Neurodevelopment May Be Entirely Normal in Children Born to ...

ClinicalTHYROIDOLOGYNeurodevelopment May Be EntirelyNormal in Children Born to Women with HypothyroidismWho Are Restored to Euthyroidism by Late PregnancyMomotani N, Iwama S, Momotani K. Neurodevelopment in children born to hypothyroid mothersrestored to normal thyroxine (T 4 ) concentration by late pregnancy in Japan: No apparent influence ofmaternal T 4 deficiency. J Clin Endocrinol Metab. February 8, 2012 [Epub ahead of print].SUMMARYBackgroundThyroid hormone is essential for brain developmentboth before and after birth. Maternal T 4 has beenshown to have a crucial role in brain developmentin fetuses with sporadic congenital hypothyroidism.The importance of maternal T 4 has also been shownin basic studies in fetal neurodevelopment before theonset of fetal thyroid function, which corresponds tothe first trimester in humans. Moreover, the correlationbetween mild maternal T 4 deficiency at 12 to17 weeks’ gestation and disturbance of neurodevelopmentin progeny has been shown in case–controlstudies in The Netherlands and the United States.These observations have given rise to the perceptionthat maternal hypothyroidism or T 4 deficiency inearly pregnancy leads to a defect in neuropsychologicaldevelopment. On the other hand, the absence ofintellectual impairment among children, irrespectiveof the severity of T 4 deficiency in the mother in earlypregnancy after T 4 normalization by late pregnancy,has been reported from Japan. This points to uncertaintyabout whether the neurologic impairment is aresult of reduced availability of maternal T 4 in earlypregnancy. The authors reported five cases showingno apparent effect of maternal T 4 deficiency on neurodevelopmentin progeny in whom low T 4 levels hadbeen corrected by late pregnancy.MethodsFive women with overt hypothyroidism detected at6 to 16 weeks’ gestation initiated T 4 treatment. Theserum TSH levels at detection ranged from 23.3 to 657mU/L and the serum FT 4 from 0.09 to 0.66 ng/dl. Infour women, euthyroidism was restored by the 20thweek. One remained in a subclinical hypothyroid state.Developmental scores of their children were evaluatedbetween 25 months and 11 years of age by either theTsumori-Inage Infant’s Developmental Test or theWechsler Intelligence Scale for Children-Third Edition(WISC-III) and compared with those of siblings withno exposure to maternal hypothyroidism.ResultsInitial serum TSH and FT 4 levels were monitored at2- to 6-week intervals; they normalized by 20 weeksin 4 patients; in the other woman, subclinical hypothyroidismremained for the rest her gestation. TheWISC-III scores of 3 children were compared withtheir 3 siblings born when mothers were euthyroidduring a subsequent pregnancy; the scores werewithin the normal range and not significantly differentbetween the siblings. In the other 2 infants, the scoreon the Tsumori-Inage infant psychomotor developmenttest was within the normal range at age 25 and35 months. Their siblings were not tested.ConclusionsIn iodine-sufficient areas, maternal T 4 deficiency inearly pregnancy does not necessarily affect neurodevelopment.However, early detection by routinescreening would be crucial where recovery fromhypothyroidism by late pregnancy is essential fornormal brain development. Therefore, other factorsthat could potentially alter neurodevelopment, suchas iodine deficiency, must be investigated.continued on next pageCLINICAL THYROIDOLOGY • APRIL 2012 8 VOLUME 24 • ISSUE 4 • © 2012Back to Contents

Neurodevelopment May Be Entirely Normal in ChildrenBorn to Women with Hypothyroidism Who AreRestored to Euthyroidism by Late PregnancyMomotani N, et al.ANALYSIS AND COMMENTARYIn this study, IQ and DQ (development quotient) scoresindicated no apparent neurodevelopmental deficitin children whose mothers had overt hypothyroidismduring the first trimester of pregnancy and wererestored to normal serum T 4 levels by late pregnancy.Haddow et al. (1) reported lower IQs in children ofuntreated pregnant women with hypothyroidism. Atabout the same time, Pop et al. (2) described impairedpsychomotor development in infants of women withhypothyroxinemia who had serum TSH levels withinthe reference range. In the Pop study, children ofwomen with hypothyroxinemia with FT 4 levels belowthe 5th percentile (11 mothers) and below the 10thpercentile (22 mothers) at 12 weeks’ gestation wereevaluated at 10 months of age using the Bailey PsychomotorDevelopment Index scale; they had significantlylower scores as compared with children ofmothers with higher FT 4 values. Since this study wascarried out in an area with iodine sufficiency, therewas no clear cause to explain isolated cases of hypothyroxinemia.It is well known that in areas of chroniciodine deficiency, serum iodine and T 4 are low, witha corresponding increase in T3 production (3). Otherstudies from areas of iodine deficiency describe deleteriousneurocognitive defects in offspring of womenwith hypothyroxinemia (4). In Japan in 1994, Liu etal. (5) studied IQs of eight children born of womenwith severe hypothyroidism (mean [±SD] serum TSH,116±59 µU/ml; FT 4 ,

Neurodevelopment May Be Entirely Normal in ChildrenBorn to Women with Hypothyroidism Who AreRestored to Euthyroidism by Late PregnancyMomotani N, et al.3. Pharoah PO, Lawton NF, Ellis SM et al. The roleof triiodothyronine (T 3 ) in the maintenance ofeuthyroidism in endemic goitre. Clin Endocrinol(Oxf) 1973;2:193-9.4. Henrichs J, Bongers-Schokking JJ, Schenck JJ, et al.Maternal thyroid function during early pregnancyand cognitive functioning in early childhood:the generation R study. J Clin Endocrinol Metab2010;95:4227-34. Epub June 9, 2010.5. Liu H, Momotani N, Noh JY, Ishikawa N, TakebeK, Ito K. Maternal hypothyroidism during earlypregnancy and intellectual development of theprogeny. Arch Intern Med 1994;154:7857.6. Pop VJ, Brouwers EP, Vader HL, Vulsma T, vanBaar AL, de Vijlder JJ. Maternal hypothyroxinemiaduring early pregnancy and subsequent childdevelopment: a 3-year follow-up study. ClinEndocrinol (Oxf) 2003;59:282-8.7. Orito Y, Oku H, Kubota S, et al. Thyroid functionin early pregnancy in Japanese healthy women:relation to urinary iodine excretion, emesis, andfetal and child development J Clin EndocrinolMetab 2009;94:1683-8. Epub March 3, 2009.8. Belfort MB, Pearce EN, Braverman LE, He X, BrowRS. Low iodine content in the diets of hospitalizedpreterm infants. J Cin Endocrinol Metab. February15, 2012 [Epub ahead of print].9. Moleti M, Lo Presti VP, Campolo MC, et al.Iodine prophylaxis using iodized salt and riskof maternal thyroid failure in conditions ofmild iodine deficiency. J Clin Endocrinol Metab2008;93:2616–21. Epub April 15, 2008.www.thyroid.orgWe invite you to join the ATA!Are You Intrigued by the Study of the Thyroid? You Belong in the ATA!• ATA members are leaders in thyroidology who promote excellence andinnovation in clinical care, research, education, and public policy.• Join us as we advance our understanding of the causes and improve the clinicalmanagement of thyroid diseases in this era of rapid pace biomedical discovery.• A close-knit, collegial group of physicians and scientists, the ATA is dedicatedto the reseach and treatment of thyroid diseases. ATA's rich history dates back to1923 and its members are respected worldwide as leaders in thyroidology.• The ATA encourages you to apply for membership. We want you to experience thewealth of knowledge and enjoy the benefits of being active in this highly specializedand regarded society. The ATA looks forward to having you as a member!CLINICAL THYROIDOLOGY • APRIL 2012 10 VOLUME 24 • ISSUE 4 • © 2012Back to Contents