Thyroid
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
Liothyronine (T3) is compatible with all stages of pregnancy. Untreated or undertreated maternal hypothyroidism is associated with low birth weight secondary to medically indicated preterm delivery, preeclampsia, or placental abruption (1) and with lower neuropsychological development of their offspring (2).
FETAL RISK SUMMARY
T3 is a naturally occurring thyroid hormone produced by the mother and the fetus. It is used during pregnancy for the treatment of hypothyroidism (see also Levothyroxine and Thyroid). Although early studies found little or no transplacental passage of T3 at physiologic serum concentrations (3–5), as well as limited passage following very high doses (6,7), a 1994 review cited evidence that small amounts of T3 do cross the human placenta (8).
In a large prospective study, 34 mother–child pairs were exposed to T3 during the 1st trimester. No association between the drug and fetal defects was found (9). Maternal hypothyroidism itself has been reported to be responsible for poor pregnancy outcome (10). Others have not found this association, claiming that fetal development is not directly affected by maternal thyroid function (11). However, untreated maternal hypothyroidism during pregnancy has been shown to result in lower scores relating to intelligence, attention, language, reading ability, school performance, and visual–motor performance in children 7–9 years of age (2).
Combination therapy with thyroid–antithyroid drugs was advocated at one time for the treatment of hyperthyroidism but is now considered inappropriate (see Propylthiouracil).
BREASTFEEDING SUMMARY
T3 is excreted into breast milk in low concentrations. The effect on the nursing infant is not thought to be physiologically significant, although at least one report concluded otherwise (12). An infant was diagnosed as athyrotic shortly after breastfeeding was stopped at age 10 months. Growth was at the 97th percentile during breastfeeding, but the bone age remained that of a newborn. Mean levels of T3 in breast milk during the last trimester (12 patients) and within 48 hours of delivery (22 patients) were 1.36 and 2.86 ng/mL, respectively (12).
A 1978 study reported milk concentrations varying between 0.4 and 2.38 ng/mL (range 0.1–5 ng/mL) from the day of delivery to 148 days postpartum (13). No T3 was detected in a number of samples. Levels in three instances, collected 16, 20, and 43 months postpartum, ranged from 0.68 to 4.5 ng/mL with the highest concentration measured at 20 months. From the first week through 148 days postdelivery, the calculated maximum amount of T3 that a nursing infant would have ingested was 2.1–2.6 mcg/day, far less than the dose required to treat congenital hypothyroidism. However, it was concluded that this was enough to mask the symptoms of the disease without halting its progression (13).
In a study comparing serum T3 levels between 22 breastfed and 29 formula-fed infants, significantly higher levels were found in the breastfeeding group. The levels, 2.24 and 1.79 ng/mL, were comparable with previous reports and probably were of doubtful clinical significance (14).
A 1980 report described four exclusively breastfed infants with congenital hypothyroidism who were diagnosed between the ages of 2 and 79 days. Breastfeeding did not hinder making the diagnosis (15). Another report, evaluating clinical and biochemical thyroid parameters in hypothyroid infants, found no differences between breastfed (N = 12) and bottle-fed (N = 33) babies. These results lead to the conclusion that breast milk does not offer protection against the effects of congenital hypothyroidism (16). As reported in a 1985 paper, serum concentrations of T3 were similar in breastfed and bottle-fed infants at 5, 10, and 15 days postpartum. The levels were too low to interfere with neonatal thyroid screening programs (17).
Japanese researchers found a T3 milk:plasma ratio of 0.36 (18). No correlation was discovered between serum T3 and milk T3 or total daily T3 excretion, nor was there a correlation between milk T3 levels and milk protein concentration or daily volume of milk. They concluded that breastfeeding has no influence on the pituitary–thyroid axis of normal babies (18). A Swedish investigation measured higher levels of T3 in milk 1–3 months after delivery as compared with T3 levels in early colostrum (19). The concentrations were comparable with those in the studies cited above.
T3 breast milk concentrations are too low to protect a hypothyroid infant completely from the effects of the disease.
References
1.American College of Obstetricians and Gynecologists. Thyroid disease in pregnancy. ACOG Practice Bulletin. No. 37, August 2002.
2.Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, O’Heir CE, Mitchell ML, Hermos RJ, Waisbren SE, Faix JD, Klein RZ. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999;341:549–55.
3.Grumbach MM, Werner SC. Transfer of thyroid hormone across the human placenta at term. J Clin Endocrinol Metab 1956;16:1392–5.
4.Kearns JE, Hutson W. Tagged isomers and analogues of thyroxine (their transmission across the human placenta and other studies). J Nucl Med 1963;4:453–61.
5.Fisher DA, Lehman H, Lackey C. Placental transport of thyroxine. J Clin Endocrinol Metab 1964;24:393–400.
6.Raiti S, Holzman GB, Scott RI, Blizzard RM. Evidence for the placental transfer of tri-iodothyronine in human beings. N Engl J Med 1967;277:456–9.
7.Dussault J, Row VV, Lickrish G, Volpe R. Studies of serum triiodothyronine concentration in maternal and cord blood: transfer of triiodothyronine across the human placenta. J Clin Endocrinol Metab 1969;29:595–606.
8.Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. N Engl J Med 1994;331:1072–8.
9.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:388–400.
10.Potter JD. Hypothyroidism and reproductive failure. Surg Gynecol Obstet 1980;150:251–5.
11.Montoro M, Collea JV, Frasier SD, Mestman JH. Successful outcome of pregnancy in women with hypothyroidism. Ann Intern Med 1981;94:31–4.
12.Bode HH, Vanjonack WJ, Crawford JD. Mitigation of cretinism by breast-feeding. Pediatrics 1978;62:13–6.
13.Varma SK, Collins M, Row A, Haller WS, Varma K. Thyroxine, triiodothyronine, and reverse triiodothyronine concentrations in human milk. J Pediatr 1978;93:803–6.
14.Hahn HB Jr, Spiekerman AM, Otto WR, Hossalla DE. Thyroid function tests in neonates fed human milk. Am J Dis Child 1983;137:220–2.
15.Abbassi V, Steinour TA. Successful diagnosis of congenital hypothyroidism in four breast-fed neonates. J Pediatr 1980;97:259–61.
16.Letarte J, Guyda H, Dussault JH, Glorieux J. Lack of protective effect of breast-feeding in congenital hypothyroidism: report of 12 cases. Pediatrics 1980;65:703–5.
17.Franklin R, O’Grady C, Carpenter L. Neonatal thyroid function: comparison between breast-fed and bottle-fed infants. J Pediatr 1985;106:124–6.
18.Mizuta H, Amino N, Ichihara K, Harade T, Nose O, Tanizawa O, Miyai K. Thyroid hormones in human milk and influence on thyroid function of breast-fed babies. Pediatr Res 1983;17:468–71.
19.Jansson L, Ivarsson S, Larsson I, Ekman R. Tri-iodothyronine and thyroxine in human milk. Acta Paediatr Scand 1983;72:703–5.