Cognitive and Behavioral Development of 9-Year-Old Children After Maternal Cancer During Pregnancy: A Prospective Multicenter Cohort Study

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education.

Long‐term outcomes of children after prenatal exposure to maternal cancer and its treatment

“…Previous studies have identified maternal mortality as a significant contributor to adverse neurocognitive and behavioral outcomes, 19–21 which is supported by previous findings from the INCIP cohort, showing subtle differences in both child language development and the child's need of supportive care after maternal death 9,21 . A subanalysis on chemotherapy‐exposed children with a median age of 9 years ( n = 151) also showed a trend of a need for supportive care after maternal bereavement, although this trend was not statistically significant and may be confounded by the high incidence of prematurity in this cohort 11 . Further research, especially in the long‐term, is thus required to elucidate the psychosocial and neurocognitive impact of maternal separation and maternal death on the child.…”

“…Regarding neurocognitive development, previous cohort studies on children prenatally exposed to chemotherapy, showed an overall reassuring development until the age of 6 years 8,9 . Furthermore, a report on the 9‐year‐old cohort, described a normal cognitive and behavioral development in late childhood when complex and executive functions are developing 11 . Also, a Danish nation‐wide cohort study examined the general mortality, somatic diagnoses, and psychiatric diagnoses observed in offspring exposed to maternal cancer during pregnancy.…”

“… 8 , 9 Furthermore, a report on the 9‐year‐old cohort, described a normal cognitive and behavioral development in late childhood when complex and executive functions are developing. 11 Also, a Danish nation‐wide cohort study examined the general mortality, somatic diagnoses, and psychiatric diagnoses observed in offspring exposed to maternal cancer during pregnancy. The authors did not find any evidence of an elevated risk of mortality or severe morbidity among children exposed to cancer in utero.…”

Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study

“…Therefore, it is advised to start chemotherapy in the second or third trimester, that is, after week 14 of pregnancy 3–5. Previous studies have shown that chemotherapy during the second and/or third trimester of pregnancy does not affect the short-term cardiac and neurocognitive development of children, which is reassuring 2 6–9. Additionally, administering chemotherapy treatment to pregnant women has led to an increase in livebirths and decrease in iatrogenic preterm deliveries 1.…”

“…Furthermore, although overall, children born from pregnancies complicated by maternal cancer perform within normal ranges for their age, chemotherapy-exposed children had a significantly lower verbal IQ at 6 years, and were 3 times more likely to wear glasses than non-exposed children. However, since there are many confounding factors in neurocognitive development of children, a direct link with prenatal chemotherapy exposure cannot be accurately established 1 6–8…”