Association of infertility and recurrent pregnancy loss with the risk of dementia.

Emerging evidence has shown the association between female reproductive histories (e.g., menarche age, parity, premature and early menopause) and the risk of dementia. However, little attention has been given to infertility and pregnancy loss. To examine the associations of infertility, recurrent miscarriages, and stillbirth with the risk of dementia, this study used data from four cohorts in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. Women with data on at least one of the reproductive exposures of interest, dementia, and all covariates were included. Histories of infertility, miscarriage, and stillbirth were self-reported. Dementia (including Alzheimer's disease) was identified through surveys, aged care, pharmaceutical, hospital, and death registry data. Cause-specific Cox regression models were used to estimate the hazard ratios of dementia, accounting for well-established risk factors of dementia, study variability, and within-study correlation. Overall, 291,055 women were included at a median (interquartile range) age of 55.0 (47.0-62.0) at baseline. During the median (interquartile range) follow-up period of 13.0 (12.0-14.0) years, 3334 (1.2%) women developed dementia. Compared to women without stillbirth, a history of recurrent stillbirths (≥ 2) was associated with 64% higher risk of dementia (adjusted hazard ratio = 1.64, 95% confidence interval: 1.46-1.85). Compared to women without miscarriage, women with recurrent miscarriages (≥ 3) were at 22% higher risk of dementia (adjusted hazard ratio = 1.22, 95% confidence interval: 1.19-1.25). These findings suggest that recurrent stillbirths is a risk factor for dementia and may need to be considered in risk assessment of dementia in women.

Is there a link between infertility, miscarriage, stillbirth, and premature or early menopause? Results from pooled analyses of 9 cohort studies.

BACKGROUND: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women. OBJECTIVE: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian). STUDY DESIGN: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women. RESULTS: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history. CONCLUSION: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history.

Symptom patterns and health service use of women in early adulthood: a latent class analysis from the Australian Longitudinal Study on Women's Health.

BACKGROUND: Symptoms can be strong drivers for initiating interaction with the health system, especially when they are frequent, severe or impact on daily activities. Research on symptoms often use counts of symptoms as a proxy for symptom burden, however simple counts don't provide information on whether groups of symptoms are likely to occur together or whether such groups are associated with different types and levels of healthcare use. Women have a higher symptom burden than men; however studies of symptom patterns in young women are lacking. We aimed to characterise subgroups of women in early adulthood who experienced different symptom patterns and to compare women's use of different types of health care across the different symptom subgroups. METHODS: Survey and linked administrative data from 7 797 women aged 22-27 years in 2017 from the 1989-95 cohort of the Australian Longitudinal Study on Women's Health were analysed. A latent class analysis was conducted to identify subgroups of women based on the frequency of 16 symptom variables. To estimate the associations between the latent classes and health service use, we used the "Bolck, Croon and Hagenaars" (BCH) approach that takes account of classification error in the assignment of women to latent classes. RESULTS: Four latent classes were identified, characterised by 1) low prevalence of most symptoms (36.6%), 2) high prevalence of menstrual symptoms but low prevalence of mood symptoms (21.9%), 3) high prevalence of mood symptoms but low prevalence of menstrual symptoms, (26.2%), and high prevalence of many symptoms (15.3%). Compared to the other three classes, women in the high prevalence of many symptoms class were more likely to visit general practitioners and specialists, use more medications, and more likely to have had a hospital admission. CONCLUSIONS: Women in young adulthood experience substantially different symptom burdens. A sizeable proportion of women experience many co-occurring symptoms across both physical and psychological domains and this high symptom burden is associated with a high level of health service use. Further follow-up of the women in our study as they enter their late 20 s and early 30 s will allow us to examine the stability of the classes of symptoms and their associations with general health and health service use. Similar studies in other populations are needed to assess the generalisability of the findings.

