Infertility treatments and cyanotic congenital heart defects among livebirths in the USA: findings from a contemporary cohort.

STUDY QUESTION: Is there an elevated risk of cyanotic congenital heart defects (CCHD) among livebirths following infertility treatments? SUMMARY ANSWER: In this population-based study of single livebirths, infertility treatment (either ART or non-ART) was associated with a higher prevalence of CCHD among livebirths. WHAT IS KNOWN ALREADY: The use of infertility treatment has been on the rise over the past few decades. However, there are limited studies assessing the risk of major cardiac defects following infertility treatments. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of livebirth data from the National Vital Statistics System (NVSS) was conducted, comprising of 9.6 million singleton livebirths among first-time mothers aged 15-49 years from 2016 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on infertility treatment use and CCHD was obtained from the health and medical information section of birth certificates, which was completed by healthcare staff after reviewing medical records. Logistic regression models were used to estimate odds ratios (OR) and 95% CI. Entropy balancing weighting analysis and probabilistic bias analysis were also performed. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of births following infertility treatment increased from 1.9% (27 116) to 3.1% (43 510) during the study period. Overall, there were 5287 cases of CCHD resulting in a prevalence of 0.6 per 1000 livebirths. The prevalence was 1.2 per 1000 live births among infertility treatment users (ART: 1.1 per 1000 livebirths; non-ART: 1.3 per 1000 livebirths) while that for naturally conceived births was 0.5 per 1000 livebirths. Compared to naturally conceived births, the use of any infertility treatment (OR: 2.06, 95% CI: 1.82-2.33), either ART (OR: 2.02, 95% CI: 1.73-2.36) or other infertility treatments (OR: 2.12, 95% CI: 1.74-2.33), was associated with higher odds of CCHD after adjusting for maternal and paternal age, race and ethnicity, and education, as well as maternal nativity, marital status, source of payment, smoking status, and pre-pregnancy measures of BMI, hypertension and diabetes. This association did not differ by the type of infertility treatment (ART versus other infertility treatments) (OR: 1.04, 95% CI: 0.82-1.33, P = 0.712), and was robust to the presence of exposure and outcome misclassification bias and residual confounding. LIMITATIONS, REASONS FOR CAUTION: The findings are only limited to livebirths. We did not have the capacity to examine termination data, but differential termination by mode of conception has not been supported by previous studies designed to consider it. Infertility treatment use was self-reported, leading to the potential for selection bias and misclassification for infertility treatment and CCHD. However, the association persisted when systematic bias as well as exposure and outcome misclassification bias were accounted for in the analyses. Information on the underlying etiology of infertility relating to either maternal, paternal, or both factors, data on specific types of ART and other infertility treatments, as well as information on subtypes of CCHD, were all not available. WIDER IMPLICATIONS OF THE FINDINGS: In light of the increasing trend in the use of infertility treatment in the USA, and elsewhere, the finding of the current study holds significant importance for the clinical and public health of reproductive-aged individuals. The data show that the use of infertility treatment may expose offspring to elevated odds of severe congenital heart defects such as CCHD studied here. These findings cannot be interpreted causally. While our findings can assist in preconception counseling and prenatal care for pregnancies conceived by either ART or other infertility treatments, they also support some current recommendations that pregnancies resulting from infertility treatments undergo fetal echocardiography screening. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for the study. The authors declare that they have no conflict of interest. TRIAL REGISTRAION NUMBER: N/A.

ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging.

