Maternal and Umbilical Cord Levels of T 4 , FT 4 , TSH, TPOAb, and TgAb in Term Infants and Neurodevelopmental Outcome at 5.5 Years Fiona L. R. Williams, Jennifer Watson, Simon A. Ogston, Theo J. Visser, Robert Hume, and Peter Willatts Population Health Sciences (F.L.R.W., J.W., S.A.O., R.H.), University of Dundee, Ninewells Hospital and Medical School Campus, Dundee DD2 4BF, Scotland; Department of Internal Medicine (T.J.V.), Erasmus University Medical Centre, 3015 GE Rotterdam, The Netherlands; and Department of Psychology (P.W.), University of Dundee, Dundee DD1 4HN, Scotland Context: Relatively little is known in euthyroid populations about the changes in maternal thyroid hormones during pregnancy, the nature of the relationship to cord thyroid hormone levels, and subsequent infant neurodevelopment. Objectives: The aim of the study was to describe the relationship between maternal and cord thyroid hormone parameters and to describe their associations with neurodevelopment at 5.5 years. Design: We conducted a follow-up of women and their children born at or over 37 weeks’ gestation. Main Outcomes: We measured maternal levels of TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), T 4 , and free T 4 (FT 4 ) at 10 and 34 weeks and at delivery, and cord levels of T 4 , FT 4 , TPOAb, and TgAb. The association of cord thyroid hormone parameters with McCarthy scale scores adjusted for the major confounders of neurodevelopment. Results: Fifteen percent of the women were TPOAb-positive, and 12% were TgAb-positive; the proportion of women with mildly elevated TSH levels increased during pregnancy with the max- imum (14%) at delivery. Lower perceptual performance and motor scores were found with TgAb- positive women and lower perceptual performance scores with TgAb-positive cord levels; other- wise, unadjusted maternal levels of TPOAb, TgAb, and TSH and unadjusted cord levels of FT 4 , TPOAb, and TgAb were not associated with neurodevelopment at 5.5 years. Low cord T 4 levels were associated with significant increments in four McCarthy scales: General Cognitive Index, Verbal, Quantitative, and Memory scales—increments that persisted after adjustment at 11.4, 7.8, 7.6, and 7.8 points, respectively. Conclusions: Lower levels of cord T 4 were associated with increments in the McCarthy scales in the domains that tested cognitive and verbal abilities at 5.5 years. (J Clin Endocrinol Metab 98: 829 – 838, 2013) T he brain is critically dependent on T 4 for normal growth and development in utero and for the first 2 years of life (1). Postnatal deficiency of T 4 is associated in observational studies with brain compromise (2– 6). In utero it is thought that a sufficient supply of T 4 is provided from the maternal circulation because infants with total organification defect have cord serum T 4 levels of 35 to 70 nmol/L (7), but provided T 4 replacement therapy is started ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2013 by The Endocrine Society doi: 10.1210/jc.2012-3572 Received October 9, 2012. Accepted November 30, 2012. First Published Online January 15, 2013 Abbreviations: BPVS II, British Picture Vocabulary Scale; FT 4 , free T 4 ; GCI, General Cognitive Index; PPVT, Peabody Picture Vocabulary Test; TBG, T 4 binding globulin; TgAb, thyroglob- ulin antibody; TPOAb, thyroid peroxidase antibody. ORIGINAL ARTICLE Endocrine Research J Clin Endocrinol Metab, February 2013, 98(2):829 – 838 jcem.endojournals.org 829