Years Of Child's Life Research Articles

ОЦЕНКА БЕЗОПАСНОСТИ И ВЛИЯНИЯ ПНЕВМОКОККОВОЙ ВАКЦИНЫ «ПРЕВЕНАР-13» НА ПОКАЗАТЕЛИ ЗАБОЛЕВАЕМОСТИ ПНЕВМОНИЕЙ И ОТИТОВ У ДЕТЕЙ ПЕРВЫХ ПЯТИ ЛЕТ ЖИЗНИ

The scientific article presents an assessment of the clinical effectiveness and safety of the use of the pneumococcal conjugate 13-valent vaccine (PCV13, PCV 13) «Prevenar 13» in children from 0 to 5 years old, observed in the children's department of the State Budgetary Institution of Healthcare of the Secondary Educational Institution «SGKP N 15» in the city Samara. The study included 590 children, who were divided into 2 groups. The first (main, group PC-13) group included children born in 2018 - 2020 and vaccinated with the Prevenar 13 vaccine according to the «2 + 1» (n=490), the second (control) group included children born in 2013 and not vaccinated with a vaccine against pneumococcal infection, including Prevenar 13 (n=100). The study revealed that during the 2nd year of life in children of the first group, the incidence rate after vaccination decreased by 2 times. The incidence rate of pneumonia in the group of vaccinated children also decreased in all age periods, and the incidence rate of otitis media during the entire observation period in the second group of children (unvaccinated) was higher. Based on the data presented, we can conclude that vaccination with Prevenar-13 is a safe and effective measure in the prevention of ARI (acute respiratory infections) in children.

67 A population-based cohort study of endocrine outcomes within the first 5 years of life in children born preterm

Abstract Background Preterm birth (<37 weeks’ gestational age [GA]) occurs in 8% of live births in Canada. While advancements in neonatal medicine have led to increased survival in preterm births, infants born preterm continue to sustain short- and long-term health sequelae. There is paucity of large population studies evaluating childhood health care outcomes, including endocrine-related outcomes, in recent birth cohorts. Objectives To evaluate the rates of endocrine conditions during the first 5 years of life in children born preterm and term. Design/Methods The study cohort included liveborn infants at 22-44 weeks’ GA in British Columbia, Canada between 2004-2014. Follow-up data to December 2019 included linked health services use information from four BC provincial databases (perinatal database, hospitalizations, outpatient services, and outpatient prescriptions). Rates of outcomes were compared by GA at birth (37-44 weeks reference category) using robust Poisson regression. Results There were 455,960 children included in this study with 42,820 (9.4%) born at <37 weeks GA. Results are summarized in Table 1 and Table 2. Compared to children born at 37-44 weeks’ gestations, infants born at 36 weeks’ gestation or younger have an increased rate of thyroid disorders between 0 months and 5 years (rate ratio [RR]: 1.45, 95% confidence interval [CI]: 0.78-2.43; RR: 1.83, 95% CI 1.51-2.20; RR: 1.41 95% CI 1.26-1.57 for 22-27 weeks, 28-33 weeks and 34-36 weeks GA, respectively). Similarly, infants born at 36 weeks’ gestation or younger have a higher rate of conditions in growth and development (RR: 3.05, 95% CI: 0.76-7.96; RR: 3.20, 95% CI 2.04-4.76; RR: 1.42 95% CI 1.02-1.94 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively) and bone health conditions (RR: 1.38, 95% CI: 1.27-1.49; RR: 1.04, 95% CI 1.00-1.08; RR: 1.05 95% CI 1.03-1.07 for 22-27 weeks, 28-33 weeks and 34-36 weeks gestations, respectively). There was no difference in rates of conditions related to glucose metabolism such as diabetes mellitus or hypoglycemia. Conclusion Children born preterm have increased rates of endocrine conditions by age 5. Disorders of thyroid, growth and development are increased in infants born preterm. Children born preterm have an increase rate of bone-related disorders, including those born late-preterm. These results provide useful prognostic information for follow-up care for preterm children and for healthcare resource planning. Furthermore, these results highlight areas of future research in endocrine health among preterm infants.

