COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.

The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.

Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation.

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.

Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence.

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Attrition in Conversational Agent-Delivered Mental Health Interventions: Systematic Review and Meta-Analysis.

BACKGROUND: Conversational agents (CAs) or chatbots are computer programs that mimic human conversation. They have the potential to improve access to mental health interventions through automated, scalable, and personalized delivery of psychotherapeutic content. However, digital health interventions, including those delivered by CAs, often have high attrition rates. Identifying the factors associated with attrition is critical to improving future clinical trials. OBJECTIVE: This review aims to estimate the overall and differential rates of attrition in CA-delivered mental health interventions (CA interventions), evaluate the impact of study design and intervention-related aspects on attrition, and describe study design features aimed at reducing or mitigating study attrition. METHODS: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science, and conducted a gray literature search on Google Scholar in June 2022. We included randomized controlled trials that compared CA interventions against control groups and excluded studies that lasted for 1 session only and used Wizard of Oz interventions. We also assessed the risk of bias in the included studies using the Cochrane Risk of Bias Tool 2.0. Random-effects proportional meta-analysis was applied to calculate the pooled dropout rates in the intervention groups. Random-effects meta-analysis was used to compare the attrition rate in the intervention groups with that in the control groups. We used a narrative review to summarize the findings. RESULTS: The systematic search retrieved 4566 records from peer-reviewed databases and citation searches, of which 41 (0.90%) randomized controlled trials met the inclusion criteria. The meta-analytic overall attrition rate in the intervention group was 21.84% (95% CI 16.74%-27.36%; I2=94%). Short-term studies that lasted ≤8 weeks showed a lower attrition rate (18.05%, 95% CI 9.91%- 27.76%; I2=94.6%) than long-term studies that lasted >8 weeks (26.59%, 95% CI 20.09%-33.63%; I2=93.89%). Intervention group participants were more likely to attrit than control group participants for short-term (log odds ratio 1.22, 95% CI 0.99-1.50; I2=21.89%) and long-term studies (log odds ratio 1.33, 95% CI 1.08-1.65; I2=49.43%). Intervention-related characteristics associated with higher attrition include stand-alone CA interventions without human support, not having a symptom tracker feature, no visual representation of the CA, and comparing CA interventions with waitlist controls. No participant-level factor reliably predicted attrition. CONCLUSIONS: Our results indicated that approximately one-fifth of the participants will drop out from CA interventions in short-term studies. High heterogeneities made it difficult to generalize the findings. Our results suggested that future CA interventions should adopt a blended design with human support, use symptom tracking, compare CA intervention groups against active controls rather than waitlist controls, and include a visual representation of the CA to reduce the attrition rate. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42022341415; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022341415.

Prevalence and Factors Associated with Behavioral Problems in 5-Year-Old Children Born with Cleft Lip and/or Palate from the Cleft Collective.

OBJECTIVES: To determine the UK prevalence of behavioral problems in 5-year-old children born with isolated or syndromic cleft lip and/or palate (CL/P) compared to the general population and identify potentially associated factors. DESIGN: Observational study using questionnaire data from the Cleft Collective 5-Year-Old Cohort study and three general population samples. MAIN OUTCOME MEASURE: The Strengths and Difficulties Questionnaire (SDQ). PARTICIPANTS: Mothers of children (age: 4.9-6.8 years) born with CL/P (n = 325). UK general population cohorts for SDQ scores were: Millennium Cohort Study (MCS) (n = 12 511), Office of National Statistics (ONS) normative school-age SDQ data (n = 5855), and Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 9386). RESULTS: By maternal report, 14.2% of children born with CL/P were above clinical cut-off for behavioral problems, which was more likely than in general population samples: 7.5% of MCS (OR = 2.05 [1.49-2.82], P < 0.001), 9.8% of ONS (OR = 1.52 [1.10-2.09], P = 0.008), and 6.6% of ALSPAC (OR = 2.34 [1.70-3.24], P < 0.001). Children in the Cleft Collective had higher odds for hyperactivity, emotional and peer problems, and less prosocial behaviors. Maternal stress, lower maternal health-related quality of life and family functioning, receiving government income support, and maternal smoking showed evidence of association (OR range: 4.41-10.13) with behavioral problems, along with maternal relationship status, younger age, and lower education (OR range: 2.34-3.73). CONCLUSIONS: Findings suggest elevated levels of behavioral problems in children born with CL/P compared to the general population with several associated maternal factors similar to the general population.

