For fetal protection, the administration of chemotherapy is considered contraindicated until a gestational age of 10 weeks. If a ‘safety period’ of 4 weeks is respected, chemotherapy may start from a gestational age of 14 weeks.
After in utero exposure to chemotherapy, no increase in congenital malformations is seen and reports on middle-long term outcome seem reassuring. An increased risk for intrauterine growth restriction has been described after prenatal exposure to chemotherapy, while normal fetal growth was seen in the other series.
Data on long term outcome after prenatal exposure to chemotherapy are scarce. A study that includes 84 children who were born to mothers who received chemotherapy during pregnancy for haematological malignancies and with a median follow-up of 19 years, did not show any congenital, neurological, immunological and psychological abnormalities including normal learning and educational behavior. Hahn et al surveyed 57 parents/guardians regarding outcomes of children exposed to chemotherapy in utero. At ages ranging from 2 to 157 months, most children had a normal development. Only 2 children required special attention in school: 1 had attention deficit disorder, whereas the other was the child with Down syndrome. A first report from our registration was based on 70 children between 17 months and 18 years with a median follow-up of 22.6 months. Full neurologic (IQ, attention and memory) and cardiologic examination were performed and showed an overall fetal safety after intra-uterine exposure to chemotherapy. Both children of a twin pregnancy revealed an important developmental delay. Wheter the occurrence of a cortical malformation in one of the twins was related to cytotoxic drugs remains unclear. However, all other children were thought to have normal development. 21% of the children were born with a birth weight below the 10th percentile, however during long-term follow-up we notice a normal further weight and height development. Lower IQ or mental developmental index scores were usually found for children born preterm.
The few studies that looked at the cardiac effect of chemotherapy in the foetus showed that acute myocardial dysfunction can appear during pregnancy with anthracyclines (Idarubicin, a highly liposoluble anthracycline). The risk of this cardiotoxicity is influenced by the cumulative dose (>250 mg/m²), gender, age, and association with radiotherapy, stem cell transplantation or other cardiotoxic chemotherapeutic agents (Herceptin, Cyclophosphamide, Amsacrine). However, we did not encounter this in our series and follow-up with cardiac ultrasound in 81 children who received anthracycline treatment in utero ( age 9 - 29 years, mean 17 year) was reassuring. In our study on 70 children, the global heart function remained normal compared to controls. Only small differences in the ejection fraction (EF), fractional shortening (FS), and some of the diastolic parameters (isovolumic relaxation time (IVRT), mitral A-duration) were seen. Global strain analysis and tissue Doppler imaging (TDI) are more sensitive and early parameters of cardiotoxicity. Implementation of these novel measurements may improve the detection of anthracycline induced cardiotoxicity.
