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CME / ABIM MOC / CE

Does In Utero Exposure to Cancer and Chemotherapy Increase Health Risks in Offspring?

  • Authors: News Author: Patricia McKnight; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 2/24/2023
  • Valid for credit through: 2/24/2024, 11:59 PM EST
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for hematologists/oncologists, family medicine/primary care clinicians, obstetricians/gynecologists/women’s health clinicians, pediatricians, public health and prevention officials, nurses, pharmacists, physician assistants, and other members of the health care team for pregnant women with cancer and their offspring.

The goal of this activity is for learners to be better able to describe short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero, alone or with chemotherapy, based on a nationwide cohort study identifying all children in Denmark who were live-born between January 1978 and December 2018.

Upon completion of this activity, participants will:

  • Assess the short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero, alone or with chemotherapy, based on a nationwide cohort study
  • Determine the clinical implications of short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero, alone or with chemotherapy, based on a nationwide cohort study
  • Outline implications for the healthcare team


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News Author

  • Patricia McKnight

    Freelance writer, Medscape

    Disclosures

    Patricia McKnight has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD has no relevant financial relationships.

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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CME / ABIM MOC / CE

Does In Utero Exposure to Cancer and Chemotherapy Increase Health Risks in Offspring?

Authors: News Author: Patricia McKnight; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 2/24/2023

Valid for credit through: 2/24/2024, 11:59 PM EST

processing....

Clinical Context

Cancer diagnosed during pregnancy period affects approximately 2 in 10,000 live births. Many intrauterine exposures, including teratogenic drugs, radiation, smoking, alcohol, placental hypoperfusion during surgery, maternal illness, and poor maternal nutritional state, may affect fetal development, which plays an essential role in the offspring’s general health and neurocognitive development.

Children exposed to cancer in utero are at increased risk for prematurity. Outcomes in children exposed to maternal cancer in utero have been reported in case-based studies. In Denmark, a shift in treatment strategy of cancer in pregnancy occurred around 2000, when recommendations were introduced regarding use of chemotherapy during pregnancy.

Study Synopsis and Perspective

Children who were exposed in utero to maternal cancer and treatment do not appear to have any long-term health consequences as a result of this exposure, a nationwide Danish study suggests.

The study evaluated live-born children between January 1978 and December 2018 whose mothers were diagnosed with cancer during pregnancy. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality and no increased risk for congenital malformations.

Researchers also determined that exposure to chemotherapy was not associated with somatic diseases and congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy.

“These findings suggest that fetal exposure to maternal cancer and treatment did not have implications for the long-term somatic and psychiatric health of the children, which is reassuring for the affected families and their health care providers,” the researchers commented.

The article was published online July 7, 2022, in the Journal of Clinical Oncology.

Approached for comment, Katherine Van Loon, MD, MPH, director of the Global Cancer Program at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, said that the results offer “promising news.”

“In the balance between administering needed oncologic therapy to save a mother’s life versus considering potential risks to the fetus, this data is reassuring that there is not an increased risk of catastrophic outcomes for the fetus,” Dr Van Loon said. She noted, however, that the exposed children were not prospectively evaluated for adverse outcomes, which may have been more subtle than this study could detect.

The authors used data from the Danish Civil Registration System and Danish Medical Birth Register. They found that of 2,526,163 live-born children, 690 (0.03%) were exposed to maternal cancer in utero. Children born to mothers younger than 15 years or older than 54 years and children with an outcome diagnosis were excluded from the study.

Researchers found that children exposed to maternal cancer in utero did not demonstrate a higher overall mortality than the unexposed reference group (adjusted hazard ratio [aHR] 0.8; 95% CI, 0.4-1.5). There was also no excess of congenital malformations (aHR, 1.0; 95% CI, 0.8-1.2). In addition, there were no excesses of puberty disturbances or respiratory, cardiovascular, urinary tract, or neurologic disease.

Researchers also conducted a subgroup analysis on in utero exposure to chemotherapy, which involved 1,053,109 children born after 2002. There were 378 (0.03%) children exposed to maternal cancer in utero, 42 (12.5%) of whom were exposed to chemotherapy. Chemotherapy was given during the second trimester in 73.8% of the mothers and during the third trimester in 26.2%.

No deaths or events of cancer, autism spectrum disorder, attention-deficit hyperactivity disorder, hearing loss, or suppressed myelopoiesis were identified during follow-up of the 42 children exposed to chemotherapy in utero.

