Mia Madsen

Leisure time physical exercise during pregnancy and the risk of miscarriage: a study within the Danish National Birth Cohort

Objective  To examine the association between leisure time physical exercise during pregnancy and the risk of miscarriage.

Socio-economic inequality in preterm birth: a comparative study of the Nordic countries from 1981 to 2000

During the 1980s and 1990s, there were large social and structural changes within the Nordic countries. Here we examine time changes in risks of preterm birth by maternal educational attainment in Denmark, Finland, Norway and Sweden. Information on gestational age and maternal socio-economic position was obtained from the NorCHASE database, which includes comparable population-based register data of births from Denmark, Finland, Sweden and Norway from 1981 to 2000. The risks of very preterm birth (<32 gestational weeks) and moderately preterm birth (32-36 gestational weeks) were calculated by maternal educational attainment and analysed in 5-year intervals from 1981 to 2000. Compared with mothers with >12 years of education, mothers with <10 years of education had similarly increased risks of very, and to a lesser extent moderately, preterm birth in all four countries. The educational gradient increased slightly over time in very preterm births in Denmark, while there was a slight narrowing of the gap in Sweden. In moderately preterm births, the educational inequality gap was constant over the study period in Denmark, Norway and Sweden, but narrowed in Finland. The educational gradient in preterm birth remained broadly stable from 1981 to 2000 in all four countries. Consequently, the socio-economic inequalities in preterm birth were not strongly influenced by structural changes during the period.

Does Educational Status Impact Adult Mortality in Denmark? A Twin Approach

To disentangle an independent effect of educational status on mortality risk from direct and indirect selection mechanisms, the authors used a discordant twin pair design, which allowed them to isolate the effect of education by means of adjustment for genetic and environmental confounding per design. The study is based on data from the Danish Twin Registry and Statistics Denmark. Using Cox regression, they estimated hazard ratios for mortality according to the highest attained education among 5,260 monozygotic and 11,088 dizygotic same-sex twin pairs born during 1921–1950 and followed during 1980–2008. Both standard cohort and intrapair analyses were conducted separately for zygosity, gender, and birth cohort. Educational differences in mortality were demonstrated in the standard cohort analyses but attenuated in the intrapair analyses in all subgroups but men born during 1921–1935, and no effect modification by zygosity was observed. Hence, the results are most compatible with an effect of early family environment in explaining the educational inequality in mortality. However, large educational differences were still reflected in mortality risk differences within twin pairs, thus supporting some degree of independent effect of education. In addition, the effect of education may be more pronounced in older cohorts of Danish men.

Do childhood and adult socioeconomic circumstances influence health and physical function in middle-age?

This study examines the joint and separate contribution of social class in early and adult life to differences in health and physical function in middle-aged men. We use data from the Metropolit project which includes men born in 1953 in Copenhagen and a study of middle-aged Danish twins (MADT). In total 6292 Metropolit participants in a follow-up survey on health in 2004 were included in the study together with 2198 male twins of which 1294 were part of a male twin pair (N=647 pairs). Logistic regression was used to investigate the association between social class in early and adult life, respectively and health in midlife, measured as limitations in running 100 m, poor dental status, poor self-rated health, and fatigue. In both datasets, men with low childhood or adult social class had a higher risk of being unable to run 100 m, having poor dental status, having poor self-rated health and fatigue than men from the highest social classes. When childhood and adult social class were mutually adjusted, the estimates for both measures were attenuated. Adjustment for living without a partner, body mass index (BMI) and smoking in midlife, which were also related to the four outcomes, had marginal effects on the estimates for childhood social class, but attenuated the effect of adult social class somewhat. Among male twin pairs discordant on adult social class, the twin in the lowest class seemed to be unable to run 100 m, rate own health poorer and being fatigued more often than the high class co-twin, while there seemed to be no twin pair difference in dental status. This suggests that the associations of adult social class with functional limitations, poor self-rated health and fatigue may partly be due to causal effects related to adult social class exposures, while social class differences in dental status might be consistent with an effect of factors mainly operating early in life.

