Bleomycin Use in Pregnancy
Bleomycin can be administered to pregnant women after 14 weeks of gestation when clinically indicated, particularly for nonepithelial ovarian cancer (germ cell tumors), but is absolutely contraindicated in the first trimester due to teratogenic risk.
Gestational Age-Specific Recommendations
First Trimester (< 14 weeks): Contraindicated
Bleomycin is contraindicated in the first trimester due to a 10-20% risk of major malformations when chemotherapy is given during organogenesis 1.
The FDA label explicitly warns that bleomycin is teratogenic in animal studies, causing skeletal malformations, shortened innominate artery, and hydroureter in rats at doses approximately 1.6 times the human dose 2.
Treatment should be delayed until the second trimester unless maternal life is immediately threatened, in which case the fetal benefit of delay must be balanced against maternal risk 1.
Second and Third Trimesters (≥ 14 weeks): Feasible with Appropriate Indication
After 14 weeks of gestation, bleomycin administration is feasible and appears relatively safe when used in combination regimens for appropriate indications 1.
The 2019 Annals of Oncology international consensus guidelines specifically list bleomycin-containing regimens (BEP or EP) as preferred treatment for nonepithelial ovarian cancer during pregnancy 1.
Bleomycin use in combination with cisplatin and etoposide has been described and appears safe, although the numbers of cases are limited 1.
Clinical Evidence Supporting Second/Third Trimester Use
Multiple case reports document favorable pregnancy outcomes after bleomycin exposure in the second and third trimesters, with no evidence of major or minor malformations and normal neurological development at follow-up 3, 4.
One case series reported two women who received bleomycin, etoposide, and cisplatin starting at 22 and 30 weeks gestation respectively, with both infants showing normal development at 6 and 2 years of follow-up 3.
Another case described successful treatment starting at 29 weeks with normal infant development at 1.5 years 4.
Timing and Dosing Considerations
Chemotherapy should not be administered beyond 35 weeks gestation to allow a 3-week window between the last cycle and delivery for maternal and fetal bone marrow recovery 1.
For weekly regimens, administration should not extend beyond 37 weeks gestational age 1.
Dosing should be based on actual weight using the same dose/m² as in nonpregnant patients 1.
Critical Pitfalls and Caveats
The FDA label warns that bleomycin can cause fetal harm and women of childbearing potential should avoid becoming pregnant during therapy 2.
Most chemotherapeutic drugs, including bleomycin, cross the placenta due to their relatively small molecular weight 1.
The 3-week window before delivery is particularly important in preterm infants who lack enzymes to metabolize chemotherapy adequately 1.
While the rate of fetal malformations with second/third trimester chemotherapy appears comparable to the general population, investigators caution that fetal damage including genetic impairment may not appear until later in life 5.
Breastfeeding is not recommended for women receiving bleomycin, as most investigators agree that women being treated for malignancy should not breastfeed 5.