The diagnosis of cancer in a pregnant woman causes concerns for both the mother and her unborn child. But studies suggest that most chemotherapy regimens can be delivered with reasonable safety after the first trimester. Cancer is diagnosed in about 1 per 1,000 to 2,000 pregnancies, mostly breast cancer, cervical cancer, and hematologic malignancies.
At the 2011 European Multidisciplinary Cancer Congress in Stockholm, George Pentheroudakis, MD, of the University of Ioannina in Greece, told attendees at the Presidential Session, “In addition to retrospective evidence, there is emerging prospective evidence that the mid- and long-term health of children born to mothers receiving chemotherapy after the first trimester is normal.”
Multicenter Prospective Study
The prospective study to which Dr. Pentheroudakis referred was reported at the Stockholm meeting by Frederic Amant, MD, of the University Hospitals Leuven in Belgium.1
“Fear of chemotherapy is not an indication to terminate pregnancy and not a reason to delay maternal treatment for cancer,” Dr. Amant agreed, based on the findings of a multicenter prospective study of 70 children exposed prenatally to chemotherapy (anthracycline-based in 78%). Children were examined at birth, 18 months, age 5 to 6, and every 3 years thereafter until age 18. The study is ongoing, and median follow-up is 22 months.
Testing comprised a clinical neurologic examination and age-appropriate testing of cognitive function (Bayley Scales of Infant Development, IQ test), learning, memory, behavior, and so forth. Children also received electro/echocardiography and audiometry.
A total of 236 cycles of chemotherapy were administered during 68 pregnancies. Median gestational age at diagnosis was 18 weeks, and median gestational age at birth was 35.7 weeks; 9% were born between 32 and 34 weeks, and 7% between 28 and 32 weeks. Median birth weight was 2,612 g, and intrauterine growth retardation was observed in 21%.
The neonatal neurologic examination was normal in 64 infants (91.4%), and congenital malformations and other health problems did not occur in excess of the general population. The childrens’ behavior, general health, hearing, and growth during follow-up were also within normal ranges, and they demonstrated “age-adequate” neurologic development and cardiac function, Dr. Amant reported.
However, in children born prematurely, some impairment in cognitive development was recorded. Neurocognitive impairment (< 2 SD below the mean) was observed in 2% of children of gestational age ≥ 34 weeks but in 19% of those born at < 34 weeks. “We have to take care to reduce iatrogenic prematurity,” he commented.
Hearing loss was documented in three children. Cardiac testing revealed no congenital heart malformation and normal functional parameters. Twins born prematurely constituted the “outliers” with serious mental/motor retardation and developmental delay, but a genetic syndrome was believed responsible for this.
Body of Data for Safety
Dr. Pentheroudakis said the current study fits with what has been observed in retrospective studies.
In the European Registry of 315 pregnant women with breast cancer, those who received chemotherapy (51%) had neonatal outcomes no different from those who did not. Loibl et al2 concluded, in their report at the 2010 CTRC-AACR San Antonio Breast Cancer Symposium, “Pregnant patients with breast cancer should be treated as closely as possible to standard recommendations. Early delivery with the risk of prematurity of the newborns is unnecessary.”
Hahn et al3 evaluated 57 children exposed to CAF (cyclophosphamide, doxorubicin, fluorouracil) after the first trimester and found normal cognitive and intellectual development and general health at 38 months, although two malformations were seen in three preterm deliveries. Aviles et al followed into adulthood 81 children exposed to anthracyclines4 and another 84 children whose mothers had hematologic malignancies (38 exposed to chemotherapy during the first trimester)5 and found all outcomes normal.
As for the current study, its strengths were its “meticulous methodology, large sample size for a rare clinical situation, cardiology follow-up in all patients, and neurocognitive tests in the majority,” Dr. Pentheroudakis said. However, he noted the follow-up period is short, and few children were observed long-term. Participation was refused for eight patients, and their neurocognitive status is unknown. Details were also lacking as to the mother’s cancer and treatment, and the cause of prematurity in 16 children.
“The take-home message is that abortion beyond the first trimester is not necessary and does not seem to improve maternal outcomes,” he said. “The fetal risks, if any, do not outweigh the maternal risks stemming from no treatment, although prematurity is associated with neurocognitive impairment and should be avoided if possible.” ■
Disclosure: Drs. Pentheroudakis and Amant reported no potential conflicts of interest.
1. Amant F, Van Calsteren K, Halaska M, et al: Cognitive and cardiac outcome after prenatal exposure to chemotherapy in children 18 months or older. European Multidisciplinary Cancer Congress. Abstract 12LBA. Presented September 27, 2011.
2. Loibl S, Amant F, Kaufmann M, et al: 313 patients with breast cancer during pregnancy—results from a prospective and retrospective registry (GBG-20/BIG02-03). Abstract S6-2. Breast Cancer Res Treat 70(24 suppl):91s, 2010.
3. Hahn KM, Johnson PH, Gordon N, et al: Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer 107:1219-1226, 2006.
4. Aviles A, Neri N, Nambo MJ: Long-term evaluation of cardiac function in children who received anthracyclines during pregnancy. Ann Oncol 17:286-288, 2006.
5. Aviles A, Neri N: Hematological malignancies and pregnancy: A final report of 84 children who received chemotherapy in utero. Clin Lymphoma 2:173-177, 2001.
Chemotherapy delivered in the first trimester is associated with a 10% to 30% risk of abortion and 10% to 25% risk of malformations. Therefore, it should be postponed until the second or third trimester, when most regimens appear to be safe, according to Nicholas Pavlidis, MD, of the University of...