A Data-Based Approach to Evaluating Representation by Gender and Affiliation in Key Presentation Formats at the Annual Meeting of the Society for Epidemiologic Research.

The annual meeting of the Society for Epidemiologic Research (SER) is a major forum for sharing new research and promoting the career development of participants. Because of this, evaluating representation in key presentation formats is critical. For the 3,257 presentations identified at the 2015-2017 SER annual meetings, we evaluated presenter characteristics, including gender, affiliation, subject area, and h-index, and representation in 3 highlighted presentation formats: platform talks (n = 382), invited symposium talks (n = 273), and chairing a concurrent contributed session or symposium (n = 188). Data were abstracted from SER records, abstract booklets, and programs. Gender was assessed using GenderChecker software, and h-index was determined using the Scopus application programming interface. Log-binomial models were adjusted for participant characteristics and conference year. In adjusted models, women were less likely than men to present an invited symposium talk (relative risk = 0.60, 95% confidence interval: 0.45, 0.81) compared with all participants with accepted abstracts. Researchers from US public universities, US government institutions, and international institutions were less likely to present a symposium talk or to chair a concurrent contributed session or symposium than were researchers from US private institutions. The research areas that were most represented in platform talks were epidemiologic methods, social epidemiology, and cardiovascular epidemiology. Our findings suggest differences in representation by gender, affiliation, and subject area after accounting for h-index.

Preconception leukocyte telomere length and pregnancy outcomes among women with demonstrated fecundity.

STUDY QUESTION: Is preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1-2 prior pregnancy losses? SUMMARY ANSWER: Preconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth. WHAT IS KNOWN ALREADY: As women increasingly delay childbearing, accessible preconception biomarkers to predict pregnancy outcomes among women seeking natural conception could improve preconception counseling. Findings of small case-control or cross-sectional studies suggest that telomere attrition is associated with adverse pregnancy outcomes among women undergoing fertility treatment, but prospective studies in non-clinical populations are lacking. STUDY DESIGN, SIZE, DURATION: Participants included 1228 women aged 18-40 years with a history of 1-2 prior pregnancy losses who were recruited at four university medical centers (2006-2012). PARTICIPANTS/MATERIALS, SETTING, METHODS: Preconception leukocyte telomere length was measured at baseline using PCR and reported as a ratio (T/S) in relation to population-specific standard reference DNA. Women were followed for up to six cycles while attempting to conceive. Associations of telomere length with fecundability, live birth and pregnancy loss were estimated using discrete Cox proportional hazards models and log-binomial models. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for age, BMI, smoking and other factors, preconception telomere length was not associated with fecundability (Q4 vs Q1 FOR = 1.00; 95% CI = 0.79, 1.27), live birth (Q4 vs Q1 RR = 1.00; 95% CI = 0.85, 1.19), or pregnancy loss (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62). LIMITATIONS, REASONS FOR CAUTION: Telomere length was measured in leukocytes, which is an accessible tissue in women attempting natural conception but may not reflect telomere length in oocytes. Most women were younger than 35 years, limiting our ability to evaluate associations among older women. Participants had a history of 1-2 prior pregnancy losses; therefore, our findings may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS: Despite prior research suggesting that telomere length may be associated with pregnancy outcomes among women seeking fertility treatment, our findings suggest that leukocyte telomere length is not a suitable biomarker of pregnancy establishment or maintenance among women attempting natural conception. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424 and HHSN267200603426). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: The trial was registered with ClinicalTrials.gov, number NCT00467363.

Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl.

Sex hormone-binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries, and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient's SHBG level was remarkably low for her age, at less than 5 nmol/L (reference range for a girl with a bone age of 10 years, 73 nmol/L [SEM = 10]) [1]. On genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554C>T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient's phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.

First Somatic PRKAR1A Defect Associated With Mosaicism for Another PRKAR1A Mutation in a Patient With Cushing Syndrome.

CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS) associated mostly with Carney complex (CNC), a rare autosomal dominant multiple neoplasia syndrome. More than two-thirds of familial cases and approximately one-third of sporadic cases of CNC harbor germline inactivating PRKAR1A defects. Increasingly sensitive technologies for the detection of genetic defects such as next-generation sequencing (NGS) have further highlighted the importance of mosaicism in human disease. CASE DESCRIPTION: A 33-year-old woman was diagnosed with ACTH-independent CS with abdominal computed tomography showing bilateral micronodular adrenal hyperplasia with a left adrenal adenoma. She underwent left adrenalectomy with pathology demonstrating PPNAD with a 1.5-cm pigmented adenoma. DNA analysis by Sanger sequencing revealed 2 different PRKAR1A variants in the adenoma that were absent from DNA extracted from blood and saliva: c.682C > T and c.974-2A > G. "Deep" NGS revealed that 0.31% of DNA copies extracted from blood and saliva did in fact carry the c.682C > T variant, suggesting low-level mosaicism for this defect. CONCLUSIONS: We present a case of PPNAD due to low-level mosaicism for a PRKAR1A defect which led to the formation of an adenoma due to a second, adrenal-specific, somatic PRKAR1A mutation. The identification of mosaicism for PRKAR1A, depending on the number and distribution of cells affected has implications for genetic counseling and tumor surveillance. This is the first recorded case of a patient with PRKAR1A mosaicism, PPNAD, and an adenoma forming due to complete inactivation of PRKAR1A in adrenal tissue from a second, somatic-only, PRKAR1A coding sequence mutation.

Low Intake of Vegetable Protein is Associated With Altered Ovulatory Function Among Healthy Women of Reproductive Age.

CONTEXT: Diets high in plant-based protein have gained popularity due to increasing health concerns regarding consumption of animal products. Though links between intakes of certain protein-rich foods and reproductive disorders have been suggested, the relationship of overall animal and vegetable proteins with reproductive hormones among reproductive-aged women is unknown. OBJECTIVE: To evaluate the associations between the intake of dietary protein with reproductive hormones and sporadic anovulation among reproductive-aged women. DESIGN: A prospective cohort study, 2005-2007. SETTING: University at Buffalo, western New York, United States. PARTICIPANTS: A total of 259 premenopausal women (18-44 years) without dietary restrictions. MAIN OUTCOME MEASURE(S): Serum reproductive hormones were determined up to 8 times per cycle for 2 cycles. Protein intake was assessed the day prior to hormone assessment at 4 visits/cycle using 24-hour recalls. RESULTS: Overall, 84% of participants met the recommended dietary allowance for total protein set for reproductive-aged women. Neither total nor animal protein intake were associated with reproductive hormones or anovulation. However, vegetable protein intake in the lowest tertile was associated with lower luteal phase progesterone (-18.0%, 95% confidence interval [CI] -30.2, -3.6), higher follicle-stimulating hormone (3.8%, 95% CI 0.2, 7.6), and a higher risk of anovulation (risk ratio [RR] 2.53, 95% CI 1.21, 5.26), compared with the middle tertile. Nuts and seeds were the only protein-rich foods associated with an elevated risk of anovulation (RR 2.12, 95% CI 1.17, 3.85). CONCLUSIONS: Findings suggest that among women who meet the recommended dietary allowance for total protein, low intake of vegetable, but not animal, protein may disturb normal ovulatory function.

Vegetarian diets during pregnancy, and maternal and neonatal outcomes.

