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Despite the significant reductions seen in under-5 child mortality in Ethiopia over the last two decades, more than 10,000 children still die each year in Tigray Region alone, of whom 75% die from preventable diseases. Using an equity lens, this study aimed to investigate the social determinants of child health in one particularly vulnerable district as a means of informing the health policy decision-making process. An exploratory qualitative study design was adopted, combining focus group discussions and qualitative interviews. Seven Focus Group Discussions with mothers of young children, and 21 qualitative interviews with health workers were conducted in Wolkayit district in May-June 2015. Data were subjected to thematic analysis. Mothers’ knowledge regarding the major causes of child mortality appeared to be good, and they also knew about and trusted the available child health interventions. However, utilization and practice of these interventions was limited by a range of issues, including cultural factors, financial shortages, limited female autonomy on financial resources, seasonal mobility, and inaccessible or unaffordable health services. Our findings pointed to the importance of a multi-sectoral strategy to improve child health equity and reduce under-5 mortality in Wolkayit. Recommendations include further decentralizing child health services to local-level Health Posts, and increasing the number of Health Facilities based on local topography and living conditions.

Services that aim to prevent mother-to-child HIV transmission (PMTCT) can simultaneously reduce the overall impact of HIV infection in a population while also improving maternal and child health outcomes. By taking a health equity perspective, this retrospective case control study aimed to compare the health status of under-5 children born to HIV-positive and HIV-negative mothers in Tigray Region, Ethiopia. Two hundred and thirteen HIV-positive women (cases), and 214 HIV-negative women (controls) participated through interviews regarding their oldest children. Of the children born to HIV-positive mothers, 24% had not been tested, and 17% of those who had been tested were HIV-positive themselves. Only 29% of the HIV-positive children were linked to an ART programme. Unexpectedly, exposed HIV-negative children had fewer reports of perceived poor health as compared to unexposed children. Over 90% of all the children, regardless of maternal HIV status, were breastfed and up-to-date with the recommended immunizations. The high rate of HIV infection among the babies of HIV-positive women along with their low rates of antiretroviral treatment raises serious concerns about the quality of outreach to pregnant women in Tigray Region, and of the follow-up for children who have been exposed to HIV via their mothers.

Objectives: To assess completeness and accuracy of the family folder in terms of capturing community-level health data.

Study design: A capture–recapture method was applied in six randomly selected districts of Tigray Region, Ethiopia.

Participants: Child health data, abstracted from randomly selected 24 073 family folders from 99 health posts, were compared with similar data recaptured through household survey and routine health information made by these health posts.

Primary and secondary outcome measures: Completeness and accuracy of the family folder data; and coverage selected child health indicators, respectively.

Results: Demographic data captured by the family folders and household survey were highly concordant, concordance correlation for total population, women 15–49 years age and under 5-year child were 0.97 (95% CI 0.94 to 0.99, p<0.001), 0.73 (95% CI 0.67 to 0.88) and 0.91 (95% CI 0.85 to 0.96), respectively. However, the live births, child health service indicators and child health events were more erratically reported in the three data sources. The concordance correlation among the three sources, for live births and neonatal deaths was 0.094 (95% CI −0.232 to 0.420) and 0.092 (95% CI −0.230 to 0.423) respectively, and for the other parameters were close to 0.

Conclusion: The family folder system comprises a promising development. However, operational issues concerning the seamless capture and recording of events and merging community and facility data at the health centre level need improvement.

OBJECTIVE: To investigate cross-sectional associations between self-reported recent pain and alcohol use/abstinence, and previous-day pain and previous-week alcohol consumption in adults aged 50 + in six low- and middle-income countries (LMICs). METHODS: The WHO Study on global AGEing and adult health (SAGE) Wave 1 (2007-2010) in China, Ghana, India, Mexico, Russia and South Africa is the data source. Prevalence of alcohol use/abstinence is reported by previous-day and previous-month pain. Multinomial logistic regressions (crude and adjusted for sex and country) tested associations between recent pain and alcohol use in the pooled multicountry sample. RESULTS: Across the six SAGE countries, about one-third of respondents reported alcohol use, being highest in Russia (74%) and lowest in India (16%). Holding the effects of sex and country constant, compared with abstainers, people with previous-day pain were more likely to be previous-day or other users. With regard to the quantity and frequency of alcohol use, people with previous-day pain were more likely to be non-heavy drinkers. CONCLUSION: Overall, we found that, in this population of older adults in six LMICs, recent pain was associated with moderate use of alcohol, although there were differences between countries. The findings provide a platform for country-specific research to better understand bi-directional associations between pain and alcohol in older adults.

BACKGROUND: Electroconvulsive therapy (ECT) has long been used for treating individuals with treatment-resistant depression (TRD). Esketamine has recently emerged as a new treatment for TRD due to its rapid antidepressant effects. To further inform the decision regarding choice of treatment, this paper aims to evaluate whether ECT or esketamine is the more cost-effective option.

