Pregnancy complications as markers for subsequent maternal cardiovascular disease: Validation of a maternal recall questionnaire

Background: We designed and tested the validity of a questionnaire to characterize maternal recall of pregnancy complications associated with increased future cardiovascular disease risk, based on the 2011 American Heart Association (AHA) guidelines. Methods: A maternal recall questionnaire of pregnancy history was administered to 971 patients who had participated in a previous cohort study of 1,608 pregnant women. Medical records from the study pregnancy served as the gold standard. Prevalence, sensitivity (sens), specificity (spec), positive predictive value (PPV), negative predictive value (NPV), and/or Spearman's correlation coefficients (r) were calculated for each question. Results: A total of 526 (54%) individuals recontacted responded. Respondents were more likely to be older, white, educated, and nulliparous and were less likely to deliver low-birthweight infants in the study pregnancy than were individuals who did not respond. Mean length of recall was 4.35 years (standard deviation [SD] 0.46) postpartum. Maternal recall was most accurate for gestational diabetes (sens: 92%, spec: 98%, PPV: 79%, NPV: 99%), infant birthweight (r=0.95), and gestation length (r=0.85). Maternal recall was modest for preeclampsia (sens: 79%, spec: 97%, PPV: 68%, NPV: 98%) and pregnancy-associated hypertension, including preeclampsia or gestational hypertension (sens: 60%, spec: 95%, PPV: 64%, NPV: 94%). Conclusions: This validation study demonstrated that the majority of women could accurately recall a history of gestational diabetes, infant birthweight, and gestational age at delivery, 4 years postpartum on average. Recall of preeclampsia and pregnancy-associated hypertension overall was modest. Maternal report of these pregnancy conditions may help clinicians identify women at increased risk for cardiovascular disease

Menstrual cycle regularity and length across the reproductive lifespan and risk of cardiovascular disease

Importance: Menstrual cycle characteristics may be associated with an increased risk of cardiovascular disease (CVD). However, existing studies are limited, and few have explored the mediating role of established CVD risk factors. Objective: To explore the associations of menstrual cycle characteristics across the reproductive lifespan with the risk of CVD and to what extent these associations were mediated by hypercholesterolemia, chronic hypertension, and type 2 diabetes. Design, Setting, and Participants: This cohort study prospectively followed Nurses’ Health Study II participants between 1993 and 2017 who reported menstrual cycle regularity and length for ages 14 to 17 years and 18 to 22 years at enrollment in 1989 and updated current cycle characteristics in 1993 (at ages 29 to 46 years). Data analysis was performed from October 1, 2019, to January 1, 2022. Exposures: Menstrual cycle regularity and length across the reproductive lifespan. Main Outcomes and Measures: Incident CVD events of interest, including fatal and nonfatal coronary heart disease (CHD; myocardial infarction [MI] or coronary revascularization) and stroke. Results: A total of 80 630 Nurses’ Health Study II participants were included in the analysis, with a mean (SD) age of 37.7 (4.6) years and body mass index of 25.1 (5.6) at baseline. Over 24 years of prospective follow-up, 1816 women developed their first CVD event. Multivariable Cox proportional hazards models showed that, compared with women reporting very regular cycles at the same ages, women who had irregular cycles or no periods at ages 14 to 17, 18 to 22, or 29 to 46 years had hazard ratios for CVD of 1.15 (95% CI, 0.99-1.34), 1.36 (95% CI, 1.06-1.75), and 1.40 (95% CI, 1.14-1.71), respectively. Similarly, compared with women reporting a cycle length of 26 to 31 days, women reporting a cycle length 40 days or more or a cycle too irregular to estimate from ages 18 to 22 or 29 to 46 years had hazard ratios for CVD of 1.44 (95% CI, 1.13-1.84) and 1.30 (95% CI, 1.09-1.57), respectively. Mediation analyses showed that subsequent development of hypercholesteremia, chronic hypertension, and type 2 diabetes only explained 5.4% to 13.5% of the observed associations. Conclusions and Relevance: In this cohort study, both irregular and long menstrual cycles were associated with increased rates of CVD, which persisted even after accounting for subsequently established CVD risk factors

