Long‐term effects of growth hormone therapy on patients with Prader–Willi syndrome

Aim: To assess the effects of recombinant human growth hormone (rhGH) treatment in children with Prader–Willi syndrome. Design: A 1‐year study and an observational follow‐up visit 10 years later. Methods: In 20 patients with Prader–Willi syndrome (PWS): clinical assessment, laboratory tests, body composition analysis by dual energy X‐ray absorptiometry, sleep polygraphy, health‐related quality of life assessed by 16D. Results: Only two patients had normal growth hormone secretion at baseline. All patients were significantly shorter than their expected heights, but experienced catch‐up growth during growth hormone treatment. At follow‐up, 13 patients had reached adult heights and were markedly taller than historical controls. The cumulative dose of rhGH over 10 years correlated inversely with the total body fat percentage (p = 0.033). However, patients remained severely obese at 10 years. Sleep polygraphy was abnormal in more than half of the patients. Health‐related quality of life of the patients remained substantially below that of normal population. Conclusion: Growth hormone markedly improved adult height in subjects with PWS when compared to historical data. The cumulative dose of growth hormone correlated with reduction in body fat; nevertheless, patients remained severely obese.     

1p36 deletion syndrome associated with Prader–Willi‐like phenotype

Background: 1p36 deletion syndrome is one of the most common subtelomeric deletion syndromes, characterized by moderate to severe mental retardation, characteristic facial appearance, hypotonia, obesity, and seizures. The clinical features often overlap with those of Prader–Willi syndrome (PWS). To elucidate the phenotype–genotype correlation in 1p36 deletion syndrome, two cases involving a PWS‐like phenotype were analyzed on molecular cytogenetics. Methods: Two patients presenting with the PWS‐like phenotype but having negative results for PWS underwent fluorescence in situ hybridization (FISH). The size of the chromosome 1p36 deletions was characterized using probes of BAC clones based on the University of California, Santa Cruz (UCSC) Genome Browser. Results: PWS was excluded on FISH and methylation‐specific polymerase chain reaction. Subsequent FISH using the probe D1Z2 showed deletion of the 1p36.3 region, confirming the diagnosis of 1p36 deletion syndrome. Further analysis characterized the 1p36 deletions as being located between 4.17 and 4.36 Mb in patient 1 and between 4.89 and 6.09 Mb in patient 2. Conclusion: Patients with 1p36 deletion syndrome exhibit a PWS‐like phenotype and are therefore probably underdiagnosed. The possible involvement of the terminal 4 Mb region of chromosome 1p36 in the PWS‐like phenotype is hypothesized.     

Prader-Willi syndrome in Victoria: mortality and causes of death

Aim: The aim of this study was to describe the rates, predictors and causes of mortality in a population sample of individuals with Prader–Willi syndrome (PWS). Methods: One hundred sixty‐three individuals with PWS (90 males and 73 females, ages: 3 weeks to 60 years) were identified from the Victorian PWS Register. Information on demographics, age at diagnosis, genetic mechanism, age at which obesity developed and last known body mass index measurement were extracted. Notification and causes of death were obtained through linkage with Australian national and state of Victoria death indexes. Survival analysis was used to estimate the probability of survival and the effect of obesity on survival. Mortality rate ratios were calculated to investigate the effect of the factors listed above on mortality. Results: Fifteen deaths were recorded (nine males and six females), corresponding to an 87% probability of survival to 35 years. The probability of survival was significantly lower for individuals with known obesity (P= 0.03), but there was no strong evidence for an effect on survival for the other factors studied. Cardiac or respiratory conditions were common causes of death after the age of 15 years. Conclusions: The effect of known obesity on the probability of survival and the causes of death reported in this and other studies suggest an important association between obesity and early death in adults with PWS. This finding highlights the critical nature of preventative and intervention strategies aimed at minimising the effects of hyperphagia in individuals with PWS.     

