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Background Autoimmune diseases disproportionately impact women and female-specific aspects of reproduction are thought to play a role. We investigated the time-varying association between pregnancy complications and new-onset autoimmune disease in females during the reproductive and midlife years. Methods We conducted a population-based cohort study of 1 704 553 singleton births to 1 072 445 females in Ontario, Canada (2002–17) with no pre-existing autoimmune disease. Pregnancy complications were preeclampsia, stillbirth, spontaneous preterm birth and severe small for gestational age (SGA). Royston-Parmar models were used to estimate the time-varying association between pregnancy complications and a composite of 25 autoimmune diseases from date of delivery to date of autoimmune disease diagnosis or censoring at death, loss of health insurance, or 31 March 2021. Models were adjusted for baseline socio-demographics, parity and comorbidities. Results At 19 years (median = 10.9 years of follow-up), cumulative incidence of autoimmune disease was 3.1% in those with a pregnancy complication and 2.6% in those without complications. Adjusted hazard ratio (AHR) curves as a function of time since birth were generally L-shaped. Universally, risks were most elevated within the first 3 years after birth [at 1 year: preeclampsia AHR 1.22, 95% confidence interval (CI) 1.09–1.36; stillbirth AHR 1.36, 95% CI 0.99–1.85; spontaneous preterm birth AHR 1.30, 95% CI 1.18–1.44; severe SGA AHR 1.14, 95% CI 0.99–1.31] and plateaued but remained elevated thereafter. Conclusions Prior history of pregnancy complications may be an important female-specific risk factor to consider during clinical assessment of females for possible autoimmune disease to facilitate timely detection and treatment. [ABSTRACT FROM AUTHOR]

Background: Individuals with disabilities may require specific medications in pregnancy. The prevalence and patterns of medication use, overall and for medications with known teratogenic risks, are largely unknown. Methods: This population-based cohort study in Ontario, Canada, 2004–2021, comprised all recognized pregnancies among individuals eligible for public drug plan coverage. Included were those with a physical (n = 44,136), sensory (n = 13,633), intellectual or developmental (n = 2,446) disability, or multiple disabilities (n = 5,064), compared with those without a disability (n = 299,944). Prescription medication use in pregnancy, overall and by type, was described. Modified Poisson regression generated relative risks (aRR) for the use of medications with known teratogenic risks and use of ≥2 and ≥5 medications concurrently in pregnancy, comparing those with versus without a disability, adjusting for sociodemographic and clinical factors. Results: Medication use in pregnancy was more common in people with intellectual or developmental (82.1%), multiple (80.4%), physical (73.9%), and sensory (71.9%) disabilities, than in those with no known disability (67.4%). Compared with those without a disability (5.7%), teratogenic medication use in pregnancy was especially higher in people with multiple disabilities (14.2%; aRR 2.03, 95% confidence interval [CI]: 1.88–2.20). Furthermore, compared with people without a disability (3.2%), the use of ≥5 medications concurrently was more common in those with multiple disabilities (13.4%; aRR 2.21, 95% CI: 2.02–2.41) and an intellectual or developmental disability (9.3%; aRR 2.13, 95% CI: 1.86–2.45). Interpretation: Among people with disabilities, medication use in pregnancy is prevalent, especially for potentially teratogenic medications and polypharmacy, highlighting the need for preconception counseling/monitoring to reduce medication-related harm in pregnancy. [ABSTRACT FROM AUTHOR]