METHODS: The cost-effectiveness was derived as cost per quality-adjusted life-year (QALY) using a Markov model from a societal and life-time perspective. The incremental cost-effectiveness ratio (ICER) was calculated. Health states included different depression and remission states and death. Data to populate the model was derived from randomised controlled trials and other research. Various sensitivity analyses were carried out to test the robustness of the model.

RESULTS: The base case scenario shows that ECT is cost-effective compared to esketamine and yields more QALYs at a lower cost. The sensitivity analysis shows that ECT is cost-effective in all scenarios and ECT dominates esketamine in 12 scenarios.

CONCLUSIONS: This study found that, from a cost-effectiveness point of view, ECT should be the first-hand option for individuals with TRD, when other first line treatments have failed. Considering the lack of economic evaluation of ECT and esketamine, this study is of great value to decision makers.

BACKGROUND: The lack of adequate documentation of deaths, and particularly their cause, is often noted in African and Asian settings, but practical solutions for addressing the problem are not always clear. Verbal autopsy methods (interviewing witnesses after a death) have developed rapidly, but there remains a lack of clarity as to how these methods can be effectively applied to large unregistered populations. This paper sets out practical details for undertaking a representative survey of cause-specific mortality in a population of several million, taking Tigray Region in Ethiopia as a prototype.

SAMPLING: Sampling was designed around an expected level of maternal mortality ratio of 400 per 100,000 live births, which needed measuring within a 95% confidence interval of approximately ±100. Taking a stratified cluster sample within the region at the district level for logistic reasons, and allowing for a design effect of 2, this required a population of around 900,000 people, equating to six typical districts. Since the region is administered in six geographic zones, one district per zone was randomly selected.

IMPLEMENTATION: The survey was implemented as a two-stage process: first, to trace deaths that occurred in the sampled districts within the preceding year, and second to follow them up with verbal autopsy interviews. The field work for both stages was undertaken by health extension workers, working in their normally assigned areas. Most of the work was associated with tracing the deaths, rather than undertaking the verbal autopsy interviews.

DISCUSSION: This approach to measuring cause-specific mortality in an unregistered Ethiopian population proved to be feasible and effective. Although it falls short of the ideal situation of continuous civil registration and vital statistics, a survey-based strategy of this kind may prove to be a useful intermediate step on the road towards full civil registration and vital statistics implementation.

OBJECTIVES: Between 1984 and 1996, Sweden experienced an "epidemic" of clinical celiac disease in children <2 years of age, attributed partly to changes in infant feeding. Whether infant feeding affects disease occurrence and/or the clinical presentation remains unknown. We investigated and compared the total prevalence of celiac disease in 2 birth cohorts of 12-year-olds and related the findings to each cohort's ascertained infant feeding.

METHODS: A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios.

RESULTS: The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60-0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding).

CONCLUSIONS: A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable.

BACKGROUND: Both undiagnosed celiac disease and some chronic childhood diseases are associated with lower academic achievement. However, there is little knowledge of achievements in those diagnosed with celiac disease. Our aim was to investigate school achievements in upper secondary school among Swedish adolescents with celiac disease.

METHODS: We performed a retrospective cohort study using register data. We analyzed choice of upper secondary school program, completion of upper secondary school including achievements of basic eligibility for college/university, and final grade in individuals with celiac disease diagnosed before 15 years of age, born 1991-97. We compared with the Swedish population of the same birth years. Analyses were adjusted for sex, year of birth, living region at 17 years of age, and parental education as well as income.

RESULTS: The cohort included 734 074 individuals, whereof 3 257 (62% females) with celiac disease. There was no significant difference in choice of upper secondary school program. No significant difference was found in completion or achieving basic eligibility for college/university in adjusted analyses. The mean final grade in the celiac disease group was 13.34 (standard deviation 4.85) compared to 12.78 (standard deviation 5.01) in the reference population (p < 0.001), out of a maximum of 20. The effect of celiac disease on final grade remained in adjusted analyses (p = 0.012).

CONCLUSIONS: We found that diagnosed celiac disease does not negatively affect school achievements in upper secondary school. This finding suggests the diagnosis, treatment and follow-up programs of celiac disease could reverse potential deleterious academic processes.

Objectives: The aims of the study were to ascertain whether the Celiac Dietary Adherence Test (CDAT) could contribute in determining adherence to a gluten-free diet in celiac disease patients and to evaluate the diet adherence and well-being of a study population five years after a celiac disease screening known as “Exploring the Iceberg of Celiacs in Sweden”.

Methods: Through the screening, 90 adolescents (born 1997) were diagnosed with biopsy-proven celiac disease at twelve-years of age. Of them, 70 (78%) came to a five-year follow-up where anti–tissue transglutaminase antibodies 2 (TG2-IgA) was tested and a questionnaire was filled in, including CDAT, which consists of seven questions related to adherence. Non-parametrical tests were utilized to determine associations between adherence measures.

Results: Among the adolescents, 86% were adherent to a gluten-free diet five years after screening, 38% reported their general well-being as excellent, 50% very well, and 12% well. Statistically significant associations were seen between TG2-IgA and the CDAT score (p=0.033), and the self-reported adherence question and the CDAT score (p < 0.001).

Conclusions: The screening-detected adolescents reported a high level of well-being and adherence to a gluten-free diet five years after screening. We conclude that the CDAT can be used in clinical practice as an estimation of adherence to a gluten-free diet. It would be most suitable to use in conjunction with currently used adherence measures, but can also be used as a stand-alone method when others are not accessible.

Aims: Between 1985 and 1996, Sweden experienced an "epidemic" of celiac disease with a fourfold increase in incidence in young children. Timing and amount of gluten introduced during infancy have been thought to explain this "epidemic". We aimed to study whether the cumulative incidence of type 1 diabetes differs between children born during the "epidemic" compared to children born after.

Methods: This is a national register study in Sweden comparing the cumulative incidence of type 1 diabetes in two birth cohorts of 240 844 children 0-17 years old born 1992-1993, during the "epidemic", and 179 530 children born 1997-1998, after the "epidemic". Children diagnosed with type 1 diabetes were identified using three national registers.

Results: The cumulative incidence of type 1 diabetes by the age of 17 was statistically significantly higher in those born after the "epidemic" 0.77% than in those born during the "epidemic" 0.68% (p < 0.001).

Conclusion: The incidence of type 1 diabetes is higher in those born after the epidemic compared to those born during the epidemic, which does not support the hypothesis that gluten introduction increases the incidence of T1D. Changes in gluten introduction did not halt the increased incidence of type 1 diabetes in Sweden.

OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk.

METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guerin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis.

RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60-1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31-0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years.

CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies. Pediatrics 2012;130:e63-e70

Background: Celiac disease occurs worldwide in approximately 1% of the population, whereof the majority of cases are undiagnosed. Sweden experienced an epidemic (1984-1996) of clinically detected celiac disease in children below 2 years of age, partly attributed to changes in infant feeding. Whether the epidemic constituted a change in disease occurrence and/or a shift in the proportion of diagnosed cases remains unknown. Moreover, the cause of the epidemic is not fully understood.

Objective: To increase the knowledge regarding the occurrence of celiac disease in Sweden, with focus on the epidemic period and thereafter, as well as the etiology of celiac disease in general, by investigating the Swedish epidemic and its potential causes.

Methods: We performed a two-phased cross-sectional multicenter screening study investigating the total prevalence, including both clinically- and screening-detected cases, of celiac disease in 2 birth cohorts of 12-year-olds (n=13 279): 1 of the epidemic period (1993) and 1 of the post-epidemic period (1997). The screening strategy entailed serological markers analyses, with subsequent small intestinal biopsy when values were positive. Diagnosis was ascertained in clinical cases detected prior to screening. Infant feeding practices in the cohorts were ascertained via questionnaires. An ecological approach combined with an incident case-referent study (475 cases, 950 referents) performed during the epidemic were used for investigating environmental- and lifestyle factors other than infant feeding. Exposure information was obtained via register data, a questionnaire, and child health clinic records. All studies utilized the National Swedish Childhood Celiac Disease Register.

Results: The total prevalences of celiac disease were 2.9% and 2.2% for the 1993 and 1997 cohorts, respectively, with 2/3 cases unrecognized prior to screening. Children born in 1997 had a significantly lower celiac disease prevalence compared to those born in 1993 (prevalence ratio, 0.75; 95% confidence interval [CI], 0.60-0.93). The cohorts differed in infant feeding; more specifically in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding. Of the environmental and lifestyle factors investigated, no additional changes over time coincided with the epidemic. Early vaccinations within the Swedish program were not risk factors for celiac disease. Early infections (≥3 parental-reported episodes) were associated with increased risk for celiac disease (adjusted odds ratio [OR] 1.5; 95% CI, 1.1-2.0), a risk that increased synergistically if, in addition to having ≥3 infectious episodes, the child was introduced to gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10). Early infections probably made a minor contribution to the Swedish epidemic through the synergistic effect with gluten, which changed concurrently. In total, approximately 48% of the epidemic could be explained by infant feeding and early infections.

Conclusion: Celiac disease is both unexpectedly prevalent and mainly undiagnosed in Swedish children. Although the cause of the epidemic is still not fully understood, the significant difference in prevalence between the 2 cohorts indicates that the epidemic constituted a change in disease occurrence, and importantly, corroborates that celiac disease can be avoided in some children, at least up to 12 years of age. Our findings suggest that infant feeding and early infections, but not early vaccinations, have a causal role in the celiac disease etiology and that the infant feeding practice – gradually introducing gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding – is favorable.

