Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood.
—Frederic Amant, MD, PhD, and colleagues
In a study reported in The New England Journal of Medicine, Frederic Amant, MD, PhD, of University Hospitals Leuven, Belgium, and colleagues in the International Network on Cancer, Infertility, and Pregnancy found that cancer diagnosed during pregnancy did not appear to affect cognitive, cardiac, or general development in offspring during early childhood irrespective of whether the mothers received cancer treatment.1
The study was published concurrently with its presentation by Dr. Amant at the European Cancer Congress in Vienna, Austria (see related article).
This multicenter case-control study included 129 children whose mothers received a diagnosis of cancer during pregnancy (see sidebar) and 129 matched children of women without a cancer diagnosis who had uncomplicated pregnancy and delivery. Cases were recruited from referral centers in Belgium, the Netherlands, Italy, and the Czech Republic, and controls were recruited from the general population of each country.
A health questionnaire and medical files were used to obtain data on neonatal and general health. All children were assessed by neurologic examination and the Bayley Scales of Infant Development at 18 months, 36 months, or both. Cardiac assessment was performed at 36 months.
In addition to being matched for age at the time of cognitive assessment, children in the control group were also matched with those in the prenatal-exposure group for gestational age at birth, country, and edition of the Bayley scale used in assessment. Children in the prenatal-exposure group had a median age of 22 months (range = 12–42 months).
During pregnancy, 96 children in the prenatal-exposure group (74.4%) were exposed to chemotherapy alone or in combination with other treatments, 11 (8.5%) to radiotherapy alone or in combination, 13 (10.1%) to surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment.
Birth and Growth
Median gestational age at birth was 36 weeks in the prenatal-exposure group; 61.2% (79 children) were born preterm, compared with a general percentage of 6.8% to 8.0% in the countries of birth (control children were matched for gestational age at birth). Median birth weight was 2,705 g. Birth weight was below the 10th percentile (small for gestational age) in 28 (22.0%) of 127 children in the prenatal-exposure group and in 19 (15.2%) of 125 children in the control group (P = .16). Among children with available data, the status of small for gestational age was reported for 24 (25%) of 95 exposed to chemotherapy and 4 (36%) of 11 exposed to radiotherapy.
The frequencies of medical problems and need for surgery or medical care were similar in the two groups. Biometric data showed similar results in the two groups for weight, height, and head circumference during growth. In 22 children of mothers who received chemotherapy and were small for gestational age, catch-up weight was observed at the time of testing (18 months for 17) in 14 (63.3%).
Control group parents were more highly educated than prenatal-exposure group parents and parental education levels were significantly related to cognitive outcome testing in children. Thus, analyses comparing the two groups included parental education level as a covariate.
There were no significant differences between groups in cognitive development according to children’s country of origin. Most children in both groups had normal cognitive development based on Bayley score; no significant difference between groups was observed (P = .08) including after adjustment for parental education level (P = .52). Cognitive outcome also did not differ significantly between children exposed to chemotherapy and the control group (P = .43).
Univariate linear regression analysis including 238 children from both groups with available data showed that average cognitive score increased by 2.9 points for each additional week in gestational age at birth (P < .001). In a regression model including gestational age, study group, and the interaction between gestational age and study group, the interaction term was not significant (P = .68; P = .05 for gestational age, P = .62 for study group). After adjustment for sex, test age, country, parental education level, and race, the average increase was 2.2 points for each additional week of gestational age (P < .001).
Cardiologic evaluation of 47 prenatal-exposure children and 47 sex-matched control children at 36 months of age showed generally normal cardiac findings. No significant differences between groups were observed for heart rate, blood pressure, ejection fraction, fractional shortening, values for global longitudinal strain and circumferential strain, or echocardiographic measurement of diastolic function.
No structural abnormalities were detected by echocardiography in any children, and all measures of cardiac-chamber dimensions and wall thickness were within normal ranges. Small but significant differences were observed in tissue Doppler imaging measurements of the basal segment of the interventricular septum, with higher mean peak systolic and early diastolic velocities in the control group (P = .003 for both); no differences were observed in the left-ventricular lateral wall. The differences were not observed in the 26 children exposed to anthracyclines compared with the control group.
The investigators concluded: “Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment.”
Tineke Vandenbroucke, MSc, Magali Verheecke, MD, and Dr. Amant, all from University Hospitals Leuven, Belgium, contributed equally to The New England Journal of Medicine article. ■
Disclosure: The study was supported by Research Foundation–Flanders, Stichting tegen Kanker, Belgian Cancer Plan (Ministry of Health), KU Leuven, and University Hospitals Leuven.
1. Amant F, Vandenbroucke T, Verheecke M, et al: Pediatric outcome after maternal cancer diagnosed during pregnancy. N Engl J Med. September 28, 2015 (early release online).
The majority of women with cancer treated during pregnancy had a diagnosis of breast cancer (69 mothers, including 2 twin pregnancies [55%]) or a hematologic malignancy (20 mothers [16%], including 1 mother with acute lymphoid leukemia, 4 with acute myeloid leukemia, 1 with chronic myeloid...