Did She or Didn't She? Perceptions of Operative Status of Female Genitalia.

BACKGROUND: While extensive research has explored why women undergo labiaplasty, little attention has been paid to societal and professional abilities to distinguish between altered and unaltered labia, impacting both patient concerns and broader societal perceptions. OBJECTIVES: This study aimed to evaluate the accuracy of the general public and healthcare professionals in identifying labiaplasty and to pinpoint the misconceptions driving their perceptions. The goal was to inform more effective patient counseling strategies and challenge existing stigmas around cosmetic genital surgery. METHODS: We conducted an online survey with 511 lay adults and a group of 21 gynecologists and aesthetic vulvar surgeons, assessing their ability to detect labiaplasty from images, focusing on aesthetic appearance, hair patterns, and size. The analysis involved Pearson correlation and Z-tests to compare perceptions against actual operative status. RESULTS: Our analysis revealed a pronounced difficulty among participants in accurately discerning labiaplasty, with neither group showing a significant ability to identify surgical alterations. Misinterpretations were notably influenced by expectations of aesthetic appearance, with 49% associating an "odd" or "fake" look with surgery, and hair and size misconceptions also misleading respondents. Additionally, 20% of participants mistakenly related surgical changes to gender affirming surgery or female genital mutilation. CONCLUSIONS: The study highlights a gap in the ability of both the general public and medical professionals to accurately identify labiaplasty, pointing to a broad misunderstanding of cosmetic genital surgery's visual outcomes. Addressing these misconceptions through targeted education could substantially improve patient counseling and help dismantle the stigmas associated with labiaplasty.

Patient Perspectives on Intimate Relationship Outcomes After Labiaplasty: A Preliminary Qualitative Analysis.

BACKGROUND: The popularity of labiaplasty has increased over the last decade and patients consistently report high levels of satisfaction with outcomes. Specifically, patients generally experience improved sexual satisfaction, but there is very limited research on the impacts on intimate relationships more broadly, even though these experiences are often crucial to women's lives. OBJECTIVES: The aim of this study was to conduct an in-depth qualitative exploration of the impacts of labiaplasty on intimate relationship quality. Qualitative semistructured telephone interviews were conducted with adult women (n = 15), who had undergone labiaplasty between 1 and 72 months previously (mean [standard deviation], 28.1 [24.3] months). Participants were asked about any perceived changes to their intimate relationships and how labiaplasty may have influenced those changes (if any). Thematic analysis of the transcribed interview data was performed. RESULTS: The results showed that most women reported greater confidence engaging in new relationships, and partaking in subsequent sexual experiences was also commonly reported. However, other women reported no changes to their intimate relationship quality after labiaplasty. Over half of the women reported concerns that their current or a future partner may perceive their postsurgery genital appearance as not "natural." CONCLUSIONS: The current study adds some novel depth and nuance to the impacts of labiaplasty on intimate relationship quality. Although most women experience improved sexual confidence in their intimate relationships, a proportion may also experience concerns around their partner's reactions to the surgery.

Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation.

