The association between first-trimester omega-3 fatty acid supplementation and fetal growth trajectories.

BACKGROUND: Prenatal omega-3 fatty acid supplementation, particularly docosahexaenoic acid and eicosapentaenoic acid, has been associated with greater birthweight in clinical trials; however, its effect on fetal growth throughout gestation is unknown. OBJECTIVE: This study aimed to examine the association between first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation and growth trajectories of estimated fetal weight and specific fetal biometrics measured longitudinally from the second trimester of pregnancy to delivery. STUDY DESIGN: In a multisite, prospective cohort of racially diverse, low-risk pregnant women, we used secondary data analysis to examine fetal growth trajectories in relation to self-reported (yes or no) first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation. Fetal ultrasonographic measurements, including abdominal circumference, biparietal diameter, femur length, head circumference, and humerus length, were measured at enrollment (8-13 weeks) and up to 5 follow-up visits. Estimated fetal weight and head circumference-to-abdominal circumference ratio (a measure of growth symmetry) were calculated. Fetal growth trajectories were modeled for each measure using a linear mixed model with cubic splines. If significant differences in fetal growth trajectories between groups were observed (global P<.05), weekly comparisons were performed to determine when in gestation these differences emerged. Analyses were adjusted for maternal sociodemographics, parity, infant sex, total energy consumption, and diet quality score. All analyses were repeated using dietary docosahexaenoic acid and eicosapentaenoic acid intake, dichotomized at the recommended cutoff for pregnant and lactating women (≥0.25 vs <0.25 g/d), among women who did not report supplement intake in the first trimester of pregnancy were repeated. RESULTS: Among 1535 women, 143 (9%) reported docosahexaenoic acid and eicosapentaenoic acid supplementation in the first trimester of pregnancy. Overall, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with statistically significant differences (P-value <.05) in fetal growth trajectories during pregnancy. Specifically, estimated fetal weight was larger among women with docosahexaenoic acid and eicosapentaenoic acid supplementation than among those without supplementation (global P=.028) with significant weekly differences in median estimated fetal weight most apparent between 38 to 41 weeks of gestation (median estimated fetal weight difference at 40 weeks of gestation, 114 g). Differences in fetal growth trajectories for abdominal circumference (P=.003), head circumference (P=.003), and head circumference-to-abdominal circumference ratio (P=.0004) were also identified by supplementation status. In weekly comparisons, docosahexaenoic acid and eicosapentaenoic acid supplement use was associated with larger median abdominal circumference (changed from 2 to 9 mm) in midpregnancy onward (19 to 41 weeks), larger median head circumference between 30 to 33 weeks of gestation, and smaller median head circumference-to-abdominal circumference ratio in the second and third trimesters of pregnancy. There was no specific weekly difference in fetal femur length or humerus length by docosahexaenoic acid and eicosapentaenoic acid supplementation. First-trimester dietary sources of docosahexaenoic acid and eicosapentaenoic acid among women with no first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation (n=1392) were associated with differences in fetal biparietal diameter (P=.043), but not other metrics of fetal growth. At the recommended dietary docosahexaenoic acid and eicosapentaenoic acid levels compared with below-recommended levels, biparietal diameter was larger between 38 to 41 weeks of gestation. CONCLUSION: In this racially diverse pregnancy cohort, first-trimester docosahexaenoic acid and eicosapentaenoic acid supplementation was associated with significant increases in fetal growth, specifically greater estimated fetal abdominal circumference in the second and third trimesters of pregnancy.

Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes - a prospective study.

BACKGROUND: Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life. OBJECTIVE: This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM. METHODS: We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption. RESULTS: A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003). CONCLUSIONS: Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile.

Racial/Ethnic Differences in Prenatal Supplement and Medication Use in Low-Risk Pregnant Women.

