Botulinum toxin A during pregnancy, still a debate

Sir, In 2004, Newman et al., [1] reported the first case of a woman who received onabotulinumtoxinA (OT/A) treatment during pregnancy. Since then, 24 case reports, including those from a US survey conducted on 900 physicians, have been published [2–7]. OT/A is still considered by the FDA a Class C medication during pregnancy: ‘animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.’ The use of botulinum toxin has increased recently not only for medical purposes but also for esthetic applications in older women (http://www.cosmeticplasticsurgerystatistics.com/index). Moreover, there is an increased trend toward delayed childbearing in developed countries (http://www.cdc.gov/nchs/data_access/vitalstats/VitalStats_Births.htm). In consequence, the likelihood of pregnant women receiving OT/A for cosmetic reasons is expected to raise. We report another case of OT/A injection during pregnancy. A 41 year old woman with idiopathic painful cervical dystonia was referred to the Movement Disorders unit of our center in 2009. During the previous 18 months, she received treatment with OT/A five times in our department for this reason. The dose of each injection was between 200 and 250 IU (International Units). In September 2010, she got pregnant. The patient was informed of the potential risks of OT/A during pregnancy and she was referred to the toxicology services and obstetrics for counseling and the ethics committee approved the treatment. Despite the risk, the patient decided to proceed with the treatment. She was injected with 250 IU of OT/A, twice during the pregnancy: one in the second trimester and other during the third one. The injections were the same as before pregnancy: 40 IU in left sternocleidomastoid muscle, 150 IU in right splenius muscle and another 60 IU divided between right trapecius and right elevator scapula muscles. All the injections were well tolerated and the total dose during the entire pregnancy was 500 IU. In June 2011, at 40 weeks’ gestation, the patient spontaneously delivered a healthy, 3400-g boy. His Apgar score was 7/10. The child’s growth and development during the first 7th months of life were normal. After delivery she continued the treatment with OT/A achieving symptomatic relief. OnabotulinumtoxinA was approved by the FDA as Class C during pregnancy based on the studies carried out in mice, rats, and rabbits. The side effects when injected intramuscularly during the period of organogenesis in pregnant mice and rats were related to a dose of 8 and 16 U/kg and consisted in reduction in fetal body weight and/or decreased fetal skeletal ossification. In rabbits, toxicity was reported at a dose of 0.5 U/Kg. Moreover. these doses were also associated with significant maternal toxicity, including abortions, early deliveries, and maternal death [8]. During the past years, other cases of injections of OT/A during pregnancy have been reported. The injection in these reports was during the first trimester [2,3,8], the second (1, 3) and the third one (3, 9) and during the entire pregnancy (1,3). The indications are described in Table 1. There were two miscarriages [2,3], and interestingly, both cases had a history of previous miscarriages without botulinum toxin treatment. The rest of the cases ended with a healthy child. There have been also five reports of botulism acquired during pregnancy [9–13], and in none of these cases, was there evidence of transport of the toxin across the placenta. Growing evidence suggests that whilst OT/A may be safely used during pregnancy to treat severe or painful conditions (such as cervical dystonia), pregnant women should be advised of the potential risks. In addition, careful monitoring should be enforced to avoid inadverted injection in pregnant women for mild conditions (such as cosmetic ones). Moreover, in the event of injection in a pregnant woman, a close follow-up of the entire pregnancy must be performed. Whilst our case study represents another example of safe administration of OT/A in the second and third trimesters, there is an unmet need to revise the safety of OT/A during pregnancy by carrying out carefully con-