Long-term impact of prenatal exposure to chemotherapy on executive functioning: An ERP study

Abstract

This study examines the long-term impact of prenatal exposure to chemotherapy on executive functioning and the contribution of late-prematurity to this effect, using eventrelated potentials. METHODS Mothers of the prenatal-exposed children (n=20) were diagnosed with cancer and received chemotherapeutic treatment during pregnancy. We recruited healthy controls (n=20) who were matched on a 1:1 ratio regarding prematurity, age and sex. We assessed executive functioning at the age of nine, using two event-related potential paradigms: a Go/Nogo paradigm to investigate processes of response inhibition and conflict monitoring, as well as a Posner paradigm to investigate spatial attention. RESULTS Lower potentials were found in prenatal-exposed children compared to controls in the Go/Nogo P3 and Posner positive slow wave. Moreover, prenatal-exposed children responded slower on the Posner paradigm compared to controls (p<.033), with more incorrect responses (p=.023). In the control group, the N2 Go/Nogo wave was more pronounced in children born after a longer gestation. CONCLUSIONS This is the first study that demonstrates an effect of prenatal exposure to chemotherapy on the development of executive functioning, not limited to the effect of late-prematurity. SIGNIFICANCE This study emphasizes the necessity of a long-term follow-up of prenatal-exposed children to re-inform clinical practice on the costs and benefits of late-premature induction over treatment during pregnancy.

Long-Term Neurodevelopmental Outcome of Children after in Utero Exposure to Chemotherapy

“…A summary of the studies describing the type of maternal cancer and the chemotherapy schemes administered during pregnancy while evaluating the neurodevelopmental outcome of children in utero exposed to chemotherapy is demonstrated in Tables 1 and 2. [16] Acute leukemia (7) Non-Hodgkin's lymphoma (18) Hodgkin's lymphoma (14 Acute leukemia (14) Non-Hodgkin's lymphoma (25) Hodgkin's lymphoma (19) COPA (6 Breast cancer (26) Ovarian cancer (4) Hodgkin's lymphoma (4) Acute leukemia (1) [27] and Van Gerwen et al, 2020 [28] Breast cancer (69) Hematological malignancy (20) Cervical cancer 10Ovarian cancer (10) Brain cancer (4) Oral cavity and oropharyngeal cavity cancer 4Nasopharyngeal cancer (1) Gastric cancer 2Colon cancer 1Melanoma 2 Breast cancer and hematological cancer (e.g., acute leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma) were the most frequently diagnosed malignancies during gestation [13][14][15][16][17][18][19][20][21][22][23][25][26][27][28][29]. Additionally, several cases of cervical, ovarian, brain and gastric cancer were also reported [13,14,[20][21][22]24,[26][27][28][29...…”

“…Additionally, several cases of cervical, ovarian, brain and gastric cancer were also reported [13,14,[20][21][22]24,[26][27][28][29]. Some studies focused on a single type of pregnancy-related cancer analyzing its treatment along with the maternal and the fetal outcomes [15][16][17][18][23][24][25], whereas other studies integrated data regarding multiple cancer types, as shown in Table 1 [13,14,[20][21][22][26][27][28][29]. Furthermore, various chemotherapy regimens were administered during the course of pregnancy, depending on the type of maternal cancer diagnosed; a combination of anthracycline-based regimens was most commonly used [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

“…Some studies focused on a single type of pregnancy-related cancer analyzing its treatment along with the maternal and the fetal outcomes [15][16][17][18][23][24][25], whereas other studies integrated data regarding multiple cancer types, as shown in Table 1 [13,14,[20][21][22][26][27][28][29]. Furthermore, various chemotherapy regimens were administered during the course of pregnancy, depending on the type of maternal cancer diagnosed; a combination of anthracycline-based regimens was most commonly used [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Cyclophosphamide, 5-fluorouracil, taxanes, and platinum derivatives were also regularly administered [13][14][15][16][17][18][19][20][21][22][23][24][2...…”

“…Furthermore, various chemotherapy regimens were administered during the course of pregnancy, depending on the type of maternal cancer diagnosed; a combination of anthracycline-based regimens was most commonly used [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Cyclophosphamide, 5-fluorouracil, taxanes, and platinum derivatives were also regularly administered [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. In the majority of the studies included in the review, the antineoplastic agents were administered in the second and third trimester of pregnancy [13,14,[20][21][22][23][24][25][26][27][28][29]; however, in all studies mainly investigating hematological malignancies, chemotherapy was administered in the first trimester as well [15]…”

“…Cyclophosphamide, 5-fluorouracil, taxanes, and platinum derivatives were also regularly administered [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. In the majority of the studies included in the review, the antineoplastic agents were administered in the second and third trimester of pregnancy [13,14,[20][21][22][23][24][25][26][27][28][29]; however, in all studies mainly investigating hematological malignancies, chemotherapy was administered in the first trimester as well [15][16][17][18][19].…”