Turner's syndrome in Italy: familial characteristics, neonatal data, standards for birth weight and for height and weight from infancy to adulthood

In 1990, the Italian Study Group for Turner's Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross-sectional data and longitudinal growth profiles of 772 girls with Turner's syndrome born between 1950 and 1990. The study was carried out in 29 pediatric endocrinological centers. In this first report, the familial characteristics and neonatal data of Turner girls are described, compared to those of the general population, and related to postnatal somatic development. Furthermore, charts for birth weight and growth standards for height and weight from infancy to adulthood are presented (these are the first charts based on a large sample from the Mediterranean area). The main findings were: (1) incidence of Turner births increases with parental age or parity; (2) most of the neonates are small for dates; (3) girls with normal birth weight tend to be both taller and heavier than girls with low birth weight during the whole growth period; and (4) a 10-cm difference in midparental height leads to a 6.5-cm difference in adult stature.     

Newborn weight change and predictors of underweight in the neonatal period in Guinea‐Bissau,Nepal, Pakistan and Uganda

In low‐ and middle‐income countries (LMIC), growth impairment is common; however, the trajectory of growth over the course of the first month has not been well characterised. To describe newborn growth trajectory and predictors of growth impairment, we assessed growth frequently over the first 30 days among infants born ≥2000 g in Guinea‐Bissau, Nepal, Pakistan and Uganda. In this cohort of 741 infants, the mean birth weight was 3036 ± 424 g. For 721 (98%) infants, weight loss occurred for a median of 2 days (interquartile range, 1–4) following birth until weight nadir was reached 5.9 ± 4.3% below birth weight. At 30 days of age, the mean weight was 3934 ± 592 g. The prevalence of being underweight at 30 days ranged from 5% in Uganda to 31% in Pakistan. Of those underweight at 30 days of age, 56 (59%) had not been low birth weight (LBW), and 48 (50%) had reached weight nadir subsequent to 4 days of age. Male sex (relative risk [RR] 2.73 [1.58, 3.57]), LBW (RR 6.41 [4.67, 8.81]), maternal primiparity (1.74 [1.20, 2.51]) and reaching weight nadir subsequent to 4 days of age (RR 5.03 [3.46, 7.31]) were highly predictive of being underweight at 30 days of age. In this LMIC cohort, country of birth, male sex, LBW and maternal primiparity increased the risk of impaired growth, as did the modifiable factor of delayed initiation of growth. Interventions tailored to infants with modifiable risk factors could reduce the burden of growth impairment in LMIC.     

EFFECTS ON THE CHILD OF ALCOHOL ABUSE DURING PREGNANCY: Retrospective and Prospective Studies

Abstract. Olegård, R., Sabel, K.-G., Aronsson, M., Sandin, B., Johansson, P. R. Carlsson, C., Kyllerman, M., Iversen, K. and Hrbek, A. (Departments of Paediatrics, East Hospital, University of Göteborg and Psychiatric Clinic II and Nordhem Alcoholic Clinic, Lillhagen Hospital, Göteborg, Sweden). Effect on the child of alcohol abuse during pregnancy. Retrospective and prospective studies. Retrospective and prospective investigations of children to alcoholic women gave an incidence of fetal alcohol lesion of one per 300 deliveries of whom half had the complete fetal alcohol syndrome. Perinatal and infant mortalities were increased seven to tenfold and low birth weight (<2500 g), preterm deliveries (<37 weeks) and smallness for gestational age (<-2 S.D.) were increased eightfold, threefold and twelvefold, respectively. Small size at birth correlated with reduced mental performance later in life, 58% had IQ below 85 and 19% below 70. 8% had cerebral palsy. The incidence of cerebral palsy associated with maternal inebriety was 1/5000 deliveries, i.e. every sixth case of cerebral palsy. Tracing of alcoholic women during pregnancy and treatment gave favourable effect on intrauterine growth when sobriety could be induced early in pregnancy but could not protect from functional brain disturbance measured by neurological performance and by evoked response electroencephalography. Damage to the fetus by alcohol is now the largest known health hazard by a noxious agent that is preventable.     