ZFYVE21 is an ancient, endosome-associated protein that is highly expressed in endothelial cells (ECs) but whose function(s) in vivo are undefined. Here, we identified ZFYVE21 as an essential regulator of vascular barrier function in the aging kidney. ZFYVE21 levels significantly decline in ECs in aged human and mouse kidneys. To investigate attendant effects, we generated EC-specific Zfyve21-/- reporter mice. These knockout mice developed accelerated aging phenotypes including reduced endothelial nitric oxide (ENOS) activity, failure to thrive, and kidney insufficiency. Kidneys from Zfyve21 EC-/- mice showed interstitial edema and glomerular EC injury. ZFYVE21-mediated phenotypes were not programmed developmentally as loss of ZFYVE21 in ECs during adulthood phenocopied its loss prenatally, and a nitric oxide donor normalized kidney function in adult hosts. Using live cell imaging and human kidney organ cultures, we found that in a GTPase Rab5- and protein kinase Akt-dependent manner, ZFYVE21 reduced vesicular levels of inhibitory caveolin-1 and promoted transfer of Golgi-derived ENOS to a perinuclear Rab5+ vesicular population to functionally sustain ENOS activity. Thus, our work defines a ZFYVE21- mediated trafficking mechanism sustaining ENOS activity and demonstrates the relevance of this pathway for maintaining kidney function with aging.

Magnetically functionalized hydrogels for high-throughput genomic applications.

Single-cell genomics has revolutionized tissue analysis by revealing the genetic program of individual cells. The key aspect of the technology is the use of barcoded beads to unambiguously tag sequences originating from a single cell. The generation of unique barcodes on beads is mainly achieved by split-pooling methods, which are labor-intensive due to repeated washing steps. Towards the automation of the split-pooling method, we developed a simple method to magnetize hydrogel beads. We show that these hydrogel beads provide increased yields and washing efficiencies for purification procedures. They are also fully compatible with single-cell sequencing using the BAG-Seq workflow. Our work opens the automation of the split-pooling technique, which will improve single-cell genomic workflows.

Mechanosensing regulates tissue repair program in macrophages.

Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a noncanonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by colony-stimulating factor 1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study identifies an "amoeboid" mode of ECM mechanosensing through which macrophages may regulate tissue repair and fibrosis.

Academic publishing requires linguistically inclusive policies.

Scientific knowledge is produced in multiple languages but is predominantly published in English. This practice creates a language barrier to generate and transfer scientific knowledge between communities with diverse linguistic backgrounds, hindering the ability of scholars and communities to address global challenges and achieve diversity and equity in science, technology, engineering and mathematics (STEM). To overcome those barriers, publishers and journals should provide a fair system that supports non-native English speakers and disseminates knowledge across the globe. We surveyed policies of 736 journals in biological sciences to assess their linguistic inclusivity, identify predictors of inclusivity, and propose actions to overcome language barriers in academic publishing. Our assessment revealed a grim landscape where most journals were making minimal efforts to overcome language barriers. The impact factor of journals was negatively associated with adopting a number of inclusive policies whereas ownership by a scientific society tended to have a positive association. Contrary to our expectations, the proportion of both open access articles and editors based in non-English speaking countries did not have a major positive association with the adoption of linguistically inclusive policies. We proposed a set of actions to overcome language barriers in academic publishing, including the renegotiation of power dynamics between publishers and editorial boards.

Migraines, vasomotor symptoms, and cardiovascular disease in the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes. METHODS: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) using Cox proportional hazards regression models and adjustment for traditional CVD risk factors (age, cigarette use, and levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides) and reproductive factors. RESULTS: Among women with minimal VMS (n = 835), increasing VMS (n = 521), and persistent VMS (n = 598), there were 81 incident CVD events including 42 strokes. Women with histories of migraine and persistent VMS had greater risk of CVD (hazard ratio [HR], 2.25; 95% CI, 1.15-4.38) after adjustment for age, race, estrogen use, oophorectomy, and hysterectomy compared with women without migraine histories and with minimal/increasing VMS. After adjustment for CVD risk factors, these associations were attenuated (HR, 1.51; 95% CI, 0.73-3.10). Similarly, women with histories of migraine and persistent VMS had greater risk of stroke (HR, 3.15; 95% CI, 1.35-7.34), but these associations were attenuated after adjustment for CVD risk factors (HR, 1.70; 95% CI, 0.66-4.38). CONCLUSIONS: Migraines and persistent VMS jointly associate with greater risk for CVD and stroke, although risk is attenuated with adjustment for traditional CVD risk factors.

