The fact that neonates who subsequently have severe hypothyroidism have no evidence of the condition at birth suggests the possibility of the placental transfer of thyroid hormones. Recent studies have demonstrated the existence of such transfer in hypothyroid rats. To determine whether there is a transfer of thyroxine (T4) from mother to fetus, we studied 25 neonates born with a complete inability to iodinate thyroid proteins and therefore to synthesize T4. This total organification defect is an autosomal recessive disorder with an incidence of approximately 1 in 60,000 neonates in the Netherlands. In the cord serum of affected neonates, T4 levels ranged from 35 to 70 nmol per liter. Since these patients were unable to produce any T4, the T4 must have originated in their mothers. The estimated biologic half-life of serum T4 was 3.6 days (95 percent confidence interval, 2.7 to 5.3). In 15 neonates with thyroid agenesis, the serum levels and the disappearance kinetics of T4 were the same as those in the neonates with a total organification defect, suggesting that in these infants, the T4 also had a maternal origin. We conclude that in infants with severe congenital hypothyroidism, substantial amounts of T4 are transferred from mother to fetus during late gestation.
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Department of Experimental Pediatric Endocrinology, Academic Hospital, University of Amsterdam, the Netherlands.
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[Abstract][Full Text]
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[Abstract][Full Text]
Yen, P. M.
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[Abstract][Full Text]
Smallridge, R. C., Ladenson, P. W.
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86: 2349-2353
[Full Text]
Morreale de Escobar, G., Jesús Obregón, M., Escobar del Rey, F.
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85: 3975-3987
[Abstract][Full Text]
Bakker, B., Bikker, H., Vulsma, T., de Randamie, J. S. E., Wiedijk, B. M., de Vijlder, J. J. M.
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85: 3708-3712
[Abstract][Full Text]
Venihaki, M., Carrigan, A., Dikkes, P., Majzoub, J. A.
(2000). Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency. Proc. Natl. Acad. Sci. USA
97: 7336-7341
[Abstract][Full Text]
Dowling, A. L. S., Martz, G. U., Leonard, J. L., Zoeller, R. T.
(2000). Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Gene Expression in Fetal Rat Brain. J. Neurosci.
20: 2255-2265
[Abstract][Full Text]
Muller, A. F., Verhoeff, A., Mantel, M. J., de Jong, F. H., Berghout, A.
(2000). Decrease of Free Thyroxine Levels after Controlled Ovarian Hyperstimulation. J. Clin. Endocrinol. Metab.
85: 545-548
[Abstract][Full Text]
Utiger, R. D.
(1999). Maternal Hypothyroidism and Fetal Development. NEJM
341: 601-602
[Full Text]
Yasuda, T., Ohnishi, H., Wataki, K., Minagawa, M., Minamitani, K., Niimi, H.
(1999). Outcome of a Baby Born from a Mother with Acquired Juvenile Hypothyroidism Having Undetectable Thyroid Hormone Concentrations. J. Clin. Endocrinol. Metab.
84: 2630-2632
[Abstract][Full Text]
Leon, M. B., Baim, D. S., Popma, J. J., Gordon, P. C., Cutlip, D. E., Ho, K. K.L., Giambartolomei, A., Diver, D. J., Lasorda, D. M., Williams, D. O., Pocock, S. J., Kuntz, R. E., The Stent Anticoagulation Restenosis Study Investi,
(1998). A Clinical Trial Comparing Three Antithrombotic-Drug Regimens after Coronary-Artery Stenting. NEJM
339: 1665-1671
[Abstract][Full Text]
Richard, K., Hume, R., Kaptein, E., Sanders, J. P., van Toor, H., de Herder, W. W., den Hollander, J. C., Krenning, E. P., Visser, T. J.
(1998). Ontogeny of Iodothyronine Deiodinases in Human Liver. J. Clin. Endocrinol. Metab.
83: 2868-2874
[Abstract][Full Text]
Bajoria, R., Fisk, N. M., Contractor, S. F.
(1997). Liposomal Thyroxine: A Noninvasive Model for Transplacental Fetal Therapy. J. Clin. Endocrinol. Metab.
82: 3271-3277
[Abstract][Full Text]
Oppenheimer, J. H., Schwartz, H. L.
(1997). Molecular Basis of Thyroid Hormone-Dependent Brain Development. Endocr. Rev.
18: 462-475
[Abstract][Full Text]
Ares, S., Escobar-Morreale, H. F., Quero, J., Duran, S., Presas, M. J., Herruzo, R., Morreale de Escobar, G.
(1997). Neonatal Hypothyroxinemia: Effects of Iodine Intake and Premature Birth. J. Clin. Endocrinol. Metab.
82: 1704-1712
[Abstract][Full Text]
Burrow, G. N., D., M.
(1997). Editorial: Mothers Are Important!. Endocrinology
138: 3-4
[Full Text]
Piosik, P. A., van Groenigen, M., van Doorn, J., Baas, F., de Vijlder, J. J. M.
(1997). Effects of Maternal Thyroid Status on Thyroid Hormones and Growth in Congenitally Hypothyroid Goat Fetuses during the Second Half of Gestation. Endocrinology
138: 5-11
[Abstract][Full Text]
Vulsma, T., Kok, J. H.
(1996). Prematurity-Associated Neurologic and Developmental Abnormalities and Neonatal Thyroid Function. NEJM
334: 857-858
[Full Text]
Hetzel, B. S.
(1994). Iodine Deficiency and Fetal Brain Damage. NEJM
331: 1770-1771
[Full Text]
Burrow, G. N., Fisher, D. A., Larsen, P. R.
(1994). Maternal and Fetal Thyroid Function. NEJM
331: 1072-1078
[Full Text]
Tillotson, S L, Fuggle, P W, Smith, I, Ades, A E, Grant, D B
(1994). Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect. BMJ
309: 440-4
[Abstract][Full Text]
Liu, H., Momotani, N., Noh, J. Y., Ishikawa, N., Takebe, K., Ito, K.
(1994). Maternal Hypothyroidism During Early Pregnancy and Intellectual Development of the Progeny. Arch Intern Med
154: 785-792
[Abstract]
ROOT, A. W.
(1992). The Role of Maternal Autoimmune Thyroid Disease in Neonatal Hypothyroidism. Arch Pediatr Adolesc Med
146: 1029-1030
[Abstract]
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