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Chemo during pregnancy likely to be safe

“Children born to women undergoing cancer drug treatment show normal results in physical and mental development tests” The Guardian has reported.

The news is based on research that examined the health of 70 children who were exposed to chemotherapy in the womb during the final two-thirds of pregnancy. Between the ages of 18 months and 18 years of age the children were given examinations of their general health, brain and heart function and hearing. Their cognitive function, hearing, heart function, growth and development were all comparable with the general population. However, being born prematurely was associated with lower cognitive scores, leading the researchers to recommend against doctors inducing early delivery in women requiring chemotherapy. The researchers also say their results do not support delaying chemotherapy in pregnant women.

During pregnancy treatment decisions have to be made that are in the best interest of the mother’s health, while trying to avoid the risk of harm to the fetus. Unfortunately though, this relatively small dataset cannot provide conclusive proof that chemotherapy poses no risk at all to the unborn child. The researchers say that their study is currently gathering longer-term data on wider numbers of children to help explore the issue further.

 

Where did the story come from?

The study was carried out by researchers from Leuven Cancer Institute and Katholieke Universiteit Leuven in Belgium, and other institutions in Czech Republic, the Netherlands and Canada. The study was funded by a number of European medical research and technology funds and the Belgian Ministry of Health. The study was published in the peer-reviewed medical journal The Lancet.

In general the news provided balanced coverage of this study. The Daily Mail’s headline declared that pregnant women with breast cancer can have chemotherapy and surgery and “still give birth safely”. However, this is slightly confusing as the focus of this study was not women with breast cancer, and the study looked at children’s long-term development rather than the safety of their delivery. The researchers’ main finding was actually that premaurity was associated with lower IQ scores, meaning that planned premature delivery may not be the best option.

 

What kind of research was this?

This was a cohort study looking at how foetal exposure to maternal cancer and treatment, including chemotherapy, affected the physical and cognitive development of child at various points through their childhood.

While it is known that exposure to chemotherapy during the first 12 weeks of pregnancy can increase the risk of congenital defects in the baby, there is uncertainty over whether exposure during later stages of pregnancy can also affect heart and brain development. The researchers say that up until now, limited data has been available on the longer-term outcomes of children exposed to chemotherapy in the uterus. With this in mind they intended to record the general health, cardiac function, and brain development in children who were exposed to chemotherapy in the uterus.

Cohort studies such as this are the best way of assessing harms from chemotherapy in pregnancy, as it is generally believed to be potentially harmful to the baby, but is sometimes unavoidable in clinical practice. Setting up a trial randomising pregnant women with cancer to receive cancer treatment or not in order to assess developmental effects on the offspring would be unethical, both for the mother (who may be denied the treatment she needs) and baby (who may put at unnecessary risk of harm). Therefore a cohort study is likely to be the most appropriate way of exploring the issue.

 

What did the research involve?

From 2005 onwards researchers began gathering study subjects from cancer referral centres in Belgium, the Netherlands and the Czech Republic. This included both pregnant women receiving chemotherapy at the time, and children and mothers who had been exposed to chemotherapy several years prior to the study. Dependent on the age of the child the researchers carried out assessments at ages of 18 months, 5–6 years, 8–9 years, 11–12 years, 14–15 years, or 18 years. The study is ongoing, and in time these children will be given further examinations.

The researchers carried out neurological examinations, tests of cognitive function (using recognised  child development tests or IQ tests), heart examinations (electrocardiography and echocardiography), and administered a questionnaire on general health and development. Children who were over five years of age also received hearing tests in addition the Child Behavior Checklist, a questionnaire that screens for behavioural and emotional problems.

The researchers compared their findings with available norms such as national data for height, weight, head circumference, as well as national and international reference data for neurodevelopmental tests, and heart examination tests.

 

What were the basic results?

The current analysis of this ongoing study looked at the participating children’s development until March 2011. The researchers assessed 70 children (27 born between 1991 and 2004, and 43 born after 2004) from 68 pregnancies (two of the women had given birth to twins). All women had received chemotherapy; some were also given radiotherapy, surgery or both. Across the group, 19 different chemotherapy regimens had been given, in which 236 cycles of chemotherapy were administered.

On average the babies were born at a pregnancy duration of 35.7 weeks (i.e. most were premature); only 23 babies (33% of the cohort) were born at full term (37 weeks or over). The average period of follow-up for each child was 22.3 months.

The children’s behavior, general health, hearing, growth, and heart function were comparable to the general population. Most children were recorded as having normal cognitive development, with most children with scores below the normal range having been born prematurely. After the researchers adjusted for age, sex, and country, they found an 11.6 point increase in IQ score for each additional month of pregnancy that the baby was carried for. The researchers found that both members of one of the twin pregnancies had severe neurodevelopmental delay, and could not be assessed with the complete set of cognitive tests.

 

How did the researchers interpret the results?

The researchers conclude that children exposed to chemotherapy in the uterus do not have increased likelihood of neurological, cardiac, hearing or general health and growth impairments compared with the general population.

However, prematurity was common and was associated with impaired cognitive development; therefore, planned premature delivery should be avoided where possible.

 

Conclusion

During pregnancy difficult treatment decisions have to be made bearing in mind the best interests of both a mother and her unborn child. This valuable cohort study provides follow-up data on children who were exposed to chemotherapy while in the uterus, from young childhood through to adolescence and beyond.

Its findings are reassuring and suggest that a child’s exposure to chemotherapy during later stage pregnancy (beyond the first 12 weeks) is not associated with brain, heart or other developmental complications in the child. As the researchers note, their findings do not support the practice of delaying chemotherapy or performing planned premature delivery in order to administer chemotherapy to the mother after birth (the study suggests that premature birth may carry greater risk of adverse cognitive outcome than chemotherapy exposure itself).

However, though it does provide some reassurance, unfortunately this relatively small dataset cannot provide conclusive proof that chemotherapy poses no risk at all to the unborn child:

  • As the researchers acknowledge, two children born to a twin pregnancy had important neurodevelopmental delay and they cannot exclude the possibility that exposure to chemotherapy during a critical time of brain development was the cause. However, the researchers considered that the broad nature of the problems in one of the twins suggested that chemotherapy was less likely to be the cause.
  • Also, though the general neurodevelopmental assessments for the cohort were within the normal range expected among the general population, the researchers noted that a sample of children had some discrepancy between verbal performance and IQ values on intelligence tests, while a sample of others had raised problem scores on a child behavior checklist. The researchers say that these findings show that it is possible that chemotherapy has more subtle effects on neurodevelopment.
  • Additionally, other longer-term effects that this study has not looked at need to be assessed, including risks of cancer in the offspring themselves or fertility effects.
  • It is important to note that all chemotherapy in this study was given after the first 12 weeks of pregnancy: chemotherapy in the first trimester is associated with increased risk of congenital malformations, and this study does not assess or refute this.
  • The study lacked a direct comparison group of children not exposed to chemotherapy in the uterus. Though the researchers did compare to national averages, the ideal comparison method would have been performing the same range of tests in children who were born at the same pregnancy gestation but who had not been exposed to chemotherapy.
  • The researchers say that their Cancer in Pregnancy initiative will need to continue to gather longer-term follow-up on much wider numbers of children exposed to chemotherapy in pregnancy.
 

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