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We consider pricing of a specialised critical illness and life insurance contract for breast cancer (BC) risk. We compare (a) an industry-based Markov model with (b) a recently developed semi-Markov model, which accounts for unobserved BC cases and progression through clinical stages of BC, and (c) an alternative Markov model derived from (b). All models are calibrated using population data in England and data from the medical literature. We show that the semi-Markov model aligns best with empirical evidence. We then consider net premiums of specialized life insurance products under various scenarios of cancer diagnosis and treatment. The results show strong dependence on the time spent with diagnosed or undiagnosed pre-metastatic BC. This proves to be significant for refining cancer survival estimates and accurately estimating related age dependence by cancer stage. In contrast, the industry-based model, by overlooking this critical factor, is more sensitive to the model assumptions, underscoring its limitations in cancer estimates.
The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.
Methods
The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.
Results
About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.
Conclusions
The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.
Dogs are considered omnivores based on their evolution consuming diets including animal tissue. Few feeding trials evaluating the nutritional suitability of exclusively plant-based (vegan) diets in dogs have been published, and the efficacy of vitamin D2 in maintaining canine serum vitamin D levels has not been clearly determined. A blinded dietary trial included sixty-one healthy desexed adult dogs: thirty-one fed an experimental extruded vegan diet (PLANT) and thirty fed a commercial extruded meat-based diet (MEAT) for 3 months. Dogs were screened via veterinary examination and routine laboratory analyses prior to enrolment, at baseline and exit timepoints. Body composition was measured by dual-energy X-ray absorptiometry and blood was collected for vitamin D profiling. All dogs maintained health parameters, body weight and composition throughout the study. Dogs maintained on PLANT demonstrated a significant reduction in platelet count, creatinine, blood urea nitrogen and cholesterol, though values remained within normal reference ranges. Dogs fed PLANT also demonstrated a shift from vitamin D3 to vitamin D2 metabolites, though total vitamin D analogue levels were unchanged, with the exception of 24,25-dihydroxyvitamin D. Bone mineral content and density did not differ from baseline values. Health status was maintained in dogs fed PLANT and vitamin D2 appeared efficacious in maintaining serum total vitamin D concentrations and bone mineralisation. Findings support the hypothesis that PLANT was comparable to MEAT for maintenance of healthy adult dogs for at least 3 months and identified areas where further research is warranted to elucidate the potential risks and benefits of plant-based (vegan) diets.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
The COVID-19 pandemic caused significant disruption to the lives of children and their families. Pre-school children may have been particularly vulnerable to the effects of the pandemic, with the closure of childcare facilities, playgrounds, playcentres and parent and toddler groups limiting their opportunities for social interaction at a crucial stage of development. Additionally, for parents working from home, caring for pre-school aged children who require high levels of support and care, was likely challenging
Objectives
We aimed to conduct an intensive longitudinal study to examine trajectories of pre-schoolers’ mental symptoms in the United Kingdom during the first year of the COVID-19 pandemic.
Methods
UK‐based parents and carers (n = 1520) of pre-school‐aged children (2 to 4 years) completed monthly online surveys about their pre-schoolers’ mental health between April 2020 and March 2021. The survey examined changes in children’s emotional symptoms, conduct problems and hyperactivity/inattention.
Results
Pre-schoolers’ emotional problems and hyperactivity/inattention symptoms declined from April through summer 2020 and then increased again during the autumn and winter 2020/2021 as lockdowns were re-introduced. Pre-schoolers who attended childcare showed greater decline in symptom severity than those who did not. Older children, compared to younger, showed greater lability of emotion symptom severity. Attending childcare predicted lower symptom severity across all three domains of conduct problems, emotional symptoms, and hyperactivity/inattention, while the opposite pattern was observed for children whose parent had a mental health problem.
Conclusions
Our findings reinforce the importance of examining pre-schoolers’ mental health in the context of micro and macro-level factors. Interventions focusing on family factors such as parent mental health, as well as continued provision of childcare, may have most potential to mitigate the impact of COVID-19 on young children’s mental health.
An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns.
Methods and Results:
An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.
Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20).
Conclusion:
A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.
To determine the proportion of hospitals that implemented 6 leading practices in their antimicrobial stewardship programs (ASPs). Design: Cross-sectional observational survey.
Setting:
Acute-care hospitals.
Participants:
ASP leaders.
Methods:
Advance letters and electronic questionnaires were initiated February 2020. Primary outcomes were percentage of hospitals that (1) implemented facility-specific treatment guidelines (FSTG); (2) performed interactive prospective audit and feedback (PAF) either face-to-face or by telephone; (3) optimized diagnostic testing; (4) measured antibiotic utilization; (5) measured C. difficile infection (CDI); and (6) measured adherence to FSTGs.
