Background
Late preterm birth is associated with short-term respiratory and adaptive problems.
Although antenatal corticosteroids seem to reduce the respiratory burden, this may
come at the cost of adverse neuropsychological outcomes later in life. This impact
has not been investigated.
Objective
Herein, we investigate what the short- and long-term neurodevelopmental effects of
a single course of betamethasone in simulated late preterm birth.
Study Design
Time-mated pregnant does received 0.1 mg/kg betamethasone (n=8) or 1 mL saline intramuscular
(n=6) at the postconceptional ages of 28 and 29 days. The antenatal corticosteroid
dose and scheme were based on previous studies and were comparable with routine clinical
use. Cesarean delivery was done on postconceptional age 30 days (term=31 days), and
new-born rabbits were foster-cared for 28 days and were thereafter cared for in group
housing. Neonatal lung function testing and short-term neurobehavioral testing was
done. Open field, spontaneous alternation, and novel object recognition tests were
subsequently performed at 4 and 8 weeks of age. On postnatal day 1 and at 8 weeks,
a subgroup was euthanized and transcardially perfuse fixated. Ex vivo high-resolution
Magnetic Resonance Imaging was used to calculate the Diffusion Tensor Imaging-derived
fractional anisotropy and mean diffusivity. Fixated brains underwent processing and
were serial sectioned, and a set of 3 coronal sections underwent anti-NeuN, Ki67,
and terminal deoxynucleotidyl transferase dUTP nick end labeling staining.
Results
Antenatal corticosteroid exposure was associated with improved neonatal lung function,
yet resulted in a long-term growth deficit that coincided with a persistent neurobehavioral
deficit. We demonstrated lower neonatal motor scores; a persistent anxious behavior
in the open field test with more displacements, running, and self-grooming episodes;
persistent lower alternation scores in the T-Maze test; and lower discriminatory indexes
in the novel object recognition.
On neuropathological assessment, antenatal corticosteroid exposure was observed to
result in a persistent lower neuron density and fewer Ki67+ cells, particularly in
the hippocampus and the corpus callosum. This coincided with lower diffusion tensor
imaging-derived fractional anisotropy scores in the same key regions.
Conclusion
Clinical equivalent antenatal corticosteroid exposure in this late preterm rabbit
model resulted in improved neonatal lung function. However, it compromised neonatal
and long-term neurocognition.
Key words
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Article Info
Publication History
Published online: December 04, 2021
Accepted:
November 23,
2021
Received in revised form:
November 5,
2021
Received:
June 20,
2021
Footnotes
The authors report no conflict of interest.
J.v.d.M. and L.v.d.V. are funded with support of the Erasmus + Programme of the European Union (framework agreement number: 2013-0040). I.V. is funded by the European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement number: 765274). This publication reflects the views of the author only, and the Commission cannot be held responsible for any use which may be made of the information contained therein.
Data sharing: All the data generated or analyzed during this study are included in this published article and its supplementary information files.
Cite this article as: van der Merwe J, van der Veeken L, Inversetti A, et al. Neurocognitive sequelae of antenatal corticosteroids in a late preterm rabbit model. Am J Obstet Gynecol 2022;226:850.e1-21.
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