The potential fetal risks associated with the use of cytotoxic treatment during pregnancy depend on the gestational period at exposure. During the first 10 days post-conception (fertilization/implantation) cells are omnipotent and can develop in the three different embryological layers. Toxic exposure in this stage will result in an ‘all-or-nothing’ phenomenon. If a sufficient number of cells survive, the embryo will develop normally, otherwise a miscarriage occurs. The period between 10 days and 8 weeks after conception, is characterized by the organogenesis, making this phase at risk for congenital malformations. During the second and third trimester of pregnancy, organogenesis is completed with the exception of eyes, gonads and the central nervous system. Consequently no major malformations are expected to be caused by cytotoxic treatment. However, cases of growth restriction, prematurity, intra-uterine and neonatal death, and hematopoietic suppression have been reported. The long term outcome in particular when related to potential problems of neurodevelopment delay, sterility, carcinogenesis and genetic defects needs to be further elaborated.
The decision to administer chemotherapy should follow the same guidelines as in nonpregnant patients, taking into account the gestational age and the overall treatment plan (timing of surgery, need of radiotherapy, etc.). 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. The timing of delivery should be balanced according to the oncological treatment schedule and the maturation of the foetus. As in non cancer patients, term delivery (> 37 weeks) should be aimed for. The potential to give chemotherapy during pregnancy is an important manner to prevent prematurity. Early labour induction results in prematurity and low birth weight that have been identified as contributing factors in the cognitive and emotional development of children. In the event that preterm delivery is inevitable, fetal lung maturation should be performed according to local policy. The mode of delivery should be determined based on obstetrical indications. To allow the bone marrow to recover and to minimize the risk of maternal and fetal sepsis and hemorrhage, delivery should be planned at least 3 weeks after the last cycle of chemotherapy, and chemotherapy should not be administered after 35-37 weeks since spontaneous labor becomes more likely. This can be monitored by measuring the cervical length by transvaginal ultrasound. Furthermore, neonates, especially preterm babies, have limited capacity to metabolize and eliminate drugs due to liver and renal immaturity. The delay of delivery after chemotherapy will allow foetal drug excretion via the placenta. Chemotherapy can be restarted immediately after vaginal delivery, but an interval of one week after an uncomplicated caesarean section is suggested.