Parents' Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease.

The clinical advantages of the newborn screening programme (NBS) in the UK are well described in the literature. However, there has been little exploration of the psychosocial impact on the family. This study followed the principles of grounded theory to explore parents' experiences of receiving the initial positive NBS result for their child with cystic fibrosis (CF) or sickle cell disease (SCD). Semi-structured, qualitative interviews were conducted with 22 parents (12 mothers and 10 fathers) whose children had been diagnosed with CF or SCD via NBS and were under the age of 1 year at the time of interview. The main themes that arose from the data were; parents previous knowledge of the condition and the NBS programme, the method of delivery and parental reactions to the result, sharing the results with others, the impact on parental relationships and support strategies. Study conclusions indicate that most parents thought initial positive NBS results should be delivered by a health professional with condition specific knowledge, preferably with both parents present. Genetic counselling needs to include a focus on the impact of NBS results on parental relationships. Careful consideration needs to be given to strategies to support parents of babies who have positive NBS results both in terms of the psychological health and to assist them in sharing the diagnosis.

Vitamin D deficiency and its correction in children with sickle cell anaemia.

Vitamin D deficiency is common in sickle cell anaemia (SCA, HbSS), although its significance and optimal means of correction are unknown. We conducted an audit to assess the clinical significance of 25-hydroxy vitamin D (25-OHD) deficiency in children with SCA and to evaluate two methods of vitamin D supplementation. We audited 25-OHD levels in 81 children with SCA and looked for statistical associations with biochemical, haematological and clinical parameters. In a separate group of regularly transfused children with SCA, we compared changes in 25-OHD blood concentrations following treatment with either high-dose intramuscular ergocalciferol (n = 15) or 4 days of high-dose oral cholecalciferol (n = 64). Ninety-one percent of children with SCA had 25-OHD levels <20 µg/L. The 25-OHD levels were negatively correlated with increasing age (P < 0.001) but showed no significant relationship to laboratory measurements, transcranial Doppler velocities or hospital attendance. Both intramuscular ergocalciferol and oral cholecalciferol supplementations resulted in increases of 25-OHD blood concentration to normal levels. The mean dose of ergocalciferol was greater than that of cholecalciferol (7,729 versus 5,234 international units (IU)/kg, P < 0.001), but the increment in 25-OHD levels was significantly greater in the oral cholecalciferol group (6.44 versus 2.82 (ng/L)/(IU/kg), P < 0.001). Both approaches resulted in vitamin D sufficiency for about 120 days. Increased 25-OHD concentration was significantly associated with increased serum calcium concentration. Vitamin D deficiency is very common in SCA and can be effectively corrected with high-dose intramuscular ergocalciferol or 4 days of high-dose oral cholecalciferol. Prospective, randomised studies are needed to assess the clinical value of vitamin D supplementation.

Changing pattern of hospital admissions of children with sickle cell disease over the last 50 years.

A study published in 1981 examined the causes of hospital admission for a cohort of children with sickle cell disease (SCD). Since that time, the incidence and prevalence of SCD has increased markedly in the UK, and there have been many changes in the management of this disease. We undertook a study examining the causes of hospital admission of children with SCD to the same hospital as the previous study, over the 2-year period from 2008 to 2009. We found that the numbers of children being cared for by our hospital had dramatically increased over the last 50 years, but rates of hospital admission had significantly fallen (41 hospital admissions per 100 patient-years, compared with 111.3 admissions per 100 patient-years in the original study). This fall in admission rates is accounted for by 2 major components: acute painful episodes (15.7 admissions per 100 patient-years compared with 39.3 in the previous study) and admission for elective blood transfusion (0.2 admissions per 100 patient-years compared with 26.7 in the previous study). It is interesting to note that, 541 elective transfusions were carried out during the study period, but in a day-care setting rather than requiring overnight admission. This study illustrates the changes in management of SCD over the past 30 years, and reflects the overall trend common to most hospital specialties of increasing community and ambulatory care.

Portacaths are safe for long-term regular blood transfusion in children with sickle cell anaemia.

