Association of Chemotherapy Timing in Pregnancy With Congenital Malformation

Chemotherapy puts a developing fetus at risk of teratogenic effects. The standard recommendation is that chemotherapy be administered after organogenesis is complete, however, the exact gestational age that chemotherapy can be administered safely and avoid causing congenital malformations remains unknown. The goal of this study was to assess the teratogenic role of prenatal chemotherapy by gestational age, to evaluate for the presence of major and minor congenital malformations during pregnancy or at birth.This was a multicenter study that evaluated all pregnant women who received chemotherapy in the International Network on Cancer, Infertility and Pregnancy (INCIP) database between 1977 and 2019.A total of 755 pregnant women treated with chemotherapy between 1977 and 2019 were included in analysis. The median age at cancer diagnosis was 33 (14-48) years. The major congenital malformation rate was 3.6% (95% confidence interval [CI], 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%) among offspring. Chemotherapy exposure before 12 weeks' gestational age was associated with a high rate of major congenital malformations, at 21.7%(95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after 12 weeks' gestation, the frequency of major congenital malformations decreased to 3.0% (95% CI, 1.9%-4.6%), which was comparable to the anticipated rates in the general population. Minor malformations were similar when exposure occurred before or after 12 weeks' gestation (4.3% [95% CI, 0.1%-21.9%] vs 1.8% [95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy before 12 weeks' gestation, 17 (58.6%) were not aware of their pregnancy, and 6 (20.7%) had a miscarriage (3 women [10.3%]) or elected to terminate their pregnancy (3 women [10.3%]).Overall, this study found that chemotherapy was associated with an increased risk of major congenital malformations only when it administered during in the first 12 weeks of pregnancy. This risk and the high number of incidental pregnancies during cancer treatment in the INCIP registry emphasize the importance of contraceptive counseling and pregnancy testing at the start of chemotherapy treatment in women of childbearing age with cancer.