Quality of Care in the Last Two Years of Life for Children With Complex Chronic Conditions

ContextLimited data exists about care received by children with complex chronic conditions (CCCs) in the final years of their disease and end-of-life (EOL). ObjectiveTo examine hospital performance on EOL quality measures and to describe healthcare services during the last two years of life for children with CCCs who died in-hospital. MethodsRetrospective automated electronic health record review of children with ≥1 CCC ICD-10 diagnosis code, who died inpatient between October 2020 and March 2023 at a single quaternary U.S. children's hospital. Quality was assessed based on performance on 15 measures across five domains: healthcare utilization, interprofessional supports, medical intensity, symptom management, and communication. Quality EOL care and healthcare services in the last two years of life were determined overall by age group and per patient. Descriptive statistics were used to evaluate demographic differences by age. Results266 children with CCCs died in the study timeframe; 45% were infants (n = 120), 52% (n = 137) were male, 42% (n = 113) were white, 64% (n = 170) were non-Hispanic, and 59% (n=156) had public insurance. Children had a median of three CCCs (IQR 2.4; range 1–8). On average, children met 69% (SD 13%) of EOL quality measures for which they were eligible. In the two years prior to death, 98% (n = 261) had an ICU admission, 75% (n = 200) had a procedure requiring sedation, and 29% (n = 79) had received cardiopulmonary resuscitation. 86% (n = 229) died in the ICU. ConclusionIn this study, children with CCCs met 69% of quality measures and received high-intensity healthcare in the last two years of life.

Investigating Parental Observations of Early Autism Development in Simplex and Multiplex Families.

Past research has highlighted the importance of early identification of developmental differences to improve targeted access to early interventions or supports. As such, it is of particular importance in the context of children at elevated likelihood of autism (such as where an older sibling has a diagnosis of autism), to better understand when and which early concerns are important as predictors of which children will benefit from pre-diagnostic supports. This study explored the number and frequency of retrospective parent reported concerns within the first year of life for children diagnosed with autism, both those who had an older sibling diagnosed with autism and those who did not, as well as for undiagnosed siblings. We found that at both 0-6 and 7-12 months, the only factor related to the presence or absence of early parent reported concerns was child diagnostic status, with the presence of reported early concerns more likely for children with a diagnosis of autism. These findings suggest that for children at elevated likelihood of autism, parents' concerns are driven primarily by developmental differences, with child's birth order and sibling diagnostic status not impacting on parent early concerns.

Days alive and out of hospital for children born with single-ventricle heart disease.

This study describes the illness burden in the first year of life for children with single-ventricle heart disease, using the metric of days alive and out of hospital to characterize morbidity and mortality. This is a retrospective single-centre study of single-ventricle patients born between 2005 and 2021 who had their initial operation performed at our institution. Patient demographics, anatomical details, and hospitalizations were extracted from our institutional single-ventricle database. Days alive and out of hospital were calculated by subtracting the number of days hospitalized from number of days alive during the first year of life. A multivariable linear regression with stepwise variable selection was used to determine independent risk factors associated with fewer days alive and out of hospital. In total, 437 patients were included. Overall median number of days alive and out of hospital in the first year of life for single-ventricle patients was 278 days (interquartile range 157-319 days). In a multivariable analysis, low birth weight (<2.5kg) (b = -37.55, p = 0.01), presence of a dominant right ventricle (b = -31.05, p = 0.01), moderate-severe dominant atrioventricular valve regurgitation at birth (b = -37.65, p <0.05), index hybrid Norwood operation (b = -138.73, p < 0.01), or index heart transplant (b = -158.41, p < 0.01) were all independently associated with fewer days alive and out of hospital. Children with single-ventricle heart defects have significant illness burden in the first year of life. Identifying risk factors associated with fewer days alive and out of hospital may aid in counselling families regarding expectations and patient prognosis.

Nutritional status of under-two years old children of depressive mothers presented to Hayatabad Medical Complex Peshawar.