Infertility, Miscarriage, Stillbirth, and the Risk of Stroke Among Women: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of mortality, and women are impacted more from stroke than men in terms of their absolute number and in having worse outcomes. A growing number of studies have explored the association between pregnancy complications, pregnancy outcomes, and stroke. Limited studies, however, have investigated links involving infertility, miscarriage, and stillbirth, which could plausibly be associated via a background of endocrine conditions, endothelial dysfunction, and chronic systematic inflammation. This review aims to summarize current evidence and provide up-to-date information on the associations of infertility, miscarriage, and stillbirth, with stroke incidence. METHODS: A comprehensive literature search was conducted for cohort and case-control studies on associations between infertility, miscarriage, stillbirth, and stroke up to September 26, 2020. Seven databases were searched: PubMed, Embase, Cochrane, CINIHL, PsyclNFO, Wanfang, and CNKI. Random-effects models were used to estimate the pooled hazard ratios (HRs) and 95% CIs. RESULTS: Sixteen cohort studies and 2 case-control studies enrolling 7 808 521 women were included in this meta-analysis. Women who had experienced miscarriage or stillbirth were at higher risk of stroke (miscarriage: HR, 1.07 [95% CI, 1.00-1.14]; stillbirth: HR, 1.38 [95% CI, 1.11-1.71]) than other women. The HRs of stroke for each additional miscarriage and stillbirth were 1.13 (95% CI, 0.96-1.33) and 1.25 (95% CI, 1.06-1.49), respectively. In subgroup analysis, increased risk of stroke was associated with repeated miscarriages and stillbirths (miscarriage ≥3: HR, 1.42 [95% CI, 1.05-1.90]; stillbirth ≥2: HR, 1.14 [95% CI, 1.04-1.26]). Associations between infertility and stroke were inconsistent and inconclusive (HR, 1.07 [95% CI, 0.87-1.32]). CONCLUSIONS: Miscarriage and stillbirth are associated with increased risk of stroke among women, which could be used as a contributing risk factor to help identify women at higher risk of stroke.

Menopause, hysterectomy, menopausal hormone therapy and cause-specific mortality: cohort study of UK Biobank participants.

STUDY QUESTION: What is the association between menopausal hormone therapy (MHT) and cause-specific mortality? SUMMARY ANSWER: Self-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes. WHAT IS KNOWN ALREADY: Evidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality. STUDY DESIGN, SIZE, DURATION: Cohort study (the UK Biobank), 178 379 women, recruited in 2006-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74). LIMITATIONS, REASONS FOR CAUTION: Self-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT. WIDER IMPLICATIONS OF THE FINDINGS: The current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The association between childhood sexual abuse and historical intimate partner violence with body mass index and diabetes: Evidence from the Australian Longitudinal Study on Women's Health.

The purpose of this study was to investigate the associations of childhood sexual abuse and historical intimate partner violence with body mass index and diabetes among mid-age women. Data from 5782 participants in the 1946-51 cohort of the Australian Longitudinal Study on Women's Health were used. The association of abuse reported to have occurred before 1996 with body mass index and incident diabetes during 20 years of follow-up were examined using longitudinal logistic regression. Women who experienced childhood sexual abuse only, historical intimate partner violence only, or both forms of abuse had higher risk of obesity compared to women who did not experience either form of abuse. The associations between experiencing childhood sexual abuse only, historical intimate partner violence only, or both forms of abuse and incident diabetes (adjusted odds ratios, AOR = 1.28, 95%CI = 1.00, 1.65, AOR = 1.27 (1.02, 1.58) and AOR = 1.74 (1.27, 2.38) respectively) were attenuated by adding body mass index and other variables in the model (AOR = 1.16, 95%CI = 0.90, AOR = 1.49, 1.17 (0.94, 1.46) and AOR = 1.41 (1.03, 1.95) respectively) compared with women who did not experience abuse. The clinical implication is that awareness of a woman's early life experience of abuse may provide insight into managing her weight and risk of diabetes.

History of pre-pregnancy maternal symptoms of binge eating and childhood behavioral problems in girls and boys.

