“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, the children were given examinations of their general health, brain and heart function, and hearing. Their brain function, hearing, heart function, growth and development were all comparable with the general population. However, being born prematurely was associated with lower scores in IQ tests, leading the researchers to recommend against doctors inducing early delivery in women who need chemotherapy. The researchers also say their results do not support delaying chemotherapy in pregnant women.
During pregnancy, decisions about treatment 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 foetus. However, this relatively small study cannot conclusively prove 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 the 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 media 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, the study did not focus on women with breast cancer, and looked at children’s long-term development rather than the safety of their delivery. The researchers’ main finding was that being born prematurely was associated with lower IQ scores, which means that planned premature delivery may not be the best option.
What kind of research was this?
This cohort study looked at how foetal exposure to maternal cancer and treatment, including chemotherapy, affected the physical and cognitive development of children 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 have 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.
A cohort study is likely to be the most appropriate way of exploring the harms of chemotherapy in pregnancy. Chemotherapy in pregnancy is generally believed to be potentially harmful to the baby, but is sometimes unavoidable in clinical practice. Setting up a trial that randomly assigned pregnant women with cancer to receive cancer treatment or no treatment to assess developmental effects on children would be unethical, both for the mother (who may be denied the treatment she needs) and the baby (who may be put at unnecessary risk of harm).
What did the research involve?
From 2005, 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 before the study. Depending on the age of the child the researchers carried out assessments at the 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 to 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 and head circumference, as well as national and international reference data for neurodevelopmental 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, and 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 35.7 weeks of pregnancy (most were premature). Only 23 babies (33% of the cohort) were born at full term (37 weeks or over). Each child was followed up for an average of 22.3 months.
The children’s behaviour, general health, hearing, growth and heart function were comparable to the general population. Most children were recorded as having normal cognitive development. Most children with scores below the normal range were born prematurely. After the researchers adjusted their results 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 concluded that children exposed to chemotherapy in the uterus are not more likely to have neurological, cardiac, hearing or general health and growth impairments compared with the general population.
However, premature birth was common and was associated with impaired cognitive development. Therefore, planned premature delivery should be avoided where possible.
During pregnancy difficult treatment decisions have to be made in the best interests of both the mother and her unborn child. This valuable cohort study provides follow-up data on children (from young childhood through to adolescence and beyond) who were exposed to chemotherapy while in the uterus.
The study's 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 so that chemotherapy can be given to the mother after birth (the study suggests that premature birth may carry greater risk of adverse cognitive outcomes than exposure to chemotherapy itself).
However, though it does provide some reassurance, this relatively small study cannot conclusively prove that chemotherapy poses no risk to the unborn child:
- As the researchers acknowledge, two children born to a twin pregnancy had significant neurodevelopmental delay. The researchers could not exclude the possibility that this may have been caused by exposure to chemotherapy during a critical time of brain development. However, they 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 for 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 higher problem scores on a child behaviour checklist. The researchers say that these findings show that chemotherapy may have more subtle effects on neurodevelopment.
- Additionally, other longer-term effects, which this study did not look at, need to be assessed, including risks of cancer in the children or effects on fertility.
- 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 did not assess or refute this.
- The study lacked a direct comparison group of children who were not exposed to chemotherapy in the uterus. Though the researchers did use national averages for comparison, it would have been better to perform the same range of tests in children who were born at the same pregnancy stage 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 data on much wider numbers of children exposed to chemotherapy in pregnancy.