Objective: Maternal mental health is an important factor for wellbeing of babies. The aim of present study was to determine the frequency of malnutrition among less than2-year-old children of depressed mother presented to HMC. Study Design: Cross-sectional study. Setting: Psychiatry Unit, Hayatabad Medical Complex, Peshawar. Period: July 2021 to February 2022. Material &amp; Methods: A sample size 364 mothers were selected through random sampling technique. Data was collected on a structured questionnaire and analyzed using SPSS version 24 for windows. Results: Mean age of mothers were 26±3 SD. Among 364 women, 130(35.72%) were normal, 125(34.34%) were having moderate depression and 109(29.94%) were having severe depression. Nutritional status of their children showed 88(24.18%) normal children, 152(41.75%) were moderate and 124(34.06%) were having severe malnutrition. Depression showed significant association with child nutrition. Conclusion: Depression in women is the major cause of malnutrition in first two year of child life. Effective strategies especially during postnatal period can help to alleviate the depression in women.

Prediction of frequent acute respiratory infections in the first year of life in children with cerebral ischemia, survivors of cytomegalovirus infection in the neonatal period

Objective: to develop prognostic criteria for frequent respiratory diseases in the first year of life in children with cerebral ischemia who had a cytomegalovirus infection in the neonatal period. Research methods: 73 children of the first year of life with cerebral ischemia, who underwent cytomegalovirus infection in the neonatal period, were deployed. All observed patients at the age of three months underwent a study of the population composition of peripheral blood T-lymphocytes using flow cytometry for the expression of membrane markers, taking into account the results on a Beckman Coulter Epics XL II laser flow cytometer. Typing of lymphocytes was carried out using monoclonal antibodies to differentiation clusters CD3+, CD3+CD69+, CD3+CD71+, CD3+CD95+ from Immunotech (France). The observation groups consisted of 30 children (41.1%) with frequent acute respiratory infections (4—5 episodes per year) in the first year of life and 43 people (58.9%) — children with no acute respiratory infection’sepisodes in the first-year life. Results. From the set of studied T-lymphocytes, statistically significant for the prognosis of frequent acute respiratory infections in the first year of life in children with cerebral ischemia who underwent cytomegalovirus infection in the neonatal period were found: CD3+ CD71+, CD3+ CD95+. It was revealed that in children with a reduced level of CD3+ CD71+ and an increased level of CD3+ CD95+ in blood serum at the age of 3 months, frequent acute respiratory infections occurred in the first year of life.

Study to assess incidence and type of congenital heart defect in children with down syndrome presenting to tertiary care teaching hospital of Southern Rajasthan

Background: Down syndrome occurs in people of all races and economic levels. Cardiac anomalies with a prevalence of about 50% are the most common anomaly responsible for death during the 1st two years of life in children with down syndrome. Objective of the study was to Assess the incidence and type of congenital heart disease in children with down syndrome presenting to a tertiary care hospital. Methods: Hospital based descriptive study. Participants: All children (0 to 18 years) diagnosed (clinically or on karyotyping) with Down syndrome, presenting in RNT Medical College, Udaipur Each patient was evaluated with a pre-set Performa which contained detailed sociodemographic profile, maternal and clinical history including age of conception, detailed physical examination to look for features of down syndrome. Degree of Intellectual / Developmental retardation was assessed by Vineland Social Maturity Scale. 2D- echo, karyotyping was done in all patient. CBC, thyroid profile, CXR, USG- abdomen, Invertogram were done as per need. Results: Total 144 participants included in the study, 75 (52%) were females and rest were males 48%. Out of these 111 (77%) were aware about dog bite causes disease and among these 52 (46.8%) were aware that dog bite causes rabies. Among the participants, 138 (95.8%) were aware about the vaccine availability and 125 (90.5%) knew vaccine is available in Government Hospital. In the study 88% of dog bite victims received treatment. Conclusions: More than half of children with Down syndrome have congenital heart disease, mostly Acyanotic, more specifically VSD. Early screening and diagnosis re the key to avoid irreversible hemodynamic consequences.

