Effects of in-utero exposure to chemotherapy on fetal brain growth

Sofia Passera, Valeria Contarino, Giovanna Scarfone, Elisa Scola, Camilla Fontana, Fedro Peccatori, Claudia Cinnante, Serena Counsell, Maneula Ossola, Silvia Pisoni, Nicola Pesenti, Elena Grossi, Frédéric Amant, Fabio Mosca, Fabio Triulzi, Monica Fumagalli

Research output: Contribution to journalArticle

Abstract

Objective: Children exposed to chemotherapy in the prenatal period demonstrate normal neurocognitive development at 3 years but concerns regarding fetal brain growth remain high considering its vulnerability to external stimuli. Our aim was to evaluate the impact of in-utero chemotherapy exposure on brain growth and its effects on neurodevelopmental outcome. Methods: The protocol was approved by the local ethics committee. Brain regional volumes at term postmenstrual age were measured by MRI in children exposed to in-utero chemotherapy and compared with normal MRI controls. Brain segmentation was performed by Advanced Normalization Tools (ANTs)-based transformations of the Neonatal Brain Atlas (ALBERT). Neurodevelopmental assessment (Bayley-III scales) was performed at 18 months corrected age in both exposed infants and in a group of healthy controls. Multiple linear regressions and false discovery rate correction for multiple comparisons were performed. Results: Twenty-one newborns prenatally exposed to chemotherapy (epirubicin administered in 81% of mothers) were enrolled in the study: the mean gestational age was 36.4±2.4 weeks and the mean birthweight was 2,753±622 g. Brain MRI was performed at mean postmenstrual age of 41.1±1.4 weeks. No statistically significant differences were identified between the children exposed to chemotherapy and controls in both the total (398±55 cm3 vs 427±56 cm3, respectively) and regional brain volumes. Exposed children showed normal Bayley-III scores (cognitive 110.2±14.5, language 99.1±11.3, and motor 102.6±7.3), and no significant correlation was identified between the brain volumes and neurodevelopmental outcome. Conclusion: Prenatal exposure to anthracycline/cyclophosphamide-based chemotherapy does not impact fetal brain growth, thus supporting the idea that oncological treatment in pregnant women seems to be feasible and safe for the fetus.

Original languageEnglish
Pages (from-to)1195-1202
JournalInternational Journal of Gynecological Cancer
Volume29
Issue number7
DOIs
Publication statusPublished - Jan 1 2019

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Fetal Development
Drug Therapy
Brain
Epirubicin
Ethics Committees
Atlases
Anthracyclines
Cyclophosphamide
Gestational Age
Pregnant Women
Linear Models
Fetus
Language
Mothers
Newborn Infant
Control Groups
Growth

Keywords

  • gynecology

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

Effects of in-utero exposure to chemotherapy on fetal brain growth. / Passera, Sofia; Contarino, Valeria; Scarfone, Giovanna; Scola, Elisa; Fontana, Camilla; Peccatori, Fedro; Cinnante, Claudia; Counsell, Serena; Ossola, Maneula; Pisoni, Silvia; Pesenti, Nicola; Grossi, Elena; Amant, Frédéric; Mosca, Fabio; Triulzi, Fabio; Fumagalli, Monica.

In: International Journal of Gynecological Cancer, Vol. 29, No. 7, 01.01.2019, p. 1195-1202.

Research output: Contribution to journalArticle

Passera, Sofia ; Contarino, Valeria ; Scarfone, Giovanna ; Scola, Elisa ; Fontana, Camilla ; Peccatori, Fedro ; Cinnante, Claudia ; Counsell, Serena ; Ossola, Maneula ; Pisoni, Silvia ; Pesenti, Nicola ; Grossi, Elena ; Amant, Frédéric ; Mosca, Fabio ; Triulzi, Fabio ; Fumagalli, Monica. / Effects of in-utero exposure to chemotherapy on fetal brain growth. In: International Journal of Gynecological Cancer. 2019 ; Vol. 29, No. 7. pp. 1195-1202.
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abstract = "Objective: Children exposed to chemotherapy in the prenatal period demonstrate normal neurocognitive development at 3 years but concerns regarding fetal brain growth remain high considering its vulnerability to external stimuli. Our aim was to evaluate the impact of in-utero chemotherapy exposure on brain growth and its effects on neurodevelopmental outcome. Methods: The protocol was approved by the local ethics committee. Brain regional volumes at term postmenstrual age were measured by MRI in children exposed to in-utero chemotherapy and compared with normal MRI controls. Brain segmentation was performed by Advanced Normalization Tools (ANTs)-based transformations of the Neonatal Brain Atlas (ALBERT). Neurodevelopmental assessment (Bayley-III scales) was performed at 18 months corrected age in both exposed infants and in a group of healthy controls. Multiple linear regressions and false discovery rate correction for multiple comparisons were performed. Results: Twenty-one newborns prenatally exposed to chemotherapy (epirubicin administered in 81{\%} of mothers) were enrolled in the study: the mean gestational age was 36.4±2.4 weeks and the mean birthweight was 2,753±622 g. Brain MRI was performed at mean postmenstrual age of 41.1±1.4 weeks. No statistically significant differences were identified between the children exposed to chemotherapy and controls in both the total (398±55 cm3 vs 427±56 cm3, respectively) and regional brain volumes. Exposed children showed normal Bayley-III scores (cognitive 110.2±14.5, language 99.1±11.3, and motor 102.6±7.3), and no significant correlation was identified between the brain volumes and neurodevelopmental outcome. Conclusion: Prenatal exposure to anthracycline/cyclophosphamide-based chemotherapy does not impact fetal brain growth, thus supporting the idea that oncological treatment in pregnant women seems to be feasible and safe for the fetus.",
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T1 - Effects of in-utero exposure to chemotherapy on fetal brain growth

