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Association of Chemotherapy Timing in Pregnancy With Congenital Malformation

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International Network on Cancer, Infertility and Pregnancy & Storgaard, L 2021, 'Association of Chemotherapy Timing in Pregnancy With Congenital Malformation', JAMA network open, bind 4, nr. 6, e202113180, s. e2113180. https://doi.org/10.1001/jamanetworkopen.2021.13180

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International Network on Cancer, Infertility and Pregnancy ; Storgaard, Lone . / Association of Chemotherapy Timing in Pregnancy With Congenital Malformation. I: JAMA network open. 2021 ; Bind 4, Nr. 6. s. e2113180.

Bibtex

@article{1d80541257bf490b92437c074dc1fee4,
title = "Association of Chemotherapy Timing in Pregnancy With Congenital Malformation",
abstract = "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.",
keywords = "Abnormalities, Drug-Induced/etiology, Adolescent, Adult, Antineoplastic Agents/adverse effects, Cohort Studies, Drug Administration Schedule, Female, Fetal Development/drug effects, Gestational Age, Humans, Middle Aged, Neoplasms/drug therapy, Odds Ratio, Pregnancy, Pregnancy Trimester, First, Pregnant Women, Time Factors, Young Adult",
author = "{van Gerwen}, Mathilde and Charlotte Maggen and Elyce Cardonick and Verwaaijen, {Emma J} and {van den Heuvel-Eibrink}, Marry and Shmakov, {Roman G} and Ingrid Boere and Gziri, {Mina M} and Ottevanger, {Petronella B} and Lok, {Christianne A R} and Michael Halaska and Shao, {Long Ting} and Ilana Struys and {van Dijk-Lokkart}, {Elisabeth M} and {Van Calsteren}, Kristel and Robert Fruscio and Paolo Zola and Giovanna Scarfone and Fr{\'e}d{\'e}ric Amant and {International Network on Cancer, Infertility and Pregnancy} and Lone Storgaard",
year = "2021",
month = jun,
day = "1",
doi = "10.1001/jamanetworkopen.2021.13180",
language = "English",
volume = "4",
pages = "e2113180",
journal = "JAMA network open",
issn = "2574-3805",
publisher = "American Medical Association",
number = "6",

}

RIS

TY - JOUR

T1 - Association of Chemotherapy Timing in Pregnancy With Congenital Malformation

AU - van Gerwen, Mathilde

AU - Maggen, Charlotte

AU - Cardonick, Elyce

AU - Verwaaijen, Emma J

AU - van den Heuvel-Eibrink, Marry

AU - Shmakov, Roman G

AU - Boere, Ingrid

AU - Gziri, Mina M

AU - Ottevanger, Petronella B

AU - Lok, Christianne A R

AU - Halaska, Michael

AU - Shao, Long Ting

AU - Struys, Ilana

AU - van Dijk-Lokkart, Elisabeth M

AU - Van Calsteren, Kristel

AU - Fruscio, Robert

AU - Zola, Paolo

AU - Scarfone, Giovanna

AU - Amant, Frédéric

AU - International Network on Cancer, Infertility and Pregnancy

A2 - Storgaard, Lone

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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.

AB - 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.

KW - Abnormalities, Drug-Induced/etiology

KW - Adolescent

KW - Adult

KW - Antineoplastic Agents/adverse effects

KW - Cohort Studies

KW - Drug Administration Schedule

KW - Female

KW - Fetal Development/drug effects

KW - Gestational Age

KW - Humans

KW - Middle Aged

KW - Neoplasms/drug therapy

KW - Odds Ratio

KW - Pregnancy

KW - Pregnancy Trimester, First

KW - Pregnant Women

KW - Time Factors

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85107988462&partnerID=8YFLogxK

U2 - 10.1001/jamanetworkopen.2021.13180

DO - 10.1001/jamanetworkopen.2021.13180

M3 - Journal article

C2 - 34106263

VL - 4

SP - e2113180

JO - JAMA network open

JF - JAMA network open

SN - 2574-3805

IS - 6

M1 - e202113180

ER -

ID: 70645937