EPS7.06 Hospital admissions due to pulmonary exacerbation in the first five years of life in children with cystic fibrosis in Ireland: the Irish Comparative Outcome Study of cystic fibrosis (ICOS)

Objectives: ICOS is a historical cohort study comparing children clinically diagnosed with Cystic Fibrosis (CF) to those diagnosed through the newborn screening programme. Newborn screening was introduced in 2011 in Ireland. This study aims to assess prevalence and factors associated with hospitalisation for pulmonary exacerbation of CF in the first five years of life.

Examining core vocabulary with language development for early symbolic communicators

Purpose Core vocabulary lists are frequently used to select vocabulary for early symbolic communicators who require augmentative and alternative communication (AAC). The current study extended existing work by investigating how core vocabulary lists overlap and diverge from typical language development. Method We investigated when the words on seven core vocabulary lists emerge in typical language development, the composition of the lists based on their parts of speech, and how the composition of the words on the lists compare to the MacArthur Bates Communication Development Inventories (CDI). Result On average, the words on the seven core vocabulary lists appear after the second year of life in children with typical spoken language development (25, 27, 37, 45, 47, 50, and 66 months). Verbs were the most prevalent part of speech in all but one of the core vocabulary lists. Core vocabulary words made up only a small percentage of words on the CDI. Conclusion The words on the core vocabulary lists do not emerge until later points in typical lexical development. Focussing on core words when working with early symbolic communicators who require AAC may lead to limited and variable lexicons with wide gaps.

Increased levels of anti-BSA antibodies in children with Down syndrome.

Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls. Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP). Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated. Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.

Prospective study of loss of health-related quality adjusted life years in children and their families due to uncomplicated and hospitalised varicella.

Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. Children with varicella in the community and admitted to hospitals in Portugal were included over 18months from January 2019. Children's and carers' HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0days (95% CI 1.9-2.2, n=101) (mean 5.4 QALYs/1000 children (95% CI 5.3-6.1) and 1.3days/primary carer (95% CI 1.2-1.6, n=103) (mean 3.6 QALYs /1000 carers (95% CI 3.4-4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8days (95% CI 9.4-10.6, n=114) (mean 26.8 QALYs /1000 children (95% CI 25.8-29.0) and 8.5days/primary carer (95% CI 7.4-9.6, n=114) (mean 23.4 QALYs/1000 carers (95% CI 20.3-26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95% CI 43.9-97.6)]. Estimates for children's QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.

Impact of enteropathogens on faltering growth in a resource-limited setting.

Environmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy. A community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3-6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens. Giardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), and Cryptosporidium spp. were the most prevailing enteropathogens in terms of overall positivity at both time points. Detection of protozoa at enrollment and 9 months was negatively correlated with rate of change in height-for-age Z (ΔHAZ) scores during the first and second years of life. A positive association was found between Giardia, fecal lipocalin (LCN), and alpha 1-Acid Glycoprotein (AGP), while Campylobacter spp. showed positive associations with neopterin (NEO) and myeloperoxidase (MPO). Protozoal colonization is associated with a decline in linear growth velocity during the first 2 years of life in children living in Environmental enteric dysfunction (EED) endemic settings. Mechanistic studies exploring the role of cumulative microbial colonization, their adaptations to undernutrition, and their influence on gut homeostasis are required to understand symptomatic enteropathogen-induced growth faltering.

PEGASE Program: Identification of babies in the child protection system at risk of developmental delays or disorders and the implementation of a ‘supra‐optimal’ care pathway

