Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis.

STUDY QUESTION: What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause <40 years) and early menopause (EM; menopause 40-44years)? SUMMARY ANSWER: Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective. WHAT IS KNOWN ALREADY: Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women. STUDY DESIGN, SIZE, DURATION: The Australian Longitudinal Study on Women's Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data. PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results. MAIN RESULTS AND THE ROLE OF CHANCE: Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio [OR] 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication. LIMITATIONS, REASONS FOR CAUTION: Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007. WIDER IMPLICATIONS OF THE FINDINGS: This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Australian NHMRC Centre of Research Excellence Women's Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin. TRIAL REGISTRATION NUMBER: N/A.

Levels of physical activity and sitting time in women with infants, toddlers and preschoolers: a population-based cross-sectional study.

OBJECTIVES: Insufficient physical activity (PA) and prolonged sitting time (ST) increase the risk of chronic disease and mortality. Caring for young children can potentially impact maternal PA and sedentary behaviours. The aims of this study were to explore the levels of PA and ST in women with young children (infants, toddlers and preschoolers) and sociodemographic and behavioural factors associated with these. STUDY DESIGN: This was a population-based cross-sectional study. METHODS: Survey 5 data collected in 2009 (n = 4290) of the 1973-1978 birth cohort of the Australian Longitudinal Study on Women's Health were used. Multiple linear and logistic regression models were used to examine associations. RESULTS: In adjusted models, compared with women with preschoolers, women whose youngest child was an infant aged 0-6 months, aged >6-12 months or toddler had lower PA (-321.3 MET.min/week [95% confidence interval (CI) -416.2, -226.4], -147.9 MET.min/week [95% CI -237.6, -58.1] and -106.4 MET.min/week [95% CI -172.3, -40.5]). ST was higher in women whose youngest child was an infant aged 0-6 months (0.48 h/day; 95% CI 0.19, 0.77) but lower with infants aged >6-12 months (-0.33 h/day; 95% CI -0.60, -0.05) and toddlers (-0.40 h/day; 95% CI -0.60, -0.20) than in those with preschoolers. The findings were similar in the logistic model. Sociodemographic and behavioural factors such as occupation and marital status also influenced PA and ST. CONCLUSIONS: Women with infants and toddlers have lower PA than women with preschoolers. Women are more likely to sit more in the first 6 months after childbirth. These findings can inform resources and intervention development to improve activity levels in women with young children through consideration of the age of the youngest child, sociodemographic and behavioural factors.

Asthma severity and impact on perinatal outcomes: an updated systematic review and meta-analysis.

BACKGROUND: Large-scale studies exploring the associations of asthma severity, exacerbations and medication use with adverse perinatal outcomes have been published in recent years. OBJECTIVES: To update evidence on the associations of asthma severity, exacerbations and medication use with the adverse perinatal outcomes of preterm delivery (PD), low birthweight (LBW) and small-for-gestational-age (SGA). SEARCH STRATEGY: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) from inception to 1 January 2021. SELECTION CRITERIA: Cohort studies comparing the likelihood of adverse perinatal outcomes in groups of asthmatic women stratified by asthma severity, asthma exacerbations or medication use, or comparing the likelihood of adverse perinatal outcomes between non-asthmatic women and asthmatics of various levels of severity and exacerbation. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. Random-effects models were used to meta-analyse the results. MAIN RESULTS: Twenty studies met the inclusion criteria. The odds of delivering SGA babies increased with maternal asthma severity. Pregnant women with an asthma exacerbation had higher odds of delivering LBW babies and SGA babies, compared with pregnant women with asthma but without an exacerbation (pooled adjusted odds ratio [OR] 1.15, 95% CI 1.02-1.29 for LBW; number of studies with adjusted OR 3; I2 = 0%) (pooled adjusted OR 1.13, 95% CI 1.04-1.23 for SGA; number of studies with adjusted OR 4; I2 = 0%) and compared to pregnant women without asthma. Oral corticosteroids use during pregnancy was associated with increased odds of LBW, but not PD. CONCLUSIONS: The available data suggest that maternal asthma severity and exacerbations are associated with increased odds of LBW and SGA babies. TWEETABLE ABSTRACT: A systematic review and meta-analysis found that maternal asthma severity and exacerbations are associated with increased odds of delivering low birthweight and small-for-gestational-age babies.

