Reduced reproductive success is associated with selective constraint on human genes.

Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants1. Although genes under the strongest selective constraint are highly enriched for associations with Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known2. Here we show that genetic variants that damage these genes are associated with markedly reduced reproductive success, primarily owing to increased childlessness, with a stronger effect in males than in females. We present evidence that increased childlessness is probably mediated by genetically associated cognitive and behavioural traits, which may mean that male carriers are less likely to find reproductive partners. This reduction in reproductive success may account for 20% of purifying selection against heterozygous variants that ablate protein-coding genes. Although this genetic association may only account for a very minor fraction of the overall likelihood of being childless (less than 1%), especially when compared to more influential sociodemographic factors, it may influence how genes evolve over time.

Pathways from education to mortality, mediated through income.

Lower levels of education are associated with higher mortality. Lower levels of education are also associated with lower income, which is also associated with higher mortality. We investigate the impact of education on mortality and the extent to which this is mediated through income over the life course. We account for both selective educational attainment and selective income over the life course, through inverse propensity weighting (IPW) of the mortality hazard. We decompose the educational gain, that is, the decrease in mortality from more education, in the hazard into an indirect effect of education, running through changes in income and a direct effect of education, running through other factors. We use Swedish conscription data (men only), linked to parental information and individual annual income for the period 1968 till 2012. Our empirical results indicate large educational gains in mortality. We also find that this educational gradient runs through changes in income, especially for the more educated, and does not run through other factors related to education. We conduct several robustness and sensitivity checks that indicate that the results are robust.

Birth Spacing and Parents' Physical and Mental Health: An Analysis Using Individual and Sibling Fixed Effects.

An extensive literature has examined the relationship between birth spacing and subsequent health outcomes for parents, particularly for mothers. However, this research has drawn almost exclusively on observational research designs, and almost all studies have been limited to adjusting for observable factors that could confound the relationship between birth spacing and health outcomes. In this study, we use Norwegian register data to examine the relationship between birth spacing and the number of general practitioner consultations for mothers' and fathers' physical and mental health concerns immediately after childbirth (1-5 and 6-11 months after childbirth), in the medium term (5-6 years after childbearing), and in the long term (10-11 years after childbearing). To examine short-term health outcomes, we estimate individual fixed-effects models: we hold constant factors that could influence parents' birth spacing behavior and their health, comparing health outcomes after different births to the same parent. We apply sibling fixed effects in our analysis of medium- and long-term outcomes, holding constant mothers' and fathers' family backgrounds. The results from our analyses that do not apply individual or sibling fixed effects are consistent with much of the previous literature: shorter and longer birth intervals are associated with worse health outcomes than birth intervals of approximately 2-3 years. Estimates from individual fixed-effects models suggest that particularly short intervals have a modest negative effect on maternal mental health in the short term, with more ambiguous evidence that particularly short or long intervals might modestly influence short-, medium-, and long-term physical health outcomes. Overall, these results are consistent with small to negligible effects of birth spacing behavior on (non-pregnancy-related) parental health outcomes.

Health outcomes of only children across the life course: An investigation using Swedish register data.

Only children (with no full biological siblings) are a growing subgroup in many high-income settings. Previous studies have largely focused on the short-term developmental outcomes of only children, but there is limited evidence on their health outcomes. Using Swedish population register data for cohorts born 1940-75, we compare the health of only children with that of children from multi-child sibling groups, taking into account birth order, family size, and presence of half-siblings. Only children showed lower height and fitness scores, were more likely to be overweight/obese in late adolescence, and experienced higher later-life mortality than those with one or two siblings. However, only children without half-siblings were consistently healthier than those with half-siblings, suggesting that parental disruption confers additional disadvantages. The health disadvantage was attenuated but not fully explained by adjustment for parental characteristics and after using within-family maternal cousin comparison designs.

Body mass index in early adulthood and transition to first birth: Racial/ethnic and sex differences in the United States NLSY79 Cohort.

