Bromides

Name: BROMIDES
Class: Anticonvulsant/Sedative
Risk Factor: D

Fetal Risk Summary

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 986 of which had 1st trimester exposure to bromides (1, pp. 402–406). For use anytime during pregnancy, 2,610 exposures were recorded (1, p. 444). In neither group was evidence found to suggest a relationship to large categories of major or minor malformations. Four possible associations with individual malformations were found, but the statistical significance of these is unknown and independent confirmation is required: Polydactyly (14 cases) Gastrointestinal anomalies (10 cases) Clubfoot (7 cases) Congenital dislocation of hip (use anytime) (92 cases) Two infants with intrauterine growth retardation from a mother who chronically ingested a proprietary product containing bromides (Bromo-Seltzer) have been described (2). Both male infants were microcephalic (one at the 2nd percentile and one at less than the 2nd percentile) and one had congenital heart disease (atrial septal defect with possible pulmonary insufficiency). The mother did not use the product in three other pregnancies, two before and one after the affected children, and all three of these children were of normal height. In a similar case, a woman chronically ingested tablets containing bromides throughout gestation and eventually gave birth to a female infant who was growth retarded (all parameters below the 10th percentile) (3). Follow-up of the infant at 2.5 years of age indicated persistent developmental delay.
Neonatal bromide intoxication from transplacental accumulation has been described in four infants (4,5,6 and 7). In each case, the mother had either taken bromide-containing medications (three cases) or was exposed from employment in a photographic laboratory (one case). Bromide concentrations in three of the four infants were 3650, 2000, and 2420 µg/mL on days 6, 5, and 5, respectively (4,5 and 6). In the fourth case, a serum sample, not obtained until 18 days after birth, contained 150 µg/mL (7). All four infants exhibited symptoms of neonatal bromism consisting of poor suck, weak cry, diminished Moro reflex, lethargy, and hypotonia. One of the infants also had cyanosis and a large head with dysmorphic face (7). Subsequent examinations of three of the above infants revealed normal growth and development after several months (4,5 and 6). One infant, however, had mild residual hypotonia of the neck muscles persisting at 6 and 9.5 months (7).
Cord serum bromide levels were determined on 1,267 newborn infants born in Rochester, NY, during the first half of 1984 (8). Mean bromide concentrations were 8.6 µg/mL (range 3.1–28.5 µg/mL), well below the serum bromide level (>720 µg/mL) that is considered toxic (8). The measured concentrations were not related to Apgar scores, neonatal condition, or congenital abnormalities. None of the mothers was taking bromide-containing drugs (most of which have been removed from the market), and the concentrations in cord blood were thought to have resulted from occupational exposure to photographic chemicals or from the low levels encountered in food and water.

Breast Feeding Summary

The excretion of bromides into breast milk has been known since at least 1907 (9). A 1938 report reviewed this topic and demonstrated the presence of bromides in milk in an additional 10 mothers (9). A 1935 report measured milk concentrations of 1666 µg/mL in two patients treated with 5 g daily for 1 month (10). Rash and sedation of varying degrees in several nursing infants have been reported as a result of maternal consumption of bromides during lactation (9,10 and 11). Although bromide-containing medications are no longer available in the United States, these drugs may be available in other countries. In addition, high maternal serum levels may be obtained from close, frequent exposure to chemicals used in photographic developing. Women who are breast feeding and are exposed to such chemicals should be alert for symptoms of sedation or drowsiness and unexplained rashes in their infants. Monitoring of bromide levels in these women may be beneficial. Breast feeding is not recommended for women receiving bromide-containing medications, although the American Academy of Pediatrics considers bromides to be compatible with breast feeding (12).

References

1. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
2. Opitz JM, Grosse RF, Haneberg B. Congenital effects of bromism? Lancet 1972;1:91–2.
3. Rossiter EJR, Rendel-Short TJ. Congenital effects of bromism? Lancet 1972;2:705.
4. Finken RL, Robertson WO. Transplacental bromism. Am J Dis Child 1963;106:224–6.
5. Mangurten HH, Ban R. Neonatal hypotonia secondary to transplacental bromism. J Pediatr 1974;85:426–8.
6. Pleasure JR, Blackburn MG. Neonatal bromide intoxication: prenatal ingestion of a large quantity of bromides with transplacental accumulation in the fetus. Pediatrics 1975;55:503–6.
7. Mangurten HH, Kaye CI. Neonatal bromism secondary to maternal exposure in a photographic laboratory. J Pediatr 1982;100:596–8.
8. Miller ME, Cosgriff JM, Roghmann KJ. Cord serum bromide concentration:variation and lack of association with pregnancy outcome. Am J Obstet Gynecol 1987;157:826–30.
9. Tyson RM, Shrader EA, Perlman HH. Drugs transmitted through breast milk. III. Bromides. J Pediatr 1938;13:91–3.
10. Kwit NT, Hatcher RA. Excretion of drugs in milk. Am J Dis Child 1935;49:900–4.
11. Van der Bogert F. Bromin poisoning through mother's milk. Am J Dis Child 1921;21:167.
12. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.

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