Variation in incidence of neurodevelopmental disorders with season of birth

BACKGROUND: The etiologies of autism spectrum disorder and many neurodevelopmental disorders are largely unknown. The detection of a seasonal variation of birth of children diagnosed with a certain disorder could suggest etiological factors that follow a seasonal pattern. We examined the seasonal variation of births of children diagnosed with any of 4 common childhood neuropsychiatric disorders: autism spectrum disorder, hyperkinetic disorder, Tourette syndrome, and obsessive-compulsive disorder. METHODS: The study cohort consisted of all children born in Denmark from 1990 through 1999 identified in the Danish Medical Birth Register (n = 669,995). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry from 1995 through 2004 using the International Classification of Diseases, 10th edition, diagnostic coding system. Logistic regression combined with spline (a smoothing method) was used to estimate the variation with season of birth for each disorder. Estimates of risk of each disorder with season of birth were adjusted for differences in follow-up time and change in incidence over time. RESULTS: No convincing variations in season of birth were observed for any of the 4 disorders, or for the autism-spectrum-disorder subtypes. CONCLUSION: Although we cannot rule out the possibility of seasonal variation of birth for a range of childhood neurodevelopmental disorders, we find little evidence that seasonal environmental factors are related to these disorders.     

Socioeconomic status and risk of childhood leukaemia in Denmark

AIMS: The aim of this study was to assess the influence of socioeconomic status on the risk of childhood leukaemia. METHODS: A matched case-control design was used. The study population comprised all children (0-14 years old) born and reported to the Danish Cancer Registry between 1976 and 1991 for a diagnosis of leukaemia (n=377). Controls were selected from the Central Population Registry and matched by sex, age, and time of birth. Each child was assigned three categories of socioeconomic status, one corresponding to the annual average income in the municipality of residence at the time of birth, another corresponding to that at the time of diagnosis, and, finally, each family was assigned one of five social classes by use of the job titles of the parents. Conditional logistic regression was used to estimate the effect of socioeconomic status on the risk of childhood leukaemia. RESULTS: Children born in low-income municipalities had a significantly increased risk of leukaemia (RR=2.71; 95% CI=1.41-5.21; p=0.003), which was higher among those who received their diagnosis before age five (RR=3.43; 95% CI=1.52-7.74; p=0.003). Neither individual social class nor the socioeconomic status of the residential area at the time of diagnosis was convincingly associated with the risk of childhood leukaemia. CONCLUSIONS: The results suggest that socioeconomic factors associated with community characteristics rather than individual lifestyle are related to the risk of childhood leukaemia and that these factors act early in life.     

Accuracy of adults' recall of childhood social class: findings from the Aberdeen children of the 1950s study

BACKGROUND: Although adult reported childhood socioeconomic position has been related to health outcomes in many studies, little is known about the validity of such distantly recalled information. This study evaluated the validity of adults' reports of childhood paternal social class. METHODS: Data are drawn from the Aberdeen children of the 1950s study, a cohort of 12 150 people born in Aberdeen (Scotland) who took part in a school based survey in 1962. In this survey, two indices of early life socioeconomic position were collected: occupational social class at birth (abstracted from maternity records) and occupational social class in childhood (reported during the 1962 survey by the study participants). Between 2000 and 2003, a questionnaire was mailed to traced middle aged cohort members in which inquiries were made about their fathers' occupation when they were aged 12 years. The level of agreement between these reports and prospectively collected data on occupational social class was assessed. RESULTS: In total, 7183 (63.7%) persons responded to the mid-life questionnaire. Agreement was moderate between social class of father recalled in adulthood and that measured in early life (kappa statistics were 0.47 for social class measured at birth, and 0.56 for social class reported by the child). The relation of occupational social class to birth weight and childhood intelligence was in the expected directions, although weaker for adults' reports in comparison with prospectively gathered data. CONCLUSIONS: In studies of adult disease aetiology, associations between childhood social class based on adult recall of parental occupation and health outcomes are likely to underestimate real effects.     

