The Relation of Transient Hypothyroxinemia in Preterm Infants to Neurologic Development at Two Years of Age
Mary Lynne Reuss, M.D., M.P.H., Nigel Paneth, M.D., M.P.H., Jennifer A. Pinto-Martin, Ph.D., John M. Lorenz, M.D., and Mervyn Susser, M.B., B.Ch., D.P.H.
Background Transient hypothyroxinemia, a common finding in prematureinfants, is not thought to have long-term sequelae or to requiretreatment. We investigated whether hypothyroxinemia in prematureinfants is a cause of subsequent motor and cognitive abnormalities.
Methods In this historical cohort study, we retrieved bloodthyroxine values, obtained on routine screening in the firstweek of life, from state screening records of children who weighed2000 g or less at birth, who were born at 33 weeks' gestationor earlier, and who were enrolled in a population-based studyof the late sequelae of neonatal brain hemorrhage. We investigatedthe relation of these values to the odds for disabling cerebralpalsy among 463 subjects for whom data were available and tothe mental-development score on the Bayley Scales of InfantDevelopment or the StanfordBinet Intelligence Scalesfor Children at the age of two years in 400 subjects. The effectsof severe hypothyroxinemia, defined as a blood thyroxine valuemore than 2.6 SD below the mean for New Jersey newborns, wereassessed before and after adjustment for gestational age andpotentially confounding variables.
Results In analyses adjusted for gestational age, infants withsevere hypothyroxinemia had a risk of disabling cerebral palsythat was nearly 11 times that of infants without hypothyroxinemia(odds ratio, 10.8; 95 percent confidence interval, 3.0 to 39.3)and a mean mental-development score at the age of two that was15.4 points lower (95 percent confidence interval, 8.1 to 22.6points) than the mean score of children with normal neonatalblood thyroxine concentrations. After adjustment for gestationalage and multiple prenatal, perinatal, and early and late neonatalvariables, severe hypothyroxinemia was still associated withan increased risk of disabling cerebral palsy (odds ratio, 4.4;95 percent confidence interval, 1.0 to 18.6) and a reductionof nearly 7 points (95 percent confidence interval, 0.3 to 13.2points) in the mental-development score.
Conclusions Severe hypothyroxinemia in preterm infants may bean important cause of problems in neurologic and mental developmentdetected at the age of two years.
Source Information
From the Sergievsky Center (M.L.R., M.S.) and the Department of Obstetrics and Gynecology (M.L.R.), Columbia University, New York; the Program in Epidemiology (N.P.) and the Department of Pediatrics and Human Genetics (N.P., J.M.L.), the College of Human Medicine, Michigan State University, East Lansing; and the School of Nursing, University of Pennsylvania, Philadelphia (J.A.P.-M.).
Address reprint requests to Dr. Reuss at 2 Beach Ct., Saratoga Springs, NY 12866.
Forghani, N., Aye, T.
(2008). Hypothyroxinemia and Prematurity. NeoReviews
9: e66-e71
[Abstract][Full Text]
Whitaker, A. H., Feldman, J. F., Lorenz, J. M., Shen, S., McNicholas, F., Nieto, M., McCulloch, D., Pinto-Martin, J. A., Paneth, N.
(2006). Motor and cognitive outcomes in nondisabled low-birth-weight adolescents: early determinants.. Arch Pediatr Adolesc Med
160: 1040-1046
[Abstract][Full Text]
Negro, R., Formoso, G., Mangieri, T., Pezzarossa, A., Dazzi, D., Hassan, H.
(2006). Levothyroxine Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: Effects on Obstetrical Complications. J. Clin. Endocrinol. Metab.
91: 2587-2591
[Abstract][Full Text]
Buimer, M., van Wassenaer, A. G., Ganzevoort, W., Wolf, H., Bleker, O. P., Kok, J. H.
(2005). Transient Hypothyroxinemia in Severe Hypertensive Disorders of Pregnancy. Obstet Gynecol
106: 973-979
[Abstract][Full Text]
Williams, F. L. R., Ogston, S. A., van Toor, H., Visser, T. J., Hume, R., with collaboration from the Scottish Preterm Thyro,
(2005). Serum Thyroid Hormones in Preterm Infants: Associations with Postnatal Illnesses and Drug Usage. J. Clin. Endocrinol. Metab.
90: 5954-5963
[Abstract][Full Text]
van Wassenaer, A. G., Westera, J., Houtzager, B. A., Kok, J. H.
(2005). Ten-Year Follow-up of Children Born at <30 Weeks' Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial. Pediatrics
116: e613-e618
[Abstract][Full Text]
Williams, F. L. R., Mires, G. J., Barnett, C., Ogston, S. A., van Toor, H., Visser, T. J., Hume, R., with collaboration from the Scottish Preterm Thyro,
(2005). Transient Hypothyroxinemia in Preterm Infants: The Role of Cord Sera Thyroid Hormone Levels Adjusted for Prenatal and Intrapartum Factors. J. Clin. Endocrinol. Metab.
90: 4599-4606
[Abstract][Full Text]
Simpson, J., Williams, F. L. R., Delahunty, C., van Toor, H., Wu, S.-Y., Ogston, S. A., Visser, T. J., Hume, R., with collaboration from the Scottish Preterm Thyro,
(2005). Serum Thyroid Hormones in Preterm Infants and Relationships to Indices of Severity of Intercurrent Illness. J. Clin. Endocrinol. Metab.
90: 1271-1279
[Abstract][Full Text]
Paneth, N., Korzeniewski, S., Hong, T.
(2005). The Role of the Intrauterine and Perinatal Environment in Cerebral Palsy. NeoReviews
6: e133-e140
[Full Text]
Lim, D. J., Herring, M. K., Leef, K. H., Getchell, J., Bartoshesky, L. E., Paul, D. A.
(2005). Hypothyroxinemia in Mechanically Ventilated Term Infants Is Associated With Increased Use of Rescue Therapies. Pediatrics
115: 406-410
[Abstract][Full Text]
Williams, F. L. R., Simpson, J., Delahunty, C., Ogston, S. A., Bongers-Schokking, J. J., Murphy, N., van Toor, H., Wu, S.-Y., Visser, T. J., Hume, R., with Collaboration from the Scottish Preterm Thyro,
(2004). Developmental Trends in Cord and Postpartum Serum Thyroid Hormones in Preterm Infants. J. Clin. Endocrinol. Metab.
89: 5314-5320
[Abstract][Full Text]
Hume, R., Simpson, J., Delahunty, C., van Toor, H., Wu, S. Y., Williams, F. L. R., Visser, T. J.
(2004). Human Fetal and Cord Serum Thyroid Hormones: Developmental Trends and Interrelationships. J. Clin. Endocrinol. Metab.
89: 4097-4103
[Abstract][Full Text]
Murphy, N., Hume, R., van Toor, H., Matthews, T. G., Ogston, S. A., Wu, S.-Y., Visser, T. J., Williams, F. L. R.
(2004). The Hypothalamic-Pituitary-Thyroid Axis in Preterm Infants; Changes in the First 24 Hours of Postnatal Life. J. Clin. Endocrinol. Metab.
89: 2824-2831
[Abstract][Full Text]
Chan, S., Kachilele, S., Hobbs, E., Bulmer, J. N., Boelaert, K., McCabe, C. J., Driver, P. M., Bradwell, A. R., Kester, M., Visser, T. J., Franklyn, J. A., Kilby, M. D.
(2003). Placental Iodothyronine Deiodinase Expression in Normal and Growth-Restricted Human Pregnancies. J. Clin. Endocrinol. Metab.