Maternal use of nicotine replacement therapy during pregnancy and offspring birthweight: a study within the Danish National Birth Cohort

Smoking is a well-established risk factor for fetal growth restriction and other adverse pregnancy outcomes, and nicotine may be one of the chemical compounds that drive these associations. Nicotine replacement therapy (NRT) is a smoking cessation aid, which can facilitate smoking cessation. It is, however, unknown whether NRT used during pregnancy impairs fetal growth. The aim of this study was to estimate the association between the use of NRT during pregnancy and offspring birthweight. The study population consisted of 72 761 women enrolled in the Danish National Birth Cohort between 1996 and 2002. Information on NRT and potential confounders was obtained from two computer-assisted telephone interviews conducted in the second and third trimesters, respectively. Multiple linear regression in a multilevel model was used to estimate the association between NRT use and birthweight adjusted for gestational age and potential confounders. The adjusted analyses showed no significant association between the duration of NRT use and birthweight (b = 0.25 g per week of NRT use [95% CI -2.31, 2.81]) and neither was the type of NRT product (patch, gum, inhaler) associated with reduced birthweight. However, simultaneous use of more than one NRT product was associated with reduced birthweight (b = -10.73 g per week of NRT use [95% CI -26.51, 5.05]), although the association was not statistically significant. The results of this study suggest that maternal use of NRT in pregnancy does not seriously affect birthweight, but there could be a negative effect on birthweight associated with simultaneous use of more than one type of NRT product.

Are the educational differences in incidence of cardiovascular disease explained by underlying familial factors? A twin study

To isolate the effect of education from the influence of potential underlying factors, we investigated the association of education with the risk of cardiovascular disease (CVD) and ischemic heart disease (IHD) using twin data to adjust for familial factors shared within twins, including genetic make-up and childhood environment. The study was based on data from the Danish Twin Registry linked to administrative and heath registers in Statistics Denmark. A total of 11,968 monozygotic and 20,464 dizygotic same sexed twins were followed from 1980 to 2009, including more than 8000 events of CVD. Unpaired and intra-pair analyses were compared. In the unpaired analyses, an inverse educational gradient in CVD- and IHD risk was observed. This association was not replicated in the intra-pair analyses that control for shared familial factors exploiting that twins share their intrauterine- and childhood environment and are matched partly or fully on genetic setup. The attenuation of association of education with CVD and IHD in the intra-pair analyses suggests that shared familial factors account for a substantial part of the observed association of education with CVD and IHD in Denmark.

Does Shared Family Background Influence the Impact of Educational Differences on Early Mortality

The mechanisms behind social differences in mortality rates have been debated. The authors examined the extent to which shared family background and health in early life could explain the association between educational status and all-cause mortality rates using a sibling design. The study was register-based and included all individuals born in Denmark between 1950 and 1979 who had at least 1 full sibling born in the same time period (n = 1,381,436). All individuals were followed from 28 years of age until death, emigration, or December 2009. The authors used Cox regression analyses to estimate hazard ratios for mortality according to educational level. Conventional cohort and intersibling analyses were carried out and conducted separately for deaths occurring before and after the age of 45 years, respectively. The cohort analyses showed an inverse association between educational status and all-cause mortality that was strongest for males, increased with younger birth cohorts, and tended to be strongest in the analyses of death before 45 years of age. The associations were attenuated slightly in the intersibling analyses and after adjustment for serious health conditions in early life. Hence, health selection and confounding by factors shared by siblings explained only a minor part of the association between educational level and all-cause mortality.

Commentary: Strengths and limitations of the discordant twin-pair design in social epidemiology. Where do we go from here?

It has become increasingly recognized that many of the associations between various exposures and health outcomes measured in adulthood are confounded by social and behavioural factors acting early in life, 1 and recent research has questioned

Does the association of education with breast cancer replicate within twin pairs? A register-based study on Danish female twins.

Background:A positive association between socio-economic position and breast cancer has been widely observed, but not hitherto within twin pairs, where shared familial factors were adjusted for.Methods:We used data on education and other factors from the Danish Twin Registry, The Danish Cancer Registry, and official registers on a total of 16 310 twins. Unpaired and intrapair Cox regression analyses were compared.Results:In the unpaired analysis, an educational gradient in breast cancer risk was found. Similar results were seen in the intrapair analyses of all twins, although no longer statistically significant. When intrapair analyses were stratified on zygosity, the effect of education was attenuated in the monozygotic twins.Conclusion:The main findings support an effect of education beyond shared familial factors.

Matched survival data in a co-twin control design

When using the co-twin control design for analysis of event times, one needs a model to address the possible within-pair association. One such model is the shared frailty model in which the random frailty variable creates the desired within-pair association. Standard inference for this model requires independence between the random effect and the covariates. We study how violations of this assumption affect inference for the regression coefficients and conclude that substantial bias may occur. We propose an alternative way of making inference for the regression parameters by using a fixed-effects models for survival in matched pairs. Fitting this model to data generated from the frailty model provides consistent and asymptotically normal estimates of regression coefficients, no matter whether the independence assumption is met.