Prenatal n-3 long-chain fatty acid status and offspring metabolic health in early and mid-childhood: results from Project Viva.

Higher maternal and biomarker levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have been associated with improved perinatal outcomes and may also influence offspring metabolic health. Past studies were not powered to examine metabolic outcomes and few have specifically targeted metabolically vulnerable populations. We examined the associations of prenatal n-3 LCPUFA status with markers of metabolic health in early and mid-childhood in the full population as well as stratified by maternal glucose tolerance. Our data consisted of 1418 mother-child dyads from Project Viva, a longitudinal, prospective pre-birth cohort enrolled in eastern Massachusetts. We assessed maternal dietary intake of fish and n-3 LCPUFA in mid-pregnancy using a validated food frequency questionnaire. N-3 LCPUFA levels were quantified in maternal second trimester and umbilical cord plasma using liquid-gas chromatography. We assessed offspring anthropometry, adiposity, and blood pressure at early (median age: 3.2 years) and mid-childhood (median age: 7.7 years); and assayed blood samples collected at these visits for metabolic biomarkers. We report here multivariable effect estimates and 95% CI. Early childhood BMI z-score was on average 0.46 (1.03) units and waist circumference 51.3 (3.7) cm. At mid-childhood these measures were 0.39 (1.00) units and 60.0 (8.3) cm, respectively. Higher cord plasma DHA levels were associated with lower BMI z-score ((Q)uartile 4 vs. Q1: -0.21, 95% CI: -0.38, -0.03), waist circumference (Q4 vs. Q1: -0.63, 95% CI: -1.27, 0.00 cm), and leptin levels (Q4 vs. Q1: -0.36, 95% CI: -0.77, 0.05 ng/mL) in early childhood. These associations were strongest and reached significance in offspring of women with isolated hyperglycemia vs. better or worse glycemic status. Higher maternal DHA + EPA (Q4 vs. Q1: -1.59, 95% CI: -2.80, -0.38 µg/mL) and fish (≥3 vs. 0 portions/week: -2.18, 95% CI: -3.90, -0.47 µg/mL) intake was related to lower adiponectin in early childhood. None of these associations persisted with mid-childhood outcomes. We did not find associations with any of the other outcomes. This study supports early and possibly transient effects of prenatal n-3 LCPUFA status on anthropometric measures and adipokine levels. It also raises the possibility that offspring of women with isolated hyperglycemia derive the most benefits from higher n-3 LCPUFA status.

Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology.

Importance: Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. Objective: To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART). Design, Setting, and Participants: This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes. Main Outcomes and Measures: Adjusted probabilities of clinical pregnancy and live birth per treatment cycle. Results: In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (<1.0 servings/d), women in the highest quartile (≥2.3 servings/d) had 18% (95% CI, 5%-30%) lower probability of clinical pregnancy and 26% (95% CI, 13%-37%) lower probability of live birth. Intake of low-pesticide residue FVs was not significantly related to ART outcomes. Conclusions and Relevance: Higher consumption of high-pesticide residue FVs was associated with lower probabilities of pregnancy and live birth following infertility treatment with ART. These data suggest that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences.

Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania.

OBJECTIVE: To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania. STUDY DESIGN: Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood. RESULTS: One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood. CONCLUSIONS: Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00197730 and NCT00421668.

Maternal prenatal fish consumption and cognition in mid childhood: Mercury, fatty acids, and selenium.

BACKGROUND: Few studies of maternal prenatal fish intake have included biomarkers of exposure to mercury, long-chain n-3 fatty acids, and selenium, which are hypothesized to mediate associations with child neurodevelopment. OBJECTIVES: Examine associations of maternal prenatal fish intake with child neurodevelopment accounting for biomarkers. METHODS: In 1999-2002 we enrolled pregnant women into the Project Viva cohort. At median 27.9weeks gestation, we estimated maternal fish intake using food frequency questionnaires, and collected blood. We assayed erythrocytes for total mercury and selenium, and plasma for fatty acids including n-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). In mid-childhood (median 7.7years), we administered cognitive tests including the Kauffman Brief Intelligence Test (KBIT). We performed multivariable linear regression analyses adjusting for maternal and child characteristics including home environment and maternal intelligence. RESULTS: Among 1068 pairs (872 with blood), mean (SD) exposures were: maternal fish intake 1.7 (1.5)servings/week, mercury 4.0 (3.6)ng/g, DHA+EPA 98.4 (41.8)mcg/ml, selenium 205.6 (34.6)ng/ml. Child KBIT verbal scores (mean 112.2, SD 15.0) were not related to any exposures: maternal fish intake (0.15; 95% CI: -0.50, 0.79), mercury (0.08; -0.18, 0.35), DHA+EPA (0.01; -0.22, 0.24), and selenium (0.20; -0.09, 0.50). Associations with KBIT nonverbal scores and tests of memory and visual motor abilities were similarly null. Mutual adjustment for each of the exposure measures did not substantially change estimates. CONCLUSIONS: In this population with an average fish consumption of about 1 1/2 weekly servings, we did not see any evidence for an association of maternal prenatal fish intake, or of mercury, DHA+EPA, or selenium status, with verbal or non-verbal intelligence, visual motor function, or visual memory at median 7.7years of age.

Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization.

BACKGROUND: The role of early-life vitamin D in childhood allergy is controversial. OBJECTIVE: We sought to assess vitamin D exposure in early life by multiple modalities and ascertain its association with childhood allergic rhinitis and allergic sensitization. METHODS: One thousand two hundred forty-eight mother-child pairs from a US prebirth cohort unselected for any disease were studied. Vitamin D exposure was assessed by measures of maternal intake during the first and second trimesters of pregnancy and serum 25-hydroxyvitamin D (25[OH]D) levels in mothers during pregnancy, cord blood, and children at school age (median age, 7.7 years; interquartile range, 1.0 years). Tests for associations between vitamin D exposure with ever allergic rhinitis, serum total IgE level, and allergen sensitization at school age were conducted. RESULTS: The correlations between maternal intake of vitamin D during pregnancy and serum 25(OH)D levels in pregnant mothers, cord blood, and children at school age were weak to moderate (r = -0.03 to 0.53). Each 100 IU/d of food-based vitamin D intake during the first and second trimesters (equivalent to the amount of vitamin D in an 8-ounce serving of milk) was associated with 21% and 20% reduced odds of ever allergic rhinitis at school age (odds ratios of 0.79 [95% CI, 0.67-0.92] and 0.80 [95% CI, 0.68-0.93]), respectively. There were no associations between maternal supplemental vitamin D intake or serum 25(OH)D levels at any time point with ever allergic rhinitis. There were no associations between any vitamin D exposure and serum total IgE level or allergen sensitization at school age. CONCLUSIONS: Inclusion of foods containing vitamin D in maternal diets during pregnancy may have beneficial effects on childhood allergic rhinitis.

Early Pregnancy Cravings, Dietary Intake, and Development of Abnormal Glucose Tolerance.

BACKGROUND: Little is known about the relationships between pregnancy cravings, maternal diet, and development of abnormal glucose tolerance. OBJECTIVES: We examined relationships of pregnancy cravings with dietary intake and risk of developing isolated hyperglycemia (IH), impaired glucose tolerance (IGT), or gestational diabetes (GDM) later in pregnancy. DESIGN/SETTING: Among 2,022 mothers in Project Viva, a prospective birth cohort recruited from medical practices in eastern Massachusetts between 1999 and 2002, we assessed type of pregnancy craving based on self-report at mean gestation of 10.9 weeks. MAIN OUTCOME MEASURES: The outcomes were cross-sectional dietary intake from a food frequency questionnaire and incident IH, IGT, or GDM determined by glucose tolerance screening at 26 to 28 weeks. STATISTICAL ANALYSES PERFORMED: We used linear regression to analyze the cross-sectional relationships between pregnancy cravings and dietary intake and multinomial logistic regression to analyze the prospective relationships among pregnancy cravings and development of IH, IGT, or GDM. RESULTS: During the first trimester, 443 (22%) women craved sweets, 225 (11%) craved salty foods, 261 (13%) craved savory foods, and 100 (4.9%) craved starchy foods. Sweet cravings were associated with increased intake of sucrose (1.9 g/day; 95% CI 0.1 to 3.7), total fat (1.5 g/day; 95% CI 0.1 to 2.9), and saturated fat (0.8 g/day; 95% CI 0.2 to 1.4); salty cravings were associated with increased fiber (0.7 servings/day; 95% CI -0.1 to 1.6); savory cravings were associated with increased n-3 fatty acids (0.10 g/day; 95% CI 0.02 to 0.17); and starchy cravings were associated with increased carbohydrates (8.0 g/day; 95% CI 0.3 to 15.7) and decreased total fat (-2.6 g/day; 95% CI -5.2 to -0.1). Salty cravings were associated with lower risk of GDM (adjusted odds ratio 0.34, 95% CI 0.12-0.97). CONCLUSIONS: New cravings in the first trimester of pregnancy were associated with dietary intake. Craving salty foods may predict reduced risk of developing GDM, whereas craving sweet food does not appear to alter one's risk.

Dietary folate and reproductive success among women undergoing assisted reproduction.

OBJECTIVE: To prospectively evaluate the associations of folate with assisted reproductive technology outcomes within a population in the United States. METHODS: This analysis included women (n=232) in a prospective cohort study at the Massachusetts General Hospital Fertility Center. Diet was assessed before assisted reproductive technology treatment using a validated food frequency questionnaire. Intermediate and clinical endpoints of assisted reproductive technology were abstracted from medical records. Generalized linear mixed models with random intercepts to account for multiple cycles per woman were used to evaluate the association of folate intake with assisted reproductive technology outcomes adjusting for calorie intake, age, body mass index, race, smoking status, infertility diagnosis, and protocol type. RESULTS: Among the 232 women (median age 35.2 years, median folate intake 1,778 micrograms/day), higher folate intake was associated with higher rates of implantation, clinical pregnancy, and live birth. The adjusted percentage (95% confidence interval [CI]) of initiated assisted reproductive technology cycles resulting in a live birth for women in increasing quartiles of folate intake were 30% (95% CI 21-42%), 47% (95% CI 35-59%), 42% (95% CI 30-35%) and 56% (95% CI 43-67%) (P for trend=0.01). Live birth rates were 20% (95% CI 8-31%) higher among women in the highest quartile of supplemental folate intake (more than 800 micrograms/day) than among women in the lowest quartile (less than 400 micrograms/day). Higher supplemental folate intake was associated with higher fertilization rates and lower cycle failure rates before embryo transfer (P for trend=0.03 and 0.02). CONCLUSION: Higher intake of supplemental folate was associated with higher live birth rates after assisted reproductive technology treatment. LEVEL OF EVIDENCE: : II.

Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth.

OBJECTIVE: To evaluate prospectively the relationship between prepregnancy folate intake and risk of spontaneous abortion and stillbirth. METHODS: Women in the Nurses' Health Study II who self-reported a pregnancy between 1992 and 2009 were included in this analysis. Dietary folate and supplement use was assessed every 4 years, starting in 1991, by a food frequency questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously (spontaneous abortion less than 20 weeks of gestation and stillbirth 20+ weeks of gestation) and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Among the 11,072 women, 15,950 pregnancies were reported of which 2,756 (17.3%) ended in spontaneous abortion and 120 (0.8%) ended in stillbirth. Compared with women in the lowest quintile of prepregnancy folate intake (less than 285 micrograms/d), those in the highest quintile (greater than 851 micrograms/d) had a relative risk of spontaneous abortion of 0.91 (95% confidence interval [CI] 0.82-1.02) after multivariable adjustment (P trend=.04). This association was primarily attributable to intake of folate from supplements. Compared with women without supplemental folate intake (0 micrograms/d), those in the highest category (greater than 730 micrograms/d) had a relative risk of spontaneous abortion of 0.80 (95% CI 0.71-0.90) after multivariable adjustment (P trend <.001). The association of prepregnancy supplemental folate with risk of spontaneous abortion was consistent across gestational period of loss. A similar inverse trend was observed with the risk of stillbirth, which fell short of conventional significance (P trend=.06). CONCLUSIONS: Higher intake of folate from supplements was associated with reduced risk of spontaneous abortion. Women at risk of pregnancy should use supplemental folate for neural tube defect prevention and because it may decrease the risk of spontaneous abortion. LEVEL OF EVIDENCE: : II.

Vitamin D status and hypertensive disorders in pregnancy.

PURPOSE: Several studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25[OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear. METHODS: Among women enrolled in the Project Viva prenatal cohort in Massachusetts, we examined associations of 25(OH)D levels obtained at 16.4-36.9 weeks of gestation (mean 27.9 weeks) with hypertensive disorders of pregnancy, including preeclampsia (56/1591, 3.5%) and gestational hypertension (109/1591, 6.9%). RESULTS: We did not detect an association between plasma 25(OH)D concentration (mean 58, standard deviation 22 nmol/L) and preeclampsia. For each 25 nmol/L increase in 25(OH)D, the adjusted odds ratio for preeclampsia was 1.14 (95% confidence interval, 0.77-1.67). By contrast and contrary to hypothesis, higher 25(OH)D concentrations were associated with higher odds of gestational hypertension: adjusted odds ratio for gestational hypertension was 1.32 (95% confidence interval, 1.01-1.72) per each 25 nmol/L increment in 25(OH)D. Vitamin D intake patterns suggest that this association was not because of reverse causation. Although the elevated hypertension risk may be due to chance, randomized trials of vitamin D supplementation during pregnancy should monitor for gestational hypertension. CONCLUSIONS: These data do not support the hypothesis that higher 25(OH)D levels lower the overall risk of hypertensive disorders of pregnancy.

Choline intake during pregnancy and child cognition at age 7 years.

Animal models indicate that exposure to choline in utero improves visual memory through cholinergic transmission and/or epigenetic mechanisms. Among 895 mothers in Project Viva (eastern Massachusetts, 1999-2002 to 2008-2011), we estimated the associations between intakes of choline, vitamin B12, betaine, and folate during the first and second trimesters of pregnancy and offspring visual memory (measured by the Wide Range Assessment of Memory and Learning, Second Edition (WRAML2), Design and Picture Memory subtests) and intelligence (measured using the Kaufman Brief Intelligence Test, Second Edition (KBIT-2)) at age 7 years. Mean second-trimester intakes were 328 (standard deviation (SD), 63) mg/day for choline, 10.5 (SD, 5.1) µg/day for vitamin B12, 240 (SD, 104) mg/day for betaine, and 1,268 (SD, 381) µg/day for folate. Mean age 7 test scores were 17.2 (SD, 4.4) points on the WRAML 2 Design and Picture Memory subtests, 114.3 (SD, 13.9) points on the verbal KBIT-2, and 107.8 (SD, 16.5) points on the nonverbal KBIT-2. In a model adjusting for maternal characteristics, the other nutrients, and child's age and sex, the top quartile of second-trimester choline intake was associated with a child WRAML2 score 1.4 points higher (95% confidence interval: 0.5, 2.4) than the bottom quartile (P-trend = 0.003). Results for first-trimester intake were in the same direction but weaker. Intake of the other nutrients was not associated with the cognitive tests administered. Higher gestational choline intake was associated with modestly better child visual memory at age 7 years.

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.

Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort.

BACKGROUND: Exposure to polyunsaturated fatty acids (PUFAs) in early life may influence adiposity development. OBJECTIVE: We examined the extent to which prenatal n-3 (omega-3) and n-6 (omega-6) PUFA concentrations were associated with childhood adiposity. DESIGN: In mother-child pairs in the Project Viva cohort, we assessed midpregnancy fatty acid intakes (n = 1120), maternal plasma PUFA concentrations (n = 227), and umbilical cord plasma PUFA concentrations (n = 302). We performed multivariable regression analyses to examine independent associations of n-3 PUFAs, including docosahexaenoic and eicosapentaenoic acids (DHA + EPA), n-6 PUFAs, and the ratio of n-6:n-3 PUFAs, with child adiposity at age 3 y measured by the sum of subscapular and triceps skinfold thicknesses (SS + TR) and risk of obesity (body mass index ≥95th percentile for age and sex). RESULTS: Mean (±SD) DHA + EPA intake was 0.15 ± 0.14 g DHA + EPA/d, maternal plasma concentration was 1.9 ± 0.6%, and umbilical plasma concentration was 4.6 ± 1.2%. In children, SS + TR was 16.7 ± 4.3 mm, and 9.4% of children were obese. In the adjusted analysis, there was an association between each SD increase in DHA + EPA and lower child SS + TR [-0.31 mm (95% CI: -0.58, -0.04 mm) for maternal diet and -0.91 mm (95% CI: -1.63, -0.20 mm) for cord plasma] and lower odds of obesity [odds ratio (95% CI): 0.68 (0.50, 0.92) for maternal diet and 0.09 (0.02, 0.52) for cord plasma]. Maternal plasma DHA + EPA concentration was not significantly associated with child adiposity. A higher ratio of cord plasma n-6:n-3 PUFAs was associated with higher SS + TR and odds of obesity. CONCLUSION: An enhanced maternal-fetal n-3 PUFA status was associated with lower childhood adiposity.

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.

Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use.

OBJECTIVE: To determine first-trimester thyroid function values and associations with thyroperoxidase antibody (TPO-Ab) status, smoking, emesis, and iodine-containing multivitamin use. METHODS: We collected information by interview, questionnaire, and blood draw at the initial obstetric visit in 668 pregnant women without known thyroid disease. We compared thyroid-stimulating hormone (TSH), total thyroxine (T4), and free T4 index (FT4I) values by TPO-Ab status. Multiple regression was used to identify characteristics associated with thyroid function values. RESULTS: The following median (range containing 95% of the data points) thyroid function test values were obtained in 585 TPO-Ab-negative women: TSH, 1.1 mIU/L (0.04-3.6); FT4I, 2.1 (1.5-2.9); and T4, 9.9 microg/dL (7.0-14.0). The following median (range containing 95% of the data points) thyroid function test values were obtained in 83 TPO-Ab-positive women: TSH, 1.8 mIU/L (0.3-6.4) (P<.001); FT4I, 2.0 (1.4-2.7) (P = .06); and T4, 9.3 microg/dL (6.8-13.0) (P = .03) (P values denote statistically significant differences between TPO-Ab-positive and negative participants). Among TPO-Ab-negative participants, TSH level was not associated with use of iodine-containing multivitamins, smoking, or race. TSH increased 0.03 mIU/L for every year of maternal age (P = .03) and decreased by 0.3 mIU/L for every increase in parity (P<.001). T4 decreased 0.04 microg/dL for every year of maternal age (P = .04). Mean FT4I was 2.05 in smokers and 2.20 in nonsmokers (P<.01). There were no relationships between T4 or FT4I and parity, race, or iodine-containing multivitamin use. CONCLUSION: TPO-Ab status of pregnant women should be considered when constructing trimester-specific reference ranges because elevated serum TPO-Ab levels are associated with higher TSH and lower T4 values.

Diet during pregnancy and risk of preeclampsia or gestational hypertension.

PURPOSE: We sought to examine associations of first-trimester intake of calcium, n-3 and n-6 fatty acids, trans fatty acids, magnesium, folate, and vitamins C, D, and E with preeclampsia (PE) and gestational hypertension (GH). METHODS: We studied associations of diet with PE or GH among 1718 women in the prospective cohort study Project Viva, using logistic regression and adjusting for maternal age, prepregnancy body mass index, first trimester systolic blood pressure, race/ethnicity, education, and parity. We assessed first-trimester diet using a validated semiquantitative food frequency questionnaire. RESULTS: A total of 59 (3%) women developed PE, and 119 developed (7%) GH. We found a somewhat-lower risk of PE associated with higher intake of the elongated n-3 fatty acids docosahexaenoic and eicosapentaenoic acids (odds ratio [OR] 0.84, 95% confidence interval [95% CI]: 0.69-1.03 per 100 mg/day), fish (OR 0.91, 95% CI 0.75-1.09 per serving/day), and the ratio of docosahexaenoic + eicosapentaenoic to arachadonic acid (OR 0.82, 95% CI 0.66-1.01). We did not observe a lower risk of GH or PE with a greater intake of calcium; vitamin C, D, or E; milk; magnesium; folate; or with lower intake of n-6 or trans fatty acids. CONCLUSIONS: Our results support a potential benefit for elongated n-3 fatty acids in preventing preeclampsia.

Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age.

BACKGROUND: Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown. OBJECTIVE: We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age. DESIGN: The participants were 1194 mother-child pairs in Project Viva-a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index (>or=2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma). RESULTS: The mean (+/-SD) total vitamin D intake during pregnancy was 548 +/- 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend < 0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results. CONCLUSION: In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood.

Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age.

BACKGROUND: Low intakes of dietary antioxidants may contribute to increases in asthma and allergy. OBJECTIVE: We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children. DESIGN: Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated, and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year. RESULTS: No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% CI: 0.48, 1.03] and zinc (OR: 0.59; 95% CI: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% CI: 0.27, 0.90) and zinc (OR: 0.49; 95% CI: 0.27, 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively). CONCLUSION: Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.

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.