88: 4488-4495
[Abstract][Full Text]
Ibrahim, M, de Escobar, G M., Visser, T J, Duran, S, van Toor, H, Strachan, J, Williams, F L R, Hume, R
(2003). Iodine deficiency associated with parenteral nutrition in extreme preterm infants. Arch. Dis. Child. Fetal Neonatal Ed.
88: F56-57
[Abstract][Full Text]
van Wassenaer, A. G., Briet, J. M., van Baar, A., Smit, B. J., Tamminga, P., de Vijlder, J. J. M., Kok, J. H.
(2002). Free Thyroxine Levels During the First Weeks of Life and Neurodevelopmental Outcome Until the Age of 5 Years in Very Preterm Infants. Pediatrics
110: 534-539
[Abstract][Full Text]
Arii, J., Tanabe, Y., Makino, M., Sato, H., Kohno, Y.
(2002). Children With Irreversible Brain Damage Associated With Hypothyroidism and Multiple Intracranial Calcifications. J Child Neurol
17: 309-313
[Abstract]
Stanley, E. L., Hume, R., Visser, T. J., Coughtrie, M. W. H.
(2001). Differential Expression of Sulfotransferase Enzymes Involved in Thyroid Hormone Metabolism during Human Placental Development. J. Clin. Endocrinol. Metab.
86: 5944-5955
[Abstract][Full Text]
Smallridge, R. C., Ladenson, P. W.
(2001). Hypothyroidism in Pregnancy: Consequences to Neonatal Health. J. Clin. Endocrinol. Metab.
86: 2349-2353
[Full Text]
Briet, J. M., van Wassenaer, A. G., Dekker, F. W., de Vijlder, J. J. M., van Baar, A., Kok, J. H.
(2001). Neonatal Thyroxine Supplementation in Very Preterm Children: Developmental Outcome Evaluated at Early School Age. Pediatrics
107: 712-718
[Abstract][Full Text]
Morreale de Escobar, G., Jesús Obregón, M., Escobar del Rey, F.
(2000). Is Neuropsychological Development Related to Maternal Hypothyroidism or to Maternal Hypothyroxinemia?. J. Clin. Endocrinol. Metab.
85: 3975-3987
[Abstract][Full Text]
Paul, D. A., Leef, K. H., Stefano, J. L., Bartoshesky, L.
(2000). Thyroid Function in Very-Low-Birth-Weight Infants with Intraventricular Hemorrhage. CLIN PEDIATR
39: 651-656
[Abstract]
Hack, M., Wilson-Costello, D., Friedman, H., Taylor, G. H., Schluchter, M., Fanaroff, A. A.
(2000). Neurodevelopment and Predictors of Outcomes of Children With Birth Weights of Less Than 1000 g: 1992-1995. Arch Pediatr Adolesc Med
154: 725-731
[Abstract][Full Text]
van Wassenaer, A. G., Kok, J. H.
(2000). Thyroid Function and Thyroid Hormone Requirements of Very Preterm Infants. NeoReviews
1: e116-121
[Full Text]
Herzmann, C., Torrens, J. K., de Escobar, G. M., del Rey, F. E., Fukushi, M., Honma, K., Fujita, K., Hollowell, J. G., Garbe, P. L., Miller, D. T., Haddow, J. E., Klein, R. Z., Mitchell, M., Utiger, R. D.
(1999). Maternal Thyroid Deficiency during Pregnancy and Subsequent Neuropsychological Development of the Child. NEJM
341: 2015-2017
[Full Text]
BIZOLLON, T, TREPO, C
(1999). Transplantation in HCV: whither immunosuppression. Gut
45: 327-328
[Full Text]
Dammann, O., Leviton, A.
(1999). Brain Damage in Preterm Newborns: Might Enhancement of Developmentally Regulated Endogenous Protection Open a Door for Prevention?. Pediatrics
104: 541-550
[Abstract][Full Text]
Dembinski;, J., Paul, D. A., Leff, K. H., Stefano, J. L., Bartoshesky, L.
