Fluconazole-Induced Congenital Anomalies in Three Infants

Abstract

Fluconazole has been associated with various teratisms in animals, including craniofacial ossification defects, thin, wavy ribs, and renal pelvis defects. We describe three infants born to women who were receiving fluconazole through or beyond the first trimester of pregnancy. All of the infants had congenital anomalies; no other drug was implicated. Only one of the three infants survived. Their anomalies, similar to those observed in animal studies, were largely craniofacial, skeletal (i.e., thin, wavy ribs and ossification defects), and cardiac. One of these infants was previously reported as having Antley-Bixler syndrome; however, given the chronology described herein and the similarity of this infant to the others, we conclude that her deformities also represent the potent teratogenic effect of fluconazole.

Fluconazole-Associated Birth Defects: A Comprehensive Review

“…The same 22-year old mother described by Lee et al 11 had two subsequent pregnancies that were reported by Pursley et al 12 in 1996. During her third pregnancy, the patient was nonadherent to therapy, delivered a healthy boy, and resumed FLU therapy.…”

“…9 In August 2011, the U.S. Food and Drug Administration (FDA) issued a safety announcement concerning the use of FLU in pregnancy. On the basis of several published case reports in humans [11][12][13][14] , and animals showing similar causative effects 15 , the FDA changed the pregnancy category of FLU from category C to category D for all indications except FLU 150 mg as a single dose for treatment of vaginal candidiasis, citing trends of "a rare and distinct set of birth defects in infants whose mothers were treated with the drug during the first trimester of pregnancy".included a short, broad head, abnormal looking face, abnormal development of the skullcap, oral cleft, bowing of the thigh bones, thin ribs and long bones, muscle weakness and joint deformities, and congenital heart disease. 16 Created in 1980, the FDA's drug-associated pregnancy risk categories, which consist of the letter designations of A, B, C, D, or X, are assigned according to the known or potential fetal harm associated with drug therapy.…”

“…The infant died at 3 months of age from pneumonia, presumably secondary to tracheomalacia. 12 Pursley et al 12 also reported the case of a 25-year old mother treated for coccidioidal meningitis with FLU 800 mg/day through delivery at 38 weeks gestation (with a FLU hiatus during weeks 7-9). Congenital abnormalities found upon examination were as follows: flattened occiput, brachycephaly, trigonocephaly, supraorbital ridge hypoplasia, bitemporal narrowing, open cranial sutures, large anterior fontanel, maxillary hypoplasia, short ear helices, micrognathia, exotropia, bowed femurs, diffuse osteopenia, thin ribs, clavicles, and long bones, long metacarpals and phalanges, hypoplastic facial bones, craniofacial disproportion, slanted orbital roofs, tetralogy of Fallot, patent ductus arteriosus, right and left pulmonary artery hypoplasia, patent foramen ovale, and large ventricular septal defect.…”

“…Congenital abnormalities found upon examination were as follows: flattened occiput, brachycephaly, trigonocephaly, supraorbital ridge hypoplasia, bitemporal narrowing, open cranial sutures, large anterior fontanel, maxillary hypoplasia, short ear helices, micrognathia, exotropia, bowed femurs, diffuse osteopenia, thin ribs, clavicles, and long bones, long metacarpals and phalanges, hypoplastic facial bones, craniofacial disproportion, slanted orbital roofs, tetralogy of Fallot, patent ductus arteriosus, right and left pulmonary artery hypoplasia, patent foramen ovale, and large ventricular septal defect. 12 In 1996, Wiesinger et al 18 described the case of a 24-year old female admitted at 16-weeks gestation with Candida sepsis.…”

No association between vulvovaginitis-bacterial vaginosis, related drug treatments of pregnant women, and congenital abnormalities in their offspring — A population-based case-control study

“…On the other hand, the potential teratogenic effect of drugs used for the treatment of maternal VV-BV during pregnancy was frequently evaluated. For example the high dose of fluconazole [11,12] was found to be teratogenic in human beings.…”