Dr Van Loon said that many cancer treatments are safe during pregnancy, but added that every situation is nuanced, with a number of variables to consider.

“All treatment decisions must take into account the diagnosis and prognosis of the mother, the gestational age of the fetus, and the potential teratogenic effects of the proposed treatments,” she said.

The study was supported by grants from The Research Fund of Rigshospitalet, Copenhagen University Hospital, The Novo Nordisk Foundation, Johannes Clemmesen Research Foundation, Helsefonden, Holm Memorial Foundation, and the Danish Cancer Research Foundation. Researcher disclosures are listed in the study paper.

J Clin Oncol. 2022; 40(34):3975-3984.[1]

Study Highlights

  • This nationwide cohort study identified 2,526,163 children live-born in Denmark between December 1978 and December 2018.
  • Exposure was defined as maternal cancer diagnosis during pregnancy (n=690; 0.03%), with chemotherapy during pregnancy in a subgroup.
  • Follow-up for overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers started at birth and ended at an event, death, emigration, or end of 2018.
  • Median duration of follow-up was 14.4 years (interquartile range, 6.4-25.0 years) for children exposed to maternal cancer and 19.7 years (interquartile range, 9.9-29.2 years) for unexposed children.
  • Children exposed to maternal cancer in utero were more often born premature and had lower birth weight than unexposed children.
  • The most common cancers diagnosed during pregnancy were melanoma (38.1%), breast (17.5%), cervical (13.8%), and ovarian (4.5%) cancer.
  • Compared with unexposed fetuses, children exposed to maternal cancer in utero had no higher overall mortality (aHR, 0.8; 95% CI, 0.4-1.5), nor increased risk for congenital malformations (aHR, 1.0; 95% CI, 0.8-1.2), overall somatic or psychiatric disease, congenital malformations, puberty disturbances, or respiratory, cardiovascular, urinary tract, or neurologic disease, using Cox regression analysis adjusted for potential confounders.
  • Risk for cancer was elevated compared with the unexposed reference group (aHR, 2.2; 95% CI, 1.0-4.9), but this was based on only 6 events in the exposed group.
  • For children exposed to maternal cancer in utero versus no exposure, aHR for all endocrine diseases was 1.2 (95% CI, 1.0-1.6), and for preselected autoimmune endocrine diagnoses (thyroid disease and type 1 diabetes; 12 events), it was 1.9 (95% CI, 1.1-3.3).
  • From 2002 to 2018, 378 children (0.03%) were exposed to cancer in utero, of whom 42 (12.5%) were exposed to chemotherapy: 73.8% during the second trimester and 26.2% during the third trimester.
  • Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases or congenital malformations, deaths or events of cancer, autism spectrum disorder, attention-deficit hyperactivity disorder, hearing loss, or suppressed myelopoiesis compared with in utero exposure to maternal cancer without chemotherapy. The investigators concluded that their findings did not indicate excess risk for mortality or severe somatic or psychiatric morbidity, except for increased risk for specific endocrine disorders, among children exposed to cancer in utero, nor among those with fetal exposure to chemotherapy.
  • Comparison with children of mothers with prepregnancy cancer suggests that excess risk for cancer is likely explained by familial predisposition among children of mothers with cancer in pregnancy.
  • The possible association between exposure to cancer in pregnancy and endocrine dysfunction (thyroid disease and type 1 diabetes) is a new finding warranting further investigation.
  • The results suggest that fetal exposure to maternal cancer and treatment did not have implications for long-term somatic and psychiatric health among children, which is reassuring for affected families and their clinicians.
  • However, all treatment decisions should consider maternal diagnosis and prognosis, gestational age, and potential teratogenicity of the proposed treatments.
  • Study limitations include small numbers of events; short follow-up, especially in the chemotherapy-exposed group; risk for type I error because of multiple comparisons; possible residual confounding; and lack of prospective evaluation for adverse outcomes in exposed children.

Clinical Implications

  • Findings of a nationwide cohort study did not indicate excess risk for mortality or severe somatic or psychiatric morbidity, except for increased risk for specific endocrine disorders, among children exposed to cancer in utero, nor among those with fetal exposure to chemotherapy.
  • The results suggest that fetal exposure to maternal cancer and treatment did not have implications for long-term somatic and psychiatric health among children, which is reassuring for affected families and their clinicians.
  • Implications for the Health Care Team: The healthcare team should keep in mind that all treatment decisions for cancer in pregnancy should consider maternal diagnosis and prognosis, gestational age, and potential teratogenicity of the proposed treatments.

 

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