BACKGROUND: Celiac disease is defined as a 'chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Sweden has experienced an "epidemic" of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic.

METHODS: A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child's general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents.

RESULTS: Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001).

CONCLUSION: This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.

Objetive: Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases.

Patients and methods: All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease.

Results: Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7-11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17-23). The total prevalence was 29/1000 (95% CI 25-33).

Conclusions: The celiac disease prevalence of 29/1000 (3%)-with two thirds of cases undiagnosed before screening-is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.

BACKGROUND: Knowledge regarding the health-related quality of life (HRQoL) of children with celiac disease remains limited and inconclusive. We investigated the HRQoL of three groups of 12-year-olds with: i) undetected celiac disease ii) clinically diagnosed celiac disease, and iii) without celiac disease.

METHODS: A school-based cross-sectional multicenter screening study invited 18 325 children, whereof 68% consented to participate. Participants provided a blood sample, which was later analyzed for anti-tissue-tranglutaminase antibodies, and alongside filled in a questionnaire. When anti-tissue-tranglutaminase antibodies were elevated, a small intestinal biopsy verified the screening-detected celiac disease diagnosis. Self-reported HRQoL was measured using Kidscreen, a generic 52 items instrument with proven reliability and validity. Scores were linearly transformed into a 0-100 scale with higher values indicating better HRQoL. Mean values with standard deviations (mean +/- SD) were compared, and uni- and multivariate logistic regression models tested the odds of a low HRQoL among children with undetected or diagnosed celiac disease, respectively.

RESULTS: Children with undetected celiac disease (n = 238) reported similar HRQoL as children without celiac disease (n = 12 037) (83.0 +/- 11.0 vs. 82.5 +/- 11.3, P = 0.51), and also similar HRQoL (82.2 +/- 12.2, P = 0.28) to that of children with diagnosed celiac disease (n = 90), of whom 92% were adherent to treatment. Having undetected celiac disease did not increase the odds of low overall HRQoL, independent of sex, area of residence, study year and occurrence of gastrointestinal symptoms (adjusted odds ratio 0.77, 95% CI 0.54-1.10). Comparable results were seen for diagnosed celiac disease cases (adjusted odds ratio 1.11, 95% CI 0.67-1.85) CONCLUSION: Children with undetected celiac disease reported comparable HRQoL as their peers with diagnosed celiac disease, and those without celiac disease, when reporting prior to receiving the diagnosis through screening. Thus, children with celiac disease, both untreated and diagnosed, perceive their HRQoL as unimpaired by their disease.

BACKGROUND AND AIMS: The only treatment for celiac disease is strict adherence to a gluten-free diet (GFD). We performed a systematic review to investigate the rate of adherence to a GFD in children with celiac disease, risk factors that affect adherence, and outcomes of non-adherence.

METHODS: We searched PubMed, Cochrane Library, EBSCO, and Scopus for studies through January 2019. We included observational studies of ≥50 children diagnosed with celiac disease and recommended for placement on a GFD. We collected data on adherence assessment (self-report, serology tests, structured dietary interview, biopsies, or assays for gluten immunogenic peptides), risk factors, and outcomes related to adherence. Findings were presented with medians, range, and a narrative synthesis.

RESULTS: We identified 703 studies; of these, 167 were eligible for full-text assessment and 49 were included in the final analysis, comprising 7850 children. Rates of adherence to a GFD ranged from 23% to 98%. Comparable rates (median rates of adherence, 75%-87%) were found irrespective of how assessments were performed. Adolescents were at risk of non-adherence and children whose parents had good knowledge about celiac disease adhered more strictly. Non-adherence associated with patient growth, symptoms, and quality of life.

CONCLUSION: In a systematic review of 49 studies of children with celiac disease, we found substantial variation in adherence to a GFD among patients. Rate of adherence was not associated with method of adherence measurement, so all methods appear to be useful, with lack of consensus on the ideal metric. Studies are needed to determine the best method to ensure adherence and effects on long-term health.

Aim: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction.

Methods: In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies.

Results: All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia.

Conclusion: The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine health care two years after their introduction.

Background: Celiac disease (CD) is increasing worldwide, which might be due to the changing environmental and lifestyle exposures. We aimed to explore how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood.

Methods: Using Sweden’s national registers we had access to information on 1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age. Logistic regression analyses were performed to determine how CD is associated with maternity, delivery and the neonatal period.

Results: Regardless of sex, a reduction in CD risk was observed in children born to mothers aged ≥35 years (odds ratio [OR] 0.8; 95 % confidence interval [CI] 0.7–0.9) and with high maternal income (OR 0.9; 95 % CI 0.8–0.9). Being a second-born child, however, was positively associated with CD. Among boys, elective caesarean delivery increased the risk of CD (OR 1.2; 95 % CI 1.0–1.4), while maternal overweight (OR 0.9; 95 % CI 0.8-0.9), premature rupture of the membrane (OR 0.4; 95 % CI 0.2–0.8) and low birth weight showed a negative association. Girls had an increased CD risk compared to boys and in girls the risk was increased by repeated maternal urinary tract infections (OR 1.1; 95 % CI 1.0–1.2).

Conclusions: Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD onset during childhood, suggesting the role of dysbiosis during early life. High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style.

AIM: To explore how 12-year-old Swedish children experienced being involved in a coeliac disease (CD) screening. METHODS: A qualitative approach was used to analyse short narratives written by children who had taken part in a school-based CD screening. Narratives were written after blood sampling, but prior to learning of the test results. Through an oscillation between the texts, codes, subcategories and four categories, a theme was generated describing the children's experience. RESULTS: The theme ''A Journey towards Confidence'' captures the overall experience of the screening. It illustrates that, although some children faced fear or anxiety, overall they had or were provided tools allowing them to cope well and experience a journey towards confidence. The categories describe conditions that contributed to the experience. The first, being involved, reflects the importance of involvement in receiving information and deciding to participate. Being a ''good citizen'' refers to feeling a duty to help and a trust to be treated fairly. Being able to cope with the screening was influenced by the children's ability to manage sensations and support received. The last category, being able to balance risk, illustrates that the children were able to balance the risks of screening when they had a realistic understanding of the disease and their vulnerability and had tamed their anxiety. CONCLUSIONS: This study increases the understanding of how 12-year-old Swedish children experienced participating in a CD screening and describes conditions important for a positive experience. We show that, although some children faced anxiety, they had, or were provided with, tools allowing them to cope well and gain confidence.

Background: Living with undiagnosed symptomatic coeliac disease is connected with deteriorated health, and persons with coeliac disease often wait a long time for their diagnosis. A mass screening would lower the delay, but its cost-effectiveness is still unclear. Our aim was to determine the cost-effectiveness of a coeliac disease mass screening at 12 years of age, taking a life course perspective on future benefits and drawbacks.

Methods: The cost-effectiveness was derived as cost per quality-adjusted life-year (QALY) using a Markov model. As a basis for our assumptions, we mainly used information from the Exploring the Iceberg of Celiacs in Sweden (ETICS) study, a school-based screening conducted in 2005/2006 and 2009/2010, where 13,279 12-year-old children participated and 240 were diagnosed with coeliac disease, and a study involving members of the Swedish Coeliac Association with 1031 adult participants.

Results: The cost for coeliac disease screening was 40,105 Euro per gained QALY. Sensitivity analyses support screening based on high compliance to a gluten-free diet, rapid progression from symptom-free coeliac disease to coeliac disease with symptoms, long delay from celiac disease with symptoms to diagnosis, and a low QALY score for undiagnosed coeliac disease cases.

Conclusions: A coeliac disease mass screening is cost-effective based on the commonly used threshold of 50,000 Euro per gained QALY. However, this is based on many assumptions, especially regarding the natural history of coeliac disease and the effects on long-term health for individuals with coeliac disease still eating gluten.

AIM: The aim of our study was to examine whether there is a difference in coeliac disease prevalence in regard to parents' education level and occupation, and whether this differs between screened and clinically diagnosed children at the age of 12 years.

METHODS: The study, Exploring the Iceberg of Celiacs in Sweden (ETICS), was a school-based screening study of 12-year-old children that was undertaken during the school years 2005/2006 and 2009/2010. Data on parental education and occupation were reported from parents of the children. Specifically, by parents of 10 710 children without coeliac disease, 88 children diagnosed with coeliac disease through clinical care, and 231 who were diagnosed during the study.

RESULTS: There were no statistically significant associations between occupation and coeliac disease for either the clinically detected (prevalence ratio 1.16; confidence interval 0.76-1.76) or screening-detected coeliac disease cases (prevalence ratio 0.86; confidence interval 0.66-1.12) in comparison with children with no coeliac disease. Also, there were no statistically significant associations for parental education and coeliac disease diagnosis.

CONCLUSION: There was no apparent relationship between coeliac disease and socio-economic position. Using parents' socio-economic status as a tool to help identify children more likely to have coeliac disease is not recommended.

OBJECTIVES: Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. However, data are lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers.

METHODS: A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1,695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid stimulating hormone and free thyroxine.

RESULTS: TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were: 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46).

