Respiratory Drug (Expectorant)
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 2nd and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Because a large number of prescription and over-the-counter medications contain iodide or iodine, pregnant patients should consult with their physician before using these products. The American Academy of Pediatrics considers the use of iodides as expectorants during pregnancy to be contraindicated (1).
FETAL RISK SUMMARY
The primary concern with the use of potassium iodide and the anti-infective, iodine, during pregnancy relates to the effect of iodide on the fetal thyroid gland. Because aqueous solutions of iodine are in equilibrium with the ionized form, all iodide or iodine products are considered as one group.
Iodide readily crosses the placenta to the fetus (2). When used for prolonged periods or close to term, iodide may cause hypothyroidism and goiter in the fetus and newborn. Short-term use, such as a 10-day preparation course for maternal thyroid surgery, does not carry this risk and is apparently safe (3,4). A 1983 review tabulated 49 cases of congenital iodide goiter dating back to 1940 (66 references) (5). In 14 cases, the goiter was large enough to cause tracheal compression resulting in death. Cardiomegaly was present in three surviving newborns and in one of the fatalities. In a majority of the cases, exposure to the iodide was a result of maternal asthma treatment.
Four studies have shown the potential hazard resulting from the use of povidone-iodine during pregnancy (6–9). In each case, significant absorption of iodine occurred in the mother and fetus following topical, vaginal, or perineal use before delivery. Transient hypothyroidism was demonstrated in some newborns (6,9).
BREASTFEEDING SUMMARY
Iodide is concentrated in breast milk (5,10,11). In one report, a breastfeeding mother used povidone-iodine vaginal gel daily for 6 days without douching (10). Two days after stopping the gel, the mother noted an odor of iodine on the 7.5-month-old baby. The free iodide serum:milk ratio 1 day later was approximately 23:1. By day 7, the ratio had fallen to about 4:1 but then rose again on day 8 to 10:1. Serum and urine iodide levels in the infant were grossly elevated. No problems or alterations in thyroid tests were noted in the baby.
In a 2000 case report, a woman delivered a female infant at 29 weeks’ gestation by cesarean section (11). An abscess of the abdominal wall 1 week after delivery was treated with IV antibiotics and iodine tampons (each tampon contained about 10.5 mg of iodine). Full breastfeeding of the infant was begun approximately 20 days after birth. At 29 days, neonatal hypothyroidism was diagnosed: the thyroid-stimulating hormone (TSH) level was 287.9 µU/mL (normal range 0.45–10.0 microU/mL). Iodine levels in the mother’s milk and infant urine were 4410 mcg/L (normal range 29–490 mcg/L) and 3932 mcg/L (normal <185 mcg/L), respectively. At 32 days, iodine tampons and breastfeeding were stopped and the infant was given levothyroxine (25 mcg/day). Six days later, thyroid function had normalized and breastfeeding was restarted. The infant’s thyroid function remained normal over a 4-month follow-up period (11).
The use of povidone-iodine immediately before delivery as a topical anesthetic for epidural anesthesia or cesarean section produced iodine overload in newborn infants who were breastfed as evidenced by increased neonatal TSH concentrations (12). Breastfed infants had a 25- to 30-fold increase in the recall rate at screening for congenital hypothyroidism (TSH >50 mU/L) compared with bottle-fed infants.
The normal iodine content of human milk has been recently assessed (13). Mean iodide levels in 37 lactating women were 178 mcg/L. This is approximately 4 times the recommended daily allowance (RDA) for infants. The RDA for iodine was based on the amount of iodine found in breast milk in earlier studies (13). The higher levels now are probably caused by dietary supplements of iodine (e.g., salt, bread, cow’s milk). The significance to the nursing infant from the chronic ingestion of higher levels of iodine is not known. The American Academy of Pediatrics, although recognizing that the maternal use of iodides during lactation may affect the infant’s thyroid activity by producing elevated iodine levels in breast milk, classifies the agents as compatible with breastfeeding (14).
References
1.Committee on Drugs. American Academy of Pediatrics. Adverse reactions to iodide therapy of asthma and other pulmonary diseases. Pediatrics 1976;57:272–4.
2.Wolff J. Iodide goiter and the pharmacologic effects of excess iodide. Am J Med 1969;47:101–24.
3.Herbst AL, Selenkow HA. Hyperthyroidism during pregnancy. N Engl J Med 1965;273:627–33.
4.Selenkow HA, Herbst AL. Hyperthyroidism during pregnancy. N Engl J Med 1966;274:165–6.
5.Mehta PS, Mehta SJ, Vorherr H. Congenital iodide goiter and hypothyroidism: a review. Obstet Gynecol Surv 1983;38:237–47.
6.I’Allemand D, Gruters A, Heidemann P, Schurnbrand P. Iodine-induced alterations of thyroid function in newborn infants after prenatal and perinatal exposure to povidone iodine. J Pediatr 1983;102:935–8.
7.Bachrach LK, Burrow GN, Gare DJ. Maternal–fetal absorption of povidone-iodine. J Pediatr 1984;104:158–9.
8.Jacobson JM, Hankins GV, Young RL, Hauth JC. Changes in thyroid function and serum iodine levels after prepartum use of a povidone-iodine vaginal lubricant. J Reprod Med 1984;29:98–100.
9.Danziger Y, Pertzelan A, Mimouni M. Transient congenital hypothyroidism after topical iodine in pregnancy and lactation. Arch Dis Child 1987;62:295–6.
10.Postellon DC, Aronow R. Iodine in mother’s milk. JAMA 1982;247:463.
11.Casteels K, Punt S, Bramswig J. Transient neonatal hypothyroidism during breastfeeding after post-natal maternal topical iodine treatment. Eur J Pediatr 2000;159:716–7.
12.Chanoine JP, Boulvain M, Bourdoux P, Pardou A, Van Thi HV, Ermans AM, Delange F. Increased recall rate at screening for congenital hypothyroidism in breast fed infants born to iodine overloaded mothers. Arch Dis Child 1988;63:1207–10.
13.Gushurst CA, Mueller JA, Green JA, Sedor F. Breast milk iodide: reassessment in the 1980s. Pediatrics 1984;73:354–7.
14.Committee on Drugs. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.