OBJECTIVE: This study aimed to describe the overall quantity and type of supplements and medications used during pregnancy in a low-risk cohort and to examine any racial/ethnic differences in intake. STUDY DESIGN: We used data from 2,164 racially/ethnically diverse, nonobese, and low-risk pregnant women participating without pre-pregnancy chronic conditions in a prospective cohort study at 12 sites across the United States. Medication data were self-reported as free text in enrollment, follow-up visit questionnaires, and abstracted from medical records at delivery. Supplements and medications data were mapped to their active ingredients and categorized into corresponding classes using the Slone Drug Dictionary. The total number and classes of supplements and medications consumed during pregnancy were calculated. Modified Poisson regression models were used to estimate the racial/ethnic differences in supplements and medications intake. All models were adjusted for maternal sociodemographic factors and study site. RESULTS: 98% of women took at least one supplement during pregnancy, with prenatal vitamins/multivitamins being most common. While only 31% reported taking no medications during pregnancy, 23% took one, 18% took two, and 28% took three or more. The percentage of women taking at least one medication during pregnancy was highest among non-Hispanic white women and lowest among Asians (84 vs. 55%, p < 0.001). All racial/ethnic groups reported taking the same top four medication classes including central nervous system agents, gastrointestinal drugs, anti-infective agents, and antihistamines. Compared with non-Hispanic white women, Hispanic (adjusted relative risk [aRR]: 0.84, 95% confidence interval [CI]: 0.71-0.98), and Asian women (aRR: 0.83, 95% CI: 0.70-0.98) were less likely to take central nervous system agents, as well as gastrointestinal drugs (Hispanics aRR: 0.79, 95% CI: 0.66-0.94; Asians aRR = 0.75, 95% CI: 0.63-0.90), and antihistamines (Hispanics aRR: 0.65, 95% CI: 0.47-0.92). CONCLUSION: Supplement intake was nearly universal. Medication use was also common among this low-risk pregnancy cohort and differed by race/ethnicity. GOV IDENTIFIER: NCT00912132. KEY POINTS: · In women without chronic conditions, medication use is common.. · Racial/ethnic differences exist in prenatal medications use.. · Almost all women use supplements during pregnancy..

Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies.

BACKGROUND: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM). METHODS AND FINDINGS: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (

Preconception and Prenatal Nutrition and Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis.

Preconception and prenatal nutrition is critical for fetal brain development. However, its associations with offspring neurodevelopmental disorders are not well understood. This study aims to systematically review the associations of preconception and prenatal nutrition with offspring risk of neurodevelopmental disorders. We searched the PubMed and Embase for articles published through March 2019. Nutritional exposures included nutrient intake or status, food intake, or dietary patterns. Neurodevelopmental outcomes included autism spectrum disorders (ASD), attention deficit disorder-hyperactivity (ADHD) and intellectual disabilities. A total of 2169 articles were screened, and 20 articles on ASD and 17 on ADHD were eventually reviewed. We found an overall inverse association between maternal folic acid or multivitamin supplementation and children's risk of ASD; a meta-analysis including six prospective cohort studies estimated an RR of ASD of 0.64 (95% CI: 0.46, 0.90). Data on associations of other dietary factors and ASD, ADHD and related outcomes were inconclusive and warrant future investigation. Future studies should integrate comprehensive and more objective methods to quantify the nutritional exposures and explore alternative study design such as Mendelian randomization to evaluate potential causal effects.

A Prospective Study of Early Pregnancy Essential Metal(loid)s and Glucose Levels Late in the Second Trimester.

