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Objectives To investigate associations between leisure-time physical activity (LPA) and injurious falls in older women and explore modification of associations by physical function and frailty. Methods Women born during 1946–51 from the Australian Longitudinal Study on Women's Health, injurious falls (self-reported fall with injury and/or medical attention) and self-reported weekly LPA (duration and type). We undertook cross-sectional and prospective analyses using data from 2016 [ n  = 8,171, mean (SD) age 68 (1)] and 2019 surveys (n  = 7,057). Associations were quantified using directed acyclic graph-informed logistic regression and effect modification examined using product terms. Results Participation in LPA as recommended by World Health Organization (150–300 min/week) was associated with lower odds of injurious falls in cross-sectional (adjusted Odds Ratio (OR) 0.74, 95% CI 0.61–0.90) and prospective analyses (OR 0.75, 95% CI 0.60–0.94). Compared with those who reported no LPA, cross-sectionally, odds of injurious falls were lower in those who reported brisk walking (OR 0.77, 95% CI 0.67–0.89) and vigorous LPA (OR 0.86, 95% CI 0.75–1.00). No significant association was found between different types of LPA and injurious falls prospectively. Only cross-sectionally, physical function limitation and frailty modified the association between LPA and injurious falls, with tendencies for more injurious falls with more activity in those with physical limitation or frailty, and fewer injurious falls with more activity among those without physical function limitation or frailty. Conclusion Participation in recommended levels of LPA was associated with lower odds of injurious falls. Caution is required when promoting general physical activity among people with physical limitation or frailty. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost-effectiveness of planned observation on cranial CT use in children with minor head trauma.Design: Planned secondary analysis of a multicentre prospective observation study.Setting: Australia and New Zealand.Patients: An analytic cohort of 18 471 children aged <18 years with Glasgow Coma Scale scores 14-15 presenting <24 hours after blunt head trauma stratified by the Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) risk categories.Intervention: A plan for observation and immediate CT scan were documented after the initial assessment. The planned observation group included those with planned observation and no immediate plan for CT.Main Outcome Measures: Taking an Australian public-funded healthcare perspective, we estimated the cost-effectiveness of planned observation on the adjusted mean costs per child and CT use reduction by net benefit regression analysis using ordinary least squares with robust SEs and bootstrapping. All costs presented in 2018 euros.Results: Planned observation in 4945 (27%) children was cost-saving of €85 (95% CI -120 to -51) with 10.4% lower CT use (95% CI 9.6 to 11.2). This strategy was cost-saving for the PECARN high-risk (-€757 (95% CI -961 to -554)) and intermediate-risk (-€52 (95% CI -99 to -4.3)) categories, with 43% (95% CI 39 to 47) and 11% (95% CI 9.6 to 12.4) lower CT use, respectively. The very low-risk category incurred more cost of €86 (95% CI 67 to 104) with planned observation and 0.05% lower CT use (95% CI -0.61 to 0.71).Conclusion: Planned ED observation in selected children with minor head trauma is cost-effective for reducing CT use for the PECARN intermediate-risk and high-risk categories.Trial Registration Number: ACTRN12614000463673. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of a person‐centred and thriving‐promoting intervention on nursing home residents´ experiences of thriving and person‐centredness of the environment, and to evaluate if the effects varied between female and male residents. Design: A multi‐centre, non‐equivalent controlled group before‐after intervention design. Methods: Six nursing homes in Australia, Norway and Sweden were allocated to either intervention or control group. The intervention comprised a staff educational programme. A survey using proxy‐ratings by staff was administered before (T0), immediately after (T1) and six months after (T2) the intervention. The sample varied between 205 and 292 residents. Linear regression models were used to explore effects. Results: Statistically significant effects were found on experiences of thriving and person‐centredness of the environment. These effects were significant for male residents but not for female residents. The results emphasize the importance of individually tailored social and recreational activities. [ABSTRACT FROM AUTHOR]

Study Question: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course?Summary Answer: Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS.What Is Known Already: The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research.Study Design, Size, Duration: This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included.Participants/materials, Setting, Methods: In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria.Main Results and the Role Of Chance: A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information.Limitations, Reasons For Caution: There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches.Wider Implications Of the Findings: Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations.Study Funding/competing Interest(s): This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women's Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare.Registration Number: Prospero registration number: CRD42020165546. [ABSTRACT FROM AUTHOR]

