Chemotherapy Generally Safe in Pregnancy

Stockholm, Sweden—The diagnosis of cancer in a pregnant patient is always unsettling, with fears for both the mother’s and the baby’s health. But a recent study found that fetal exposure to common chemotherapy regimens after the first trimester was generally safe.

“Fear of chemotherapy is not an indication to terminate pregnancy and not a reason to delay maternal treatment for cancer,” said Frederic Amant, MD, University Hospitals Leuven, Belgium.

Results of the large prospective study, which involved centers in Belgium, the Netherlands, and the Czech Republic, were presented at the 2011 European Multidisciplinary Cancer Congress.

“What adds to the complexity of the treatment of cancer during pregnancy is the unknown effect of chemotherapy on the children,” Dr Amant said. Cancer is diagnosed in about 1 per 1000 to 2000 pregnancies (0.05%-0.1%), yielding up to 5000 cases of fetal exposure in Europe each year, mainly for breast cancer (42%) followed by hematologic malignancy (16%), according to Dr Amant.

The study prospectively followed children who were prenatally exposed to chemotherapy, which was an anthracycline- based regimen in 78% of cases. The children were examined at age 18 months, then from age 5 to 6 years, and every 3 years thereafter until age 18.

“The children’s behavior, general health, hearing, and growth were in the range of the general population. Most of the children have age-adequate neurological development and cardiac function,” Dr Amant reported. “But prematurity was frequently encountered, and this was associated with some impairment in cognitive development.”

“We have to take care to reduce iatrogenic prematurity,” he added.

Comprehensive Testing Done
Testing comprised a clinical neurologic examination, testing of cognitive function (Bayley and IQ tests), electro/ echocardiography and questionnaire for general health and development. Beginning at age 5, the children were also evaluated with audiometry and the Auditory Verbal Learning Test, subtasks of the Children’s Memory Scale, Test of Everyday Attention for Children, and the Child Behavior Checklist.

Altogether, 236 cycles of chemotherapy were administered during 68 pregnancies, involving 70 children whose median gestational age at maternal cancer diagnosis was 18 weeks. The study is ongoing, and the average child has been followed for 22 months at this point.

Neonatal Outcomes
Dr Amant said that the 70 children who were exposed to chemotherapy before birth were born at a median gestational age of 35.7 weeks. Specifically:

• • 23% of them were born at ?37 weeks gestation
• • 31% were born at 34 to 37 weeks of gestational age
• • 9% were born between 32 and 34 weeks
• • 7% were born between 28 and 32 weeks.

The median birth weight was 2612 g (range, 720-3970 g). Intrauterine growth retardation was observed in 14 children (20.6%). Neonatal neurologic examination was normal in 64 infants (91.4%). Transient hypotonia was observed in 5 (7.1%), and benign sleep myoclonus and contracture of the right elbow in 1 infant each (1.4%). There were no excess congenital malformations or health problems, compared with the general population.

The Bayley test at 18 months and the IQ test between 5 and 18 years were normal although there was a tendency for worse outcomes in children born prematurely, he said.

There was a correlation between pregnancy duration and IQ score, with IQ scores increasing by an average of 2.5 points for each additional week of gestation.

“While 2.5 points doesn’t sound like much, if you induce delivery at 32 weeks you may be risking 20 IQ points,” Dr Amant pointed out. “This is a significant clinical message.”

Hearing was tested in 21 children, and 18 were normal though 3 had some hearing loss (1 had infection as a confounder). Cardiac testing revealed no congenital heart malformation and normal functional parameters. In children exposed to anthracyclines, echocardiography showed some shortening fraction and decreased ejection fraction, compared with matched controls, but this was “modest,” he said.

Whereas the vast majority of outcomes were normal, there were 2 “outliers,” twins who were born prematurely with birth weights of 1630 g and 1390 g. One had autistic disorder, and mental and motor retardation; the other had delayed neurologic development.

“We are most likely observing a genetic syndrome, not a chemotherapyinduced one, although we could not diagnose it. All other neuropsychological results were within normal ranges, so this was reassuring,” he said.