The lasting impact of childhood health and circumstance

We quantify the lasting effects of childhood health and economic circumstances on adult health, employment and socioeconomic status, using data from a birth cohort that has been followed from birth into middle age. Controlling for parental income, education and social class, children who experience poor health have significantly lower educational attainment, poorer health, and lower social status as adults. Childhood health and circumstance appear to operate both through their impact on initial adult health and economic status, and through a continuing direct effect of prenatal and childhood health in middle age. Overall, our findings suggest more attention be paid to health as a potential mechanism through which intergenerational transmission of economic status takes place: cohort members born into poorer families experienced poorer childhood health, lower investments in human capital and poorer health in early adulthood, all of which are associated with lower earnings in middle age-the years in which they themselves become parents.     

Early life determinants of musculoskeletal sickness absence in a cohort of Norwegians born in 1967-1976

In order to investigate the extent to which musculoskeletal sickness absence was influenced by a range of circumstances concerning family background and health in early life, we established a register-based cohort of all live-born in Norway between 1967 and 1976. Personal data on parental factors and health early in life were recorded prospectively from birth onward in the Medical Birth Registry of Norway, the National Insurance Administration, Statistics Norway, and the Central Population Register. We collected data in the National Insurance Administration on the first spell of medically certified long-term (>16 days) musculoskeletal (International Classification of Primary Care group L) sickness absence in 2000-2003 among 378, 356 participants who were considered to be at risk of sickness absence on January 1st, 2000. The 4-year musculoskeletal absence risk was 0.264 for women and 0.156 for men. Parental education level was associated with musculoskeletal sickness absence, with increasing adjusted relative risks by decreasing educational level for both genders. Associations with other early determinants (birth weight, childhood disease, parental survival, parental disability, parental income, and parental marital status) were all close to unity. Parental education level attributed 36% (95% confidence interval 33-38) to the population risk for women and 67% (64-70) for men. The parental education association was partly mediated through own educational attainment, which was strongly associated with musculoskeletal sickness absence in itself. Our data suggest that mechanisms acting early in life could influence later risk of musculoskeletal sickness absence.     

Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life

As colorectal cancers have a long latency period, their origins may lie early in life. Therefore childhood body mass index (BMI; kg/m²) and height may be associated with adult colorectal cancer. Using a cohort design, 257,623 children from The Copenhagen School Health Records Register born from 1930 to 1972 with measured heights and weights at ages 7 to 13 years were followed for adult colon and rectal adenocarcinomas by linkage to the Danish Cancer Registry. Hazard ratios (HRs) with 95% confidence intervals (CI) were estimated by Cox proportional hazard regressions. During follow-up, 2676 colon and 1681 rectal adenocarcinomas were diagnosed. No sex differences were observed in the associations between child BMI or height and adult colon or rectal cancers. Childhood BMI and height were positively associated with colon cancer; at age 13 years the HRs were 1.09 (95% CI 1.04–1.14) and 1.14 (95% CI 1.09–1.19) per z-score, respectively. Children who were persistently taller or heavier than average, had increased risk of colon cancer. Similarly, growing taller or gaining more weight than average was positively associated with colon cancer. No associations were observed between BMI or height and rectal cancer. Childhood BMI and height, along with above average change during childhood are significantly and positively associated with adult colon cancers, but not with rectal cancer, suggesting different etiologies.     

