Clinical Review

Hypothyroidism: Should we screen all pregnant women?

OBG Manag. 2004 May;16(5):33-45

References

1. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol(Oxf). 2003;59:282-288.

2. Blazer S, Moreh-Waterman Y, Miller-Lotan R, Tamir A, Hochberg Z. Maternal hypothyroidism may affect fetal growth and neonatal thyroid function. Obstet Gynecol. 2003;102:232-241.

3. Contempre B, Jauniaux E, Calvo R, Jurkovic D, Campbell S, de Escobar GM. Detection of thyroid hormones in human embryonic cavities during the first trimester of pregnancy. J Clin Endocrinol Metab. 1993;77:1719-1722.

4. Vulsma T, Gons MH, de Vijlder JJ. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to total organification defect or thyroid agenesis. N Engl J Med. 1989;321:13-16.

5. Oppenheimer JH, Schwartz HL. Molecular basis of thyroid hormone-dependent brain development. Endocr Rev. 1997;18:462-475.

6. Morreale De Escobar G, Obregon MJ, Escobar del Rey F. Is neurodevelopment related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab. 2000;85:3975-3987.

7. Kamijo K, Saito T, Sato M, et al. Transient subclinical hypothyroidism in early pregnancy. Endocrinol Jpn. 1990;37:397-403.

8. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18:404-433.

9. Utiger RD. Maternal hypothyroidism and fetal development. N Engl J Med. 1999;341:601-602.

10. Allan WC, Haddow JE, Palomaki GE, et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen. 2000;7:127-130.

11. Mandel SJ, Larsen PR, Seely EW, Brent GA. Increased need for thyroxine during pregnancy in women with primary hypothyroidism. N Engl J Med. 1990;323:91-96.

12. Usenko V, Lepekhin E, Lyzogubov V, Kornilovska I, Ushakova G, Witt M. The influence of low doses 131I-induced maternal hypothyroidism on the development of rat embryos. Exp Toxicol Pathol. 1999;51:223-227.

13. Lavado-Autric R, Auso E, Garcia-Velasco JV, et al. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J Clin Invest. 2003;111:1073-1082.

14. Man EB, Jones WS. Thyroid function in human pregnancy. V. Incidence of maternal serum low butanol-extractable iodines and of normal gestational TBG and TBPA capacities; retardation of 8-month-old infants. Am J Obstet Gynecol. 1969;104:898-908.

15. Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549-555.

16. The Endocrine Society. The Endocrine Society issues recommendations in response to major hypothyroidism study. August 1999. Available at: www.endosociety.org/pubrelations/pressreleases/archives/1999/hypothyroid.cfm. Accessed March 26, 2004.

17. AACE Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8:457-469.

18. American College of Obstetricians and Gynecologists. Thyroid disease in pregnancy. Clinical management guidelines for obstetrician-gynecologists. ACOG practice bulletin No. 37. Obstet Gynecol. 2002;100:387-396.

19. Lazarus JH, Wald NJ, Angele C, et al. The controlled antenatal thyroid screening study (CATS): first observations. Endocrine Abstracts. 2003;5:P262.-

20. Brent GA. Maternal thyroid function: interpretation of thyroid function tests in pregnancy. Clin Obstet Gynecol. 1997;40:3-15.

21. Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. N Engl J Med. 1994;311:1072-1078.

Considering the adverse effects that maternal hypothyroidism, even subclinical, can have on the offspring, the question arises: Is universal periconceptional screening for thyroid dysfunction appropriate? The current recommendations on this subject are unclear:

The Endocrine Society in 1999 called for a cost-effective screening program for hypothyroidism in all women before conception or in early pregnancy.¹⁶

The American Association of Clinical Endocrinologists recommended in 2002 that routine TSH measurement be performed before pregnancy or during the first trimester in all women.¹⁷

The American College of Obstetricians and Gynecologists, in contrast, stated in 2002 that data are insufficient to warrant routine screening of asymptomatic pregnant women; thyroid function tests should be performed only in gravidas with symptoms or a personal history of thyroid disease.¹⁸

Why routine screening is not yet justified

In view of the findings of adverse events associated with maternal hypothyroidism, a universal screening program appears warranted for timely initiation of therapy. However, data on the efficacy of T4 replacement in averting such effects is insufficient. Thus, it is premature to implement routine screening for thyroid function of all women contemplating pregnancy or early in gestation.

Well-designed clinical trials are needed to determine method and timing of testing, precise diagnostic criteria for maternal hypothyroidism, and ways to assure the adequacy and efficacy of therapy.

A randomized controlled antenatal screening study¹⁹ underway in South Wales aims to recruit 22,000 pregnant women.

Is current treatment inadequate?

These observations call into question the adequacy of current therapeutic regimens:

no significant differences were seen in the IQ scores of children of untreated and treated hypothyroid mothers,¹⁵ and
infants of treated hypothyroid women demonstrated restricted intrauterine growth and abnormal neonatal thyroid function.²

Take-home message. Although findings indicate hypothyroidism during pregnancy may have an adverse effect on fetal growth and neurodevelopment, evidence is insufficient to justify universal screening. Still, what we have learned to date enables us to formulate a reasonable monitoring and follow-up protocol (see “Clinical recommendations”).

CLINICAL RECOMMENDATIONS

In the general population, thyroid function testing—specifically, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) studies—prior to conception or in early pregnancy is reasonable, but the decision should be left to the individual patient and her physician.
TSH and FT4 testing should be performed prior to conception and during pregnancy in women with a family history of thyroid disease, symptoms of thyroid disease, or an immune disorder.
For women with a personal history of hypothyroidism who are taking thyroxine (T4) replacement, serum TSH should be closely monitored in early pregnancy. Most of these patients will become hypothyroid as detected by a rise in TSH unless the T4 dose is increased in early pregnancy.
For pregnant women found to be hypothyroid, close monitoring (4 to 6 week intervals) of TSH and FT4 throughout pregnancy and careful adjustment of the thyroid supplementation dosage are warranted.

The authors report no financial relationships relevant to this article.