CONCLUSIONS: The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicate that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

Coeliac disease (CD) is one of the most common chronic diseases of childhood. Follow-up of CD aims to ensure dietary adherence and prevent disease complications, but there are few real-world data on how its management in children is conducted. This study aimed to survey the follow-up practice of pediatric CD in Western Sweden. Two web-based surveys were distributed to all 22 pediatric outpatient clinics rendering answers from 48 physicians and 12 dietitians. Overall, clinical practice was similar throughout the region and in line with national and international CD guidelines, including an annual to biannually follow-up frequency and dietary adherence assessment through unstructured interviewing and serology measurements. The study identified possible areas of improvement, such as implementing a formal transition process to adult care and the use of validated questionaries to assess dietary adherence. Additionally, a positive attitude towards electronic-health technologies (eHealth) as part of CD follow-up was identified.

Recurrent pain and school failures are common problems in children visiting the school nurses office. The overall aim of the current study was to investigate the relationship between recurrent pain and academic achievement in school-aged children. Literature was searched in seven electronic databases and in relevant bibliographies. Study selection, data extraction, and study and evidence quality assessments were performed systematically with standardized tools. Twenty-one studies met the inclusion criteria and 13 verified an association between recurrent pain (headache, stomachache, and musculoskeletal pain) and negative academic achievement. Two longitudinal studies indicated a likely causal effect of pain on academic achievement. All studies had substantial methodological drawbacks and the overall quality of the evidence for the identified associations was low. Thus, children’s lack of success in school may be partly attributed to recurrent pain problems. However, more highquality studies are needed, including on the direction of the association and its moderators and mediators.

Monitoring adherence to a gluten-free diet is an important goal of coeliac disease management. Urine and stool gluten immunogenic peptide (GIP) assays provide an objective readout of gluten ingestion, with the former favoured due to its convenience and acceptability. This study assessed stool GIP excretion after low-dose gluten challenge designed to mimic accidental gluten exposure. A total of 52 coeliac participants undertook a randomised, double-blind gluten (50–1000 mg) or placebo challenge. Stool and urinary GIP, serology, dietary adherence and symptoms were assessed. Stool GIP was 100% sensitive for gluten intake ≥250 mg and 71% for 50 mg. Peak GIP detection was 12–36 h after gluten exposure. The mean stool GIP after 1000 mg gluten ingestion remained above the limit of quantification for 5 days. Urine GIP assessment had poor sensitivity for GIP excretion compared to stool. Serology, dietary adherence score and symptoms did not correlate with gluten excretion during lead-in. We conclude that stool GIP detection is highly sensitive, with levels related to gluten dose and time from ingestion. Weekly or bi-weekly testing will detect low-level exposure more effectively than urine GIP assessments or traditional methods. In this seronegative, apparently well-treated cohort, a high frequency of baseline-positive GIP suggests ongoing gluten exposure, but the assessment of patient behaviour and assay specificity is needed.

OBJECTIVE: We previously performed a population-based mass screening of coeliac disease in children aged 12 years in two birth cohorts resulting in 296 seropositive children, of whom 242 were diagnosed with coeliac disease after duodenal biopsies. In this follow-up study, we wanted to identify new cases in the screening population that tested negative-either converting from potential coeliac disease (seropositive but normal duodenal mucosa) or converting from seronegative at screening to diagnosed coeliac disease.

METHODS: All seropositive children were invited to a follow-up appointment 5 years after the screening with renewed serological testing and recommended endoscopic investigation if seropositive. Seronegative children in the screening study (n=12 353) were linked to the National Swedish Childhood Coeliac Disease Register to find cases diagnosed in healthcare during the same period.

RESULTS: In total, 230 (77%) came to the follow-up appointment, including 34 of 39 with potential coeliac disease. Of these, 11 (32%) had converted to coeliac disease. One new case was found in the National Swedish Childhood Coeliac Disease Register who received the diagnosis through routine screening in children with type 1 diabetes.

CONCLUSIONS: There is a high risk of conversion to coeliac disease among those with potential disease. However, a negative screening test was associated with a very low risk for a clinical diagnosis within a follow-up period of 5 years.

OBJECTIVE: Gastrointestinal problems are often seen in children with cerebral palsy, although the etiology and underlying mechanisms are not fully understood. Recent data point to significantly elevated levels of IgG antibody to dietary gluten in cerebral palsy independent of celiac disease, a gluten-mediated autoimmune enteropathy. We aimed to further characterize this antibody response by examining its subclass distribution and target reactivity in the context of relevant patient symptom profile.

METHODS: Study participants included children with cerebral palsy (n = 70) and celiac disease (n = 85), as well as unaffected controls (n = 30). Serum IgG antibody to gluten was investigated for subclass distribution, pattern of reactivity towards target proteins, and relationship with gastrointestinal symptoms and motor function.