OBJECTIVE: To explore whether children of mothers with pre-pregnancy binge eating (BE) symptoms have more behavioral difficulties compared with those without and whether associations are moderated by ED symptoms and other maternal health and social factors measured during childhood. METHOD: Pre-pregnancy BE symptoms were collected by the Australian Longitudinal Study on Women's Health at Survey 1 (in 1996) and/or at Survey 2 (in 2000) using questions mapped to DSM BE criterion 1. In 2016/7, 2180 women from the 1973-78 cohort provided data on externalizing and internalizing behavior, measured by Strengths and Difficulties Questionnaire, on 4054 of their children (2-12 years) in the Mothers and their Children's Health study. Covariates were markers of other ED symptoms, sociodemographic, social support, and mental health factors collected proximally to the child outcomes. Hierarchical multivariable regression models, using generalized estimating equations accounting for clustering of children within mothers, were used. RESULTS: Pre-pregnancy BE symptoms were associated with child behavior, with associations only moderated after adjustment for proximal markers of ED (girls internalizing behavior, b (95%CI) .30 (-.02, .61); boys externalizing behavior .34 (-.04, .73)) or social support (girls externalizing behavior 0.26 (-.08, .61)). Pre-pregnancy BE symptoms were not associated with boys internalizing behavior (-.27 (-.02, 0.57)). DISCUSSION: Studies with repeated ED measures should test hypotheses that these associations vary by timing of ED measurement. Identification of young women at risk of BE symptoms pre-pregnancy, as well as when children are older, may enable health services, treatment programs, and supports to minimize longer term effects on children. PUBLIC SIGNIFICANCE STATEMENT: A history of binge eating symptoms up to 10 years pre-pregnancy in mothers is associated with behavior problems in their girls and boys at average age of 7. However, the association is moderated by behaviors of eating disorders and social support in the mothers during childhood. Identification of ED symptoms prior to pregnancy, and then after childbirth, might enable health services to intervene to maximize child and mother outcomes.

Maternal factors associated with interbirth intervals in Australia: Results from a population-based longitudinal study.

BACKGROUND AND OBJECTIVE: Short and long intervals between successive births are associated with adverse birth outcomes, especially in low-income and middle-income countries, yet the birth intervals in high-income countries remain relatively understudied. The aim was to examine maternal factors associated with birth intervals in Australia. METHODS: The sample comprised 6130 participants in the Australian Longitudinal Study on Women's Health who were born in 1973-1978, had two or more births, and responded to regular surveys between 1996 and 2018. Interbirth interval (IBI) was defined as the time between successive live births. Maternal factors were examined using accelerated failure time models. RESULTS: For women with only two births (n = 3802), the median time to the second birth was 34.0 months (IQR 23.1, 46.2) with shorter IBI associated with higher socioeconomic status (eg, university education (31.9 months), less income stress (31.1)), and longer IBI associated with age over 35 (39.7), fair/poor health (43.0), untreated fertility problems (45.5), miscarriage (39.4), or abortion (41.0). For women with three or more births (n = 2328), the median times to the second and third births were 31.2 months (19.9, 42.1) and 36.5 months (25.3, 50.1), respectively; some factors were consistent between the first IBI and second IBI (eg, university education and being married were associated with shorter IBI), whereas income stress was associated with longer first IBI but not with second IBI. CONCLUSIONS: Understanding maternal factors associated with birth intervals in a high-income country like Australia may enable more nuanced tailoring of guidelines for prepregnancy care.

Associations Between Socioeconomic Status, Patient Risk, and Short-Term Intensive Care Outcomes.