Delayed diagnosis of endometriosis disadvantages women in ART: a retrospective population linked data study.

STUDY QUESTION: Do the outcomes and use of ART differ between women with and without endometriosis? SUMMARY ANSWER: ART use and outcome do not appear to differ for women with and without endometriosis, as long as endometriosis is diagnosed prior to commencing ART. WHAT IS KNOWN ALREADY: Approximately 40% of women with endometriosis have infertility and ART is the recommended treatment option for these women. However, diagnosis of endometriosis can be complex and lengthy, and a delay in diagnosis can reduce the likelihood of achieving a live birth. STUDY DESIGN, SIZE, DURATION: This retrospective national cohort study used longitudinal self-report data (collected 1996-2018) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health (ALSWH). The study also used linked administrative data on Endometriosis (1970-2018), ART (1996-2020) and births (1996-2018). PARTICIPANTS/MATERIALS, SETTING, METHODS: The outcome measures were: age at first ART cycle; use of ART treatments (IVF only; IUI only/and IVF); number of ART cycles (1-3; 4-10; 11-36); and births after first ART (no; yes) (note that births could not be tied to ART). MAIN RESULTS AND THE ROLE OF CHANCE: One in three (34.7%, n = 459/1322) women using ART had endometriosis, with 65.6% of these diagnosed before first ART and 34.4% after. Adjusted regression analyses showed women with endometriosis diagnosed before first ART were not significantly different to women without endometriosis on any outcome. However, women with endometriosis diagnosed after first ART were more likely to use IUI (adjusted odds ratio (aOR) 2.14, 95% CI 1.48, 3.09) and do more cycles (11-36 cycles: aOR 4.09, 95% CI 2.41, 6.95), and less likely to report a birth (aOR 0.67, 95% CI 0.45, 0.99), compared to women without endometriosis, despite no significant difference in starting age (coefficient = -0.62, 95% CI -1.36, 0.13). LIMITATIONS, REASONS FOR CAUTION: We did not have information on the severity of endometriosis, or the reasons for using ART, which can influence treatment and outcomes. We were not able to reliably link births with ART treatment. Finally, it is possible that some of the women in our 'no endometriosis' group did have endometriosis and were unaware of it, although prevalence rates match population estimates. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that have found no difference in outcome of ART for women with endometriosis, but add the new insight that this is only true if endometriosis is diagnosed prior to commencing ART. A delayed diagnosis can create disadvantage during ART treatment. Early recourse to IVF may be advantageous for pregnancy prospects for women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health. G.D.M. is supported by an NHMRC Principal Research Fellowship (APP11218449). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The diabetes-fracture association in women with type 1 and type 2 diabetes is partially mediated by falls: a 15-year longitudinal study.

This study evaluated mediators of fracture risk in postmenopausal women with type 1 (T1D) and type 2 diabetes (T2D), over a 15-year follow-up period. This study provides evidence that the increased fracture risk in women with T1D or T2D is partially explained by falls. Furthermore, a shorter reproductive lifespan in women with T1D contributes modestly to fracture risk in this cohort. PURPOSE: Skeletal fragility is associated with diabetes mellitus, while limited estrogen exposure during the reproductive years also predisposes to lower bone mass and higher fracture risk. We aimed to determine osteoporosis diagnosis, fall and fracture rates in women with type 1 (T1D) and type 2 (T2D) diabetes mellitus, and explore mediators of the diabetes-fracture relationship. METHODS: Prospective observational data drawn from the Australian Longitudinal Study in Women's Health (ALSWH) from 1996 to 2010. Women were randomly selected from the national health insurance database. Standardized data collection occurred at six survey time points, with main outcome measures being self-reported osteoporosis, incident fracture, falls, and reproductive lifespan. Mediation analyses were performed to elucidate relevant intermediaries in the diabetes-fracture relationship. RESULTS: Exactly 11,313 women were included at baseline (T1D, n = 107; T2D, n = 333; controls, n = 10,873). A total of 885 new cases of osteoporosis and 1099 incident fractures were reported over 15 years. Women with T1D or T2D reported more falls and fall-related injuries; additionally, women with T1D had a shorter reproductive lifespan. While fracture risk was increased in women with diabetes (T1D: OR 2.28, 95% CI 1.53-3.40; T2D: OR 2.40, 95% CI 1.90-3.03), compared with controls, adjustment for falls attenuated the risk of fracture by 10% and 6% in T1D and T2D, respectively. In women with T1D, reproductive lifespan modestly attenuated fracture risk by 4%. CONCLUSION: Women with T1D and T2D have an increased risk of fracture, which may be partially explained by increased falls, and to a lesser extent by shorter reproductive lifespan, in T1D.

Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Duration of estrogen exposure during reproductive years, age at menarche and age at menopause, and risk of cardiovascular disease events, all-cause and cardiovascular mortality: a systematic review and meta-analysis.

BACKGROUND: Little is known about the estrogen exposure measurement and mutual effect of age at menarche and age at menopause in the risk of cardiovascular disease (CVD) events. OBJECTIVES: To evaluate estrogen exposure measurement and describe mutual effect of age at menarche and age at menopause in the risk of CVD events. SEARCH STRATEGY: Systematic review of literature in PubMed, Embase and Web of Science for studies published up to 28 June 2020. SELECTION CRITERIA: Observational studies related to estrogen exposure measurement, including mutual effect of age at menarche and age at menopause and risk of CVD events. DATA COLLECTION AND ANALYSIS: Synthesis of evidence was conducted by reviewing individual estimates, followed by meta-analysis. The study received no external funding. MAIN RESULTS: A total of 75 studies were included in synthesis of evidence, of which 17 studies were included in meta-analysis. Reproductive lifespan (age at menopause - age at menarche), endogenous estrogen exposure and total estrogen exposure were used for estrogen exposure measurement. Reproductive lifespan was by far the most commonly used method for estrogen exposure measurement. A shorter reproductive lifespan was associated with a higher risk of CVD events; the pooled relative risk (95% CI) was 1.31 (1.25-1.36) for stroke events. Robust epidemiological studies with measurement of estrogen exposure and associated health risk would strengthen the evidence. CONCLUSIONS: Reproductive lifespan was the most commonly used method for estrogen exposure measurement in epidemiological studies. A shorter reproductive lifespan was associated with a higher risk of CVD events, particularly stroke. TWEETABLE ABSTRACT: A systematic review and meta-analysis found that women with a shorter reproductive lifespan have a higher risk of stroke events.

Prevalence and incidence of endometriosis in Australian women: a data linkage cohort study.

OBJECTIVE: To estimate the prevalence and incidence of endometriosis among Australian women. DESIGN: Population-based cohort study linked to administrative health records. SETTING: Secondary analysis of seven surveys collected between 2000 and 2018 from a population-based cohort study. POPULATION: A total of 13 508 Australian women, born 1973-78, from a prospective cohort study of 14 247 women conducted between 1996 and 2018. METHODS: During 2000 and 2018, self-reported longitudinal survey data were linked to three administrative health databases to separately identify women with clinically confirmed or suspected endometriosis across the multiple data sources. MAIN OUTCOME MEASURES: Prevalence and incidence of clinically confirmed endometriosis in the cohort were first estimated using national hospital data. Data were then combined with other administrative health databases and the survey data to capture all clinically confirmed and suspected diagnoses of endometriosis. RESULTS: The cumulative prevalence of clinically confirmed endometriosis was 6.0% (95% CI 5.8-6.2%) by age 40-44 years. The cumulative prevalence increased to 11.4% (95% CI 11.1-11.7%) when adding diagnoses of clinically suspected endometriosis. Age-specific incidence estimates peaked to 6 per 1000 person-years at age 30-34 years. CONCLUSIONS: Among 13 508 Australian women followed for 20 years, one in nine women had clinically confirmed or suspected endometriosis by the age of 44, with most diagnosed during their early thirties. Endometriosis is a significant public health issue requiring increased surveillance, clinical awareness and management. Efforts to expand knowledge on the aetiology of the disease and optimal methods for disease management are crucial to women's health. TWEETABLE ABSTRACT: In a national study of 13 508 Australian women, one in nine women were diagnosed with endometriosis by age 44.

