Externally validated prediction models for pre-eclampsia: systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the performance of existing externally validated prediction models for pre-eclampsia (specifically for any- early- late-onset and preterm pre-eclampsia). METHODS: A systematic search was conducted in five databases (MEDLINE, Embase, Emcare, CINAHL, and Maternity and Infant Care Database) to identify studies based on Population, Index model, Comparator, Outcome, Timing, and Setting (PICOTS) approach until May 20, 2023. We extracted data using the CHARMS checklist and appraised risk of bias using PROBAST tool. Discrimination and calibration performance were meta-analysed when appropriate. RESULTS: Twenty-three publications reported 52 externally validated prediction models on pre-eclampsia (twenty any-onset, seventeen early-onset, fourteen late-onset, and one preterm pre-eclampsia). No model had the same set of predictors. Fifteen, two, and three any-onset pre-eclampsia models were externally validated once, twice, and thrice, respectively, and the Fetal Medicine Foundation (FMF) preterm model was widely validated in sixteen different settings. The most common predictors were maternal characteristics (pre-pregnancy BMI, prior pre-eclampsia, family history of pre-eclampsia, chronic medical conditions, and ethnicity) and biomarkers (uterine artery pulsatility index and pregnancy-associated plasma protein-A). The model for preterm pre-eclampsia (triple test FMF) had the best performances with a pooled area under the receiver operating characteristics curve (AUROC) of 0.90 (95% prediction interval (PI) 0.76 - 0.96) and was well-calibrated. The other models generally had poor to fair discrimination performance (AUROC median 0.66, range 0.53 to 0.77) and were overfitted in calibration after external validation. Apart from the FMF model, only the two most validated models in any-onset pre-eclampsia using isolated maternal characteristics, produced reasonable pooled AUROCs of 0.71 (95% PI 0.66 - 0.76) and 0.73 (0.55 - 0.86). CONCLUSION: Existing externally validated prediction models for any-, early-, and late-onset pre-eclampsia have limited discrimination and calibration performance with inconsistent input variables. The triple test FMF model had excellent discrimination performance in predicting preterm pre-eclampsia in numerous settings, but the inclusion of specialised biomarkers may limit feasibility and implementation outside of high-resource settings. This article is protected by copyright. All rights reserved.

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.

Informing a PCOS Lifestyle Program: Mapping Behavior Change Techniques to Barriers and Enablers to Behavior Change Using the Theoretical Domains Framework.

This article aimed to identify the behavior change techniques (BCTs) based on facilitators and barriers to lifestyle management in women with polycystic ovary syndrome (PCOS) according to the behavior change wheel (BCW). This qualitative study design using inductive thematic analysis following semistructured interviews (n = 20) identified barriers and enablers to lifestyle management. These were then mapped to Capability, Opportunity, Motivation-Behavioral Model (COM-B) constructs and the corresponding Theoretical Domains Framework (TDF) domains. This study included women with PCOS residing in Australia. Main outcome measures include intervention functions, policy categories, and BCTs described in the BCW. Twenty-three BCTs were recognized to influence behavior change in women with PCOS. Factors were categorized into the subcomponents of the COM-B: psychological capability (e.g., lack of credible information), physical capability (e.g., managing multiple health conditions), physical opportunity (e.g., limited access to resources), social opportunity (e.g., adequate social support), reflective motivation (e.g., positive health expectancies following behavior change), and automatic motivation (e.g., emotional eating). Future research should use this work to guide PCOS lifestyle intervention development and then test intervention effectiveness through an experimental phase to provide empirical evidence for wider use and implementation of tailored, theory-informed PCOS lifestyle programs as part of evidence-based PCOS management.

Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.

INTRODUCTION: Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta-analysis and meta-regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta-regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high-density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2-hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA-IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.

