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

Int J Gynecol Cancer. 2019 Sep;29(7):1195-1202. doi: 10.1136/ijgc-2019-000416. Epub 2019 Aug 7.

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.

Keywords: gynecology.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / embryology*
  • Case-Control Studies
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Epirubicin / administration & dosage
  • Epirubicin / adverse effects
  • Female
  • Fetal Development / drug effects*
  • Humans
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Neoplasms / drug therapy
  • Pregnancy
  • Pregnancy Complications, Neoplastic / drug therapy*
  • Prenatal Exposure Delayed Effects / chemically induced*

Substances

  • Epirubicin
  • Cyclophosphamide