Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PL03

Poster Communications

Sex, drugs and rock and roll: Tales from preterm fetal life

L. Bennet1

1. The University of Auckland, Grafton, New Zealand.


Globally around 15 million babies are born preterm each year (less than 37 weeks gestation) and prematurity is the leading cause of neonatal death. Survivors are at significantly greater risk of both short and long-term complications such as necrotising enterocolitis, renal failure, feeding difficulties and hypoglycaemia, jaundice, retinopathy, cardio-respiratory complications, brain injury and impaired brain development. Thus, preterm birth can be rightly said to be a major systems physiology challenge. Preterm organ structure and function are, by definition, immature, and the stress of adapting to an environment the baby is not physiologically prepared for significantly contributes to injury and illness. Adapting to preterm newborn life is further complicated by exposure to adverse events such as hypoxia and infection before birth. Thus to advance the development of treatments to reduce or prevent preterm morbidity requires that we understand the adaptive responses of both the newborn, and the fetus, under a variety of physiological and pathological conditions. While younger and low-birthweight prems are at greater risk of injury and illness, we now know that even late preterm infants and near-term infants are at greater risk of poor outcomes compared to their term counterparts. Thus there is something about living in utero which promotes normal development, and this further highlights the need to understand fetal physiology. The focus of this talk is on the fetal responses to asphyxia and I will demonstrate that our perception of the fragile, delicate preterm newborn should not colour our understanding about how the preterm fetus may respond to challenges to its environment. I will explore how we have challenged the traditional concept that the preterm fetus must be less capable than full term fetuses in mounting a defence to hypoxia due to immaturity of chemoreflex and other adaptive responses, and that this must in part underpin vulnerability to injury. I will outline the triphasic behavioural, neural, cardiovascular and cerebrovascular compensation and decompensation responses of the preterm fetus to asphyxia. This will highlight the phenomenal tolerance of the preterm fetus, and how this tolerance paradoxically places the preterm fetus at greater risk of injury. I will discuss why the sex of the fetus makes a difference to neonatal survival and risk injury and present data on how male and female fetuses respond to asphyxia. I will show how this study revealed the importance of metabolism and how it raises the question of whether we should augment fetal glucose and other metabolic substrates. Hypoglycaemia is significantly associated with adverse neurodevelopmental outcomes in preterm babies, however there is potential risk in manipulating glucose. I will discuss new evidence showing that the glucose paradox, well described for the adult but not for the fetus and newborn, does occur in perinatal life. I will demonstrate that while increased glucose during asphyxia may help the fetus survive, this comes at a potentially dramatic cost to the brain. Finally, I will discuss how common insults such infection and standard antenatal therapies such as glucocorticoids can interact with the fetal adaptation to asphyxia to modulate brain injury.

Where applicable, experiments conform with Society ethical requirements