Peripheral venous access in children with sickle cell anaemia (SCA) requiring regular blood transfusions can become difficult over time. Previous reports have suggested the use of totally implantable venous access devices, Portacaths (PAC) in this patient group are associated with unacceptable high rates of complications. We present our experience in seven children with SCA over a 9-year period. Seven devices were placed for a total of 9754 PAC days during the study period. The median age at insertion was 6.3 years (range 3-15 years). The rate of PAC associated infection was 0.2 per 1000 PAC days. There were no episodes of thrombosis. The median length of time in situ during the study period was 3.7 years (range 1.3-7.5 years). Our experience highlights the safe and reliable use of PAC in children with SCA requiring regular blood transfusions when venous access has become a major problem.

Outcome of children with sickle cell disease admitted to intensive care - a single institution experience.

We retrospectively audited children with sickle cell disease (SCD) admitted to paediatric intensive care (PICU) at King's College Hospital between January 2000 and December 2008. Forty-six children with SCD were admitted, on 49 separate occasions. Ages ranged from 4 months to 15 years (median 7.6 years). Three children died in PICU, however two presented to hospital in cardiorespiratory arrest; overall mortality was 6%. The most common reason for admission was acute chest syndrome (43%). 88% of admissions required blood transfusion, of which 74% had exchange blood transfusions. The mortality among children with SCD admitted to PICU is low.

Stroke prevention in the young child with sickle cell anaemia.

Cerebrovascular disease resulting in stroke is a serious and preventable complication of sickle cell anaemia (SCA). Children at high risk of preventable stroke can be identified by transcranial Doppler ultrasound (TCD). Current guidelines in the UK recommend annual TCD screening from 3 years, although studies suggest an earlier peak incidence, between 2 and 5 years. A single centre retrospective review was undertaken to identify the prevalence of stroke and success of TCD screening in young children. We report five episodes of stroke in under 3s and outcome of TCD screening in children under 3, compared to over 3. TCD analysis was as successful in the 2-3-year age group as in the 3-4-year group. We therefore propose that all children with SCA should be offered TCD screening from the age of 2 years. Furthermore, infants with high risk features of SCA should undergo a first attempt at TCD screening even earlier.

The effects of air quality on haematological and clinical parameters in children with sickle cell anaemia.

Sickle cell anaemia (SCA; HbSS) is characterised by its clinical variability, which is only partly explained by known genetic factors. Environmental factors are known to contribute to acute problems but their importance in chronic complications has not been analysed. We have studied 93 children with SCA in a single institution, who underwent transcranial Doppler scanning and steady-state blood tests in 2006. These data were correlated with each individual's exposure to pollution from dust (PM(10)), nitric oxide (NO) and nitrogen dioxide (NO(2)). This exposure was derived from patient postcodes and detailed street-level maps of average pollutant levels in 2006. All the pollutants correlated closely with each other. Increased exposure to pollution correlated with a significant reduction in total bilirubin levels, with a trend towards lower levels of lactate dehydrogenase and aspartate transaminase. There was significant correlation between extracranial internal carotid artery blood velocity and PM(10) exposure. These studies suggest that chronic exposure to air pollutants could explain some variability in SCA. The lower levels of bilirubin and other markers of haemolysis with increased exposure to air pollutants could be mediated by increased exposure to NO.

A simple index using age, hemoglobin, and aspartate transaminase predicts increased intracerebral blood velocity as measured by transcranial Doppler scanning in children with sickle cell anemia.