BACKGROUND: Vegetarian diets are becoming increasingly popular in the USA. Limited research has examined the health consequences of vegetarian diets during pregnancy. We comprehensively examined associations of vegetarianism during pregnancy with maternal and neonatal outcomes. METHODS: We used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Fetal Growth Studies-Singletons, a prospective multi-site cohort of 1948 low-risk pregnant women of four races/ethnicities (White, Black, Hispanic, Asian/Pacific Islander) in the USA (2009-2013). Vegetarianism was self-reported and also defined based on dietary patterns measured using a self-administered first-trimester food-frequency questionnaire (full [lacto-ovo and vegan], pesco-, semi- and non-vegetarians). Neonatal outcomes included birthweight and neonatal anthropometric measures, small for gestational age, small for gestational age with neonatal morbidity and preterm delivery. Maternal outcomes included gestational weight gain, gestational diabetes, hypertensive disorders of pregnancy and gestational anaemia. RESULTS: Ninety-nine (6.2%) women self-reported being vegetarian. The diet-based definition identified 32 (2.0%) full vegetarians, 7 (0.6%) pesco-vegetarians and 301 (17.6%) semi-vegetarians. Neonates of diet-based full vegetarians had higher odds of being small for gestational age [adjusted odds ratio (ORadj) = 2.51, 95% confidence interval: 1.01, 6.21], but not of being small for gestational age with a postnatal morbidity. Full vegetarians had marginally increased the odds of inadequate second-trimester gestational weight gain (ORadj = 2.24, 95% confidence interval: 0.95, 5.27). CONCLUSION: Vegetarian diets during pregnancy were associated with constitutionally smaller neonatal size, potentially via the mothers' reduced gestational weight gain. Notably, vegetarianism was not associated with small-for-gestational-age-related morbidities or other adverse maternal outcomes.

Is opioid use safe in women trying to conceive?

Background: Opioids are commonly prescribed to women of reproductive age, including after delivery and miscarriage. However, to our knowledge, opioid use has not been frequently studied in relation to the common reproductive complications of impaired fecundability and pregnancy. We examined the association of opioid use during the critical window of pregnancy establishment with fecundability and pregnancy loss. Methods: We measured opioid use by urine screening and self-report at multiple time points during preconception and early pregnancy in a prospective cohort of women attempting conception (n=1228). The main outcomes included time to hCG-detected pregnancy and incidence of live birth and pregnancy loss. We estimated fecundability odds ratios (FOR) and risk ratios (RR) with 95% confidence intervals (CI) adjusting for sociodemographic characteristics, reproductive characteristics, and use of antidepressants, tobacco, alcohol, and marijuana. Results: Prevalence of preconception opioid use was 18% (n=226 of 1228), and in early pregnancy was 5% (n=33 of 685). Opioid use while attempting pregnancy was associated with reduced fecundability (FOR: 0.71; 95% CI: 0.50, 1.0). Risk of pregnancy loss increased as opioid exposure was detected later in gestation, from the beginning of the cycle of conception (RR: 1.5; 95% CI 0.85, 2.6), to week 4 of pregnancy (RR: 2.1; 95% CI: 1.1, 4.1), and to week 4 and 8 of pregnancy (RR: 2.5; 95% CI: 1.3, 5.0). Conclusions: Our results are consistent with the hypothesis that opioid exposure while trying to conceive may be harmful, even among healthy, non-opioid-dependent women. Possible risks to fecundability and pregnancy viability are relevant to patients and providers when evaluating pain management approaches.ClinicalTrials.gov registration number: #NCT00467363.

Preconception Blood Pressure and Its Change Into Early Pregnancy: Early Risk Factors for Preeclampsia and Gestational Hypertension.

Preeclampsia and gestational hypertension are common complications of pregnancy associated with significant maternal and infant morbidity. Despite extensive research evaluating risk factors during pregnancy, most women who develop a hypertensive disorder of pregnancy are not considered high-risk and strategies for prevention remain elusive. We evaluated preconception blood pressure and its change into early pregnancy as novel risk markers for development of a hypertensive disorder of pregnancy. The EAGeR (Effects of Aspirin in Gestation and Reproduction) trial (2007-2011) randomized 1228 healthy women with a history of pregnancy loss to preconception-initiated low-dose aspirin versus placebo and followed participants for up to 6 menstrual cycles attempting pregnancy and throughout pregnancy if they became pregnant. Blood pressure was measured during preconception and throughout early gestation. The primary outcomes, preterm preeclampsia, term preeclampsia, and gestational hypertension, were abstracted from medical records. Among 586 women with a pregnancy >20 weeks' gestation, preconception blood pressure levels were higher for preterm preeclampsia (87.3±6.7 mm Hg mean arterial pressure), term preeclampsia (88.3±9.8 mm Hg), and gestational hypertension (87.9±9.1 mm Hg) as compared with no hypertensive disorder of pregnancy (83.9±8.6 mm Hg). Change in blood pressure from preconception into very early pregnancy was associated with development of preeclampsia (relative risk, 1.13 [95% CI, 1.02-1.25] per 2 mm Hg increase in mean arterial pressure at 4 weeks' gestation), particularly preterm preeclampsia (relative risk, 1.21 [95% CI, 1.01-1.45]). Randomization to aspirin did not alter blood pressure trajectory or risk of hypertension in pregnancy. Preconception blood pressure and longitudinal changes during early pregnancy are underexplored but crucial windows in the detection and prevention of hypertensive disorders of pregnancy. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00467363.