Epigenetic age acceleration is associated with speed of pubertal growth but not age of pubertal onset.

Using data from a longitudinal cohort of children, we examined whether epigenetic age acceleration (EAA) was associated with pubertal growth and whether these associations were mediated by adiposity. We examined associations between EAA at approximately 10 years of age with pubertal growth metrics, including age at peak height velocity (PHV), PHV, and sex steroid levels and whether these associations were mediated by measures of adiposity including body mass index (BMI) and MRI-assessed visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Children (n = 135) with accelerated EAA had higher PHV (ß 0.018, p = 0.0008) although the effect size was small. The association between EAA and age at PHV was not significant (ß - 0.0022, p = 0.067). Although EAA was associated with higher BMI (ß 0.16, p = 0.0041), VAT (ß 0.50, p = 0.037), and SAT (ß 3.47, p = 0.0076), BMI and VAT did not mediate associations between EAA and PHV, while SAT explained 8.4% of the association. Boys with higher EAA had lower total testosterone (ß - 12.03, p = 0.0014), but associations between EAA and other sex steroids were not significant, and EAA was not associated with sex steroid levels in girls. We conclude that EAA did not have strong associations with either age at onset of puberty or pubertal growth speed, although associations with growth speed were statistically significant. Studies with larger sample sizes are needed to confirm this pattern of associations.

Prospective early adulthood risk factors for vasomotor symptoms in the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: Previous studies have assessed potential risk factors for vasomotor symptoms (VMS) beginning in midlife. We examined whether early adulthood risk factors predict VMS trajectories over time. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort. We included women who answered questions about VMS at three or more examinations (n = 1,966). We examined whether risk factors at baseline (when participants were aged 18-30 y; average age, 25 y) and the year 15 (Y15) exam (at ages 33-45 y; average age, 40 y) were associated with VMS trajectories from Y15 through Y35. Logistic regression models were used to evaluate the associations with VMS trajectories. RESULTS: We identified three trajectories of VMS presence: minimal (40%), increasing over time (27%), and persistent (33%). Baseline factors associated with persistent VMS over time included Black race, less than a high school education, depressive symptoms, migraines, cigarette use, and at Y15 hysterectomy. Baseline factors associated with increasing VMS over time included Black race and lower body mass index. Risk factors for bothersome VMS were similar and also included thyroid disease, although thyroid disease was not associated with persistence of VMS over time. Associations were similar among women who had not undergone hysterectomy and in Black and White women. CONCLUSIONS: Risk factors for VMS may be identified in early adulthood. Further examination of risk factors such as migraines and depressive symptoms in early adulthood may be helpful in identifying therapies for VMS.

Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

Associations of Polycystic Ovary Syndrome With Indicators of Brain Health at Midlife in the CARDIA Cohort.

