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Review
. 2023 Nov;601(21):4667-4689.
doi: 10.1113/JP284191. Epub 2023 Aug 17.

Does fetal growth restriction induce neuropathology within the developing brainstem?

Elham Ahmadzadeh  1   2 , Graeme R Polglase  1   2 , Vanesa Stojanovska  1   2 , Eric Herlenius  3   4 , David W Walker  1   5 , Suzanne L Miller  1   2 , Beth J Allison  1   2
Affiliations
Review

Does fetal growth restriction induce neuropathology within the developing brainstem?

Elham Ahmadzadeh et al. J Physiol. 2023 Nov.

Abstract

Fetal growth restriction (FGR) is a complex obstetric issue describing a fetus that does not reach its genetic growth potential. The primary cause of FGR is placental dysfunction resulting in chronic fetal hypoxaemia, which in turn causes altered neurological, cardiovascular and respiratory development, some of which may be pathophysiological, particularly for neonatal life. The brainstem is the critical site of cardiovascular, respiratory and autonomic control, but there is little information describing how chronic hypoxaemia and the resulting FGR may affect brainstem neurodevelopment. This review provides an overview of the brainstem-specific consequences of acute and chronic hypoxia, and what is known in FGR. In addition, we discuss how brainstem structural alterations may impair functional control of the cardiovascular and respiratory systems. Finally, we highlight the clinical and translational findings of the potential roles of the brainstem in maintaining cardiorespiratory adaptation in the transition from fetal to neonatal life under normal conditions and in response to the pathological environment that arises during development in growth-restricted infants. This review emphasises the crucial role that the brainstem plays in mediating cardiovascular and respiratory responses during fetal and neonatal life. We assess whether chronic fetal hypoxaemia might alter structure and function of the brainstem, but this also serves to highlight knowledge gaps regarding FGR and brainstem development.

Keywords: brain injury; brainstem; cardiovascular; fetal; fetal growth restriction; neuropathology.

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Conflict of interest statement

Authors have no competing interests to declare.

Figures

Figure 1
Figure 1. Transverse sections (left) and sagittal view (right) of the brainstem cardiorespiratory centres (BCRCs) within the ovine pons and medulla oblongata
A, the pons contains respiratory groups including the nucleus raphe pontis (NRpn), Kölliker–Fuse nucleus (KFN), parabrachial nuclei (PBN) and the rostral portion of the nucleus raphe magnus (NRmg). B, the medulla oblongata houses the caudal portion of the NRmg, retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). C, nucleus raphe obscurus (NRob), nucleus raphe pallidus (NRpa), solitary tract (ST) and nucleus of the solitary tract (NTS), the dorsal motor nucleus of the vagus (DMNV), nucleus ambiguus (NA) Bötzinger complex (BC) and rostral ventral respiratory medulla (RVLM). D, NRob, ST, NTS, DMNV, hypoglossal nucleus (HN), pre‐Bötzinger complex (preBötC), and caudal ventrolateral medulla (CVLM). E, ST, NTS, DMNV, HN and rostral ventral respiratory groups (RVRG). The caudal ventral respiratory groups (CVRG) exist in the lower sections towards the spinal cord. Images taken by E.A. from ovine fetal brainstem and annotated with brainstem regions (Lindsey et al., ; Moreira et al., ; Stockx et al., 2007).
See this image and copyright information in PMC

Comment in

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