Background: Adequate dietary protein intake is recommended for older adults to optimise muscle health and function, and support recovery from illness, however, its effect on health-related quality of life (HRQoL) is unclear. The aim of this study was to examine the association between total protein intake and different sources of dietary protein and HRQoL in Australians aged 60 years and older over a 12-year period.Methods: This study used data from the Australian Diabetes, Obesity and Lifestyle study (AusDiab), a 12-year population-based prospective study. The sample included 752 (386 females) adults aged 60 years and older. Protein intake was estimated at baseline (1999/2000) from a 74-item Food Frequency Questionnaire, and HRQoL using the 36-item Short-form Health Survey assessed at baseline (1999/2000) and after 12 years (2011/12). The association between protein intake and change in HRQoL was evaluated using multivariate regression analysis adjusted for relevant confounders. The difference in change in HRQoL between participants with total protein intakes of < 1.0 g/kg/day, intakes of between 1.0-1.2 g/kg/day and intakes of > 1.2 g/kg/day were assessed using one-way ANCOVA.Results: Total protein intake at baseline was not associated with 12-year changes in physical component summary (PCS) or mental component summary (MCS) scores of HRQoL. Higher animal, red meat and processed animal protein intakes were associated with deteriorations in PCS scores after adjusting for relevant confounders (β = - 0.04; 95% CI: - 0.07, -0.01 ; p = 0.009; β = - 0.05; 95% CI: - 0.08, - 0.01; p = 0.018; β = - 0.17; 95% CI: - 0.31, - 0.02; p = 0.027 respectively). Higher red meat protein intake was associated with deteriorations in MCS scores after adjusting for relevant confounders (β = - 0.04; 95% CI: - 0.08, - 0.01; p = 0.011). There was no difference in 12-year changes in PCS or MCS between participants consuming total protein of < 1.0 g/kg/day, 1.0-1.2 g/kg/day and intakes of > 1.2 g/kg/day.Conclusion: There was no relationship between total dietary protein intake and HRQoL, but higher protein intakes from animal, red meat and processed animal sources were associated with a deterioration in HRQoL scores over 12 years. Due to the number of associations examined and high drop out of older less healthy participants, further research is required to confirm the associations detected in healthy and less healthy participants, with a view to making protein intake recommendations for older adults. [ABSTRACT FROM AUTHOR]

Background: Depression treatments are typically less effective for young people than for adults. However, treatments rarely target loneliness, which is a key risk factor in the onset, maintenance and development of depression.Aims: This study evaluated the efficacy of a novel loneliness intervention, Groups 4 Health (G4H), relative to the best-practice treatment of cognitive-behavioural therapy (CBT) in reducing loneliness and depression over a 12-month period (Australian New Zealand Clinical Trial Registry: ACTRN12618000440224).Method: The study was a phase 3 randomised non-inferiority trial comparing G4H with dose-controlled group CBT. Participants were 174 people aged 15-25 years experiencing loneliness and clinically significant symptoms of depression, who were not in receipt of adjunct treatment. Participants were recruited from mental health services in Southeast Queensland, Australia. Randomisation was conducted using computer software. Follow-up assessments and statistical analyses were masked to allocation. Both interventions consisted of five 75 min group-based psychotherapy sessions. The primary outcomes were depression and loneliness, with a non-inferiority margin of 2.20 for depression.Results: The trial enrolled 174 participants between 24 April 2018 and 25 May 2019, with 84 in the G4H condition and 90 in the CBT condition. All randomised participants were included in the intention-to-treat analyses (n = 174). The pre-post effect sizes for depression were dG4H = -0.71 and dCBT = -0.91. For loneliness, they were dG4H = -1.07 and dCBT = -0.89. At 12-month follow-up, the absolute difference between groups on depression was 1.176 (95% CI -1.94 to 4.29) and on loneliness it was -0.679 (95% CI -1.43 to 0.07). No adverse effects were observed.Conclusions: G4H was non-inferior to CBT for depression and showed a slight advantage over CBT for loneliness that emerged after treatment completion. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between plant-based diets (PBD) and overweight/obesity compared to regular meat eaters in older women.Design: Cross-sectional analysis.Setting: 1946-1951 birth cohort of the Australian Longitudinal Study on Women's Health (ALSWH). PBD were categorised as vegan, lacto-ovo vegetarian, pesco-vegetarian, semi-vegetarian and regular meat eaters. Outcomes included body weight (BW), BMI and waist circumference (WC).Participants: Women who completed Survey 7 (n 9102) with complete FFQ data.Results: Compared to regular meat eaters, BW, BMI and WC were significantly lower in pesco-vegetarians (-10·2 kg (95 % CI -5·1, -15·2); -3·8 kg/m2 (95 % CI -2·0, -5·6); -8·4 cm (95 % CI -3·9, -12·9)) and BW and BMI lower in lacto-ovo vegetarians (-7·4 kg (95 % CI -1·2, -13·6); -2·9 kg/m2 (95 % CI -0·6, -5·1)). In regular meat eaters, individuals consuming meat daily or multiple times/d had significantly higher BW, BMI and WC compared to those consuming meat >2 times/week but 1 but ≤2 times/week (6·8 kg (95 % CI 1·8, 11·8); 2·1 kg/m2 (95 % CI 0·3, 4·0) and 6·0 cm (95 % CI 1·7, 10·4)). This association was dose-dependent such that for every increase in category of weekly meat intake (i.e. >1 time/week but ≤2 times/week; >2 times/week but less than daily, and daily or multiple times/d), an associated 2·6 kg (95 % CI 1·8, 3·4) increase in BW, 0·9 kg/m2 (95 % CI 0·6, 1·2) increase in BMI and 2·3 cm (95 % CI 1·6, 3·0) increase in WC was reported.Conclusions: BW, BMI and WC are lower in women following PBD and positively associated with increasing meat consumption. Results were robust to adjustment for confounders including physical activity levels, smoking status, habitual alcohol intake, use of supplements, and hormone replacement therapy. [ABSTRACT FROM AUTHOR]

Study Question: Do extrinsic factors including lifestyle, psychosocial factors and healthcare professional engagement independently contribute to weight gain in women with and without polycystic ovary syndrome (PCOS)?Summary Answer: Women with PCOS had a higher rate of weight gain than women without PCOS which was most marked in those with unhealthy lifestyles.What Is Known Already: Women with PCOS have a higher prevalence of overweight/obesity and greater weight gain than women without PCOS. The association of lifestyle factors with weight change in PCOS is not known.Study Design, Size, Duration: The study was a population-based observational study with data collected from seven surveys over 19 years (N = 14 127; Survey 1) involving women with and without PCOS.Participants/materials, Setting, Methods: We used data from the 1973-1978 birth cohort of the Australian Longitudinal Study on Women's Health.Main Results and the Role Of Chance: Women with PCOS gained more weight annually (0.26 kg/year; 95% CI 0.12, 0.39; P < 0.0001) and over 19 years (4.62 kg; 95% CI 3.04, 6.21; P < 0.0001) than women without PCOS (adjusted analyses). For all women, there were positive associations between weight gain and energy intake, sitting time and stress; inverse associations with fibre intake and physical activity (PA); and no associations with diet quality, glycaemic index, healthcare utilization, depression or anxiety. There were interactions between lifestyle factors (energy intake P = 0.006, glycaemic index P = 0.025, sitting time P = 0.041 and PA P = 0.021), PCOS status and time such that weight gain varied between women with and without PCOS according to these factors.Limitations, Reasons For Caution: The limitations of this study include the use of self-reported measures such as diet, PA, sitting time, psychological factors and health care utilization.Wider Implications Of the Findings: While women with PCOS are more prone to weight gain, lifestyle factors have a more profound impact on weight gain in women with PCOS than without PCOS. These study findings have implications for understanding the mechanisms of weight gain in women with PCOS. They also highlight the importance of early lifestyle intervention as soon as PCOS is diagnosed to address modifiable extrinsic factors and prevent excess weight gain and worsening of the clinical features of PCOS.Study Funding/competing Interest(s): M.A.A. is funded by the Monash International Tuition Scholarship and Monash Graduate Scholarship and L.J.M. is funded by a National Heart Foundation Future Leader Fellowship. The authors declared no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Introduction: Family violence (FV) is one of the most urgent health issues of our generation. While nurses play a vital role in identifying and supporting victim/survivors of violence, little is known about nursing readiness to respond across clinical areas. Objective: This study aimed to compare and contrast the knowledge, confidence, clinical skills, and perceived barriers of nurses across three clinical areas of a tertiary trauma hospital in Melbourne, Australia, in responding to FV. Method: A prospective, mixed methods design was used. The nursing staff at a large trauma hospital were approached to participate. Participants completed a brief online survey to quantify clinician-reported knowledge, clinical skills, and barriers to managing FV. Results: Two hundred and forty-two nursing staff electronically completed a brief survey to capture self-reported confidence, knowledge, clinical skills, and barriers to working effectively in the area. The descriptive analysis reflected service-wide deficits in knowledge, confidence, and self-reported clinical skills, irrespective of the work area. Deficits were identified on a background of limited structured training for FV among this cohort. Significantly higher rates of FV confidence and knowledge were identified among emergency department nurses relative to acute and subacute clinical counterparts. Conclusion: Nurse respondents overall reported low rates of confidence, knowledge, and clinical skills in responding to disclosures of FV. Findings reinforce the need for imbedded training programs to support frontline responses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Serious injuries and fatalities among vulnerable road users on two wheeled motorised vehicles have increased across Australia and