Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: prospective results from a folate-replete population.

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = -0.08% (95% confidence interval (CI): -0.14,-0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [-0.10%, 95% CI: -0.17,-0.03 for each SD (~63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation.

Maternal calcium intake during pregnancy and blood pressure in the offspring at age 3 years: a follow-up analysis of the Project Viva cohort.

A previous analysis of the Project Viva cohort (eastern Massachusetts, 1999-2002 recruitment) found an association between higher second-trimester supplemental maternal calcium intake and lower systolic blood pressure in offspring at 6 months. The authors analyzed 5,527 systolic blood pressure measurements from 1,173 mother-child pairs from this same cohort when the children were aged 3 years. They estimated the change in offspring blood pressure for a 500-mg difference in maternal total, dietary-only, and supplemental-only calcium intake during the first 2 trimesters of pregnancy. Mean daily total calcium intake was 1,311 mg (standard deviation, 421) in the first trimester and 1,440 mg (standard deviation, 386) in the second trimester. Mean systolic blood pressure of the offspring at age 3 years was 92.1 mm Hg (standard deviation, 10.3). None of the maternal calcium intake measures during the first and second trimesters was associated with systolic blood pressure in the offspring. For example, for each 500-mg increment in maternal total elemental calcium intake in the second trimester, child's 3-year systolic blood pressure was 0.1 mm Hg lower (95% confidence interval: -0.9, 0.6). Maternal calcium intake during pregnancy was not associated with offspring blood pressure at the age of 3 years.

Cancer screening before and after switching to a high-deductible health plan.

BACKGROUND: Health plans with high deductibles could lead patients to avoid preventive care, such as cancer screening. OBJECTIVE: To determine the effect of membership in a high-deductible health plan on cervical, breast, and colorectal cancer screening. DESIGN: Before-after comparison between groups. SETTING: A high-deductible health plan and an HMO in Massachusetts. The high-deductible health plan fully covered mammography, Papanicolaou tests, and fecal occult blood testing (FOBT) but not colonoscopy, flexible sigmoidoscopy, or double-contrast barium enema (DCBE). PARTICIPANTS: 3169 high-deductible health plan members and 27,022 HMO members (who served as controls). MEASUREMENTS: Change in the proportions of patients undergoing breast, cervical, and colorectal cancer screening. RESULTS: Cancer screening in the high-deductible health plan group was unchanged from baseline to follow-up (adjusted ratios of change, 1.04 [95% CI, 0.91 to 1.19] for breast cancer, 1.04 [CI, 0.92 to 1.17] for cervical cancer, and 1.02 [CI, 0.89 to 1.16] for colorectal cancer). High-deductible health plan members had colonoscopy, flexible sigmoidoscopy, and DCBE less often (ratio of change, 0.73 [CI, 0.56 to 0.95]) and FOBT more often (ratio of change, 1.16 [CI, 1.01 to 1.33]) than HMO members. LIMITATIONS: Population screening frequency was probably underestimated because the study could not assess screening before the baseline year. The study may have included people ineligible for screening because of previous colectomy, mastectomy, or hysterectomy. The findings are limited to a population with relatively high socioeconomic status, which is typical of employed, commercially insured populations. CONCLUSION: Members of a high-deductible health plan did not seem to change their use of breast, cervical, and colorectal cancer screening when tests were fully covered. However, members may have substituted a fully covered screening test (FOBT) for tests subject to the deductible (colonoscopy, flexible sigmoidoscopy, and DCBE).

Changes in dietary intake from the first to the second trimester of pregnancy.

Maternal diet may influence outcomes of pregnancy and childhood. Diet in the first trimester may be more important to development and differentiation of various organs, whereas diet later in pregnancy may be important for overall fetal growth as well as for brain development. To our knowledge, no studies have examined individual-level changes in food and nutrient intake from the 1st to 2nd trimester of pregnancy. The objective of this study was to examine changes in dietary intake from the 1st to 2nd trimester of pregnancy. As part of the ongoing US prospective cohort study, Project Viva, we studied 1543 women who completed food-frequency questionnaires that assessed dietary intakes during the 1st and 2nd trimester of pregnancy. For both foods and energy-adjusted nutrients, we examined changes in dietary intake from 1st to 2nd trimester. Reported mean energy intake was similar for the 1st (2046 kcal) and 2nd (2137 kcal) trimesters. Foods and energy-adjusted nutrients from foods whose overall mean intakes increased more than 5% from 1st to 2nd trimester were skim or 1% dairy foods (22%), whole-fat dairy foods (15%), red and processed meat (11%), saturated fat (6%) and vitamin D (7%). Intake of caffeinated beverages (-30%) and alcoholic beverages (-88%) decreased more than 5%. Because mean multivitamin intake increased by 35% from the 1st to 2nd trimester, total micronutrient intake increased appreciably more than micronutrient intake from foods only. Correlations across trimesters ranged from 0.32 for vitamin B12 to 0.68 for fruit and vegetables. In conclusion, for many outcomes of pregnancy and childhood, the incremental information obtained from assessing complete diet in both early and late pregnancy may not outweigh the burden to participants and investigators. However, investigators should assess caffeine, alcohol, and vitamin and supplement use in both the 1st and 2nd trimester, and consider doing so for foods and nutrients for which trimester-specific hypotheses are well substantiated.

Associations of seafood and elongated n-3 fatty acid intake with fetal growth and length of gestation: results from a US pregnancy cohort.

Previous studies, mainly among populations with high consumption of seafood, have suggested that increased marine n-3 polyunsaturated fatty acid (PUFA) intake during pregnancy promotes longer gestation and higher birth weight. Few studies have isolated the contribution of fetal growth to birth weight. Using data from 2,109 pregnant women in Massachusetts enrolled in Project Viva from 1999 to 2002, the authors examined associations of marine n-3 PUFA and seafood intake with birth weight and birth-weight-for-gestational-age z value (fetal growth) using linear regression; length of gestation using median regression; and low birth weight, preterm delivery, and being small for gestational age using logistic regression. After adjustment for maternal and child factors, birth weight was 94 (95% confidence interval: 23, 166) g lower and fetal growth z value 0.19 (95% confidence interval: 0.08, 0.31) units lower in the highest compared with the lowest quartile of first-trimester n-3 PUFA intake. Results for the second and third trimesters were similar, and findings for seafood paralleled those for n-3 PUFA. Elongated n-3 PUFA intake and seafood intake were not associated with length of gestation or risk of preterm birth. Results from this US cohort support the conclusion that seafood intake during pregnancy is associated with reduced fetal growth.

Maternal calcium intake and offspring blood pressure.

BACKGROUND: Few data exist on the intergenerational influence of calcium intake during pregnancy on offspring blood pressure. METHODS AND RESULTS: As part of the ongoing US prospective cohort study Project Viva, we analyzed 4091 Dinamap blood pressure measurements from 936 six-month-old infants whose mothers had completed food frequency questionnaires during the second trimester of pregnancy. We used mixed models to estimate effects of maternal calcium intake on offspring systolic blood pressure. Mean+/-SD daily total maternal calcium intake was 1494+/-523 mg, consisting of 1230+/-486 mg from foods and 264+/-191 mg from supplements. Mean+/-SD 6-month blood pressure was 89.9+/-12.9 mm Hg. From bottom to top quartile of dietary calcium from foods adjusted for energy intake and measurement conditions, mean infant systolic blood pressures were 91.0, 90.2, 90.9, and 90.2 mm Hg (trend P=0.62). From calcium supplements only, the values were 91.5, 90.2, 90.4, and 88.4 mm Hg (trend P=0.006). After further adjustment for demographic, anthropometric, dietary, social, and economic variables, the decrease in 6-month systolic blood pressure was -3.0 mm Hg (95% CI, -4.9 to -1.1) for each 500-mg increment of maternal supplemental calcium intake during pregnancy. We did not find evidence of effect modification by maternal vitamin D or potassium intake or by infant body mass index. First-trimester calcium intake was not associated with offspring blood pressure. CONCLUSIONS: These observational data suggest that supplementing maternal midgestational calcium intake may lower offspring blood pressure, thus helping to prevent hypertension in the next generation.