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• W2118628812 abstract "During the last decades there has been an upsurge of studies investigating how early life exposures may affect subsequent health outcomes in childhood. For instance, low birth weight and exposure to antibiotics during fetal or early life have been suggested to increase the risk of childhood asthma. Twinand sibling comparisons can help to account for confounding factors shared within families and to shed light on potential causal pathways. Thus, in Study I, we aimed to investigate if low birth weight, as a proxy for fetal growth restriction in twins, was associated with the development of asthma in a cohort of 10 918 Swedish twins aged 9 or 12 years. We found a significant association which was thought to be explained by unique individual factors and not due to familial confounding or gestational age. It can be speculated that restricted fetal growth affects lung development in utero which influences the risk of developing asthma in childhood. In Study II, we aimed to further understand the adverse effects of restricted fetal growth, by specifically investigating its association with childhood lung function in a cohort of 576 twins aged 9-14 years at invitation to the study. We found a significant association between fetal growth restriction and reduced forced expiratory volume in the first second, which could be explained by unique factors of each twin. Similar effects were found in non-asthmatic individuals, whereas other factors may be of importance for the association between fetal growth and lung function in individuals with asthma. To be able to study asthma in register-based studies, a valid measure of the disease is needed. In Study III, medical records for roughly 1700 individuals, corresponding to prescription dates of asthma medications or to discharge dates accompanying asthma diagnoses and identified from population-based drugand patient registers, were collected from health care units and evaluated against pre-defined criteria of asthma. We found a high positive predictive value for asthma medication as a proxy for asthma in older children and the majority of children with an asthma diagnosis in the patient register fulfilled pre-defined criteria of asthma. In Study IV, the previously suggested association between antibiotic exposure in fetal and early life and childhood asthma (based on the validated outcome measure from Study III) was investigated in a cohort of 493 785 children. We found an association between antibiotic exposure both in fetal and early life and asthma. Yet, sibling control analyses suggested that the associations were due to shared factors within families, and confounding by indication or reverse causation due to respiratory infections. In conclusion, shared genetic and environmental factors contributed to the association between antibiotics and asthma, but not between fetal growth and asthma and lung function, respectively. Genetically informed designs to control for familial confounding are useful tools to help provide a clearer understanding of the etiology of asthma. In addition, asthma identified from population-based registers can be used as a validated outcome measure and contribute towards future studies on asthma using register-based data. SVENSK SAMMANFATTNING Under de senaste decennierna har ett stort fokus lagts pa att forsoka forsta hur faktorer under fosterlivet eller tidiga barnar paverkar individens halsa senare i livet. Det har exempelvis foreslagits att lag fodelsevikt, exponering for antibiotika under fostertiden eller att barnet sjalv har blivit behandlat med antibiotika tidigt i livet leder till en okad risk for astma senare i barndomen. Tvillingoch syskonstudier kan bidra till okad forstaelse om sambanden ar kausala eller om de ar orsakade av genetikoch miljofaktorer som delas inom familjer. I studie I undersokte vi sambandet mellan lag fodelsevikt och astma i barndomen. Studien omfattade 10 918 tvillingar, 9 eller 12 ar gamla, och vara resultat tyder pa att lag fodelsevikt okar risken for astma oavsett om barnet fods for tidigt eller i fullgangen tid, samt oberoende av delade genetikoch