CONTEXT: Studies suggest many essential trace metal(loid)s are involved in glucose metabolism, but the associations among pregnant women are unclear. OBJECTIVE: To assess associations between early pregnancy plasma zinc, selenium, copper, and molybdenum levels and blood glucose levels later in the second trimester. DESIGN: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies‒Singleton Cohort is a prospective cohort study conducted between July 2009 and January 2013. SETTING: Twelve academic research hospitals in the United States. PATIENTS: A total of 1857 multiracial, nonobese, healthy women. MAIN OUTCOME MEASURE: Blood glucose levels from 1-hour 50-g gestational load test (GLT) at 24 to 28 weeks of gestation. RESULTS: Higher concentrations of first-trimester copper were associated with higher glucose levels from the GLT (i.e., every 50% increase in copper concentration was related to 4.9 mg/dL higher glucose level; 95% CI: 2.2, 7.5 mg/dL) adjusted for maternal sociodemographic characteristics and reproductive history. In contrast, every 50% increase in molybdenum concentration was associated with 1.2 mg/dL lower mean glucose level (95% CI: -2.3, -0.1 mg/dL). The magnitude of these associations was greater at the upper tails of glucose level distribution based on quantile regressions of the 10th, 50th, and 90th percentiles. CONCLUSIONS: Higher copper and lower molybdenum concentrations could increase the risk of glucose dysregulation during pregnancy, with women at higher risk of gestational diabetes mellitus potentially affected to a greater extent. Further work is needed to understand the mechanisms involved with early pregnancy essential metal(loid)s to inform clinical diagnosis and prevention of glucose intolerance during pregnancy.

Prepregnancy Habitual Intakes of Total, Supplemental, and Food Folate and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.

OBJECTIVE: To identify novel modifiable risk factors of gestational diabetes mellitus (GDM) by examining the association between prepregnancy habitual folate intake and GDM risk. RESEARCH DESIGN AND METHODS: The study included 14,553 women in the Nurses' Health Study II who reported at least one singleton pregnancy between the 1991 and 2001 questionnaires. Prepregnancy intakes of total folate, supplemental folate, and food folate were assessed using a food frequency questionnaire administered every 4 years. Incident GDM was ascertained from a self-reported physician diagnosis. Relative risks (RRs) of GDM were estimated using log-binomial models, with adjustment for demographic, lifestyle, and dietary factors. RESULTS: Over the study follow-up, 824 incident GDM cases were reported among 20,199 pregnancies. Women with adequate total folate intake (≥400 µg/day) had an RR of GDM of 0.83 (95% CI 0.72, 0,95, P = 0.007) compared with women with inadequate intake (<400 µg/day). This association was entirely driven by supplemental folate intake. The RRs of GDM for 1-399, 400-599, and ≥600 µg/day of supplemental folate intake were 0.83, 0.77, and 0.70, respectively, compared with no supplemental folate intake (P trend = 0.002). The association between supplemental folate intake and GDM risk largely persisted after additional adjustment for intake of multivitamins and other micronutrients, as well as among women who likely planned for the pregnancy. CONCLUSIONS: Higher habitual intakes of supplemental folate before pregnancy were significantly associated with lower GDM risk. If confirmed, these findings indicate that prepregnancy folic acid supplementation could offer a novel and low-cost avenue to reduce GDM risk.

Longitudinal Maternal Vitamin D Status during Pregnancy Is Associated with Neonatal Anthropometric Measures.

Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the current study was to examine the associations of longitudinal measures of maternal 25(OH)D and neonatal anthropometry at birth. This study included 321 mother⁻offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies⁻Singletons. This study was a prospective cohort design without supplementation and without data on dietary supplementation. Nevertheless, measurement of plasma 25(OH)D reflects vitamin D from different sources, including supplementation. Maternal concentrations of total 25(OH)D were measured at 10⁻14, 15⁻26, 23⁻31, and 33⁻39 GW and categorized as <50 nmol/L, 50⁻75 nmol/L, and >75 nmol/L. Generalized linear models were used to examine associations of 25(OH)D at each time-point with neonate birthweight z-score, length, and sum of skinfolds at birth. At 10⁻14 GW, 16.8% and 49.2% of women had 25(OH)D <50 nmol/L and between 50⁻75 nmol/L, respectively. The association of maternal 25(OH)D with neonatal anthropometry differed by GW and women's prepregnancy BMI (normal (<25.0 kg/m²), overweight/obese (25.0⁻44.9 kg/m²)). All analyses were stratified by prepregnancy BMI status. Among women with an overweight/obese BMI, 25(OH)D <50 nmol/L at 10⁻14 GW was associated with lower birthweight z-score (0.56; 95% CI: -0.99, -0.13) and length (-1.56 cm; 95% CI: -3.07, -0.06), and at 23⁻31 GW was associated with shorter length (-2.77 cm; 95% CI: -13.38, -4.98) and lower sum of skinfolds (-9.18 mm; 95% CI: -13.38, -4.98). Among women with a normal BMI, 25(OH)D <50 nmol/L at 10⁻14 GW was associated with lower sum of skinfolds (-2.64 mm; 95% CI: -5.03, -0.24), at 23⁻31 GW was associated with larger birthweight z-scores (0.64; 95% CI: 0.03, 1.25), and at 33-39 GW with both higher birthweight z-score (1.22; 95% CI: 0.71, 1.73) and longer length (1.94 cm; 95% CI: 0.37, 3.52). Maternal 25(OH)D status during pregnancy was associated with neonatal anthropometric measures, and the associations were specific to GW of 25(OH)D measurement and prepregnancy BMI.

Prepregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the effect of vitamin D intake, either from the diet or from supplements, on the development of gestational diabetes mellitus (GDM) remains unclear. We prospectively examined the association of prepregnancy habitual intake of vitamin D from diet and supplements with the risk of incident GDM in a well-established cohort. METHODS: The present study was performed on 21 356 singleton pregnancies from 15 225 women in the Nurses' Health Study II cohort. Diet information, including vitamin D intake from food sources and supplements, was assessed in 1991 and every 4 years thereafter by validated food frequency questionnaires. Log-binomial models with generalized estimating equations were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During 10 years of follow-up, 865 incident GDM cases were documented. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1-399, and ≥400 IU/day were 1.00 (reference), 0.80 (0.67-0.96), and 0.71 (0.56-0.90), respectively (Ptrend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. CONCLUSIONS: Prepregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.

Dietary iron intake, iron status, and gestational diabetes.

Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM.

A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort.

AIMS/HYPOTHESIS: The aim of this study was to prospectively and longitudinally investigate maternal iron status during early to mid-pregnancy, and subsequent risk of gestational diabetes mellitus (GDM), using a comprehensive panel of conventional and novel iron biomarkers. METHODS: A case-control study of 107 women with GDM and 214 controls (matched on age, race/ethnicity and gestational week during blood collection) was conducted within the the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort (2009-2013), a prospective and multiracial pregnancy cohort. Plasma hepcidin, ferritin and soluble transferrin receptor (sTfR) were measured and sTfR:ferritin ratio was derived, twice before GDM diagnosis (gestational weeks 10-14 and 15-26) and at weeks 23-31 and 33-39. GDM diagnosis was ascertained from medical records. Adjusted ORs (aORs) for GDM were estimated using conditional logistic regression analysis, adjusting for demographics, prepregnancy BMI and other major risk factors. RESULTS: Hepcidin concentrations during weeks 15-26 were 16% higher among women with GDM vs controls (median 6.4 vs 5.5 ng/ml; p = 0.02 ), and were positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.61 (1.07, 6.36). Ferritin levels were also positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.43 (1.12, 5.28) at weeks 10-14 and 3.95 (1.38, 11.30) at weeks 15-26. The sTfR:ferritin ratio was inversely related to GDM risk; the aOR (95% CI) for highest vs lowest quartile was 0.33 (0.14, 0.80) at weeks 10-14 and 0.15 (0.05, 0.48) at weeks 15-26. CONCLUSIONS/INTERPRETATION: Our findings suggest that elevated iron stores may be involved in the development of GDM from as early as the first trimester. This raises potential concerns for the recommendation of routine iron supplementation among iron-replete pregnant women.

Dietary fat intake and reproductive hormone concentrations and ovulation in regularly menstruating women.

BACKGROUND: Emerging evidence suggests potential links between some dietary fatty acids and improved fertility, because specific fatty acids may affect prostaglandin synthesis and steroidogenesis. OBJECTIVE: The objective of this exploratory study was to evaluate associations between total and specific types of dietary fat intake and 1) hormone concentrations and 2) the risk of sporadic anovulation in a cohort of 259 regularly menstruating women in the BioCycle Study. DESIGN: Endogenous reproductive hormones were measured up to 8 times/cycle for up to 2 cycles, with visits scheduled with the use of fertility monitors. Dietary intake was assessed with up to four 24-h recalls/cycle. Linear mixed models and generalized linear models were used to evaluate the associations between dietary fatty acids and both reproductive hormone concentrations and ovulatory status. All models were adjusted for total energy intake, age, body mass index, and race. RESULTS: Relative to the lowest levels of percentage of energy from total fat, the highest tertile was associated with increased total and free testosterone concentrations (total: percentage change of 4.0%; 95% CI: 0.7%, 7.3%; free: percentage change of 4.1%; 95% CI: 0.5%, 7.7%). In particular, the percentage of energy from polyunsaturated fatty acids (PUFAs) in the highest tertile was associated with increases in total and free testosterone (total: percentage change of 3.7%; 95% CI: 0.6%, 6.8%; free: percentage change of 4.0%; 95% CI: 0.5%, 7.5%). The PUFA docosapentaenoic acid (22:5n-3) was not significantly associated with testosterone concentrations (P-trend = 0.86 in energy substitution models) but was associated with increased progesterone and a reduced risk of anovulation (highest tertile compared with the lowest tertile: RR: 0.42; 95% CI: 0.18, 0.95). Fat intakes were not associated with other reproductive hormone concentrations. CONCLUSIONS: These results indicate that total fat intake, and PUFA intake in particular, is associated with very small increases in testosterone concentrations in healthy women and that increased docosapentaenoic acid was associated with a lower risk of anovulation.

Long-term risk of type 2 diabetes in relation to habitual iron intake in women with a history of gestational diabetes: a prospective cohort study.

BACKGROUND: An iron overload may induce pancreatic islet damage and increase risk of diabetes. Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. OBJECTIVE: We aimed to examine the association of habitual iron intake with long-term risk of T2DM in this high-risk population. DESIGN: We included 3976 women with a history of GDM from the Nurses' Health Study II cohort as part of the ongoing Diabetes & Women's Health Study. The women were followed up through 2009. Iron intake was assessed with the use of a validated food-frequency questionnaire in 1991 and every 4 y thereafter. We used Cox proportional hazards models to estimate HRs and 95% CIs. RESULTS: We documented 641 incident T2DM cases during 57,683 person-years of observation. Adjusted HRs for T2DM for the highest quartile compared with the lowest quartile were 1.64 (95% CI: 1.20, 2.25; P-trend = 0.02) for total iron intake and 1.80 (95% CI: 1.18, 2.74; P-trend = 0.005) for dietary heme iron intake. In addition, women who consumed ≥30.0 mg supplemental Fe/d, compared with nonusers, had an adjusted HR of 1.83 (95% CI: 1.25, 2.70; P-trend = 0.002). CONCLUSION: In women with a history of GDM, greater intakes of total iron, dietary heme iron, and supplemental iron were associated with higher risk of T2DM.

Pre-pregnancy potato consumption and risk of gestational diabetes mellitus: prospective cohort study.

STUDY QUESTION: What is the association between potato consumption before pregnancy and the risk of gestational diabetes mellitus (GDM)? METHODS: This prospective cohort study included 15,632 women from the Nurses' Health Study II (1991-2001). They had no previous GDM or chronic diseases before pregnancy. Consumption of potatoes and other foods was assessed every four years. Incident first time GDM was ascertained from self reports of a physician diagnosis of GDM, which was previously validated by medical records. STUDY ANSWER AND LIMITATIONS: Over the 10 year follow-up there were 854 incident cases of GDM among 21,693 singleton pregnancies. After adjustment for age, parity, and dietary and non-dietary factors, women who consumed more potatoes before pregnancy had higher rates of developing GDM. Substitution of two servings a week of total potatoes with other vegetables, legumes, and whole grain foods was significantly associated with a 9-12% lower risk of GDM. Consumption and diabetes were self reported, and severity of diabetes was unknown. More than 90% of women were white. A causal association cannot be assumed. WHAT THIS PAPER ADDS: Higher levels of potato consumption before pregnancy are associated with greater risk of GDM, and substitution of potatoes with other vegetables, legumes, or whole grain foods might lower the risk. FUNDING, COMPETING INTERESTS, DATA SHARING: Funding was received from the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, and the American Diabetes Association (No 7-12-MN-34). The authors have no competing interests or additional data to share.

Validation of different instruments for caffeine measurement among premenopausal women in the BioCycle study.

Effects of caffeine on women's health are inconclusive, in part because of inadequate exposure assessment. In this study we determined 1) validity of a food frequency questionnaire compared with multiple 24-hour dietary recalls (24HDRs) for measuring monthly caffeine and caffeinated beverage intakes; and 2) validity of the 24HDR compared with the prior day's diary record for measuring daily caffeinated coffee intake. BioCycle Study (2005-2007) participants, women (n = 259) aged 18-44 years from western New York State, were followed for 2 menstrual cycles. Participants completed a food frequency questionnaire at the end of each cycle, four 24HDRs per cycle, and daily diaries. Caffeine intakes reported for the food frequency questionnaires were greater than those reported for the 24HDRs (mean = 114.1 vs. 92.6mg/day, P = 0.01) but showed high correlation (r = 0.73, P < 0.001) and moderate agreement (К = 0.51, 95% confidence interval: 0.43, 0.57). Women reported less caffeinated coffee intake in their 24HDRs compared with their corresponding diary days (mean = 0.51 vs. 0.80 cups/day, P < 0.001) (1 cup = 237 mL). Although caffeine and coffee exposures were highly correlated, absolute intakes differed significantly between measurement tools. These results highlight the importance of considering potential misclassification of caffeine exposure.

The impact of dietary folate intake on reproductive function in premenopausal women: a prospective cohort study.

BACKGROUND: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women. METHODOLOGY/PRINCIPAL FINDINGS: The BioCycle study (2005-2007) prospectively followed 259 healthy women aged 18-44 years from the western New York region for up to 2 menstrual cycles. Total folate and specific sources of folate were assessed up to 4 times per cycle by 24-hour recall. Estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured in serum up to 8 times per cycle, timed using fertility monitors. Anovulation was defined as a cycle with peak progesterone concentration ≤ 5 ng/mL and no LH peak in the mid/late luteal phase. Higher intake of dietary folate (in dietary equivalents) across tertiles had a marginally significant association with greater luteal progesterone levels (P trend 0.08). Higher intake of synthetic folate was significantly associated with higher luteal progesterone levels (P trend 0.05). Specifically, women in the 3(rd) tertile of synthetic folate intake had, on average, 16.0% (95% CI, 0.5-33.8%) higher luteal progesterone levels compared to women in the 1(st) tertile. Moreover, consumption of synthetic folate was significantly and inversely associated with anovulation such that women in the 3(rd) tertile had a 64% (95% CI, 8-86%) decreased odds of anovulation compared to the women in the 1(st) tertile (P trend 0.03). CONCLUSIONS/SIGNIFICANCE: These findings suggest that a diet high in synthetic folate may be associated with increased progesterone levels and lower risk of sporadic anovulation. Further study of the effect of dietary folate and folic acid supplement use on reproductive health is warranted.

Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study.

BACKGROUND: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. OBJECTIVE: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. DESIGN: Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. RESULTS: Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (ß = -0.15; 95% CI: -0.26, -0.05) and positively associated among Asian women (ß = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: ß = 0.14 (95% CI: 0.06, 0.22) and ß = 0.26 (95% CI: 0.07, 0.45), respectively. CONCLUSIONS: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race.

A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus.

OBJECTIVE: It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic ß-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM. RESEARCH DESIGN AND METHODS: A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses' Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors. RESULTS: Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87-1.43), 1.31 (1.03-1.68), 1.51 (1.17-1.93), and 1.58 (1.21-2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10-1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk. CONCLUSIONS: These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.