A survey on awareness, knowledge, and attitudes toward epilepsy in an urban community in Turkey.

BACKGROUND AND AIM: Epilepsy is one of the most common chronic neurological disorders with a high prevalence. Epileptic people and their family members suffer more from social stigma than the disorder itself. Among various complex reasons knowledge and awareness about epilepsy are the two important factors underlying discriminatory attitudes towards epileptic people. Community pharmacists play a major role in the care of these patients. In this study we mainly aimed to gain insights into the knowledge and awareness of and attitudes (AKA) towards epilepsy both in epileptic and healthy individuals in an urban community. To this end we also aimed at developing a reliable and valid measurement tool to assess AKA levels. MATERIALS AND METHODS: This study was conducted in 13 community pharmacies with 219 respondents. Factor analysis yielded three clear subscales. RESULTS: It was found that a vast majority of the participants were familiar with epilepsy; yet only 18 of them had detailed information. The community pharmacists were indicated as a main source of information about epilepsy at the same rate to that of physicians. Although most of the respondents knew that epilepsy was not a form of mental illness only about one forth of them knew the real cause. More than half of the respondents supported the epileptics' socialization in the community. CONCLUSION: We believe that the questionnaire developed in the study is a promising instrument for determining educational needs and offering guidance to healthcare professionals in developing standardized educational tools and programs.

Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex.

The MHC is recognized for its importance in human health and disease. However, many disease-associated variants throughout the region remain of unknown significance, residing predominantly within non-coding regions of the MHC. The characterization of non-coding RNA transcripts throughout the MHC is thus central to understanding the genetic contribution of these variants. Therefore, we characterize novel miRNA transcripts throughout the MHC by performing deep RNA sequencing of two B lymphoblastoid cell lines with completely characterized MHC haplotypes. Our analysis identifies 89 novel miRNA transcripts, 48 of which undergo Dicer-dependent biogenesis and are loaded onto the Argonaute silencing complex. Several of the identified mature miRNA and pre-miRNA transcripts are unique to specific MHC haplotypes and overlap common SNPs. Furthermore, 43 of the 89 identified novel miRNA transcripts lie within linkage disequilibrium blocks that contain a disease-associated SNP. These disease associated SNPs are associated with 65 unique disease phenotypes, suggesting that these transcripts may play a role in the etiology of numerous diseases associated with the MHC. Additional in silico analysis reveals the potential for thousands of putative pre-miRNA encoding loci within the MHC that may be expressed by different cell types and at different developmental stages.

The dichotomy between disease phenotype databases and the implications for understanding complex diseases involving the major histocompatibility complex.

Many genes related to innate and adaptive immunity reside within the major histocompatibility complex (MHC) and have been associated with a multitude of complex, immune-related disorders. Despite years of genetic study, this region has seen few causative determinants discovered for immune-mediated diseases. Reported associations have been curated in various databases including the Genetic Association Database, NCBI database of clinically relevant variants (ClinVar) and the Human Gene Mutation Database and together capture genetic associations and annotated pathogenic loci within the MHC and across the genome for a variety of complex, immune-mediated diseases. A review of these three distinct databases reveals disparate annotations between associated genes and pathogenic loci, alluding to the polygenic, multifactorial nature of immune-mediated diseases and the pleiotropic character of genes within the MHC. The technical limitations and inherent biases imposed by current approaches and technologies in studying the MHC create a strong case for the need to perform targeted deep sequencing of the MHC and other immunologically relevant loci in order to fully elucidate and study the causative elements of complex immune-mediated diseases.

Prognostic significance of thyroglobulin antibody epitopes in differentiated thyroid cancer.