Vasomotor menopausal symptoms and cardiovascular disease risk in midlife: A longitudinal study.

OBJECTIVE: To ascertain the association between vasomotor menopausal symptoms (VSM), hot flushes and night sweats, and cardiovascular disease, coronary heart disease and cerebrovascular disease. STUDY DESIGN: The study sample comprised 8881 women (aged 45-50 years) with available hospital separation data from the 1946-51 cohort (1996-2016) of the ongoing Australian Longitudinal Study on Women's Health, a national prospective cohort study. MAIN OUTCOME MEASURES: First fatal or non-fatal cardiovascular disease, coronary heart disease, and cerebrovascular disease events were obtained through linkage with hospital admission data, the National Death Index, and Medicare Benefits Schedule. Hot flushes and night sweats were assessed via questionnaires at each main survey. Additionally, we calculated the duration of symptoms based on whether or not women reported vasomotor menopausal symptoms in each survey. RESULTS: There were 925 cardiovascular disease, 484 coronary heart disease and 154 cerebrovascular disease events. There was no consistent evidence of any association with vasomotor menopausal symptoms, hot flushes and night sweats. We did find marginally statistically significant associations between presence of night sweats and cardiovascular disease (Hazard Ratio = 1.18, 95 % Confidence Interval: 1.01-1.38), and between the duration of vasomotor menopausal symptoms [years] and coronary heart disease (Hazard Ratioper year = 1.03, 95 % Confidence Interval: 1.00-1.05). However, given the number of associations tested, these findings could very well have arisen by chance. CONCLUSION: In this large longitudinal study with 20 years of follow-up and clinical outcomes we did not find a convincing association between vasomotor menopausal symptoms, hot flushes, night sweats and cardiovascular disease, coronary heart disease and cerebrovascular disease.

The role of offspring's birthweight on the association between pre-pregnancy obesity and offspring's childhood anthropometrics: a mediation analysis.

While birthweight of offspring is associated with pre-pregnancy body mass index (BMI) and later risk of obesity, its mediating effect between the association of maternal pre-pregnancy BMI and offspring's childhood anthropometrics has rarely been investigated. This study aimed to examine whether offspring birthweight is a mediator in the association between pre-pregnancy BMI and offspring's childhood anthropometrics. The study included 1,618 mother-child pairs from the Australian Longitudinal Study on Women's Health and Mothers and their Children's Health Study. Children's anthropometrics [mean age 8.6 (s.d. =3.0) years] were calculated from the mothers' self-reported child weight and height measures. G-computation was used to estimate the natural direct and indirect (via birthweight) effects of pre-pregnancy BMI. In the fully adjusted model for maternal sociodemographic and lifestyle factors, the natural direct effects of pre-pregnancy obesity on child BMI-for-age, height-for-age, weight-for-age and weight-for-height outcomes were, ß (95% confidence interval, CI), 0.75 (0.55, 0.95), 0.13 (-0.07, 0.32), 0.62 (0.44, 0.80) and 0.57 (0.24, 0.90), respectively. The corresponding natural indirect effects were 0.04 (-0.04, 0.12), -0.01 (-0.09, 0.07), -0.01 (-0.08, 0.07) and 0.09 (-0.05, 0.23). Similar results were observed for pre-pregnancy overweight and pre-pregnancy BMI as a continuous scale. Most of the effect of pre-pregnancy obesity on childhood weight-related anthropometric outcomes appears to be via a direct effect, not mediated through offspring's birthweight.

Maternal preconception weight trajectories, pregnancy complications and offspring's childhood physical and cognitive development.