A Prospective Study of Endometriosis and Breast Health: Findings From the Nurses' Health Study II

Endometriosis is a chronic gynecologic disease affecting approximately ten percent of women in the United States. Endometriosis lesions depend on estrogen for growth and maintenance and it is hypothesized that women with endometriosis have an altered hormonal and inflammatory state. Emerging evidence suggests that women with endometriosis may be at increased risk of breast cancer. Using data from the Nurses’ Health Study II, a prospective cohort of 116,430 women, this thesis investigates endometriosis and breast health. Specifically we investigated whether endometriosis influences risk of breast cancer and benign breast disease and alters mammographic density. Lastly, we investigated whether breastfeeding duration influenced endometriosis risk. Across all analyses, endometriosis was confirmed using laparoscopy, considered the clinical diagnostic gold standard. Information on breast cancer and benign breast disease was collected every two years and confirmed by medical record or pathology slides respectively. Mammographic density was measured from mammograms of a subset of participants without breast cancer using a computer assisted thresholding technique. Detailed breastfeeding information was collected between 1997-2001. Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals (CI) and linear regression using generalized estimating equations was used to estimate difference in mammographic density measurements. We found that while women with endometriosis were not at increased risk of overall breast cancer (HR:1.05, CI:0.95-1.16), they did appear to be at an increased risk of ER+/PR- tumors (HR:1.72, CI:1.27-2.32). Endometriosis moderately increased risk of biopsy confirmed benign breast disease, both proliferative (HR:1.23, CI:1.01-1.51) and non-proliferative lesions (HR:1.25, CI:0.93-1.69). Endometriosis did not significantly alter mammographic density. History of breastfeeding was inversely associated with endometriosis (P-value, test for linear trend: <0.0001), which was partially, but not fully mediated through postpartum amenorrhea. Our findings report novel associations with endometriosis and ER+/PR- breast tumors and benign breast disease lesions and no difference in mammographic density. This may elucidate avenues of research on how endometriosis lesions may alter chronic disease risk. Given the debilitating symptoms and few known modifiable risk factors of endometriosis, our findings of an inverse relationship with breastfeeding and endometriosis may inform treatments and prevention strategies for endometriosis in the future

Menstrual Phase Identification Questionnaire (MPIQ): Development and validation of a cross-sectional survey to identify follicular and luteal phases

Evidence continues to accumulate on the influence of the menstrual phase on several biobehavioral outcomes (e.g., substance misuse). Expansion of this knowledge is limited due to the burdensomeness of accurate menstrual phase assessment. Thus, we sought to create and validate a questionnaire that can be used as a stand-alone item within low-resource settings and numerous study designs (e.g., cross-sectional) to accurately identify both the follicular phase (FP) and the luteal phase (LP). Participants completed the self-administered four-item Menstrual Phase Identification Questionnaire (MPIQ) in two recently completed clinical trials. We assessed the accuracy of two MPIQ scoring criteria (less restrictive and more restrictive), as compared to self-report of onset of menses alone, with progesterone confirmation via dried blood spots. Participants (n = 59) were, on average, 33.7 (standard deviation [SD]: ± 4.3) years old and provided a total of 83 responses. Assessing FP and LP using the self-reported onset of menses alone classified 65.1% of the responses with an overall phase identification accuracy of 60.2%. While the more restrictive MPIQ scoring classified 100% of the responses, it yielded a similar accuracy (68.4%). In contrast, the less restrictive MPIQ scoring classified 100% of the responses and also significantly improved phase identification accuracy to 92.1% (p < .001). The MPIQ, as a stand-alone item, allows all cross-sectional responses to be classified with a high level of accuracy. This low-burden questionnaire can be used alone to identify FP and LP in studies that may be otherwise limited by study design, finances, and/or participant burden.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Birthweight and subsequent risk for thyroid and autoimmune conditions in postmenopausal women