CONTEXT: Thyroglobulin antibodies (TgAbs) are surrogate markers of disease recurrence or persistence in differentiated thyroid cancer (DTC). However, the prognostic significance of TgAb heterogeneity in DTC has not been investigated. OBJECTIVE: To evaluate the relationship between TgAb epitope specificities and clinical outcomes in DTC patients. DESIGN: We studied 61 TgAb-positive patients with DTC, post-thyroidectomy and remnant ablation (7 males, 54 females; age-range 16-80 years, median follow-up duration 8.9 years). TgAb epitope reactivities were mapped using a panel of 10 thyroglobulin (Tg) monoclonal antibodies delineating six antigenic Tg clusters in competitive ELISA studies. Sera from 45 patients with Hashimoto's thyroiditis (HT) and 22 TgAb-positive healthy subjects served as autoimmune and healthy controls. Tg was measured by immunoradiometric assay (IRMA), electrochemiluminescence immunoassay (ECLIA), and RIA, while TgAbs was measured by ELISA and ECLIA methods. RESULTS: Samples from 26 DTC patients showed TgAb epitope restriction similar to HT patients, while 35 patients exhibited nonspecific reactivity comparable to healthy controls. DTC patients with epitope restriction had higher rates of recurrent/persistent disease (81% vs 17%, P < .001), higher median TgAb concentration (887.0 vs 82.0 kIU/L; P < .001), and a higher prevalence of thyroid lymphocytic infiltration (71.4% vs 26.8%; P < .001) compared to patients with nonspecific reactivity. Samples with epitope restriction also had a lower median Tg-IRMA/RIA ratio (3.0% vs 36.0%; P < .001) denoting greater degrees of Tg assay interference. CONCLUSIONS: TgAb epitope restriction is associated with a less favorable prognosis than nonspecific reactivity in DTC patients. TgAb epitope specificities may have prognostic value in DTC.

A public health approach to musculoskeletal health.

An ageing, physically inactive and increasingly obese population, coupled with finite health and social care resources, requires a shift from treating musculoskeletal disease when it arises to a preventive approach promoting lifelong musculoskeletal health. A public health approach to musculoskeletal health ensures that people are able to live not only long, but also well. Supporting self-management, addressing common misconceptions about the inevitability of musculoskeletal conditions, and offering brief interventions to support necessary lifestyle changes are basic public health functions that all health professionals can deliver. More specialist public health skills including needs assessment, data interpretation and service planning are also needed to deliver high quality services. These will require improvements in the data collected about musculoskeletal health nationally. A public health approach would benefit individuals through reduced pain and improved function due to musculoskeletal conditions, and wider society by minimising lost economic productivity and lowering health and social care costs.

Sedation and analgesia in intensive care: a comparison of fentanyl and remifentanil.

Optimal sedation and analgesia are of key importance in intensive care. The aim of this study was to assess the quality of sedoanalgesia and outcome parameters in regimens containing midazolam and either fentanyl or remifentanil. A prospective, randomized, open-label, controlled trial was carried out in the ICU unit of a large teaching hospital in Istanbul over a 9-month period. Thirty-four patients were randomly allocated to receive either a remifentanil-midazolam regimen (R group, n = 17) or a fentanyl-midazolam regimen (F group, n = 17). A strong correlation between Riker Sedation-Agitation Scale (SAS) and Ramsey Scale (RS) measurements was observed. Comparatively, remifentanil provided significantly more potent and rapid analgesia based on Behavioral-Physiological Scale (BPS) measurements and a statistically nonsignificantly shorter time to discharge. On the other hand, remifentanil also caused a significantly sharper fall in heart rate within the first six hours of treatment.

Challenges for the endocrine laboratory in critical illness.

The endocrine laboratory must provide accurate and timely results for the critically ill patient. A number of pathophysiological factors affect assay systems for adrenal, thyroid and gonadal function tests. The effects are primarily on estimates of 'free hormone' concentration through abnormal binding protein concentrations and the effects of drugs and metabolites on hormone-protein binding. The limitations of the principal analytical techniques (immunoassay and chromatography-mass spectrometry) include drug effects, endogenous antibody interference and ion suppression. These effects are not always easily identified. Analytical specificity and standardisation result in differences in bias between assays and thus a requirement for assay specific decision limits and reference ranges. Good communication between clinician and laboratory is needed to minimise these effects. Developments in mass spectrometry should lead to greater sensitivity and wider applicability of the technique. International efforts to develop higher order reference materials and reference method procedures should lead to greater comparability of results.

Falling asleep: the determinants of sleep latency.

BACKGROUND: Difficulty falling asleep (prolonged sleep latency) is a frequently reported problem in school-aged children. AIMS: This study aimed to describe the distribution of sleep latency and factors that influence its duration. METHODS: 871 children of European mothers were recruited at birth. 591 (67.9%) children took part in the follow-up at 7 years of age. Sleep and daytime activity were measured objectively by an actigraph worn for 24 h. RESULTS: Complete sleep data were available for 519 children (87.8%) with a mean age of 7.3 years (SD 0.2). Median sleep latency was 26 minutes (interquartile range 13-42). Higher mean daytime activity counts were associated with a decrease in sleep latency (-1.2 minutes per 102 movement count per minute, p = 0.05). Time spent in sedentary activity was associated with an increase in sleep latency (3.1 minutes per hour of sedentary activity, p = 0.01). CONCLUSIONS: These findings emphasise the importance of physical activity for children, not only for fitness, cardiovascular health and weight control, but also for promoting good sleep.