internationally in the past decade yet fallen for motor vehicle occupants. Almost half of all reported motorcycle injury crashes cause serious injury or death, nearly double that of motor vehicle police-reported crashes. This study explores associations with sociodemographic and pre-injury health characteristics and health outcomes after a road traffic injury; aiming to compare motorcyclists with other road users and inform recovery care.Methods: An inception cohort study recruited 1854 individuals aged > 17 years, injured following land-transport crashes in New South Wales, Australia (July 2013-November 2016). Interviews conducted at baseline, 6-and 12-months post-injury elicited demographic, socioeconomic, and self-reported health conditions.Results: Primary analysis involved 1854 participants who were recruited at baseline as three distinct road user groups; 628 (33.9%) motorcyclists, 927 (50%) vehicle occupants and 299 (16.1%) bicyclists. At baseline, injury patterns differed significantly between road user groups; motorcyclists were more than twice as likely to sustain lower extremity injury (p < 0.001); to have more severe injury severity scores (p < 0.001) and longer hospital stays versus vs vehicle occupants and bicyclists (< 0.001) across these measures. Injured motorcyclists were predominantly male (88.1%, p < 0.001), were younger on average (38 years) than bicyclists (41.5 years), had lower income and education levels, and poorer pre-injury physical health than other road user groups. Despite these differences, at 12 months post-injury motorcyclists had better physical health (SF12-PCS 2.07 (0.77, 3.36), p = 0.002) and reported lower pain scores (- 0.51 (- 0.83, - 0.2), p < 0.001) than vehicle occupants. Motorcyclists displayed less evidence of psychological distress than vehicle occupants, but more than bicyclists across several measures used.Conclusions: Road user types differ in important characteristics, including pre-injury health status and recovery after injury. As vulnerable road users experiencing transport crash and considering their higher initial injury severity, the degree of recovery among motorcyclists compared with other user types is remarkable and unexplained. Health and recovery outcomes after land-transport crashes is least favourable among vehicle occupants despite their higher levels of protection in a crash. This information is valuable for targeting early intervention strategies by road user type during the post-crash care phase, to improve long-term recovery. [ABSTRACT FROM AUTHOR]

Objectives: To examine changes in micronutrient intake over 3 years and identify any associations between socio-economic, health, lifestyle and meal-related factors and these changes in micronutrient intakes among older men.Design: Prospective study.Setting: Dietary adequacy of individual micronutrient was compared to the estimated average requirement of the nutrient reference values (NRV). Attainment of the NRV for twelve micronutrients was incorporated into a dichotomised variable 'not meeting' (meeting ≤ 6) or 'meeting' (meeting ≥ 7) and categorised into four categories to assess change in micronutrient intake over 3 years. The multinomial logistic regression analyses were conducted to model predictors of changes in micronutrient intake.Participants: Seven hundred and ninety-four men participated in a detailed diet history interview at the third wave (baseline nutrition) and 718 men participated at the fourth wave (3-year follow-up).Results: The mean age was 81 years (range 75-99 years). Median intakes of the majority of micronutrients decreased significantly over a 3-year follow-up. Inadequacy of the NRV for thiamine, dietary folate, Zn, Mg, Ca and I were significantly increased at a 3-year follow-up than baseline nutrition. The incidence of inadequate micronutrient intake was 21 % and remained inadequate micronutrient intake was 16·4 % at 3-year follow-up. Changes in micronutrient intakes were significantly associated with participants born in the UK and Italy, low levels of physical activity, having ≥2 medical conditions and used meal services.Conclusions: Micronutrient intake decreases with age in older men. Our results suggest that strategies to improve some of the suboptimal micronutrient intakes might need to be developed and implemented for older men. [ABSTRACT FROM AUTHOR]

Background: Many studies have reported an inferred causal association of income poverty with physical health among children; but making causal inference is challenging due to multiple potential sources of systematic error. We quantified the short-run effect of changes in household poverty status on children's health (asthma and ear infections) and service use (visits to the doctor and parent-reported hospital admissions), using a national longitudinal study of Australian children, with particular attention to potential residual confounding and selection bias due to study attrition.Methods: We use four modelling approaches differing in their capacity to reduce residual confounding (generalized linear, random effects (RE), hybrid and fixed effects (FE) regression modelling) to model the effect of income poverty (<60% of median income) on health for 10 090 children surveyed every 2nd year since 2004. For each method, we simulate the potential impact of selection bias arising due to attrition related to children's health status.Results: Of the 10 090 children included, 20% were in families in poverty at survey baseline (2004). Across subsequent years, ∼25% experienced intermittent and <2% persistent poverty. No substantial associations between poverty and child physical health and service use were observed in the FE models least prone to residual confounding [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.81-1.10 for wheeze], in contrast to RE models that were positive (consistent with previous studies). Selection bias causing null findings was unlikely.Conclusions: While poverty has deleterious causal effects on children's socio-behavioural and educational outcomes, we find little evidence of a short-run causal effect of poverty on asthma, ear infections and health service use in Australia. [ABSTRACT FROM AUTHOR]

