Associations of birth characteristics with perimenopausal disorders: a prospective cohort study.

Perimenopausal disorders (PDs) are prevalent and importantly affect quality of life among middle-aged women. Yet, very little is known about the developmental origins of these disorders. The objective of this study was to investigate the associations of birth characteristics with PDs. This cohort study is based on archived birth records for birth weight and gestational age, and followed prospectively in Swedish inpatient and outpatient registers for 8 years (n=3212). The main outcomes were menopausal and climacteric states (e.g. flushing, sleeplessness), perimenopausal bleeding and other PDs (e.g. atrophic vaginitis). Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) for three subtypes of PDs separately. During the follow-up, 218 women had PDs, among whom 125 had menopausal and climacteric states, 61 had perimenopausal bleeding and 58 had other PDs as first recorded disorder. Birth weight was linearly associated with incidence rate of menopausal and climacteric states [HR=1.66 per 1 kg increase, 95% confidence interval (95% CI)=1.14-2.41]. Gestational age (rather than birth weight) was associated with incidence rate of other PDs (HR=0.87 per 1 week increase, 95% CI=0.79-0.95). Neither birth weight nor gestational age was associated with perimenopausal bleeding. Similar results were found after adjustment for other early-life and adult socio-demographic characteristics. This observational study provides, for the first time, evidence regarding the developmental origins of PDs. Future research is required to investigate the underlying causal mechanisms, which may shed further light on the etiology of this class of disorders.

Socioeconomic Position and Reproduction: Findings from the Australian Longitudinal Study on Women's Health.

OBJECTIVE: To investigate the association of socioeconomic position (SEP) with reproductive outcomes among Australian women. METHODS: Data from the Australian Longitudinal Study on Women's Health's (population-based cohort study) 1973-1978 cohort were used (N = 6899, aged 37-42 years in 2015). The association of SEP (childhood and own, multiple indicators) with age at first birth, birth-to-pregnancy (BTP) intervals and total number of children was analysed using multinomial logistic regression. RESULTS: 14% of women had their first birth aged < 24 years. 29% of multiparous women had a BTP interval within the WHO recommendation (18-27 months). Women with a low SEP had increased odds of a first birth < 24 years: low (OR 7.0: 95% C.I. 5.3, 9.3) or intermediate education (OR 3.8: 2.8, 5.1); living in rural (OR 1.8: 1.5, 2.2) or remote (OR 2.1: 1.7, 2.7) areas; who found it sometimes (OR 1.8: 1.5, 2.2) or always difficult (OR 2.0: 1.6, 2.7) to manage on their income; and did not know their parent's education (OR 4.5: 3.2, 6.4). Low SEP was associated with having a much longer than recommended BTP interval. CONCLUSION: As the first Australian study describing social differences in reproductive characteristics, these findings provide a base for reducing social inequalities in reproduction. Assisting adequate BTP spacing is important, particularly for women with existing elevated risks due to social disadvantage; including having a first birth < 24 years of age and a longer than recommended BTP interval. This includes reviewing services/access to postnatal support, free family planning/contraception clinics, and improved family policies.

Birth characteristics and all-cause mortality: a sibling analysis using the Uppsala birth cohort multigenerational study.

This paper investigates the association between perinatal health and all-cause mortality for specific age intervals, assessing the contribution of maternal socioeconomic characteristics and the presence of maternal-level confounding. Our study is based on a cohort of 12,564 singletons born between 1915 and 1929 at the Uppsala University Hospital. We fitted Cox regression models to estimate age-varying hazard ratios of all-cause mortality for absolute and relative birth weight and for gestational age. We found that associations with mortality vary by age and according to the measure under scrutiny, with effects being concentrated in infancy, childhood or early adult life. For example, the effect of low birth weight was greatest in the first year of life and then continued up to 44 years of age (HR between 2.82 and 1.51). These associations were confirmed in within-family analyses, which provided no evidence of residual confounding by maternal characteristics. Our findings support the interpretation that policies oriented towards improving population health should invest in birth outcomes and hence in maternal health.

Maternal pelvic size, fetal growth and risk of stroke in adult offspring in a large Swedish cohort.