Laboratory services for thyroglobulin and implications for monitoring of differentiated thyroid cancer.

Serum thyroglobulin is used as a marker for monitoring differentiated thyroid cancer. There are a number of analytical challenges: the need for stability of the assay over decades, differences in assay bias, and interference in immunoassays by endogenous thyroglobulin antibodies. Improved precision at low analyte concentrations is desirable. Approaches to identifying assay interference are discussed. No single approach is likely to be successful on all occasions. Decision limits should be assay-specific, and clinicians should be aware of the limitations of current immunoassays.

Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor.

AIMS/HYPOTHESIS: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are released from intestinal endocrine cells in response to luminal glucose. Glucokinase is present in these cells and has been proposed as a glucose sensor. The physiological role of glucokinase can be tested using individuals with heterozygous glucokinase gene (GCK) mutations. If glucokinase is the gut glucose sensor, GLP-1 and GIP secretion during a 75 g OGTT would be lower in GCK mutation carriers compared with controls. METHODS: We compared GLP-1 and GIP concentrations measured at five time-points during a 75 g OGTT in 49 participants having GCK mutations with those of 28 familial controls. Mathematical modelling of glucose, insulin and C-peptide was used to estimate basal insulin secretion rate (BSR), total insulin secretion (TIS), beta cell glucose sensitivity, potentiation factor and insulin secretion rate (ISR). RESULTS: GIP and GLP-1 profiles during the OGTT were similar in GCK mutation carriers and controls (p = 0.52 and p = 0.44, respectively). Modelled variables of beta cell function showed a reduction in beta cell glucose sensitivity (87 pmol min(-1) m(-2) [mmol/l](-1) [95% CI 66-108] vs 183 pmol min(-1) m(-2) [mmol/l](-1) [95% CI 155-211], p < 0.001) and potentiation factor (1.5 min [95% CI 1.2-1.8] vs 2.2 min [95% CI 1.8-2.7], p = 0.007) but no change in BSR or TIS. The glucose/ISR curve was right-shifted in GCK mutation carriers. CONCLUSIONS/INTERPRETATION: Glucokinase, the major pancreatic glucose sensor, is not the main gut glucose sensor. By modelling OGTT data in GCK mutation carriers we were able to distinguish a specific beta cell glucose-sensing defect. Our data suggest a reduction in potentiation of insulin secretion by glucose that is independent of differences in incretin hormone release.

Risk factors for asthma at 3.5 and 7 years of age.

BACKGROUND: It has been suggested that factors in early life including exposure to allergens and microbes may influence the development of asthma. OBJECTIVE: To identify risk factors for asthma in early childhood. Methods Eight-hundred and seventy-one children of European mothers were enrolled at birth, of whom 385 (44.2%) were born small for gestational age (SGA) and 486 were appropriate for gestational age (AGA). Data were collected at birth, 12 months, 3.5 years of age (y) and 7 y. The outcome of interest (current wheeze) was defined as a positive response to the question: 'Has your child had wheezing or whistling in the chest in the last 12 months?' RESULTS: Participation rate was 85.4% at 1 y, 63.1% at 3.5 y and 68.0% at 7 y. The prevalence of asthma was 23.8% at 3.5 y and 18.1% at 7 y. Antibiotic use in the first year of life and day care in the first year of life were associated with increased risk of wheeze at 7 y [odds ratio (OR)=4.3 95% confidence interval (CI) (1.8-10.1) and OR=2.8 95% CI (1.2-6.5), respectively], but not at 3.5 y. Exposure to dogs was a risk factor for asthma at both ages [OR=2.1 95% CI (1.1-3.8)] as was sleeping on a used cot mattress in the first year of life [OR=1.8 95% CI (1.0-3.2)]. CONCLUSIONS: There was a significant association between antibiotic use and day care in the first year of life and wheezing at 7 y but not at 3.5 y. This strengthens the argument that these factors increase the risk of asthma. We have also made the novel observation that sleeping on a used mattress in the first year of life is a risk factor for wheezing at 3.5 and 7 y. Capsule summary This prospective study of 871 children made the novel observation that sleeping on a used mattress in the first year of life was a risk factor for wheezing at 3.5 and 7 y.