AbstractThe importance of the first three years of life for children's development and the consequences for their general health in adulthood have been widely documented in the international literature, including the benefits of early identification and intervention programs. Additionally, convergent research has highlighted wide‐ranging negative trajectories attributable to both the short and long‐term consequences of abuse and neglect and their neurobiological impact on health and development. However, formal identification processes and the use of standardised screening tools in child protection remain relatively rare despite the potential societal impact of child maltreatment in terms of public and economic health. Moreover, delays between the initial identification of mental health problems and health and developmental disorders, and the introduction of appropriate interventions persist. Abused and neglected infants risk an exacerbation of the consequences of early maltreatment due to insufficient access to prompt assessment and treatment, including appropriate responses to their health needs.The aim of this article is to present the PEGASE program, an innovative French program for very young children in care, which is modelled on the care of premature babies. By setting up an early care pathway, it aims to ensure adequate medical follow‐up – both somatic and psychiatric – through standardised examination and tailored interventions in order to limit the adverse health and developmental consequences of abuse. The presentation of the PEGASE program is supplemented by a case study.

Treatment of Congenital Hypothyroidism: Impact of Secular Changes in Levothyroxine Initial Dose on Early Growth

Introduction: Newborn screening of congenital hypothyroidism (CH) has enabled early treatment with levothyroxine (LT4), ensuring normal growth and development. The initial LT4 dose recommendation has increased over decades. We evaluated whether the increased LT4 dosing influenced thyroid-stimulating hormone (TSH) and thyroxine (fT4) concentrations, growth, or treatment-related symptoms. Methods: LT4 doses, TSH, fT4, anthropometrics, and treatment-related symptoms until age 2 years were evaluated in 172 Finnish CH patients born between 1980 and 2018. The patients were grouped according to birth decade: 1980s (n = 19, mean LT4 starting dose 6.8 μg/kg/day), 1990s (n = 50, 7.4 μg/kg/day), 2000s (n = 59, 9.7 μg/kg/day), and 2010s (n = 44, 10.8 μg/kg/day). Results: TSH concentrations were higher during the first 2 years of life in children born in the 1980s compared to children born later. TSH concentrations were often subnormal in children receiving higher LT4 doses (children born in the 2000s and 2010s). However, symptoms of overtreatment were uncommon. Linear or head growth showed no differences between the groups during the first 2 years of life. Although growth was within the normal spectrum, children in all groups were shorter than their target length at 2 years and their weight-for-length was above the mean through the first 2 years of life. Discussion: Current treatment practice with higher LT4 dose normalizes TSH rapidly without significant increase in side effects. However, irrespective of initial LT4 dose, children were shorter than expected at 2 years of age. Effects of different initial LT4 dose on cognitive development urges further investigation.

The needs of children receiving end of life care and the impact of a paediatric palliative care team: a retrospective cohort study.

Early implementation of PPC optimises the use of hospital resources, minimises invasive procedures and therapies, and may develop effective and sustainable alternatives which are better suited to the needs of children and families. • In recent years, there has been an increased prevalence of complex chronic condition (CCC), which has led to more specialised and prolonged medical care until the end of life. • There are few paediatric studies on use of hospital resources and the invasiveness of procedures in the last year of life for children. • This study is one of the few to provide a comprehensive characterisation of the last year of life of children/adolescents with CCC. • Timely referral to a specialised PPC team optimises the use of hospital resources, minimise invasive procedures and develop effective and sustainable alternatives which are better suited to the needs of children and/or families.

Long-Term Follow-up of Dutch Patients with Sickle Cell Disease Diagnosed By Newborn Screening - Effect on the Morbidity and Mortality in the Netherlands

