Using data on biomarkers and siblings to study early-life economic determinants of type-2 diabetes.

We study the effect of economic conditions early in life on the occurrence of type-2 diabetes in adulthood using contextual economic indicators and within-sibling pair variation. We use data from Lifelines: a longitudinal cohort study and biobank including 51,270 siblings born in the Netherlands from 1950 onward. Sibling fixed-effects account for selective fertility. To identify type-2 diabetes we use biomarkers on the hemoglobin A1c concentration and fasting glucose in the blood. We find that adverse economic conditions around birth increase the probability of type-2 diabetes later in life both in males and in females. Inference based on self-reported diabetes leads to biased results, incorrectly suggesting the absence of an effect. The same applies to inference that does not account for selective fertility.

The causal effects of education on adult health, mortality and income: evidence from Mendelian randomization and the raising of the school leaving age.

BACKGROUND: On average, educated people are healthier, wealthier and have higher life expectancy than those with less education. Numerous studies have attempted to determine whether education causes differences in later health outcomes or whether another factor ultimately causes differences in education and subsequent outcomes. Previous studies have used a range of natural experiments to provide causal evidence. Here we compare two natural experiments: a policy reform, raising the school leaving age in the UK in 1972; and Mendelian randomization. METHODS: We used data from 334 974 participants of the UK Biobank, sampled between 2006 and 2010. We estimated the effect of an additional year of education on 25 outcomes, including mortality, measures of morbidity and health, ageing and income, using multivariable adjustment, the policy reform and Mendelian randomization. We used a range of sensitivity analyses and specification tests to assess the plausibility of each method's assumptions. RESULTS: The three different estimates of the effects of educational attainment were largely consistent in direction for diabetes, stroke and heart attack, mortality, smoking, income, grip strength, height, body mass index (BMI), intelligence, alcohol consumption and sedentary behaviour. However, there was evidence that education reduced rates of moderate exercise and increased alcohol consumption. Our sensitivity analyses suggest that confounding by genotypic or phenotypic confounders or specific forms of pleiotropy are unlikely to explain our results. CONCLUSIONS: Previous studies have suggested that the differences in outcomes associated with education may be due to confounding. However, the two independent sources of exogenous variation we exploit largely imply consistent causal effects of education on outcomes later in life.

Food abundance in men before puberty predicts a range of cancers in grandsons.

Nutritional conditions early in human life may influence phenotypic characteristics in later generations. A male-line transgenerational pathway, triggered by the early environment, has been postulated with support from animal and a small number of human studies. Here we analyse individuals born in Uppsala Sweden 1915-29 with linked data from their children and parents, which enables us to explore the hypothesis that pre-pubertal food abundance may trigger a transgenerational effect on cancer events. We used cancer registry and cause-of-death data to analyse 3422 cancer events in grandchildren (G2) by grandparental (G0) food access. We show that variation in harvests and food access in G0 predicts cancer occurrence in G2 in a specific way: abundance among paternal grandfathers, but not any other grandparent, predicts cancer occurrence in grandsons but not in granddaughters. This male-line response is observed for several groups of cancers, suggesting a general susceptibility, possibly acquired in early embryonic development. We observed no transgenerational influence in the middle generation.

The effects of a daycare reform on health in childhood - Evidence from Sweden.

This paper studies the impact of a daycare reform on children's mental and physical health development in Sweden. The reform effectively reduced daycare fees by a significant amount and went along with an expansion of supply. We draw on a unique set of comprehensive individual-level healthcare register data over the period 1999-2008. By exploiting variation in reform exposure by birth cohort, we estimate short and medium-run effects on child health at different ages. We find a significant reduction in mental disorders in the medium-run for children affected by the reform. The reform leads to strong and immediate increases in probabilities of diagnosis with physical health conditions that fade out as children get older. Sub-sample analyses indicate that the reform effects are strongly associated with children from disadvantaged backgrounds. An analysis of healthcare utilization shows that affected children have more overall medical visits at younger ages but fewer sickness-related visits in primary school than non-affected children.

Consistency of noncognitive skills and their relation to educational outcomes in a UK cohort.

Noncognitive skills have been shown to associate with a range of health and socioeconomic outcomes. Many studies have relied on cross sectional data and have been unable to assess the longitudinal consistency of noncognitive skill measures. Using data from a UK birth cohort, we investigated a range of noncognitive skills: behavioural problems, social skills, communication, self-esteem, persistence, locus of control, empathy, impulsivity and personality. We assessed their consistency over a 17-year period throughout childhood and adolescence (age 6 months to 18 years), their genomic architecture, and their associations with socioeconomic outcomes. We found high longitudinal measurement consistency for behavioural and communication skills, but low consistency for other noncognitive skills, suggesting a high noise to signal ratio. We observed consistent non-zero heritability estimates and genetic correlations for only behavioural difficulties. Using aggregate measures of each skill over time, we found evidence of phenotypic correlations and heritability ([Formula: see text] = 0.1-0.2) for behaviour, communication, self-esteem and locus of control. Associations between noncognitive skills and educational outcomes were observed for skills measured in mid to late childhood but these were at most a third of the size of IQ-education associations. These results suggest that measures designed to capture noncognitive skills may be subject to considerable response heterogeneity or measurement error. Aggregate measures that leverage repeat responses from longitudinal data may offer researchers more reliable measures that better identify underlying noncognitive skills than cross sectional measures.

Grandchild's IQ is associated with grandparental environments prior to the birth of the parents.

Background. Despite convincing animal experiments demonstrating the potential for environmental exposures in one generation to have demonstrable effects generations later, there have been few relevant human studies. Those that have been undertaken have demonstrated associations, for example, between exposures such as nutrition and cigarette smoking in the grandparental generation and outcomes in grandchildren. We hypothesised that such transgenerational associations might be associated with the IQ of the grandchild, and that it would be likely that there would be differences in results between the sexes of the grandparents, parents, and children. Method. We used three-generational data from the Avon Longitudinal Study of Parents and Children (ALSPAC).  We incorporated environmental factors concerning grandparents (F0) and focussed on three exposures that we hypothesised may have independent transgenerational associations with the IQ of the grandchildren (F2): (i) UK Gross Domestic Product (GDP) at grandparental birth year; (ii) whether grandfather smoked; and (iii) whether the grandmother smoked in the relevant pregnancy. Potential confounders were ages of grandparents when the relevant parent was born, ethnic background, education level and social class of each grandparent. Results. After adjustment, all three target exposures had specific associations with measures of IQ in the grandchild. Paternal grandfather smoking was associated with reduced total IQ at 15 years; maternal grandfather smoking with reduced performance IQ at 8 years and reduced total IQ at 15.  Paternal grandmother smoking in pregnancy was associated with reduced performance IQ at 8, especially in grandsons. GDP at grandparents' birth produced independent associations of reduced IQ with higher GDP; this was particularly true of paternal grandmothers. Conclusions. These results are complex and need to be tested in other datasets. They highlight the need to consider possible transgenerational associations in studying developmental variation in populations.

Associations of parental age with offspring all-cause and cause-specific adult mortality.

People are having children later in life. The consequences for offspring adult survival have been little studied due to the need for long follow-up linked to parental data and most research has considered offspring survival only in early life. We used Swedish registry data to examine all-cause and cause-specific adult mortality (293,470 deaths among 5,204,433 people, followed up to a maximum of 80 years old) in relation to parental age. For most common causes of death adult survival was improved in the offspring of older parents (HR for all-cause survival was 0.96 (95% CI: 0.96, 0.97) and 0.98 (0.97, 0.98) per five years of maternal and paternal age, respectively). The childhood environment provided by older parents may more than compensate for any physiological disadvantages. Within-family analyses suggested stronger benefits of advanced parental age. This emphasises the importance of secular trends; a parent's later children were born into a wealthier, healthier world. Sibling-comparison analyses can best assess individual family planning choices, but our results suggested a vulnerability to selection bias when there is extensive censoring. We consider the numerous causal and non-causal mechanisms which can link parental age and offspring survival, and the difficulty of separating them with currently available data.

Economic conditions at birth and cardiovascular disease risk in adulthood: Evidence from post-1950 cohorts.

Much of the literature that studies long-run effects of early-life economic conditions on health outcomes is based on pre-1940 birth cohorts. Early in these individuals' lives, public social safety nets were at best rudimentary, and female labor force participation was relatively low. We complement the evidence by studying the effects of regional business cycle variations in the post-1950 Netherlands on cardiovascular disease risk in adulthood. We use data from Lifelines, a large cohort study that covers socio-economic, biological and health information from over 75,000 individuals aged between 20 and 63. Cardiovascular risk index is constructed from an extensive set of biomarkers. The results show that for women a 1 percentage point increase in the provincial unemployment level leads to a 0.02 percentage point increase in the risk of a fatal cardiovascular event in the coming 10 years while the effect in men is not significant. We conclude that women born in adverse economic conditions experience higher cardiovascular risk.

Paternal grandfather's access to food predicts all-cause and cancer mortality in grandsons.

Studies of animals and plants suggest that nutritional conditions in one generation may affect phenotypic characteristics in subsequent generations. A small number of human studies claim to show that pre-pubertal nutritional experience trigger a sex-specific transgenerational response along the male line. A single historical dataset, the Överkalix cohorts in northern Sweden, is often quoted as evidence. To test this hypothesis on an almost 40 times larger dataset we collect harvest data during the pre-pubertal period of grandparents (G0, n = 9,039) to examine its potential association with mortality in children (G1, n = 7,280) and grandchildren (G2, n = 11,561) in the Uppsala Multigeneration Study. We find support for the main Överkalix finding: paternal grandfather's food access in pre-puberty predicts his male, but not female, grandchildren's all-cause mortality. In our study, cancer mortality contributes strongly to this pattern. We are unable to reproduce previous results for diabetes and cardiovascular mortality.

Mortality and the business cycle: Evidence from individual and aggregated data.

There has been much interest recently in the relationship between economic conditions and mortality, with some studies showing that mortality is pro-cyclical, while others find the opposite. Some suggest that the aggregation level of analysis (e.g. individual vs. regional) matters. We use both individual and aggregated data on a sample of 20-64 year-old Swedish men from 1993 to 2007. Our results show that the association between the business cycle and mortality does not depend on the level of analysis: the sign and magnitude of the parameter estimates are similar at the individual level and the aggregate (county) level; both showing pro-cyclical mortality.

Associations of parental age with health and social factors in adult offspring. Methodological pitfalls and possibilities.

Parental age is increasing rapidly in many countries. Analysis of this potentially important influence on offspring well-being is hampered by strong secular trends and socioeconomic patterning and by a shortage of follow-up data for adult offspring. We used Swedish national data on up to 3,653,938 offspring to consider the associations of parental age with a suite of outcomes in adult offspring, comparing the results from an array of statistical methods for optimal causal inference. The offspring of older mothers had higher BMI, blood pressure, height, intelligence, non-cognitive ability and socioeconomic position. They were less likely to smoke or to be left-handed. Associations with paternal age were strongly, but not completely, attenuated by adjustment for maternal age. Estimates from the commonly-used sibling comparison method were driven primarily by a pathway mediated by offspring date of birth when outcomes showed strong secular trends. These results suggest that the intra-uterine and early life environments provided by older mothers may be detrimental to offspring cardiovascular health, but that their greater life experience and social position may bring intellectual and social advantages to their offspring. The analysis of parental age presents particular challenges, and further methodological developments are needed.

Does the Size of the Effect of Adverse Events at High Ages on Daily-Life Physical Functioning Depend on the Economic Conditions Around Birth?

This paper considers determinants of physical functional limitations in daily-life activities at high ages. Specifically, we quantify the extent to which the impact of adverse life events on this outcome is larger in case of exposure to adverse economic conditions early in life. Adverse life events include bereavement, severe illness in the family, and the onset of chronic diseases. We use a longitudinal data set of individuals born in the first decades of the 20th century. The business cycle around birth is used as an indicator of economic conditions early in life. We find that the extent to which functional limitations suffer from the onset of chronic diseases is larger if the individual was born in a recession. The long-run effect of economic conditions early in life on functional limitations at high ages runs primarily via this life event. Copyright © 2015 John Wiley & Sons, Ltd.

Transgenerational effects of childhood conditions on third generation health and education outcomes.

This paper examines the extent to which pre-puberty nutritional conditions in one generation affect productivity-related outcomes in later generations. Recent findings from the biological literature suggest that the so-called slow growth period around age 9 is a sensitive period for male germ cell development. We build on this evidence and investigate whether undernutrition at those ages transmits to children and grandchildren. Our findings indicate that third generation males (females) tend to have higher mental health scores if their paternal grandfather (maternal grandmother) was exposed to a famine during the slow growth period. These effects appear to reflect biological responses to adaptive expectations about scarcity in the environment, and as such they can be seen as an economic correctional mechanism in evolution, with marked socio-economic implications for the offspring.

The role of marriage in the causal pathway from economic conditions early in life to mortality.

This paper analyzes the interplay between early-life conditions and marital status, as determinants of adult mortality. We use individual data from Dutch registers (years 1815-2000), combined with business cycle conditions in childhood as indicators of early-life conditions. The empirical analysis estimates bivariate duration models of marriage and mortality, allowing for unobserved heterogeneity. Results show that conditions around birth and school going ages are important for marriage and mortality. Men typically enjoy a protective effect of marriage, whereas women suffer during childbearing ages. However, having been born under favorable economic conditions reduces female mortality during childbearing ages.

Long-run effects of gestation during the Dutch Hunger Winter famine on labor market and hospitalization outcomes.

The Dutch Hunger Winter (1944/45) is the most-studied famine in the literature on long-run effects of malnutrition in utero. Its temporal and spatial demarcations are clear, it was severe, it was not anticipated, and nutritional conditions in society were favorable and stable before and after the famine. This is the first study to analyze effects of in utero exposure on labor market outcomes and hospitalization late in life, and the first to use register data covering the full Dutch population to examine long-run effects of this famine. We provide results of famine exposure by sub-interval of gestation. We find a significantly negative effect of exposure during the first trimester of gestation on employment outcomes 53 or more years after birth. Hospitalization rates in the years before retirement are higher after middle or late gestational exposure.

Can individual conditions during childhood mediate or moderate the long-term cognitive effects of poor economic environments at birth?

Recent analyses revealed that the business cycle at the time of birth influences cognitive functioning at older ages, and that those individuals born during economic boom periods on average display better cognitive functioning later in life. The current study examines the impact of childhood conditions on late-life cognitive functioning and investigates whether they mediate or moderate the effects of the business cycle at the time of birth. The underlying purpose is to find potential starting points for societal interventions that may counterbalance the negative long-term outcomes of adverse living conditions early in life. We use data from 7935 respondents at ages 60+ in eleven European countries from the first three waves of the Survey of Health, Ageing and Retirement in Europe (SHARE). The survey data was collected in 2004, 2006/07, and 2008/09. Country fixed-effects models are used to examine the impact of macro-economic deviations in the year of birth and the indicators of childhood circumstances on late-life cognitive functioning. This study shows that the effects of boom and recession periods at birth are not simply mediated or moderated by living conditions during childhood. Conditions at birth have biological long-run effects on late-life cognitive functioning. Individuals born during boom periods display signs of having better cognitive functioning later in life, whereas recessions negatively influence cognition. Furthermore, a series of childhood conditions in and of themselves influence late-life cognition. Good childhood cognition, high education as well as a high social status, favourable living arrangements, and good health have a positive impact. Policy interventions should aim at a better access to school or measures to improve the economic and social situations of disadvantaged households.

Ambient temperature during gestation and cold-related adult mortality in a Swedish cohort, 1915-2002.

For all climatic regions, mortality due to cold exceeds mortality due to heat. A separate line of research indicates that season of birth predicts lifespan after age 50. This and other literature implies the hypothesis that ambient temperature during gestation may influence cold-related adult mortality. We use data on over 13,500 Swedes from the Uppsala Birth Cohort Study to test whether cold-related mortality in adulthood varies positively with unusually benign ambient temperature during gestation. We linked daily thermometer temperatures in Uppsala, Sweden (1915-2002) to subjects beginning at their estimated date of conception and ending at death or the end of follow-up. We specified a Cox proportional hazards model with time-dependent covariates to analyze the two leading causes of cold-related death in adulthood: ischemic heart disease (IHD) and stroke. Over 540,450 person-years, 1313 IHD and 406 stroke deaths occurred. For a one standard deviation increase in our measure of warm temperatures during gestation, we observe an increased hazard ratio of 1.16 for cold-related IHD death (95% confidence interval: 1.03-1.29). We, however, observe no relation for cold-related stroke mortality. Additional analyses show that birthweight percentile and/or gestational age do not mediate discovered findings. The IHD results indicate that ambient temperature during gestation--independent of birth month--modifies the relation between cold and adult mortality. We encourage longitudinal studies of the adult sequelae of ambient temperature during gestation among populations not sufficiently sheltered from heat or cold waves.

Economic conditions at the time of birth and cognitive abilities late in life: evidence from ten European countries.

With ageing populations, it becomes increasingly important to understand the determinants of cognitive ability among the elderly. We apply survey data of 17,070 respondents from ten countries to examine several domains of cognitive functioning at ages 60+, and we link them to the macro-economic deviations in the year of birth. We find that economic conditions at birth significantly influence cognitive functioning late in life in various domains. Recessions negatively influence numeracy, verbal fluency, recall abilities, as well as the score on the omnibus cognitive indicator. The results are robust; controlling for current characteristics does not change effect sizes and significance. We discuss possible causal social and biological pathways.