Children Exposed to Maternal Cancer Show Normal Cognitive and Behavioral Outcomes

The mean cognitive and behavioral outcomes for children aged 9 years who had prenatal exposure to their mother’s cancer were within normal ranges and comparable to the general population, at a long-term follow-up published in the Journal of Clinical Oncology.¹

Full scale intelligence quotient (FSIQ) was not found to be different by cancer treatment types (P = .776). Neither cancer stage (P = .776) nor gender (P = .802) were found to have a significant impact. Moreover, for children who were exposed to therapy (n = 109), no associations between the FSIQ and chemotherapeutic agent, exposure level, or timing of treatment emerged.

On average, the FSIQ score increased by 1.6 points for each week increase in gestational age at birth (95% CI, 0.7-2.5; P < .001).

“Cognitive and behavioral outcomes of 9-year-old children born to mothers diagnosed with cancer during pregnancy did not differ with norms of the general population,” wrote Indra A. Van Assche, MSc, a PhD researcher in neuropsychology at the University of Leuven, in Leuven, Belgium, and co-investigators, in the study. “We reported average group scores for all intelligence index scores, verbal and visuospatial memory outcomes, attentional functioning outcomes, and behavioral questionnaire measures. We found no impact of sex, treatment type, and cancer stage.”

Previous reports from this study suggested that fetal exposure to chemotherapy was not associated with increased central nervous system, cardiac or auditory morbidity and that the impairments that these children faced in regard to their general health and growth were comparable to the general population.² At the same time, subtle changes in cardiac and neurocognitive measurements emphasized the importance of long-term follow-up. In this analysis premature birth was the greatest driver of cognitive development impairments.²

In total, investigators used neurocognitive tests and parent-reported behavioral questionnaires to assess 151 children (mean age, 9.3 years; range, 7.8-10.6), including 96 from Belgium, 24 from the Netherlands, 9 from Italy, 6 from the Czech Republic, and 7 from New Jersey. In this set of participants, 109 (72.2%) had been exposed to chemotherapy (alone or combination with other treatment modalities), 18 (11.9%) had surgery alone, 16 (10.6%) had been expressed to radiotherapy, 1 to trastuzumab (Herceptin), and 16 (10.6%) had not been exposed to cancer treatment.¹

As part of the International Network on Cancer, Infertility and Pregnancy Child Follow-up study, children were assessed longitudinally at the age of 18 months, 36 months, and again every 3 years until age 18. This current 9-year analysis used FISQ, which is derived from the Wechsler Intelligence Scale for Children. Secondary outcomes were neurocognitive test scores and behavioral questionnaire results. All children also underwent a clinical neurologic and general pediatric examinations, and parents filled out a survey regarding their children general health and education level. All tests were conducted in the child’s native language.

Of note, gestational age at birth did show a positive association with full FISQ. Observations were also observed with maternal death and maternal education.

Gestational age was linked to verbal intelligence (β, 1.49 points/week; CI, 0.6-2.4; P = .02), performance intelligence (β, 1.39 points/week; CI, 0.6-2.2; P = .002), and processing speed (β, 1.21 points/week; CI, 0.3-2.1; P = .009).

Moreover, maternal bereavement was linked to lower FSIQ scores (P = .022). Children whose mothers passed away before they age 2 years demonstrated lower FSIQs (93.13 ± 12.65) than those with a surviving mother (104.08 ± 14.88). However, adjustments for gestational age caused this association to disappear (P < .3). Of note, children whose mother passed away before they were 2 years were, on average, born earlier (33.4 weeks ± 2.7), than those whose mother passed away after they were 2 years (37.1 weeks ± 1.7) and those with a surviving mother at the time of follow-up (36.4 weeks ± 2.5; P < .001).

In terms of general health, the patient-reported health questionnaire revealed no specific group across the population. Four children had been diagnosed with attention-deficit hyperactivity disorder, 3 of whom needed supportive medication. One child was on the autistic spectrum. Thirty-one children (24.4%) received remedial care, including speech therapy (n = 17), remedial teaching at school (n = 10), a type of physical or exercise therapy (n = 4), and neurofeedback therapy (n = 1).

Study authors noted that maternal death was not associated with not associated with a specific cancer type, cancer stage, or treatment type in this study and that, therefore, children who consequently developed cognitive development problems may have been equally affected by the maternal stress or an insecure mother-child attachment as they were by treatments. Moreover, for children who were prenatally exposed to chemotherapy, maternal education level was the only driving factor in FSIQ scores; prematurity was not found to have an effect, suggesting that more research into the effect of prematurity may be warranted in a larger chemotherapy group.

“Seventeen percent of the children in this study had lost their mother (of which almost 58% died before their child turned 2 years old),” study authors concluded. “The results suggest a relationship between maternal bereavement in the first 1000 days of life and full-scale intelligence, although a larger sample is necessary to disentangle effects of maternal loss and often coinciding premature birth.”

In accordance with the study guidelines, follow-up with this group of children will continue to be ongoing until they are age 18 years.

Reference

1. Van Assche IA, Huis In 't Veld EA, Van Calsteren K, et al. Cognitive and behavioral development of 9-year-old children after maternal cancer during pregnancy: a prospective multicenter cohort study. J Clin Oncol. Published online January 12, 2023. doi:10.1200/JCO.22.02005
2. Amant F, Van Calsteren K, Halaska MJ, et al: Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: An observational study. Lancet Oncol. 2012;13(3):256-264. doi:10.1016/S1470-2045(11)70363-1