Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy
Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy
The investigators want to obtain a fundamental understanding if and which chemotherapeutic
 agents used for treating cancer during pregnancy are associated with placental and/or
 offspring (epi)genetic changes, potentially causing FGR and childhood/adult diseases later in
 life.
Rationale: Cancer is the second leading cause of death during the reproductive years and
 affects between 1:1000 and 2000 pregnant women. Previous studies from our group have shown
 that chemotherapeutic cancer treatment in pregnancy has reassuring outcomes in terms of
 cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care.
 However fetal growth restriction (FGR), which places an infant at significant risk of
 perinatal morbidity and mortality, is more common in women who were systemically treated
 during pregnancy compared to the non-cancer population. The possibility that chemotherapy
 during pregnancy causes placental (epi)genetic damage, and consequently induces FGR, or
 affects offspring DNA leading to potential deleterious effects later in life, such as cancer
 or other diseases, has not been investigated so far. As the cytotoxic effects of chemotherapy
 at DNA level have been well established, it could be speculated that chemotherapy-induced DNA
 damage may interfere with fetal and childhood health in the long term. The results of this
 study will lead to an increased understanding of potential toxic effects of chemotherapy for
 the unborn child and may therefore contribute to the development of safe and solid treatment
 regimens for pregnant cancer patients and their children.

 Objectives: To obtain a fundamental understanding if and which chemotherapeutic agents used
 for treating cancer during pregnancy are associated with placental and/or offspring
 (epi)genetic changes, potentially causing FGR and childhood/adult diseases later in life.

 Study design: This international multicentre prospective observational trial functions as an
 extension of the CIP-study (Cancer in Pregnancy, S25470) and aims to collect placental
 tissue, cord blood and meconium and neonatal buccal cells at birth. Parental peripheral blood
 and buccal cells will be collected and used as reference. Minimal requirement to participate
 in this study is participation in Part I.IA of the original CIP-study. Through this CIP-study
 the investigators are able to gather pregnancy-, malignancy- and placenta-related data.
 Placental tissue is only collected from women who are also willing to participate or are
 already participating in Part I.IB (placental histopathology) of the CIP-study.

 Study population: All patients with histological proven cancer during pregnancy and an
 ongoing pregnancy (≥24 weeks of gestation) treated with chemotherapy (alkylating agents,
 anthracyclines, taxanes and/or platinum derivates) or other treatment options (surgery,
 radiotherapy and/or systemic treatment other than chemotherapy, or none).

 Main study parameters/endpoints: determination of potential (sub)chromosomal alterations
 and/or changes in DNA methylation in placental tissue, and in cord blood and buccal cells of
 the newborn, and the association with chemotherapy concentrations measured in respectively
 placental or newborn tissue.

 Nature and extent of the burden and risks associated with participation, benefit and group
 relatedness: There are no risks associated nor benefits expected with participation in this
 study.
Inclusion Criteria:

 -  Cancer in pregnancy - CT-treated arm

 -  Histological proven cancer during pregnancy (any type and stage)

 -  (Former) participation in part I.IA of the CIP-study S25470 (and I.IB for the
 placental sub study)

 -  Treatment during pregnancy with one or a combination of the following
 chemotherapeutic agents:

 -  Cyclophosphamide

 -  Anthracyclines

 -  Taxanes

 -  Platinum derivates

 -  Gestational age (GA) at birth ≥24 weeks Cancer in pregnancy - CT-untreated arm

 -  No treatment during pregnancy or surgery only (subgroup 1)

 -  Radiotherapy and/or systemic treatment (other than CT) during pregnancy (subgroup
 2)

 -  GA at birth ≥24 weeks Healthy pregnant controls

 -  matched for maternal age, gestation at birth and infant gender with CT-treated
 arm

 -  GA at birth ≥24 weeks (only for placental study)

 Exclusion Criteria:

 -  GA at birth <24 weeks (miscarriage or termination of pregnancy) (placental study)

 -  Mentally disabled women or patients who have a significantly altered mental status
 that would prohibit the understanding and giving of informed consent

 -  Any comorbidity that is associated with an enhanced risk of placental pathology or FGR
 such as hypertensive disorders, preeclampsia, (gestational) diabetes, SLE, Crohn's
 disease, renal or cardiac pathology (healthy pregnant controls)