Associations of Physical Activity and Lactation Duration With Cardiometabolic Risk Factors: The CARDIA Study.

BACKGROUND: Physical activity (PA) and lactation benefit cardiometabolic health. OBJECTIVES: The purpose of this study was to describe the joint associations of PA and lactation with cardiometabolic risk. METHODS: We averaged PA across exams and summed lifetime lactation in Black and White parous women in the Coronary Artery Risk Development in Young Adults Study. Categories were created for PA (-PA:

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.

Reduced cardiovascular risks in women with endometriosis or polycystic ovary syndrome carrying a common functional IGF1R variant.

STUDY QUESTION: Is the increased future cardiovascular risk seen in women with endometriosis or polycystic ovary syndrome (PCOS) mitigated by functional insulin-like growth factor-1 receptor (IGF1R) single-nucleotide polymorphism (SNP) rs2016347 as previously shown in women with hypertensive disorders of pregnancy? SUMMARY ANSWER: This cohort study found that women with endometriosis or PCOS who carry a T allele of IGF1R SNP rs2016347 had a reduced future risk of developing cardiovascular disease (CVD) and associated risk factors, with risk reduction dependent on cohort era. WHAT IS KNOWN ALREADY: Women with endometriosis or PCOS have been shown to have an increased future risk of CVD and associated risk factors with limited predictive ability. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study took place in the Nurses' Health Study 2 (NHS2), which enrolled 116 430 participants in 1989 who were followed through 2015. The study population was analyzed in its entirety, and subdivided into entry (pre-1989) and after entry (post-1989) exposure cohorts. All NHS2 participants were eligible for inclusion in the study, 9599 (8.2%) were excluded for missing covariates. PARTICIPANTS/MATERIALS, SETTING, METHODS: The NHS2 enrolled female registered nurses from 14 different states who ranged in age from 25 to 42 years at study entry. Data were collected from entry and biennial questionnaires, and analysis conducted from November 2020 to June 2021. Cox proportional hazard models were used to assess risk of CVD, hypertension (HTN), hypercholesterolemia (HC) and type 2 diabetes, both with and without genotyping for rs2016347. MAIN RESULTS AND THE ROLE OF CHANCE: While women without endometriosis or PCOS, as a whole, demonstrated no impact of genotype on risk in either cohort, women with endometriosis carrying a T allele had a lower risk of CVD (hazard ratio (HR), 0.48; 95% CI, 0.27-0.86, P = 0.02) and HTN (HR, 0.80; 95% CI, 0.66-0.97, P = 0.03) in the pre-1989 cohort, while those in the post-1989 cohort had a decrease in risk for HC (HR, 0.76; 95% CI, 0.62-0.94, P = 0.01). Women with PCOS in the post-1989 cohort showed a significant protective impact of the T allele on HTN (HR, 0.44; 95% CI, 0.27-0.73, P = 0.002) and HC (HR, 0.62; 95% CI, 0.40-0.95, P = 0.03). LIMITATIONS, REASONS FOR CAUTION: Data on specific endometriosis lesion locations or disease stage, as well as on PCOS phenotypes were lacking. In addition, data on systemic medical treatments beyond the use of oral contraceptives were missing, and these treatments may have confounded the results. WIDER IMPLICATIONS OF THE FINDINGS: These findings implicate systemic dysregulation of the insulin-like growth factor-1 axis in the development of HTN, HC and clinical CVD in endometriosis and PCOS, suggesting a common underlying pathogenetic mechanism. STUDY FUNDING/COMPETING INTEREST(S): The NHS2 infrastructure for questionnaire data collection was supported by National Institute of Health (NIH) grant U01CA176726. This work was also supported in part by NIH and National Cancer Institute grant U24CA210990; as well, research effort and publication costs were supported by the Elizabeth MA Stevens donor funds provided to the Buck Institute for Research on Aging. The authors declare they have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Perinatal Complications in Individuals in California With or Without SARS-CoV-2 Infection During Pregnancy.

Importance: Additional research from population-based studies is needed to inform the treatment of SARS-CoV-2 infection during pregnancy and to provide health risk information to pregnant individuals. Objective: To assess the risk of perinatal complications associated with SARS-CoV-2 infection and to describe factors associated with hospitalizations. Design, Setting, and Participants: This population-based cohort study included 43 886 pregnant individuals with longitudinal electronic health record data from preconception to delivery who delivered at Kaiser Permanente Northern California between March 1, 2020, and March 16, 2021. Individuals with diagnostic codes for COVID-19 that did not have a confirmatory polymerase chain reaction test for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 infection detected by polymerase chain reaction test (from 30 days before conception to 7 days after delivery) as a time varying exposure. Main Outcomes and Measures: Severe maternal morbidity including 21 conditions (eg, acute myocardial infarction, acute renal failure, acute respiratory distress syndrome, and sepsis) that occurred at any time during pregnancy or delivery; preterm birth; pregnancy hypertensive disorders; gestational diabetes; venous thromboembolism (VTE); stillbirth; cesarean delivery; and newborn birth weight and respiratory conditions. Standardized mean differences between individuals with and without SARS-CoV-2 were calculated. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for the association between SARS-CoV-2 infection and perinatal complications and hospitalization and to consider the timing of SARS-CoV-2 infection relative to outcomes. Results: In this study of 43 886 pregnant individuals (mean [SD] age, 30.7 [5.2] years), individuals with a SARS-CoV-2 infection (1332 [3.0%]) were more likely to be younger, Hispanic, multiparous individuals with a higher neighborhood deprivation index and obesity or chronic hypertension. After adjusting for demographic characteristics, comorbidities, and smoking status, individuals with SARS-CoV-2 infection had higher risk for severe maternal morbidity (HR, 2.45; 95% CI, 1.91-3.13), preterm birth (<37 weeks; HR, 2.08; 95% CI, 1.75-2.47), and VTE (HR, 3.08; 95% CI, 1.09-8.74) than individuals without SARS-CoV-2. SARS-CoV-2 infection was also associated with increased risk of medically indicated preterm birth (HR, 2.56; 95% CI, 2.06-3.19); spontaneous preterm birth (HR, 1.61; 95% CI, 1.22-2.13); and early (HR, 2.52; 95% CI, 1.49-4.24), moderate (HR, 2.18; 95% CI, 1.25-3.80), and late (HR, 1.95; 95% CI, 1.61-2.37) preterm birth. Among individuals with SARS-CoV-2 infection, 76 (5.7%) had a hospitalization; pregestational diabetes (HR, 7.03; 95% CI, 2.22-22.2) and Asian or Pacific Islander (HR, 2.33; 95% CI, 1.06-5.11) and Black (HR, 3.14; 95% CI, 1.24-7.93) race and ethnicity were associated with an increased risk of hospitalization. Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with increased risk of severe maternal morbidity, preterm birth, and VTE. The study findings inform clinicians and patients about the risk of perinatal complications associated with SARS-CoV-2 infection in pregnancy and support vaccination of pregnant individuals and those planning conception.

Adverse Pregnancy Outcomes and Incident Heart Failure in the Women's Health Initiative.

Importance: Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective: To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI). Design, Setting, and Participants: In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021. Exposures: APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery). Main Outcomes and Measures: All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods. Results: Of 10 292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF. Conclusions and Relevance: In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.

The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: The CARDIA Study.

BACKGROUND: Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women. METHODS: Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-1986) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams. RESULTS: At baseline, the average age of women (48% black, 52% white) was 24 ±â€…3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity, and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation [none (n = 221), 1-5 months (n = 306), 6-11 months (n = 210), and ≥12 months (n = 173)] were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5, and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively. CONCLUSIONS: In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.

Cancer and Cardiovascular Risk in Women With Hypertensive Disorders of Pregnancy Carrying a Common IGF1R Variant.

OBJECTIVE: To evaluate the impact of insulin-like growth factor 1 receptor variant rs2016347 on the risk for breast and nonbreast cancers and cardiovascular disease in women with a history of hypertensive disorders of pregnancy (HDP). PATIENTS AND METHODS: This retrospective cohort study included all parous women in the UK Biobank with prior rs2016347 genotyping (N=204,155), with enrollment taking place from March 2006 to July 2010. History of HDP was self-reported, and outcomes included breast and all nonbreast cancers, hospital diagnoses of hypertension and cardiovascular disease, and direct blood pressure measurements. RESULTS: Women with previous HDP had a higher risk for future hypertension and cardiovascular diagnoses, increased blood pressures, and lower risk for breast cancer compared with women without HDP, consistent with prior studies. Hazard ratios for all nonbreast cancers were unchanged. However, when taking genotype into account, HDP-positive women carrying at least 1 thymine (T) allele of rs2016347 had a lower risk for nonbreast cancer (hazard ratio, 0.59; 95% CI, 0.37 to 0.92; P=.02) and lower systolic blood pressure (-2.08±0.98 mm Hg; P=.03) compared with women with the guanine/guanine (GG) genotype with positive evidence of interaction (HDP:T allele) for both outcomes; P=.04 and P=.03, respectively. CONCLUSION: Women who experience HDP and carry a T allele of rs2016347 have 41% lower risk for developing nonbreast cancer and a lower systolic blood pressure of 2.08 mm Hg when compared with those with the GG genotype, suggesting a possible role of the insulin-like growth factor 1 axis for both cardiovascular and cancer risk in women with HDP.

A longitudinal study of pre-pregnancy antioxidant levels and subsequent perinatal outcomes in black and white women: The CARDIA Study.

BACKGROUND: Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes. METHODS AND FINDINGS: Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race. RESULTS: In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81). CONCLUSIONS: Higher preconception antioxidant levels are not associated with better birth outcomes.

The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature. OBJECTIVES: The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes. POPULATION: A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation. DESIGN: The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages. METHODS: Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors. PRELIMINARY RESULTS: Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data. CONCLUSIONS: The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.

Fasting glucose variability in young adulthood and incident diabetes, cardiovascular disease and all-cause mortality.

AIMS/HYPOTHESIS: The aim of this study was to determine whether long-term intra-individual variability in fasting glucose (FG) during young adulthood is associated with incident diabetes, cardiovascular disease (CVD) and mortality. METHODS: We included participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 18-30 years at baseline (1985-1986) and followed with eight examinations for up to 30 years. Long-term glucose variability was assessed using the CV (CV-FG) and the absolute difference between successive FG measurements (average real variability; ARV-FG). For participants who developed any event (diabetes, CVD or mortality), FG variability measurement was censored at the examination prior to event ascertainment. We estimated HRs for incident diabetes, CVD and mortality with adjustment for demographics, baseline FG, change in FG (censor - baseline) and time-varying education, smoking, alcohol consumption, BMI, physical activity, systolic BP, BP medications, LDL-cholesterol and cholesterol medications (and incident diabetes and diabetes medications for CVD and mortality outcomes). RESULTS: Among 3769 black and white participants, there were 317 incident diabetes cases (102,677 person-years), 159 incident CVD events (110,314 person-years) and 174 deaths (111,390 person-years). After adjustment, HRs per 1 SD higher ARV-FG were 1.64 (95% CI 1.52, 1.78) for diabetes, 1.15 (95% CI 1.01, 1.31) for CVD and 1.25 (95% CI 1.11, 1.40) for mortality. The HRs per 1 SD higher CV-FG were 1.39 (95% CI 1.21, 1.58) for diabetes, 1.32 (95% CI 1.13, 1.54) for CVD and 1.08 (95% CI 0.92, 1.27) for mortality, after adjustment. The cause-specific HRs per 1 SD higher ARV-FG were 1.29 (95% CI 1.14, 1.47) for non-CVD death and 1.05 (95% CI 0.76, 1.45) for CVD death. We did not observe evidence for effect modification of any association by sex or race. CONCLUSIONS/INTERPRETATION: Our results suggest that higher intra-individual FG variability during young adulthood before the onset of diabetes is associated with incident diabetes, CVD and mortality.

Pre-pregnancy kidney function and subsequent adverse pregnancy outcomes.

BACKGROUND: Renal insufficiency is associated with pregnancy complications including fetal growth restriction, preterm birth (PTB), and pre-eclampsia. OBJECTIVE: To determine the effect of preconception kidney function within the normal range on pregnancy outcome. METHOD: 1043 (50% black, 50% white) women who participated in the CARDIA study who had kidney function and biochemical analyses measured before at least one pregnancy delivered during the 20 years post-baseline period were included in analysis. Kidney function estimated as glomerular filtration rate (eGFR) via modified CKD-EPI equations, serum creatinine, and urinary albumin/creatinine ratio were evaluated as predictors of infant birthweight, gestational age, birthweight-for-gestational-age, and hypertensive disorders of pregnancy via self-report, using multiple regression with adjustment for confounders (age, race, smoking, BMI, center, parity, systolic blood pressure at baseline). Serum uric acid was also examined at both baseline and year 10. RESULTS: Unadjusted pre-pregnancy eGFR (baseline) was associated with lower average birthweight-for-gestational-age, but this disappeared after adjustment for confounders. A decline in GFR from baseline to year 10 was associated with lower birthweight (adjusted estimate -195 g, p = 0.03 overall), especially among whites. After adjustment for confounders, no association was found with gestational age or hypertensive disorders. CONCLUSIONS: No strong evidence for an association between preconception kidney function in the normal range and birthweight or gestational age was found. Possible racial differences in these relationships warrant further examination.

Longer lactation duration is associated with decreased prevalence of non-alcoholic fatty liver disease in women.

BACKGROUND & AIMS: Lactation lowers blood glucose and triglycerides, and increases insulin sensitivity. We hypothesized that a longer duration of lactation would be associated with lower prevalence of non-alcoholic fatty liver disease (NAFLD), which is the leading cause of chronic liver disease in the United States. METHODS: Participants from the Coronary Artery Risk Development in Young Adults cohort study who delivered ≥ 1 child post-baseline (Y0: 1985-1986), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n = 844). The duration of lactation was summed for all post-baseline births, and NAFLD at Y25 was assessed by central review of CT images and defined by liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of hepatic steatosis. Unadjusted and multivariable logistic regression analyses were performed using an a priori set of confounding variables; age, race, education, and baseline body mass index. RESULTS: Of 844 women who delivered after baseline (48% black, 52% white, mean age 49 years at Y25 exam), 32% reported lactation duration of 0 to 1 month, 25% reported >1 to 6 months, 43% reported more than 6 months, while 54 (6%) had NAFLD. Longer lactation duration was inversely associated with NAFLD in unadjusted logistic regression. For women who reported >6 months lactation compared to those reporting 0-1 month, the odds ratio for NAFLD was 0.48 (95% CI 0.25-0.94; p = 0.03) and the association remained after adjustment for confounders (adjusted odds ratio 0.46; 95% CI 0.22-0.97; p = 0.04). CONCLUSIONS: A longer duration of lactation, particularly greater than 6 months, is associated with lower odds of NAFLD in mid-life and may represent a modifiable risk factor for NAFLD. LAY SUMMARY: A longer duration of breastfeeding has been associated with multiple potential health benefits for the mother including reduction in heart disease, diabetes and certain cancers. In this study we found that breastfeeding for longer than 6 months was associated with a lower risk of non-alcoholic fatty liver disease in mid-life.

Prepregnancy Fitness and Risk of Gestational Diabetes: A Longitudinal Analysis.

PURPOSE: This study aimed to assess the associations of prepregnancy cardiorespiratory fitness, moderate- to vigorous-intensity physical activity (MVPA), and time spent watching television with subsequent development of gestational diabetes mellitus (GDM). METHODS: Participants were 1333 women enrolled in the Coronary Artery Risk Development in Young Adults study who did not have diabetes either at baseline (1985-86) or before births occurring after baseline. Baseline fitness was estimated using a graded symptom-limited maximal exercise treadmill test and expressed in MET units. Baseline MVPA (exercise units per day) was measured using the Coronary Artery Risk Development in Young Adults physical activity history questionnaire, and television viewing (h·d) was assessed by self-report in 1990-1991. Logistic regression analysis was used to derive odds ratios and 95% confidence intervals, adjusting for time from baseline to delivery and baseline study center, age, race, education, parity, family history of diabetes, smoking, alcohol, saturated fat intake, waist circumference, homeostasis model assessment of insulin resistance, and HDL cholesterol. RESULTS: Over 25 yr of follow-up, 164 women developed GDM. The odds of developing GDM were 21% lower for each 1 SD increment in baseline level of fitness (2.3 METs, odds ratio = 0.79, 95% confidence interval = 0.65-0.96). Prepregnancy MVPA and television viewing were not statistically associated with the development of GDM. CONCLUSION: Study findings indicate that objectively assessed prepregnancy fitness, but not self-reported MVPA or television time, is associated with GDM. Clinicians should counsel women on the benefits of improving fitness in the preconception period, particularly among women at greater risk for GDM.

Association Between Gestational Diabetes and Incident Maternal CKD: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risk for diabetes mellitus, metabolic syndrome, and cardiovascular disease. We evaluated whether GDM is associated with incident chronic kidney disease (CKD), controlling for prepregnancy risk factors for both conditions. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Of 2,747 women (aged 18-30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study in 1985 to 86, we studied 820 who were nulliparous at enrollment, delivered at least 1 pregnancy longer than 20 weeks' gestation, and had kidney function measurements during 25 years of follow-up. PREDICTOR: GDM was self-reported by women for each pregnancy. OUTCOMES: CKD was defined as the development of estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 or urine albumin-creatinine ratio ≥ 25mg/g at any one CARDIA examination in years 10, 15, 20, or 25. MEASUREMENTS: HRs for developing CKD were estimated for women who developed GDM versus women without GDM using complementary log-log models, adjusting for prepregnancy age, systolic blood pressure, dyslipidemia, body mass index, smoking, education, eGFR, fasting glucose concentration, physical activity level (all measured at the CARDIA examination before the first pregnancy), race, and family history of diabetes. We explored for an interaction between race and GDM. RESULTS: During a mean follow-up of 20.8 years, 105 of 820 (12.8%) women developed CKD, predominantly increased urine albumin excretion (98 albuminuria only, 4 decreased eGFR only, and 3 both). There was evidence of a GDM-race interaction on CKD risk (P=0.06). Among black women, the adjusted HR for CKD was 1.96 (95% CI, 1.04-3.67) in GDM compared with those without GDM. Among white women, the HR was 0.65 (95% CI, 0.23-1.83). LIMITATIONS: Albuminuria was assessed by single untimed measurements of urine albumin and creatinine. CONCLUSIONS: GDM is associated with the subsequent development of albuminuria among black women in CARDIA.

Risk of Type 2 Diabetes Mellitus following Gestational Diabetes Pregnancy in Women with Polycystic Ovary Syndrome.

BACKGROUND: This study examines gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) and the risk of type 2 diabetes mellitus (DM) following GDM pregnancy. METHODS: A cohort of 988 pregnant women with PCOS who delivered during 2002-2005 was examined to determine the prevalence and predictors of GDM, with follow-up through 2010 among those with GDM to estimate the risk of DM. RESULTS: Of the 988 pregnant women with PCOS, 192 (19%) developed GDM. Multivariable predictors of GDM included older age, Asian race, prepregnancy obesity, family history of DM, preconception metformin use, and multiple gestation. Among women with PCOS and GDM pregnancy, the incidence of DM was 2.8 (95% confidence interval (CI) 1.9-4.2) per 100 person-years and substantially higher for those who received pharmacologic treatment for GDM (6.6 versus 1.5 per 100 person-years, p < 0.01). The multivariable adjusted risk of DM was fourfold higher in women who received pharmacologic treatment for GDM (adjusted hazard ratio 4.1, 95% CI 1.8-9.6). The five-year incidence of DM was 13.1% overall and also higher in the pharmacologic treatment subgroup (27.0% versus 7.1%, p < 0.01). CONCLUSIONS: The strongest predictors of GDM among women with PCOS included Asian race and prepregnancy obesity. Pharmacologic treatment of GDM is associated with fourfold higher risk of subsequent DM.

Association of Gestational Diabetes Mellitus With Left Ventricular Structure and Function: The CARDIA Study.

OBJECTIVE: Gestational diabetes mellitus (GDM) predicts incident cardiovascular disease (CVD). However, mechanisms linking GDM to CVD beyond intervening incident diabetes are not well understood. We examined the relation of GDM with echocardiographic parameters of left ventricular (LV) structure and function, which are important predictors of future CVD risk. RESEARCH DESIGN AND METHODS: We studied 609 women (43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who delivered one or more births during follow-up and had echocardiograms in 1990-1991 (mean age 28.8 years) and 2010-2011. RESULTS: During the 20-year follow-up, 965 births were reported, with GDM developing in 64 women (10.5%). In linear regression models adjusted for sociodemographic factors, BMI, physical activity, parity, smoking, use of oral contraceptives, alcohol intake, family history of coronary heart disease, systolic blood pressure, and lipid levels, women with GDM had impaired longitudinal peak strain (-15.0 vs. -15.7%, P = 0.025), circumferential peak strain (-14.8 vs. -15.6%, P = 0.028), lateral e' wave velocity (11.0 vs. 11.8 cm/s, P = 0.012), and septal e' wave velocity (8.6 vs. 9.3 cm/s, P = 0.015) in 2010-2011 and a greater 20-year increase in LV mass indexed to body surface area (14.3 vs. 6.0 g/m(2), P = 0.006) compared with women with non-GDM pregnancies. Further adjustment for incident type 2 diabetes after pregnancy did not attenuate these associations. CONCLUSIONS: Pregnancy complicated by GDM is independently associated with increased LV mass and impaired LV relaxation and systolic function. Implementation of postpartum cardiovascular health interventions in women with a history of GDM may offer an additional opportunity to reduce future CVD risk.

Lactation Duration and Midlife Atherosclerosis.

OBJECTIVE: To evaluate lactation duration in relation to subsequent atherosclerosis in women during midlife. METHODS: The Coronary Artery Risk Development in Young Adults study is a multicenter prospective cohort that enrolled 2,787 women in 1985-1986 (ages 18-30 years, 52% black, 48% white), of whom 2,014 (72%) attended the 20-year follow-up examination in 2005-2006. We selected 846 women (46% black) without heart disease or diabetes at baseline who delivered one or more times after the baseline evaluation, had cardiometabolic risk factors measured at baseline, and had maximum common carotid intima-media thickness (mm) measured at the 20-year follow-up examination in 2005-2006. Lactation duration was summed across all postbaseline births for each woman and (n, women) categorized as: 0 to less than 1 month (n=262), 1 to less than 6 months (n=210), 6 to less than 10 months (n=169), and 10 months or greater (n=205). Multiple linear regression models estimated mean common carotid intima-media thickness (95% confidence interval) and mean differences among lactation duration groups compared with the 0 to less than 1-month group adjusted for prepregnancy obesity, cardiometabolic status, parity, and other risk factors. RESULTS: Lactation duration had a graded inverse association with common carotid intima-media thickness; mean differences between 10 months or greater compared with 0 to less than 1 month ranged from -0.062 mm for unadjusted models (P trend <.001) to -0.029 mm for models fully adjusted for prepregnancy body mass index (BMI) and cardiometabolic risk factors, parity, smoking, and sociodemographics (P trend=.010). Stepwise addition of potential mediators (BMI, systolic blood pressure at the 20-year follow-up examination) modestly attenuated the lactation and common carotid intima-media thickness association to -0.027 and -0.023 mm (P trend=.019 and .054). CONCLUSION: Shorter lactation duration is associated with subclinical atherosclerosis independent of prepregnancy cardiometabolic risk factors and traditional risk factors. The magnitude of differences in carotid artery intima-media thickness may represent greater vascular aging. Lactation may have long-term benefits that lower cardiovascular disease risk in women. LEVEL OF EVIDENCE: II.

Breastfeeding, PAM50 tumor subtype, and breast cancer prognosis and survival.

BACKGROUND: Breastfeeding is associated with decreased breast cancer risk, yet associations with prognosis and survival by tumor subtype are largely unknown. METHODS: We conducted a cohort study of 1636 women from two prospective breast cancer cohorts. Intrinsic tumor subtype (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2]-enriched, basal-like) was determined by the PAM50 gene expression assay. Breastfeeding history was obtained from participant questionnaires. Questionnaires and medical record reviews documented 383 recurrences and 290 breast cancer deaths during a median follow-up of nine years. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between breastfeeding and tumor subtype. Cox regression was used to estimate hazard ratios (HRs) for breast cancer recurrence or death. Statistical significance tests were two-sided. RESULTS: Breast cancer patients with basal-like tumors were less likely to have previously breastfed than those with luminal A tumors (OR = 0.56, 95% CI = 0.39 to 0.80). Among all patients, ever breastfeeding was associated with decreased risk of recurrence (HR = 0.70, 95% CI = 0.53 to 0.93), especially breastfeeding for six months or more (HR = 0.63, 95% CI = 0.46 to 0.87, P trend = .01). Similar associations were observed for breast cancer death. Among women with luminal A subtype, ever breastfeeding was associated with decreased risks of recurrence (HR = 0.52, 95% CI = 0.31 to 0.89) and breast cancer death (HR = 0.52, 95% CI = 0.29 to 0.93), yet no statistically significant associations were observed among the other subtypes. Effects appeared to be limited to tumors with lower expression of proliferation genes. CONCLUSIONS: History of breastfeeding might affect prognosis and survival by establishing a luminal tumor environment with lower proliferative activity.

Changes in weight and health behaviors after pregnancies complicated by gestational diabetes mellitus: the CARDIA study.

OBJECTIVE: Prepregnancy to postpregnancy change in weight, body mass index (BMI), waist circumference, diet, and physical activity in women with and without gestational diabetes mellitus (GDM) were compared. DESIGN AND METHODS: Using the Coronary Artery Risk Development in Young Adults study, women with at least one pregnancy during 20 years of follow-up (n = 1,488 with 3,125 pregnancies) was identified. Linear regression with generalized estimating equations to compare prepregnancy to postpregnancy changes in health behaviors and anthropometric measurements between 137 GDM pregnancies and 1,637 non-GDM pregnancies, adjusted for parity, age at delivery, outcome measure at the prepregnancy exam, race, education, mode of delivery, and interval between delivery and postpregnancy examination were used. RESULTS: When compared with women without GDM in pregnancy, women with GDM had higher prepregnancy mean weight (158.3 vs. 149.6 lb, P = 0.011) and BMI (26.7 vs. 25.1 kg/m(2) , P = 0.002), but nonsignificantly lower total daily caloric intake and similar levels of physical activity. Both GDM and non-GDM groups had higher average postpartum weight of 7-8 lbs and decreased physical activity on average 1.4 years after pregnancy. CONCLUSIONS: Both groups similarly increased total caloric intake but reduced fast food frequency. Prepregnancy to postpregnancy changes in body weight, BMI, waist circumference, physical activity, and diet did not differ between women with and without GDM in pregnancy. Following pregnancy, women with and without GDM increased caloric intake, BMI, and weight and decreased physical activity, but reduced their frequency of eating fast food. Given these trends, postpartum lifestyle interventions, particularly for women with GDM, are needed to reduce obesity and diabetes risk.

Preterm birth and future maternal blood pressure, inflammation, and intimal-medial thickness: the CARDIA study.

Preterm birth (PTB, <37 weeks) may be a marker of endothelial dysfunction and a proinflammatory phenotype; both are risk factors for cardiovascular disease. We studied 916 women (46% black) with 1181 live births between enrollment in the Coronary Artery Risk Development in Young Adults study (age 18-30 years) and 20 years later. C-reactive protein was measured at years 7, 15, and 20. Interleukin-6 and carotid intima-media thickness, which incorporated the common carotid arteries, bifurcations, and internal carotid arteries, were measured at year 20. Blood pressure, lipids, anthropometrics, and pregnancy events were assessed at all visits. Change in risk factors and differences in inflammatory markers and intima-media thickness according to PTB were evaluated. Women with PTBs (n=226) had higher mean systolic blood pressures before pregnancy (106 versus 105 mm Hg, respectively; P=0.03). Systolic and diastolic blood pressure increased more rapidly over 20 years compared with women with term births (P<0.01 time interaction), even after removing women with self-reported hypertension in pregnancy. Women with PTB versus term births had similar mean intima-media thickness adjusted for age, body mass index, race, lifestyle, and cardiovascular risk factors. C-reactive protein and interleukin-6 did not differ according to PTB. Women with PTB, regardless of hypertension during pregnancy, had higher blood pressure after pregnancy compared with women with term births. In the United States, where rates of PTB are high and race disparities persist, PTB may identify women with higher blood pressure in the years after pregnancy.