The long-term impact on offspring of exposure to hyperglycaemia in utero due to maternal glucokinase gene mutations.

AIMS/HYPOTHESIS: There is strong evidence that maternal diabetes while offspring are in utero results in offspring beta cell dysfunction and diabetes or glucose intolerance. Offspring born to mothers with a mutation in the glucokinase gene (GCK) are a good model for studying exposure to moderate hyperglycaemia, as mutation carriers have fasting hyperglycaemia throughout life including during pregnancy. We assessed the long term effects of exposure to maternal hyperglycaemia in utero on beta cell function and glucose tolerance in adult offspring. MATERIALS AND METHODS: We studied 86 adult offspring (mean age 40 years), 49 born to glucokinase mothers (exposed to hyperglycaemia in utero) and 37 born to glucokinase fathers (controls). We measured glucose tolerance during an OGTT and beta cell function using early insulin response (EIR); we also measured anthropometric data including birthweight. RESULTS: Offspring of glucokinase mothers had a higher birthweight by 450 g (p<0.001), but no evidence of deterioration in glucose tolerance (2-h glucose 9.1 vs 8.6 mmol/l p=0.50) or reduced beta cell function (log EIR 1.40 vs 1.26, p=0.11) compared with offspring born to glucokinase fathers. CONCLUSIONS/INTERPRETATION: The marked increase in birthweight shows that offspring born to affected mothers were exposed to increased glycaemia in utero. Despite this, there was no evidence of altered beta cell function or glucose tolerance. As previous human examples of marked programming by hyperglycaemia in utero have been in genetically predisposed offspring, we propose that our finding reflects the lack of genetic predisposition in the offspring to progressive beta cell dysfunction.

Growth response of broilers to spray-dried plasma in pelleted or expanded feed processed at high temperature.

A series of 4 experiments evaluated effects of mash conditioning temperature from a pellet mill or expander on performance of broilers fed pelleted diets containing spray-dried plasma (SDP). All experiments utilized Ross x Ross 308 male broilers randomly assigned to their respective treatments (6 or 10 broilers/pen and 8 or 10 pens/treatment). Treatments in Exp. 1 consisted of a control (0% SDP), SDP coated postpelleting, or SDP blended into the meal prepelleting. Experiment 2 and 3 included the same 3 treatments as in Exp. 1 but with additional treatments of SDP blended into the meal and conditioned at 90 or 95 degrees C before pelleting. In Exp. 4, treatments consisted of a control (0% SDP) or SDP blended into the meal and pelleted (85 degrees C conditioning temperature) or expanded (149 degrees C final effective temperature) and then pelleted. Corn-soybean meal-based diets were formulated to be equal in lysine and ME in all experiments. Pelleted diets were conditioned for 15 s at 85 degrees C, and expanded diets were conditioned at 95 degrees C, 29.7 MJ/t, 13.95 kg/cm2 cone pressure, exit temperature of 149 degrees C, and then pelleted through a 4 x 32-mm die. In Exp. 1, ADG and feed intake were improved (P < 0.05) for broilers fed SDP from d 1 to 28 of age, with greater BW at d 42. In Exp. 2, both in early (d 1 to 28 of age) phases, and overall (d 1 to 42 of age), broilers fed SDP had improved (P < 0.05) gain and efficiency. In Exp. 3, ADG, feed intake, efficiency of gain, and BW were improved (P < 0.01) for broilers fed SDP from d 1 to 21 of age, regardless of conditioning temperature. In Exp. 4, broilers fed SDP had improved (P < 0.05) gain, BW, and feed intake regardless of processing method. Overall, the results of all of the experiments demonstrated that pellet conditioning temperature from 85 to 95 degrees C and expander temperatures to 149 degrees C did not impair the positive growth effects of SDP in pelleted or expanded broiler feed.

Paternal insulin resistance and its association with umbilical cord insulin concentrations.

AIMS/HYPOTHESIS: Fetal growth is influenced by genetic factors as well as the intra-uterine environment. We hypothesised that some genetic factors may alter fetal insulin secretion and insulin action. SUBJECTS, MATERIALS AND METHODS: To assess this, we analysed plasma insulin concentration in umbilical cord blood from 644 normal, term, UK Caucasian deliveries from the Exeter Family Study of Childhood Health. We tested for associations between cord insulin and each of parental anthropometry, fasting glucose, insulin and lipids. RESULTS: As expected, cord insulin concentrations correlated with all measures of birth size (weight, length, head and arm circumferences, sum of skinfold thicknesses, ponderal index: r=0.16-0.4, p<0.01 for all) and maternal BMI (r=0.11, p=0.005), maternal glucose (r=0.25, p<0.001) and maternal insulin resistance (r=0.23, p<0.001). Paternal fasting insulin and insulin resistance were correlated with cord insulin (r=0.15, p=0.006; r=0.13, p=0.001, respectively), and this was independent of paternal BMI. Multiple linear regression analysis revealed paternal insulin resistance to be a predictor of cord insulin concentrations, independently of maternal factors. CONCLUSION: Our results show an independent relationship between paternal insulin resistance and cord insulin concentrations. This is consistent with heritability of insulin resistance from father to offspring and a compensatory increase in fetal insulin secretion, the latter occurring pre-natally before the homeostatic feedback loop between glucose and insulin is established.

Determinants of insulin concentrations in healthy 1-week-old babies in the community: applications of a bloodspot assay.

BACKGROUND: Epidemiological research into insulin secretion and insulin action would be helped by improved ability to measure insulin concentrations in large groups of healthy babies in the neonatal period. Such research is often restricted by the invasive nature of blood sampling. AIMS: We assessed the use of an assay that can measure insulin from bloodspots taken during routine Guthrie testing 7 days after delivery. STUDY DESIGN AND SUBJECTS: Insulin and glucose were measured in 366 seven-day-old infants from heel-prick bloodspots. Time since last feed and type of feed were recorded. RESULTS: Bloodspot insulin concentrations in normal 7-day-old infants were much lower (median (IQR): 15.4 pmol/l (<10-28.5)) than fasting insulin concentrations in adult males (44.3 pmol/l (30.6-72.6)) (p<0.001). Insulin and glucose concentrations were correlated (r=0.33, p<0.001). Insulin and glucose fell significantly with time from feed. Bottle fed infants had higher insulin concentrations but similar glucose concentrations compared to breast fed infants. Detailed analysis to account for confounders was limited due to the skewed distribution of time since feed and the lower limit of the assay leading to non-continuous insulin data. CONCLUSIONS: In the largest study of normal 7-day-old children to date we have shown insulin concentrations are low compared to adults and vary with glucose, time from feed, and type of feed. This validates the use of the bloodspot insulin assay as a potential research tool for large-scale epidemiological studies. However, careful study design would be required in future use to reduce the variation caused by timing and type of feeding and the problem of one third of values being at or below the lower limit of this assay.

Breastfeeding and intelligence of preschool children.

AIM: To investigate whether breastfeeding during infancy is a determinant of intelligence at 3.5 y. METHODS: Five hundred and fifty European children enrolled at birth in the Auckland Birthweight Collaborative Study were assessed at 3.5 y of age. Approximately half were small for gestational age (SGA < or =10th percentile) at birth and half were appropriate for gestational age (AGA >10th percentile). Duration of breastfeeding was recorded at maternal interview, and the intelligence of children was assessed using the Stanford Binet Intelligence Scale. Regression analysis was used to calculate estimates of difference in intelligence scores between breastfeeding groups for the total sample and the group of SGA children. Analyses of the total sample were weighted to account for the disproportionate sampling of SGA children. RESULTS: Breastfeeding was not significantly related to intelligence scores in the total sample despite a trend for longer periods of breastfeeding to be associated with higher intelligence scores. However, in the SGA group, breastfeeding was significantly related to IQ at 3.5 y. Small for gestational age children who were breastfed for longer than 12 mo had adjusted scores 6.0 points higher than those who were not breastfed (p=0.06). CONCLUSION: Breastfeeding may be particularly important for the cognitive development of preschool children born small for gestational age.

Maternal stress, social support and preschool children's intelligence.

BACKGROUND: Despite some research suggesting maternal stress may be associated with cognitive impairment in preschool children, there has been little direct investigation of the association between maternal stress, social support and children's intelligence. AIM: To determine whether maternal stress and social support during pregnancy and during the child's early years of life are associated with the intelligence test performance of preschool children. STUDY DESIGN: Five hundred and fifty European mothers and children enrolled in the Auckland Birthweight Collaborative Study at birth were interviewed when the child was 3 1/2 years of age. SUBJECTS: All children were full term gestation and approximately half the sample were small for gestational age at birth (SGA = birthweight < or = 10th percentile). OUTCOME MEASURE: The cognitive ability of children aged 3 1/2 years was assessed using the Stanford Binet Intelligence Scale 4th Edition. RESULTS: In the total sample, maternal stress and lack of social support during pregnancy were significantly associated with lower intelligence test scores of children. In the group of SGA children, maternal stress post pregnancy was significantly associated with lower intelligence test scores in children. There is evidence that for some children the presence of good social support for mothers may reduce the negative effects of maternal stress on children's cognitive development. CONCLUSION: Maternal stress and lack of social support appear to be associated with lower intelligence test scores of preschool children. Social support may attenuate some of the negative effects of maternal stress on intelligence in children born small for gestational age.

Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.

AIMS/HYPOTHESIS: Heterozygous mutations in the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families. We investigated the genetics and phenotype of HNF-4alpha mutations in a large European Caucasian collection. METHODS: HNF-4alpha was sequenced in 48 MODY probands, selected for a phenotype of HNF-1alpha MODY but negative for HNF-1alpha mutations. Clinical characteristics and biochemistry were compared between 54 HNF-4alpha mutation carriers and 32 familial controls from ten newly detected or previously described families. RESULTS: Mutations in HNF-4alpha were found in 14/48 (29%) probands negative for HNF-1alpha mutations. The mutations found included seven novel mutations: S34X, D206Y, E276D, L332P, I314F, L332insCTG and IVS5nt+1G>A. I314F is the first reported de novo HNF-4alpha mutation. The average age of diagnosis was 22.9 years with frequent clinical evidence of sensitivity to sulphonylureas. Beta cell function, but not insulin sensitivity, was reduced in diabetic mutation carriers compared to control subjects (homeostasis model assessment of beta cell function 29% p<0.001 vs controls). HNF-4alpha mutations were associated with lower apolipoprotein A2 (p=0.001), A1 (p=0.04) and total HDL-cholesterol (p=0.02) than in control subjects. However, in contrast to some previous reports, levels of triglycerides and apolipoprotein C3 were normal. CONCLUSIONS/INTERPRETATION: HNF-4alpha mutations are common when no HNF-1alpha mutation is found in strictly defined MODY families. The HNF-4alpha clinical phenotype and beta cell dysfunction are similar to HNF-1alpha MODY and are associated with reduced apolipoprotein A2 levels. We suggest that sequencing of HNF-4alpha should be performed in patients with clinical characteristics of HNF-1alpha MODY in whom mutations in HNF-1alpha are not found.

Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age.

BACKGROUND: The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. OBJECTIVES: To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. METHODS: The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight < or = 10th centile; controls were appropriate for gestational age, with birthweight > 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. RESULTS: Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L(-1), and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: < 6 months, adjusted OR 6.13, 95% CI 1.45-25.86; > or = 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for environmental factors and a personal history of atopy. AD at 3.5 years was associated with owning a cat at 3.5 years (adjusted OR 0.45, 95% CI 0.21-0.97) but not with owning a dog at 3.5 years, pets at 1 year, nor with older siblings. Furthermore, AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, damp, mould, immunizations, body mass index or antibiotic use in first year of life. CONCLUSIONS: A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with those factors implicated by the hygiene hypothesis. This study suggests that breastfeeding should not be recommended for the prevention of AD.

Maternal nutritional risk factors for small for gestational age babies in a developed country: a case-control study.

AIMS: To assess the effect of maternal diet during pregnancy on the risk of delivering a baby who is small for gestational age (SGA). METHODS: Case-control study of 844 cases (SGA) and 870 controls (appropriate size for gestational age (AGA)). Only term (37+ completed weeks of gestation) infants were included. Retrospective food frequency questionnaires were completed at birth on the diet at the time of conception and in the last month of pregnancy. RESULTS: At the time of conception, mothers of AGA infants ate significantly more servings of carbohydrate rich food and fruit, and were more likely to have taken folate and vitamin supplements than mothers of SGA infants. There was some evidence that mothers of AGA infants also ate more servings of dairy products, meat, and fish (0.05 < p < 0.1). However, after adjustment for maternal ethnicity, smoking, height, weight, hypertension, and occupation, fish intake (p = 0.04), carbohydrate-rich foods (p = 0.04), and folate supplementation (p = 0.02) were associated with a reduced risk of SGA. In the last month of pregnancy, only iron supplementation was associated with a reduced risk of SGA (p = 0.05) after adjustment for potential confounders. CONCLUSIONS: This study suggests that small variations in maternal diets within the normal range during pregnancy in developed countries are associated with differences in birth weight.