Earlier research suggests that maternal pelvic size is associated with offspring's stroke risk in later life. We followed 6362 men and women from Uppsala, Sweden, born between 1915 and 1929 from 1964 to 2008 to assess whether maternal pelvic size was associated with incidence of thrombotic stroke (TS), haemorrhagic stroke (HS) and other stroke (OS). Offspring whose mothers had a flat pelvis had lower birth weight and birth-weight-for-gestational-age compared with those who did not. Inverse linear associations of birth-weight-for-gestational-age were observed with TS and OS. Female offspring whose mothers had a flat pelvis had increased risk of TS, but flat pelvis was not associated with other types of stroke. A smaller difference between intercristal and interspinous diameters and a smaller external conjugate diameter were independently associated with HS, whereas no pelvic measurements were associated with OS. We conclude that a smaller pelvis in women may impact the health of their offspring in adulthood.

Do eating disorders in parents predict eating disorders in children? Evidence from a Swedish cohort.

OBJECTIVE: We investigated whether parental eating disorders (ED) predict ED in children, using a large multigeneration register-based sample. METHOD: We used a subset of the Stockholm Youth Cohort born 1984-1995 and resident in Stockholm County in 2001-2007 (N = 286,232), The exposure was a diagnosed eating disorder in a parent; the outcome was any eating disorder diagnosis in their offspring, given by a specialist clinician, or inferred from an appointment at a specialist eating disorder clinic. A final study sample of 158,697 (55.4%) had data on these variables and confounding factors and contributed a total of 886,241 person years to the analysis. RESULTS: We found good evidence in support of the hypothesis that ED in either parent are independently associated with ED in their female children (HR 1.97 (95% CI: 1.17-3.33), P = 0.01) and that ED in mothers are independently associated with ED in their female children (HR 2.35 (95% CI: 1.39-3.97) P = 0.001). Numbers were too low to permit separate analysis of ED in parents and their male children. CONCLUSION: Eating disorders in parents were associated with ED in children. This study adds to our knowledge about the intergenerational transmission of ED, which will help identify high-risk groups and brings about the possibility of targeted prevention.

Placental weight and foetal growth rate as predictors of ischaemic heart disease in a Swedish cohort.

Studies on placental size and cardiovascular disease have shown inconsistent results. We followed 10,503 men and women born in Uppsala, Sweden, 1915-1929 from 1964 to 2008 to assess whether birth characteristics, including placental weight and placenta/birth weight ratio, were predictive of future ischaemic heart disease (IHD). Adjustments were made for birth cohort, age, sex, mother's parity, birth weight, gestational age and social class at birth. Placental weight and birth weight were negatively associated with IHD. The effect of placental weight on IHD was stronger in individuals from medium social class at birth and in those with low education. Men and women from non-manual social class at birth had the lowest risk for IHD as adults. We conclude that low foetal growth rate rather than placental weight was more predictive of IHD in the Swedish cohort. However, the strong effect of social class at birth on risk for IHD did not appear to be mediated by foetal growth rate.

Social inequality in excessive gestational weight gain.

OBJECTIVE: Optimal gestational weight gain (GWG) leads to better outcomes for both the mother and child, whereas excessive gains can act as a key stage for obesity development. Little is known about social inequalities in GWG. This study investigates the influence of education level on pre-pregnancy body mass index (BMI) and GWG. DESIGN: Register-based population study. SETTING: Sweden PARTICIPANTS: Four thousand and eighty women born in Sweden who were a part of the third generation Uppsala Birth Cohort Study. Register data linkages were used to obtain information on social characteristics, BMI and GWG of women with singleton first births from 1982 to 2008. MAIN OUTCOME MEASURE: Pre-pregnancy BMI and the Institute of Medicine's (IOM) categories of GWG for a given pre-pregnancy BMI. RESULTS were adjusted for calendar period, maternal age, living arrangements, smoking, history of chronic disease and pre-pregnancy BMI when appropriate. RESULTS: Although most women (67%) were of healthy pre-pregnancy BMI, 20% were overweight and 8% were obese. Approximately half of all women in the sample had excessive GWG, with higher pre-pregnancy BMI associated with higher risk of excessive GWG, regardless of education level; this occurred for 76% of overweight and 75% of obese women. Lower educated women with a healthy pre-pregnancy BMI were at greater risk of excessive GWG-odds ratio 1.76 (95% confidence interval 1.28-2.43) for elementary and odds ratio 1.32 (1.06-1.64) for secondary compared with tertiary educated, adjusted for age and birth year period. Nearly half of women with an elementary or secondary education (48%) gained weight excessively. CONCLUSION: Education did not provide a protective effect in avoiding excessive GWG among overweight and obese women, of whom ∼75% gained weight excessively. Lower educated women with a BMI within the healthy range, however, are at greater risk of excessive GWG. Health professionals need to tailor their pre-natal advice to different groups of women in order to achieve optimal pregnancy outcomes and avoid pregnancy acting as a stage in the development of obesity.

