BACKGROUND: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. METHODS: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. RESULTS: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5-101.8, versus 104.4, 95% CI: 100.4-108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6-4.3, versus 4.5, 95% CI: 4.1-4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). CONCLUSIONS: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, NCT00330447.

Center for Gynecologic Oncology Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam the Netherlands; Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

Clinic of Obstetrics and Gynecology University of Milan Bicocca and San Gerardo Hospital Monza Italy

Department of Cardiology The Hospital for Sick Children University of Toronto Toronto ON Canada

Department of Cardiology University Hospitals Leuven Leuven Belgium

Department of Internal Medicine Radboud UMC Nijmegen the Netherlands

Department of Neonatology University Hospitals Leuven Leuven Belgium

Department of Obstetrics and Gynecology 3rd Medical Faculty Charles University Prague Czech Republic; Faculty Hospital Kralovske Vinohrady Prague Czech Republic

Department of Obstetrics and Gynecology Amsterdam UMC Location VU University Medical Center the Netherlands

Department of Obstetrics and Gynecology University Hospitals Leuven Leuven Belgium; Department of Development and Regeneration KU Leuven Leuven Belgium

Department of Obstetrics and Gynecology University Hospitals Leuven Leuven Belgium; Department of Oncology KU Leuven Leuven Belgium

Department of Obstetrics Cliniques Universitaires St Luc Brussels Belgium

Department of Oncology KU Leuven Leuven Belgium; Center for Gynecologic Oncology Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam the Netherlands; Department of Obstetrics and Gynecology Amsterdam UMC Location Amsterdam Medical Center and University of Amsterdam the Netherlands

Department of Pediatrics University Hospitals Leuven Leuven Belgium

Department of Public Health and Primary Care Faculty of Medicine KU Leuven Leuven Belgium; Data Scientist Knowledge Center SD Worx Antwerp Belgium

Faculty of Psychology and Educational Sciences KU Leuven Leuven Belgium

Neonatal Intensive Care Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy; Department of Clinical Sciences and Community Health University of Milan Milan Italy

Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

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ClinicalTrials.gov
NCT00330447