Background: Sickle cell disease (SCD) is associated with increased morbidity and mortality compared to the general population. To enable early preventive measures to improve clinical outcome, newborn screening for SCD was introduced in January 2007 in the Netherlands. The objective of this study is to assess the residual risk of death and the incidence of major disease-related complications during the first fifteen years of life in children diagnosed with SCD by newborn screening. Methods: In this prospective, national multicenter cohort study, all children born after 1 January 2007 and diagnosed with SCD by newborn screening were included. Following informed consent, data were collected from medical files on SCD genotype, treatment, mortality and occurrence of major disease-related complications including hospitalization for vaso-occlusive crises (VOC), severe infections (sepsis, meningitis, osteomyelitis) and neurological complications. Overall survival and survival without specific SCD-related complications were analyzed by Kaplan-Meier curves. Results: Preliminary data of 197 (38%) of the 520 eligible subjects from 8 centers in the Netherlands, with a total follow-up of 1,585 patient-years are presented. The median age on July 1st 2022 was 8.0 years (IQR range: 4.0 - 11.0 years). The majority of children (55%) had severe SCD (genotypes HbSS or HbSβ0 thalassemia), the remainder had another genotype including HbSC or HbSβ+ thalassemia. Survival at the age of 15 years was 99.5%. One patient died at the age of 1 year due to pneumococcal sepsis. Eight patients (4%) had a severe infection (meningitis, sepsis, osteomyelitis) caused by Streptococcus Pneumoniae in 3/8 cases with 1 fatal outcome as described above. Two patients experienced a symptomatic cerebral infarction at the age of 11 months and 1.5 years, respectively. Both patients had comorbidities, increasing the risk of a cerebral infarction. The mean survival time without admission for VOC was 7.3 years (95% CI: 6.2-8.5) for HbSS/HbSβ0 thalassemia and 11.5 years (95% CI: 10.1-12.8) for HbSC/HbSβ+ thalassemia, respectively (p < 0.001) (Figure 1). Conclusion: In this Dutch cohort of neonatally screened patients with SCD, infectious complications were the main cause of severe comorbidity and mortality. Further analysis to identify risk factors for infectious complications will be performed in the final analyses to target additional preventive measures that may lower the risk of infection in this specific group of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An EQ-5D-Y-3L Value Set for Belgium.

In Belgium, a value set for children and adolescents for a generic health-related quality-of-life measure is not available. To inform drug pricing and make resource allocation decisions for children and adolescents, national tax-payers' preferences for youth health states should be known. We aimed to obtain a value set for EQ-5D-Y-3L in Belgium, following the international youth valuation protocol for data collection. Composite Time Trade-Off interviews were conducted in a sample of 200 adults, either face to face or via video conferencing. Another sample of 1000 adults completed an online discrete choice experiment survey. All adults were asked to take the perspective of a 10-year-old child for both methods. Both samples were representative for Belgium in terms of age, sex and region. A latent class analysis was selected to obtain the relative importance of the five dimensions and their levels based on the discrete choice experiment data, which were anchored with the composite Time Trade-Off censored value for the worst health state (33333). Preferences from Belgian adults revealed a mean censored value for 33333 for children and adolescents of -0.475. All the estimated coefficients of the modelwith 4 latent classes were statistically significant and showed higher disutility as severity levels increase. The most important health dimension was pain/discomfort, followed by feeling sad/worried/unhappy. This study presents the Belgian EQ-5D-Y-3L value set, which will be included in the Belgian pharmacoeconomic guidelines. The value set enables the calculation of quality-adjusted life-years in children and adolescents, allowing a cost-effectiveness evaluation of health technologies and their youth-specific price setting.

Incidence, kinetics, and risk factors for intra- and extracranial cerebral arteriopathies in a newborn sickle cell disease cohort early assessed by transcranial and cervical color Doppler ultrasound.