OBJECTIVES: To investigate the association of socioeconomic status as measured by the average socioeconomic status of the area where a person resides on short-term mortality in adults admitted to an ICU in Queensland, Australia. DESIGN: Secondary data analysis using de-identified data from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation linked to the publicly available area-level Index of Relative Socioeconomic Advantage and Disadvantage from the Australian Bureau of Statistics. SETTING: Adult ICUs from 35 hospitals in Queensland, Australia, from 2006 to 2015. PATIENTS: A total of 218,462 patient admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcome measure was inhospital mortality. The main study variable was decile of Index of Relative Socioeconomic Advantage and Disadvantage. The overall crude inhospital mortality was 7.8%; 9% in the most disadvantaged decile and 6.9% in the most advantaged decile (p < 0.001). Increasing socioeconomic disadvantage was associated with increasing severity of illness as measured by Acute Physiology and Chronic Health Evaluation III score, admission with a diagnosis of sepsis or trauma, cardiac, respiratory, renal, and hepatic comorbidities, and remote location. Increasing socioeconomic advantage was associated with elective surgical admission, hematological and oncology comorbidities, and admission to a private hospital (all p < 0.001). After excluding patients admitted after elective surgery, in the remaining 106,843 patients, the inhospital mortality was 13.6%, 13.3% in the most disadvantaged, and 14.1% in the most advantaged. There was no trend in mortality across deciles of socioeconomic status after excluding elective surgery patients. In the logistic regression model adjusting for severity of illness and diagnosis, there was no statistically significant difference in the odds ratio of inhospital mortality for the most disadvantaged decile compared with other deciles. This suggests variables used for risk adjustment may lie on the causal pathway between socioeconomic status and outcome in ICU patients. CONCLUSIONS: Socioeconomic status as defined as Index of Relative Socioeconomic Advantage and Disadvantage of the area in which a patient lives was associated with ICU admission diagnosis, comorbidities, severity of illness, and crude inhospital mortality in this study. Socioeconomic status was not associated with inhospital mortality after excluding elective surgical patients or when adjusted for severity of illness and admission diagnosis. Commonly used measures for risk adjustment in intensive care improve understanding of the pathway between socioeconomic status and outcomes.

Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies.

STUDY QUESTION: How does the risk of cardiovascular disease (CVD) vary with type and age of menopause? SUMMARY ANSWER: Earlier surgical menopause (e.g. <45 years) poses additional increased risk of incident CVD events, compared to women with natural menopause at the same age, and HRT use reduced the risk of CVD in women with early surgical menopause. WHAT IS KNOWN ALREADY: Earlier age at menopause has been linked to an increased risk of CVD mortality and all-cause mortality, but the extent that this risk of CVD varies by type of menopause and the role of postmenopausal HRT use in reducing this risk is unclear. STUDY DESIGN, SIZE, DURATION: Pooled individual-level data of 203 767 postmenopausal women from 10 observational studies that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE) consortium were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Postmenopausal women who had reported menopause (type and age of menopause) and information on non-fatal CVD events were included. Type of menopause (natural menopause and surgical menopause) and age at menopause (categorised as <35, 35-39, 40-44, 45-49, 50-54 and ≥55 years) were exposures of interest. Natural menopause was defined as absence of menstruation over a period of 12 months (no hysterectomy and/or oophorectomy) and surgical menopause as removal of both ovaries. The study outcome was the first non-fatal CVD (defined as either incident coronary heart disease (CHD) or stroke) event ascertained from hospital medical records or self-reported. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CI for non-fatal CVD events associated with natural menopause and surgical menopause. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with natural menopause, surgical menopause was associated with over 20% higher risk of CVD (HR 1.22, 95% CI 1.16-1.28). After the stratified analysis by age at menopause, a graded relationship for incident CVD was observed with lower age at menopause in both types of natural and surgical menopause. There was also a significant interaction between type of menopause and age at menopause (P < 0.001). Compared with natural menopause at 50-54 years, women with surgical menopause before 35 (2.55, 2.22-2.94) and 35-39 years (1.91, 1.71-2.14) had higher risk of CVD than those with natural menopause (1.59, 1.23-2.05 and 1.51, 1.33-1.72, respectively). Women who experienced surgical menopause at earlier age (<50 years) and took HRT had lower risk of incident CHD than those who were not users of HRT. LIMITATIONS, REASONS FOR CAUTION: Self-reported data on type and age of menopause, no information on indication for the surgery (e.g. endometriosis and fibroids) and the exclusion of fatal CVD events may bias our results. WIDER IMPLICATIONS OF THE FINDINGS: In clinical practice, women who experienced natural menopause or had surgical menopause at an earlier age need close monitoring and engagement for preventive health measures and early diagnosis of CVD. Our findings also suggested that timing of menopause should be considered as an important factor in risk assessment of CVD for women. The findings on CVD lend some support to the position that elective bilateral oophorectomy (surgical menopause) at hysterectomy for benign diseases should be discouraged based on an increased risk of CVD. STUDY FUNDING/COMPETING INTEREST(S): InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). GDM is supported by Australian National Health and Medical Research Council Principal Research Fellowship (APP1121844). There are no competing interests.

