Warfarin Pregnancy and Breastfeeding Warnings
Warfarin Pregnancy Warnings
Warfarin has been assigned to pregnancy category X by the FDA. Problems associated with perinatal administration of warfarin have included central nervous system defects, spontaneous abortion, stillbirth, prematurity, hemorrhage, and ocular defects when given anytime during pregnancy, and a fetal warfarin syndrome when given during the first trimester. Warfarin is considered contraindicated during pregnancy.
Limited data suggest warfarin fetal complications may be dose dependent. A study of 58 pregnancies with 31 healthy babies revealed an increased incidence of complications at dosages greater than 5 mg daily. Fetal warfarin syndrome is characterized by nasal hypoplasia, hypoplasia of the extremities, and developmental retardation. In a review of 418 reported pregnancies during which warfarin was administered, one-sixth resulted in fetal abnormalities, one-sixth resulted in abortion or stillbirths, and two-thirds resulted in normal infants. Nasal hypoplasia, varying in severity, is the most common feature of warfarin embryopathy. Epiphyseal stippling, primarily in the axial skeleton, proximal femurs, and the calcanei is present in the majority of cases. In addition, hypoplasia of the extremities, low birth weight, eye abnormalities (i.e. optic atrophy, microphthalmia, and blindness), and developmental retardation may be present. In one review, the common time of exposure was from the sixth to the ninth week of gestation in all 24 cases of warfarin embryopathy. Central nervous system abnormalities include dorsal midline dysplasia with agenesis of the corpus callosum, Dandy-Walker malformation, midline cerebellar atrophy, and ventral midline dysplasia with optic atrophy. Exposure time does not appear to play a role in the development of CNS anomalies. Cases have been reported in the absence of first trimester exposure. However, in one review, all cases of CNS anomalies involved second and/or third trimester exposure. Hall, et al (1980) reviewed and analyzed published cases involving coumarin use during pregnancy. A total of 418 pregnancies were evaluated. In 156 pregnancies, coumarin derivatives were used throughout pregnancy. Of these, 76% resulted in normal liveborn infants. Fetal complications, including spontaneous abortion, stillbirth, prematurity, CNS anomalies, embryopathy, and fetal hemorrhage, occurred in the remaining 24% of cases. In another literature review, Ginsberg and Hirsh (1989) documented 45 cases of warfarin embryopathy and 26 cases of CNS abnormalities out of 970 pregnancies in which warfarin was used. After excluding pregnancies with maternal comorbid conditions, analysis of cases in which oral anticoagulants were used alone revealed a 26.5% incidence of adverse pregnancy outcome. Again, use of warfarin between weeks six and twelve of gestation appeared to be associated with warfarin embryopathy. Forty-three women with mechanical heart valves, maintained throughout pregnancy on warfarin, and carrying out 58 pregnancies were observed. In the group of 25 pregnancies taking greater than 5 mg warfarin daily, 22 fetal complications and 3 full term pregnancies occurred. Complications included 18 spontaneous abortions, 2 warfarin embryopathies (spontaneously aborted in the 6 month), 1 stillbirth, and 1 ventricular septal defect (closed in the first year of life). The group of 33 pregnancies receiving less than 5 mg warfarin daily delivered 27 full term babies and 1 premature baby. Five fetal complications in this group included 4 spontaneous abortions and 1 infant with growth retardation (no skeletal, mental, or neurologic retardation, and now fully developed).
Warfarin Breastfeeding Warnings
Orme, et al (1977) evaluated the excretion of warfarin into breast milk of 13 women treated with warfarin 5 to 12 mg per day. Warfarin was undetectable (< 0.08 mmol/L) in all milk samples. Seven women elected to continue breast-feeding their infants. Warfarin was undetectable in plasma samples from all seven infants. In addition, all seven infants had normal prothrombin times. McKenna, et al (1983) reported similar results. Two women who required warfarin anticoagulation after delivery and their infants were followed, in one case for 56 days and in the other for 131 days. Both women elected to continue to breast-feed. At no time was warfarin detected in the milk of either mother nor were any changes in prothrombin activity in either infant.
Based on limited data, warfarin has not been detected in human milk. However, changes in prothrombin time in breast-feeding infants of mothers treated with warfarin have been reported. The manufacturer recommends that caution be used when administering warfarin to nursing women.
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