Early or late pregnancy loss and development of clinical cardiovascular disease risk factors: a prospective cohort study.

OBJECTIVE: To assess the association between the outcome of a woman's first pregnancy and risk of clinical cardiovascular disease risk factors. DESIGN: Prospective cohort study. SETTING AND POPULATION: Nurses' Health Study II. METHODS: Multivariable-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between first pregnancy outcome and hypertension, type 2 diabetes, and hypercholesterolemia. MAIN OUTCOME MEASURES: Hypertension, type 2 diabetes, and hypercholesterolemia. RESULTS: Compared to women who reported a singleton live first birth, women with early spontaneous abortion (<12 weeks) had a greater rate of type 2 diabetes (HR: 1.20; 95% CI: 1.07-1.34) and hypercholesterolemia (HR: 1.06; 95% CI: 1.02-1.10), and a marginally increased rate of hypertension (HR: 1.05, 95% CI: 1.00-1.11). Late spontaneous abortion (12-19 weeks) was associated with an increased rate of type 2 diabetes (HR: 1.38; 95% CI: 1.14-1.65), hypercholesterolemia (HR: 1.11; 95% CI: 1.03-1.19), and hypertension (HR: 1.15; 95% CI: 1.05-1.25). The rates of type 2 diabetes (HR: 1.45; 95% CI: 1.13-1.87) and hypertension (HR: 1.15; 95% CI: 1.01-1.30) were higher in women who delivered stillbirth. In contrast, women whose first pregnancy ended in an induced abortion had lower rates of hypertension (HR: 0.87; 95% CI: 0.84-0.91) and type 2 diabetes (HR: 0.89; 95% CI: 0.79-0.99) than women with a singleton live birth. CONCLUSIONS: Several types of pregnancy loss were associated with an increased rate of hypertension, type 2 diabetes, and hypercholesterolemia, which may provide novel insight into the pathways through which pregnancy outcomes and CVD are linked. TWEETABLE ABSTRACT: Pregnancy loss is associated with later maternal risk of hypertension, type 2 diabetes, and hypercholesterolemia.

Birth weight and cardiac function assessed by echocardiography in adolescence: Avon Longitudinal Study of Parents and Children.

OBJECTIVE: Maternal hemodynamics in pregnancy is associated with fetal growth and birth weight, which in turn are associated with offspring cardiovascular disease later in life. The aim of this study was to quantify the extent to which birth weight is associated with cardiac structure and function in adolescence. METHODS: A subset of offspring (n = 1964; 55% female) of the Avon Longitudinal Study of Parents and Children were examined with echocardiography at a mean age of 17.7 (SD, 0.3) years. The associations of birth-weight Z-score for sex and gestational age with cardiac structure (assessed by relative wall thickness, left ventricular mass index (LVMI) and left atrial diameter index), systolic function (assessed by ejection fraction and left ventricular wall velocity) and diastolic function (assessed by early/late mitral inflow velocity (E/A) and early mitral inflow velocity/mitral annular early diastolic velocity (E/e')) were evaluated. Linear regression models were adjusted for several potential confounders, including maternal prepregnancy body mass index, age, level of education and smoking during pregnancy. RESULTS: Higher birth-weight Z-score was associated with lower E/A (mean difference, -0.024; 95% CI, -0.043 to -0.005) and E/e' (mean difference, -0.05; 95% CI, -0.10 to -0.001) and higher LVMI (mean difference, 0.38 g/m2.7 ; 95% CI, 0.09 to 0.67). There was no or inconsistent evidence of associations of birth-weight Z-score with relative wall thickness, left atrial diameter and measurements of systolic function. Further analyses suggested that the association between birth-weight Z-score and LVMI was driven mainly by an association observed in participants born small-for-gestational age and it did not persist when risk factors in adolescence were accounted for. CONCLUSIONS: Higher birth weight adjusted for sex and gestational age was associated with differences in measures of diastolic function in adolescence, but the observed associations were small. It remains to be determined the extent to which these associations translate into increased susceptibility to cardiovascular disease later in life. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

A prospective cohort study of endometriosis and subsequent risk of infertility.

STUDY QUESTION: Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates. WIDER IMPLICATIONS OF THE FINDINGS: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.

Is grand-parental smoking associated with adolescent obesity? A three-generational study.

BACKGROUND/OBJECTIVES: Data from previous studies consistently suggest that maternal smoking is positively associated with obesity later in life. Whether this association persists across generations is unknown. We examined whether grand-parental smoking was positively associated with overweight status in adolescence. SUBJECT/METHODS: Participants were grandmother-mother-child triads in the Nurses' Health Study II (NHS II), the Nurses Mothers' Cohort Study and the Growing up Today Study (GUTS). Grandmothers provided information on their and their partner's smoking during pregnancy with the child's mother. Information on child's weight and height at ages 12 (N=3094) and 17 (N=3433) was obtained from annual or biennial GUTS questionnaires. We used logistic regression to estimate the odds ratios (ORs) of being overweight or obese, relative to normal weight. RESULTS: Grand-maternal smoking during pregnancy was not associated with overweight status in adolescence. After adjusting for covariates, the OR of being overweight or obese relative to normal weight at age 12 years in girls whose grandmothers smoked 15+ cigarettes daily during pregnancy was 1.21 (95% confidence interval (CI) 0.74-1.98; P(trend)=0.31) and 1.07 (0.65-1.77; P(trend)=0.41) in boys. Grand-paternal smoking during pregnancy was associated with being overweight or obese at age 12 in girls only, but not at age 17 for either sex: the OR for being overweight or obese at age 12 was 1.38 (95% CI 1.01-1.89; P(trend)=0.03) in girls and 1.31 (95% CI 0.97-1.76; P(trend)=0.07) in boys. Among children of non-smoking mothers, the OR for granddaughter obesity for grand-paternal smoking was attenuated and no longer significant (OR 1.28 (95% CI 0.87-1.89; P(trend)=0.18)). CONCLUSIONS: Our findings suggest that the association between maternal smoking and offspring obesity may not persist beyond the first generation. However, grand-paternal smoking may affect the overweight status of the granddaughter, likely through the association between grand-paternal smoking and maternal smoking.

Job strain and changes in the body mass index among working women: a prospective study.

OBJECTIVE: The relationship between job strain and weight gain has been unclear, especially for women. Using data from over 52,000 working women, we compare the association between change in job strain and change in body mass index (BMI) across different levels of baseline BMI. SUBJECTS/METHODS: We used data from participants in the Nurses' Health Study II (n=52,656, mean age=38.4 years), an ongoing prospective cohort study. Using linear regression, we modeled the change in BMI over 4 years as a function of the change in job strain, baseline BMI and the interaction between the two. Change in job strain was characterized in four categories combining baseline and follow-up levels as follows: consistently low strain (low at both points), decreased strain (high strain at baseline only), increased strain (high strain at follow-up only) and consistently high strain (high at both points). Age, race/ethnicity, pregnancy history, job types and health behaviors at baseline were controlled for in the model. RESULTS: In adjusted models, women who reported high job strain at least once during the 4-year period had a greater increase in BMI (ΔBMI=0.06-0.12, P<0.05) compared with those who never reported high job strain. The association between the change in job strain exposure and the change in BMI depended on the baseline BMI level (P=0.015 for the interaction): the greater the baseline BMI, the greater the BMI gain associated with consistently high job strain. The BMI gain associated with increased or decreased job strain was uniform across the range of baseline BMI. CONCLUSIONS: Women with higher BMI may be more vulnerable to BMI gain when exposed to constant work stress. Future research focusing on mediating mechanisms between job strain and BMI change should explore the possibility of differential responses to job strain by initial BMI.

Maternal experiences of racial discrimination and child weight status in the first 3 years of life.

Among US racial/ethnic minority women, we examined associations between maternal experiences of racial discrimination and child growth in the first 3 years of life. We analyzed data from Project Viva, a pre-birth cohort study. We restricted analyses to 539 mother-infant pairs; 294 were Black, 127 Hispanic, 110 Asian and 8 from additional racial/ethnic groups. During pregnancy, mothers completed the Experiences of Discrimination survey that measured lifetime experiences of racial discrimination in diverse domains. We categorized responses as 0, 1-2 or ≥3 domains. Main outcomes were birth weight for gestational age z-score; weight for age (WFA) z-score at 6 months of age; and at 3 years of age, body mass index (BMI) z-score. In multivariable analyses, we adjusted for maternal race/ethnicity, nativity, education, age, pre-pregnancy BMI, household income and child sex and age. Among this cohort of mostly (58.2%) US-born and economically non-impoverished mothers, 33% reported 0 domains of discrimination, 33% reported discrimination in 1-2 domains and 35% reported discrimination in ≥3 domains. Compared with children whose mothers reported no discrimination, those whose mothers reported ≥3 domains had lower birth weight for gestational age z-score (ß -0.25; 95% CI: -0.45, -0.04), lower 6 month WFA z-score (ß -0.34; 95% CI: -0.65, -0.03) and lower 3-year BMI z-score (ß -0.33; 95% CI: -0.66, 0.00). In conclusion, we found that among this cohort of US racial/ethnic minority women, mothers' report of experiencing lifetime discrimination in ⩾ 3 domains was associated with lower fetal growth, weight at 6 months and 3-year BMI among their offspring.

Stress and the risk of multiple sclerosis.

OBJECTIVE: Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of multiple sclerosis (MS) exacerbations. We wanted to study prospectively whether stress can increase the risk of developing the disease itself. METHODS: We studied 2 cohorts of female nurses: the Nurses' Health Study (NHS) (n = 121,700) followed from 1976 and the Nurses' Health Study II (NHS II) (n = 116,671) followed from 1989. The risk of MS after self-report on general stress at home and at work in the NHS in 1982 was studied prospectively using Cox regression. Logistic regression was used to retrospectively estimate the effects of physical and sexual abuse in childhood and adolescence collected in the NHS II 2001. We identified 77 cases of MS in the NHS by 2005 and 292 in the NHS II by 2004. All analyses were adjusted for age, ethnicity, latitude of birth, body mass index at age 18, and smoking. RESULTS: We found no increased risk of MS associated with severe stress at home in the NHS (hazard ratio 0.85 [95% confidence interval (CI)] 0.32-2.26). No significantly increased risk of MS was found among those who reported severe physical abuse during childhood (odds ratio [OR] 0.68, 95% CI 0.41-1.14) or adolescence (OR 0.77, 95% CI 0.46-1.28) or those having been repeatedly forced into sexual activity in childhood (OR 1.47, 95% CI 0.87-2.48) or adolescence (OR 1.21, 95% CI 0.68-2.17). CONCLUSIONS: These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS.

Hypertension in adult survivors of child abuse: observations from the Nurses' Health Study II.

BACKGROUND: Limited research has shown a possible association between exposure to physical or sexual abuse prior to age 18 and the risk of developing hypertension as an adult. The factors mediating this relationship are unknown. METHODS: Questionnaire data from 68 505 female participants in the Nurses' Health Study II were analysed regarding exposure to physical and sexual abuse prior to age 18. Cox proportional hazards regression was used to assess the relationship between abuse exposure and hypertension. RESULTS: 64% of the participants (n=41 792) reported physical and/or sexual abuse prior to age 18; 17% reported hypertension. All forms of abuse had a dose-response relationship with hypertension. Adjustments for smoking, alcohol, family history of hypertension, exercise and oral contraceptives did not alter risk estimates. Adjustment for body mass index (BMI) significantly attenuated the associations between abuse and risk of hypertension and accounted for approximately 50% of the observed association between abuse exposure and hypertension. Women experiencing forced sexual activity as a child and as an adolescent had a 20% increased risk for developing hypertension (95% CI 8% to 32%) that was independent of BMI. Similarly, women reporting severe physical abuse in childhood and/or adolescence had risk estimates ranging from 14% (95% CI 5% to 24%) to 22% (95% CI 11% to 33%). CONCLUSION: Early interpersonal violence may be a widespread risk factor for the development of hypertension in women. BMI is a significant mediator in the relationship between early abuse and adult hypertension.

A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility.

OBJECTIVE: To evaluate whether the amount or quality of carbohydrate in diet is associated with ovulatory infertility. SUBJECTS AND METHODS: In total, 18,555 married, premenopausal women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an 8-year period. Diet was assessed two times during follow-up using a validated food-frequency questionnaire and prospectively related to the incidence of infertility due ovulatory disorder. RESULTS: During follow-up, 438 women reported ovulatory infertility. Total carbohydrate intake and dietary glycemic load were positively related to ovulatory infertility in analyses adjusted for age, body mass index, smoking, parity, physical activity, recency of contraception, total energy intake, protein intake and other dietary variables. The multivariable-adjusted risk ratio (RR) (95% confidence interval (CI)) of ovulatory infertility comparing the highest-to-lowest quintile of total carbohydrate intake was 1.91 (1.27-3.02). The corresponding RR (95% CI) for dietary glycemic load was 1.92 (1.26-2.92). Dietary glycemic index was positively related to ovulatory infertility only among nulliparous women. Intakes of fiber from different sources were unrelated to ovulatory infertility risk. CONCLUSIONS: The amount and quality of carbohydrate in diet may be important determinants of ovulation and fertility in healthy women.

Elevated midpregnancy corticotropin-releasing hormone is associated with prenatal, but not postpartum, maternal depression.

CONTEXT: Elevated hypothalamic CRH has been implicated in melancholic major depression in nonpregnant individuals, but the role of placental CRH in maternal prenatal and postpartum depression is largely unexplored. OBJECTIVE: The objective of the study was to examine the association of maternal midpregnancy plasma CRH levels with prenatal and postpartum depression. PARTICIPANTS: The study included 800 participants in Project Viva, a pregnancy and childhood cohort. METHODS: CRH levels were analyzed from blood samples obtained at mean 27.9 wk gestation (+/- 1.3 sd; range 24.6-37.4 wk) and were normalized on the logarithmic scale. Depression was assessed with the Edinburgh Postpartum Depression Scale (range 0-30 points) in midpregnancy and at 6 months postpartum. We used logistic regression to estimate the odds of scoring 13 or more points on the Edinburgh Postpartum Depression Scale as indicative of major or minor depression. RESULTS: Seventy (8.8%) and 46 (7.5%) women had prenatal and postpartum depression symptoms, respectively. Mean log CRH was 4.93 (+/- 0.62 sd). After adjusting for confounders, an sd increase in log CRH was associated with nearly 50% higher odds of prenatal depression symptoms (odds ratio 1.48, 95% confidence interval 1.14-1.93). Higher CRH levels during pregnancy were unassociated with greater risk of postpartum depressive symptoms. In fact, there was a suggestion that prenatal CRH levels might be inversely associated with risk of postpartum depressive symptoms (odds ratio 0.82, 95% confidence interval 0.58-1.15). CONCLUSIONS: Elevated placental CRH levels in midpregnancy are positively associated with risk of prenatal depression symptoms but not postpartum depression symptoms.

A prospective study of dairy foods intake and anovulatory infertility.

BACKGROUND: Dairy foods and lactose may impair fertility by affecting ovulatory function. Yet, few studies have been conducted in humans and their results are inconsistent. We evaluated whether intake of dairy foods was associated with anovulatory infertility and whether this association differed according to fat content. METHODS: We prospectively followed 18,555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant during an 8-year period. Diet was assessed twice during the study using food-frequency questionnaires. RESULTS: During follow-up, 438 women reported infertility due to an ovulatory disorder. The multivariate-adjusted relative risks (RR) [95% confidence interval (CI); P, trend] of anovulatory infertility comparing women consuming > or = 2 servings per day to women consuming < or = 1 serving per week was 1.85 (1.24-2.77; 0.002) for low-fat dairy foods. The RR (95% CI; P, trend) comparing women consuming > or = 1 serving per day of high-fat dairy foods to those consuming < or = 1 serving per week was 0.73 (0.52-1.01; 0.01). There was an inverse association between dairy fat intake and anovulatory infertility (P, trend = 0.05). Intakes of lactose, calcium, phosphorus and vitamin D were unrelated to anovulatory infertility. CONCLUSIONS: High intake of low-fat dairy foods may increase the risk of anovulatory infertility whereas intake of high-fat dairy foods may decrease this risk. Further, lactose (the main carbohydrate in milk and dairy products) may not affect fertility within the usual range of intake levels in humans.

Reproducibility and validity of maternal recall of pregnancy-related events.

We assessed the reproducibility and validity of a questionnaire that asks mothers to recall pregnancy-related events from thirty or more years ago. Among 146 women who completed the questionnaire twice, responses were highly reproducible for pre-pregnancy height and weight (r = 0.95), pregnancy complications (r = 0.74), substance use (r = 0.80), preterm delivery (r = 0.82), birthweight (r = 0.94), and breastfeeding (r = 0.89). Among 154 women whose questionnaire responses were compared to data collected during their pregnancies, recall was highly accurate for height (r = 0.90), pre-pregnancy weight (r = 0.86), birthweight (r = 0.91), and smoking (sensitivity = 0.86, specificity = 0.94). These findings suggest that long-term maternal recall is both reproducible and accurate for many factors related to pregnancy and delivery.

Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.

CONTEXT: Although many studies suggest that physical activity may reduce risk of type 2 diabetes, the role of moderate-intensity activity such as walking is not well understood. OBJECTIVES: To examine the relationship of total physical activity and incidence of type 2 diabetes in women and to compare the benefits of walking vs vigorous activity as predictors of subsequent risk of type 2 diabetes. DESIGN AND SETTING: The Nurses' Health Study, a prospective cohort study that included detailed data for physical activity from women surveyed in 11 US states in 1986, with updates in 1988 and 1992. PARTICIPANTS: A total of 70,102 female nurses aged 40 to 65 years who did not have diabetes, cardiovascular disease, or cancer at baseline (1986). MAIN OUTCOME MEASURE: Risk of type 2 diabetes by quintile of metabolic equivalent task (MET) score, based on time spent per week on each of 8 common physical activities, including walking. RESULTS: During 8 years of follow-up (534, 928 person-years), we documented 1419 incident cases of type 2 diabetes. After adjusting for age, smoking, alcohol use, history of hypertension, history of high cholesterol level, and other covariates, the relative risks (RRs) of developing type 2 diabetes across quintiles of physical activity (least to most) were 1.0, 0.77, 0.75, 0.62, and 0.54 (P for trend <.001); after adjusting for body mass index (BMI), RRs were 1.0, 0.84, 0.87, 0.77, and 0.74 (P for trend = .002). Among women who did not perform vigorous activity, multivariate RRs of type 2 diabetes across quintiles of MET score for walking were 1.0, 0.91,0.73, 0.69, and 0.58 (P for trend <.001). After adjusting for BMI, the trend remained statistically significant (RRs were 1.0, 0.95, 0.80, 0.81, 0.74; P for trend = .01). Faster usual walking pace was independently associated with decreased risk. Equivalent energy expenditures from walking and vigorous activity resulted in comparable magnitudes of risk reduction. CONCLUSIONS: Our data suggest that greater physical activity level is associated with substantial reduction in risk of type 2 diabetes, including physical activity of moderate intensity and duration.

A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.

BACKGROUND: The role of walking, as compared with vigorous exercise, in the prevention of coronary heart disease remains controversial, and data for women on this topic are sparse. METHODS: We prospectively examined the associations between the score for total physical activity, walking, and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986. Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed questionnaires about physical activity. During eight years of follow-up, we documented 645 incident coronary events (nonfatal myocardial infarction or death from coronary disease). RESULTS: There was a strong, graded inverse association between physical activity and the risk of coronary events. As compared with women in the lowest quintile group for energy expenditure (expressed as the metabolic-equivalent [MET] score), women in increasing quintile groups had age-adjusted relative risks of 0.77, 0.65, 0.54, and 0.46 for coronary events (P for trend <0.001). In multivariate analyses, the inverse gradient remained strong (relative risks, 0.88, 0.81, 0.74, and 0.66 for women in increasing quintile groups as compared with those in the lowest quintile group; P for trend=0.002). Walking was inversely associated with the risk of coronary events; women in the highest quintile group for walking, who walked the equivalent of three or more hours per week at a brisk pace, had a multivariate relative risk of 0.65 (95 percent confidence interval, 0.47 to 0.91) as compared with women who walked infrequently. Regular vigorous exercise (> or =6 MET) was associated with similar risk reductions (30 to 40 percent). Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary. CONCLUSIONS: These prospective data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women.

Birthweight and the risk for type 2 diabetes mellitus in adult women.

BACKGROUND: Previous reports have suggested an association between birthweight and type 2 diabetes mellitus. OBJECTIVE: To investigate the association between birthweight and type 2 diabetes in a large cohort of adult women, taking into account potential explanatory factors in childhood and adult life. DESIGN: Cohort study. Birthweight was ascertained at the end of follow-up. SETTING: The Nurses' Health Study, a cohort of 121,701 U.S. women born from 1921 to 1946 who have been followed since 1976. PARTICIPANTS: 69,526 women in the Nurses' Health Study who were free of diabetes at baseline and reported their own birthweight on the 1992 questionnaire. MEASUREMENT: 2123 cases of confirmed type 2 diabetes diagnosed from 1976 to 1992. RESULTS: Low birthweight was associated with increased risk for type 2 diabetes. Age-adjusted relative risks suggested a reverse J-shape association between birthweight and risk for type 2 diabetes. However, after adjustment for adult body mass index and maternal history of diabetes, an inverse association across the entire range of birthweight became apparent; compared with the reference group, relative risks by ascending birthweight category were 1.83 (95% CI, 1.55 to 2.16) for birthweight less than 5.0 lb, 1.76 (CI, 1.49 to 2.07) for birthweight 5.0 to 5.5 lb, 1.23 (CI, 1.11 to 1.37) for birthweight 5.6 to 7.0 lb, 0.95 (CI, 0.82 to 1.10) for birthweight 8.6 to 10.0 lb, and 0.83 (CI, 0.63 to 1.07) for birthweight of more than 10 lb (P for trend < 0.001). Adjustment for ethnicity, childhood socioeconomic status, and adult lifestyle factors did not substantially alter this association. The association between birthweight and risk for type 2 diabetes was strongest among women whose mothers had no history of diabetes. CONCLUSIONS: Birthweight is inversely associated with risk for type 2 diabetes during adulthood. Examination of prenatal nutrition and other potential in utero determinants of both birthweight and risk for type 2 diabetes may yield new means to prevent type 2 diabetes.

Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976.

OBJECTIVE: To examine the association between birth weight and non-fatal adult cardiovascular disease while controlling for potential confounders such as socioeconomic group and adult lifestyle. DESIGN: Retrospective self report of birth weight in an ongoing longitudinal cohort of nurses followed up by postal questionnaire every two years. SETTING: Nurses' health study, a cohort of 121700 women followed up since 1976. MAIN OUTCOME MEASURES: Non-fatal cardiovascular disease, including myocardial infarction, coronary revascularisation, and stroke. RESULTS: Among the 70297 women free of cardiovascular disease at baseline who reported birth weight in the 1992 questionnaire there were 1309 first cases of non-fatal cardiovascular disease. Increasing birth weight was associated with decreasing risk of non-fatal cardiovascular disease. There were 1216 first cases of non-fatal cardiovascular disease among women who were singletons and had been born full term; their relative risks adjusted for several cardiovascular risk factors were 1.49 (95% confidence interval 1.05 to 2.10) for birth weight < 2268 g (< 5 lb 0 oz); 1.25 (0.98 to 1.61) for birth weight 2268-2495 g (5 lb 0 oz to 5 lb 8 oz); 1.12 (0.98 to 1.27) for birth weight > 2495-3175 g (> 5 lb 8 oz to 7 lb 0 oz); 1.00 (referent) for birth weight > 3175-3856 g (> 7 lb 0 oz to 8 lb 8 oz); 0.96 (0.80 to 1.15) for birth weight > 3856-4536 g (> 8 lb 8 oz to 10 lb 0 oz); and 0.68 (0.46 to 1.00) for birth weight > 4536 g (> 10 lb 0 oz) (P value for trend = 0.0004). The inverse trend was apparent for both coronary heart disease and stroke. CONCLUSIONS: These data provide strong evidence of an association between birth weight and adult coronary heart disease and stroke.

A prospective study of body mass index, weight change, and risk of stroke in women.

OBJECTIVE: To examine the associations of body mass index (BMI) and weight change with risk of stroke in women. SETTING AND DESIGN: Prospective cohort study among US female registered nurses participating in the Nurses' Health Study. PARTICIPANTS: A total of 116759 women aged 30 to 55 years in 1976 who were free from diagnosed coronary heart disease, stroke, and cancer. MAIN OUTCOME MEASURE: Incidence of ischemic stroke, hemorrhagic stroke (subarachnoid or intraparenchymal hemorrhage), and total stroke. RESULTS: During 16 years of follow-up, 866 total strokes (including 403 ischemic strokes and 269 hemorrhagic strokes) were documented. In multivariate analyses adjusted for age, smoking, postmenopausal hormone use, and menopausal status, women with increased BMI (> or =27 kg/m2) had significantly increased risk of ischemic stroke, with relative risks (RRs) of 1.75 (95% confidence interval [CI], 1.17-2.59) for BMI of 27 to 28.9 kg/m2; 1.90 (95% CI, 1.28-2.82) for BMI of 29 to 31.9 kg/m2; and 2.37 (95% CI, 1.60-3.50) for BMI of 32 kg/m2 or more (P for trend<.001), as compared with those with a BMI of less than 21 kg/m2. For hemorrhagic stroke there was a nonsignificant inverse relation between obesity and hemorrhagic stroke, with the highest risk among women in the leanest BMI category (P for trend=.20). For total stroke the RRs were somewhat attenuated compared with those for ischemic stroke but remained elevated for women with higher BMI (P for trend<.001). In multivariate analyses that also adjusted for BMI at age 18 years, weight gain from age 18 years until 1976 was associated with an RR for ischemic stroke of 1.69 (95% CI, 1.26-2.29) for a gain of 11 to 19.9 kg and 2.52 (95% CI, 1.80-3.52) for a gain of 20 kg or more (P for trend<.001), as compared with women who maintained stable weight (loss or gain <5 kg). Although weight change was not related to risk of hemorrhagic stroke (P for trend=.20), a direct relationship was observed between weight gain and total stroke risk (P for trend<.001). CONCLUSIONS: These prospective data indicate that both obesity and weight gain in women are important risk factors for ischemic and total stroke but not hemorrhagic stroke. The relationship between obesity and total stroke depends on the distribution of stroke subtypes in the population.