Maternal social characteristics and mortality from injuries among infants and toddlers in Estonia.

BACKGROUND: Injuries are a major cause of ill health among children, with a social gradient in child injuries documented in many countries. The effects of maternal sociodemographic characteristics on injury mortality in Estonian infants and toddlers were investigated. METHODS: A population-based study using linkage of data from the Estonian Medical Birth Registry with Mortality Database. A total of 148 521 children born 1992-2002 were followed for injury mortality (ICD-9 E800-E999) from birth to third birthday. Associations of maternal age, education, marital status, nationality, place of residence and child's birth order and multiplicity with risk of injury death were studied using logistic regression. RESULTS: Maternal age (<20 years compared with > or =30 years: OR 2.12; 95% CI 1.00 to 4.51), education (basic compared with secondary or higher: OR 3.22; 95% CI 2.12 to 4.87), marital status (single, divorced or widowed compared with married: OR 2.74; 95% CI 1.53 to 4.91), nationality (other compared with Estonian: OR 2.00; 95% CI 1.32 to 3.02), birth order (fourth or higher compared with first: OR 6.66; 95% CI 3.42 to 12.99), and multiple birth (twin or triplet compared with singleton: OR 3.12; 95% CI 1.44 to 6.73) affected the risk of injury death among infants (<1 year). Among toddlers (1-2 years), boys were at higher risk than girls (OR 1.75; 95% CI 1.15 to 2.66) and low mother's education (basic compared with secondary or higher OR 2.08; 95% CI 1.28 to 3.37) and high birth order (fourth or higher compared with first: OR 7.88; 95% CI 3.90 to 15.90) increased the risk of injury death. CONCLUSIONS: Maternal sociodemographic characteristics are associated with injury mortality among infants and toddlers. Substantial variation in injury mortality rates within Estonia suggests potential for prevention.

Lifetime reproductive output over two generations in patients with psychosis and their unaffected siblings: the Uppsala 1915-1929 Birth Cohort Multigenerational Study.

BACKGROUND: Schizophrenic patients have fewer offspring than the general population but it is unclear whether (i) this persists for more than one generation, (ii) the reduced fertility is compensated by increased fertility in unaffected relatives, (iii) sociodemographic factors confound or interact with the association, and (iv) patients with affective psychosis have a similar fertility disadvantage. This study measured biological fitness over two generations in patients with schizophrenia or affective psychosis, and their unaffected siblings. METHOD: We conducted a historical cohort study using a Swedish birth cohort of 12 168 individuals born 1915-1929 and followed up until 2002. We compared biological fitness over two generations in patients with schizophrenia (n=58) or affective psychosis (n=153), and their unaffected siblings, with the population, adjusting for a range of sociodemographic variables from throughout the lifespan. RESULTS: Patients with schizophrenia had fewer children [fertility ratio (FR) 0.42, 95% confidence interval (CI) 0.29-0.61] and grandchildren (FR 0.51, 95% CI 0.33-0.80) than the population. Some of this reduction was related to lower marriage rates in schizophrenic patients. The unaffected siblings of schizophrenic patients showed no evidence of any compensatory increase in fitness, but there was a trend towards enhanced fertility among the offspring of schizophrenia patients. Patients with affective psychosis and their relatives did not differ from the general population on any fertility measure. CONCLUSIONS: Schizophrenia, but not affective psychosis, is associated with reduced biological fertility; this disadvantage is partly explained by marital status and persists into the second generation.

Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life?