Study Question: Is cord blood DNA methylation associated with having been conceived by medically assisted reproduction?Summary Answer: This study does not provide strong evidence of an association of conception by medically assisted reproduction with variation in infant blood cell DNA methylation.What Is Known Already: Medically assisted reproduction consists of procedures used to help infertile/subfertile couples conceive, including ART. Due to its importance in gene regulation during early development programming, DNA methylation and its perturbations associated with medically assisted reproduction could reveal new insights into the biological effects of assisted reproductive technologies and potential adverse offspring outcomes.Study Design, Size, Duration: We investigated the association of DNA methylation and medically assisted reproduction using a case-control study design (N = 205 medically assisted reproduction cases and N = 2439 naturally conceived controls in discovery cohorts; N = 149 ART cases and N = 58 non-ART controls in replication cohort).Participants/materials, Settings, Methods: We assessed the association between medically assisted reproduction and DNA methylation at birth in cord blood (205 medically assisted conceptions and 2439 naturally conceived controls) at >450 000 CpG sites across the genome in two sub-samples of the UK Avon Longitudinal Study of Parents and Children (ALSPAC) and two sub-samples of the Norwegian Mother, Father and Child Cohort Study (MoBa) by meta-analysis. We explored replication of findings in the Australian Clinical review of the Health of adults conceived following Assisted Reproductive Technologies (CHART) study (N = 149 ART conceptions and N = 58 controls).Main Results and the Role Of Chance: The ALSPAC and MoBa meta-analysis revealed evidence of association between conception by medically assisted reproduction and DNA methylation (false-discovery-rate-corrected P-value < 0.05) at five CpG sites which are annotated to two genes (percentage difference in methylation per CpG, cg24051276: Beta = 0.23 (95% CI 0.15,0.31); cg00012522: Beta = 0.47 (95% CI 0.31, 0.63); cg17855264: Beta = 0.31 (95% CI 0.20, 0.43); cg17132421: Beta = 0.30 (95% CI 0.18, 0.42); cg18529845: Beta = 0.41 (95% CI 0.25, 0.57)). Methylation at three of these sites has been previously linked to cancer, aging, HIV infection and neurological diseases. None of these associations replicated in the CHART cohort. There was evidence of a functional role of medically assisted reproduction-induced hypermethylation at CpG sites located within regulatory regions as shown by putative transcription factor binding and chromatin remodelling.Limitations, Reasons For Cautions: While insufficient power is likely, heterogeneity in types of medically assisted reproduction procedures and between populations may also contribute. Larger studies might identify replicable variation in DNA methylation at birth due to medically assisted reproduction.Wider Implications Of the Findings: Newborns conceived with medically assisted procedures present with divergent DNA methylation in cord blood white cells. If these associations are true and causal, they might have long-term consequences for offspring health.Study Funding/competing Interests(s): This study has been supported by the US National Institute of Health (R01 DK10324), the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no. 669545, European Union's Horizon 2020 research and innovation programme under Grant agreement no. 733206 (LifeCycle) and the NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. Methylation data in the ALSPAC cohort were generated as part of the UK BBSRC funded (BB/I025751/1 and BB/I025263/1) Accessible Resource for Integrated Epigenomic Studies (ARIES, http://www.ariesepigenomics.org.uk). D.C., J.J., C.L.R. D.A.L and H.R.E. work in a Unit that is supported by the University of Bristol and the UK Medical Research Council (Grant nos. MC_UU_00011/1, MC_UU_00011/5 and MC_UU_00011/6). B.N. is supported by an NHMRC (Australia) Investigator Grant (1173314). ALSPAC GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (Contract no. N01-ES-75558), NIH/NINDS (Grant nos. (i) UO1 NS 047537-01 and (ii) UO1 NS 047537-06A1). For this work, MoBa 1 and 2 were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and the Norwegian Research Council/BIOBANK (Grant no. 221097). This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, Project no. 262700.D.A.L. has received support from national and international government and charity funders, as well as from Roche Diagnostics and Medtronic for research unrelated to this study. The other authors declare no conflicts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]