Ebstein's anomaly (& Lithium, Phenytoin Syndrome, Coumarin Exposure)

Several retrospective studies have provided evidence that lithium is a human teratogen, with malformation rates as high as 12% in exposed infants. Among the most common defects are cardiac anomalies, including Ebstein anomaly, which is a rare malformation characterized by a malformed tricuspid valve and secondary abnormalities of the right ventricle and atrium. Atrial septal defect is another commonly reported abnormality. More recent studies have provided conflicting data about the degree of risk associated with maternal lithium use, leading some to suggest that it can be used cautiously in pregnancy among patients for whom other medications are not efficacious in controlling bipolar disorder. In general, even among those who would consider the use of lithium during pregnancy, it is reserved for patients at substantial risk of relapse if lithium is discontinued. It still is discontinued in these patients in very early pregnancy during embryogenesis and restarted if deterioration occurs. If lithium is administered during the second or third trimesters, care must be taken to avoid high serum levels; a neonatal concentration of lithium equivalent to the maternal level leads to sedation in the newborn period. Thyroid function disturbances also have been reported in infants of mothers treated with lithium. Patients must be counseled in detail about the relative risks and benefits of this approach. Lactating women should be advised that breastfeeding also might produce significant lithium concentrations in the infant.

Fetal alcohol syndrome is characterized by prenatal-onset growth retardation and facial dysmorphia. Although cardiac defects occur, they usually are septal defects. Fetal coumarin exposure results in nasal hypoplasia, stippling of the epiphyses, and low birthweight. Phenytoin syndrome includes growth deficiency, facial dysmorphia, and hypoplasia of the distal phalanges. Cardiac anomalies are less frequent and do not include Ebstein anomaly. Retinoic acid embryopathy is a severe syndrome characterized by central nervous system defects, microtia, and conotruncal malformations.

References:
Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML. A
reevaluation of risk of in utero exposure to lithium. JAMA.
1994;271:146-150
Jacobson SJ, Jones K, Johnson K, et al. Prospective multicentre study
of pregnancy outcome after lithium exposure during first trimester.
Lancet. 1992;339:530-533