In a Danish nationwide cohort study reported in the Journal of Clinical Oncology, Greiber et al found no apparent increased risk of mortality, overall somatic disease, or overall psychiatric disease among children exposed in utero to maternal cancer compared with to children without such exposure.
Study Details
The study included 2,526,163 children born between January 1978 and December 2018.
The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Somatic conditions included cancer, congenital malformations, and puberty disturbances/infertility, as well as prespecified endocrine, respiratory, cardiovascular, urinary tract, and neurologic diseases. In an analysis of children also exposed to chemotherapy in utero, additional outcomes of interest were hearing loss and anemia, leukocytopenia, and thrombocytopenia. Hazard ratios were adjusted for potential confounding factors.
Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.— Greiber et al
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Key Findings
Among the 2,526,163 children, 690 (0.03%) were exposed to maternal cancer in utero. Median duration of follow-up was 14.4 years (interquartile range [IQR] = 6.4–25.0 years) for exposed children and 19.7 years (IQR = 9.9–29.2 years) for unexposed children.
For exposed vs unexposed children, the hazard ratio for overall mortality was 0.8 (95% confidence interval [CI] = 0.4–1.5).
There was no significant difference in risk for exposed vs unexposed children for overall somatic diagnoses. The hazard ratio for congenital malformations was 1.0 (95% CI = 0.8–1.2). The hazard ratio for cancer was 2.2 (95% CI = 1.0–4.9); in a sensitivity analysis comparing exposed children with unexposed children of mothers with prepregnancy cancer, the hazard ratio was 1.2 (95% CI = 0.5–2.7). The hazard ratio for all endocrine diseases was 1.2 (95% CI = 1.0–1.6). No excesses in risks for puberty disturbances or respiratory, cardiovascular, urinary tract, or neurologic diseases were observed. The hazard ratio for overall psychiatric disease was 1.0 (95% CI = 0.8–1.3).
In a subgroup analysis including 1,053,109 children born after 2002, 378 (0.03%) were exposed to maternal cancer in utero and 42 of these (12.5%) were exposed to chemotherapy in utero. Compared with children with in utero exposure to cancer but not to chemotherapy, those with exposure to chemotherapy did not have increased risk of overall somatic diseases or congenital malformations. No deaths; cancer diagnoses; or cases of autism spectrum disorder, attention-deficit hyperactivity disorder, hearing loss, or suppressed myelopoiesis were identified during follow-up among those exposed to chemotherapy.
The investigators concluded, “Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.”
Iben K. Greiber, MD, of the Department of Gynecology and Obstetrics, Rigshospitalet, Copenhagen, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by The Research Fund of Rigshospitalet, Novo Nordisk Foundation, Danish Cancer Research Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