Life course exposure and later disease: a follow-up study based on medical examinations carried out in Glasgow University (1948-68)

Evidence for the relationship between exposures in fetal life, infancy, childhood and early adulthood, and risk of chronic disease in later middle-age continues to accumulate. Further understanding of the associations between exposures acting over the life course and current morbidity and mortality in middle-age and later must depend upon the follow-up of previously established cohorts. This paper describes the design of, and background to, a follow-up of individuals who participated in a survey of student health in the University of Glasgow between 1948 and 1968. 15 332 students, almost a quarter of whom were female, had detailed medical information collected from a doctor-administered questionnaire and physical examination. Participation was voluntary; approximately 50% of the student population took part and these students were rep-resentative of the entire student population. Data collected include: socio-demographic, behavioural, developmental, anthropometric, and clinical details, as well as details of medical history and family health and structure. Data are over 95% complete for most variables. Over 40% of students were examined on two or more occasions with 1026 students (6.8%) having four or more examinations. Over 90% of students were from social classes I-III. Eighty-two per cent (12 533/15 322) of the students have been traced and flagged through the National Health Service Central Register and attempts are on-going to increase this figure. Those study members who have been traced are representative of the original cohort. To date 1111 (7.2%) of those traced have died. These data constitute a unique record of the health and physical development of a large cohort of students from Glasgow. Follow-up to investigate the relationship between indices of health and development, (height, weight, blood pressure), health behaviours and social circumstances in childhood and young adulthood, and mortality and morbidity in later adulthood is under way.     

Are the cause(s) responsible for urban-rural differences in schizophrenia risk rooted in families or in individuals?

Many studies have identified urban-rural differences in schizophrenia risk. Hypothetical underlying cause(s) may include toxic exposures, diet, infections, and selective migration. The authors investigated whether the underlying cause(s) responsible for the urban-rural differences were rooted in families or in individuals. Linking data from the Danish Civil Registration System and the Danish Psychiatric Central Register, a population-based cohort of 711,897 people aged 15 years or more was established. Overall, 2,720 persons developed schizophrenia during the period 1970-2001. The authors evaluated whether the nearest older sibling's place of birth had an independent effect on schizophrenia risk. If the cause(s) responsible for the urban-rural differences are rooted in individuals only, the nearest older sibling's place of birth should have no independent effect. In this analysis, the nearest older sibling's place of birth had an independent effect; among persons who lived in a rural area during their first 15 years of life, the relative risk was 1.59 (95% confidence interval: 1.10, 2.30) if their nearest older sibling had been born in the capital area as compared with a rural area. Some of the cause(s) responsible for the urban-rural differences in schizophrenia risk are rooted in families, but some might also be rooted in individuals.     

Risk of cancer in children with the diagnosis immaturity at birth

Cancer risk in children born before term has been assessed in a large number of case-control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977-89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case-control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention.     

Age at any birth is associated with breast cancer risk

The period before the first birth is traditionally viewed as particularly critical for a woman's breast cancer risk. Nonetheless, the importance of early timing of a woman's first compared with subsequent births is not well understood. In the present study we examine this question using a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1968 and 1994, 13,049 incident cases of breast cancer were identified in the Danish Cancer Registry. According to our results, a woman's breast cancer risk is related to her age at any of her births. The risk increase per 5 year's increase in maternal age at first, second, third, and fourth birth was 9%, 7%, 5%, and 14%, respectively. For fifth and sixth births it was 5%. We observed a risk reduction after any birth occurring before 30 years of age (in uniparous women before 25 years of age). These effects were strongest more than 10 years after birth. Thus, our study shows that early timing of any additional birth induces an additional long-term reduction in maternal risk of breast cancer; that is, early reproductive years, rather than just the nulliparous years, constitute the critical period.     

The influence of maternal childhood and adulthood social class on the health of the infant

The aim of this study is to investigate how maternal childhood and adulthood social class contribute to social inequalities in low birth weight, neonatal mortality and postneonatal mortality. In particular I consider the combined influence of childhood and adult class, and compare outcomes with regard to the time distance from birth. Analyses were performed on a large sample of Swedish births from 1973 to 1990, restricted to infants of women with both childhood and adult class, classified as manual or non-manual. Logistic regression is used to compare odds ratios for social classes. The results indicate that manual maternal childhood class is consistently associated with higher risks for low birth weight and neonatal mortality, even when adult class was adjusted for. The influence of adult class was greater than that of childhood class for all health outcomes. Compared to higher/middle non-manual workers, unskilled workers in the service sector and workers in the manufacturing sector displayed the highest odds ratios for all adverse health outcomes. When both childhood and adult class were taken into account, social differences were greater for low birth weight and neonatal mortality than for postneonatal mortality. Maternal childhood class had more influence on low birth weight and neonatal mortality than on postneonatal mortality. I conclude that maternal childhood and adulthood social class are both independently associated with inequalities in health-related birth outcomes, and that social differences are greater for health outcomes closer to birth.     