There is limited evidence on the association between maternal preconception body mass index (BMI) trajectories and pregnancy complications and child development. This study examined the relationships of maternal BMI trajectories, diabetes and hypertensive disorders during pregnancy and offspring's childhood physical and cognitive development. Data were from the Australian Longitudinal Study on Women's Health and the Mothers and their Children's Health study (n=771). Women's preconception BMI trajectories were identified using group-based trajectory modelling. Children's physical and cognitive development (up to the average age of 5 years) were obtained from the Ages and Stages Questionnaire (suspected gross motor delay) and the Australian Early Development Census (AEDC). Generalized estimating equation models, adjusted for maternal sociodemographic and lifestyle factors, were used for analyses. Three distinct BMI trajectories were identified (normative, chronically overweight and chronically obese). Children born to chronically obese women were more likely to be classified as developmentally vulnerable/at-risk on AEDC domains; gross and fine motor skills [risk ratio (RR)=1.64, 95% confidence interval (CI): 1.04, 2.61] and communication skills and general knowledge (RR=1.71, 95% CI: 1.09, 2.68). They also had an elevated risk of suspected gross motor delay (RR=2.62, 95% CI: 1.26, 5.44) compared with children born to women with a normative BMI trajectory. Maternal diabetes or hypertensive disorders during pregnancy were not associated with child outcomes. Maternal preconception BMI trajectories were associated with poorer childhood development. This study finding underscores the importance of excessive weight gain prevention throughout the reproductive stage of life.

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.

A pro-inflammatory diet is associated with increased risk of developing hypertension among middle-aged women.

BACKGROUND AND AIMS: A pro-inflammatory diet is thought to lead to hypertension through oxidative stress and vessel wall inflammation. We therefore investigated the association between the dietary inflammatory index (DII) and developing hypertension in a population-based cohort of middle-aged women. METHODS AND RESULTS: The Australian Longitudinal Study on Women's Health included 7169 Australian women, aged 52 years (SD 1 year) at baseline in 2001, who were followed up through 4 surveys until 2013. The DII, a literature-derived dietary index that has been validated against several inflammatory markers, was calculated based on data collected via a validated food-frequency questionnaire administered at baseline. Hypertension was defined as new onset of doctor-diagnosed hypertension, ascertained through self-report between 2001 and 2013. Generalised Estimating Equation analyses were used to investigate the association between the DII and incident hypertension. The analyses were adjusted for demographic and hypertension risk factors. During 12-years follow-up we identified 1680 incident cases of hypertension. A more pro-inflammatory diet was associated with higher risk of hypertension in dichotomised analyses with an ORfully adjusted of 1.24, 95% CI: 1.06-1.45. CONCLUSION: A pro-inflammatory diet might lead to a higher risk of developing hypertension. These results need to be replicated in other studies.

Protective effect of hormone therapy among women with hysterectomy/oophorectomy.

Study question: Does exposure to menopausal hormone therapy (MHT) in mid-aged women alter their risk of cardiovascular disease (CVD) mortality and all-cause mortality? Summary answer: MHT soon after menopause is unlikely to increase the risk of CVD mortality or all-cause mortality and may have a protective effect for women with hysterectomy/oophorectomy. What is known already: The balance of benefits and risks of MHT are currently unclear and may differ according to when treatment starts and whether women have an intact uterus. Study design size, duration: A total of 13 715 participants from the mid-aged population-based cohort (born 1946-1951) of the Australian Longitudinal Study on Women's Health (ALSWH) were followed from 1998 to 2013. Participants/materials setting methods: The measures included cardiovascular and all-cause mortality, exposure to MHT and menopausal status (based on 3-yearly self-reports). Electronic prescriptions data on MHT were also available from mid-2002 onwards. At each follow-up survey wave, participants were classified as: an existing user of MHT, an initiator of MHT or a non-initiator of MHT. Main results and the role of chance: After adjusting for confounding variables, existing users of MHT had a reduced risk (hazard ratio 0.63; 95% CI, 0.43-0.92) of CVD mortality compared with non-initiators. Insufficient evidence of an association was identified for initiators of MHT (0.66; 0.35-1.24). For all-cause mortality, risks were reduced for both initiators (0.69; 0.55-0.87) and existing users (0.80; 0.70-0.91). In a subgroup analysis, women with hysterectomy/oophorectomy had lower risks of CVD mortality for both initiators (0.14; 0.02-0.98) and existing users (0.55; 0.34-0.90), but no evidence of an association was found for women whose MHT commenced during or after menopause. Similarly for all-cause mortality, only the women with hysterectomy/oophorectomy had lower risks for both initiators (0.47; 0.31-0.70) and existing users (0.69; 0.58-0.82). Limitations, reasons for caution: Limitations include the observational nature of the study, the small number of deaths, MHT use being self-reported and the classification of menopausal status also being based on self-reported information. Wider implications of the findings: Women considering MHT soon after menopause can be reassured that the treatment is unlikely to increase their risk of CVD mortality or all-cause mortality. Study funding/competing interest(s): The Australian Longitudinal Study on Women's Health is funded by the Australian Department of Health. G.D.M. is funded by the Australian Research Council Future Fellowship. L.C. was funded by a China scholarship council (CSC) graduate scholarship. All authors report no conflict of interest. Trial registration number: N/A.

Maternal pre-pregnancy obesity and childhood physical and cognitive development of children: a systematic review.

OBJECTIVE: Maternal obesity, usually associated with the adverse birth outcomes, has been a serious public health concern. Studies examining its effect on the physical and cognitive development of children have only recently emerged and the findings are inconsistent. This review aimed to systematically examine the role of maternal obesity on children's physical and cognitive development using the available evidence. METHODS: The CINAHL, EMBASE, PSYCINFO, PUBMED and SCOPUS databases were searched. Studies addressing children's (⩽12 years) physical and cognitive development as outcome and maternal pre-pregnancy body mass index as an exposure were included. Data were extracted and evaluated for quality by two independent reviewers. RESULTS: A total of 17 articles were eligible for this systematic review; 10 of them were birth cohorts from the USA. Nine of the 14 studies supported an adverse association between maternal pre-pregnancy obesity and childhood cognitive development. A few studies also demonstrated a negative association between the maternal obesity and gross motor function in children (5 of 10), but not with fine motor function (none out of five studies). Whether the observed negative association between the maternal obesity and children's cognitive and gross motor abilities is casual or due to residual confounding effects is unclear. The current evidence is based on a limited number of studies with heterogeneous measurement scales and obesity definition. CONCLUSIONS: From the available evidence, it seems that exposure to maternal pre-pregnancy obesity in the intrauterine environment has a detrimental effect on children's cognitive development. However, evidence of the association between the maternal obesity and physical development of children is too scarce to offer a conclusion. More research work is required to delineate the intrauterine effect of the maternal obesity from the residual confounding effects.

Young women's psychological distress after a diagnosis of polycystic ovary syndrome or endometriosis.

STUDY QUESTION: Do young women with polycystic ovary syndrome (PCOS) or endometriosis report more psychological distress than their peers without a history of these conditions? SUMMARY ANSWER: Young women (aged 18-23 years) with PCOS or endometriosis had a greater risk of moderate to severe psychological distress than women without a history of these conditions. WHAT IS KNOWN ALREADY: Psychological distress appears common among women with PCOS and endometriosis. However, population-based studies that examine the psychological outcomes for adolescents and young women are generally absent from the literature. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of data collected from 17 015 young, Australian women participating in a national, longitudinal cohort study. Women were first surveyed in 2012-2013 when they were aged 18-23 years. In 2014, women completed the second survey when they were aged 19-24 years and 11324 (67%) women responded. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analysed data from 11 238 women who participated in both Surveys 1 and 2 and who responded to questions about PCOS and endometriosis. Using logistic regression, we compared the odds of moderate to severe psychological distress at Surveys 1 and 2 for women reporting a recent diagnosis (within the last 12 months) of PCOS or endometriosis and women with a pre-existing diagnosis, with that for women without a history of these conditions. MAIN RESULTS AND THE ROLE OF CHANCE: At Survey 2, around 60% of women reporting a diagnosis of PCOS or endometriosis had moderate to severe levels of psychological distress. Compared to women without a history of these conditions, the odds of moderate to severe psychological distress at Survey 2 were significantly higher for women recently diagnosed with PCOS [Adjusted Odds Ratio (AOR) = 1.62, 95% CI = 1.21-2.18] or endometriosis (AOR= 1.77; 95% CI = 1.20-2.63) and for women with a pre-existing diagnosis of PCOS (AOR = 1.57, 95% CI = 1.30-1.89) or endometriosis (AOR = 1.61; 95% CI = 1.26-2.06). Women recently diagnosed with PCOS or endometriosis also had a greater likelihood of moderate to severe distress in the year prior to their diagnosis. The association between PCOS and psychological distress was attenuated when adjusting for BMI, but hormonal contraceptive use did not attenuate the risk of distress among the women with PCOS or endometriosis. LIMITATIONS, REASONS FOR CAUTION: All data were self-reported and, therefore, the diagnoses of PCOS or endometriosis were not confirmed by a medical practitioner. WIDER IMPLICATIONS OF THE FINDINGS: Health professionals should be aware of the potential psychosocial and healthcare needs among young women with these conditions, particularly women with PCOS who are obese. While hormonal contraceptives may help to regulate the hormonal aspects of these conditions, they do not appear to reduce women's psychological distress. Because psychological distress among the young women in this study remained elevated even after diagnosis, this supports the need for multidisciplinary health care to help women adjust to their diagnosis and treatment regimens and facilitate positive, long-term mental health outcomes. Future research that examines medical and psychosocial sources of distress for young women with PCOS and endometriosis is needed. STUDY FUNDING/COMPETING INTERESTS: I.J.R. was supported by an Australian National Health and Medical Research Council Centre for Research Excellence (grant number: APP1000986). G.D.M. is funded by the Australian Research Council Future Fellowship (FT120100812). The Australian Longitudinal Study on Women's Health is funded by the Australian Government Department of Health. H.T. is supported by an Australian National Health and Medical Research Council Practitioner Fellowship. The authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: N/A.

Association of diet and lifestyle with glycated haemoglobin in type 1 diabetes participants in the EURODIAB prospective complications study.

BACKGROUND/OBJECTIVES: Diet and lifestyle advice for type 1 diabetes (T1DM) patients is based on little evidence and putative effects on glycaemic control. Therefore, we investigated the longitudinal relation between dietary and lifestyle variables and HbA1c levels in patients with type 1 diabetes. SUBJECTS/METHODS: A 7-year prospective cohort analysis was performed in 1659 T1DM patients (52% males, mean age 32.5 years) participating in the EURODIAB Prospective Complications Study. Baseline dietary intake was assessed by 3- day records and physical activity, smoking status and alcohol intake by questionnaires. HbA1c during follow-up was centrally assessed by immunoassay. Analysis of variance (ANOVA) and restricted cubic spline regression analyses were performed to assess dose-response associations between diet and lifestyle variables and HbA1c levels, adjusted for age, sex, lifestyle and body composition measures, baseline HbA1c, medication use and severe hypoglycaemic attacks. RESULTS: Mean follow-up of our study population was 6.8 (s.d. 0.6) years. Mean HbA1c level was 8.25% (s.d. 1.85) (or 66.6 mmol/mol) at baseline and 8.27% (s.d. 1.44) at follow-up. Physical activity, smoking status and alcohol intake were not associated with HbA1c at follow-up in multivariable ANOVA models. Baseline intake below the median of vegetable protein (<29 g/day) and dietary fibre (<18 g/day) was associated with higher HbA1c levels. Restricted cubic splines showed nonlinear associations with HbA1c levels for vegetable protein (P (nonlinear)=0.008) and total dietary fibre (P (nonlinear)=0.0009). CONCLUSIONS: This study suggests that low intake of vegetable protein and dietary fibre are associated with worse glycaemic control in type 1 diabetes.

Developmental trajectories of adiposity from birth until early adulthood and association with cardiometabolic risk factors.