AIMS/HYPOTHESIS: Several studies have identified associations between type 2 diabetes and DNA methylation (DNAm). However, the causal role of these associations remains unclear. This study aimed to provide evidence for a causal relationship between DNAm and type 2 diabetes. METHODS: We used bidirectional two-sample Mendelian randomisation (2SMR) to evaluate causality at 58 CpG sites previously detected in a meta-analysis of epigenome-wide association studies (meta-EWAS) of prevalent type 2 diabetes in European populations. We retrieved genetic proxies for type 2 diabetes and DNAm from the largest genome-wide association study (GWAS) available. We also used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) when associations of interest were not available in the larger datasets. We identified 62 independent SNPs as proxies for type 2 diabetes, and 39 methylation quantitative trait loci as proxies for 30 of the 58 type 2 diabetes-related CpGs. We applied the Bonferroni correction for multiple testing and inferred causality based on p<0.001 for the type 2 diabetes to DNAm direction and p<0.002 for the opposing DNAm to type 2 diabetes direction in the 2SMR analysis. RESULTS: We found strong evidence of a causal effect of DNAm at cg25536676 (DHCR24) on type 2 diabetes. An increase in transformed residuals of DNAm at this site was associated with a 43% (OR 1.43, 95% CI 1.15, 1.78, p=0.001) higher risk of type 2 diabetes. We inferred a likely causal direction for the remaining CpG sites assessed. In silico analyses showed that the CpGs analysed were enriched for expression quantitative trait methylation sites (eQTMs) and for specific traits, dependent on the direction of causality predicted by the 2SMR analysis. CONCLUSIONS/INTERPRETATION: We identified one CpG mapping to a gene related to the metabolism of lipids (DHCR24) as a novel causal biomarker for risk of type 2 diabetes. CpGs within the same gene region have previously been associated with type 2 diabetes-related traits in observational studies (BMI, waist circumference, HDL-cholesterol, insulin) and in Mendelian randomisation analyses (LDL-cholesterol). Thus, we hypothesise that our candidate CpG in DHCR24 may be a causal mediator of the association between known modifiable risk factors and type 2 diabetes. Formal causal mediation analysis should be implemented to further validate this assumption.

Establishing the relationships between adiposity and reproductive factors: a multivariable Mendelian randomization analysis.

BACKGROUND: Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's health. Here we assess whether adiposity at different points in the lifecourse affects reproductive factors differently and independently, and the plausibility of the impact of reproductive factors on adiposity. METHODS: We used genetic data from UK Biobank (273,238 women) and other consortia (EGG, GIANT, ReproGen and SSGAC) for eight reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners, and two adiposity traits: childhood and adulthood body size. We applied multivariable Mendelian randomization to account for genetic correlation and to estimate the causal effects of childhood and adulthood adiposity, independently of each other, on reproductive factors. Additionally, we estimated the effects of reproductive factors, independently of other relevant reproductive factors, on adulthood adiposity. RESULTS: We found a higher childhood body size leads to an earlier age at menarche, and an earlier age at menarche leads to a higher adulthood body size. Furthermore, we find contrasting and independent effects of childhood and adulthood body size on age at first birth (beta 0.22 SD (95% confidence interval: 0.14, 0.31) vs - 2.49 (- 2.93, - 2.06) per 1 SD increase), age at last birth (0.13 (0.06,0.21) vs - 1.86 (- 2.23, - 1.48) per 1 SD increase), age at menopause (0.17 (0.09, 0.25) vs - 0.99 (- 1.39, - 0.59) per 1 SD increase), and likelihood of having children (Odds ratio 0.97 (0.95, 1.00) vs 1.20 (1.06, 1.37) per 1 SD increase). CONCLUSIONS: Our findings demonstrate the importance of considering a lifecourse approach when investigating the inter-relationships between adiposity measures and reproductive events, as well as the use of 'age specific' genetic instruments when evaluating lifecourse hypotheses in a Mendelian randomization framework.

Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.

Ethical Challenges in AI Approaches to Eating Disorders.

The use of artificial intelligence (AI) to assist with the prevention, identification, and management of eating disorders and body image concerns is exciting, but it is not without risk. Technology is advancing rapidly, and ensuring that responsible standards are in place to mitigate risk and protect users is vital to the success and safety of technologies and users.

Men's Experiences and Psychological Outcomes of Nonsurgical Medical Penile Girth Augmentation: A Preliminary Prospective Study.

