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Logo of archdischArchives of Disease in ChildhoodVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Arch Dis Child. 2007 April; 92(Suppl1): A4–A5.
PMCID: PMC2066119


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P11 Pulmonary arterial Hypertension in children with sickle cell disease: how common is it?

R.. Chaudry, presenting, T. Karu, C. Hutchinson, S. Ball, G. Sutherland, A. Bush, M. Rosenthal, S. Crowley. Royal Brompton Hospital, London; St George's Hospital, London, UK

IntroductionThe prevalence of pulmonary arterial hypertension (PAH) in adults with sickle cell disease (SCD) is estimated to be 32%, 2‐year mortality of 50% from diagnosis.

AimsTo prospectively determine the prevalence of PAH in children with SCD and define associated risk factors such as hyper‐haemolytic state defined by haemoglobin [less-than-or-eq, slant]8.5 g/dl and number of acute chest syndrome events

MethodsFifty (F = 26) patients with SCD, range 10–18 years, and 50 (F = 25) sex, age, race‐matched healthy controls were recruited. Tricuspid regurgitant jet velocity was measured using detailed 2D‐Doppler echo; all subjects were at baseline state of health. Patients were free of any vaso‐occlusive crisis for [gt-or-equal, slanted]14 days. Hb was measured and a detailed medical history was taken with verification from hospital notes.

ResultsThe youngest patient with elevated TRV was 10 years.

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ConclusionThese data show a significant number of children with SCD have echo evidence of PAH. We were unable to identify an association between elevated TRV and hyper‐haemolysis, number of ACS events or increasing age in the patient group. We suggest all children with SCD be screened for PAH from 5 years onwards. Longitudinal studies with therapeutic intervention are required to enable monitoring of disease progression and response to treatment.

P12 The role of androgens in fetal growth

H. Miles, presenting, K. Ong, I. Hughes. University of Cambridge, Cambridge, UK

IntroductionConsistent reports of lower mean birth weights in male infants with hypospadias have lead to the suggestion that androgen activity in the fetus promotes fetal growth and explains the 300 g larger birth weight of males compared to females. We tested this hypothesis in genetic models of decreased androgen receptor activity.

MethodsIn 64 male infants with hypospadias, gestational age adjusted birth weight SD scores were compared between the 11 infants with partial androgen insensitivity (PAIS) confirmed by androgen receptor (AR) gene mutation, and the 53 infants without an AR gene mutation. Birth weight data were also available for 22 female infants with complete androgen insensitivity (CAIS).

ResultsInfants with hypospadias without AR mutation had lighter adjusted birth weights than infants with hypospadias and PAIS (mean (SD) UK 1990 birth weight SD score −1.6 (1.7) versus −0.2 (0.7); p = 0.01), and were born earlier (gestational age: 35.3 (4.2) v 38.5 (2.9) weeks; p = 0.02). 41.5% (22/53) of the hypospadias without AR mutation group were born both premature (<37 weeks) and IUGR (birth weight <−2 SDS) compared to none (0/11) of the PAIS infants (χ2 p = 0.008). Female infants with CAIS had a birth weight distribution very similar to the UK 1990 data for normal boys (mean (SD) birth weight SD score −0.1 (1.0)).

ConclusionThe lack of reduction in birth weights of infants with confirmed complete or partial androgen insensitivity strongly indicates that androgen activity has little role in overall fetal growth. We propose that other factors that effect both global embryonic growth and the urological growth plate early in gestation may explain the association between hypospadias, IUGR and preterm delivery. Candidate factors include environmental endocrine disruptors which may influence gene expression in the first trimester.

P13 The BPSU study of biliary atresia: outcome at 13 years

P. McKiernan1, A. Baker2, C. Lloy1, G. Mieli‐Vergani2, D. Kelly1. 1Liver Unit, Birmingham Children's Hospital, Birmingham; 2Paediatric Liver Unit, King's College Hospital, London, UK

IntroductionAll cases of biliary atresia in the British Isles diagnosed between March 1993 and February 1995 have been followed prospectively. Analysis after a median follow up of 3 years showed that outcome was better, with higher overall survival and survival without liver transplantation, in surgical centres managing >5 cases yearly.1

AimTo describe the current outcome of a national cohort of children with biliary atresia.

SubjectsNinety three children with biliary atresia diagnosed between March 1993 and February 1995. Median age at last follow‐up was 12 years (range 0.25–14).

ResultsFifteen children (16%) have died. 10 died following unsuccessful Kasai portoenterostomy 1 from sepsis following successful Kasia and 4 following liver transplantation. 42 (44%) have undergone liver transplantation at median age 1 year (0.5–9), with 90% survival after median follow up of 11 years (0–13 years). All 41 children with failed Kasai (and 2 without Kasai) have died or undergone liver transplantation at median age of 0.8 years (0.25–6.5). Where the Kasai was successful 41/50 (82%) were alive without liver transplantation. For the whole group 13‐year actuarial survival without liver transplantation was 44%, and was better in children managed in centres treating >5 cases yearly, (57% v 27%, p = 0.003).

ConclusionsIn biliary atresia: (1) If the Kasai portoenterostomy is successful few will need transplant prior to adolescence. (2) Children should be managed in experienced centres in order to maximise the chance of successful surgery. (3) The medium‐term outcome for liver transplantation is excellent.