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with an adverse cardiometabolic profile early in life. Increasing evidence links cardiovascular risk factors, such as diabetes and hypertension, to accelerated cognitive aging. However, less is known about PCOS and its relationship to brain health, particularly at midlife. Our goal was to investigate possible associations between PCOS and midlife cognitive function and brain MRI findings in an ongoing prospective study. METHODS: We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a geographically diverse prospective cohort study of individuals who were 18-30 years at baseline (1985-1986) and followed for 30 years. We identified women with PCOS from an ancillary study (CARDIA Women's study (CWS); n = 1,163) as those with elevated androgen levels and/or hirsutism in conjunction with symptoms of oligomenorrhea. At year 30, participants completed cognitive testing, including the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test (RAVLT) (verbal learning and memory), Digit Symbol Substitution Test (processing speed and executive function), Stroop test (attention and cognitive control), and category and letter fluency tests (semantics and attention). A subset completed brain MRI to assess brain structure and white matter integrity. Multivariable linear regression models estimated the association between PCOS and outcomes, adjusting for age, race, education, and study center. RESULTS: Of the 1163 women in CWS, 907 completed cognitive testing, and of these, 66 (7.1%) met criteria for PCOS (age 54.7 years). Women with and without PCOS were similar for age, BMI, smoking/drinking status, and income. At year 30, participants with PCOS performed lower (mean z score; 95% CI) on Stroop (-0.323 (-0.69 to -7.37); p = 0.008), RAVLT (-0.254 (-0.473 to -0.034); p = 0.002), and category fluency (-0.267 (-0.480 to -0.040); p = 0.02) tests. Of the 291 participants with MRI, 25 (8.5%) met PCOS criteria and demonstrated lower total white matter fractional anisotropy, a measure of white matter integrity (coefficient (95% CI) -0.013 (-0.021 to -0.005); p = 0.002), though not abnormal white matter. DISCUSSION: Our results suggest that women with PCOS have lower cognitive performance and lower white matter integrity at midlife. Additional research is needed to confirm these findings and to determine potential mechanistic pathways including potential modifiable factors.

Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.

Efficacy of a Flavored Lubricating Oral Spray on Medication Swallowing in Older Individuals.

Background Difficulty swallowing occurs in up to 35% of patients 50 years of age or older and can contribute to medication nonadherence and other alterations. The use of a flavored lubricating spray, available over-the-counter and found to be helpful in children to swallow oral solid medications, is not well studied in older adults. Objective To evaluate the effect of a flavored lubricating spray on the ability to swallow oral solid medication in older people. Methods A randomized, open-label, crossover study included community-dwelling individuals 65 to 88 years of age who took at least one solid oral medication daily and were not diagnosed with dysphagia, Parkinson's disease, or esophageal tumor. Participants were randomized to the strawberry-flavored lubricating spray or usual care and then crossed over to the alternate option. The median rating for swallowing difficulty for their regular medications was compared using a Likert scale, from 1 (very difficult) to 5 (very easy). To provide a degree of standardization between participants, all participants were also instructed to swallow a vitamin C (1,000 mg) tablet both with and without the flavored spray and rate their difficulty swallowing the tablet using the same Likert scale. Results There were 39 (90.7%) participants who completed the study. The median rating for swallowing difficultly was 5 (very easy) with the spray vs. 4 (easy) with usual care (P < 0.0001). For the 66.7% who took the vitamin C tablets, the median rating for swallowing difficulty was 5 (very easy) with the spray vs. 3.5 (between neutral and easy) without (P < 0.0001). There were 94.8% of participants who found the spray easy/ very easy to use, and 89.7% reported it tasted okay to delicious. Conclusion The use of a flavored lubricating spray provided an effective and easy-to-use tool to make medication swallowing easier in community-dwelling older adults without a diagnosis associated with difficulty swallowing.

The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women's study.

In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.

Sex Hormones and Cardiovascular Disease in Relation to Menopause.

Natural menopause is defined as the cessation of menstruation among women who have not undergone hysterectomy or bilateral oophorectomy. The implications of menopause management are particularly important with the aging of the population and increasing awareness of the importance of midlife risk upon longevity. Our understanding of the relationships between reproductive milestones and cardiovascular disease continues to evolve particularly regarding shared determinants of health.

An improved reference of the grapevine genome reasserts the origin of the PN40024 highly homozygous genotype.

