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Haddow J.E.,Brown University | Haddow J.E.,Savjani Institute for Health Research | Craig W.Y.,Foundation for Blood Research | Palomaki G.E.,Brown University | And 8 more authors.
Thyroid | Year: 2013

Background: Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg/m2) than in the overall study population. We explore this relationship further. Methods: Among 9351 women with second trimester thyrotropin (TSH) measurements between 1st and 98th centiles, we examine: (i) the weight/FT4 relationship; (ii) percentages of women in three weight categories at each FT4 decile; (iii) FT4 concentrations in three weight categories at each TSH decile; and (iv) impact of adjusting FT4 for weight-in the reference group and in 190 additional women with elevated TSH measurements. Results: FT4 values decrease steadily as weight increases (p<0.0001 by ANOVA) among women in the reference group (TSH 0.05-3.8 IU/L). TSH follows no consistent pattern with weight. When stratified into weight tertiles, 48% of women at the lowest FT4 decile are heavy; the percentage decreases steadily to 22% at the highest FT4 decile. Median FT4 is lowest in heaviest women regardless of the TSH level. In the reference group, weight adjustment reduces overall variance by 2.9%. Fewer FT4 measurements are at either extreme (below the 5th FT4 centile: 4.8% before adjustment, 4.7% after adjustment; above the 95th FT4 centile: 5.0% and 4.7%, respectively). Adjustment places more light weight women and fewer heavy women below the 5th FT4 centile; the converse above the 95th centile. Between TSH 3.8 and 5 IU/L, the FT4 percentage below the 5th FT4 centile is not elevated (3.8% before adjustment, 3.1% after adjustment). Percentage of FT4 values above the 95th centile, however, is lower (1.5% before adjustment, 0.8% after adjustment). Above TSH 5 IU/L, 25% of women have FT4 values below the 5th FT4 centile; weight adjustment raises this to 30%; no FT4 values remain above the 95th FT4 centile. Conclusions: During early pregnancy, TSH values are not associated with weight, unlike nonpregnant adults. Lower average FT4 values among heavy women at all TSH deciles partially explain interindividual differences in FT4 reference ranges. The continuous reciprocal relationship between weight and FT4 explains lower FT4 with higher weight. Weight adjustment refines FT4 interpretation. © 2013, Mary Ann Liebert, Inc.


Chen Q.,University of Pittsburgh | Reis S.E.,University of Pittsburgh | Kammerer C.,University of Pittsburgh | Craig W.,Foundation for Blood Research | And 7 more authors.
Journal of Lipid Research | Year: 2011

Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. Recent studies show that inflammation and autoimmune reactions are also relevant in atherosclerosis. In this study, we examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women's Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (<20%, 20%-49%, >50% stenosis). We also examined the relationship of anti-oxLDL with serum lipid levels and nine candidate genes including APOE, APOH, APOA5, LPL, LRP1, HL, CETP, PON1, and OLR1. IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the ∩20% stenosis group in whites (0.69 ± 0.02 vs. 0.64 ± 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r2 = 0.01; P = 0.03) and LDL cholesterol (r2 = 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG antioxLDL (P = 0.02) and IgM anti-oxLDL (P = 0.07), as well as between IgM anti-oxLDL and the OLR1/3′UTR SNP (P = 0.020). Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.


Haddow J.E.,Brown University | Haddow J.E.,Savjani Institute for Health Research | Craig W.Y.,Foundation for Blood Research | Neveux L.M.,Brown University | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Lower birth weight has been reported in conjunction with high maternal free T4 (FT4) in euthyroid pregnancies, raising concerns for suboptimal outcomes. Objective: The objective of the study was to explore the relationships between high maternal FT4 and pregnancy complications in euthyroidwomenand to further examine the relationshipsamong maternal size, FT4, and birth weight. Design: This was an observational multicenter cohort study. Setting: The study was conducted at prenatal clinics. Study Subjects: A total of 9209 euthyroid women with singleton pregnancies participated in the study. Interventions: There were no interventions. Main Outcome Measures: Relationships between second-trimester high maternal FT4 and pregnancy/ delivery complications and, among FT4, maternal weight and birth weight were measured. Results: Women in the highest FT4 quintile are younger and weigh less than women in quintiles 1-4; gestational diabetes and preeclampsia occur less often (P = < .001, P < .001, P < .001, and P=.05, respectively). Lowest median birth weight occursamongwomenin the highest FT4 quintile (P = < .001), but deliveries less than 37 weeks' gestation are not increased. Labor/delivery complications do not differ by FT4 quintile. Restricting analyses to maternal weight-adjusted smallfor- gestational-age deliveries yields similar results, except for preeclampsia. In the highest maternal weight decile, adjusted median birth weight is 266 g higher (8.3%) than in the lowest weight decile; adjusted median FT4 is 0.91 pmol/L lower (6.8%). Among women in the highest FT4 decile, adjusted median birth weight is 46 g lower (1.3%) than in the lowest FT4 decile. All three relationships are statistically significant (P < .001, P < .001, and P = .004, respectively). Conclusions: Lower median birth weight among euthyroid women with high FT4 is not associated with adverse pregnancy outcomes. Further investigation is indicated to determine how the variations in thyroid hormone concentration influence birth weight. © 2014 by the Endocrine Society.


Madan J.,Dartmouth Hitchcock Medical Center | Goodman E.,Tufts Medical Center | Allan W.,Foundation for Blood Research | Dammann O.,Hannover Medical School | Dammann O.,Neuroepidemiology Unit
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2010

Objective. To study maternal obesity as a risk factor for preterm delivery. Methods. Maine State Birth Records Database from 1996 through 2006 was evaluated to investigate obese pregnant women compared with normal weight women regarding risk for preterm delivery. Multiple risk factors and outcomes were studied in univariable and multivariable models. Results. Among 58,112 pregnant women, 8% (n = 4653) gave birth to preterm infants. Univariable analyses revealed a relationship between obesity and increased risk of prematurity. In multivariable regressions, the most important intermediate variable appears to be gestational hypertension/preeclampsia. Conclusions. As maternal body mass index increases in pregnancy, the risk of preterm delivery and other maternal complications increases. The obesity-prematurity relationship is complex, with hypertensive disorders of pregnancy playing a crucial role. More detailed analyses of causal pathways are warranted. © 2010 Informa UK Ltd.


Lee I.,Santa Fe Institute | Martin F.,University of Massachusetts Lowell | Denner J.,ETR Associates | Coulter B.,Missouri Botanical Garden | And 4 more authors.
ACM Inroads | Year: 2011

been described as the use of abstraction, automation, and analysis in problem-solving [3]. We examine how these ways of thinking take shape for middle and high school youth in a set of NSF-supported programs. We discuss opportunities and challenges in both in-school and after-school contexts. Based on these observations, we present a "use-modify-create" framework, representing three phases of students' cognitive and practical activity in computational thinking. We recommend continued investment in the development of CT-rich learning environments, in educators who can facilitate their use, and in research on the broader value of computational thinking. © 2011 ACM.

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