OBJECTIVE: To identify developmental trajectories of adiposity from birth until early adulthood, and to investigate how they relate with cardiometabolic risk factors at 21 years of age. METHODS: Participants' weight and height measurements were obtained using the EPITeen cohort protocol at 13, 17 and 21 years of age, and extracted from child health books as recorded during health routine evaluations since birth. Blood pressure, triglycerides, cholesterol and insulin resistance (HOMA-IR) were assessed at 21 years. Trajectories were defined using 719 participants contributing 11 459 measurements. The individual growth curves were modelled using mixed-effects fractional polynomial, and the trajectories were estimated using normal mixture modelling for model-based clustering. Differences in cardiometabolic risk factors at 21 years according to adiposity trajectories were estimated through analysis of covariance (ANCOVA), and adjusted means are presented. RESULTS: Two trajectories-'Average body mass index (BMI) growth' (80.7%) and 'Higher BMI growth' (19.3%)-were identified. Compared with those in 'Average BMI growth', 'Higher BMI growth' participants were more frequently delivered by caesarean section, mothers were younger and had higher BMI, and parental education was lower; and at 21 years showed higher adjusted mean systolic (111.6 vs 108.3 mm Hg, P<0.001) and diastolic blood pressure (71.9 vs 68.4 mm Hg, P<0.001), and lower high-density lipoprotein cholesterol (53.3 vs 57.0 mg dl(-1), P=0.001). As there was a significant interaction between trajectories and sex, triglycerides and HOMA-IR were stratified by sex and we found significantly higher triglycerides, in males, and higher HOMA-IR in both sexes in 'Higher BMI growth' trajectory. All the differences were attenuated after adjustment for BMI at 21 years. CONCLUSIONS: In this long-term follow-up, we were able to identify two adiposity trajectories, statistically related to the BMI and cardiometabolic profile in adulthood. Our results also suggest that the impact of the adiposity trajectory on cardiometabolic profile is mediated by current BMI.

The influence of long-term exposure and timing of physical activity on new joint pain and stiffness in mid-age women.

OBJECTIVE: To examine the influence of long-term exposure and timing of physical activity (PA) on new joint pain/stiffness in mid-age women. METHODS: Data were from 5105 participants (born 1946-51) in the Australian Longitudinal Study on Women's Health (ALSWH) who completed survey items on PA (1998, 2001 and 2004) and joint pain/stiffness (2007 and 2010). PA was categorized in five levels at each survey and summed into a cumulative PA score (CPA, range 0-12). Associations were analysed using logistic regression, with separate models for the cumulative model (using CPA), the sensitive periods model (i.e., PA measured at each survey in one regression model) and the critical periods model (i.e., separate regression models for PA at each survey). RESULTS: 951 (18.6%) participants reported new-onset joint pain/stiffness. In the cumulative model, CPA was associated joint pain/stiffness when included as a continuous variable (adjusted odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.95-0.99), but not when included as a categorical variable. In both the sensitive periods and critical periods models, low to high levels of PA in 2001 and 2004 had stronger inverse associations with joint pain/stiffness than PA levels in 1998. The model fit was better for the sensitive periods than the cumulative or critical periods models. CONCLUSIONS: In mid-age women, PA between the ages 47 and 58 was associated with a lower risk of joint pain/stiffness 9 years later. Associations were stronger for PA in the last 6 years than for earlier PA.

Fruit and vegetable consumption and prevalence and incidence of depressive symptoms in mid-age women: results from the Australian longitudinal study on women's health.

BACKGROUND/OBJECTIVES: There is continued interest in the associations between diet and depression and several studies have focused on individual dietary factors or diet patterns to investigate the relationship. We investigated the association between fruit and vegetables and symptoms of depression in the mid-age cohort of the Australian Longitudinal Study on Women's Health. SUBJECTS/METHODS: A total of 6271 women with a mean age of 55.45 (1.45 s.d.) years were followed up at three surveys over 6 years. A score of ⩾ 10 on the Center for Epidemiological Studies Depression-10 scale indicated depressive symptoms. Fruit and vegetable intake was assessed using short questions. RESULTS: A total of 381 women (6.1%) were depressed at all three surveys over the 6-year survey period. Cross-sectional logistic regression analysis using general estimating equations showed a reduced odds of depressive symptoms (odds ratio (OR) 0.86 (95% confidence interval (CI) 0.79-0.95, P=0.001)) among women who ate ⩾ 2 of fruit/day even after adjustment for several factors including smoking, alcohol, body mass index, physical activity, marital status, education, energy, fish intake and comorbidities. The predictive model also showed a reduced odds of depressive symptoms (OR 0.82 (95% CI 0.70-0.96, P=0.012)) among women who ate ⩾ 2 pieces of fruit/day. There was also an association between vegetable intake and prevalence of depressive symptoms at higher levels of intake. CONCLUSIONS: Increasing fruit consumption may be one important factor for reducing both the prevalence and incidence of depressive symptoms in mid-age women.