The genome sequence of the diploid and highly homozygous Vitis vinifera genotype PN40024 serves as the reference for many grapevine studies. Despite several improvements to the PN40024 genome assembly, its current version PN12X.v2 is quite fragmented and only represents the haploid state of the genome with mixed haplotypes. In fact, being nearly homozygous, this genome contains several heterozygous regions that are yet to be resolved. Taking the opportunity of improvements that long-read sequencing technologies offer to fully discriminate haplotype sequences, an improved version of the reference, called PN40024.v4, was generated. Through incorporating long genomic sequencing reads to the assembly, the continuity of the 12X.v2 scaffolds was highly increased with a total number decreasing from 2,059 to 640 and a reduction in N bases of 88%. Additionally, the full alternative haplotype sequence was built for the first time, the chromosome anchoring was improved and the number of unplaced scaffolds was reduced by half. To obtain a high-quality gene annotation that outperforms previous versions, a liftover approach was complemented with an optimized annotation workflow for Vitis. Integration of the gene reference catalogue and its manual curation have also assisted in improving the annotation, while defining the most reliable estimation of 35,230 genes to date. Finally, we demonstrated that PN40024 resulted from 9 selfings of cv. "Helfensteiner" (cross of cv. "Pinot noir" and "Schiava grossa") instead of a single "Pinot noir". These advances will help maintain the PN40024 genome as a gold-standard reference, also contributing toward the eventual elaboration of the grapevine pangenome.

Racial and ethnic disparities in the association of maternal infection during pregnancy and risk of cyanotic congenital heart defects in the United States, 2011-2020.

PURPOSE: The etiology of cyanotic congenital heart defects (CCHD) is not well understood. There are scarce data on racial/ethnic disparities in maternal infection and CCHD. We evaluated the relation of maternal infections during pregnancy and risk of CCHD in the United States, and to assess if this association varies by race/ethnicity. METHODS: Data were from the National Vital Statistics System comprising 35.3 million singleton livebirths among mothers aged 15-49 years from 2011 to 2020. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: After adjustment for sociodemographic and maternal health factors, including prepregnancy body mass index, diabetes, hypertension, and smoking during pregnancy, time to prenatal care was initiated and pregnancy complications, any maternal infection, was associated with elevated odds of CCHD (OR: 1.25, 95% CI: 1.15-1.37). The odds of CCHD were mainly evident for sexually transmitted infections, namely chlamydia and hepatitis-C viral infection. The association was limited to non-Hispanic Black (OR: 1.22, 95% CI: 1.03-1.45), Hispanic (OR: 1.61, 95% CI: 1.33-1.95), and Asian (OR: 2.03, 95% CI: 1.42-2.91) mothers. CONCLUSIONS: In this population-based study, maternal infection during pregnancy was associated with a modest risk of CCHD in offspring, which was the highest in racial/ethnic minority mothers.

Women's Reproductive Milestones and Cardiovascular Disease Risk: A Review of Reports and Opportunities From the CARDIA Study.

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population-based reports to note Black-White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti-Müllerian hormone, have facilitated examination of reproductive health in a population-based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid-60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.

The role of postoperative radiation after radical hysterectomy for women with early-stage neuroendocrine carcinoma of the cervix: A meta-analysis.

INTRODUCTION: Neuroendocrine carcinoma of the cervix (NECC) is an aggressive disease with high rates of nodal disease spread even in seemingly cervix-confined disease. Many providers routinely prescribe postoperative radiation therapy in an effort to reduce recurrences despite a lack of supporting studies. The objective of this study was to determine recurrence and mortality in patients with early-stage NECC who had pelvic radiation after radical hysterectomy compared to those who did not receive radiation. METHODS: We performed a meta-analysis of 13 unique studies that reported recurrence and/or mortality for patients with early-stage NECC who underwent radical hysterectomy with or without adjuvant radiation therapy. RESULTS: In 5 studies that reported overall recurrence rates, 63 (52.5%) of 120 patients who received postoperative radiation recurred compared to 70 (37.8%) of 185 patients who did not (RR 1.21, 95% CI: 0.85-1.70, p = 0.29). In 5 studies that reported pelvic recurrence rates, there were 15 pelvic recurrences (12.5%) in the 120 patients who received postoperative radiation compared to 45 pelvic recurrences (24.3%) in the 185 patients who did not (RR 0.60, 95% CI: 0.34-1.08, p = 0.09). In 13 studies that reported mortality rate, there were 138 deaths (34.8%) in 396 patients who received postoperative radiation therapy compared to 223 (35.2%) in 632 patients who did not (RR 1.08, 95% CI: 0.75-1.56, p = 0.66). CONCLUSIONS: The addition of routine postoperative radiation therapy in all patients with early-stage NECC after radical hysterectomy may reduce pelvic recurrences but does not appear to decrease overall recurrence or death. However, there may still be a role for postoperative radiation therapy in patients with additional high-risk pathologic factors.