The effects of maternal postnatal depression and child sex on academic performance at age 16 years: a developmental approach

Background: Postnatal depression (PND) is associated with poor cognitive functioning in infancy and the early school years; long‐term effects on academic outcome are not known. Method: Children of postnatally depressed (N = 50) and non‐depressed mothers (N = 39), studied from infancy, were followed up at 16 years. We examined the effects on General Certificate of Secondary Education (GCSE) exam performance of maternal depression (postnatal and subsequent) and IQ, child sex and earlier cognitive development, and mother–child interactions, using structural equation modelling (SEM). Results: Boys, but not girls, of PND mothers had poorer GCSE results than control children. This was principally accounted for by effects on early child cognitive functioning, which showed strong continuity from infancy. PND had continuing negative effects on maternal interactions through childhood, and these also contributed to poorer GCSE performance. Neither chronic, nor recent, exposure to maternal depression had significant effects. Conclusions: The adverse effects of PND on male infants’ cognitive functioning may persist through development. Continuing difficulties in mother–child interactions are also important, suggesting that both early intervention and continuing monitoring of mothers with PND may be warranted.     

Birth weight and adult lung function: a within-pair analysis of twins followed up from birth

Background  The aim of the study was to evaluate whether there is any association between intrauterine growth and later lung function or bronchial reactivity in early adulthood in line with Barker’s hypothesis. Methods  Nineteen twin pairs with disproportionate intrauterine growth pattern were followed up from birth: either one of the pairs had intrauterine growth retardation (birth weight <2 SD) or the within-pair birth weight difference was >1.3 SD. Flow-volume spirometry, followed by isocapnic hyperventilation of cold air, was performed at the ages of 8–16 and 14–22 years in 1993 and 1999. Wilcoxon’s matched-pairs analysis was used to compare smaller and larger twin pairs. Results  In 1993, there were no significant differences between the groups in either spirometry or cold air challenge. In 1999, such a difference was found in forced expiratory volume % (FEV%) and forced expiratory flow (FEF) at 25%–75%, the smaller twin pairs having lower values. In 1993, nine subjects reacted to cold air (>9% decrease in FEV in 1 second). In 1999, only four subjects reacted to cold air, and they all belonged to the group of smaller twins (P=0.04). Conclusion  Lung function evaluated by FEV% and FEF25–75 was lower and responses to cold air were more common at the median age of 16 years in twins with impaired intrauterine growth.     

Factor V Leiden and prothrombin 21210G>A mutation and paediatric ischaemic stroke: a case–control study and two meta‐analyses

Aim: To determine whether factor V Leiden (FVL) and prothrombin (PT) 20210G>A mutation are associated with paediatric ischaemic stroke. Methods: The study consisted of two parts. Case–control study included neuroradiologically confirmed paediatric ischaemic stroke patients from two tertiary children’s hospitals in Estonia. For control group, DNA was obtained from 400 anonymous screening test cards of newborns born consecutively in all delivery departments of Estonia in January 2005. Meta‐analyses was performed to assess the association between paediatric sinovenous thrombosis and FVL and PT 20210G>A. Results: A total of 75 children (45 boys, 30 girls) were included into the case–control study: 19 with childhood arterial ischaemic stroke, 49 with perinatal arterial ischaemic stroke and seven with cerebral venous thrombosis. Both FVL and PT 20210G>A occurred significantly more frequently among patients with sinovenous thrombosis compared with controls (OR = 12.9; 95% CI: 2.3–73.0 and OR = 11.9; 95% CI: 2.1–67.2, respectively). The difference was not significant between childhood/perinatal arterial ischaemic stroke and controls. Meta‐analyses (including our study) revealed that both FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis (OR = 3.1; 95% CI: 1.8–5.5 and OR = 3.1; 95% CI: 1.4–6.8, respectively). Conclusion: FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis.