Standards for the management of sickle cell disease in children.

Sickle cell disease is now the commonest genetic condition in England with a birth prevalence of 1 in 2000. It causes significant morbidity and mortality particularly in the early years unless prophylactic measures have been put in place. By the end of 2006 newborn screening had been introduced all over England, its prime aim being to minimise mortality from pneumococcal sepsis in the first few years of life. Plans are currently underway to roll out programmes in Scotland and Wales. Standards and guidelines for the care of children with sickle cell disease were written to accompany the newborn screening programme and to offer a management plan for those working in areas of low prevalence where resources and expertise were possibly less well developed. This article describes the existing evidence base for treatment and the current consensus of good practice. It is acknowledged that more work needs to be carried out to develop guidelines further.

Outcome of stroke in patients with sickle cell disease

Cerebral vasculopathy is a major cause of morbidity in sickle cell disease (SCD). We report the first UK population-based study of stroke in SCD. Of 669 SCD patients (HbSS 429, HbSC 193, HbS-thalassaemia 48, HbSO 1) followed at the King's College hospital between 1970 and 1995, 21 (3.1 percent) developed stroke. A further ten patients were referred. 29 had HbSS and 2, HbSC. 3 (10 percent) suffered subarachnoid haemorrhage, the remaining 28 strokes were ischaemic. Median age at initial stroke was 6 years (19 mo- 31 yr) with 24 (80 percent) patients aged >10. Precipitating factors included parvovirus associated aplastic crisis in 2/25 98 percent) evaluable patients and bacterial meningitis in 2 (8 percent). 9 (36 percent) patients experienced transient neurological disturbance prodromally. 27 (87 percent) presented with paresis, 5 (16 percent) cranial nerve defects. 11 (35 percent) dysphasia and 3 (10 percent) seizures. No patient died during the acute episode. Patients with stroke had significantly lower Hb and higher WCC at age 1 compared to matched controls. Exchanged transfusion was performed with 26 patients following which 15 (58 percent) recovered neurologically. 19 patients subsequently entered a transfusion programme to maintain HbS <30 percent. Transfusion was stopped in 10 patients. Of these, 6 (60 percent) had recurrent stroke at a median of 4.5 months. A similar recurrence rate (50 percent) was observed among patients who did not receive regular transfusion whilst no patient maintained on monthly transfusions suffered further stroke. Recurrence was more common in patients suffering initial stroke at an early age and in whom no trigger was identified. Median follow-up after initial stroke is 8 years. 14 (45 percent) patients have no residual neurological deficit, 6 (19 percent) are severely disabled, 13 (42 percent) have learning disabilities and 7 (23 percent) epilepsy. There were two deaths in both patients with recurrent stroke. 1 patient with moyamoya-type disease has undergone extracranial-intracranial bypass and 1 allogeneic-BMT. In conclusion, whilst transfusion is effective in prevention of further stroke, cessation is associated with a high rate of recurrence which frequently results in severe physical and/or neuropsychological disability. The 6.5 percent mortality following stroke supports the rationale for early consideration of allogeneic-BMT in these patients. (AU)

Neonatal Screening for Haemoglobinopathies in South East London: findings and comparisons with Jamaica

INTRODUCTION: Neonatal screening for sickle cell disorders has been shown to reduce mortality and morbidity. Methods of screening vary but in 1994, the local Health Authority funded universal neonatal screening across the whole of Lambeth, Southwark and Lewisham. This paper will report the findings of the first three years of operation of the programme and compare findings with the screening programme currently operating in Jamaica. METHOD: since May 1994 dried bloo[d] spots of all infants have been screened at King's College Hospital and screen positive cases followed up by counsellors. Infants are followed up at four sites (Guy's, King's, Lewisham and St.Thomas') according to parental preference. Minimum standards for follow-ups have been agreed by clinicians across all four sites and information of the success in achieving these standards is now being collected. RESULTS: Overall there have been 122 affected infants detected in the first two years 10 months of the programmes operation. This is made up of 83 HbSS, 35 HbSC, 4HbSBThal. This gives a birth preference of 23.4 per 1000 total population (2.3HbSS, 1.0 HbSC). Allowing for a termination rate of 20 percent this indicates that the expected birth prevalence in the district would be 4.2 per 1000 births. This compares with birth prevalence of of 0.3 per 1000 for congenital hypothyroidism, 06. per 1000 for cystic fibrosis and 0.1 for phenylketonuria. The distribution of the births is unevem with 57 in Southwark, 40 in Lambeth and 25 in Lewisham. The paper will report on the follow-up and outcome of care provided for this population to date. Discussion: South East London has the highest prevalence of sickle cell disorders of any district in the UK. Sickle cell disorder is now as common in South East London as it is in Jamaica. The follow-up arrangements established in South East London provide an opportunity for colloboration with the West Indies which may help to determine some of the reasons for differences in the natural course of the disease in these populations. The population based approach established should allow monitoring of the impact of community education and antenatal screening programmes on the birth prevalence over time. (AU)

Improving the effectiveness of screening for haemoglobinopathies in primary and community care in Lambeth: antenatal findings

An antenatal screening programme for haemoglobinopathies aims to allow couples to make informed choices about reproductive options. Screening must be carried out early in pregnancy and must be supported with accurate information and a genetic counselling service. An audit in 1990 at St. Thomas' found that couples were referred for genetic counselling late in pregnancy or not at all. The aim of the study was to icrease the uptake of screening and counselling in the antenatal clinic by improving midwives knowledge of the condition and available counselling services. A research worker was employed to evaluate the intervention. METHODS: Knowledge of haemoglobionpathies, genetic risk and available services was assessed by means of a questionnaire. An audit of ante-natal screening was undertaken before and after the introduction of specific guidelines and a porforma by reviewing over 1400 antenatal notes of those recieving community or shared care. Laboratory data on the number of tests requested for both the women and their partners was obtained for the year of the first audit. RESULTS: 23/44 midwives completed the questionnaire (65 percent). Analysis of the responses indicated that hospital midwives were better informed on every question. There was a significant difference (p<<0.001 in the proportion of questions answered correctly by hospital midwives compared to community midwives (77 percent of 45 percent, 95 percent CI 17-45 percent). (AU)

Neonatal screening for sickle cell diseases in Camberwell: results and recommendations of a two year pilot study.

The sickle cell diseases are a major health problem for Afro-Caribbean peoples. Neonatal detection and prophylactic management can reduce mortality and morbidity in childhood. A study was therefore conducted analysing the results of the first two years of cord blood screening in the Camberwell health area. Thirteen cases of sickle cell disease and two of haemoglobin (Hb)C disease were identified among 2202 non-white infants screened. The carrier state, sickle cell trait (HbAS), was present in 11.9% and HbC trait (HbAC) in 4.1% of Afro-Caribbean infants. The incidence of disease and of carrier states was much higher in West Africans than in Caribbeans. The wider implications of screening and the need for a comprehensive plan of care are emphasised.

Biliary scintigraphy with DISIDA. A simpler way of showing bile duct patency in suspected biliary atresia.

99mTC-diisopropyl iminodiacetic acid (DISIDA) scintigraphy after oral phenobarbitone treatment accurately indicated bile duct patency or obstruction in 28 of 32 (87%) infants, aged less than 12 weeks, with suspected biliary atresia. This investigation is more rapid than and as accurate as the 131I Rose-Bengal faecal excretion test.

Hepatitis syndrome in infancy--an epidemiological survey with 10 year follow up.

Fifty four infants with hepatobiliary disease and conjugated hyperbilirubinaemia of more than two weeks' duration were identified in a defined area of south east England in a prospective study between January 1971 and December 1973. The overall incidence was one case per 2500 live births. The cases were regularly reviewed and all survivors except one were assessed at age 10 years. Nine of 11 with extrahepatic biliary atresia died from liver disease by 2 years of age, one died at 5 years, and the survivor has cirrhosis with portal hypertension. Four out of seven with alpha 1 antitrypsin deficiency died aged 1 to 3 years from liver disease and one of the survivors has cirrhosis. All three infants with intrauterine infection and one with chromosomal abnormality died in infancy. Three children with other associated factors, choledochal cyst, galactosaemia, and rhesus isoimmunisation, recovered completely with no persisting liver disease. Two of 29 with cryptogenic hepatitis died, but only a further two have signs of persisting liver disease. Perinatal complications were more common in this group. Four of the 27 children surviving to the age of 10 years are educationally subnormal. Prognosis for infants with intrahepatic liver disease in the absence of known associated factors is good and every effort should be made to minimise the short term effects of cholestasis.