Urinary levels of environmental phenols and parabens and antioxidant enzyme activity in the blood of women.

BACKGROUND: The balance between oxidative stress and antioxidant enzymes is one biological mechanism by which environmental and lifestyle exposures affect health outcomes. Yet, no studies have examined the relationship between environmental phenolic compounds and parabens or their mixtures in relation to antioxidant enzyme activity in women of reproductive age. METHODS: Sixteen environmental phenols and parabens were measured in urine 2-5 times across two months of follow-up in 143 women aged 18-44 years. Four antioxidant enzymes, erythrocyte and plasma glutathione peroxidase (eGPx, pGPx), glutathione reductase (GSHR), superoxide dismutase (SOD) were measured in plasma. Linear mixed models were adjusted for age, body mass index, race, and creatinine and were weighted with inverse probability of exposure weights. Multi-chemical exposures were estimated using hierarchical principal component analysis (PCA). RESULTS: In line with our hypothesis that environmental phenols and parabens would be associated with decreased antioxidant enzymes, butyl, benzyl, ethyl, and propyl parabens were associated with lower levels of eGPx. Methyl paraben, 2,4-dichlorophenol and 2,5-dichlorophenol were associated with reduced SOD. 2,4,6-trichlorophenol was associated with increased levels of pGPx and GSHR. Several parabens were associated with modest decreases in eGPx and SOD, biomarkers of antioxidant defense. Increases in pGPx and GSHR were noted in relation to butyl and ethyl parabens. Co-exposures to parabens were associated with decreased eGPx (ß = -1.08, 95% CI: -1.74, -0.43) in principal components mixed models, while co-exposure to benzophenones-3 and -1 were associated with increased eGPx (ß = 0.92, 95% CI: 0.20, 1.64). CONCLUSION: These findings indicate that nonpersistent chemicals altered antioxidant enzyme activity. Further human studies are necessary to delineate the relationship between environmental phenol and paraben exposures with erythrocyte and plasma activities of antioxidant enzymes.

Prediction of pregnancy loss by early first trimester ultrasound characteristics.

BACKGROUND: Pregnancy loss prediction based on routinely measured ultrasound characteristics is generally aimed toward distinguishing nonviability. Physicians also use ultrasound indicators for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. To improve clinical utility, allocation of cut-points should be based on clinical data for multiple sonographic characteristics, be specific to gestational week, and be determined by methods that optimize prediction. OBJECTIVES: To identify routinely measured features of the early first trimester ultrasound and the gestational age-specific cut-points that are most predictive of pregnancy loss. MATERIALS AND METHODS: This was a secondary analysis of 617 pregnant women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial; all women had 1-2 previous pregnancy losses and no documented infertility. Each participant had a single ultrasound with a detectable fetal heartbeat between 6 weeks 0 days and 8 weeks 6 days. Cut-points for low fetal heart rate and small crown-rump length were separately defined for gestational weeks 6, 7, and 8 to optimize prediction. Identity and log-binomial regression models were used to estimate absolute and relative risks, respectively, and 95% confidence intervals between jointly categorized low fetal heart rate, small crown-rump length, and clinical pregnancy loss. Adjusted models accounted for gestational age at ultrasound in weeks. Missing data were addressed using multiple imputation. RESULTS: A total of 64 women experienced a clinical pregnancy loss following the first ultrasound (10.4%), 7 were lost to follow-up (1.1%), and 546 women (88.5%) had a live birth. Low fetal heart rate and small crown-rump length (≤122, 123, and 158 bpm; ≤6.0, 8.5, and 10.9 mm for gestational weeks 6, 7, and 8, respectively) were independent predictors of clinical pregnancy loss, with greatest risks observed for pregnancies having both characteristics (relative risk, 2.08; 95% confidence interval, 1.24-2.91). The combination of low fetal heart rate and small crown-rump length was linked to a 16% (95% confidence interval, 9.1-23%) adjusted absolute increase in risk of subsequent loss, from 5.0% (95% confidence interval, 1.5-8.5%) to 21% (95% confidence interval, 15-27%). Abnormal yolk sac diameter or the presence of a subchorionic hemmhorage did not improve prediction of clinical pregnancy loss. CONCLUSION: Identified cut-points can be used by physicians for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. The specified criteria should not be used to diagnose nonviability.