The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women's Health Initiative (n = 80,806) were used to examine the associations between birthweight category (&lt;6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn's disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6-7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing &lt;6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions

Recreational and residential sun exposure and risk of endometriosis: a prospective cohort study

Study question: Is recreational and residential sun exposure associated with risk of endometriosis? Summary answer: Tanning bed use in early adulthood, sunscreen use and history of sunburns were associated with a greater risk of endometriosis; however, higher residential UV exposure was associated with a lower endometriosis risk. What is known already: Previous research has reported an association between endometriosis and skin cancer, with evidence of shared risk factors between the two diseases. We investigated the potential associations between ultraviolet radiation and endometriosis risk. Study design, size, duration: The Nurses' Health Study II is a prospective cohort of 116 429 female US nurses aged 25-42 years at enrolment in 1989. Participants completed self-administered biennial questionnaires through June 2015. Participants/materials, settings, methods: We investigated self-reported measures of recreational sun-exposure and geocoded residential UV exposure in childhood and adulthood in relation to risk of laparoscopically confirmed endometriosis among premenopausal white women. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs. Main results and the role of chance: During follow-up, 4791 incident cases of laparoscopically confirmed endometriosis were reported among 1 252 248 person-years. Tanning bed use during high school/college (≥6 times per year vs. never use: HR = 1.19, 95% CI = 1.01-1.40; Ptrend = 0.04) and at ages 25-35 (HR = 1.24, 95% CI = 1.12-1.39; Ptrend ≤ 0.0001), number of sunburns during adolescence (Ptrend = 0.03) and percentage of time using sunscreen in adulthood (Ptrend = 0.002) were positively associated with risk of endometriosis. In contrast, residential UV level at birth (highest vs. lowest quintile: HR = 0.81, 95% CI = 0.72-0.92; Ptrend = 0.0001), at age 15 (HR = 0.79, 95% CI = 0.70-0.88; Ptrend ≤ 0.0001) and at age 30 (HR = 0.90, 95% CI = 0.82-0.99; Ptrend = 0.21) were associated with a decreased risk of endometriosis. Limitations, reasons for caution: Self-reported endometriosis diagnosis may be prone to misclassification; however, we restricted our definition to laparoscopically confirmed endometriosis, which has been shown to have high validity compared to medical records. Wider implications of the findings: Our results suggest that tanning bed use in early adulthood increases endometriosis risk, potentially through a harmful effect of ultraviolet A wavelengths, and that residential UV exposure reduces risk, possibly via optimal vitamin D synthesis. These findings should be investigated further to enhance our understanding of endometriosis aetiology

Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes

IntroductionStudies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET).Research design and methodsThis is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer's disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models.ResultsAmong 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15).ConclusionsAmong patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia

Association of maternal birth weight and maternal preterm birth with subsequent risk for adverse reproductive outcomes: The Women\u27s Health Initiative.

BACKGROUND: Advancements in medical technology and pharmacologic interventions have drastically improved survival of infants born preterm and low birth weight, but knowledge regarding the long-term health impacts of these individuals is limited and inconsistent. AIM: To investigate whether an individual\u27s birthweight or history of being born preterm increases the risk of an adverse reproductive outcome. STUDY DESIGN: Nested case-control study within the Women\u27s Health Initiative. SUBJECTS: 79,934 individuals who self-reported their personal birthweight category and/or preterm birth status. OUTCOMES MEASURES: Self-reported pregnancy outcomes: subfertility, miscarriage, stillbirth, preeclampsia, gestational diabetes, gestational hypertension, preterm birth, low birthweight infant, high birthweight infant. Logistic regression models were used to estimate unadjusted and adjusted odds ratios (OR). RESULTS: After adjustments, individuals reporting their birthweight CONCLUSIONS: As more individuals born preterm and/or low birthweight survive to adulthood, the incidence and prevalence of poor reproductive outcomes may increase. Women born at extremes of birthweight and prematurity may need to be monitored more closely during their own pregnancies