Lars Åke Persson

Epidemic of coeliac disease in Swedish children.

Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population‐based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore, we collected national data on a yearly basis on duration of breastfeeding, intake of gluten‐containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200‐240 cases per 100 000 person years, followed from 1995 by a sharp decline to the previous level of 50‐60 cases per 100 000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified.

Dietary factors and the risk of developing insulin dependent diabetes in childhood.

OBJECTIVE--To study different nutrients and food additives as risk factors for insulin dependent diabetes mellitus in childhood. DESIGN--Prospective case-control study. Parents of the children being studied were asked to fill in a questionnaire regarding the childrens frequency of consumption of various foods. Parents of children with diabetes were asked about the period before onset of the disease. SETTING--Population based study throughout Sweden. SUBJECTS--339 Children aged 0-14 who had recently developed insulin dependent diabetes mellitus and 528 control children matched for age, sex, and county of residence who were traced through the official Swedish population register. MAIN OUTCOME MEASURES--Foods were classified according to their content of protein, fat, carbohydrates, monosaccharides or disaccharides, nitrosamines, nitrates or nitrites, vitamin C, and fibres. The frequency of intake was categorised as high, medium, and low and the relative risk for developing insulin dependent diabetes was estimated for the three frequencies of intake and calculated as odds ratios. RESULTS--Significant linear trends for dose response in odds ratios by frequency of intake were shown for solid foods containing high amounts of protein (odds ratio for low frequency of intake 1.0; medium 2.3; and high 5.5), and nitrosamines (1.0; 1.7; 2.6) and significant but non-linear trends were found for carbohydrates (1.0; 1.3; 4.4) and nitrates or nitrites (1.0; 0.8; 2.4). The significant trends were not affected when the results were standardised for possible confounders. No significant increases in odds ratios were found for protein, monosaccharides and disaccharides, vitamin C, and fibres. CONCLUSION--Nutrients and food additives such as protein, carbohydrate, and nitrosamine compounds may influence the risk of developing insulin dependent diabetes in childhood and significant trends in odds ratios indicate a causal relation.

Arsenic Exposure During Pregnancy and Size at Birth: A Prospective Cohort Study in Bangladesh

The authors evaluated the association of prenatal arsenic exposure with size at birth (birth weight, birth length, head and chest circumferences). This prospective cohort study, based on 1,578 mother-infant pairs, was conducted in Matlab, Bangladesh, in 2002-2003. Arsenic exposure was assessed by analysis of arsenic in urine collected at around gestational weeks 8 and 30. The association of arsenic exposure with size at birth was assessed by linear regression analyses. In analysis over the full range of exposure (6-978 microg/L), no dose-effect association was found with birth size. However, significant negative dose effects were found with birth weight and head and chest circumferences at a low level of arsenic exposure (<100 microg/L in urine). In this range of exposure, birth weight decreased by 1.68 (standard error (SE), 0.62) g for each 1-microg/L increase of arsenic in urine. For head and chest circumferences, the corresponding reductions were 0.05 (SE, 0.03) mm and 0.14 (SE, 0.03) mm per 1 microg/L, respectively. No further negative effects were shown at higher levels of arsenic exposure. The indicated negative effect on birth size at a low level of arsenic exposure warrants further investigation.

High prevalence of undiagnosed coeliac disease in adults: a Swedish population-based study

Objective. To determine the prevalence of coeliac disease in a population‐based sample of Swedish adults.

Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries

BACKGROUND Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30-40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain. METHODS Using extant longitudinal birth cohorts (n=19) with data on birthweight, gestational age and child anthropometry (12-60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth. RESULTS We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5-3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively. CONCLUSIONS This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh.

Background: Arsenic is a potent human carcinogen and toxicant. Elevated concentration of arsenic in drinking water is a major public-health problem worldwide. We evaluated risks of adult mortality (due to cancer and cardiovascular and infectious diseases) in relation to arsenic exposure through drinking water. Methods: A cohort analysis was applied to survival data prospectively collected during 1991–2000 in a health and demographic surveillance system in Matlab, Bangladesh, where tubewells were installed beginning in the early 1970s. A total of 115,903 persons aged 15 or more years on 1 January 1991 were available for analysis. In this period, 9015 people died and 22,488 were lost to follow-up. Arsenic exposure data were derived from a survey in 2002–2003 of past and current water use and arsenic concentrations in all tubewells. We estimated risk of excess mortality in relation to arsenic exposure, using proportional hazards models. Results: Even at low levels (10–49 μg/L) of arsenic in drinking water, we observed increased risk of death due to all nonaccidental causes (hazard ratio = 1.16 [95% confidence interval = 1.06–1.26]). Increased risks at exposure of 50–149 μg/L were observed for death due to cancers (1.44 [1.06–1.95]), cardiovascular disease (1.16 [0.96–1.40]), and infectious diseases (1.30 [1.13–1.49]). We observed clear dose-response relationships for each of these causes. Conclusions: Arsenic exposure through drinking water has generated excess adult mortality after 20–30 years of exposure.

Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh.

Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n=140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.

Prevalence of arsenic exposure and skin lesions. A population based survey in Matlab, Bangladesh

Study objective: To assess prevalence of arsenic exposure through drinking water and skin lesions, and their variation by geographical area, age, sex, and socioeconomic conditions. Design, setting, and participants: Skin lesion cases were identified by screening the entire population above 4 years of age (n = 166 934) living in Matlab, a rural area in Bangladesh, during January 2002 and August 2003. The process of case identification involved initial skin examinations in the field, followed by verification by physicians in a clinic, and final confirmation by two independent experts reviewing photographs. The tubewell water arsenic concentrations (n = 13 286) were analysed by atomic absorption spectrometry. Drinking water history since 1970 was obtained for each person. Exposure information was constructed using drinking water histories and data on water arsenic concentrations. Main results: The arsenic concentrations ranged from <1 to 3644 μg/l, and more than 70% of functioning tubewells exceeded the World Health Organisation guideline of 10 μg/l. Arsenic exposure had increased steadily from 1970s to the late 1990s, afterwards a decrease could be noted. In total, 504 skin lesions cases were identified, and the overall crude prevalence was 3/1000. Women had significantly higher cumulative exposure to arsenic, while men had significantly higher prevalence of skin lesions (SMR 158, 95% CI 133 to 188). The highest prevalence occurred in 35–44 age groups for both sexes. Arsenic exposure and skin lesions had a positive association with socioeconomic groups and achieved educational level. Conclusions: The result showed sex, age, and socioeconomic differentials in both exposure and skin lesions. Findings clearly showed the urgency of effective arsenic mitigation activities.

Children born in the summer have increased risk for coeliac disease.

Study objective: Coeliac disease, also called permanent gluten sensitive enteropathy, is being recognised as a widespread health problem. Defining the possible role of environmental factors in its aetiology might open doors to primary prevention. This study therefore analysed if the risk for coeliac disease varies with month of birth as a proxy for a seasonal pattern for possible causal environmental exposure(s). Design: A population based incidence register of coeliac disease in children below 15 years of age covering the period from 1973 to 1997. Incidence rates were calculated by month of birth, stratified for age at diagnosis. Poisson regression analyses were used to estimate the relative risk for coeliac disease for children below 2 years of age by season of birth, also taking into account gender and time period of diagnosis. Setting: Sweden. Participants: All 2151 children in the study base with verified coeliac disease. Main results: The risk for coeliac disease was significantly higher if born during the summer as compared with the winter (RR=1.4, 95% CI 1.2 to 1.7), but only in children below 2 years of age at diagnosis. This relative seasonal risk pattern prevailed during a 10 year epidemic of coeliac disease, although incidence rates varied threefold. The incidence was constantly higher among girls as compared with boys, but boys showed a more pronounced seasonal variation in risk than girls. Conclusions: An increased coeliac disease risk in children born in the summer compared with the winter reflects causal environmental exposure(s) with a seasonal pattern. Infections might be the exposure of importance, either by means of a direct causal role and/or through interaction with other exposures, for example, gluten intake. However, non-infectious exposures should also be explored as possible contributing causal factors.

A high linear growth is associated with an increased risk of childhood diabetes mellitus

SummaryInsulin release and growth are intimately connected. The aim of the present study was to investigate height and weight in diabetic children from birth to onset of Type 1 (insulin-dependent) diabetes mellitus compared to that in referent children. Data on height and weight were collected from mailed questionnaires and from growth records obtained from the child health clinics and schools in 337 recentonset diabetic children, 0–14 years old, and from 517 age-, sex-, and geographically matched referent children. A total of 9002 paired height and weight observations were collected. The anthropometric development of the children was expressed as standard deviation scores using the National Center for Health Statistics/Centers for Disease Control (NCHS/CDC) growth reference material. On the average, the diabetic children were consistently taller than the referent children, a finding more pronounced among the boys. The diabetic boys were significantly taller from 7 to 1 years before the clinical onset of the disease, regardless of age at onset. A similar tendency was found for the girls. When mean height from 5 to 1 years before onset was used as a possible risk factor for diabetes, a linearly increasing trend in the odds ratio was found for diabetes in boys (odds ratio = 1.0; 1.57; 2.46 for height standard deviation score values <0; 0–1 and > 1, respectively; p=0.002 for trend). A similar, but statistically not significant, tendency was found for girls (odds ratio = 1.0; 1.44; 1.43). As regards height increment from birth similar trends in odds ratios were found. Weight-for-height was similar among diabetic and referent children of both sexes. We conclude that diabetic boys tend to be taller and grow faster than referent boys for several years preceding the disease. A similar, but not statistically significant tendency was found among diabetic girls. Our findings indicate that rapid linear growth is a risk factor for Type 1 diabetes in childhood, and may be either a promoter of Type 1 diabetes or else a marker of a physiological mechanism that affects both growth and the pathogenesis of Type 1 diabetes.