Persistence of social and health problems in the welfare state: A Danish Cohort experience from 1948 to 1979

A cohort of 1112 pre-school children who lived in Copenhagen around 1950 was reidentified three decades later. A historical body of information regarding living conditions during childhood was supplemented with information from public registries concerning adult life experiences of the very same individuals. Childhood conditions were analysed in relation to later occurences of hospitalization, delinquency and unemployment in adult life.A group of individuals whose childhoods were characterized by unfavourable conditions in the slum clearance sections of Copenhagen in the fifties later experienced a substantial accumulation of health and social problems in adult life.The housing conditions during childhood turned out to be a powerful predictor of later occurences of somatic as well as psychiatric hospitalization, and furthermore of conviction for criminal offences.The fundamental importance of living conditions for the development of social and health problems permeates the population experience of the highly developed Danish welfare state, in full agreement with its basic properties as a class society.     

Sibship characteristics and risk of multiple sclerosis: a nationwide cohort study in Denmark

It has been hypothesized that age at infection with a common microbial agent may be associated with the risk of multiple sclerosis (MS). The authors addressed this hypothesis by using number of older siblings and other sibship characteristics as an approximation of age at exposure to common infections. Data on family characteristics and vital status from the Danish Civil Registration System were used to establish a cohort of all Danes whose mothers had been born in Denmark since 1935. Persons diagnosed with MS during the period 1968-1998 were identified through linkage with the Danish Multiple Sclerosis Register. The cohort of 1.9 million Danes was followed for 28.1 million person-years; during that time, 1,036 persons developed MS. Overall, there was no association between number of older siblings, number of younger siblings, total number of siblings, age distance from the nearest younger sibling, or exposure to younger siblings under 2 years of age and risk of MS later in life. There was no association of MS risk with multiple birth (vs. singleton birth) or with the age of the mother or father at birth. These results do not lend support to the hypothesis that number of older siblings or any of the other sibship characteristics studied is associated with risk of MS.     

Socioeconomic position and twins' health: a life-course analysis of 1266 pairs of middle-aged Danish twins

BACKGROUND: The association between socioeconomic circumstances and health in adulthood could come about through processes that may be divided into factors experienced early in life and those experienced in later adulthood. In order to disentangle the influences on health of the early genetic, prenatal and rearing environmental factors from environmental factor later in life, we compared the health status among male and female twin pairs who lived together during childhood and were discordant or concordant on adult socioeconomic position. METHODS: A cross-sectional survey among a random sample of middle-aged Danish twins was conducted in 1998-99. The study population included 1266 like-sex twin pairs [52.5% monozygotic (MZ) and 47.6% dizygotic (DZ)]. Data were obtained on childhood and adult social class and on height, BMI, grip strength, depression symptoms, self-rated health, cognitive function, physical activity, smoking, alcohol and food intake. RESULTS: The expected associations between the individual twins' adult social class and health measures were observed. Among DZ male twins discordant on adult social class, the higher social class twin was on average significantly taller and had higher cognitive test scores. Among DZ female twins discordant on adult social class, the higher social class female twin was more physically active and had a higher cognitive test score. There were no significant health disparities or behavioural differences between the members of MZ twin pairs discordant on adult social class. For most health outcomes, the variability within twin pairs was related to zygosity (higher for DZ than for MZ) but not to social class. CONCLUSION: This study suggests that the relationship between adult social class and health outcomes in Denmark is due mainly to selection effects rather than a causal effect of social class exposures on health and behaviour.     

