Anastasia Iliadou

Genetic and Shared Environmental Factors Do Not Confound the Association Between Birth Weight and Hypertension A Study Among Swedish Twins

Background— Studies have found associations between low birth weight and increased risks of cardiovascular diseases in adulthood. However, these associations could be due to confounding by genetic or socioeconomic factors. Methods and Results— We performed a study on Swedish like-sexed twins with known zygosity who were born from 1926 to 1958. First, to obtain an overall effect of birth weight on risk of hypertension, we performed cohort analyses on all twins (n=16 265). Second, to address genetic and shared environmental confounding, we performed a nested co-twin control analysis within 594 dizygotic and 250 monozygotic twin pairs discordant for hypertension. Birth characteristics, including birth weight, were obtained from original birth records. Information from adulthood was collected from a postal questionnaire in 1973 (body mass index, height, smoking, and alcohol use) and from a telephone interview conducted from 1998 to 2002 (hypertension and socioeconomic status). Hypertension was defined as reporting both high blood pressure and treatment with antihypertensive medication. In the cohort analysis, the adjusted odds ratio for hypertension in relation to a 500-g decrease in birth weight was 1.42 (95% confidence interval, 1.25 to 1.61). In the co-twin control analyses, the corresponding odds ratios were 1.34 (95% confidence interval, 1.07 to 1.69) for dizygotic and 1.74 (95% confidence interval, 1.13 to 2.70) for monozygotic twins. Conclusions— In the largest twin study on the fetal origins of hypertension, we found that decreased birth weight is associated with increased risk of hypertension independently of genetic factors, shared familial environment, and risk factors for hypertension in adulthood, including body mass index.

Familial factors confound the association between maternal smoking during pregnancy and young adult offspring overweight

BACKGROUNDnSmoking during pregnancy has been shown to increase the risks of several adverse birth outcomes. Associations with overweight and/or obesity in the offspring have also been suggested. We aim to investigate whether familial factors confound the association between maternal smoking during pregnancy and overweight in early adulthood in young Swedish males born 1983-88.nnnMETHODSnIn a population-based Swedish cohort comprising 124 203 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of overweight in the offspring at age ∼18 years. We also investigated the association within siblings, controlling for common genes and shared environment.nnnRESULTSnIn the cohort analyses, the risk of overweight was increased in sons of smoking mothers compared with sons of non-smokers: adjusted odds ratios 1.41, 95% confidence interval (CI) 1.34-1.49, and 1.56, 95% CI 1.46-1.66, for one to nine cigarettes per day, and >10 cigarettes per day, respectively. Stratifying for maternal smoking habits across two subsequent male pregnancies, there was an increased risk of overweight for the second son only if the mother was smoking in both male pregnancies. The effect of smoking during pregnancy on the offsprings body mass index was not present when the association was evaluated within full and half sibling pairs.nnnCONCLUSIONnThe association between maternal smoking during pregnancy and offsprings risk of overweight appears to be confounded by familial factors.

Twinship influence on morbidity and mortality across the lifespan

BACKGROUNDnStudies in twins may be questioned with respect to their representativeness of the general population, not least considering the potential importance of the fetal environment for future health and disease. To better understand the influence twinning may have on health, we investigated long-term health outcomes of twins, their singleton siblings and singletons from the population.nnnMETHODSnMorbidity and mortality in twins was contrasted to that of their singleton siblings. These singletons from families with twins were then compared with singletons of the population to further reveal potential twin family influences on health. Familial relations were identified through the Swedish Multi-Generation Register. Among individuals born between 1932 and 1958, the number of twins and their singleton siblings identified were 49,156 and 35,277, respectively. Outcomes were incident overall cancer, cardiovascular disease (CVD) and death, identified in national registers. Standardized survival functions were estimated using Cox proportional hazards regression and the corresponding cumulative risks plotted against age.nnnRESULTSnCumulative risks of cancer, CVD and death in twins did not differ from singletons of families with twins, who in turn were found to be similar to singletons of families without twins. As could be expected from these findings, no differences in risks were found when twins were compared with singletons of the population.nnnCONCLUSIONSnDespite their adverse intrauterine experience, twins do not seem to fare worse than singletons with respect to adult morbidity and mortality. The findings indicate that the unique experience of twinning does not lead to adverse long-term health outcomes.