Vasomotor menopausal symptoms and risk of cardiovascular disease: a pooled analysis of six prospective studies.

BACKGROUND: Menopausal vasomotor symptoms (ie, hot flashes and night sweats) have been associated with unfavorable risk factors and surrogate markers of cardiovascular disease, but their association with clinical cardiovascular disease events is unclear. OBJECTIVE: To examine the associations between different components of vasomotor symptoms, timing of vasomotor symptoms, and risk of cardiovascular disease. STUDY DESIGN: We harmonized and pooled individual-level data from 23,365 women in 6 prospective studies that contributed to the International Collaboration for a Life Course Approach to Women's Reproductive Health and Chronic Disease Events consortium. Women who experienced cardiovascular disease events before baseline were excluded. The associations between frequency (never, rarely, sometimes, and often), severity (never, mild, moderate, and severe), and timing (before or after age of menopause; ie, early or late onset) of vasomotor symptoms and incident cardiovascular disease were analyzed. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: In the adjusted model, no evidence of association was found between the frequency of hot flashes and incident cardiovascular disease, whereas women who reported night sweats "sometimes" (hazard ratio, 1.22; 95% confidence interval, 1.02-1.45) or "often" (hazard ratio, 1.29; 95% confidence interval, 1.05-1.58) had higher risk for cardiovascular disease. Increased severity of either hot flashes or night sweats was associated with higher risk of cardiovascular disease. The hazards ratios of cardiovascular disease in women with severe hot flashes, night sweats, and any vasomotor symptoms were 1.83 (95% confidence interval, 1.22-2.73), 1.59 (95% confidence interval, 1.07-2.37), and 2.11 (95% confidence interval, 1.62-2.76), respectively. Women who reported severity of both hot flashes and night sweats had a higher risk for cardiovascular disease (hazard ratio, 1.55; 95% confidence interval, 1.24-1.94) than those with hot flashes alone (hazard ratio, 1.33; 95% confidence interval, 0.94-1.88) and night sweats alone (hazard ratio, 1.32; 95% confidence interval, 0.84-2.07). Women with either early-onset (hazard ratio, 1.38; 95% confidence interval, 1.10-1.75) or late-onset (hazard ratio, 1.69; 95% confidence interval, 1.32-2.16) vasomotor symptoms had an increased risk for incident cardiovascular disease compared with women who did not experience vasomotor symptoms. CONCLUSION: Severity rather than frequency of vasomotor symptoms (hot flashes and night sweats) was associated with increased risk of cardiovascular disease. Vasomotor symptoms with onset before or after menopause were also associated with increased risk of cardiovascular disease.

Obesity, smoking, and risk of vasomotor menopausal symptoms: a pooled analysis of eight cohort studies.