AU - Passera, Sofia

AU - Contarino, Valeria

AU - Scarfone, Giovanna

AU - Scola, Elisa

AU - Fontana, Camilla

AU - Peccatori, Fedro

AU - Cinnante, Claudia

AU - Counsell, Serena

AU - Ossola, Maneula

AU - Pisoni, Silvia

AU - Pesenti, Nicola

AU - Grossi, Elena

AU - Amant, Frédéric

AU - Mosca, Fabio

AU - Triulzi, Fabio

AU - Fumagalli, Monica

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Children exposed to chemotherapy in the prenatal period demonstrate normal neurocognitive development at 3 years but concerns regarding fetal brain growth remain high considering its vulnerability to external stimuli. Our aim was to evaluate the impact of in-utero chemotherapy exposure on brain growth and its effects on neurodevelopmental outcome. Methods: The protocol was approved by the local ethics committee. Brain regional volumes at term postmenstrual age were measured by MRI in children exposed to in-utero chemotherapy and compared with normal MRI controls. Brain segmentation was performed by Advanced Normalization Tools (ANTs)-based transformations of the Neonatal Brain Atlas (ALBERT). Neurodevelopmental assessment (Bayley-III scales) was performed at 18 months corrected age in both exposed infants and in a group of healthy controls. Multiple linear regressions and false discovery rate correction for multiple comparisons were performed. Results: Twenty-one newborns prenatally exposed to chemotherapy (epirubicin administered in 81% of mothers) were enrolled in the study: the mean gestational age was 36.4±2.4 weeks and the mean birthweight was 2,753±622 g. Brain MRI was performed at mean postmenstrual age of 41.1±1.4 weeks. No statistically significant differences were identified between the children exposed to chemotherapy and controls in both the total (398±55 cm3 vs 427±56 cm3, respectively) and regional brain volumes. Exposed children showed normal Bayley-III scores (cognitive 110.2±14.5, language 99.1±11.3, and motor 102.6±7.3), and no significant correlation was identified between the brain volumes and neurodevelopmental outcome. Conclusion: Prenatal exposure to anthracycline/cyclophosphamide-based chemotherapy does not impact fetal brain growth, thus supporting the idea that oncological treatment in pregnant women seems to be feasible and safe for the fetus.

AB - Objective: Children exposed to chemotherapy in the prenatal period demonstrate normal neurocognitive development at 3 years but concerns regarding fetal brain growth remain high considering its vulnerability to external stimuli. Our aim was to evaluate the impact of in-utero chemotherapy exposure on brain growth and its effects on neurodevelopmental outcome. Methods: The protocol was approved by the local ethics committee. Brain regional volumes at term postmenstrual age were measured by MRI in children exposed to in-utero chemotherapy and compared with normal MRI controls. Brain segmentation was performed by Advanced Normalization Tools (ANTs)-based transformations of the Neonatal Brain Atlas (ALBERT). Neurodevelopmental assessment (Bayley-III scales) was performed at 18 months corrected age in both exposed infants and in a group of healthy controls. Multiple linear regressions and false discovery rate correction for multiple comparisons were performed. Results: Twenty-one newborns prenatally exposed to chemotherapy (epirubicin administered in 81% of mothers) were enrolled in the study: the mean gestational age was 36.4±2.4 weeks and the mean birthweight was 2,753±622 g. Brain MRI was performed at mean postmenstrual age of 41.1±1.4 weeks. No statistically significant differences were identified between the children exposed to chemotherapy and controls in both the total (398±55 cm3 vs 427±56 cm3, respectively) and regional brain volumes. Exposed children showed normal Bayley-III scores (cognitive 110.2±14.5, language 99.1±11.3, and motor 102.6±7.3), and no significant correlation was identified between the brain volumes and neurodevelopmental outcome. Conclusion: Prenatal exposure to anthracycline/cyclophosphamide-based chemotherapy does not impact fetal brain growth, thus supporting the idea that oncological treatment in pregnant women seems to be feasible and safe for the fetus.

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