Background: While the benefits of levothyroxine are well‐established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women. Objective: To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data. Methods: We emulated a target trial using the United Kingdom's Clinical Practice Research Datalink to account for the staggered timing of diagnosis and treatment of SCH and the time of entry of women into prenatal care. We emulated multiple nested trials (at each gestational week) and used an intention‐to‐treat approach to define levothyroxine use (≥1 prescription in the 7 days prior to trial entry), with eligible users matched to non‐users (1:4) on time of diagnosis, gestational week of the first eligible trial and high‐dimensional propensity score. Pregnancy losses included spontaneous abortion and stillbirth. A pooled logistic regression model with bootstrap resampling was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results: Based on 159,177 eligible person‐trials (5781 women), the matched cohort included 181 initiators and 640 non‐initiators of levothyroxine, with 57 pregnancy losses occurring during follow‐up. Overall, the mean age of women was 32.2 years (SD 5.4), 25% were obese, 8% had type 2 diabetes and about 50% were nulliparous. After matching, women who initiated levothyroxine versus not had higher thyroid‐stimulating levels during pregnancy and were more likely to have a history of hypothyroidism. The cumulative incidence of pregnancy loss was lower in initiators versus non‐initiators of levothyroxine. The adjusted HR for pregnancy loss was 0.87 (95% CI 0.22, 1.56). Conclusions: Although our assessment of the effect of initiation of levothyroxine for SCH in pregnancy precludes any definitive conclusions due to wide confidence intervals, this study illustrates the feasibility of using the target trial emulation framework to examine the effectiveness of medication use in pregnancy. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: −31.4, −14.4) and 47 cm2 less SAT (95% CI: −61.8, −33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50–55 years was associated with 19.3 cm2 (95% CI: −25.4, −13.3) less VAT and 27.4 cm2 (−29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S) HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Low‐dose aspirin prophylaxis is recommended for women at risk of preeclampsia. Capturing aspirin prophylaxis within administrative databases can be challenging since it is an over‐the‐counter medication. The Better Outcome Registry and Network (BORN) database, a perinatal health registry in Ontario, Canada, includes a formal variable that captures aspirin prophylaxis for preeclampsia. This variable has not been formally validated. Objectives: To assess the accuracy of the aspirin prophylaxis variable in the BORN database against an electronic medical record (EMR). Methods: This validation study comprised 200 randomly selected women who had a livebirth at St. Michael's Hospital (SMH) in Toronto, Ontario, from January 2018 to July 2022. Recorded aspirin prophylaxis in pregnancy and maternal sociodemographic characteristics were independently extracted by two abstractors. Accuracy of aspirin prophylaxis use in the BORN database was compared to that in the SMH EMR, expressed as sensitivity, specificity, positive (PPV) and negative predictive values (NPV), Cohen's kappa (κ), and overall percent agreement, with 95% confidence intervals (CI). Sensitivity analyses were performed to account for missing or unclear aspirin prophylaxis use. Results: Among 200 women, 24 (12.0%) received aspirin prophylaxis – 12.5% within the SMH EMR and 8.0% in the BORN database. Women using aspirin were older (37.0 vs 33.0 years) and had higher median gravidity (3 vs. 2). Sensitivity and specificity of the BORN aspirin prophylaxis variable were 62.5% (95% CI 40.6, 81.2) and 100.0% (95% CI 97.3, 100.0), respectively. The corresponding positive and negative predictive values were 100.0% (95% CI 78.2, 100.0), and 93.8% (95% CI 88.6, 97.1), respectively. Cohen's κ was 0.74 (95% CI 0.58, 0.90), and overall percent agreement was 94.4% (95% CI 87.1, 100.0). Conclusions: Aspirin use within the BORN database, based on a standard variable field, appears accurate enough for the potential use in epidemiological studies of aspirin prophylaxis for preeclampsia or as a covariate in related studies. [ABSTRACT FROM AUTHOR]

Background: Multifetal gestation could be associated with higher long‐term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. Objectives: We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long‐term maternal mortality in a racially diverse U.S. cohort. Methods: We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959–1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all‐cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all‐cause and cause‐specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). Results: Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all‐cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all‐cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all‐cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). Conclusions: In a cohort with over 50 years of follow‐up, history of multifetal gestation was not associated with all‐cause mortality, but may be associated with a lower risk of premature mortality. [ABSTRACT FROM AUTHOR]

Background: Adults with multiple chronic conditions (MCC) are a heterogeneous population with elevated risk of future adverse health outcomes. Yet, despite the increasing prevalence of MCC globally, data about MCC in pregnancy are scarce. Objectives: To estimate the population prevalence of MCC in pregnancy and determine whether certain types of chronic conditions cluster together among pregnant women with MCC. Methods: We conducted a population‐based cohort study in Ontario, Canada, of all 15–55‐year‐old women with a recognised pregnancy, from 2007 to 2020. MCC was assessed from a list of 22 conditions, identified using validated algorithms. We estimated the prevalence of MCC. Next, we used latent class analysis to identify classes of co‐occurring chronic conditions in women with MCC, with model selection based on parsimony, clinical interpretability and statistical fit. Results: Among 2,014,508 pregnancies, 324,735 had MCC (161.2 per 1000, 95% confidence interval [CI] 160.6, 161.8). Latent class analysis resulted in a five‐class solution. In four classes, mood and anxiety disorders were prominent and clustered with one additional condition, as follows: Class 1 (22.4% of women with MCC), osteoarthritis; Class 2 (23.7%), obesity; Class 3 (15.8%), substance use disorders; and Class 4 (22.1%), asthma. In Class 5 (16.1%), four physical conditions clustered together: obesity, asthma, chronic hypertension and diabetes mellitus. Conclusions: MCC is common in pregnancy, with sub‐types dominated by co‐occurring mental and physical health conditions. These data show the importance of preconception and perinatal interventions, particularly integrated care strategies, to optimise treatment and stabilisation of chronic conditions in women with MCC. [ABSTRACT FROM AUTHOR]

The article discusses the impact of gestational exposure to famine on mortality risk, particularly focusing on the Dutch famine during World War II. The study found that women exposed to famine during early gestation had higher risks of overall, cardiovascular, and cancer mortality. The research highlights sex differences in the effects of famine exposure, with potential explanations including survivorship bias, different manifestations of adverse effects, and gendered factors influencing health outcomes. The study underscores the importance of understanding early-life exposures for developing effective prevention strategies and reducing health risks associated with adverse experiences. [Extracted from the article]

A study published in the journal Paediatric & Perinatal Epidemiology explores the association between hypertensive disorders of pregnancy (HDP) and cardiovascular mortality. The study found that specific subtypes of HDP, such as chronic hypertension, preeclampsia with severe features, and eclampsia, were associated with an increased risk of cardiovascular-related deaths. However, the study may have underestimated the true association due to limitations in data collection and classification of cardiovascular events. The findings highlight the need for extended postpartum care and health insurance coverage for individuals with HDP to prevent maternal cardiovascular deaths. Further research is needed to validate the underlying causes of maternal mortality and improve the quality of epidemiological data for surveillance purposes. [Extracted from the article]

The increased risk of CVD mortality in primiparous women, with either a singleton or twin pregnancy, and pregnancy complications brings to question whether pregnancy complications are independently associated with CVD mortality or whether the "stress" of pregnancy amplifies or uncovers an underlying predisposition of these women to both pregnancy complications and subsequent CVD mortality. Over the last decade, the contribution of pregnancy complications to the development of long-term cardiovascular disease (CVD) and CVD-related mortality in women has been a priority area for both perinatal and cardiovascular epidemiologists. They found that a lifetime history of one twin pregnancy was associated with an increased risk of CVD mortality compared to a lifetime history of three singleton pregnancies, with the risk comparable to women with a history of one singleton pregnancy. [Extracted from the article]

Introduction Material and Methods Results Conclusions Evidence suggests that gestational diabetes mellitus (GDM) is associated with subsequent cardiovascular disease; however, it is unclear what impact changes in screening and diagnostic criteria have had on the association of GDM with long‐term outcomes such as cardiovascular disease. The purpose of this study was to determine the association between GDM and subsequent cardiovascular disease during a period of rising gestational diabetes diagnosis in England. Specifically, associations were compared before and after 2008, when national guidelines supporting risk factor‐based screening were introduced.We conducted a cohort study using routinely collected data from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study consisted of persons aged 15–45 years with a livebirth or stillbirth between 1998 and 2017 and without a history of cardiovascular disease or pre‐pregnancy diabetes mellitus. Cox proportional hazards models, with propensity score weighting using matching weights, were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the association of GDM diagnosis in the first recorded pregnancy with subsequent cardiovascular disease.Among 232 315 individuals, the incidence of cardiovascular disease was 6.6 per 1000 person‐years among those with GDM and 2.2 per 1000 person‐years among those without GDM over a mean follow‐up duration of 5.8 years. The overall aHR, 95% CI was 1.91 (1.41, 2.60). Diagnosis of GDM increased over the study period, from 0.7% in 1998–99 to 5.3% in 2017. The effect size was not markedly different in the years before (1998–2007: adjusted HR 2.05, 95% CI 2.05 1.35, 3.12) and after 2008 (2008–2017: adjusted HR 1.79, 95% CI 1.15, 2.80).There was a strong association of GDM with cardiovascular disease after accounting for social and demographic factors and multiple comorbidities, and this association was present both before and after 2008, when national gestational diabetes screening criteria were established. [ABSTRACT FROM AUTHOR]

Our study aimed to describe levothyroxine prescription patterns and trends over time among pregnant women with subclinical hypothyroidism (SCH) in the United Kingdom. We used data from the Clinical Practice Research Datalink linked to its Pregnancy Register and the Hospital Episode Statistics database from 1998 to 2017. The study population included women with a diagnosis of SCH or an abnormal thyroid-simulated hormone (TSH) level one year prior to or during pregnancy. We compared characteristics between women who received a prescription for levothyroxine during pregnancy and those who did not. We further described the timing, dose, duration, and temporal trends of levothyroxine prescriptions. Our cohort included 6,757 pregnancies from 6,287 women with SCH, of whom 10% received levothyroxine during pregnancy. Among women who received levothyroxine, most received their first prescription during the first trimester (median gestational age: 7 weeks; interquartile range [IQR]: 0, 16) with a median daily dosage of 50 mcg (IQR: 50, 73). Levothyroxine prescription varied over time, decreasing from 23% of pregnant women in 1998 to 7.5% in 2003, remaining stable until 2014, and increasing to 12.5% in 2016. Smoking, diabetes, polycystic ovary syndrome, infertility, timing of SCH diagnosis, age, TSH level at diagnosis, and general practice regions were associated with prescription. Few women with SCH received levothyroxine during pregnancy, and treatment varied by patient characteristics and geographical regions. These results highlight the need to increase awareness among healthcare providers and will guide future studies that explore barriers to initiating levothyroxine treatment for women with SCH during pregnancy. [ABSTRACT FROM AUTHOR]