BACKGROUND: Frequent and severe vasomotor symptoms during menopause are linked with adverse health outcomes. Understanding modifiable lifestyle factors for the risk of vasomotor menopausal symptoms is important to guide preventive strategies. OBJECTIVE: We investigated the associations between body mass index and smoking, their joint effects with the risk of vasomotor symptoms, and whether the associations differed by menopausal stage. STUDY DESIGN: The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events pooled data on 21,460 midlife women from 8 studies (median age, 50 years; interquartile range, 49-51 years) for the cross-sectional analysis. Four studies provided data for the prospective analysis (n=11,986). Multinomial logistic regression models with 4 categories of frequency/severity for the outcome of vasomotor symptoms were used to estimate relative risk ratios and 95% confidence intervals that were adjusted for within-study correlation and covariates. RESULTS: At baseline, nearly 60% of the women experienced vasomotor symptoms. One-half of them were overweight (30%) or obese (21%), and 17% were current smokers. Cross-sectional analyses showed that a higher body mass index and smoking more cigarettes with longer duration and earlier initiation were all associated with more frequent or severe vasomotor symptoms. Never smokers who were obese had a 1.5-fold (relative risk ratio, 1.52; 95% confidence interval, 1.35-1.73) higher risk of often/severe vasomotor symptoms, compared with never smokers who were of normal-weight. Smoking strengthened the association because the risk of often/severe vasomotor symptoms was much greater among smokers who were obese (relative risk ratio, 3.02; 95% confidence interval, 2.41-3.78). However, smokers who quit at <40 years of age were at similar levels of risk as never smokers. Prospective analyses showed a similar pattern, but the association attenuated markedly after adjustment for baseline vasomotor symptoms. Furthermore, we found that the association between body mass index and vasomotor symptoms differed by menopausal status. Higher body mass index was associated with increased risk of vasomotor symptoms in pre- and perimenopause but with reduced risk in postmenopause. CONCLUSION: High body mass index (≥25 kg/m2) and cigarette smoking substantially increased women's risk for experiencing frequent or severe vasomotor symptoms in a dose-response manner, and smoking intensified the effect of obesity. However, the effect of body mass index on the risk of vasomotor symptoms was opposite among postmenopausal women. Maintaining a normal weight before the menopausal transition and quitting smoking at <40 years of age may mitigate the excess risk of vasomotor symptoms in midlife.

Associations between feeding practices in infancy and fruit and vegetable consumption in childhood.

A diet rich in fruits and vegetables may reduce the risk of chronic diseases. However, in many countries, the majority of children do not eat the recommended quantities of fruits and vegetables. The present study aimed to understand associations between feeding practices in infancy (breast-feeding and first complementary food) and fruit and vegetable consumption in childhood (frequency and variety). Data were from the national, observational, cross-sectional Mothers and their Children's Health study conducted in 2016/2017, a sub-study of the national Australian Longitudinal Study on Women's Health. Mothers completed a written survey on feeding practices in infancy (breast-feeding duration, use of formula, first complementary food) and children's fruit and vegetable frequency (number of times eaten) and variety (number of different types eaten) in the past 24 h, using the Children's Dietary Questionnaire. Children (n 4981, mean 7·36 (sd 2·90) years) ate vegetables 2·10 (sd 1·11) times and fruits 2·35 (sd 1·14) times and ate 3·21 (sd 1·35) different vegetables and 2·40 (sd 1·18) different fruits, on average. Compared with breast-feeding for <6 months, breast-feeding for ≥6 months was associated with higher vegetable variety. Compared with cereal as the first complementary food, fruits or vegetables were associated with higher vegetable frequency and variety, and higher fruit frequency. Overall, infancy is a window of opportunity for dietary intervention. Guidance to parents should encourage the use of fruits and vegetables at the beginning of complementary feeding.

Testing the role of the timing and chronicity of maternal depressive symptoms in the associations with child behaviour and development.

