What are the effects of chemotherapy on the fetus during pregnancy?

Effects of Chemotherapy on the Fetus During Pregnancy

Chemotherapy should be avoided during the first trimester of pregnancy due to the high risk (up to 20%) of major congenital malformations, but can be administered with relative safety during the second and third trimesters. 1

Timing of Chemotherapy and Fetal Risk

First Trimester (0-13 weeks)

• Highest risk period due to active organogenesis
• Associated with:
  • Major congenital malformations
  • Impaired organ function
  • Spontaneous abortions
  • Fetal death 1
• Absolute contraindication for certain agents:
  • Methotrexate (severe teratogenic effects)
  • Older-generation alkylating agents (procarbazine, busulfan)
  • Thalidomide, lenalidomide, pomalidomide
  • Tretinoin 1

Second and Third Trimesters (14-40 weeks)

• Generally considered safer with no significant teratogenic effects
• Potential complications include:
  • Low birth weight
  • Preterm labor
  • Intrauterine growth restriction 1
  • Bone marrow toxicity in some infants 2

Chemotherapy Administration Guidelines

1. Timing considerations:

   • Last chemotherapy dose should be administered at least 3 weeks before expected delivery date to avoid delivery during maternal nadir period 1
   • Avoid chemotherapy beyond week 33 of gestation 1

2. Dosing:

   • Standard doses should be used without pregnancy-specific adjustments
   • Calculate based on actual maternal weight 1
   • Consider weekly schedules for certain agents (doxorubicin, epirubicin, paclitaxel) to reduce hematological toxicity 1

3. Monitoring:

   • Regular fetal monitoring during gestation
   • Target full-term delivery (≥37 weeks) whenever possible 1
   • Pregnancies should be considered high-risk and managed by a multidisciplinary team 1

Specific Agents and Safety

Relatively Safer Options (Second/Third Trimester)

• Anthracycline-based regimens (most studied during pregnancy)
  • Doxorubicin
  • Epirubicin
  • No significant fetal cardiotoxicity reported 1

Contraindicated Throughout Pregnancy

• Methotrexate
• Older-generation alkylating agents
• Thalidomide and its analogs
• Hormonal agents and targeted therapies (insufficient safety data) 1

Long-term Outcomes

A multicenter, prospective case-control study showed no significant impact of second/third trimester chemotherapy on cognitive, cardiac, and general development of children born to mothers treated with chemotherapy during pregnancy 1. However, prematurity itself (independent of chemotherapy) is associated with higher rates of neurodevelopmental problems 3.

Clinical Decision-Making Algorithm

1. Determine gestational age precisely

   • First trimester: Consider delaying treatment until second trimester if possible
   • If immediate treatment needed in first trimester: Discuss pregnancy termination options

2. Cancer type and stage assessment

   • Early-stage: Consider delaying treatment until after fetal maturity
   • Advanced-stage: Carefully evaluate maternal-fetal risk-benefit ratio

3. Treatment planning

   • Select appropriate chemotherapy regimen based on:
     • Cancer type
     • Gestational age
     • Expected delivery date
   • Integrate supportive care for management of treatment-related side effects

4. Delivery planning

   • Schedule delivery at least 3 weeks after last chemotherapy dose
   • Target full-term delivery when possible

Important Caveats

• The decision to use chemotherapy during pregnancy requires a multidisciplinary approach involving medical, surgical, and radiation oncologists, obstetricians, and perinatologists 1
• Referral to tertiary centers with expertise in cancer management during pregnancy is strongly recommended 1
• Physiologic changes during pregnancy may alter pharmacokinetics of chemotherapy drugs, potentially resulting in lower maternal drug exposure 1
• Placental examination after delivery is recommended, particularly in patients with melanoma (highest risk of placental metastasis) 1