Results:
Of 948 hospitals invited, 288 (30.4%) completed the questionnaire. Among them, 82 (28.5%) had <99 beds, 162 (56.3%) had 100–399 beds, and 44 (15.2%) had ≥400+ beds. Also, 230 (79.9%) were healthcare system members. Moreover, 161 hospitals (54.8%) reported implementing FSTGs; 214 (72.4%) performed interactive PAF; 105 (34.9%) implemented procedures to optimize diagnostic testing; 235 (79.8%) measured antibiotic utilization; 258 (88.2%) measured CDI; and 110 (37.1%) measured FSTG adherence. Small hospitals performed less interactive PAF (61.0%; P = .0018). Small and nonsystem hospitals were less likely to optimize diagnostic testing: 25.2% (P = .030) and 21.0% (P = .0077), respectively. Small hospitals were less likely to measure antibiotic utilization (67.8%; P = .0010) and CDI (80.3%; P = .0038). Nonsystem hospitals were less likely to implement FSTGs (34.3%; P < .001).
Conclusions:
Significant variation exists in the adoption of ASP leading practices. A minority of hospitals have taken action to optimize diagnostic testing and measure adherence to FSTGs. Additional efforts are needed to expand adoption of leading practices across all acute-care hospitals with the greatest need in smaller hospitals.
Policies that promote conversion of antibiotics from intravenous to oral route administration are considered “low hanging fruit” for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.
We surveyed healthcare workers within the Duke Antimicrobial Stewardship Outreach Network (DASON) to describe beliefs regarding coronavirus disease 2019 (COVID-19) vaccination and their decision-making process behind vaccination recommendations. In contrast to the type of messaging that appealed most on a personal level to the healthcare workers, they preferred a more generic message emphasizing safety and efficacy when making vaccination recommendations.
This article provides an overview of the public health approach to suicide in Ireland. The authors provide detail on the current suicide prevention strategy in Ireland, Connecting for Life, which is a whole-of-government, systemic, multicomponent national strategy. As the strategy enters its final extended phase of implementation over the period 2020–2024, the public health elements of Connecting for Life are presented, including the population level and more targeted approaches. The findings of an interim review of the strategy are discussed, in addition to the local and national implementation structures which are in place to assist implementation and monitoring of the strategy.
BASF Corp. has developed p-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor–resistant cotton and soybean that will allow growers to use isoxaflutole in future weed management programs. In 2019 and 2020, a multi-state non-crop research project was conducted to examine weed control following isoxaflutole applied preemergence alone and with several tank-mix partners at high and low labeled rates. At 28 d after treatment (DAT), Palmer amaranth was controlled ≥95% at six of seven locations with isoxaflutole plus the high rate of diuron or fluridone. These same combinations provided the greatest control 42 DAT at four of seven locations. Where large crabgrass was present, isoxaflutole plus the high rate of diuron, fluridone, pendimethalin, or S-metolachlor or isoxaflutole plus the low rate of fluometuron controlled large crabgrass ≥95% in two of three locations 28 DAT. In two of three locations, isoxaflutole plus the high rate of pendimethalin or S-metolachlor improved large crabgrass control 42 DAT when compared to isoxaflutole alone. At 21 DAT, morningglory was controlled ≥95% at all locations with isoxaflutole plus the high rate of diuron and at three of four locations with isoxaflutole plus the high rate of fluometuron. At 42 DAT at all locations, isoxaflutole plus diuron or fluridone and isoxaflutole plus the high rate of fluometuron improved morningglory control compared to isoxaflutole alone. These results suggest that isoxaflutole applied preemergence alone or in tank mixture is efficacious on a number of cross-spectrum annual weeds in cotton, and extended weed control may be achieved when isoxaflutole is tank-mixed with several soil-residual herbicides.
The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).
Methods:
This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.
Results:
In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).
Conclusion:
Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
Methods:
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
Results:
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
Conclusion:
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Major psychosis and mood disorders are neuroprogressive illnesses that develop from prodrome to episodic onset to relapse and recurrence and finally chronic, debilitating illness. There is considerable evidence supporting a staged model for mental illness. Moreover, acknowledging the staged progression of major psychiatric illness creates new opportunities for intervention. Conventional treatments focus on symptom reduction and prevention of relapse, with many services requiring triage levels that exclude all but the most severe patients. This generally results in most of the mental health resources being directed towards patients in the later stages of illness. Re-conceptualising major psychosis and mood disorders as staged illnesses suggests that there is a potential for improvement with regards to illness burden for patients and reduced health care costs if a greater portion of mental health resources were directed towards patients in early stages of illness and toward treatments that may prevent neuroprogression. Successful service models for early intervention already exist, such as Orygen Youth Mental Health in Australia, and many treatments that may impede the progression of mental illness have been identified. Ongoing research is investigating mechanisms by which illness neuroprogression occurs and is evaluating the neuroprotective capabilities of treatments. There is already sufficient experience and knowledge, as well as stage appropriate treatment and possible neuroprotective agents with mechanisms of action that may counteract the mechanisms of neuroprogression. There are sufficient tools to apply the staging model to our treatment and services now, and doing so will lead to better outcomes for patients.
Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. Adverse outcomes are part of the landscape in prescribing medications and therefore management of safety issues need to be an integral part of practice.
Objectives
We have developed consensus guidelines for safety monitoring with antidepressant treatments.
Aims
To present an overview of screening and safety considerations for pharmacotherapy of clinical depressive disorders and make recommendations for safety monitoring.