BACKGROUND: There is debate regarding whether the association between maternal depressive symptoms (MDS) and child outcomes is due to the timing or chronicity of symptoms. OBJECTIVES: To investigate whether critical periods, sensitive periods, or accumulation models provided the best explanation for the association between MDS and children's behaviour and development. METHODS: Data on mothers (N = 892) were collected from 1996 to 2015 as part of the Australian Longitudinal Study on Women's Health, a prospective longitudinal epidemiological study. Data on children (N = 978, 2-12 years) were collected in 2016/17 as part of the Mothers and their Children's Health study. Mothers were categorised according to whether they reported MDS (scored ≥ 10 on the CESD-10) before pregnancy, during pregnancy, or in early childhood. Child outcomes were maternal-rated behaviour problems (Strengths and Difficulties Questionnaire; SDQ) and teacher-rated development (Australian Early Development Census; AEDC). We used a structured life course approach to rigorously test critical period, sensitive period, and accumulation (ie chronicity) theories by comparing the fit of a series of models. RESULTS: Most mothers did not report MDS at any time (69.2%), 16.9% reported MDS before pregnancy, 13.2% during pregnancy, and 16.5% in early childhood. High/very high total behaviour problems were reported for 7.0% of children, and developmental vulnerability/risk was reported for 15.9% for social competence and 15.7% for emotional maturity. An accumulation model was the best fit, with each period of MDS associated with an increase of 1.71 points (95% CI 1.26, 2.17) on the SDQ and decreases of 0.31 (95% CI -0.50, -0.12) and 0.29 points (95% CI -0.49, -0.08) on AEDC social competence and emotional maturity, respectively. CONCLUSIONS: Chronic MDS were associated with poorer child outcomes than MDS at any single time. Sensitive and critical period models were not supported. This suggests chronicity of symptoms may be more important than timing.

Menstrual symptoms and risk of preterm birth: A population-based longitudinal study.

OBJECTIVES: To examine the prospective association between menstrual symptoms before pregnancy and preterm birth. METHODS: Secondary analysis of data from 14 247 young Australian women born between 1973 and 1978 who participated in a longitudinal, population-based cohort study between 1996 and 2015. Women were first surveyed at 18-23 years, and seven waves of data were collected at roughly three-yearly intervals. At each survey, women were asked about "severe period pain," "heavy periods," and "irregular periods" within the last 12 months. From 2009 onward, information on their children was collected, including birth dates and preterm birth (<37 weeks). Logistic regression using generalized estimating equations was used to examine prospective associations between self-reported menstrual symptoms before pregnancy and risk of preterm birth. RESULTS: Data from 6615 mothers who had 12 337 live singleton births were available for analysis. Among all births, women reporting severe period pain (adjusted odds ratio [aOR] 1.34 [95% CI 1.10-1.62]) or heavy periods (1.25 [1.02-1.53]) before pregnancy had higher odds of preterm birth. However, in analyses stratified by birth order, only severe period pain (2.05 [1.41-2.99]), heavy periods (1.77 [1.23-2.55]), or irregular periods (1.58 [1.10-2.28]) before a second or subsequent birth were associated with an increased risk of preterm birth. CONCLUSIONS: Severe period pain, heavy periods, and irregular periods before a second or subsequent birth may be associated with preterm birth.

Testing competing mediators of the association between pre-conception maternal depression and child health-related quality of life: the MatCH study.

Maternal depression is a potent risk factor for poor child development across a number of domains but the mechanisms of transmission are poorly understood. This study aimed to test competing mediators of the association between pre-conception maternal depression and child psychosocial functioning. In 2016, mothers in the 1973-1978 cohort of the Australian Longitudinal Study on Women's Health were asked to be part of the Mothers and their Children's Health study and to complete surveys on the health of their three youngest children under 13 years. The current study includes children aged 0-12 years (N = 5532, M = 6.99 years, SD = 3.22 years) and their mothers (N = 2917). We used the CESD-10 to measure depression and the PedsQL to measure psychosocial functioning, and used multilevel structural equation modeling to test hypotheses. Pre-conception maternal depression was associated with poorer maternal mental health and parenting after birth. The effect of pre-conception maternal depression was mediated by post-birth maternal depression in children aged 0-4 years (unstandardized regression coefficient (B) = - 0.26, 95%CI - 0.38, - 0.13) and children aged 5-12 years (B = - 0.25, 95%CI - 0.34, - 0.16), and by post-birth maternal stress (B = - 0.04, 95%CI - 0.08, - 0.01), and parenting (B = - 0.03, 95%CI - 0.04, - 0.02) in children aged 5-12 years. Post-birth maternal depression was the strongest mediator. Pre-conception is the optimal time for depression intervention. Post-birth interventions should include a focus on reducing depression and improving negative parenting aspects such as hostility and discipline.