Cardiometabolic risks in PCOS: a review of the current state of knowledge.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to 18% women of reproductive age. It is associated with a range of metabolic, reproductive, and psychological features. Current evidence indicates a role of PCOS in the development of metabolic and increased cardiovascular risk factors (CVRF) with implications for compromised cardiovascular endpoint disease, which may have a considerable impact on health and health care costs. AREAS COVERED: Existing studies examining long-term cardiometabolic health in PCOS are heterogeneous with inconsistent findings. In the current review, we aim to explore and critically review retrospective, prospective, meta-analysis and review articles relating to PCOS on cardiometabolic risk factors and clinical consequences to summarize the evidence, note evidence gaps, and suggest implications for future research. EXPERT COMMENTARY: Although there is an established association between PCOS and metabolic health, implications on cardiac health are more uncertain with associations observed for CVRF and subclinical disease, yet limited and conflicting data on actual cardiovascular endpoints. There is a lack of population-based long-term studies examining cardiometabolic morbidity and mortality in PCOS with a need for further research to progress toward a better understanding of the long-term cardiometabolic impacts in women with PCOS.

Nutrition and listeriosis during pregnancy: a systematic review.

Listeriosis is a rare but severe foodborne illness which is more common in populations such as pregnant women, and can result in serious complications including miscarriage, prematurity, maternal and neonatal sepsis, and death in the newborn. Population recommendations exist for specific foods and food preparation practices to reduce listeriosis risk during pregnancy. The aim of the present systematic review was to assess the association between listeriosis and these practices during pregnancy to confirm appropriateness of these recommendations. We searched MEDLINE, Embase, CINAHL Plus, Web of Science Core Collection, included articles' references, and contacted clinical experts. All databases were searched until July 2017. Case-control and cohort studies were included which assessed pregnant women or their newborn offspring with known listeriosis status and a nutritional exposure consistent with international population recommendations for minimising listeriosis. Outcomes included listeriosis with or without pregnancy outcomes. Risk of bias was assessed through the Newcastle-Ottawa Scale. Results were described narratively due to clinical heterogeneity in differences in nutritional exposures. Eleven articles comprising case-control or cross-sectional studies met the inclusion criteria. Cases of maternal, fetal or neonate listeriosis were more likely to have consumed high-risk dairy products, meat products or some fruits during pregnancy in comparison with women without listeriosis. Cases of listeriosis were more likely to have consumed foods that are highlighted in population guidelines to avoid to minimise listeriosis in comparison with those without listeriosis during pregnancy. Further research is warranted assessing means of improving the reach, uptake and generalisability of population guidelines for reducing listeriosis during pregnancy.

The characterisation of overweight and obese women who are under reporting energy intake during pregnancy.

BACKGROUND: Misreporting of energy intake is common and can contribute to biased estimates of the relationship between diet and disease. Energy intake misreporting is poorly understood in pregnancy and there is limited research assessing characteristics of women who misreport energy intake or changes in misreporting of energy intake across pregnancy. METHODS: An observational study in n = 945 overweight or obese pregnant women receiving standard antenatal care who participated in the LIMIT randomised trial. Diet, physical activity, psychological factors, body image satisfaction and dieting behaviour were assessed at trial entry (10-20 weeks gestation) and 36 weeks gestation. Energy misreporting status was assessed through the ratio of daily energy intake over basal metabolic rate. Logistic regression analyses were conducted with the dependent variable of under reporting of energy intake at study entry or 36 weeks in separate analysis. RESULTS: At study entry and 36 weeks, women were classified as under reporters (38 vs 49.4%), adequate reporters (59.7 vs 49.8%) or over reporters of energy intake (2.3 vs 0.8%) respectively. The prevalence of under reporting energy intake at 36 weeks was higher than at study entry (early pregnancy). Body mass index (BMI) at study entry and 36 weeks and socioeconomic status, dieting behaviour and risk of depression at 36 weeks were independent predictors of under reporting of energy intake. CONCLUSIONS: Under reporting of energy intake was present in over a third of overweight and obese pregnant women and was higher in late compared to early pregnancy. Characteristics such as BMI, socioeconomic status, past dieting behaviour and risk of depression may aid in identifying women who either require support in accurate recording of food intake or attention for improving diet quality. Results were unable to distinguish whether under reporting reflects misreporting or a true restriction of dietary intake. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12607000161426 , registered 9/3/2007.

Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression.

BACKGROUND: Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. OBJECTIVE AND RATIONALE: We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. SEARCH METHODS: We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. OUTCOMES: We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression. WIDER IMPLICATIONS: Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes. PROSPERO REGISTRATION NUMBER: CRD42017056524.