PJMcKiernanet alLancet2000355 pp 25-9

P14 Restoration of function following mouse and human enteric nervous system transplants into an in vitro model of Hirschsprung's disease

D. Hawcutt1, presenting, R. Lindley1, D. Edgar2, S. Kenny1. 1Institute of Child Health, Royal Liverpool Children's Hospital, Liverpool; 2University of Liverpool, Liverpool, UK

AimsTo assess the functional effect of transplanting murine and human enteric nervous system stem cells (ENSC) into an in vitro mouse model of Hirschsprung's disease.

MethodsColon explanted from E11.5 embryonic mice was placed in organ culture conditions for 10 days. Given that ENSC colonise bowel in a cranio‐caudal direction, normally innervated controls were obtained by culturing the colon with caecum attached (ENSC are present in the caecum by E11.5). Aganglionic bowel was obtained by culturing colon alone. Immunohistochemistry was used to determine the presence/absence of neurones (PGP9.5) and glia (GFAP) and the distribution of neurones compared with colon from age‐matched mouse embryos. Aganglionic bowel was co‐cultured with ENSC‐containing neurospheres isolated from human neonatal colon and neonatal mouse colon. Contractions were recorded at 48 h using optical digital image acquisition and the amplitude and frequency of contractions measured using Diamtrak software. Fourier transformation was used to perform amplitude‐frequency spectral analysis. The effect of ENS blockade was assessed by adding tetrodoxin to the specimens, the effect of interstitial cell of Cajal blockade assessed using inactivating c‐kit antibodies.

ResultsUse of anti‐c‐kit antibody abolished all contractions in innervated and aganglionic distal colon. Transplantation with a murine ENS neurosphere produces an identical rate of contraction at E19.5 to normally innervated distal colon (37.1 v 42.2 mHz p = 0.32), and treatment with TTX increases the frequency to that seen in TTX treated innervated distal colon (62.5 v 73.7 mHz p = 0.22). At E21.5, transplantation with a human ENS neurosphere also produced inhibitory neural control, which was abolished with TTX (41.0 v 69.3 mHz p = 0.0003), with post TTX treatment contraction frequencies identical to that seen in E21.5 aganglionic distal colon (58.3 v 69.3 mHz p = 0.08).

ConclusionThe transplantation of embryonic murine and human ENS stem cells into aganglionic embryonic bowel results in a restoration of function. This is neurally controlled, and can be blocked by addition of TTX. This finding has potential application in the treatment of Hirchsprung's disease.

P15 Preventing secondary hyperparathyroidism reduces vascular damage and calcification in children on dialysis

R. Shroff1, presenting, A. Donald1, M. Hiorns1, A. Watson2, S. Feather3, D. Milford4, E. Ellins1, C. Storry1, J. Deanfield1, L. Rees1. 1Great Ormond Street Hospital NHS Trust and Institute of Child Health, London; 2Nottingham City Hospital, Nottingham; 3St James's University Hospital, Leeds; 4Birmingham Children's Hospital, Birmingham, UK

BackgroundCardiovascular disease is increasingly recognised as a life‐limiting problem in young patients with chronic kidney disease (CKD), but there are few studies in children that describe its determinants. We studied the impact of intact parathyroid hormone (iPTH) levels and their management on vascular structure and function in children on dialysis.

MethodsChildren aged 5–18 years who had received dialysis for [gt-or-equal, slanted]6 months and had an eGFR <30 ml/min/1.73 m2 for [gt-or-equal, slanted]3 years were studied. Cumulative data on calcium, phosphate (PO4) and iPTH levels, and doses of phosphate‐binders and calcitriol were recorded. Patients were divided into two well‐matched groups based on mean time‐integrated iPTH levels: Group I–iPTH levels [less-than-or-eq, slant] twice upper limit of normal (ULN) (n = 41) and Group II–iPTH levels > twice ULN (n = 44), and compared to age‐matched controls (n = 40). Carotid intima‐media thickness (cIMT), aortic and brachio‐radial pulse‐wave velocity (PWV) and cardiac calcification were measured.

ResultsDialysis patients had increased cIMT and PWV as compared to controls. All vascular measures in Group I were comparable to controls, but group II had thicker cIMT (p<0.001, relative risk 3.7), stiffer vessels (p = 0.03) and increased calcification (p = 0.004, relative risk 2.3) compared to Group I. Six children in Group II had moderate‐severe calcification (score >100) as compared to only 1 child in Group I. The youngest patient with cardiac calcification was 5.8 years old. All the vascular measures positively correlated with PO4 levels. Patients with increased cIMT also had stiffer vessels and an increased risk of calcification. The dose of calcitriol therapy influenced all vascular measures, but elemental calcium intake from PO4‐binders was unrelated. On multiple regression analysis iPTH, PO4 and calcitriol dose were independent predictors of IMT and iPTH and calcitriol were significant predictors of cardiac calcification.

ConclusionWe have shown that iPTH levels and the calcitriol dose are significant and independent predictors of vascular damage in children on dialysis. Maintaining the iPTH level within twice the ULN and using the lowest possible dose of calcitriol is associated with less vascular damage and potentially, reduced cardiovascular morbidity and mortality.

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