OBJECTIVE: To study whether the effect of size at birth on the risk of ischaemic heart disease (IHD) death is modified by social circumstances in childhood or in adulthood. DESIGN: A cohort study. Data on circumstances at birth were retrieved from archived obstetric records, social characteristics in adulthood and mortality follow-up through routine registers. PARTICIPANTS: 6159 men and 5663 women who were born in Uppsala University Hospital, Sweden (the Uppsala Birth Cohort) during 1915-1929, were singleton births with more than 30 weeks of gestational age and were alive in 1961. Follow-up time 1961-2002 (from age 31-46 to 73-88 years). MAIN OUTCOME MEASURE: Death from IHD. Multivariate Cox regression with age as the time scale, controlling for year of birth and stratified by gender. RESULTS: The risk of IHD death was lower among men and women with higher weight for gestational age. Lower social class in adulthood was associated with a higher risk of IHD death. The effect of size at birth on IHD mortality did not appear to be modified by social class at birth but was only present in men of higher social class in adulthood (hazard ratio per 1 SD weight for gestational age 0.84, 95% CI 0.75 to 0.93). CONCLUSIONS: Weight for gestational age was inversely associated with the risk of IHD death in men and women; this effect was present in men of non-manual adult social class only but did not appear to be modified by adult social class in women or by social class at birth in either men or women.

Social and early-life determinants of overweight and obesity in 18-year-old Swedish men.

OBJECTIVES: To investigate the combined effects of size at birth and maternal education on prevalence of overweight and obesity among 18-year-old men. METHODS: We studied the associations of weight for gestational age and maternal education with body mass index (BMI), overweight and obesity by multivariate linear and logistic regression, adjusted for mother's age, parity and diabetes in a register-based cohort of 6535 men born between 1973 and 1985. Further adjustments for mother's height, pre-pregnancy weight, weight gain and smoking during pregnancy were made in a subsample of 1103 men born between 1982 and 1985. RESULTS: Mean BMI and prevalence of overweight and obesity decreased with higher maternal education. Mother's BMI and smoking were the strongest predictors of sons' overweight and obesity and essentially accounted for the variation in son's overweight by maternal education. The association of size at birth with later overweight was present only in sons born to mothers who were nonsmokers (odds ratio per 1 standard deviation weight for gestational age z-score 1.46, 95% CI 1.18-1.81) and became substantially reduced on adjustment for mother's pre-pregnancy BMI. Length of gestation was not statistically significantly associated with BMI at age 18. CONCLUSIONS: Maternal overweight and maternal smoking were the strongest determinants of offspring overweight and its social patterning, and should be a priority for public health policies.

The Uppsala studies on developmental origins of health and disease.

Large-scale epidemiological studies on developmental origins of health running in Uppsala benefit from the accessibility of well-archived and high quality Swedish records, high participation rates in the surveys, and a long tradition of interdisciplinary research and international collaboration. The UBCoS Multigen study is unique in being able to study intergenerational determinants of health and health inequalities as 'forward in time' processes, starting at the beginning of the last century, whilst the Uppsala Family and ULSAM studies contribute evidence on gene-environment interactions and specific mechanisms of developmental origins of circulatory diseases.

Birth weight, hypertension and "white coat" hypertension: size at birth in relation to office and 24-h ambulatory blood pressure.

We investigated the association of size at birth with hypertensive status defined by office blood pressure (BP) and 24-h ambulatory BP monitoring in a historical cohort study of 736 men born 1920-1924 and examined at age 70 years. Office BP was measured after 10-min supine rest with a sphygmomanometer, ambulatory BP was recorded with Accutracker 2, and anthropometric and other measurements were taken at a clinic. Birth weight and gestational age were abstracted from the men's birth records. A total of 24% of the men were treated for hypertension at the time of the study. Among not treated subjects, there was a weak positive association of birth weight with daytime and 24-h diastolic ambulatory BP. In subjects treated for hypertension, both office and ambulatory BP were inversely related to birth weight, although these associations were not statistically significant. Birth weight did not show significant association with sustained hypertension (elevated office and daytime ambulatory BPs) but showed a strong and statistically significant inverse association with "white coat" hypertension (elevated office BP and normal daytime ambulatory BP) when adjusted for concurrent body mass index (odds ratios 1.91, 1.59, 1 and 1.21 from lowest to highest quartile of birth weight, P-value for trend 0.035). We conclude that BP measured by 24-h-ambulatory monitoring is not related to birth weight in a pattern previously reported for office BP and that factors related to growth in utero are particularly related to higher risk of "white coat" hypertension.