Studies show that body mass index during early adulthood ('early BMI') predicts the transition to first birth, but early childbearers tend to be omitted from such studies. This sample selection distorts the prevalence of childlessness, and particularly the racial/ethnic heterogeneity therein, because first birth timing differs by race/ethnicity. We imputed pre-parenthood early BMI for a larger sample, including early childbearers, for the same United States NLSY79 data used in a previous study and simulated differences in the probability of childlessness at age 40+ using posterior distributions based on the Bayesian framework. Obesity was consistently associated with higher childlessness across racial/ethnic groups in both sexes, but only among obese women were first births delayed until after early adulthood. The overall lower childlessness among the underweight women appeared largely driven by Black women. Our findings on the intersectionality of race/ethnicity and sex in the BMI-childlessness pathways encourage research on the underlying mechanisms and on more recent cohorts across different societies.

Preterm birth and educational disadvantage: Heterogeneous effects.

Although preterm birth is the leading cause of perinatal morbidity and mortality in advanced economies, evidence about the consequences of prematurity in later life is limited. Using Swedish registers for cohorts born 1982-94 (N  =  1,087,750), we examine the effects of preterm birth on school grades at age 16 using sibling fixed effects models. We further examine how school grades are affected by degree of prematurity and the compensating roles of family socio-economic resources and characteristics of school districts. Our results show that the negative effects of preterm birth are observed mostly among children born extremely preterm (<28 weeks); children born moderately preterm (32-<37 weeks) suffer no ill effects. We do not find any evidence for a moderating effect of parental socio-economic resources. Children born extremely preterm and in the top decile of school districts achieve as good grades as children born at full term in an average school district.Supplementary material for this article is available at: http://dx.doi.org/10.1080/00324728.2022.2080247.

Birth Spacing and Health and Socioeconomic Outcomes Across the Life Course: Evidence From the Utah Population Database.

The relationship between birth interval length and child outcomes has received increased attention in recent years, but few studies have examined offspring outcomes across the life course in North America. We use data from the Utah Population Database to examine the relationship between birth intervals and short- and long-term outcomes: preterm birth, low birth weight (LBW), infant mortality, college degree attainment, occupational status, and adult mortality. Using linear regression, linear probability models, and survival analysis, we compare results from models with and without sibling comparisons. Children born after a birth interval of 9-12 months have a higher probability of LBW, preterm birth, and infant mortality both with and without sibling comparisons; longer intervals are associated with a lower probability of these outcomes. Short intervals before the birth of the next youngest sibling are also associated with LBW, preterm birth, and infant mortality both with and without sibling comparisons. This pattern raises concerns that the sibling comparison models do not fully adjust for within-family factors predicting both spacing and perinatal outcomes. In sibling comparison analyses considering long-term outcomes, not even the very shortest birth intervals are negatively associated with educational or occupational outcomes or with long-term mortality. These findings suggest that extremely short birth intervals may increase the probability of poor perinatal outcomes but that any such disadvantages disappear over the extended life course.

Sibling Similarity in Education Across and Within Societies.

The extent to which siblings resemble each other measures the omnibus impact of family background on life chances. We study sibling similarity in cognitive skills, school grades, and educational attainment in Finland, Germany, Norway, Sweden, the United Kingdom, and the United States. We also compare sibling similarity by parental education and occupation within these societies. The comparison of sibling correlations across and within societies allows us to characterize the omnibus impact of family background on education across social landscapes. Across countries, we find larger population-level differences in sibling similarity in educational attainment than in cognitive skills and school grades. In general, sibling similarity in education varies less across countries than sibling similarity in earnings. Compared with Scandinavian countries, the United States shows more sibling similarity in cognitive skills and educational attainment but less sibling similarity in school grades. We find that socioeconomic differences in sibling similarity vary across parental resources, countries, and measures of educational success. Sweden and the United States show greater sibling similarity in educational attainment in families with a highly educated father, and Finland and Norway show greater sibling similarity in educational attainment in families with a low-educated father. We discuss the implications of our results for theories about the impact of institutions and income inequality on educational inequality and the mechanisms that underlie such inequality.

The Effects of Marital Status, Fertility, and Bereavement on Adult Mortality in Polygamous and Monogamous Households: Evidence From the Utah Population Database.

Although the associations among marital status, fertility, bereavement, and adult mortality have been widely studied, much less is known about these associations in polygamous households, which remain prevalent across much of the world. We use data from the Utah Population Database on 110,890 women and 106,979 men born up to 1900, with mortality follow-up into the twentieth century. We examine how the number of wife deaths affects male mortality in polygamous marriages, how sister wife deaths affect female mortality in polygamous marriages relative to the death of a husband, and how marriage order affects the mortality of women in polygamous marriages. We also examine how the number of children ever born and child deaths affect the mortality of men and women as well as variation across monogamous and polygamous unions. Our analyses of women show that the death of a husband and the death of a sister wife have similar effects on mortality. Marriage order does not play a role in the mortality of women in polygamous marriages. For men, the death of one wife in a polygamous marriage increases mortality to a lesser extent than it does for men in monogamous marriages. For polygamous men, losing additional wives has a dose-response effect. Both child deaths and lower fertility are associated with higher mortality. We consistently find that the presence of other kin in the household-whether a second wife, a sister wife, or children-mitigates the negative effects of bereavement.

Interpregnancy intervals and perinatal and child health in Sweden: A comparison within families and across social groups.

A large body of research has shown that children born after especially short or long birth intervals experience an elevated risk of poor perinatal outcomes, but recent work suggests this may be explained by confounding by unobserved family characteristics. We use Swedish population data on cohorts born 1981-2010 and sibling fixed effects to examine whether the length of the birth interval preceding the index child influences the risk of preterm birth, low birth weight, and hospitalization during childhood. We also present analyses stratified by salient social characteristics, such as maternal educational level and maternal country of birth. We find few effects of birth intervals on our outcomes, except for very short intervals (less than seven months) and very long intervals (>60 months). We find few differences in the patterns by maternal educational level or maternal country of origin after stratifying by the mother's highest educational attainment.

Cognitive ability and fertility among Swedish men born 1951-1967: evidence from military conscription registers.

We examine the relationship between cognitive ability and childbearing patterns in contemporary Sweden using administrative register data. The topic has a long history in the social sciences and has been the topic of a large number of studies, many reporting a negative gradient between intelligence and fertility. We link fertility histories to military conscription tests with intelligence scores for all Swedish men born 1951-1967. We find a positive relationship between intelligence scores and fertility, and this pattern is consistent across the cohorts we study. The relationship is most pronounced for the transition to a first child, and men with the lowest categories of IQ scores have the fewest children. Using fixed effects models, we additionally control for all factors that are shared by siblings, and after such adjustments, we find a stronger positive relationship between IQ and fertility. Furthermore, we find a positive gradient within groups at different levels of education. Compositional differences of this kind are therefore not responsible for the positive gradient we observe-instead, the relationship is even stronger after controlling for both educational careers and parental background factors. In our models where we compare brothers to one another, we find that, relative to men with IQ 100, the group with the lowest category of cognitive ability have 0.56 fewer children, and men with the highest category have 0.09 more children.

When and Where Birth Spacing Matters for Child Survival: An International Comparison Using the DHS.

A large body of research has found an association between short birth intervals and the risk of infant mortality in developing countries, but recent work on other perinatal outcomes from highly developed countries has called these claims into question, arguing that previous studies have failed to adequately control for unobserved heterogeneity. Our study addresses this issue by estimating within-family models on a sample of 4.5 million births from 77 countries at various levels of development. We show that after unobserved maternal heterogeneity is controlled for, intervals shorter than 36 months substantially increase the probability of infant death. However, the importance of birth intervals as a determinant of infant mortality varies inversely with maternal education and the strength of the relationship varies regionally. Finally, we demonstrate that the mortality-reducing effects of longer birth intervals are strong at low levels of development but decline steadily toward zero at higher levels of development. These findings offer a clear way to reconcile previous research showing that birth intervals are important for perinatal outcomes in low-income countries but are much less consequential in high-income settings.

Parity and Mortality: An Examination of Different Explanatory Mechanisms Using Data on Biological and Adoptive Parents.

A growing literature has demonstrated a relationship between parity and mortality, but the explanation for that relationship remains unclear. This study aims to pick apart physiological and social explanations for the parity-mortality relationship by examining the mortality of parents who adopt children, but who have no biological children, in comparison with the mortality of parents with biological children. Using Swedish register data, we study post-reproductive mortality amongst women and men from cohorts born between 1915 and 1960, over ages 45-97. Our results show the relative risks of mortality for adoptive parents are always lower than those of parents with biological children. Mortality amongst adoptive parents is lower for those who adopt more than one child, while for parents with biological children we observe a U-shaped relationship, where parity-two parents have the lowest mortality. Our discussion considers the relative importance of physiological and social depletion effects, and selection processes.

Birth Intervals and Health in Adulthood: A Comparison of Siblings Using Swedish Register Data.

A growing body of research has examined whether birth intervals influence perinatal outcomes and child health as well as long-term educational and socioeconomic outcomes. To date, however, very little research has examined whether birth spacing influences long-term health. We use contemporary Swedish population register data to examine the relationship between birth-to-birth intervals and a variety of health outcomes in adulthood: for men, height, physical fitness, and the probability of falling into different body mass index categories; and for men and women, mortality. In models that do not adjust carefully for family background, we find that short and long birth intervals are clearly associated with height, physical fitness, being overweight or obese, and mortality. However, after carefully adjusting for family background using a within-family sibling comparison design, we find that birth spacing is generally not associated with long-term health, although we find that men born after very long birth intervals have a higher probability of being overweight or obese in early adulthood. Overall, we conclude that birth intervals have little independent effect on long-term health outcomes.

Parental age and offspring mortality: Negative effects of reproductive ageing may be counterbalanced by secular increases in longevity.

As parental ages at birth continue to rise, concerns about the effects of fertility postponement on offspring are increasing. Due to reproductive ageing, advanced parental ages have been associated with negative health outcomes for offspring, including decreased longevity. The literature, however, has neglected to examine the potential benefits of being born at a later date. Secular declines in mortality mean that later birth cohorts are living longer. We analyse mortality over ages 30-74 among 1.9 million Swedish men and women born 1938-60, and use a sibling comparison design that accounts for all time-invariant factors shared by the siblings. When incorporating cohort improvements in mortality, we find that those born to older mothers do not suffer any significant mortality disadvantage, and that those born to older fathers have lower mortality. These findings are likely to be explained by secular declines in mortality counterbalancing the negative effects of reproductive ageing.

Advanced Maternal Age and the Risk of Low Birth Weight and Preterm Delivery: a Within-Family Analysis Using Finnish Population Registers.

Advanced maternal age at birth is considered a major risk factor for birth outcomes. It is unclear to what extent this association is confounded by maternal characteristics. To test whether advanced maternal age at birth independently increases the risk of low birth weight (<2,500 g) and preterm birth (<37 weeks' gestation), we compared between-family models (children born to different mothers at different ages) with within-family models (children born to the same mother at different ages). The latter procedure reduces confounding by unobserved parental characteristics that are shared by siblings. We used Finnish population registers, including 124,098 children born during 1987-2000. When compared with maternal ages 25-29 years in between-family models, maternal ages of 35-39 years and ≥40 years were associated with percentage increases of 1.1 points (95% confidence intervals: 0.8, 1.4) and 2.2 points (95% confidence intervals: 1.4, 2.9), respectively, in the probability of low birth weight. The associations are similar for the risk of preterm delivery. In within-family models, the relationship between advanced maternal age and low birth weight or preterm birth is statistically and substantively negligible. In Finland, advanced maternal age is not independently associated with the risk of low birth weight or preterm delivery among mothers who have had at least 2 live births.

The Long-Term Cognitive and Socioeconomic Consequences of Birth Intervals: A Within-Family Sibling Comparison Using Swedish Register Data.