Lifecourse study of bone health at age 49-51 years: the Newcastle thousand families cohort study

OBJECTIVE: To quantify the direct and indirect effects of fetal (position in family, weight, and social class at birth), childhood (breast feeding, growth, infections, and social class in childhood, age at menarche), and adult life (social class, alcohol consumption, smoking, diet, reproductive history, exercise, hormone replacement therapy use), and adult size (height, weight) on bone health at age 49-51 years, as measured by bone mineral density, total scanned bone area of the hip and lumbar spine, and femoral neck shaft angle. DESIGN: Follow up study of the Newcastle thousand families birth cohort established in 1947. PARTICIPANTS: 171 men and 218 women who attended for dual energy x ray absorptiometry scanning. MAIN RESULTS: Fetal life explained around 6% of variation in adult bone mineral density for men, but accounted for less than 1% for women. Adult lifestyle, including effects mediated through adult weight accounted for over 10% of variation in density for men and around 6% for women. Almost half of variation in bone area for men was explained by early life. However, most of this was mediated through achieved adult height and weight. In women, less than 5% of variation in bone area was accounted for by early life, after adjusting for adult size. Most of the variation in each of the indicators for both sexes was contributed either directly or indirectly by adult lifestyle and achieved adult height and weight. CONCLUSIONS: The effect of fetal life on bone health in adulthood seems to be mediated through achieved adult height.     

Birth weight,childhood size,and muscle strength in adult life: evidence from a birth cohort study

Environmental influences during gestation may have long-term effects on adult muscle strength. It is not known how early in adult life such effects are manifest and whether they are modified by childhood body size. The authors examined the relation between birth weight and hand grip strength in a prospective national birth cohort of 1,371 men and 1,404 women from the Medical Research Council National Survey of Health and Development who were aged 53 years in 1999. A positive relation between birth weight and adult grip strength remained after adjustment first for adult height and weight and then additionally for childhood height and weight (p = 0.006 for men and p = 0.01 for women). The effects of birth weight on grip strength did not vary by childhood or current body size and were not confounded by social class. To the authors' knowledge, this is the first study to show that birth weight has an important influence on muscle strength in midlife independent of later body size and social class. It suggests that birth weight is related to the number of muscle fibers established by birth and that even in middle age compensating hypertrophy may be inadequate. As the inevitable loss of muscle fibers proceeds in old age, a deficit in the number of fibers could threaten quality of life and independence.     

Socioeconomic position in early life,birth weight,childhood cognitive function,and adult mortality. A longitudinal study of Danish men born in 1953

OBJECTIVE: To examine the relation between socioeconomic position in early life and mortality in young adulthood, taking birth weight and childhood cognitive function into account. DESIGN: A longitudinal study with record linkage to the Civil Registration System and Cause of Death Registry. The data were analysed using Cox regression. SETTING: The metropolitan area of Copenhagen, Denmark. SUBJECTS: 7493 male singletons born in 1953, who completed a questionnaire with various cognitive measures, in school at age 12 years, and for whom birth certificates with data on birth and parental characteristics had been traced manually in 1965. This population was followed up from April 1968 to January 2002 for information on mortality. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular diseases, and violent deaths. RESULTS: Men whose fathers were working class or of unknown social class at time of birth had higher mortality rates compared with those whose fathers were high/middle class: hazard ratio 1.39 (95% CI 1.15 to 1.67) and 2.04 (95% CI 1.48 to 2.83) respectively. Birth weight and childhood cognitive function were both related to father's social class and inversely associated with all cause mortality. The association between father's social class and mortality attenuated (HR(working class)1.30 (1.08 to 1.56); HR(unknown class)1.81 (1.30 to 2.52)) after control for birth weight and cognitive function. Mortality from cardiovascular diseases and violent deaths was also significantly higher among men with fathers from the lower social classes. CONCLUSION: The inverse association between father's social class at time of birth and early adult mortality remains, however somewhat attenuated, after adjustment for birth weight and cognitive function.