Childhood risk factors for young adult strokes:the Northern Finland Birth Cohort Study 1966

Abstract The aim of this thesis was to explore associations between growth and development during childhood and risk of later stroke within the Northern Finland Birth Cohort 1966 (NFBC1966). Specifically, whether 1) pregnancy and birth related risk factors 2) height, weight, and BMI growth before school age or 3) childhood motor and language milestone achievement are associated with increased stroke risk in adulthood. The NFBC1966 is a population-based birth cohort consisting of 12,068 pregnant women and their 12,058 live-born children. This dissertation utilizes data that has been collected from medical records, national registers, clinical examinations, and questionnaires and a follow-up of up to 54 years. The results show that several early life factors are associated with increased risk of young adult strokes. A novel finding is the association of low maternal weight gain and offspring’s risk of ischemic stroke, which was independent of birth weight. Low weight, height and ponderal index at time of birth were markers of increased stroke risk in later life. Among girls also below average weight or height growth during the first 2 years of life and above average BMI before school age associated with adulthood stroke risk. In addition, the results suggest childhood developmental milestone achievement has predictive value for later life strokes. This study is one of the few to investigate early life factors in relation to adulthood stroke. The results of this thesis support the notion that early development, beginning during prenatal stages, can provide useful indicators of future processes influencing stroke risk.Tiivistelmä Tämän väitöskirjatutkimuksen tarkoituksena oli tutkia lapsuusajan kasvun ja kehityksen yhteyttä aikuisiän aivoverenkiertohäiriöriskiin vuoden 1966 Pohjois-Suomen syntymäkohortissa (NFBC1966). Tarkemmin eriteltynä, oliko 1) raskauden ja synnytyksen aikaisillä riskitekijöillä, 2) pituus-, paino- ja painoindeksikasvulla ennen kouluikää tai 3) lapsuuden motorisella tai kielellisellä kehityksellä yhteyttä lisääntyneeseen aivoverenkiertohäiriöön aikuisiällä. Pohjois-Suomen vuoden 1966 syntymäkohortti on valikoitumaton, yleisväestöpohjainen kohortti, joka sisältää tiedot 12068 raskaana olevasta naisesta ja heidän 12058 elävänä syntyneestä lapsestaan. Tässä väitöskirjatutkimuksessa hyödynnetiin tietoja sairauskertomuksista, kansallisista rekistereistä, kliinisistä tutkimuksista ja kyselyistä 54 vuoden seuranta-aikana. Tutkimuksen tulokset osoittivat, että useilla varhaiskehityksellisillä tekijöillä on yhteyttä lisääntyneeseen riskiin sairastua aivoverenkiertohäiriöön nuorena aikuisena. Uutena havaintona osoitettiin yhteys äidin raskaudenaikaisen vähäisen sekä suuren painonnousun ja lapsen kohonneen aivoverenkiertohäiriöriskin välillä. Yhteys oli riippumaton syntymäpainosta. Pieni paino, pituus ja ponderaali-indeksi syntymähetkellä ennustivat suurentunutta aikuisiän aivoverenkiertohäiriöriskiä. Naisilla myös keskimääräistä pienempi paino- tai pituuskasvu ensimmäisten 2 elinvuoden aikana ja keskimääräistä suurempi painoindeksi ennen kouluikää olivat yhteydessä myöhempään aivoverenkiertohäiriöriskiin. Lisäksi myös lapsuuden motorisella ja kielellisellä kehityksellä osoitettiin olevan ennustearvoa nuorten aikuisten aivoverenkiertohäiriöille. Tämä väitöskirjatutkimus on yksi harvoista, joissa tutkitaan varhaiskehityksen yhteyttä aikuisiän aivoverenkiertohäiriöriskiin. Tutkimuksen tulokset tukevat käsitystä, että varhaiskehitys, alkaen sikiökehityksestä, voi tarjota hyödyllisiä indikaattoreita tulevaisuuden aivoverenkiertohäiriöriskin kehittymiselle

Pregnancy risk factors as predictors of offspring cerebrovascular disease:the Northern Finland Birth Cohort Study 1966

Abstract Background and Purpose: For prevention of cerebrovascular diseases, it is important to understand the risk factors occurring early in life. The aim was to investigate the relationship of maternal and offspring anthropometrics and pregnancy complications with offspring’s risk of ischemic and hemorrhagic stroke and transient ischemic attack in adulthood. Methods: Within the population-based prospective Northern Finland Birth Cohort 1966, 11 991 persons were followed from early pregnancy to 52 years of age. Information on pregnancy and birth complications were collected starting between 24th and 28th gestational week and at birth. Ischemic and hemorrhagic strokes of the offspring were identified from national registers in Finland. Cox proportional hazard models were used to estimate the association of pregnancy and birth complications with incidence of cerebrovascular disease in the offspring, with adjustments for sex, family socioeconomic status, mother’s age, and smoking during pregnancy. Results: During 568 821 person-years of follow-up, 453 (3.8%) of the offspring had a stroke or transient ischemic attack. Small and large gestational weight gain among normal weight mothers were associated with increased ischemic stroke risk in offspring (adjusted hazard ratio [aHR], 1.93 [95% CI, 1.28–2.90] and aHR, 1.54 [95% CI, 1.02–2.31], respectively). Small birth weight for gestational age and small ponderal index were associated with increased risk for ischemic stroke (aHR, 1.95 [CI, 1.21–3.13] and aHR, 1.36 [CI, 1.04–1.77], respectively). Threatening miscarriage was also associated with increased risk of any stroke (aHR, 1.64 [CI 1.14–2.37]). Maternal smoking, hypertension, or birth complications were not associated with increased risk of cerebrovascular disease in the offspring. Conclusions: The results of this study suggest that disturbances in maternal and fetal growth during pregnancy may predispose offspring to developing cerebrovascular diseases in adulthood

Early childhood growth and risk of adult cerebrovascular disease:the NFBC1966

Abstract Background: Low birth weight is associated with an increased risk of adulthood cerebrovascular disease (CVD). Not much is known about effects of early childhood growth. We studied whether the risk of adult CVD is associated with growth or nutritional factors during early childhood. Methods: Within the Northern Finland Birth Cohort 1966, 11 991 persons were followed from birth to 52 years of age. CVD diagnoses were extracted from national hospital and death registers with diagnostic coding based on the World Health Organization recommendations. Cox proportional hazard models were used to estimate associations of childhood growth variables, growth trajectories (by Latent Class Growth Modeling), and nutritional factors with adult CVD, for example, ischemic and hemorrhagic strokes. The analyses were adjusted for childhood socioeconomic status and birth weight. Results: A total of 453 (3.8%) CVDs were recorded during follow-up. Among females, groups with low early childhood weight and height had an increased risk for adulthood ischemic CVDs, with an adjusted hazard ratio of 1.97 (95% CI, 1.21–3.20) and 2.05 (CI, 1.11–3.81), respectively. In addition, females with body mass index over 1 SD at body mass index rebound had an increased risk for ischemic CVDs (adjusted hazard ratio, 1.90 [CI, 1.19–3.04]) compared with females with body mass index −1 to +1 SD. These associations were not found among males. Conclusions: The findings suggest that timing of weight gain during childhood is of significance for development of CVD risk among females