Systematic review and meta-analysis of the impact of preconception lifestyle interventions on fertility, obstetric, fetal, anthropometric and metabolic outcomes in men and women.

STUDY QUESTION: What is the impact of preconception lifestyle interventions on live birth, birth weight and pregnancy rate? SUMMARY ANSWER: Lifestyle interventions showed benefits for weight loss and increased natural pregnancy rate, but not for live birth or birth weight. WHAT IS KNOWN ALREADY: Evidence on the practice and content of preconception counseling and interventions is variable and limited. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis (MA). Main search terms were those related to preconception lifestyle. Database searched were Ovid MEDLINE(R), EBM Reviews, PsycINFO, EMBASE and CINAHL Plus. No language restriction was placed on the published articles. The final search was performed on 10 January 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were non-pregnant women of childbearing age intent on conceiving or their male partners. Exclusion criteria include participants with BMI < 18 kg/m2, animal trials, hereditary disorder in one or both partners and trials focusing solely on alcohol or smoking cessation/reduction, micronutrient supplementation, or diabetes control. Anthropometric, fertility, obstetric and fetal outcomes were assessed. Bias and quality assessments were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The search returned 1802 articles and eight studies were included for analysis. Populations targeted were primarily overweight or obese subfertile women seeking reproductive assistance, with few community-based studies and none including men. MA showed greater reduction in weight (n = 3, P < 0.00001, mean difference: -3.48 kg, 95% CI: -4.29, -2.67, I2 = 0%) and BMI (n = 2, P < 0.00001, mean difference: -1.40 kg/m2, 95% CI: -1.95, -0.84, I2 = 24%) with intervention. The only significant fertility outcome was an increased natural pregnancy rate (n = 2, P = 0.003, odds ratio: 1.87, CI: 1.24, 2.81, I2 = 0%). No differences were observed for ART adverse events, clinical pregnancy, pregnancy complications, delivery complications, live birth, premature birth, birth weight, neonatal mortality or anxiety. Risk of bias were high for three studies, moderate for three studies and low for two studies, Attrition bias was moderate or high in majority of studies. LIMITATIONS, REASONS FOR CAUTION: Results were limited to subfertile or infertile women who were overweight or obese undergoing ART with no studies in men. The heterogeneous nature of the interventions in terms of duration and regimen means no conclusions could be made regarding the method or components of optimal lifestyle intervention. Attrition bias itself is an important factor that could affect efficacy of interventions. WIDER IMPLICATIONS OF THE FINDINGS: Existing preconception lifestyle interventions primarily targeted overweight and obese subfertile women undergoing ART with a focus on weight loss. It is important to note that natural conception increased with lifestyle intervention. This emphasizes the need for further research exploring optimal components of preconception lifestyle interventions in the broader population and on the optimal nature, intensity and timing of interventions. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest declared. C.L.H. is a National Heart Foundation Postdoctoral Research Fellow. B.H. is funded by an Alfred Deakin Postdoctoral Research Fellowship. H.J.T. and B.W.M. hold NHMRC Practitioner fellowships. L.J.M. is supported by a SACVRDP Fellowship; a program collaboratively funded by the NHF, the South Australian Department of Health and the South Australian Health and Medical Research Institute. PROSPERO REGISTRATION NUMBER: CRD42015023952.

The association of the lipidomic profile with features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

Weight management practices associated with PCOS and their relationships with diet and physical activity.

STUDY QUESTION: Do weight management practices differ in women with and without PCOS? SUMMARY ANSWER: Women in the general population with self-reported PCOS are more likely to be using healthy weight management practices and alternative non-lifestyle measures for weight management than women without PCOS. WHAT IS KNOWN ALREADY: Lifestyle management is the first-line treatment in PCOS. However, the specific weight management practices used by women with PCOS and their effect on diet and physical activity are unclear. STUDY DESIGN, SIZE, DURATION: The study was a population-based observational cross-sectional study involving women in the 1973-1978 cohort (n = 7767 total; n = 556 with PCOS, n = 7211 without PCOS). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with and without self-reported PCOS were included. Self-reported outcome measures included healthy lifestyle-related or alternative non-lifestyle-related (e.g. laxatives or smoking) weight management practices, dietary intake and physical activity. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS were more likely to be following both healthy [reducing meal or snack size (odds ratio (OR) 1.50, 95% CI 1.14, 1.96, P = 0.004) and reducing fat or sugar intake (OR 1.32, 95% CI 1.03, 1.69, P = 0.027) or following a low glycaemic index diet (OR 2.88, 95% CI 2.30, 3.59, P < 0.001)] and alternative [smoking (OR 1.60, 95% CI 1.02, 2.52, P = 0.043) or use of laxative, diet pills, fasting or diuretics (OR 1.45, 95% CI 1.07, 1.97, P = 0.017)] weight management practices than women without PCOS. In PCOS, the use of a range of healthy weight management practices was associated with increases in physical activity (P < 0.001), diet quality (P < 0.001), percentage protein intake (P < 0.001) and decreases in glycaemic index (P < 0.001), and percentages of fat (P = 0.001), saturated fat (P < 0.001) or fibre (P = 0.003). Use of alternative weight management practices was associated with decreases in diet quality. LIMITATIONS, REASONS FOR CAUTION: Limitations include the use of self-reported data for PCOS, height, weight, diet, physical activity and weight management behaviours. WIDER IMPLICATIONS OF THE FINDINGS: In PCOS, we should focus on improving healthy weight practices across both diet quality and quantity, and on assessing alternative weight practices and their potential adverse effect on dietary intake. STUDY FUNDING/COMPETING INTEREST(S): L.M. is supported by a South Australian Cardiovascular Research Development Program Fellowship (ID AC11S374); a program collaboratively funded by the National Heart Foundation, the South Australian Department of Health and the South Australian Health and Medical Research Institute. H.T. is supported by the NHMRC. S.A.M. is supported by an NHMRC Career Development Fellowship Level 2, ID1104636 and was previously supported by an ARC Future Fellowship (2011-2015, FT100100581). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study.

OBJECTIVE: To assess the contribution of maternal factors to major birth defects after in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and natural conception. DESIGN: Retrospective cohort study in South Australia for the period January 1986 to December 2002. SETTING: A whole of population study. POPULATION: A census of all IVF and ICSI linked to registries for births, pregnancy terminations, and birth defects (diagnosed before a child's fifth birthday). METHODS: Odds ratios (ORs) for birth defects were calculated among IVF, ICSI, and natural conceptions for maternal age, parity, pre-pregnancy BMI, smoking, pre-existing diseases, and conditions in pregnancy, with adjustment for confounding factors. MAIN OUTCOME MEASURES: Birth defects classified by International Classification of Diseases (ninth revision) and British Paediatric Association (ICD9-BPA) codes. RESULTS: There were 2211 IVF, 1399 ICSI, and 301 060 naturally conceived births. The unadjusted prevalence of any birth defect was 7.1, 9.9, and 5.7% in the IVF, ICSI, and natural conception groups, respectively. As expected, the risk of birth defects increased with maternal age among the natural conceptions. In contrast, for IVF and ICSI combined, relative to natural conceptions, births to women aged ≤29 years had a higher risk (adjusted odds ratio, aOR 1.42; 95% confidence interval, 95% CI 1.04-1.94), births to women aged 35-39 years had no difference in risk (aOR 1.01; 95% CI 0.74-1.37), and births to women aged ≥40 years had a lower risk of defects (aOR 0.45; 95% CI 0.22-0.92). Defects were also elevated for nulliparity, anaemia, and urinary tract infection in births after ICSI, but not after IVF. CONCLUSIONS: The usual age-birth defect relationship is reversed in births after IVF and ICSI, and the associations for other maternal factors and defects vary between IVF and ICSI. TWEETABLE ABSTRACT: Risk of birth defects in women over 40 years is lower after infertility treatment than for natural conceptions.

Performance of mass spectrometry steroid profiling for diagnosis of polycystic ovary syndrome.

STUDY QUESTION: How well does multi-analyte steroid mass spectrometry (MS) profiling classify women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Our liquid chromatography MS (LC-MS) steroid profiling only minimally improves discrimination of women with and without PCOS compared with a direct testosterone immunoassay (T_IA) and the free androgen index (FAI). WHAT IS KNOWN ALREADY: Blood testosterone measured by direct (non-extraction) immunoassay overlaps between women with and without PCOS. Multi-analyte MS provides greater specificity and accuracy for steroid measurement so might improve the classification. STUDY DESIGN, SIZE, DURATION: An observational, cross-sectional study of women with PCOS (n = 152) defined by Rotterdam criteria and matched non-PCOS (n = 45) control women was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum steroid profiles of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione (A4), estradiol (E2), estrone (E1), 17 hydroxy progesterone (17OHP4), progesterone (P4) and cortisol were measured by LC-MS; T_IA and sex hormone binding globulin were measured by immunoassay; and FAI, calculated free testosterone (cFT) and total androgen index (TAI) were calculated. Classification was based on logistic regression with corresponding univariate and multivariate C-statistics. MAIN RESULTS AND THE ROLE OF CHANCE: Serum testosterone by immunoassay demonstrated levels more than 100% higher than that measured by LC-MS. Compared with the controls, women with PCOS had higher serum T, DHEA, A4, TAI, T_IA, cFT, FAI and E2 but not serum DHT, E1, P4, 17OHP4 or cortisol. Univariate C-statistics were highest for FAI (0.89) and T_IA (0.82) compared with other androgens (T [0.72], DHT [0.40]), pro-androgens (A4 [0.74], DHEA[0.71]) or derivatives (cFT [0.75], TAI [0.60]). For all multivariate models, the overall correct predictions (81-86%) featured high sensitivity (92-96%) but low specificity (28-43%). and substituting LC-MS steroid measurements for T_IA and FAI produced only minimal improvements in classification. LIMITATIONS REASONS FOR CAUTION: The study cohort is limited in size and only unconjugated steroids were measured. WIDER IMPLICATIONS OF THE FINDINGS: Multi-analyte steroid profiling of unconjugated circulating steroids provides only limited improvement on direct T_IA in classifying women with and without PCOS. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Breastfeeding and obesity in PCOS.

INTRODUCTION: Polycystic ovary syndrome (PCOS), a common condition affecting up to 18% of reproductive-aged women, has complications including reproductive, metabolic and psychological dysfunction. There is a strong potentially bidirectional association of obesity with PCOS. Women with PCOS both have a higher risk of obesity and greater longitudinal weight gain and obesity increases the prevalence and severity of the reproductive, metabolic and psychological features of PCOS. In limited observational studies, PCOS is proposed as a potential factor contributing to lower breastfeeding initiation and duration. Areas covered: A narrative review using PubMed was performed covering the areas of the association of obesity and PCOS with breastfeeding success and interventions for improving breastfeeding success. Obesity impacts on breastfeeding success related to factors including impaired lactogenesis, mechanical difficulties, psychological considerations and an increased likelihood of having a caesarean section. The common coexistence of obesity in PCOS is the likely key contributor to the breastfeeding problems observed in PCOS, given the contribution of obesity to reduced breastfeeding initiation and duration. Expert review: Facilitating breastfeeding is crucial for optimising maternal and infant health benefits, highlighting the importance of lactation support for overweight and obese women with or without PCOS.

Sleep disturbances in a community-based sample of women with polycystic ovary syndrome.

STUDY QUESTION: Is there an excess of sleep disturbances in women with polycystic ovary syndrome (PCOS) in a community-based sample? STUDY ANSWER: Sleep disturbances are almost twice as common in women with PCOS compared with women of similar age without PCOS, with the association slightly accounted for by body weight and, to a greater extent, by depressive symptoms. WHAT IS KNOWN ALREADY: There is an excess of sleep-disordered breathing in clinical samples of women with PCOS, after accounting for their profile of body weight. Poor sleep patterns increase insulin resistance and thus may exacerbate PCOS symptoms and longer-term risk of metabolic disease. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 724 women, comprising 74% of a cohort study established retrospectively when women were around age 30 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Comparisons were made between 87 women with PCOS, diagnosed using the Rotterdam criteria, and 637 women without this diagnosis in Adelaide, South Australia. Differences in sleep disturbances, assessed using a modified version of the Jenkins questionnaire, were investigated using ordered logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Sleep disturbances were twice as common in women with PCOS compared with those without. Specifically, PCOS was associated with increasing occurrence of difficulty falling asleep (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.28-2.95); this association was attenuated but still statistically significant after accounting for BMI and depressive symptoms. Increasing occurrence of difficulty maintaining sleep (OR 1.92 95% CI 1.12-3.31) was mediated by obesity and depressive symptoms, together. Other factors did not change these findings. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of the study means that the direction of associations between PCOS and sleep disturbances is unclear, although bi-directionality for the mediators is likely based on data in the wider literature. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that assessment and management of both sleep and mental health problems in women with PCOS should be undertaken. Longitudinal data would be valuable to see how poor sleep affects longer-term health profiles.

Vitamin D is independently associated with depression in overweight women with and without PCOS.

BACKGROUND: Depression, anxiety, and inflammation are common in polycystic ovary syndrome (PCOS). Inflammation may adversely impact on mood and vitamin D has been associated with both mood disorders and inflammation in the general population, but these relationships have not been studied in PCOS. The aim of this study was to investigate the association among 25 hydroxy-Vitamin D (25OHVD) status, anxiety, depression, and inflammation in women with and without PCOS. METHODS: Cross-sectional study in overweight or obese premenopausal women with (n = 50) and without (n = 23) PCOS. Primary outcome measures were 25OHVD, mood (Hospital Anxiety and Depression questionnaire), and inflammation (highly sensitive C-reactive protein (hsCRP)). RESULTS: Vitamin D deficiency (25OHVD<50 nmol/L) (46% versus 39%, p = 0.311) and 25OHVD (50.4 ± 22.2 nmol/L versus 51.6 ± 19.0 nmol/L, p = 0.828) were not significantly different in women with and without PCOS. For all women combined, 25OHVD was the only significant independent predictor of depression (ß = -0.063 ± 0.021, p = 0.005) and hsCRP (ß = -0.041 ± 0.015, p = 0.010). CONCLUSIONS: Vitamin D deficiency is common in both women with and without PCOS with no differences between the groups. Vitamin D is independently associated with depression and inflammation in overweight women both with and without PCOS. Further investigation to clarify the interrelationship among vitamin D, inflammation and depression is required to identify optimal prevention and treatment strategies for psychological and metabolic dysfunction in PCOS.

Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and an increased risk of Type 2 diabetes and cardiovascular disease. Decreased SHBG and elevated testosterone are associated with metabolic syndrome and glucose intolerance in women. AIM: The aim of this study was to assess the relationship between SHBG and testosterone and metabolic syndrome and glucose intolerance in PCOS. MATERIAL/SUBJECTS AND METHODS: Cross-sectional study in overweight and obese premenopausal non-diabetic women with PCOS (no.=178: no.=55 metabolic syndrome, no.=16 glucose intolerance). Data were analyzed by multiple regression with metabolic syndrome, oral glucose tolerance test (OGTT) glucose or SHBG as dependent variables and reproductive hormones, insulin resistance, glucose tolerance, lipids or C-reactive protein as independent variables. RESULTS: Metabolic syndrome was independently associated with body mass index [odds ratio (OR) 1.084 95% confidence interval (CI) 1.034-1.170, p=0.015] and SHBG (OR 0.961 95% CI 0.932-0.995, p=0.018). Glucose tolerance was independently associated with OGTT insulin (ß=0.418, p<0.001), age (ß=0.154, p=0.033) and PRL (ß=-0.210, p=0.002). SHBG was independently associated with OGTT insulin (ß=-0.216, p=0.014) and PCOS diagnostic criteria (ß=0.197, p=0.010). CONCLUSIONS: SHBG, but not testosterone, is independently associated with metabolic syndrome in overweight women with PCOS and is associated with insulin resistance and PCOS diagnostic criteria.

The contribution of diet, physical activity and sedentary behaviour to body mass index in women with and without polycystic ovary syndrome.

