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]

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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