Birth Weight Predicts Risk of Cardiovascular Disease Within Dizygotic but Not Monozygotic Twin Pairs A Large Population-Based Co-Twin–Control Study

Background— The widely reported inverse association between birth weight and risk of cardiovascular disease (CVD) has sparked theories about early life determinants of adult disease. Within-twin-pair analysis provides a unique opportunity to investigate whether factors shared within twin pairs influence the association. Methods and Results— In a population-based cohort of like-sexed twins with known zygosity born in Sweden from 1926 to 1958, disease-discordant twin pairs were identified through linkage to the National Inpatient and Cause of Death registers between 1973 and 2006. Co-twin–control analyses were performed on twins discordant for cardiovascular disease (n=3884), coronary heart disease (n=2668), and stroke (n=1372). Overall, inverse associations between birth weight and risk of cardiovascular diseases were seen within dizygotic but not monozygotic twin pairs. In dizygotic twins, the odds ratios for a 1-kg within-pair increase in birth weight were 0.74 (95% confidence interval, 0.56 to 0.98) for coronary heart disease and 0.57 (95% confidence interval, 0.37 to 0.88) for stroke. Conversely, no statistically significant associations were found within monozygotic twins (for coronary heart disease: odds ratio, 1.10; 95% confidence interval, 0.73 to 1.68; for stroke: odds ratio, 0.92; 95% confidence interval, 0.48 to 1.80). Conclusions— We found an association between birth weight and risk of cardiovascular disease within disease-discordant dizygotic but not monozygotic twin pairs. This indicates that the association between birth weight and cardiovascular disease could be a result of common causes, and that factors that vary within dizygotic but not monozygotic twin pairs may help identify them.

Prenatal smoking exposure and offspring stress coping in late adolescence: no causal link

BACKGROUNDnIn utero exposure to tobacco smoking has been suggested to cause persistent alterations in cognitive functioning. We examined if mothers smoking during pregnancy (SDP) is associated with long-term impairment in offspring stress coping and the causal mechanism behind a possible link.nnnMETHODSnWe used a large cohort (nu2009=u2009187,106) of young males in Sweden (mean ageu2009=u200918.2 years), who underwent a semi-structured psychological assessment in 1997-2006, including an evaluation of stress coping ability, as part of the compulsory military conscript examination. We compared differentially exposed siblings within nuclear families and cousins in extended families and used multilevel structural equation models to disentangle genetic from environmental contributions to the association between SDP and stress coping.nnnRESULTSnSDP and offspring stress coping was moderately strongly associated when comparing unrelated individuals [regression coefficient (b)u2009=u2009-0.38 on a nine-point scale; 95% confidence interval (CI) -0.40 to -0.36, Pu2009<u20090.0001]. In contrast, it disappeared when siblings were compared (bu2009=u20090.11; 95% CI -0.01 to 0.23, Pu2009=u20090.071). This familial confounding was entirely due to genetic influences.nnnCONCLUSIONSnSDP is an established risk factor for pregnancy- and birth-related complications. However, we found no long-term effect of SDP on offspring stress coping. Rather, the observed association was due to familial confounding of genetic origin; women prone to SDP also transmit genes to their children that are associated with poorer coping with stress.

Effects of maternal smoking during pregnancy on offspring blood pressure in late adolescence

Objectives: Previous studies suggest that maternal smoking during pregnancy is associated with elevated offspring blood pressure during childhood. We aimed to investigate whether this association remained in late adolescence and, if so, whether it could be attributed to an intrauterine effect or to familial confounding. Methods: We used a national cohort of 87u200a223 young Swedish men born between 1983 and 1988 with information on both maternal smoking during pregnancy and blood pressure at military conscription. The cohort included 780 full brothers discordant for maternal smoking. Generalized estimation equations were used to estimate regression coefficients (&bgr;) with 95% confidence intervals (95% CIs). Results: We found a small but significant increase in both SBP and DBP for young men whose mothers had been daily smokers during pregnancy compared with sons of nonsmoking mothers: 0.26 (95% CI 0.09 to 0.44) and 0.45u200ammHg (95% CI 0.31 to 0.59) for SBP and DBP, respectively. In a within-sibling analysis comparing full brothers discordant for maternal smoking exposure, point estimates were similar but not statistically significant: 0.85 (95% CI −0.19 to 1.90) for DBP and 0.81 (−0.56 to 2.19) for SBP. Conclusion: Maternal smoking during pregnancy is associated with a small but statistically significant increase in offspring blood pressure in late adolescence. Because the association does not appear to be explained by familial confounding, our results support an intrauterine effect of prenatal smoking exposure on blood pressure in late adolescence.