Fetal growth and risk of childhood asthma and allergic disease

Introduction: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective: This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods: PubMed-search on pre-defined terms and cross-references. Results: Several studies have shown a correlation between low birth weight and/or gesta- tional age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subse- quent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that dis- eases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance: Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.Swedish Research CouncilALF KI/SLLStrategic Research Program in Epidemiology at Karolinska InstitutetPublishe

No association between macrolide treatment in infancy and later pyloric stenosis in Sweden

NoneAccepte

Directed diversity-oriented synthesis. Ring-fused 5- to 10-membered rings from a common peptidomimetic 2-pyridone precursor

AbstractA variety of ring-fused 2-pyridone-based central fragments were prepared using a strategy inspired by diversity-oriented synthesis. The produced compounds are diverse, yet focused, analogs of biologically active peptidomimetic 2-pyridones

Cohort profile : Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA)

Asthma is a common childhood disease and several risk factors have been identified, however the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (parental interview at 9 or 12 years, N~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were identified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota) and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood and saliva sampling. This article describes the design, recruitment, data collection, measures, background characteristics as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development and new leads for prevention of asthma and allergic disease.NonePublishe

Individual maternal and child exposure to antibiotics in hospital : a national population-based validation study

Aim: Exposure to antibiotics in early life may affect future health. Most antibiotics are prescribed in outpatient care, but inpatient exposure is also important. We estimated how specific diagnoses in hospitals corresponded to individual antibiotic exposure. Methods: All pregnant women and children from birth to five-years-of-age with infectious diseases and common inpatient diagnoses between July 2005 and November 2011were identified from the Swedish National Patient Register. Random samples of individuals from pre-defined groups were drawn and medical records received from the clinics were manually reviewed for antibiotics. Results: Medical records for 4,319 hospital visits were requested and 3,797 (88%) were received. A quarter (25%) of children diagnosed as premature had received antibiotics and in children from one to five-years-of-age, diagnoses associated with bacterial infections were more commonly treated with antibiotics (62.4-90.6%) than those associated with viruses (6.3-22.2%). Pregnant women who had undergone a Caesarean section were more likely to be treated with antibiotics than those who had had a vaginal delivery (40.1% versus 11.1%). Conclusions: This study defines the proportion of new mothers and young children who received individual antibiotic treatment for specific inpatient diagnoses in Sweden and provides a useful basis for future studies focusing on antibiotic use.Swedish Research Council, 2011-3060Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM), 80748301 and 340-2013- 5867Stockholm County Council (ALF)Swedish Heart Lung FoundationStrategic Research Program in Epidemiology at Karolinska InstitutetManuscrip

Validation of asthma and eczema in population-based Swedish drug and patient registers

Purpose: Validated measures of asthma and eczema at the population level remain a challenge. Our aim was to ascertain if register-based information on asthma/eczema medicat ion can function as a proxy for an asthma/eczema diagnosis and to validate register-based asthma diagnoses. Methods: Information was requested on all 0-45 year old individuals with reported asthma/eczema medication and/or diagnoses in the Swedish Prescribed Drug Register and National Patient Register, between July 2005 and December 2009 (N=250,691). Medical records for 1,952 randomly selected individuals were reviewed to estimate the proportion of individuals with 1) asthma/eczema medication that fulfilled p redefined criteria of asthma/eczema (positive predictive value, PPV); 2) a register-based asthma diagnosis verified as asthma by set criteria. Results: PPV for asthma by predefined criteria ranged between 0.75 (95% CI: 0.70-0.78) to 0.94 (95% CI: 0.91-0.96), depending on age-group. In pre-school children, PPV for asthma in combination with obstructive bronchitis was 0.87 (95% CI: 0.83-0.90) and PPV for eczema was estimated to 0.45 (95% CI: 0.38-0.51). Eighty percent of children 0-4.5 years and 99% of children >4.5-17 years with a register-based diagnosis of asthma were verified as asthmatics. Conclusion: Asthma medication is a suitable proxy for asthma in older children and adults; the same approach is insufficient for eczema. This validation study of two Swedish registers opens for future large nation-wide register-based studies on asthma.Swedish Research CouncilVetenskapsrådetALFManuscrip

Parental cancer diagnosis and child mortality : a population-based cohort study in Sweden

OBJECTIVE: Cancer diagnosis is known to induce severe psychological stress for the diagnosed patients; however, how it affects the next-of-kin is less well documented. This study aimed to assess the impact of parental cancer on the risk of childhood death. METHODS: A population-based cohort study was conducted using the Swedish national registries, including 2,871,242 children followed during the period of 1991-2009. Parental cancer diagnosis was defined as a time-varying exposure. We used Cox proportional hazards regression to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) as an estimate of the association between parental cancer and childhood mortality. We adjusted for attained age, sex, gestational age, mode of delivery and birth weight of the child, maternal age at child's birth, as well as educational level and socio-economic classification of the parents in the analyses. RESULTS: Among 113,555 children with parental cancer, 127 deaths occurred during 561,198 person-years of follow-up. A parental cancer diagnosis was associated with an increased rate of death among children at the age of 1-18 (HR for all-cause death: 1.39; 95% CI: 1.16-1.66). For young children (aged 1-12), an increased rate was only noted for death due to cancer (HR: 2.06; 95% CI: 1.13-3.75) after parental cancer diagnosis. Among adolescents (aged 13-18), an increased rate was noted for all-cause death (HR: 1.52; 95% CI: 1.25-1.86), and for both non-cancer-related (HR: 1.43; 95% CI: 1.14-1.79) and cancer-related (HR: 2.07; 95% CI: 1.33-3.24) death in the exposed children. CONCLUSION: Children have an increased rate of death if they have a parent diagnosed with cancer as compared to children without such experience; this association appears to be slightly stronger among adolescents.Swedish Research CouncilSwedish Research Council for Health Working Life & Welfare (Forte), 2012-0498Swedish Research Council SIMSAM, 80748301, 340-2013-5867China Scholarship Council, 201206100002Swedish Society for Medical Research (SSMF)Karolinska InstitutetPublishe

Registers of the Swedish total population and their use in medical research

The primary aim of the Swedish national population registration system is to obtain data that (1) reflect the composition, relationship and identities of the Swedish population and (2) can be used as the basis for correct decisions and measures by government and other regulatory authorities. For this purpose, Sweden has established two population registers: (1) The Population Register, maintained by the Swedish National Tax Agency ("Folkbokforingsregistret"); and (2) The Total Population Register (TPR) maintained by the government agency Statistics Sweden ("Registret over totalbefolkningen"). The registers contain data on life events including birth, death, name change, marital status, family relationships and migration within Sweden as well as to and from other countries. Updates are transmitted daily from the Tax Agency to the TPR. In this paper we describe the two population registers and analyse their strengths and weaknesses. Virtually 100 % of births and deaths, 95 % of immigrations and 91 % of emigrations are reported to the Population Registers within 30 days and with a higher proportion over time. The over-coverage of the TPR, which is primarily due to underreported emigration data, has been estimated at up to 0.5 % of the Swedish population. Through the personal identity number, assigned to all residents staying at least 1 year in Sweden, data from the TPR can be used for medical research purposes, including family design studies since each individual can be linked to his or her parents, siblings and offspring. The TPR also allows for identification of general population controls, participants in cohort studies, as well as calculation of follow-up time.NonePublishe

A 2-pyridone-amide inhibitor targets the glucose metabolism pathway of Chlamydia trachomatis.

UnlabelledIn a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection.ImportanceChlamydia trachomatis is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Here, by using a visual screen for compounds that affect bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggest that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections