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Association of Chemotherapy Timing in Pregnancy With Congenital Malformation
M. van Gerwen, C. Maggen, E. Cardonick, EJ. Verwaaijen, M. van den Heuvel-Eibrink, RG. Shmakov, I. Boere, MM. Gziri, PB. Ottevanger, CAR. Lok, M. Halaska, LT. Shao, I. Struys, EM. van Dijk-Lokkart, K. Van Calsteren, R. Fruscio, P. Zola, G....
Language English Country United States
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
NLK
Directory of Open Access Journals
from 2018
ProQuest Central
from 2018-01-01
Health & Medicine (ProQuest)
from 2018-01-01
- MeSH
- Abnormalities, Drug-Induced etiology MeSH
- Time Factors MeSH
- Adult MeSH
- Gestational Age MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neoplasms drug therapy MeSH
- Odds Ratio MeSH
- Antineoplastic Agents adverse effects therapeutic use MeSH
- Pregnancy Trimester, First MeSH
- Drug Administration Schedule * MeSH
- Pregnancy MeSH
- Pregnant People MeSH
- Fetal Development drug effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
Importance: Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear. Objective: To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer. Design, Setting, and Participants: This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020. Exposures: Cancer treatment with chemotherapy during pregnancy. Main Outcomes and Measures: Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth. Results: A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 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 gestational age 12 weeks, the frequency of major congenital malformations was 3.0% (95% CI, 1.9%-4.6%), which was similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (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 prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]). Conclusions and Relevance: This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer.
Cooper Medical School Rowan University Camden New Jersey
Department of Development and Regeneration KU Leuven Leuven Belgium
Department of Medical Oncology Radboud University Nijmegen Medical Center Nijmegen the Netherlands
Department of Obstetrics and Gynecology Cooper University Health Care Camden New Jersey
Department of Obstetrics and Gynecology San Gerardo Hospital Milan Italy
Department of Obstetrics University Hospitals Leuven Belgium
Department of Oncology KU Leuven Leuven Belgium
Department of Surgical Sciences University of Turin Turin Italy
Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands
University Hospital Kralovske Vinohrady 3rd Medical Faculty Charles University Prague Czech Republic
References provided by Crossref.org
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- $a Importance: Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear. Objective: To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer. Design, Setting, and Participants: This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020. Exposures: Cancer treatment with chemotherapy during pregnancy. Main Outcomes and Measures: Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth. Results: A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 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 gestational age 12 weeks, the frequency of major congenital malformations was 3.0% (95% CI, 1.9%-4.6%), which was similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (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 prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]). Conclusions and Relevance: This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer.
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