BACKGROUND: The popularity of penile augmentation procedures is increasing, but investigation into men's experiences with these procedures and their impact on psychological well-being is lacking. OBJECTIVES: The aim of this study was to investigate men's experiences with nonsurgical medical penile girth augmentation and assess, based on valid psychological measures, the impacts these procedures have on psychological well-being. METHODS: Men seeking to undergo a girth augmentation (n = 19) completed an online questionnaire prior to their procedure and 6 months later that contained standardized measures assessing impacts of the procedure, penile size self-discrepancy, body dysmorphic disorder, psychological distress, self-esteem, and body image-related quality of life. Girth size was also measured preprocedure and 6 months postprocedure for a subsample of men. RESULTS: Almost half of the men reported positive impacts of "increased self-confidence" and "increased sexual pleasure" after their procedure. Despite an average girth increase of 3.29 cm, the men still perceived that their penile girth and length was less than what they should be or less than the ideal size after their augmentation procedure. However, this perceived discrepancy was significantly smaller than before their procedures. Prior to the procedure, the men who met diagnostic criteria for body dysmorphic disorder according to self-reported questionnaire (11%, n = 2/19) and clinical interview (7%, n = 1/15) lost this diagnosis at 6 months. There were no changes in psychological distress, self-esteem, or body image-related quality of life from pre- to postprocedure. CONCLUSIONS: Men report positive impacts on their lives after penile girth augmentation, but impacts on broader psychological well-being are mixed.

Beyond Motivations: A Qualitative Pilot Exploration of Women's Experiences Prior to Labiaplasty.

BACKGROUND: The demand for labiaplasty has increased rapidly over the last 10 to 15 years. Women's reasons for pursuing the procedure have been thoroughly documented in the literature, but other preoperative aspects are less well defined. These include women's expected outcomes, concerns about having the surgery, and the impacts of support from others in their personal lives as well as their treating team. OBJECTIVES: The aim of this study was to explore women's preoperative labiaplasty experiences, particularly expectations, concerns, and interpersonal support. METHODS: Semistructured interviews were completed with 15 adult women in the United States and Australia who had undergone a labia minora reduction. The women were asked about their motivations for having a labiaplasty, expected outcomes, concerns regarding surgery, and support received from family members, friends, and the treating surgeon. The interviews were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: Two overarching themes with accompanying subthemes emerged from the analyses: (1) "motivations/influences" which included appearance concerns, physical discomfort, negative impacts on self-confidence, and negative experiences with partners and/or peers; and (2) "perceptions approaching labiaplasty procedure" where women reported concerns about recovery duration and impacts on sexual sensation as well as expectations for their postoperative vulvar appearance to be "neat," "tidy," and "natural." In addition, the women stated that they felt well supported by their surgeons prior to the procedure, but some felt too embarrassed to seek support from family members and friends. CONCLUSIONS: These new insights into women's preoperative experiences may assist clinical teams in enhancing their support and education of women seeking labiaplasty.

The Effect of Female Genital Cosmetic and Reconstructive Procedures on Body and Genital Self-Image: A Systematic Review and Meta-Analysis.

Performance of female genital cosmetic and reconstructive procedures (FGCRP) has been increasing over past decades. Appearance and functional concerns are the most common reasons for seeking FGCRP. Poor body and genital self-image may contribute to the increase in demand for surgery. The aim of this systematic review is to explore outcomes of FGCRP in the domains of body and genital self-image. A systematic literature review of PubMed, Web of Science, Scopus, PsycINFO, Embase, and the Cochrane Library was conducted to identify articles that measured body and genital self-image in females after FGCRP. The authors identified 5 articles for a systematic review of body image and 8 studies for a systematic review of genital self-image. The most common procedure performed was labia minora labiaplasty. Instruments for body image evaluation were the Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder and the Body Image Quality of Life Inventory. Genital image was assessed with the Female Genital Self-Image Scale and Genital Appearance Satisfaction (GAS) scale. Most of the studies indicated that FGCRP can improve both body image and genital self-image; meta-analysis revealed that FGCRP improved GAS scores by 17.96 (range: 0-33; P < .001). It appears that FGCRP leads to improvements in females' body and genital self-image. Inconsistencies in study design and measures, however, limit this conclusion. Future research should involve more rigorous study designs (for example randomized clinical trials with large sample sizes) for a more accurate assessment of FGCRP's consequences.

The relationships between women's reproductive factors: a Mendelian randomisation analysis.

BACKGROUND: Women's reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors. METHODS: We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap. RESULTS: LDSC indicated that most reproductive factors are genetically correlated (rg range: |0.06-0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (rg < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = -0.38 SD, CI = -0.44, -0.32). CONCLUSION: This study presents evidence that women's reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman's entire reproductive history, including the causal interplay between reproductive factors.

Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

OBJECTIVES: JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. METHODS: Four databases (MEDLINE, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to January 2020. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. RESULTS: This review includes 66 environmental factors from 39 studies (11 cohort and 28 case-control studies) over 45 years. Study sample sizes ranged from 41 to 1.9 million participants. Eight environmental factors from ten studies were meta-analysed. Caesarean section delivery was associated with increased JIA risk [pooled odds ratio (OR) 1.11, 95% CI: 1.01, 1.22]. Conversely, presence (vs absence) of siblings (pooled OR 0.60, 95% CI: 0.44, 0.81) and maternal prenatal smoking (pooled OR 0.70, 95% CI: 0.58, 0.84) were associated with decreased JIA risk. CONCLUSION: This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research undertaken over five decades. We also highlight the challenges of combining data collected over this period due to limited between study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

An Australian perspective on "clean" dietary labels: Commentary on Negowetti et al. (2021).

"Clean eating" is an increasingly popular diet trend in Western countries with links to disordered eating behaviors. However, the definition of "clean" is a highly contentious issue. Negowetti, Ambwani, Karr, Rodgers, and Austin explore this important issue from a U.S. perspective conducting a scoping review of the public health implications of the use of "clean" labels on food, including legal and policy implications. The review showed that the U.S. Food and Drug Administration (FDA) has taken little action to address regulation of the use of "clean" dietary labels. Our own brief investigations suggest that the landscape in Australia under the Food Standards Australia New Zealand authority is similar. We discuss recommendations made by Negowetti et al. to address this issue in the United States, such as the FDA providing industry guidance on the term "clean," and the issuing of warning letters to companies who contravene this guidance. However, we predict that educating consumers to be more critical of unsubstantiated food labels in public health campaigns will be the most efficient way to change consumer behavior and address the "clean eating" diet trend. We also encourage eating disorder researchers and clinicians to be an influential part of this discussion.

The relationship between disordered eating behaviour and the five factor model personality dimensions: A systematic review.

The relationship between personality and eating disorders has received significant research attention. This review aimed to synthesize research regarding the Five Factor Model (FFM) and disordered eating behaviors, to gain an improved understanding of the relationship between normal-range personality and subclinical eating disorders. Electronic Databases were used to identify studies published in English that utilized self-report measures of disordered eating and the FFM. A qualitative synthesis of 45 papers was then conducted. High scores on Neuroticism were associated with increased disordered eating behavior. Different disordered eating behaviors were found to have unique relationships with personality dimensions. Facets within domains varied in direction of correlation with disordered eating behaviors, particularly in the Agreeableness, Contentiousness, and Openness domains. The results indicate that, further research is needed before generalizing treatment approaches for eating disorders for females, males, and gender diverse populations.

Maternal Stressful Life Events During the Periconceptional Period and Orofacial Clefts: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess whether women who experience stressful life events during the periconceptional period are at higher risk of giving birth to a baby with an orofacial cleft (OFC). DESIGN: Systematic review and meta-analysis of studies reporting the proportion of babies born with OFC to mothers exposed and unexposed to population-level or personal-level stressful life events during the periconceptional period. Six electronic databases were searched from inception to August 2020. Risk of bias was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) for the odds of OFC in babies of exposed mothers relative to unexposed controls were extracted and/or calculated. Random effects meta-analysis was undertaken, stratified by cleft subtype. RESULTS: Of 12 eligible studies, 8 examined experience of personal events and 4 examined population-level events. Studies demonstrated low-moderate risk of bias and there was indication of publication bias. There was some evidence that personal stressful life events were associated with greater odds of cleft lip and/or palate (six studies, OR 1.63, 95% confidence interval (CI) 1.16, 2.30, P = 0.001) and cleft palate only (six studies, OR 1.45, 95% CI 1.02, 2.06, P = 0.04). Population-level events were associated with higher odds of OFC in studies that did not specify subtype (three studies, OR 1.64, 95% CI 1.19, 2.25, P = 0.002), but subtype stratified analyses were underpowered. Heterogeneity was high. CONCLUSIONS: Limited evidence indicated a weak positive association between maternal stressful life events during the periconceptional period and risk of OFC in the offspring, but further studies with greater consistency in research design are needed.