Correction to: Testing competing mediators of the association between pre-conception maternal depression and child health-related quality of life: the MatCH study.

The current sentence is in the discussion (sub-section The role of pre-conception maternal depression) and reads: "Pre-conception treatment of mental health issues is also associated with substantial savings in health care costs (Chojenta et al., 2018)."

Short-term weight gain is associated with accumulation of multimorbidity in mid-aged women: a 20-year cohort study.

BACKGROUND/OBJECTIVES: Although weight change has been studied in relation to many individual chronic conditions, limited studies have focused on weight change and multimorbidity. This study examines the relationship between short-term weight change and the accumulation of multimorbidity in midlife. METHODS: We used data from 7357 women aged 45-50 years without a history of any chronic conditions. The women were surveyed approximately every 3 years from 1996 to 2016. Associations between short-term weight change and accumulation of multimorbidity (two or more of nine chronic conditions) over each 3-year period, adjusting for baseline body mass index (BMI) or time-varying BMI (3-year period), were examined using repeated measures models. Short-term weight change was categorised into seven groups of annual weight change from high weight loss ( ≤ -5%) to high weight gain (> + 5%). RESULTS: Over 20 years, 60.4% (n = 4442) of women developed multimorbidity. Baseline BMI, time-varying BMI and short-term weight gain were all associated with the accumulation of multimorbidity. After controlling for sociodemographic, lifestyle factors and menopausal status, high weight gain was associated with a 25% increased odds of multimorbidity (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.08-1.45) compared with maintaining a stable weight. The results were consistent among models adjusting for baseline BMI (OR 1.24, 95% CI 1.07-1.44) or time-varying BMI (OR 1.34, 95% CI 1.16-1.54). Weight loss was associated with increased odds of multimorbidity in women with normal BMI (baseline or time-varying). CONCLUSIONS: Short-term weight gain is associated with significantly increased odds of multimorbidity in mid-aged women. This association is independent from baseline BMI (at 45-50 years) and time-varying BMI. These findings support a persistent weight management regime and prevention of weight gain throughout women's midlife.

Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women.

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.

SF-36 normative values according to level of functioning in older women.

PURPOSE: The 36-item Medical Outcome Study Short Form (SF-36) survey measures health-related quality of life. Age and disease-specific normative values have been published, but a focus on level of functioning may be more meaningful in case of multimorbidity. We estimated normative values for Australian women aged 79-90 years according to levels of functioning. METHODS: Data were from 6127 (aged 79-84 in 2005) and 3424 (aged 85-90 in 2011) participants in the Australian Longitudinal Study on Women's Health. Surveys included the SF-36 and information on housing. Record linkage to assessment data for access to the national program for aged care support was used to obtain information on participants' need for assistance with 10 activities. Normative values were calculated for physical component (PCS), mental component (MCS), and subscale scores for subsamples defined by types of assistance needed. RESULTS: At the ages of 79-84, the mean (95% confidence interval) PCS and MCS values for women not any needing assistance were 37.5 (37.2-37.9) and 53.0 (52.8-53.3) compared to 29.0 (27.8-30.2) and 45.9 (44.4-47.4) for women needing any assistance. At ages 85-90, the corresponding PCS values were 34.9 (34.5-35.4) vs. 28.2 (27.4-29.0) and the corresponding MCS values were 53.2 (52.8-53.6) vs. 48.7 (47.8-49.6). Values were higher for participants living in the community or retirement village vs. nursing homes/hostels. The PCS, MCS and 8 subscale values decreased as the need for assistance with more basic activities increased. CONCLUSIONS: These normative values facilitate meaningful interpretation of SF-36 scores from the perspective of level of functioning.