Birth signalling hormones and the developmental consequences of caesarean delivery

Abstract

Rates of delivery by caesarean section (CS) are increasing around the globe and, although several epidemiological associations have already been observed between CS and health outcomes in later life, more are sure to be discovered as this practice continues to gain popularity. The components of vaginal delivery that protect offspring from the negative consequences of CS delivery in later life are currently unknown, although much attention to date has focused on differences in microbial colonisation. Here, we present the case that differing hormonal experiences at birth may also contribute to the neurodevelopmental consequences of CS delivery. Levels of each of the ‘birth signalling hormones’ (oxytocin, arginine vasopressin, epinephrine, norepinephrine and the glucocorticoids) are lower following CS compared to vaginal delivery, and there is substantial evidence for each that manipulations in early life results in long‐term neurodevelopmental consequences. We draw from the research traditions of neuroendocrinology and developmental psychobiology to suggest that the perinatal period is a sensitive period, during which hormones achieve organisational effects. Furthermore, there is much to be learned from research on developmental programming by early‐life stress that may inform research on CS, as a result of shared neuroendocrine mechanisms at work. We compare and contrast the effects of early‐life stress with those of CS delivery and propose new avenues of research based on the links between the two bodies of literature. The research conducted to date suggests that the differences in hormone signalling seen in CS neonates may produce long‐term neurodevelopmental consequences.

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

“…OXT is a key modulator of mammalian maternal-offspring attachment and social behaviour [12][13][14][15][16]. The OXT system can be activated by stressful and anxiogenic stimuli and acts as key-modulator of the hypothalamic-pituitary-adrenal (HPA) axis [17][18][19]. Consistent with the important role of OXT in social behaviour promotion and stress regulation, OXT dysregulation has been associated with anxiety and autism spectrum disorders (ASD) [20][21][22][23].…”

Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death

“…Given the lag between stimulus onset and c-Fos protein accumulation 17,18 , the activation we observed at 3 h postnatal was presumably triggered by stimuli associated with birth or the immediate peripartum period. A vaginal birth is a complex stimulus involving marked hormonal changes associated with labor, mechanical stimuli associated with uterine contractions, passage through the birth canal, and exposure to the ex utero environment 28 . All of these factors, with the exception of exposure to the ex utero environment, are altered following a C-section delivery.…”

Selective reduction in the expression of type‐1 metabotropic glutamate receptors in the hippocampus of adult rats born by caesarean section

“…Oxytocin surge during vaginal birth is able to promote GABA switch in the neonatal mouse brain, a crucial maturational event, which can influence the life course trajectory (typical versus pathological), as shown by Tyzio et al. (2006) (for reviews see Kenkel, 2021; Zinni et al., 2018).…”

“…However, previous rat studies reported long‐term effects of C‐section on AMPA, NMDA and kainate receptors, distinct from the effects of hypoxia (El Khodor & Boksa, 2003). As a mode of delivery is increasingly studied as an effect modifier of perinatal risk factors (Kenkel, 2021), our study aimed at verifying the long term effects of either hypoxia or C‐section on a class of receptors that plays a fundamental role in brain and behaviour plasticity with potential repercussion on CNS developmental trajectory.…”