Bisphenol-A and phthalate metabolism in children with neurodevelopmental disorders.

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine. HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers. METHODS: We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP. RESULTS: (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends. CONCLUSION: ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.

Video Didactic Preparation Augments Problem-Based Learning for First Year Medical Students.

Problem-based learning (PBL) utilizes a self-directed strategy. This process relies on group participation to succeed. Students without a background in biology or medicine can feel overwhelmed by the complexity of the subject matter and unable to participate in the group learning process. We incorporated curated educational videos in the PBL curriculum to help address this situation. First year medical students participated in this study in the form of a typical PBL session. They were then assessed on basic and clinical science knowledge and their learning experience. Student basic science and clinical knowledge were similar between the student groups. However, the students given a list of suggested videos scored higher in their learning experience, perception of feeling prepared, and participating in the group PBL experience than students who were not given the video list. Results from this study indicate that videos can be utilized to enhance the PBL process.

Decreased Adiponectin Levels in Early Pregnancy Are Associated with High Risk of Prematurity for African American Women.

The relationship of low maternal serum adiponectin levels with preterm delivery among a multi-ethnic group has not been extensively investigated. We examined ethnic differences in cytokine/adipokine profiles and whether they contribute to several adverse pregnancy outcomes, particularly preterm delivery. Data and samples were from a large prospective observational cohort (n = 1776) of young, generally healthy pregnant women (African American 36.4%, Hispanic 48.0%, Caucasian 15.6%). Serum cytokine/adipokine concentrations were measured at entry (mean gestational age of 16.83 weeks) using the Liminex xMap Technology. Multivariable analyses were performed. A significant difference in adiponectin level was observed among ethnic groups. African Americans had a decreased adiponectin and increased resistin levels compared to Hispanics and Caucasians (p < 0.05 to p < 0.0001 for each). Decreased adiponectin (lowest quartile) was positively associated with preterm delivery independent of usual risk factors (adjusted odds ratio (AOR) 1.46, 95% confidence interval (CI) 1.05, 2.04 for all preterm and AOR 1.84, 95% CI 1.07, 3.17 for early preterm births). The results were unchanged when women with preeclampsia were excluded. Similar results were observed in African Americans. Decreased adiponectin levels were not related to preterm birth in either Hispanics or Caucasians. Lower adiponectin levels were also significantly associated with an increased risk of developing gestational diabetes (AOR 1.72, 95% CI 1.05, 2.84) and preeclampsia (AOR 1.45, 95% CI 1.00, 2.14) in the whole cohort and in Caucasians. We did not find any consistent relationships between the other markers with outcome variables. Dysregulation in maternal adiponectin at early gestation is associated with an increased risk of preterm delivery. An ethnic difference in adiponectin levels may contribute to a higher preterm delivery rate in African American women.

Individual free fatty acids have unique associations with inflammatory biomarkers, insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women.

Objective: We investigated the relationships of maternal circulating individual free fatty acids (FFA) with insulin resistance, insulin secretion and inflammatory biomarkers during mid-pregnancy. Research design and methods: The data were drawn from a prospective cohort of generally healthy pregnant women (n=1368, African-American 36%, Hispanic 48%, Caucasian 16%) in Camden, NJ. We quantitatively determined 11 FFAs, seven cytokine/adipokine, homeostatic model assessment of insulin resistance (HOMA-IR) and C-peptide levels from the fasting blood samples that were collected at 16 weeks of gestation. Multivariate analyses were performed along with separate analyses for each individual FFA. Results: High HOMA-IR (p<0.001) and C-peptide (p<0.0001) levels were positively associated with a twofold to fourfold increased risk for developing gestational diabetes mellitus (GDM). Negative relationships were found with specific FFAs (molecular percentage, palmitoleic, oleic, linolenic, myristic acids) and HOMA-IR and C-peptide levels (p<0.01 to p<0.0001). In contrast, palmitic, stearic, arachidonic, dihomo-γ-linolenic (DGLA) and docosahexaenoic acids were positively associated with HOMA-IR and C-peptide (p<0.01 to p<0.0001). The individual FFAs also predicted cytokine/adipokine levels. For example, women who had elevated DGLA (highest quartile) were twice as (adjusted OR 2.06, 95% CI 1.42 to 2.98) likely to have higher interleukin (IL)-8 (p<0.0001) levels. Conversely, women with high palmitoleic, oleic, and linolenic acid levels had reduced odds (≥2-fold, p<0.01 to p<0.001) for having higher IL-8, IL-6 or tumor necrosis factor-alpha levels. Conclusion: Our results suggest that maternal individual FFAs uniquely affect insulin resistance and secretion. The effects are either direct or indirect via modulation of the inflammatory response. Modifying the composition of FFAs may help in reducing the risk of GDM.

Towards human exploration of space: The THESEUS review series on nutrition and metabolism research priorities.

Nutrition has multiple roles during space flight from providing sufficient nutrients to meet the metabolic needs of the body and to maintain good health, to the beneficial psychosocial aspects related to the meals. Nutrition is central to the functioning of the body; poor nutrition compromises all the physiological systems. Nutrition is therefore likely to have a key role in counteracting the negative effects of space flight (e.g., radiation, immune deficits, oxidative stress, and bone and muscle loss). As missions increase in duration, any dietary/nutritional deficiencies will become progressively more detrimental. Moreover, it has been recognized that the human diet contains, in addition to essential macronutrients, a complex array of naturally occurring bioactive micronutrients that may confer significant long-term health benefits. It is therefore critical that astronauts be adequately nourished during missions. Problems of nutritional origin are often treatable by simply providing the appropriate nutrients and adequate recommendations. This review highlights six key issues that have been identified as space research priorities in nutrition field: in-flight energy balance; altered feeding behavior; development of metabolic stress; micronutrient deficiency; alteration of gut microflora; and altered fluid and electrolytes balance. For each of these topics, relevance for space exploration, knowledge gaps and proposed investigations are described. Finally, the nutritional questions related to bioastronautics research are very relevant to multiple ground-based-related health issues. The potential spin-offs are both interesting scientifically and potentially of great clinical importance.

Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men.

Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known as the metabolic or insulin resistance syndrome. How obesity promotes insulin resistance remains incompletely understood. Plasma concentrations of free fatty acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and oxidative stress are all elevated in obesity and have been shown to induce insulin resistance. However, they may be late events that only develop after chronic excessive nutrient intake. The nature of the initial event that produces insulin resistance at the beginning of excess caloric intake and weight gain remains unknown. We show that feeding healthy men with ~6000 kcal/day of the common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 week produced a rapid weight gain of 3.5 kg and the rapid onset (after 2 to 3 days) of systemic and adipose tissue insulin resistance and oxidative stress but no inflammatory or ER stress. In adipose tissue, the oxidative stress resulted in extensive oxidation and carbonylation of numerous proteins, including carbonylation of GLUT4 near the glucose transport channel, which likely resulted in loss of GLUT4 activity. These results suggest that the initial event caused by overnutrition may be oxidative stress, which produces insulin resistance, at least in part, via carbonylation and oxidation-induced inactivation of GLUT4.

Bisphenol A Exposure in Children With Autism Spectrum Disorders.

The etiology of autism spectrum disorders (ASD) is believed to involve genetic and environmental components. This study focused on the plasticizer, Bisphenol-A (BPA). The major pathway for BPA metabolism and excretion is via glucuronidation. To determine whether there was a relationship between BPA exposure and ASD, urine specimens were collected from 46 children with ASD and 52 controls. Free and total BPA concentrations were determined by mass spectrometry. The fraction glucuronidated was calculated from the difference. A metabolomics study was done to investigate metabolite distribution in the urine. (i) Most of the BPA excreted in the urine was as the glucuronide; (ii) about 20% of the ASD children had BPA levels beyond the 90th percentile (>50 ng/mL) of the frequency distribution for the total sample of 98 children; (iii) Mann-Whitney U tests and multiple regression analyses found significant differences (P < 0.05) between the groups in total and % bound BPA; and (iv) the metabolomics analyses showed the number of absolute partial correlations >|0.30| between metabolite concentrations and total BPA was ∼3 times greater with the ASD group than the controls (P < 0.001), and the number of absolute partial correlations > |0.30| for % bound BPA was ∼15 times higher with ASD (P < 0.001). The results suggest there is an association between BPA and ASD.

Maternal calcium metabolic stress and fetal growth.

BACKGROUND: Suboptimal maternal calcium intake and vitamin D status may or may not adversely influence fetal growth. OBJECTIVE: It was hypothesized that maternal calcium metabolic stress in early pregnancy, rather than suboptimal calcium intake or insufficient vitamin D, influences the risk of small-for-gestational-age (SGA) births and other aspects of fetal growth. Stress to calcium metabolism was defined as elevated intact parathyroid hormone (PTH) (>62 pg/mL) accompanied by a very low calcium intake [<60% of the Estimated Average Requirement (EAR)] or insufficient 25-hydroxyvitamin D [25(OH)D] (<20 ng/mL). DESIGN: This was a prospective cohort study of 1116 low-income and minority gravidae at entry to care of 13.8 ± 5.6 wk (mean ± SD). RESULTS: The PTH concentration depended on circulating 25(OH)D and total calcium intake. When 25(OH)D was insufficient, even a high calcium intake (which equaled or exceeded the Recommended Dietary Allowance) was unable to maintain PTH or to moderate the proportion of patients with an elevated PTH. When examined one at a time, very low calcium intake (<60% of EAR), very low 25(OH)D (<12 ng/mL), and elevated PTH (>62 pg/mL) each had a small but significant association with birth weight. Elevated PTH was also related to birth length and risk of SGA birth. Elevated PTH accompanied by insufficient 25(OH)D or very low calcium intake was associated with a 2- to 3-fold increased risk of SGA birth and a significantly lower birth weight, birth length, and head circumference, even after women who developed preeclampsia were excluded. Infants born to gravidae with insufficient 25(OH)D or very low calcium intake without elevated PTH or with elevated PTH alone were unaffected. CONCLUSION: Maternal calcium metabolic stress, rather than low calcium intake or insufficient vitamin D, has an adverse influence on fetal growth. This trial was registered at clinicaltrials.gov as NIH 0320070046.

Insulin regulates the unfolded protein response in human adipose tissue.

Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼ 35 to ∼ 1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.

Vitamin D, secondary hyperparathyroidism, and preeclampsia.

BACKGROUND: Secondary hyperparathyroidism, which is defined by a high concentration of intact parathyroid hormone when circulating 25-hydroxyvitamin D [25(OH)D] is low, is a functional indicator of vitamin D insufficiency and a sign of impaired calcium metabolism. Two large randomized controlled trials examined effects of calcium supplementation on preeclampsia but did not consider the vitamin D status of mothers. OBJECTIVE: We examined the association of secondary hyperparathyroidism with risk of preeclampsia. DESIGN: Circulating maternal 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone were measured at entry to care (mean ± SD: 13.7 ± 5.7 wk) using prospective data from a cohort of 1141 low-income and minority gravidae. RESULTS: Secondary hyperparathyroidism occurred in 6.3% of the cohort and 18.4% of women whose 25(OH)D concentrations were <20 ng/mL. Risk of preeclampsia was increased 2.86-fold (95% CI: 1.28-, 6.41-fold) early in gestation in these women. Gravidae with 25(OH)D concentrations <20 ng/mL who did not also have high parathyroid hormone and women with high parathyroid hormone whose 25(OH)D concentrations were >20 ng/mL were not at increased risk. Intact parathyroid hormone was related to higher systolic and diastolic blood pressures and arterial pressure at week 20 before clinical recognition of preeclampsia. Energy-adjusted intakes of total calcium and lactose and circulating 25(OH)D were correlated inversely with systolic blood pressure or arterial pressure and with parathyroid hormone. CONCLUSION: Some women who are vitamin D insufficient develop secondary hyperparathyroidism, which is associated with increased risk of preeclampsia.

Autism and phthalate metabolite glucuronidation.

Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, diethylhexyl phthalate. Spot urines were collected and analyzed for the fraction of each metabolite conjugated by isotope dilution-liquid chromatography mass spectrometry-mass spectrometry. The degree of glucuronidation was lower with the ASD group. The glucuronidation pathway may differ in some children with ASD.

Maximizing information from space data resources: a case for expanding integration across research disciplines.

Regulatory systems are affected in space by exposure to weightlessness, high-energy radiation or other spaceflight-induced changes. The impact of spaceflight occurs across multiple scales and systems. Exploring such interactions and interdependencies via an integrative approach provides new opportunities for elucidating these complex responses. This paper argues the case for increased emphasis on integration, systematically archiving, and the coordination of past, present and future space and ground-based analogue experiments. We also discuss possible mechanisms for such integration across disciplines and missions. This article then introduces several discipline-specific reviews that show how such integration can be implemented. Areas explored include: adaptation of the central nervous system to space; cerebral autoregulation and weightlessness; modelling of the cardiovascular system in space exploration; human metabolic response to spaceflight; and exercise, artificial gravity, and physiologic countermeasures for spaceflight. In summary, spaceflight physiology research needs a conceptual framework that extends problem solving beyond disciplinary barriers. Administrative commitment and a high degree of cooperation among investigators are needed to further such a process. Well-designed interdisciplinary research can expand opportunities for broad interpretation of results across multiple physiological systems, which may have applications on Earth.

Metabolic perturbance in autism spectrum disorders: a metabolomics study.

Autism spectrum disorders (ASD) are a group of biological disorders with associated metabolic derangement. This study aimed to identify a pattern of metabolic perturbance in ASD using metabolomics in urinary specimens from 48 children with ASD and 53 age matched controls. Using a combination of liquid- and gas-chromatography-based mass spectrometry, we detected the levels of 82 metabolites (53 of which were increased) that were significantly altered between the ASD and the control groups using osmolality normalized data. Pattern analysis showed that the levels of several amino acids such as glycine, serine, threonine, alanine, histidine, glutamyl amino acids and the organic acid, taurine were significantly (p≤0.05) lower in ASD children. The levels of antioxidants such as carnosine were also reduced in ASD (p=0.054). Furthermore, several gut bacterial metabolites were significantly altered in ASD children who had gastrointestinal dysfunction. Overall, this study detected abnormal amino acid metabolism, increased oxidative stress, and altered gut microbiomes in ASD. The relationship of altered gut microbial co-metabolism and the disrupted metabolisms requires further investigation.

Does protein supplementation prevent muscle disuse atrophy and loss of strength?

Recently there has been much interest in the use of dietary amino acids supplements to decrease the losses in muscle mass and strength observed after space flight or during aging using bed rest analogs. This interest persists even if the results have been mixed. Of the six published amino acid supplementation studies, three showed benefit, three did not. A recent study re-evaluating protein requirements in humans suggests that the official RDA is 41% underestimated. Interestingly, the three studies that showed benefits fed their test subjects a baseline protein level around the old RDA for protein. The three that did not show benefit gave the subjects a baseline protein intake higher than the new RDA. We suggest that the positive effects observed on protein metabolism might just reflect the benefits of adequate protein intake achieved during bed rest rather than a protective effect against bed-rest induced disuse. In conclusion, the efficiency of amino acid countermeasures for preventing the loss in protein mass during space flight or bed rest needs to be seriously questioned. These results extend to clinical situations such as serious illness and progress of aging in which physical inactivity is a significant component of the loss in muscle function.

Maternal diet, C-reactive protein, and the outcome of pregnancy.

OBJECTIVE: To examine the association of high-sensitivity C-reactive protein (hsCRP), a systemic biomarker for the inflammatory process at entry to care, with pregnancy-induced hypertension/preeclampsia, adverse outcomes of pregnancy, and the maternal diet. DESIGN: Random sample (N = 520) with normal glucose tolerance from a large prospective cohort study of urban, low income, minority gravidae. RESULTS: During pregnancy, the highest tertile of hsCRP (range, 7.06-137.41 mg/L) was associated with significantly increased risks for early preterm delivery (<34 weeks). However, after stratification by maternal pregravid body mass index (BMI), risk for early preterm delivery <34 weeks (adjusted odds ratios [AOR] = 3.58, 95% confidence interval [CI] = 1.05-12.27), and pregnancy-induced hypertension (AOR = 2.66, 95% CI = 1.03-6.86) including preeclampsia (AOR = 2.72, 95% CI = 1.08-6.85) was shown to be specific to lean women (BMI <25) with high hsCRP. Increased hsCRP was unrelated to risk among overweight and obese gravidae. We found high hsCRP to be associated with diet. After stratification by BMI, dietary differences (higher intakes of protein and cholesterol with a lower intake of carbohydrate and a higher entry dietary glycemic index) were associated with increased hsCRP only among lean gravidae and not among those who were overweight or obese. CONCLUSIONS: High hsCRP is a diet-related biomarker for serious complications and poor outcome in lean women with normal glucose tolerance.

Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat.

Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss. Each of these adaptations could turn to serious health deterioration during the long-term spaceflight needed for planetary exploration. We hypothesized that resveratrol (RES), a natural polyphenol, could be used as a nutritional countermeasure to prevent muscle metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment maintained a net protein balance, soleus muscle mass, and soleus muscle maximal force contraction. RES also fully maintained soleus mitochondrial capacity to oxidize palmitoyl-carnitine and reversed the decrease of the glutathione vs. glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular level, the protein content of Sirt-1 and COXIV in soleus muscle was also preserved. RES further protected whole-body insulin sensitivity and lipid trafficking and oxidation, and this was likely associated with the maintained expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in muscle. Finally, chronic RES supplementation maintained the bone mineral density and strength of the femur. For the first time, we report a simple countermeasure that prevents the deleterious adaptations of the major physiological functions affected by mechanical unloading. RES could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

Weight loss in humans in space.

INTRODUCTION: Bodyweight loss during spaceflight has been observed among astronauts since the early space missions. Considerable mission data has been accumulated, including data from female astronauts, on the many Shuttle and International Space Station missions. The purpose of this study was to investigate the association between observed weight loss during spaceflight and potential covariate factors. METHODS: We performed a statistical analysis of the association between bodyweight change and plausible clinical and mission covariates, using data obtained from the NASA Longitudinal Study of Astronaut Health (LSAH). RESULTS: We confirmed that spaceflight is associated with weight change (-2.1 +/- 0.1%, N = 514). Prospective predictors of weight loss included: being a first-time astronaut, preflight bodyweight and BMI, routinely performing preflight exercise sessions lasting greater than 1 h, and baseline levels of cholesterol, potassium, and chloride. Severe space motion sickness was significantly associated with greater weight loss. Unexpectedly, a higher number of extravehicular activities per mission protected against weight loss. Mission duration had the strongest association with bodyweight change (-2.4 +/- 0.4% per 100 d in space). DISCUSSION: On average, space missions are associated with cumulative loss of bodyweight over time. Unless effective countermeasures are implemented, significant weight loss will be a likely outcome in a subset of astronauts as mission durations increase. New predictors of intra-mission bodyweight changes and other associated factors are identified.

Differences in maternal circulating fatty acid composition and dietary fat intake in women with gestational diabetes mellitus or mild gestational hyperglycemia.

OBJECTIVE: We investigated the relationship between maternal circulating fatty acids (FAs) and dietary FA intake in pregnant women with gestational diabetes mellitus (GDM; n = 49), women with hyperglycemia less severe than GDM (impaired glucose challenge test [GCT] non-GDM; n = 80), and normal control subjects (n = 98). RESEARCH DESIGN AND METHODS: A case-control design was nested within a prospective cohort of healthy pregnant women. Fasting concentrations of serum total FAs (enzymatic assay) and FA composition (gas chromatography-mass spectrometry) were determined at entry and the third trimester. Dietary fat intake data were obtained from 24-h recalls. RESULTS: There was a graded increase among groups (control subjects, impaired GCT non-GDM, and GDM) during the third trimester for total FAs and individual FAs, including myristic, palmitic, palmitoleic, oleic, linoleic, linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids (P for trend <0.03 to P < 0.001). Similar relationships were observed at entry in total FAs and for four FAs (myristic, palmitic, palmitoleic, and eicosapentaenoic acids). Women with impaired GCT non-GDM with BMI >or=25 kg/m(2) had the highest levels of FAs at entry, whereas women with GDM with BMI >or=25 kg/m(2) had the highest levels during the third trimester, and all grouped FAs were significantly different from lean women with impaired GCT non-GDM or control subjects (P < 0.05). Dietary intake of polyunsaturated FAs was decreased, but saturated FAs were increased in GDM compared with impaired GCT non-GDM or control subjects (P < 0.05). CONCLUSIONS: Abnormalities in fat metabolism are present in both GDM and impaired GCT non-GDM women. Reducing pregravid weight and altering diet might prevent the associated elevation of circulating FAs.

Vitamin E: maternal concentrations are associated with fetal growth.

BACKGROUND: Few data exist on the effects of the 2 most abundant isomers of vitamin E (alpha- and gamma-tocopherols) on fetal growth. OBJECTIVE: We measured maternal plasma concentrations of alpha- and gamma-tocopherols and examined their relation with measures of fetal growth. We also examined the relation, controlled for associated maternal factors, of diet and supplement use to tocopherol concentrations at week 28 of gestation. DESIGN: A cohort of 1231 gravid women from Camden, NJ, was studied from entry to care (16.0 +/- 0.15 wk gestation); plasma tocopherol concentrations were measured at entry and at week 28. RESULTS: Plasma concentrations of alpha-tocopherol at entry and at week 28 were positively related to increased fetal growth (birth weight for gestation), a decreased risk of small-for-gestational-age births, and an increased risk of large-for-gestational-age births. Concentration of alpha-tocopherol at week 28 was positively related to use of prenatal multivitamins and dietary intake of vitamin E; concentration of gamma-tocopherol was related positively to dietary fat intake and negatively to multivitamin use. CONCLUSION: Early and late circulating concentrations of alpha-tocopherol are positively associated with fetal growth.