European Multidisciplinary Cancer Congress (EMCC) 2011, 23-27 September, Stockholm

Effects of chemotherapy during pregnancy

Professor Frederic Amant – University Hospitals Leuven, Belgium


Good morning, thank you for being here. It’s a pleasure to share with you in, let’s say, five minutes the most important results on a study on the cognitive and cardiac outcome after prenatal exposure to chemotherapy. This study is only in children who are least eighteen months old.

As you can imagine, the confrontation of the coincidence of cancer during pregnancy is very complex. At the left you see cervical cancer, basically; in the middle you can see bladder cancer during pregnancy and at the right you see that there is a high grade sarcoma actually with transperitoneal spread. Cancer treatment is by chemotherapy, radiotherapy or surgery and one of the challenges is what are the effects of chemotherapy on the child? And there are actually no good data that really describe these effects.

Cancer in pregnancy is diagnosed in, let’s say, 1 in 1,000 or 1 in 2,000 pregnancies. In European figures this means that we have about 2,500-5,000 new cases a year. So given this data, in effect we don’t know really how these children do. We initiated a study in 2005, this study is now in 114 children but some children are excluded – those who were younger than eighteen months. There were children with incomplete medical data files; 85 children were actually eligible and 15 children had to be excluded: four were lost to follow-up; there was one child with a sudden infant death syndrome; eight patients refused to participate because they could not come to the hospital anymore because it was such a trauma for them in their history, and two patients did not speak the national language. So the data I will share with you is in 70 children. What we did is actually we exposed them to cardiological examination, general health assessment and a neurological examination. We did that on predefined ages, from the moment of 18 months they received a Bayley scale of infant development and then clinical examination here, heart examination, electrocardiographic and echocardiographic, all by specialists. When they were older they received a test battery adapted to their age. So we did an intelligence test, we looked to the attention of the children, we looked to their memory, verbal and non-verbal, and we looked into their behaviour. We used for this standardised tests, questionnaires and these tests were done by psychologists.

The data show, if we look to the biometry of female and male children, actually a normal distribution. We see the weight, the head and the heart circumference and you see that it’s well between the 5th and the 95th percentile. This is an important slide; what we did here, we looked into their intelligence tests and we looked into their Bayley. So the neurodevelopmental outcome was assessed in these 70 children and what you can appreciate, let’s start at the right, this is 37 weeks, so these are major children, and there we see a fair, equal distribution of the results. Also between 34 and 37 weeks the children do well but you can appreciate at the left, children who are born less than 34 weeks of pregnancy, that there is a shift to the left. So, not all these children do perform normally but if there are any cognitive problems they are more likely to be premature. But all these children here at the right side, they received chemotherapy. So if a child is term delivered, it will develop normally, according to these results. So there is a linear correlation between intelligence and prematurity and chemotherapy is actually, according to these data, not really adding to this outcome.

These are the detailed results of the tests that were done. At the left you can see the test functions, you see the subtasks of the test that have been described, you see the numbers. These are Z scores, so everything which is between -1 and +1 is actually normal and you can appreciate that all the results actually have normal values. Those of you who are critical, you can see that there is sometimes a small trend, I will just show, for example, you see in immediate recall, it’s a bit more to the left but then by other tests, immediate recall it’s more to the right. So these data, although there might be a small shift, they do not confirm each other. What’s important is that the Teach test is the most complex test and in this Teach test the effect is a bit to the right, which is a positive effect. So these detailed tests show that these functions, attention and behaviour, are actually normal.

We also looked to the heart, why is this important? Because anthracylcines are given in the majority of women because we know that breast cancer is the most common tumour during pregnancy and also hematologic cancers are common. So in both cancer types anthracyclines are actually very important. So the majority of children, nearly 80%, received anthracyclines, they can pass through the placenta so it’s important to look into the foetal heart. However, at birth there were no congenital birth malformations, there was a normal electrocardiogram, there were normal heart diameters and both the systolic and the diastolic function appeared to be normal.

So in conclusion we can say that the child’s behaviour, their general health, hearing and growth was reported as in the general population. Most of the children have an age adequate neurological development when we look into intelligence, attention and memory, and also a normal cardiac function. Prematurity was frequently encountered, in fact in 75% of cases, and this was associated with an impaired cognitive development. We acknowledge that the numbers are still small, mean follow-up is 22 months and there is a lack of control data. But however, it’s done by experts in the field and the data are compared to normative values, which is still a good comparison. This was only thanks to an international interdisciplinary collaborative research between Leuven University in Belgium, the Radboud University in Nijmegen, the Charles University in Prague and the Hospital for Sick Children in Toronto.