RESULTS: The anti-gluten IgG antibody response in the cerebral palsy cohort was comprised of all four subclasses. However, in comparison with celiac disease, IgG1, IgG2, and IgG3 subclasses were significantly lower, whereas the IgG4 response was significantly higher in cerebral palsy. Within the cohort of cerebral palsy patients, levels of anti-gluten IgG1, IgG3, and IgG4 were greater in those with gastrointestinal symptoms, and the IgG3 subclass antibody correlated inversely with gross motor function. The anti-gluten IgG antibodies targeted a broad range of gliadin and glutenin proteins.

CONCLUSION: These findings reveal an anti-gluten IgG subclass distribution in cerebral palsy that is significantly different from that in celiac disease. Furthermore, the observed association between IgG subclass and symptom profile is suggestive of a relationship between the immune response and disease pathophysiology that may indicate a role for defects in gut immune and barrier function in cerebral palsy.

In their interesting article on coeliac disease (CD) and socio-economic status, Whyte et al (1) report that CD is more common in children living in areas of the UK with higher socio-economic status than areas with low status. In 1996, we reported that a group of 72 Swedish children with CD were breastfed for a significantly shorter time than the 288 age-matched reference children included in the study (2). In addition, infants with CD were less likely to be breastfed when gluten was introduced into their diet. This article is protected by copyright. All rights reserved.

Health system responsiveness is an indicator that can be used for evaluating how well healthcare systems respond to people's needs in non-clinical areas such as communication, autonomy and confidentiality. This study analyses health system responsiveness from the perspective of community-dwelling adults aged 50 and over in China, Ghana, India, the Russian Federation and South Africa using cross-sectional data from the World Health Organization Study on global AGEing and adult health. The aim is to assess and compare how individual, health condition and healthcare factors impact differently on outpatient and inpatient responsiveness.

Poor responsiveness is measured according to participants' responses to questions on a five-point Likert scale. Five univariate and multiple logistic regression models test associations between individual, health condition and healthcare factors and poor responsiveness. The final model adjusts for country.

Key results are that travel time is a major contributor to poor responsiveness across all countries. Similarly there are wealth inequalities in responsiveness. However no clear difference in responsiveness was observed in presentations for chronic versus other types of conditions.

This study provides an interesting baseline on older patients' perceived treatment within outpatient and inpatient facilities in five diverse low- and middle-income countries.

Background: Obesity among children and adolescents is a worldwide public health concern. Type 1 diabetes (T1D) and type 2 diabetes (T2D) incidence are increasing, with heredity and socioeconomic status as possible risk factors. How these factors affect the risk of childhood obesity remains unclear. The aim of this study was to investigate the association between obesity and parental diabetes among 12-year-olds in Sweden, and how it relates to parental education level.

Methods: We used data collected within the Exploring the Iceberg of Celiacs in Sweden (ETICS) study, a cross-sectional multicenter national screening study for celiac disease in 12-year-old children. Relative risk (RR) and confidence interval (CI) were calculated for the association between parental diabetes and obesity, also stratifying for gender and highest parental education.

Results: Among 11,050 children, for both children with parental T1D and T2D, 31% of the children were overweight or obese, compared with 21% among other children. Comparing those with parental T1D with those without parental T1D within gender, boys had a statistically significant higher risk [RR 1.6 (95% CI 1.3–2.0)], and girls had a nonsignificant increased risk [RR 1.3 (95% CI 0.95–1.8)], of being overweight. For children with parental T2D, both boys and girls had a statistically significant increased risk of 1.5. Parental education showed no sign of influencing the RRs.

Conclusions: Parental diabetes is associated with an increased risk of overweight among children, independent of parental education. Concomitant parental diabetes and overweight should be particularly alarming criteria when prioritizing preventive interventions at an early age.

Background: Untreated celiac disease is traditionally believed to be associated with malabsorption and underweight. However, studies describing body mass index (BMI) in individuals at the time of diagnosis have shown contradictory results. We investigated the differences in weight, height, and BMI in 12- year-old children with screening-detected celiac disease compared to their healthy peers.

Methods: In a population-based screening study of 12,632 12-year-old children, blood samples were analyzed for markers of celiac disease. Children with elevated markers were referred for a small bowel biopsy. Weight and height were measured in 239 out of 242 children with screening-detected celiac disease (57.3% girls) and in 12,227 children without celiac disease (48.5% girls). BMI was categorized according to the International Obesity Task Force. Age- and sex-specific cut-off points for underweight, normal weight, and overweight were used.

