Cyclophosphamide (CPA) remains one of the most widely prescribed anticancer drugs. It is also used
in the treatment of rheumatoid arthritis, childhood nephrotic syndrome and systemic lupus erythematosus. It is a
potent immunosuppressive agent. It is commonly used in blood and bone marrow transplantation. With the
growing trend among women postponing childbearing, the number of women who are diagnosed with breast
cancer is also increasing thus escalating the chances of exposure of the unborn child to antineoplastic drugs. A
review of the literature provides strong evidence for the teratogenic effects on infants prenatally exposed to CPA.
Both sporadic case reports and larger case series have demonstrated that babies with cyclophosphamide
embryopathy are afflicted with intrauterine growth restriction, small for gestational age, and craniofacial
malformations including eye anomalies, cleft/arched palate, hydrocephaly, micrognathia, low set microtia,
hearing defects, craniosynostosis, and facial asymmetry. Also observed in these cases are limb defects such as
radial, ulnar and tibial hypoplasia, club foot, digital defects of the hand and feet as well as vertebral fusion,
brevicolis, and occasional Sprengel’s deformity. These anomalies vary in consistency of occurrence and severity
of the phenotype across cases and lack the specificity of thalidomide embryopathy or rubella embryopathy.
However, they do occur is no longer in doubt. First trimester of pregnancy seems to be particularly susceptible to
fetal malformations, although CPA effects on fetuses of later stages of gestation (hearing defects, growth
restriction for example) are also reported occasionally. One of the major concerns from a mechanistic point of
view is our inability to dissect the teratogenic effects of CPA from those of other drugs administered together
with CPA as combination therapy. Animal experiments have been of particular value in that they are able to
circumvent the numerous extraneous variables inherent to human case reports. They have also revealed the
detrimental effects of CPA on gametes, preimplantation embryos, organogenesis as well as their potential
teratogenic mechanisms. Of particular importance are the role of genetic polymorphisms, male mediated
teratogenesis, ovarian failure, preimplantation embryo loss, epigenetic modifications, proxidant-antioxidant
imbalance, autophagy, apoptosis, microRNAs and postclosure neural tube defects induced by CPA -all of which
are areas for further research in CPA teratogenesis.