STUDY QUESTION: What is the contribution of diet, physical activity and sedentary behaviour to body mass index (BMI) in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: PCOS status, higher energy intake and glycaemic index and lower physical activity were independently associated with BMI. WHAT IS KNOWN ALREADY: Obesity worsens the clinical features of PCOS and women with PCOS have an elevated prevalence of overweight and obesity. It is not known whether there is a contribution of lifestyle factors such as dietary intake, physical activity or sedentary behaviour to the elevated prevalence of obesity in PCOS. STUDY DESIGN, SIZE, DURATION: This study is a population-based observational study with data currently collected at 13 year follow-up. The study commenced in 1996. For this analysis, data are analysed at one time point corresponding to the Survey 5 of the cohort in 2009. At this time 8200 participants remained (58% retention of baseline participants) of which 7466 replied to the questionnaire; 409 self-reported a diagnosis of PCOS and 7057 no diagnosis of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Australian women born in 1973-1978 from the Australian Longitudinal Study on Women's Health. MAIN RESULTS AND THE ROLE OF CHANCE: Mean BMI was higher in women with PCOS compared with non-PCOS (29.3 ± 7.5 versus 25.6 ± 5.8 kg/m(2), P < 0.001). Women with PCOS reported a better dietary intake (elevated diet quality and micronutrient intake and lower saturated fat and glycaemic index intake) but increased energy intake, increased sitting time and no differences in total physical activity compared with non-PCOS. PCOS status, higher energy intake and glycaemic index and lower physical activity, as well as age, smoking, alcohol intake, occupation, education and country of birth, were independently associated with BMI. LIMITATIONS, REASONS FOR CAUTION: The weaknesses of this study include the self-reported diagnosis of PCOS, and the women not reporting PCOS not having their control status clinically verified which is likely to underrepresent the PCOS population. We are also unable to determine if lifestyle behaviours contributed to the PCOS diagnosis or were altered in response to diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The strengths of this study include the community-based nature of the sample which minimizes selection bias to include women with a variety of clinical presentations. These results are therefore generalizable to a broader population than the majority of research in PCOS examining this research question which are performed in clinic-based populations. This study is in agreement with the literature that PCOS is independently associated with elevated BMI. We provide new insights that diet quality is subtly improved but that sedentary behaviour is elevated in PCOS and that PCOS status, higher energy intake and glycaemic index and lower physical activity are independently associated with BMI. STUDY FUNDING/COMPETING INTEREST(S): L.J.M. was supported by a South Australian Cardiovascular Research Development Program (SACVRDP) Fellowship (AC11S374); a program collaboratively funded by the National Heart Foundation of Australia, the South Australian Department of Health and the South Australian Health and Medical Research Institute, S.A.M. was funded by an Australian Research Council Future Fellowship (FT100100581), S.Z. was funded by a Heart Foundation Career Development Fellowship (ID CR10S5330) and H.J.T. was funded by an NHMRC fellowship (ID 545888). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

A decrease in diet quality occurs during pregnancy in overweight and obese women which is maintained post-partum.

BACKGROUND: Ensuring adequate dietary intake during pregnancy has important implications for optimising maternal and fetal health. It is not known whether diet quality is altered over pregnancy and the post-partum period. OBJECTIVE: The aim of this study was to perform a comprehensive assessment of diet quality in overweight and obese women during pregnancy and early post-partum. DESIGN: In a prospective cohort study, n=301 overweight or obese pregnant women completed a food frequency questionnaire at study entry (10-20 weeks gestation), 28 weeks gestation, 36 weeks gestation and 4 months post-partum for assessment of macronutrient and micronutrient intake and diet quality by the Healthy Eating Index (HEI). RESULTS: Energy, macronutrient and dietary sources of micronutrients did not alter across pregnancy or post-partum. The HEI was of below average quality in 31.0% of women at baseline. This decreased from week 28 (P<0.001) and was maintained at a lower level post-partum such that HEI levels were lower compared with study entry (53.3±12.7 versus 56.7±10.1, P<0.001). The HEI decrease occurred in association with decreases in the milk, meat and unsaturated oil components, and increases in the proportion of energy from solid fats, alcohol and added sugars (P<0.001), and was independently predicted by the socioeconomic index for areas score (ß=-0.011, s.e.=0.011, P=0.031). CONCLUSION: We report for the first time that dietary quality decreases across pregnancy and is maintained at this reduced level in the early post-partum period in overweight and obese women. Dietary interventions aimed at improving diet quality should be targeted to early pregnancy and post-partum.