Methods
Data were sourced by a literature search using Medline and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content.
Results
A guidelines document was produced after approval by all 19 co-authors. The final document gives guidance on; the decision to treat, baseline screening prior to commencement of treatment, and ongoing monitoring during antidepressant treatment. The guidelines state or reference screening protocols that may detect medical causes of depression as well as screening and monitoring protocols to investigate specific adverse effects associated with antidepressant treatments that may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment.
Conclusions
The implementation of safety monitoring guidelines for treatment of clinical depression may significantly improve outcome, by improving a patient's overall physical health status.
Bipolar disorder (BD) is a psychiatric disorder with an uncertain aetiology. Recently, special attention has been given to homocysteine (Hcy), as it has been suggested that alterations in 1-carbon metabolism might be implicated in diverse psychiatric disorders. However, there is uncertainty regarding possible alterations in peripheral Hcy levels in BD.
Methods:
This study comprises a meta-analysis comparing serum and plasma Hcy levels in persons with BD and healthy controls. We conducted a systematic search for all eligible English and non-English peer-reviewed articles.
Results:
Nine cross-sectional studies were included in the meta-analyses, providing data on 1547 participants. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD in either mania or euthymia when compared to healthy controls, with a large effect size in the mania group (g = 0.98, 95% CI: 0.8–1.17, P < 0.001, n = 495) and a small effect in the euthymia group (g = 0.3, 95% CI: 0.11–0.48, P = 0.002, n = 1052).
Conclusions:
Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.
Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.
Methods
This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges’ adjusted g using random effects.
Results
Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g = −0.99, 95% CI −2.43 to 0.43, P = 0.171), in depression (g = 0.17, 95% CI −0.45 to 0.79, P = 0.584), or in euthymia (g = 0.03, 95% CI −0.39 to 0.46, P = 0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.
Conclusions
Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.
Key lifestyle-environ risk factors are operative for depression, but it is unclear how risk factors cluster. Machine-learning (ML) algorithms exist that learn, extract, identify and map underlying patterns to identify groupings of depressed individuals without constraints. The aim of this research was to use a large epidemiological study to identify and characterise depression clusters through “Graphing lifestyle-environs using machine-learning methods” (GLUMM).
Methods
Two ML algorithms were implemented: unsupervised Self-organised mapping (SOM) to create GLUMM clusters and a supervised boosted regression algorithm to describe clusters. Ninety-six “lifestyle-environ” variables were used from the National health and nutrition examination study (2009–2010). Multivariate logistic regression validated clusters and controlled for possible sociodemographic confounders.
Results
The SOM identified two GLUMM cluster solutions. These solutions contained one dominant depressed cluster (GLUMM5-1, GLUMM7-1). Equal proportions of members in each cluster rated as highly depressed (17%). Alcohol consumption and demographics validated clusters. Boosted regression identified GLUMM5-1 as more informative than GLUMM7-1. Members were more likely to: have problems sleeping; unhealthy eating; ≤ 2 years in their home; an old home; perceive themselves underweight; exposed to work fumes; experienced sex at ≤ 14 years; not perform moderate recreational activities. A positive relationship between GLUMM5-1 (OR: 7.50, P < 0.001) and GLUMM7-1 (OR: 7.88, P < 0.001) with depression was found, with significant interactions with those married/living with partner (P = 0.001).
Conclusion
Using ML based GLUMM to form ordered depressive clusters from multitudinous lifestyle-environ variables enabled a deeper exploration of the heterogeneous data to uncover better understandings into relationships between the complex mental health factors.
We simulate the flow of two immiscible and incompressible fluids separated by an interface in a homogeneous turbulent shear flow at a shear Reynolds number equal to 15 200. The viscosity and density of the two fluids are equal, and various surface tensions and initial droplet diameters are considered in the present study. We show that the two-phase flow reaches a statistically stationary turbulent state sustained by a non-zero mean turbulent production rate due to the presence of the mean shear. Compared to single-phase flow, we find that the resulting steady-state conditions exhibit reduced Taylor-microscale Reynolds numbers owing to the presence of the dispersed phase, which acts as a sink of turbulent kinetic energy for the carrier fluid. At steady state, the mean power of surface tension is zero and the turbulent production rate is in balance with the turbulent dissipation rate, with their values being larger than in the reference single-phase case. The interface modifies the energy spectrum by introducing energy at small scales, with the difference from the single-phase case reducing as the Weber number increases. This is caused by both the number of droplets in the domain and the total surface area increasing monotonically with the Weber number. This reflects also in the droplet size distribution, which changes with the Weber number, with the peak of the distribution moving to smaller sizes as the Weber number increases. We show that the Hinze estimate for the maximum droplet size, obtained considering break-up in homogeneous isotropic turbulence, provides an excellent estimate notwithstanding the action of significant coalescence and the presence of a mean shear.
Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) – the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (β=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: β=0.338, P=0.031; 2D:4D – right: β=−0.207, P=0.040; left: β=−0.276, P=0.006; AGD-fourchette − β=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (β=0.290, P=0.048), as well as right arm circumference (β=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones.