Lifetime history of gestational diabetes and cognitive function in parous women in midlife.

AIMS/HYPOTHESIS: We aimed to determine whether a history of gestational diabetes mellitus (GDM) is associated with cognitive function in midlife. METHODS: We conducted a secondary data analysis of the prospective Nurses' Health Study II. From 1989 to 2001, and then in 2009, participants reported their history of GDM. A subset participated in a cognition sub-study in 2014-2019 (wave 1) or 2018-2022 (wave 2). We included 15,906 parous participants (≥1 birth at ≥18 years) who completed a cognitive assessment and were free of CVD, cancer and diabetes before their first birth. The primary exposure was a history of GDM. Additionally, we studied exposure to GDM and subsequent type 2 diabetes mellitus (neither GDM nor type 2 diabetes, GDM only, type 2 diabetes only or GDM followed by type 2 diabetes) and conducted mediation analysis by type 2 diabetes. The outcomes were composite z scores measuring psychomotor speed/attention, learning/working memory and global cognition obtained with the Cogstate brief battery. Mean differences (ß and 95% CI) in cognitive function by GDM were estimated using linear regression. RESULTS: The 15,906 participants were a mean of 62.0 years (SD 4.9) at cognitive assessment, and 4.7% (n=749) had a history of GDM. In models adjusted for age at cognitive assessment, race and ethnicity, education, wave of enrolment in the cognition sub-study, socioeconomic status and pre-pregnancy characteristics, women with a history of GDM had lower performance in psychomotor speed/attention (ß -0.08; 95% CI -0.14, -0.01) and global cognition (ß -0.06; 95% CI -0.11, -0.01) than those without a history of GDM. The lower cognitive performance in women with GDM was only partially explained by the development of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Women with a history of GDM had poorer cognition than those without GDM. If replicated, our findings support future research on early risk modification strategies for women with a history of GDM as a potential avenue to decrease their risk of cognitive impairment.

Prepregnancy plant-based diets and risk of hypertensive disorders of pregnancy.

BACKGROUND: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce. OBJECTIVE: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy. STUDY DESIGN: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman. RESULTS: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension. CONCLUSION: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control.

Predictors of Fertility-Awareness-Based Method Use Among Women Trying to Conceive and Women Contemplating Pregnancy.

BACKGROUND: Fertility-awareness-based methods have been linked to shorter time to conception; however, little is known about the predictors of fertility-awareness-based method use among women who are currently or will soon be trying to conceive. OBJECTIVES: The aim of this study was to identify predictors of fertility-awareness-based methods use among women trying to conceive or contemplating pregnancy within the next year. METHODS: Women participating in the Nurses' Health Study 3 were asked if they were trying to become pregnant or contemplating pregnancy and whether they are using fertility-awareness-based methods. Multivariable negative binomial regression was used to identify predictors for a number of fertility-awareness-based methods used. RESULTS: Among the 23,418 women asked about pregnancy intention since 2015, 955 were trying to conceive, and 2,282 were contemplating pregnancy within the next year. The three most used fertility-awareness-based methods among women trying to conceive were menstrual cycle tracking, ovulation prediction kits, and cervical mucus monitoring. Among women contemplating pregnancy, the three most commonly used methods were menstrual cycle tracking, cervical mucus monitoring, and basal body temperature monitoring. The ongoing duration of pregnancy attempts and gravidity were associated with the number of methods used among women actively trying to conceive. When compared with women who were trying for 2 months or less, the number of methods was 29% higher when trying for 3-5 months, 45% higher when trying for 6-12 months, and 38% higher when trying for more than 1 year. Compared with nulligravid women, the number of methods was lower for women with a history of two or more pregnancies. Among women contemplating pregnancy, those who were married or in a domestic partnership used more fertility-awareness-based methods than unpartnered women. No other significant predictors of fertility-awareness-based method use were identified. DISCUSSION: Duration of ongoing pregnancy attempt and gravidity were the only significant predictors for the number of fertility-awareness-based methods used among women actively trying to conceive, whereas partnership was the only significant predictor of the number of fertility-awareness-based methods among women contemplating pregnancy.

Women's and men's intake of omega-3 fatty acids and their food sources and assisted reproductive technology outcomes.

BACKGROUND: Long-chain omega-3 fatty acids and their food sources have garnered interest as a potential nutrient with wide-range health benefits, including fertility. OBJECTIVE: This study aimed to investigate the association of women's and men's intake of omega-3 fatty acids and omega-3 rich-foods with semen quality and outcomes of infertility treatment with assisted reproductive technologies. STUDY DESIGN: Couples presenting to the Massachusetts General Hospital were invited to enroll in a prospective cohort study (2007-2020). Male and female diets were assessed using a validated 131-item food frequency questionnaire. The primary outcomes were implantation, clinical pregnancy, and live birth probabilities. The secondary outcomes included total and clinical pregnancy loss and conventional semen parameters, for males only. We estimated the relationship between intakes of omega-3 fatty acids, nuts, and fish and the probability (95% confidence interval) of study outcomes using generalized linear mixed models to account for repeated treatment cycles per participant while simultaneously adjusting for age, body mass index, smoking status, education, dietary patterns, total energy intake, and male partner diet. RESULTS: A total of 229 couples and 410 assisted reproductive technology cycles were analyzed for primary and secondary outcomes. Of note, 343 men contributing 896 semen samples were included in analyses for semen quality measures. Women's docosahexaenoic acid + eicosapentaenoic acid intake was positively associated with live birth. The multivariable-adjusted probabilities of live birth for women in the bottom and top quartiles of eicosapentaenoic acid + docosahexaenoic acid intake were 0.36 (95% confidence interval, 0.26-0.48) and 0.54 (95% confidence interval, 0.42-0.66) (P trend=.02). Eicosapentaenoic acid + docosahexaenoic acid intake was inversely related to the risk of pregnancy loss, which was 0.53 among women in the lowest quartile of eicosapentaenoic acid + docosahexaenoic acid intake and 0.05 among women in the highest quartile (P trend=.01). Men's intake of total omega-3 fatty acids was positively related to sperm count, concentration, and motility, but unrelated to any assisted reproductive technology outcomes. Similar associations were observed when evaluating the intake of primary food sources of these fatty acids. CONCLUSION: Women's consumption of omega-3 fatty acids and omega-3-rich foods may improve the probability of conception by decreasing the risk of pregnancy loss. In addition, men's intake of omega-3 fatty acids may influence semen quality.

Pre-pregnancy menstrual cycle regularity and length and the risk of gestational diabetes mellitus: prospective cohort study.

AIMS/HYPOTHESIS: Menstrual cycle dysfunction has been associated with many endocrine-related diseases, but evidence linking menstrual cycle dysfunction with gestational diabetes mellitus (GDM) is scant. The current study investigated the association of pre-pregnancy menstrual cycle regularity and length during adolescence, early adulthood and mid-adulthood with the subsequent risk of GDM. METHODS: Between 1993 and 2009, we followed 10,906 premenopausal women participating in the Nurses' Health Study II who reported menstrual cycle characteristics during adolescence (age 14-17 years), early adulthood (age 18-22 years) and mid-adulthood (age 29-46 years). Incident GDM was ascertained from a self-reported questionnaire regarding physician diagnosis. Log-binomial models with generalised estimating equations were used to estimate the RRs and 95% CI for the associations between menstrual cycle characteristics and GDM. RESULTS: We documented 578 incident cases of GDM among 14,418 pregnancies over a 16 year follow-up. After adjusting for potential confounders, women reporting always having irregular menstrual cycles during mid-adulthood had a 65% (95% CI 21, 125%) higher risk of GDM than women reporting very regular cycles. GDM risk was also greater among women reporting that their cycles were usually ≥32 days during mid-adulthood, compared with women reporting cycles between 26 and 31 days (RR 1.42 [95% CI 1.15, 1.75]). The risk of GDM was greater for women whose cycles changed from regular early in their reproductive years to irregular or from <32 days to ≥32 days during mid-adulthood, compared with women whose cycles remained <32 days or regular, respectively. CONCLUSIONS/INTERPRETATION: Women whose cycles were long or irregular during mid-adulthood, but not in adolescence or young adulthood, were at higher risk of GDM.

Men's dietary patterns in relation to infertility treatment outcomes among couples undergoing in vitro fertilization.

PURPOSE(S): To evaluate the relationship of men's dietary patterns with outcomes of in vitro fertilization (IVF). METHODS: This is a prospective cohort study including 231 couples with 407 IVF cycles, presented at an academic fertility center from April 2007 to April 2018. We assessed diet with a validated food frequency questionnaire and identified Dietary Pattern 1 and Dietary Pattern 2 using principal component analysis. We evaluated adjusted probability of IVF outcomes across the quartiles of the adherence to two dietary patterns by generalized linear mixed models. RESULTS: Men had a median age of 36.8 years and BMI of 26.9 kg/m2. Women's median age and BMI were 35.0 years and 23.1 kg/m2, respectively. Adherence to Dietary Pattern 1 (rPearson=0.44) and Dietary Pattern 2 (rPearson=0.54) was positively correlated within couples. Adherence to Dietary Pattern 1 was positively associated with sperm concentration. A 1-unit increase in this pattern was associated with a 13.33 (0.71-25.96) million/mL higher sperm concentration. However, neither Dietary Pattern 1 nor Dietary Pattern 2 was associated with fertilization, implantation, clinical pregnancy, or live birth probabilities. CONCLUSIONS: Data-derived dietary patterns were associated with semen quality but unrelated to the probability of successful IVF outcomes.

BMI status and weight trajectories across females' reproductive years and risk of adverse pregnancy outcomes: a prospective cohort study.

BACKGROUND: Prepregnancy body mass index (BMI) is a well-established risk factor of adverse pregnancy outcomes (APOs). The associations of long-term and short-term weight trajectories with APOs are less clear. OBJECTIVES: This study aimed to determine the associations of weight trajectories during females' reproductive years, before and between pregnancies, with risk of APOs. METHODS: We followed 16,241 females (25,386 singleton pregnancies) participating in a prospective cohort, the Nurses' Health Study II. Weight at age 18 y, current weight, and height were assessed at baseline (1989), and weight was updated biennially. Pregnancy history was self-reported in 2009. The primary outcome was a composite of hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm birth, and stillbirth. Secondary outcomes were individual APOs. The associations of weight change with APOs were estimated using log-binomial regression, adjusting for demographic, lifestyle, reproductive factors, and baseline BMI (in kg/m2). RESULTS: The mean (standard deviation [SD]) age at first in-study pregnancy was 33.7 (4.1) y. The mean (SD) time from age 18 y to pregnancy, baseline to pregnancy, and between pregnancies was 16.3 (4.0), 6.1 (3.0), and 2.9 (1.6) y, with a corresponding weight change of 6.4 (9.1), 3.1 (5.8), and 2.3 (4.8) kg, respectively. Of the pregnancies, 4628 (18.2%) were complicated by ≥1 APOs. Absolute weight change since age 18 y was most strongly associated with APOs. Compared with females whose weight remained stable (0-2 kg) since age 18, females who gained >2 kg had higher risk of APO (2.1-9.9 kg, relative risk [RR]: 1.12; 95% confidence interval [CI]: 1.02, 1.23; 10.0-14.9 kg, RR: 1.43; 95% CI: 1.29, 1.60; ≥15 kg, RR: 1.87; 95% CI: 1.69, 2.08), primarily driven by HDP and GDM. The associations of per 1 kg weight gain before and between pregnancies with HDP were nearly identical. CONCLUSIONS: Weight trajectories prior to and between pregnancies were associated with the risk of APOs, particularly HDP. Longer periods of weight gain, corresponding to greater absolute weight gain, were most strongly associated with higher risk of APOs.

Association of Gestational Diabetes With Subsequent Long-Term Risk of Mortality.

Importance: Gestational diabetes has been associated with numerous chronic diseases. However, few studies have examined the association of gestational diabetes with long-term mortality risk. Objective: To investigate the associations between gestational diabetes and long-term risks of total and cause-specific mortality. Design, Setting, and Participants: This cohort study analyzed participants of the Nurses' Health Study II who were followed for 30 years (1989-2019). Participants included US female nurses aged 25 to 42 years who reported at least 1 pregnancy (≥6 months) at 18 years or older across their reproductive life span. Data were analyzed from May 1, 2022, to May 25, 2023. Exposure: Gestational diabetes across the reproductive life span. Main Outcomes and Measures: Hazard ratios (HRs with 95% CIs) for total and cause-specific mortality were estimated by Cox proportional hazards regression models. Results: A total of 91 426 parous participants were included, with a mean (SD) age of 34.9 (4.7) years and a body mass index of 24.1 (4.7) at baseline. During a follow-up period of 2 609 753 person-years, 3937 deaths were documented, including 255 deaths from cardiovascular disease and 1397 from cancer. Participants with a history of gestational diabetes had a higher crude mortality rate than those without a history of gestational diabetes (1.74 vs 1.49 per 1000 person-years; absolute difference = 0.25 per 1000 person-years). The corresponding HR for total mortality was 1.28 (95% CI, 1.13-1.44), which did not materially change after additional adjustment for potential confounders and lifestyle factors during the reproductive life span (HR, 1.25; 95% CI, 1.11-1.41). The association persisted regardless of the subsequent development of type 2 diabetes and was more robust among participants who adopted less healthy lifestyles; experienced gestational diabetes in 2 or more pregnancies (HR, 1.48; 95% CI, 0.99-2.19); had gestational diabetes both in the initial and subsequent pregnancies (HR, 1.71; 95% CI, 1.11-2.63); and concurrently reported hypertensive disorders in pregnancy (HR, 1.80; 95% CI, 1.21-2.67), preterm birth (HR, 2.46; 95% CI, 1.66-3.64), or low birth weight (HR, 2.11; 95% CI, 1.21-3.68). Cause-specific mortality analyses revealed that gestational diabetes was directly associated with the risk of mortality due to cardiovascular disease (HR, 1.59; 95% CI, 1.03-2.47). Additionally, gestational diabetes was inversely associated with cancer mortality (HR, 0.76; 95% CI, 0.59-0.98); however, it was only evident among participants who later developed type 2 diabetes. Conclusions and Relevance: Results of this cohort study suggest that participants who reported a history of gestational diabetes exhibited a small but elevated risk of subsequent mortality over 30 years. The findings emphasize the importance of considering gestational diabetes as a critical factor in later-life mortality risk.

Prepregnancy Healthy Lifestyle and Adverse Pregnancy Outcomes.

OBJECTIVE: To investigate the association of healthy lifestyle factors before pregnancy (body mass index [BMI] 18.5-24.9, nonsmoking, 150 min/wk or more of moderate-to-vigorous physical activity, healthy eating [top 40% of Dietary Approaches to Stop Hypertension score], no or low-to-moderate alcohol intake [less than 15 g/d], and use of multivitamins) with risk of adverse pregnancy outcomes. METHODS: We conducted a secondary analysis of prospectively collected data for women without chronic diseases who are participating in an ongoing cohort in the United States (the NHSII [Nurses' Health Study II]). Healthy lifestyle factors preceding pregnancy were prospectively assessed every 2-4 years from 1991 to 2009 with validated measures. Reproductive history was self-reported in 2001 and 2009. A composite outcome of adverse pregnancy outcomes that included miscarriage, ectopic pregnancy, gestational diabetes, gestational hypertension, preeclampsia, preterm birth, stillbirth, or low birth weight was assessed. RESULTS: Overall, 15,509 women with 27,135 pregnancies were included. The mean maternal age was 35.1±4.2 years. Approximately one in three pregnancies (n=9,702, 35.8%) was complicated by one or more adverse pregnancy outcomes. The combination of six low-risk factors was inversely associated with risk of adverse pregnancy outcomes in a dose-dependent manner ( P for trend <.001). Compared with women who had zero or one healthy lifestyle factor, those with six had a 37% lower risk of adverse pregnancy outcomes (relative risk 0.63, 95% CI 0.55-0.72), driven primarily by lower risks of gestational diabetes, gestational hypertension, and low birth weight. All prepregnancy healthy lifestyle factors, except avoiding harmful alcohol consumption and regular physical activity, were independently associated with lower risk of adverse pregnancy outcomes after mutual adjustment for each other. Healthy BMI, high-quality diet, and multivitamin supplementation showed the strongest inverse associations with adverse pregnancy outcomes. If the observed relationships were causal, 19% of adverse pregnancy outcomes could have been prevented by the adoption of all six healthy lifestyle factors (population attributable risk 19%, 95% CI 13-26%). CONCLUSION: Prepregnancy healthy lifestyle is associated with a substantially lower risk of adverse pregnancy outcomes and could be an effective intervention for the prevention of adverse pregnancy outcomes.

Intake of soy products and soy isoflavones in relation to ovarian reserve.

OBJECTIVE: To investigate the association between intake of soy food and isoflavone with ovarian reserve. Previous studies suggest on the relationship between soy intake and human fertility are inconsistent. Some clinical studies suggest that soy and phytoestrogens may not be deleterious to reproduction and may even be beneficial in couples undergoing infertility treatment. However, no studies have evaluated the relationship between soy or isoflavone intake with markers of ovarian reserve other than follicle-stimulating hormone (FSH). DESIGN: Cross-sectional study. SETTING: An academic fertility center. PATIENT(S): Patients presenting to an academic fertility center between 2007 and 2019 were invited to participate in the Environment and Reproductive Health Study. INTERVENTION(S): Six hundred and sixty seven participants reported their soy food intake and had an antral follicle count (AFC) assessment. Intake of 15 soy-based foods during the previous 3 months was obtained at baseline and intake of isoflavone was estimated. Participants were divided into 5 groups based on soy food and isoflavone intake considering those who did not consume soy as the reference group. MAIN OUTCOME MEASURE(S): Ovarian reserve was assessed using AFC as the primary outcome measure, with antimüllerian hormone (AMH) and FSH as secondary outcome measures. The AFC was measured on the third day of the menstrual cycle. Moreover, FSH and AMH levels were measured in blood samples obtained on the third day and the follicular phase of the menstrual cycle. To evaluate the association between soy intake and ovarian reserve, we used Poisson regression models for AFC and quantile regression models for AMH and day 3 FSH levels by adjusting for confounders. RESULT(S): Participants had a median age of 35.0 years. The median intake of soy was 0.09 servings/day and isoflavones was 1.78 mg/day. Moreover, AFC, AMH, and FSH were unrelated to soy intake in crude analyses. We found no association between soy food intake with AFC or day 3 FSH level in multivariable models. However, participants in the highest category of soy food intake had significantly low AMH levels (-1.16, 95% confidence interval: -1.92, -0.41). Soy intake had no association with AFC, AMH, or FSH in sensitivity analyses that included using different cutoff points of soy intake, excluding participants in the highest 2.5 percentile of intake, and additional statistical adjustment for dietary patterns. CONCLUSION(S): The results of this study are not consistent with a strong positive or inverse association of soy or isoflavone intakes within the observed range of intake, which substantially overlaps with that in the general population of the United States as well as the ovarian reserve among individuals presenting to fertility centers.

Women's Adherence to Healthy Dietary Patterns and Outcomes of Infertility Treatment.

Importance: Increasing evidence suggests that specific foods and nutrients may improve infertility treatment outcomes in women. However, less is known about the role of dietary patterns. Objective: To investigate whether women's adherence to a priori-defined dietary patterns promoted for the prevention of chronic conditions is associated with outcomes of infertility treatment. Design, Setting, and Participants: This prospective cohort study was conducted at a fertility center at an academic medical center in Boston, Massachusetts. Women undergoing infertility treatment cycles, including intrauterine insemination cycles and in vitro fertilization with or without intracytoplasmic sperm injection were included. Data were collected from January 2007 to October 2019, and data were analyzed from February to December 2022. Exposures: Women's pretreatment diet was assessed with a validated food frequency questionnaire from which 8 a priori-defined scores were calculated (higher score indicates greater adherence): (1) Trichopoulou Mediterranean diet, (2) alternate Mediterranean diet, (3) Panagiotakos Mediterranean diet, (4) Healthy Eating Index, (5) Alternate Healthy Eating Index, (6) American Heart Association (AHA) index, (7) Dietary Approaches to Stop Hypertension index, and (8) plant-based diet. Main Outcomes and Measures: The adjusted probability of clinically relevant outcomes (live birth as a primary outcome and clinical pregnancy and pregnancy loss as secondary outcomes) was evaluated across quartiles of adherence to each dietary pattern using multivariable generalized linear mixed models to account for repeated cycles. Results: This analysis included 612 women with a median (IQR) age of 35.0 (32.0-38.0) years. There was no association between women's adherence to the 8 a priori dietary patterns and probability of clinical pregnancy or live birth following in vitro fertilization or intrauterine insemination. However, an inverse association was found between adherence to AHA dietary pattern and risks of total and clinical pregnancy loss. Among women who became pregnant during the course of infertility treatment, the adjusted probabilities of pregnancy loss in the lowest and highest quartile of the AHA dietary pattern were 0.41 (95% CI, 0.33-0.50) and 0.28 (95% CI, 0.21-0.36), respectively (P for trend = .02). The corresponding adjusted probabilities of clinical pregnancy loss were 0.30 (95% CI, 0.22-0.39) and 0.15 (95% CI, 0.10-0.23) (P for trend = .007). A similar pattern was observed for all other dietary patterns, with the exception of the plant-based diet pattern. Conclusions and Relevance: Findings of this cohort study suggest that preconception adherence to the AHA diet may be associated with a lower likelihood of pregnancy loss during the course of infertility treatment.

Pregnancy Intention, Changes in Pregnancy Intention, and Pregnancy Incidence Among Female Nurses in North America.

Importance: Pregnancy intention assessment is a key element of preconception and contraceptive care. The association between a single screening question and the incidence of pregnancy is unknown. Objective: To prospectively evaluate the dynamics of pregnancy intention and pregnancy incidence. Design, Setting, and Participants: This prospective cohort study (the Nurses' Health Study 3) was conducted from June 1, 2010, to April 1, 2022, in 18 376 premenopausal, nonpregnant female nurses aged 19 to 44 years. Main Outcomes and Measures: Pregnancy intention and pregnancy status were assessed at baseline and approximately every 3 to 6 months thereafter. Cox proportional hazards regression models were used to estimate the association between pregnancy intention and pregnancy incidence. Results: A total of 18 376 premenopausal, nonpregnant women (mean [SD] age, 32.4 [6.5] years) participated in the study. At baseline, 1008 women (5.5%) were trying to conceive, 2452 (13.3%) were contemplating pregnancy within 1 year, and the remaining 14 916 (81.2%) were neither trying to conceive nor thought they would be pregnant within 1 year. A total of 1314 pregnancies were documented within 12 months of pregnancy intention assessment. The cumulative incidence of pregnancy was 38.8% in women actively trying to conceive (median [IQR] time to pregnancy, 3.3 [1.5-6.7] months), 27.6% in women contemplating pregnancy (median [IQR] time to pregnancy, 6.7 [4.2-9.3] months), and 1.7% in women neither trying to conceive nor contemplating pregnancy (median [IQR] time to pregnancy, 7.8 [5.2-10.5] months) among those who became pregnant. Women who were actively trying to conceive were 23.1 times (95% CI, 19.5-27.4 times) and women who were contemplating pregnancy were 13.0 times (95% CI, 11.1-15.2 times) more likely to conceive within 12 months than women who were neither attempting nor contemplating pregnancy. Among women contemplating pregnancy at baseline who did not get pregnant during follow up, 18.8% were actively trying and 27.6% were not trying by 12 months. Conversely, only 4.9% of women neither trying to conceive nor contemplating pregnancy within 1 year at baseline changed pregnancy intention during follow up. Conclusions and Relevance: In this cohort study of reproductive-aged nurses in North America, pregnancy intention was highly fluid among women who were contemplating pregnancy but relatively stable among women trying to conceive and women who were neither trying to conceive nor contemplating pregnancy. Pregnancy intention was strongly associated with pregnancy incidence, but the median time to pregnancy points to a relatively short time window to initiate preconception care.

Physical activity before pregnancy and the risk of hypertensive disorders of pregnancy.

BACKGROUND: It is unclear whether prepregnancy physical activity influences the risk of hypertensive disorders of pregnancy and whether any impact is similar for preeclampsia and gestational hypertension. OBJECTIVE: To evaluate the relation of prepregnancy physical activity with hypertensive disorders of pregnancy and its alignment with the current recommendations for physical activity for the general population. STUDY DESIGN: We studied 28,147 singleton pregnancies from 18,283 women without chronic hypertension, cardiovascular disease, or cancer, participating in the Nurses' Health Study-II between 1989 and 2010. The women self-reported their physical activity before pregnancy and pregnancy complications, including preeclampsia and gestational hypertension. Logistic regression models using generalized estimating equations to account for within-woman correlations across pregnancies were used to estimate the relative risk (95% confidence interval) of preeclampsia and gestational hypertension across quartiles of prepregnancy physical activity, adjusting for age at pregnancy, parity, smoking, multivitamin use, infertility history, marital status, race, year of pregnancy, and history of preeclampsia. RESULTS: We identified 842 (3.0%) pregnancies with preeclampsia and 905 (3.2%) pregnancies with gestational hypertension. Physical activity before pregnancy was related to a lower risk of hypertensive disorders of pregnancy (relative risk, 0.75 [95% confidence interval, 0.65-0.87] for women in the highest quartile compared with the lowest quartile). This relation was driven by a 39% lower risk of gestational hypertension (relative risk, 0.61; 95% confidence interval, 0.50-0.76) comparing women in the highest quartile of physical activity (≥30.6 metabolic equivalents of task-hours/week) vs women in the lowest quartile (<6.0 metabolic equivalents of task-hours/week). Women whose moderate physical activity levels exceeded those recommended in the Physical Activity Guidelines for Americans (>5 hours/week) had a 50% lower (relative risk, 0.50; 95% confidence interval, 0.36-0.69) risk of gestational hypertension than women who did not meet this recommendation (<2.5 hours/week). For vigorous physical activity, the risk of gestational hypertension was lower among the women who met (1.25-2.5 hours/week; relative risk, 0.77; 95% confidence interval, 0.64-0.93) or exceeded (>2.5 hours/week; relative risk, 0.76; 95% confidence interval, 0.62-0.92) the recommendations than women whose activity levels were below those recommended. Physical activity was not related to the risk of preeclampsia (relative risk, 0.93; 95% confidence interval, 0.76-1.14). CONCLUSION: Physical activity before pregnancy may lower the risk of developing gestational hypertension but not preeclampsia.

Importance of human papillomavirus vaccination leaflets focusing on the safety profile targeted pediatricians in Japan.

OBJECTIVES: To investigate the association between providing leaflets to support pediatricians in explaining the safety of the human papillomavirus (HPV) vaccine and mother's decision to vaccinate their daughters in Japan. METHODS: In this cross-sectional study, we conducted a survey of mothers to evaluate the effect of leaflets that were created to support pediatricians in explaining the safety profile of the HPV vaccine. Mothers who provided consent for vaccination before receiving an explanation were excluded from the study. The primary outcome was the mother's decision to vaccinatetheir daughters with the HPV vaccine after receiving an explanation from pediatricians using our leaflets. RESULTS: Among 161 eligible mothers, 101 decided on HPV vaccination (decided group) and 60 did not (decided against group). There was no difference in the maternal background between the 2 groups. The decided group had a significantly more positive impression of the leaflets than the undecided group. In multivariable logistic regression analysis, a detailed explanation for possible adverse events and specific solutions to them was associated with the mother's decision to have their daughters vaccinated (odds ratio 2.35, 95% confidence interval 1.02-5.44), but not the pathology of cervical cancer and the HPV vaccination process. CONCLUSION: Leaflets emphasizing an explanation of adverse events may contribute to mothers' decision making for HPV vaccination.

Beverage intake and ovarian reserve among women from a fertility center.

OBJECTIVE: To evaluate the associations of caffeinated, alcoholic, and sweetened beverage intakes with antral follicle count (AFC), a well-accepted biomarker of ovarian reserve. DESIGN: Observational prospective cohort study. SETTING: Fertility center at an academic hospital. PATIENTS: This study includes 567 women seeking fertility care at the Massachusetts General Hospital who participated in the Environment and Reproductive Health Study. INTERVENTION: None. Women self-reported consumption of caffeinated (coffee, tea, soda), alcoholic (wine, beer, liquor), sugar-sweetened, and artificially sweetened beverages using a validated food-frequency questionnaire. MAIN OUTCOME MEASURE: Antral follicle count was assessed using a transvaginal ultrasound performed on the 3rd day of an unstimulated menstrual cycle or on the 3rd day of a progesterone withdrawal bleed. RESULTS: Median (interquartile range) age and AFC were 35.0 (32.0-38.0) years and 13.0 (9.0-18.0), respectively. Median (range) intake of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages in servings/day were 1.08 (0-7.08), 0.35 (0-3.84), 0.04 (0-4.80), and 0.04 (0-7.50), respectively. All examined beverages were unrelated to AFC. The multivariable adjusted mean AFC (95% confidence interval) for women in the top and bottom quartiles of intake were 13.8 (13.0-14.7) and 13.8 (12.9-14.7) for caffeinated beverages; 13.8 (13.0-14.7) and 13.8 (13.0-14.6) for alcoholic beverages; 13.5 (12.6-14.4) and 13.3 (12.4-14.2) for sugar-sweetened beverages; and 13.2 (12.4-14.1) and 13.4 (12.6-14.3) for artificially sweetened beverages. CONCLUSION: Low-to-moderate intakes of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages were unrelated to ovarian reserve, as measured by AFC, in a cohort of women seeking fertility care.

Pre-pregnancy fat intake in relation to hypertensive disorders of pregnancy.

BACKGROUND: Many studies have linked intakes of fat and of specific fatty acids during pregnancy with preeclampsia; however, information on the association of intake before pregnancy with hypertensive disorders of pregnancy (HDP) is scant. OBJECTIVES: We evaluated the associations of intakes of major and specific types of fat before pregnancy with the risks of HDP, including preeclampsia and gestational hypertension (GHTN). METHODS: We followed 11,535 women without chronic disease participating in the Nurses' Health Study II from 1991 and 2009. Pre-pregnancy dietary fat was assessed by an FFQ. Intakes of total fat, saturated fat, trans fatty acid (TFA), MUFAs, PUFAs, and fat subtypes (omega-3 and omega-6) were categorized into quintiles of intake. HDP were self-reported. The RRs (95% CIs) of HDP were estimated by log-binomial generalized estimating equation regression models, with an exchangeable correlation matrix to account for repeated pregnancies while adjusting for potential confounders. RESULTS: During 19 years of follow-up, there were 495 cases of preeclampsia (2.9%) and 561 (3.3%) cases of GHTN in 16,892 singleton pregnancies. The mean age at pregnancy was 34.6 years (SD, 3.9 years). Among major fat types, only pre-pregnancy TFA was related to a higher risk of HDP (RR, 1.32; 95% CI: 1.05-1.66), and only for preeclampsia (RR, 1.50; 95% CI: 1.07-2.10) but not for GHTN (RR, 1.21; 95% CI: 0.87-1.70). Among specific types of PUFAs, intake of arachidonic acid was positively related with GHTN (RR, 1.43; 95% CI: 1.00-2.04) but not preeclampsia (RR, 1.08; 95% CI: 0.75-1.57). In analyses restricted to pregnancies 1 year after the diet assessment, women with the highest intake of long-chain omega-3 fatty acids had a 31% lower risk of HDP (95% CI: 3%-51%), which was driven by preeclampsia (RR, 0.55; 95% CI: 0.33-0.92). CONCLUSIONS: Pre-pregnancy intakes of total fat, saturated fat, and MUFA were unrelated to HDP, whereas TFA was positively related to HDP. These findings highlight the importance of ongoing efforts to eliminate TFA from the global food supply.

Paternal adherence to healthy dietary patterns in relation to sperm parameters and outcomes of assisted reproductive technologies.

OBJECTIVE: To investigate whether men's adherence to dietary patterns promoted for the prevention of cardiovascular disease is associated with semen parameters and couples' assisted reproductive technology (ART) outcomes. DESIGN: Prospective cohort study. SETTING: Fertility center at an academic medical center. PATIENT(S): A total of 245 men and their female partners who underwent 438 ART cycles between 2007 and 2020. INTERVENTION(S): Male pretreatment dietary intake was assessed with a 131-item food frequency questionnaire from which we calculated eight a priori defined scores: Trichopoulou Mediterranean, Alternate Mediterranean, Panagiotakos Mediterranean, Healthy Eating Index, Alternative Healthy Eating Index, American Heart Association, Dietary Approaches to Stop Hypertension, and Plant-based. MAIN OUTCOME MEASURE(S): The primary outcome was live births per treatment cycle. The secondary outcomes were fertilization, implantation, and clinical pregnancy and seminogram parameters. RESULT(S): There was an inverse association between greater adherence by men to the Panagiotakos Mediterranean diet and the American Heart Association dietary pattern and lower fertilization rate. However, there were no significant associations between men's adherence to any of the analyzed dietary patterns and the probabilities of implantation, clinical pregnancy, or live birth in multivariable-adjusted models. No significant differences in any of the semen parameters were found between participants of the lowest quartile and those of the highest quartile of the eight dietary patterns. CONCLUSION(S): These findings suggest that men's adherence to several a priori defined dietary scores with documented cardiovascular benefits is not related to major outcomes of infertility treatment with ART or semen quality.

Access to HPV vaccination in Japan: Increasing social trust to regain vaccine confidence.

Vaccine hesitancy is a growing concern in global public health, and illustrates serious problems arising from loss of social trust. Japan is experiencing a human papillomavirus (HPV) vaccine crisis that started with a rapid decline in the vaccination rate in 2013 from approximately 70% to less than 1% and lasting for 7 years. We analyze Japan's case of vaccine hesitancy for HPV vaccine, using a framework for examining barriers to access and use of health technologies according to four categories: architecture, availability, affordability, and adoption. Significant problems were identified in the architecture of the decision-making body, public information availability, adoption of evidence in policy-making process, knowledge and confidence among providers, education to the public, and communication with end-users. We propose a series of actions to address these barriers. The national government should diversify the advisory committee to include broader scientific evidence and various viewpoints. Municipalities should actively distribute information cooperating with local providers. Professional associations should create an alliance to influence policy makers and deliver education to health care providers and end-users. Politicians should integrate opinions from citizens and scientists to implement an up-to-date policy. Civil society should share individual stories from cervical cancer patients and positive experiences of vaccinated girls. Mass media should use more diverse sources of information to report more comprehensive and science-based views. These actions would help build mutual trust among stakeholders, which is required to increase social trust in the HPV vaccine in Japan and thereby regain vaccine confidence and reduce preventable deaths and complications.

A dietary score representing the overall relation of men's diet with semen quality in relation to outcomes of infertility treatment with assisted reproduction.

OBJECTIVE: To examine the impact of men's diet on outcomes of infertility treatment with assisted reproductive technology (ART) using an empirical score representing the relation of diet with semen quality. DESIGN: Prospective cohort study. SETTING: Fertility center at an academic medical center. PATIENTS: We included 296 men (688 semen samples) to identify an empirical dietary pattern and 231 couples (406 ART cycles) to investigate the association of this diet pattern with ART outcomes. INTERVENTIONS: Men's diet was assessed at baseline using a validated questionnaire. An empirical dietary pattern reflecting the overall relation of diet with semen quality was identified using reduced rank regression. MAIN OUTCOME MEASURES: The primary outcome was live birth per treatment cycle. The secondary outcomes were fertilization, implantation, and clinical pregnancy. RESULTS: Men had a median baseline age and body mass index of 36.8 years and 26.9 kg/m2, respectively. Although the empirical diet pattern was significantly associated with all semen parameters, the empirical diet score was not related to any clinical outcome of infertility treatment after ART. The adjusted probabilities of relevant clinical outcomes in the lowest and highest quartiles of the empirical score were 0.62 (0.50-0.73) and 0.55 (0.45-0.66) for implantation, 0.57 (0.46-0.69) and 0.50 (0.40-0.61) for clinical pregnancy, and 0.49 (0.37-0.62) and 0.36 (0.25-0.48) for live birth. Analyses excluding couples with a diagnosis of male factor infertility and, separately, excluding intracytoplasmic sperm injection cycles yielded similar results. CONCLUSIONS: A dietary score representing the overall association of diet with semen quality parameters was not associated with ART outcomes.