(1999). Thyroid Function and Adverse Outcome---What Is the Message?. Pediatrics
104: 129-129
[Full Text]
Asteria, C., Rajanayagam, O., Collingwood, T. N., Persani, L., Romoli, R., Mannavola, D., Zamperini, P., Buzi, F., Ciralli, F., Chatterjee, V. K. K., Beck-Peccoz, P.
(1999). Prenatal Diagnosis of Thyroid Hormone Resistance. J. Clin. Endocrinol. Metab.
84: 405-410
[Abstract][Full Text]
Kilby, M. D., Verhaeg, J., Gittoes, N., Somerset, D. A., Clark, P. M. S., Franklyn, J. A.
(1998). Circulating Thyroid Hormone Concentrations and Placental Thyroid Hormone Receptor Expression in Normal Human Pregnancy and Pregnancy Complicated by Intrauterine Growth Restriction (IUGR). J. Clin. Endocrinol. Metab.
83: 2964-2971
[Abstract][Full Text]
Wilson-Costello, D., Borawski, E., Friedman, H., Redline, R., Fanaroff, A. A., Hack, M.
(1998). Perinatal Correlates of Cerebral Palsy and Other Neurologic Impairment Among Very Low Birth Weight Children. Pediatrics
102: 315-322
[Abstract][Full Text]
Smit, B. J., Kok, J. H., de Vries, L. S., van Wassenaer, A. G., Dekker, F. W., Ongerboer de Visser, B. W.
(1998). Somatosensory Evoked Potentials in Very Preterm Infants in Relation to L-Thyroxine Supplementation. Pediatrics
101: 865-869
[Abstract][Full Text]
Paul, D. A., Leef, K. H., Stefano, J. L., Bartoshesky, L.
(1998). Low Serum Thyroxine on Initial Newborn Screening Is Associated With Intraventricular Hemorrhage and Death in Very Low Birth Weight Infants. Pediatrics
101: 903-907
[Abstract][Full Text]
DAMMANN, O., LEVITON, A.
(1998). Is some white matter damage in preterm neonates induced by a human pestivirus?. Arch. Dis. Child. Fetal Neonatal Ed.
78: 230F-231
[Full Text]
Morreale de Escobar, G.
(1998). The Hypothyroxinemia of Prematurity. J. Clin. Endocrinol. Metab.
83: 713-715
[Full Text]
Fisher, D. A.
(1997). The Hypothroxinemia of Prematurity. J. Clin. Endocrinol. Metab.
82: 1701-1703
[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]
Paneth, N., Jetton, J., Pinto-Martin, J., Susser, M., the Neonatal Brain Hemorrhage Study Analysis Group,
(1997). Magnesium Sulfate in Labor and Risk of Neonatal Brain Lesions and Cerebral Palsy in Low Birth Weight Infants. Pediatrics
99: e1-e1
[Abstract][Full Text]
Crowther, C. A., Hiller, J. E., Haslam, R. R., Robinson, J. S., the ACTOBAT Study Group,
(1997). Australian Collaborative Trial of Antenatal Thyrotropin-Releasing Hormone: Adverse Effects at 12-Month Follow-up. Pediatrics
99: 311-317
[Abstract][Full Text]
van Wassenaer, A. G., Kok, J. H., de Vijlder, J. J.M., Briet, J. M., Smit, B. J., Tamminga, P., van Baar, A., Dekker, F. W., Vulsma, T.
(1997). Effects of Thyroxine Supplementation on Neurologic Development in Infants Born at Less Than 30 Weeks' Gestation. NEJM
336: 21-26
[Abstract][Full Text]
(1996). HYPOTHYROXINEMIA: ANOTHER PROBLEM FOR PREMATURE INFANTS?. JWatch General
1996: 5-5
[Full Text]
Vulsma, T., Kok, J. H.
(1996). Prematurity-Associated Neurologic and Developmental Abnormalities and Neonatal Thyroid Function. NEJM
334: 857-858
[Full Text]