OBJECTIVE: Increased intracerebral blood velocity measured by transcranial Doppler scanning identifies children with sickle cell anemia who are at increased risk of stroke. We have tried to develop an index based on routine clinical measurements that also predicts increased intracerebral blood flow. METHOD: Routinely collected clinical and laboratory data were correlated with transcranial Doppler measurements on children with sickle cell anemia seen in a single institution in 2006. The index produced was validated on a second independent data set from children with sickle cell anemia. RESULTS: The time-averaged mean of the maximum velocity in centimeters per second in the middle cerebral artery circulation correlated significantly with age, hemoglobin, lactate dehydrogenase, and aspartate transaminase levels, white blood cell count, and creatinine level. On multiple regression, hemoglobin and aspartate transaminase levels maintained their significance, whereas age had borderline significance, and an index was developed linked to a time-averaged mean of the maximum velocity of 220 - (8 x hemoglobin) - (1.4 x age) + (0.4 x aspartate transaminase). This detected a time-averaged mean of the maximum velocity of >170 cm/second with 100% sensitivity and 58% specificity. The index was validated on the second data set and again showed 100% sensitivity with 73% specificity. CONCLUSION: This simple index has the potential to identify children who are at higher risk of cerebrovascular disease to allow them to be prioritized for transcranial Doppler scanning and other intracerebral imaging.

Serum lactate dehydrogenase activity as a biomarker in children with sickle cell disease.

Serum lactate dehydrogenase (LDH) levels were studied in children with HbSS and HbSC in a single institution, and their relationship to cerebral vasculopathy as assessed by transcranial Doppler scanning (TCD). All children with HbSS (n = 97) and HbSC (n = 18) who underwent a TCD scan in 2006 were studied. LDH levels were higher in HbSS patients than HbSC (581 IU/l vs. 305 IU/l, P < 0.001). In children with HbSS, LDH correlated significantly with haemoglobin, reticulocytes, aspartate transaminase and creatinine. LDH also correlated positively and significantly with TCD measurements in the middle and anterior cerebral artery circulations in the children with HbSS.

Transcranial Doppler scanning and the assessment of stroke risk in children with HbSC [corrected] disease.

OBJECTIVE: To assess the role of transcranial Doppler (TCD) scanning in assessing the risk of stroke in children with haemoglobin SC (HbSC) disease. TCD scanning has an established role in primary stroke prevention in sickle cell anaemia but its value in HbSC is unknown. DESIGN: A retrospective audit of routinely performed TCD scans and routinely collected clinical data. SETTING: A paediatric sickle cell clinic in a teaching hospital in south London, UK. PATIENTS: 46 children with HbSC disease who have undergone routinely performed TCD scans and steady-state blood tests. MAIN OUTCOME MEASURES: The time-averaged mean of the maximum velocity (TAMMV) in the middle cerebral artery circulation correlated with clinical and laboratory data. RESULTS: The mean TAMMV was 94 cm/s, with a 98(th) centile of 128 cm/s. This is significantly less than the published ranges for HbSS, with a mean reading of 129 cm/s. One child had a stroke at the age of 5 years, when her TAMMV was measured at 146 cm/s. CONCLUSIONS: Further studies are needed to assess stroke risk in HbSC disease, but we suggest that TCD measurements are potentially useful in this condition, and that readings greater than 128 cm/s are abnormally high and warrant further investigation.

The measurement of urinary hydroxyurea in sickle cell anaemia.

Hydroxyurea is increasingly used in the treatment of sickle cell disease (SCD) although there is little evidence on how best to monitor treatment and compliance. It is also not known why 10-50% patients do not benefit from the drug and whether some of this resistance is because of pharmacokinetic factors. We have developed an assay using mass spectrometry (MS) to measure urinary concentrations of hydroxyurea. We have used this assay to study 12 children and six adults with SCD taking hydroxyurea and found that urinary hydroxyurea was present for at least 12 h following tablet ingestion. Thirty-five urine samples were analysed that were expected to contain hydroxyurea, based on the reported timing of the last dose and hydroxyurea was detected in 29 (83%) of these. There were also marked differences in urinary hydroxyurea concentrations, suggesting pharmacokinetic variability may explain some of the differences in response to hydroxyurea. Urine samples were also analysed by MS for penicillin metabolites and 43 of the 57 (75%) contained phenoxyacetate, suggesting the ingestion of penicillin within the last 12 h. These assays are potentially useful to study hydroxyurea metabolism further, develop optimal dosing regimes and monitor compliance with treatment.