Maternal age at birth of last child and cardiovascular disease mortality later in life among a national cohort of postmenopausal women from the United States.

Maternal age at last birth (ALB) of child is increasing in the United States, and it has been reported to influence future chronic diseases. However, the relationship of ALB and cardiovascular disease (CVD) events later in life has not been widely studied. We evaluated the association of ALB with CVD mortality. Data were from 7,971 parous postmenopausal women older than 45 years who participated in the US National Health and Nutritional Examination Survey from 1999 to 2018 and had mortality follow-up data through to December 31, 2019. ALB was self-reported, whereas CVD mortality was assessed using International Classification of Diseases codes. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). The mean age of participants was 63 ± 9.8 years, with 9.5% being non-Hispanic Black, 9.7% being Hispanic women, and 21% reporting ALB ≥35 years. During a median follow-up of 8.1 years, 443 participants died from CVD. In age-adjusted models, CVD mortality was elevated for women with ALB of <25 years (HR, 1.68; 95% CI, 1.23-2.29) and ALB of ≥35 years (HR, 1.37; 95% CI, 1.00-1.88). However, after additional adjustment for race and ethnicity, foreign born, education, marital status, poverty income ratio, parity, smoking status, age at menarche, oral contraceptive pills use and family history of myocardial infarction, these estimates were attenuated resulting in no association between ALB and CVD mortality. In this study of nationally representative sample of postmenopausal women, there was no conclusive association between maternal ALB and CVD mortality later in life.

Vaccination Against Measles, Mumps, Rubella and Incident Inflammatory Bowel Disease in a National Cohort of Privately Insured Children.

BACKGROUND: Infection is believed to be a potential trigger for inflammatory bowel disease (IBD). Whether vaccination against childhood infections including measles, mumps, and rubella may reduce risk of IBD is uncertain. METHODS: We conducted a retrospective cohort study using de-identified claims data from a national private payer (Optum Clinformatics Data Mart). Eligible infants were born between 2001 and 2018 and were continuously enrolled with medical and pharmacy coverage from birth for at least 2 years (n = 1 365 447). Measles, mumps, and rubella vaccination or MMR is administered beginning at 12 months of age. Cox proportional hazard regression models were used to compare time with incident disease in children by category of vaccination, after adjustment for sex, birth year, region of country, history of allergy to vaccines, and seizure history. RESULTS: The incidence of early pediatric IBD increased between 2001 and 2018. Ten percent (n = 141 230) of infants did not receive MMR, and 90% (n = 1 224 125) received at least 1 dose of MMR. There were 334 cases of IBD, 219 cases of Crohn's disease, and 164 cases of ulcerative colitis. Children who had received at least 1 dose of MMR had lower risk for IBD than children who did not (hazard ratio, 0.71; 95% confidence interval, 0.59-0.85). These associations did not change after further adjustment for childhood comorbid conditions, preterm birth, or older siblings affected with IBD. Similar associations were observed for MMR with Crohn's disease and ulcerative colitis, although these did not reach statistical significance. CONCLUSION: MMR is associated with decreased risk for childhood IBD.

Childhood vaccination against measles, mumps, and rubella was associated with decreased risk of childhood inflammatory bowel disease in a national administrative claims database.