miljofaktorer. Resultaten skulle kunna tolkas som att hammad fostertillvaxt paverkar fostrets lungutveckling och darmed risken for astma. I studie II studerade vi darfor om fostertillvaxt paverkar lungfunktionen i barndomen och om ett eventuellt samband paverkas av astma. Vara resultat, baserade pa 576 tvillingar i aldrarna 9-14 ar, tyder pa att hammad fostertillvaxt leder till forsamrad lungfunktion. Sambandet kunde inte forklaras av for tidig fodelse eller delade genetikoch miljofaktorer, och sags aven hos barn utan astma. Det forefaller dock som att andra faktorer verkar paverka sambandet mellan fostertillvaxt och lungfunktion hos dem som har astma. I Sverige finns det flera nationella halsoregister. For att kunna studera astma i registerbaserade studier behovs ett bra utfallsmatt. I studie III validerade vi saledes matt pa astma i journaler for ca 1700 individer fran primaroch specialistsjukvarden, identifierade fran halsoregistren. Vara resultat tyder pa att astmalakemedel rapporterade i Lakemedelsregistret kan anvandas som ett precist matt pa astma hos barn, och att majoriteten av barn som har fatt en astmadiagnos i specialistsjukvarden uppfyllde forbestamda kriterier for en astmadiagnos. I studie IV undersokte vi det tidigare foreslagna sambandet mellan antibiotika under fostertiden eller tidigt i livet och astma i barndomen i en syskonstudie, dar astma identifierats fran halsoregistren (baserat pa studie III). Studien omfattande nastan en halv miljon barn och vara resultat tyder pa att antibiotika i sig inte orsakar astma utan att sambandet orsakas av delade faktorer inom familjer samt luftvagsinfektioner. Sammanfattningsvis talar vara resultat for att delade genetikoch miljofaktorer bidrog till sambandet mellan antibiotika och astma, men inte till sambandet mellan hammad fostertillvaxt och astma respektive lungfunktion. Vi har ocksa visat att astma identifierat fran halsoregister kan fungera som ett bra matt pa astma, och kan anvandas i framtida studier. Slutligen, tvillingoch syskonstudier i kombination med information fran populationsbaserade register kan bidra till okad forstaelse av tidiga orsaker till astma hos barn. LIST OF SCIENTIFIC PAPERS I. Ortqvist AK, Lundholm C, Carlstrom E, Lichtenstein P, Cnattingius S, Almqvist C. Familial factors do not confound the association between birth weight and childhood asthma. Pediatrics. 2009;124(4):e737-43. II. Ortqvist AK, Ullemar V, Lundholm C, Kuja-Halkola R, Magnusson PKE, Lichtenstein P, Hallberg J, Almqvist C. Fetal growth and childhood lung function – exploring genetic and environmental confounding in within-twin pair analyses. (Manuscript) III. Ortqvist AK, Lundholm C, Wettermark B, Ludvigsson JF, Ye W, Almqvist C. Validation of asthma and eczema in population-based Swedish drug and patient registers. Pharmacoepidemiol Drug Saf. 2013;22(8):850-60. IV. Ortqvist AK, Lundholm C, Kieler H, Ludvigsson JF, Fall T, Ye W, Almqvist C. Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis. BMJ. 2014;349:g6979. RELATED PUBLICATIONS (not included in thesis) I. Lundholm C, Ortqvist AK, Lichtenstein P, Cnattingius S, Almqvist C. Impaired fetal growth decreases the risk of childhood atopic eczema: a Swedish twin study. Clin Exp Allergy. 2010;40(7):1044-53. II. Tedner SG, Ortqvist AK, Almqvist C. Fetal growth and risk of childhood asthma and allergic disease. Clin Exp Allergy. 2012;42(10):1430-47. III. Almqvist C, Ortqvist AK, Gong T, Wallas A, Ahlen K, Ye W, Lundholm C. Individual maternal and child exposure to antibiotics in hospitala national population-based validation study. Acta Paediatr. 2014 Dec 26. [Epub ahead of print] IV. Almqvist C, Ortqvist AK, Ullemar V, Lundholm C, Lichtenstein P, Magnusson PKE. Cohort Profile: Swedish Twin study On Prediction and Prevention of Asthma (STOPPA). Twin Hum Research 2015; In Press. CONTENTS" @default.
• W2118628812 created "2016-06-24" @default.
• W2118628812 creator A5052205013 @default.
• W2118628812 date "2015-03-19" @default.
• W2118628812 modified "2023-09-26" @default.
• W2118628812 title "EARLY LIFE ORIGINS OF ASTHMA GENETIC AND ENVIRONMENTAL FACTORS IN TWIN AND KIN" @default.
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