTS: The majority of the subjects were satisfied with their decision regarding hormone treatment. Seventy seven per cent of the women and 78% of the men reported one or more side effects during treatment. Most side effects were mild. In women, only 3% stopped treatment because of an adverse event; in men, the reported side effects never stopped treatment. The frequency of reported side effects in women was higher during treatment with high doses of oestrogens than during oral contraceptive use, indicating a dose dependent relationship. Amenorrhoea of longer than six months after cessation of therapy was found in 5%. Menstrual cycle characteristics of previously treated women were comparable with controls. Malignancy was not reported. Information about a total of 127 pregnancies was obtained and revealed no distinct differences in details and outcome between previously treated women and men, and controls. CONCLUSIONS: At a mean follow up of 10 years there is no evidence that pharmacological doses of sex hormones have a long term effect on reproductive function. However, this period is still too short to draw definite conclusions.
Subject(s)
Gonadal Steroid Hormones/adverse effects , Growth Disorders/drug therapy , Growth Inhibitors/adverse effects , Reproduction/drug effects , Adult , Contraceptives, Oral/adverse effects , Drug Combinations , Ethinyl Estradiol/adverse effects , Female , Follow-Up Studies , Humans , Male , Medroxyprogesterone/adverse effects , Menstruation/drug effects , Pregnancy , Pregnancy Outcome , Testosterone/adverse effectsABSTRACT
OBJECTIVE: We have studied the effect of treatment with high doses of androgens during puberty on testicular function in adult men with constitutionally tall stature, taking into account confounding factors interfering with sperm quality, since existing published data do not include whether testicular function is impaired by such treatment. DESIGN: Historical cohort study. PATIENTS: Forty-three previously androgen treated tall men (cases) and 30 non-treated tall men (controls). MEASUREMENTS: Physical examination, semen analysis and plasma levels of LH, FSH, testosterone (T), sex hormone binding globulin (SHBG) and inhibin. RESULTS: Sperm quality and testis volume were comparable between cases and controls. Mean sperm concentration was 66.4 x 10(6)/ml in cases and 66.2 x 10(6)/ml in controls. A left-sided varicocele was found in 45% of the cases and 37% of the controls. In cases we observed a significant effect of the age at start of androgen therapy on sperm motility (regr. coeff. (SE): 4.92 (2.41)%, P = 0.048). In addition, testicular size at start of therapy had a significant effect on sperm concentration (regr. coeff. (SE): 5.57 (1.54) x 10(6)/ml, P = 0.0012) and on total sperm count (regr. coeff. (SE): 43.1 (7.73) x 10(6), P = 0.0001). Plasma levels of T, SHBG and inhibin were not statistically different between the groups. Cases had significantly higher FSH levels (mean (SD) 3.3 (2.2) vs 2.1 (0.8) IU/I, P = 0.004) and significantly lower LH levels (mean (SD) 2.3 (0.9) vs 3.1 (1.4) IU/I, P = 0.019). We found a significant effect of age at start of therapy on plasma FSH level in the treated men (regr. coeff. (SE): -0.73 (0.18) IU/I, P = 0.0003). CONCLUSIONS: Treatment with high doses of androgens for reduction of final height in constitutionally tall stature has no long-term side-effect on sperm quality, testicular volume or plasma testosterone levels. However, treated men had significantly higher plasma levels of FSH compared with controls. The meaning of this difference remains to be established. Varicocele was present in 42% of the adult tall men.
Subject(s)
Growth Disorders/drug therapy , Testis/drug effects , Testosterone/administration & dosage , Adult , Cohort Studies , Drug Administration Schedule , Growth Disorders/blood , Growth Disorders/physiopathology , Humans , Luteinizing Hormone/blood , Male , Puberty , Sperm Count/drug effects , Sperm Motility/drug effects , Testis/physiopathology , Varicocele/complicationsABSTRACT
OBJECTIVE: The pathophysiological mechanisms underlying the failure of catch up-growth in children with short stature after intrauterine growth retardation (IUGR) remain obscure. Since GH secretion disturbances might play a role in the growth retardation of these children we have investigated various aspects of the GH/IGF axis. DESIGN: Cross-sectional study in one group of patients. PATIENTS: Forty prepubertal children (15 girls/25 boys; mean age (range) 7.5 years (3.4-10.8)) with short stature (height below the third centile) after IUGR, defined as a birth length below the third centile for gestational age, were studied. MEASUREMENTS: GH secretion was determined by a 24-hour plasma GH profile (sampling every 20 minutes) and, on a separate occasion, by a standard arginine provocation test (ATT). Plasma IGF-I and IGF-II levels were measured at the start of the GH profile. Urine was collected to measure urinary GH levels. Plasma and urinary GH were determined by double antibody RIA. IGF-I and IGF-II were determined by specific RIA after acid chromatography. The 24-hour GH profiles were analysed using Pulsar. RESULTS: Endogenous GH secretion was similar for boys and girls. Boys had significantly lower mean GH levels compared to healthy controls. Forty per cent of the children met our criteria for a normal 24-hour GH profile (group A; n = 16) and 60% (n = 24) did not. We subdivided these 24 children into two groups: group B (n = 14) (children with either mean GH levels less than controls but with at least one spontaneous GH peak above 20 mU/l and children with normal mean GH levels but with no GH peak above 20 mU/l (subnormal 24-hour GH profile)) and group C (n = 10) (children with mean GH levels less than controls and no GH peak above 20 mU/l (low 24-hour GH profile)). The GH secretory abnormalities were due to a decrease in pulse amplitude, not in pulse frequency. Mean (SD) maximal GH response during ATT was 22.3 (12.1) mU/l. Nineteen children (47.5%) had a maximal GH value < 20 mU/l. Moderate, but significant, correlations were found between several 24-hour GH profile characteristics and the maximal GH response during ATT (r = 0.31-0.35; P < 0.05). Mean (SD) overnight urinary GH excretion was 3.8 (2.1) and 4.4 (3.5) microU/night for boys and girls, respectively. Compared to healthy schoolchildren, overnight urinary GH was lower in boys, but not in girls. Mean (SD) IGF-I and IGF-II SDS levels for chronological age were -0.88 (1.40) and -0.64 (1.48), respectively. Plasma IGF-I and IGF-II levels were significantly reduced compared to controls. Height SDSCA or height velocity SDSCA did not correlate with either spontaneous or stimulated GH secretion, urinary GH excretion or plasma IGF-I or IGF-II levels. CONCLUSIONS: Our study indicates that 50-60% of children with short stature after intrauterine growth retardation have 24-hour GH profile abnormalities and/or subnormal responses to arginine provocation, while mean plasma IGF-I and IGF-II levels are significantly reduced, indicating GH insufficiency. Urinary GH excretion is lower in boys, but not in girls. The precise mechanism of the failure to catch up growth needs further elucidation. It seems justified to start clinical trials in order to investigate whether treatment with exogenous GH might be beneficial for these children.