The risk of stroke in children with sickle cell disease (SCD) is detected by abnormal intracranial arterial time-averaged mean of maximum velocities (TAMVs ≥200 cm/s). Recently, extracranial internal carotid artery (eICA) arteriopathy has been reported, and a cross-sectional study showed that eICA-TAMVs ≥160 cm/s are significantly associated with eICA kinkings and stenosis. The cumulative incidence of and predictive risk factors for intracranial arteriopathy are well described in sickle cell anemia (SCA=SS/Sβ0) but are lacking for SC/Sβ+ children, as is the cumulative incidence of eICA arteriopathy. We report a prospective longitudinal cohort study including 493 children with SCD (398 SCA, 95 SC/Sβ+), all assessed by transcranial and cervical color Doppler ultrasound. Cerebral MRI/MRA data were available in 375 children with SCD and neck MRA in 365 children. eICA kinkings were defined as eICA tortuosities on neck MRA, with an internal acute angle between the two adjacent segments <90°. The median follow-up was 10.6 years. The cumulative incidence of kinkings was significantly lower in SC/Sβ+ children than in children with SCA, and no SC/Sβ+ child developed intra- or extracranial stenotic arteriopathy. The 10-year KM estimate of cumulative incidence (95% CI) for eICA-TAMVs ≥160 cm/s revealed its development in the 2nd year of life in children with SCA, reaching a plateau of 17.4% (13.2–21.6%) by about 10 years of age, while the plateau for eICA stenosis was 12.3% (8.3–16.3%). eICA assessment identified 13.5% (9.3–17.7%) patients at risk of stroke who were not detected by transcranial color Doppler ultrasound. We also show, for the first time, that in addition to a congenital origin, eICA kinkings sin patients with SCD can develop progressively with aging as a function of eICA-TAMVs, themselves related to anemia severity. Ongoing hydroxyurea treatment was significantly associated with a lower risk of abnormal intracranial arteriopathy and eICA kinkings. After adjustment with hydroxyurea, baseline low hemoglobin, high reticulocyte, and WBC counts remained independent risk factors for intracranial arteriopathy, while low hemoglobin and SEN β-haplotype number were independent risk factors for extracranial arteriopathy. The association between extracranial arteriopathy and SEN β-haplotype number suggested a genetic link between the ethnic origin and incidence of eICA kinkings. This prospective cohort study shows the importance of systematically assessing the eICA and of recording biological parameters during the 2nd year of life before any intensive therapy to predict the risk of cerebral arteriopathy and treat patients with severe baseline anemia.

P1502: LONG-TERM FOLLOW-UP OF DUTCH PATIENTS WITH SICKLE CELL DISEASE DIAGNOSED BY NEONATAL SCREENING – EFFECT ON THE MORBIDITY AND MORTALITY IN THE NETHERLANDS.

Background: Sickle cell disease (SCD) is associated with increased morbidity and mortality compared to the general population. To initiate early preventive measures, newborn screening for SCD has been introduced in January 2007 in the Netherlands. Aims: The objective of this study is to assess the effectiveness of this neonatal screening for SCD by describing the residual risks of death and major disease-related events during the first fourteen years of life in children diagnosed with SCD at birth in the Netherlands. Methods: Here we report the first data of the largest center (Amsterdam UMC) of this prospective, national multicenter cohort study. Following informed consent, data were collected from medical files of all children diagnosed by neonatal screening. Descriptive data on SCD genotype and occurrence of major disease-related events are presented, including hospitalization for vaso-occlusive crisis (VOC), acute chest syndrome, severe infections and neurological complications. Overall survival and survival without specific SCD-related complications were analyzed by Kaplan-Meier curves. Results: Up until now, 98 (56%) out of 174 eligible subjects from this institution were included, with a total follow-up of 805 patient-years. The majority (55%) had the severe genotype (HbSS/ beta0-thalassemia), the remainder had genotypes HbSC or HbS/beta+-thalassemia. Survival by the age of 14 was 98.9%, with 1 death at the age of 1 years due to sepsis, most likely related to SCD. Seven patients (7.1%) had a severe infection (meningitis, sepsis, osteomyelitis) caused by Streptococcus Pneumoniae in 3/7 cases. Antibiotic prophylaxis was prescribed for all 7 patients before they reached the age of 1 year, and 6/7 patients had been fully vaccinated with the 23 valent pneumococcal vaccine. Two patients experienced a symptomatic cerebral infarction at the age of 11 months and 1.5 years, respectively. At the age of 10 years the survival without hospitalization for vaso-occlusive crisis was 27% (95% CI: 12.7 – 43.14%) and 51% (25.3 – 72.0%) for the SS/Sβ0 and SC/Sβ+ genotype, respectively. Image:Summary/Conclusion: In this cohort of neonatally screened patients with SCD, the SCD-related mortality and morbidity is still impressive with 1% mortality, 7 severe infections, and 2 patients with a CVA. A final analysis of the effect of neonatal screening for SCD will follow after completion of data collection in all participating centers in the Netherlands.