Results: Children with celiac disease weighed less and were shorter than their peers (median weight 45.2 kg, interquartile range (IQR) 40.2-52.2 kg vs. 47.0 kg, IQR 41.1-54.4 kg, respectively, p = 0.01; median height 156.5 cm, IQR 151.0-162.0 cm vs. 157.5 cm, IQR 152.0-163.0 cm, respectively, p = 0.04). In comparing those with celiac disease to their healthy peers, 4.2% vs. 5.2% were underweight, 82.0% vs. 72.8% were normal weight, and 13.8% vs. 21.9% were overweight, respectively. There was no association between being underweight and the risk of having undiagnosed celiac disease (Odds ratio (OR) 1.3, 95% CI 0.7-2.4), but the risk was significantly lower among overweight children (OR 0.56, 95% CI 0.4-0.8). Median BMI was slightly lower among the children with screening-detected celiac disease compared to their healthy peers (18.6 kg/m(2), IQR 17.1-19.8 kg/m(2) vs. 18.8 kg/m(2), IQR 17.2-21.1 kg/m(2), respectively, p = 0.05), but most of the celiac disease cases had a normal BMI.

Conclusions: At a population level, children with celiac disease weigh less, are shorter, and have a lower BMI compared to their peers without celiac disease, and this emphasizes the importance of early recognition and treatment of the condition. However, at an individual level, growth parameters are not reliable in establishing the diagnosis.

OBJECTIVES:: In a Swedish celiac disease screening study (Exploring the Iceberg of Celiacs in Sweden), we systematically reviewed the clinical diagnostic procedures with the aim to evaluate the diagnostic accuracy and to take advantage of lessons learned for improving diagnostic routines. MATERIALS AND METHODS:: A school-based celiac disease screening study involving 5 Swedish centers, with 10,041 invited 12-year-olds with 7567 consenting participation. All 192 children with elevated serological markers were recommended to undergo small-bowel biopsy, performed and evaluated according to local clinical routines. All of the mucosal specimens were reevaluated by 1 and, when needed, 2 expert pathologists to reach diagnostic consensus. RESULTS:: Small-bowel biopsies were performed in 184 children: 130 by endoscopy and 54 by suction capsule. Endoscopic biopsies were inconclusive in 0.6%, compared with 7.4% of biopsies by suction capsule. A patchy enteropathy was found in 9.1%. Reevaluation by the expert pathologist resulted in 6 additional cases with celiac disease and 1 cleared. Sixteen children with normal or inconclusive biopsies, 4 after endoscopy, and 12 after suction capsule were endoscopically rebiopsied, resulting in another 8 cases. The celiac disease prevalence of 30 of 1000 (95% confidence interval 26-34) was not statistically different from that previously reported. CONCLUSIONS:: The present review revealed the importance of controlling each step of the diagnostic procedure. Several cases would have been missed by relying only on local routines. To improve the quality of childhood celiac disease diagnostics, we recommend multiple endoscopic biopsies from both proximal and distal duodenum and standardized evaluation by a pathologist with good knowledge of celiac disease.

OBJECTIVES: To evaluate the gluten-free diet (GFD) adherenceafter one year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS: A total of 18,325 12 year olds were invited to participate in apopulation-based CD screening (ETICS- Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This sub-study included the 210 children with TG2-IgAevaluated both at the initialbiopsy occasion and at the one-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS: After one year, 83% (179/210) had normalizedTG2-IgA levels (<5U/mL). Among those who had >50 U/mL at diagnosis,25% (16/63) still had elevated TG2-IgA but for the majority their initial values were more than halved. Most reported a high level ofGFD adherence ('always' 75%(158/193) and 'often' 14%(30/193)), and 75% (145/193) reported always adhereingcombined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely, however, a majority of these initially had the highestTG2-IgA levels. CONCLUSIONS: GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12yearolds. Almost all had normalized serology and reported GFD adherenceat the one-year follow-up. However, a few adolescents whoreported GFD adherence still had elevated TG2-IgA levelssuggesting more severe disease and/or non-adherence.

OBJECTIVES: To evaluate any potential correlation between anti-tissue transglutaminase antibodies of type immunoglobulin A (tTG-IgA) and the degree of gluten induced enteropathy in children participating in a screening study for celiac disease (CD) and to assess to what extent the revised ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) guidelines cover this group of patients.

METHODS: This is a sub-study of a cross-sectional CD screening study, ETICS (Exploring the Iceberg of Celiacs in Sweden), a two-phased study performed during 2005-2006 and 2009-2010. The 13,279 participating children had a blood test obtained and those with positive tTG-IgA were recommended a small intestinal biopsy. The tTG-IgA levels at the time of biopsy were compared with the assessment of the biopsy.

RESULTS: There were 267 children included, of whom 230 were diagnosed with CD. Out of all children, 67 children had low tTG-IgA levels (<5 U/mL), whereof 55% had Marsh 3 lesions. All children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, i.e. 50 U/mL, were diagnosed with CD. Lowering the cut-off to 3 U/mL, all but one child with 30 U/mL got CD diagnosis.

CONCLUSION: By adapting the revised ESPGHAN criteria, biopsies could have been omitted in a fourth of all cases. Our results indicate, that the criteria might be useful even on screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.