Courtesy Dr. Frédéric Amant
This woman's pregnancy was complicated by spinocellular cervical cancer stage 1b. After chemotherapy, she underwent cesarean section at 33 weeks.
Fetuses also were exposed to a variety of other drugs, including antibiotics, antiemetics, pain medications, colony stimulating factors, and anxiolytics.
Breast cancer was the most common disease type (35). There were 18 cases of hematologic cancers, 6 ovarian cancers, 4 cervical cancers, and 1 each of basal cell carcinoma, brain tumor, Ewing’s sarcoma, colorectal cancer, and nasopharyngeal cancer.
The mean gestational age at cancer diagnosis was 18 weeks, although fetuses ranged in age from 2 to 33 weeks when their mothers were diagnosed. About a third of the babies (23) were born at term.
Seven were born at 28-32 weeks, nine at 32-34 weeks, and 31 at 34-37 weeks. Weight for gestational age was below the 10th percentile in 14 children (21%).
Seven congenital anomalies were found in the group of 70 children (10%) – a rate not significantly different from that in the background population. There were only two major malformations, for a 2.9% rate. Malformations included the following:
• Hip subluxation, pectus excavatum and hemangioma, associated with chemotherapy only.
• Bilateral partial syndactyly, associated with chemotherapy plus radiotherapy.
• Bilateral small protuberance on one finger, and rectal atresia, associated with chemotherapy plus surgery.
• Bilateral double cartilage ring in a child exposed to chemotherapy, surgery and radiotherapy.
None of the children showed any congenital cardiac issues.
All of the children showed neurocognitive development that was within normal range, except for the set of twins, who were delivered by cesarean section at 32.5 weeks after a preterm premature rupture of membranes. These children were so delayed that they were not able to complete cognitive testing. Their mother developed an acute myeloid leukemia – one of the true "emergency" cancers diagnosed in pregnancy, Dr. Amant said. The babies had been exposed to idarubicin and cytosine arabinoside at 15.5, 21.5, 26.5, and 31.5 weeks’ gestation.
The boy, who weighed 1,640 g at birth, had a normal karyotype but, at 3 years, brain imaging showed a unilateral polymicrogyria in the left perisylvian area. He showed an early developmental delay; at age 9 years, he had the developmental capacity of a 12-month old.
The girl, who weighed 1,390 g at birth, also had an early developmental delay, but at age 9 years she attended school with support. Her parents refused brain imaging.
"The other 68 children did well," Dr. Amant said. "This doesn’t mean they were all normal in every way, but in any population you will see learning and developmental delay issues. We think the problem for the delayed children was not related to chemotherapy exposure, but more likely to their prematurity."
Dr. Amant saw a direct correlation between gestational age and intelligence quota. "When we controlled for age, gender, and country of birth, we found that the IQ score increased by almost 12 points for each additional month of gestation."
The U.S. Experience
Dr. Elyce Cardonick
Dr. Cardonick has found similar results. Her registry now contains information on 280 women who were enrolled over a 13-year period. The children born from these pregnancies have been assessed annually since birth. It also includes 70 controls – children whose mothers had cancer but who were not exposed to chemotherapy.
She published interim results of the registry in 2010 (Cancer J. 2010;16:76-82). At that point, it contained information on 231 women and 157 children. The most common malignancy was breast cancer (128); the mean gestational age at diagnosis was 13 weeks. About a third of the women (54) were advised to terminate their pregnancy; 12 did so.
Among those who continued both pregnancy and treatment, neonatal outcomes were generally good. There were nine premature deliveries related to preterm labor or premature rupture of membranes. The congenital anomaly rate born was 4%, which was in line with the normal background rate and slightly lower than that seen in Dr. Amant’s cohort.
The infants’ mean birth weight was 2,647 g, which was significantly less than the mean 2,873 g in the control group, but probably clinically irrelevant, Dr. Cardonick wrote in the paper.
She continues to follow these children annually. At this point, the children are a mean 5 years old; her oldest subject is 14 years. So far, the rate of neurocognitive issues in the group is no different than would be observed in any other group, and none of the children has developed any health problem that could be conclusively tied to intrauterine chemotherapy exposure.