Length of Fellowship Training in Population Health Research and Long-term Bibliometric Outcomes.

BACKGROUND: The length of research fellowships, the number of doctorates pursuing them, and the academic job market have changed dramatically in recent years. However, there is limited investigation on attributes of fellowships most relevant to future scientific achievement. We analyzed the association of a modifiable aspect of research training, fellowship length, with future achievement and differences across research discipline in the Division of Intramural Population Health Research (DIPHR), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. METHODS: Demographics of 88 DIPHR trainees from 1998 to 2016 were collected from publicly available annual reports. Research performance metrics, including total publication count and H index through 2016, were collected via Scopus. We used linear regression models for associations between fellowship length, including both total exposure to research training and duration of postdoctoral training alone, and research performance adjusted for start year, publications at entry, branch (e.g., Biostatistics and Bioinformatics, Epidemiology, and Health Behavior), and mentor seniority. RESULTS: Each additional year of research training in DIPHR was associated with a 15% increase in H index (95% confidence interval [CI] = 3.0, 28.4) and 21% more lifetime publications (95% CI = 3.0, 41.9). Results were similar, although attenuated, when evaluating postdoctoral training alone. Differences by discipline were observed, with the strongest positive associations in the Biostatistics and Bioinformatics and Epidemiology Branches. CONCLUSIONS: Longer training at DIPHR was associated with improved measures of research performance, though this relationship varied by discipline. Additional research is needed to tailor training programs to optimize success of trainees.

Pilot randomized trial of short-term changes in inflammation and lipid levels during and after aspirin and pravastatin therapy.

BACKGROUND: Inflammation and elevated blood lipids are associated with infertility. Aspirin and statin therapy may improve infertility treatment outcomes among overweight and obese women with systemic inflammation, but little is known about the short-term effects of statins in this population. We conducted a pilot study of aspirin, pravastatin, or combined treatment among a group of overweight and obese, reproductive-aged women. Our goal was to characterize short-term changes in inflammatory and lipid biomarkers during and after treatment. METHODS: In this open-label trial, women aged 18-40 years with a body mass index ≥25 kg/m2 were randomized to receive either 162 mg aspirin, 40 mg pravastatin, or both. The study medication was taken daily for 2 weeks, and participants were then followed for a two-week washout period. Participants provided blood samples at baseline, after the intervention period, and after the washout period. The outcomes were changes in biomarkers of inflammation and lipids measured in blood components at each timepoint. RESULTS: Nine, 8, and 8 women were randomized to the aspirin, pravastatin, and combined arms, respectively. Analyses were conducted among 8, 7, and 7 women in the aspirin, pravastatin, and combined arms for whom biomarker data was available at baseline. High-sensitivity C-reactive protein (hsCRP) levels were lower after treatment in all arms and continued to decrease after washout in the pravastatin and combined arms. Results were consistent between the whole sample and women with baseline hsCRP between 2 and 10 mg/L. Low-density lipoprotein (LDL) cholesterol was lower after treatment in the pravastatin and combined arms and rose slightly after washout. CONCLUSIONS: Our results provide preliminary evidence that short-term aspirin and pravastatin therapy reduces hsCRP and LDL cholesterol among overweight and obese women of reproductive age, including those with low-grade inflammation. Because of these short-term effects, these drugs may improve infertility treatment outcomes in this population, which we will assess in a future randomized trial.