We examine the relationship between birth-to-birth intervals and a variety of mid- and long-term cognitive and socioeconomic outcomes, including high school GPA, cognitive ability, educational attainment, earnings, unemployment status, and receiving government welfare support. Using contemporary Swedish population register data and a within-family sibling comparison design, we find that neither the birth interval preceding the index person nor the birth interval following the index person are associated with any substantively meaningful changes in mid- or long-term outcomes. This is true even for individuals born before or after birth-to-birth intervals of less than 12 months. We conclude that in a contemporary high-income welfare state, there appears to be no relationship between unusually short or long birth intervals and adverse long-term outcomes.

The effect of number of siblings on adult mortality: Evidence from Swedish registers for cohorts born between 1938 and 1972.

Demographic research has paid much attention to the impact of childhood conditions on adult mortality. We focus on one of the key aspects of early life conditions, sibling group size, and examine the causal effect of growing up in a large family on mortality. While previous studies have focused on low- or middle-income countries, we examine whether growing up in a large family is a disadvantage in Sweden, a context where most parents have adequate resources, which are complemented by a generous welfare state. We used Swedish register data and frailty models, examining all-cause and cause-specific mortality between the ages of 40 and 74 for the 1938-72 cohorts, and also a quasi-experimental approach that exploited multiple births as a source of exogenous variation in the number of siblings. Overall our results do not indicate that growing up in a large family has a detrimental effect on longevity in Sweden.

Workplace sex composition and ischaemic heart disease: A longitudinal analysis using Swedish register data.

AIMS: The aim of this study is to follow-up on previous research indicating that the sex composition of workplaces is related to a number of health outcomes, including sickness absenteeism and mortality. We test two hypotheses. The first is Kanter's theory of tokenism, which suggests that minority group members suffer from an increased risk of stress. Secondly, we test the hypothesis that workplaces with a higher proportion of men will have a higher incidence rate of ischaemic heart disease (IHD), as men are more likely to engage in negative health behaviours, and through peer effects this will result in a workplace culture that is detrimental to health over the long term. METHODS: Large-scale, longitudinal Swedish administrative register data are used to study the risk of overnight hospitalization for IHD amongst 67,763 men over the period 1990 to 2001. Discrete-time survival analyses were estimated in the form of logistic regression models. RESULTS: Men have an elevated risk of suffering from IHD in non-gender-balanced workplaces, but this association was only statistically significant in workplaces with 61-80% and 81-100% males. However, after adjusting for occupation no clear pattern of association could be discerned. No pattern of association was observed for women. CONCLUSIONS: This study suggests that the gender composition of workplaces is not strongly associated with the risk of suffering from IHD.

The midlife health of only children: chronic disease indicators and biomarkers by sibship size in three nationally representative UK cohorts.

BACKGROUND: Despite persistent concerns about only children's disadvantage relative to individuals with siblings, existing health-related evidence is inconsistent. Recent evidence from Nordic countries about only children having poorer health outcomes may not apply elsewhere because selection processes differ across contexts. We investigate the midlife health of only children in the UK where one-child families tend to be socio-economically advantaged relative to large families. METHODS: Using the 1946, 1958 and 1970 British birth cohort studies, we examine various biomarkers and self-reported measures of chronic disease by sibship size when respondents are aged in their mid-40s, mid-50s and mid-60s. We estimate separate linear probability models for each cohort, age and outcome, adjusting for childhood and early adulthood circumstances. RESULTS: We found no evidence of only children differing from those with one, two or three or more siblings, at any age, in any of the cohorts, on: heart problems, hypertension, high triglycerides, high glycated haemoglobin or high C-reactive protein. However, compared with only children, the probability for cancer (0.019, 95% confidence interval [CI]: 0.002, 0.035; age 46/1970) and poor general health (0.060, CI: 0.015, 0.127; age 55/1958; and 0.110, CI: 0.052, 0.168; age 63/1946) was higher among those with three or more siblings. CONCLUSIONS: There is no consistent pattern of only child health disadvantage for midlife chronic disease outcomes across ages or cohorts in the UK. Research should focus on better understanding how sibship size differentials are contingent on context.