Study participants This is a multicenter cohort study including children born to women diagnosed with cancer during pregnancy (with or without treatment during pregnancy) (study group). At predefined ages (1.5, 3, 6, 9, 12, 15 and 18 years), the children are invited for follow-up. In this study, we compare the outcome of 6-year-old children from the study group with children born after an uncomplicated pregnancy (control group). Study children were identified and enrolled prospectively (during pregnancy or between birth and 6 years) and evaluated at 6 referral centers in Belgium, the Netherlands, the Czech Republic and Italy, all members of the International Network on Cancer, Infertility and Pregnancy (INCIP). Control children were identified and enrolled at the age of 6 years.

Study testing and outcomes Oncological, obstetrical and neonatal data were collected. Cognitive development was examined using a comprehensive neuropsychological test battery to assess intelligence, memory, attention and behavior problems. Cardiac evaluation included a 12-lead electrocardiogram and an echocardiographic examination performed according to American Society of Echocardiography guidelines. The primary cardiac outcome was left ventricular shortening fraction measured by M-Mode. Secondary outcomes included the cardiac chamber dimensions (Left and Right Ventricular End-diastolic Diameter, Left Ventricular Posterior Wall Thickness, Interventricular Septum Thickness), Left Ventricular ejection fraction, the mitral valve E- and A-velocity and E/A ratio, tissue Doppler imaging velocities at the left and right ventricular wall and interventricular septum, and the longitudinal and circumferential 2D-strain measurements by speckle-tracking echocardiography.

Characteristics of the children In total, 132 children (including five pairs of dizygotic twins) born to mothers diagnosed with cancer during pregnancy were included. During pregnancy, 97 children (73.5%) were 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 children (12.1%) were born to mothers not treated during pregnancy.

Summary of results Children prenatally exposed to maternal cancer, the associated stress, diagnostic imaging and treatments have cognitive and cardiac outcomes within normal ranges at the age of 6 years. However, they are at risk for lower Verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, compared to matched controls. Additionally, they are at higher risk for need for glasses and ototoxicity in case of cisplatin exposure.