Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia

Abstract

Birth asphyxia is a significant global health problem, responsible for ~1.2 million neonatal deaths each year worldwide. Those who survive often suffer from a range of health issues including brain damage—manifesting as cerebral palsy (CP)—respiratory insufficiency, cardiovascular collapse, and renal dysfunction, to name a few. Although the majority of research is directed toward reducing the brain injury that results from intrapartum birth asphyxia, the multi-organ injury observed in surviving neonates is of equal importance. Despite the advent of hypothermia therapy for the treatment of hypoxic–ischemic encephalopathy (HIE), treatment options following asphyxia at birth remain limited, particularly in low-resource settings where the incidence of birth asphyxia is highest. Furthermore, although cooling of the neonate results in improved neurological outcomes for a small proportion of treated infants, it does not provide any benefit to the other organ systems affected by asphyxia at birth. The aim of this review is to summarize the current knowledge of the multi-organ effects of intrapartum asphyxia, with particular reference to the findings from our laboratory using the precocial spiny mouse to model birth asphyxia. Furthermore, we reviewed the current treatments available for neonates who have undergone intrapartum asphyxia, and highlight the emergence of maternal dietary creatine supplementation as a preventative therapy, which has been shown to provide multi-organ protection from birth asphyxia-induced injury in our preclinical studies. This cheap and effective nutritional supplement may be the key to reducing birth asphyxia-induced death and disability, particularly in low-resource settings where current treatments are unavailable.

Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System

“…Severe and prolonged asphyxia can result in either intrauterine fetal death and stillbirth or multiorgan failure in surviving neonates (2). Peripartum and intrapartum ischemic or hypoxic insults are, in many cases, impossible to anticipate and may be difficult to recognize before the delivery of the baby.…”

“…Creatine is considered to be a worthy contender as a good source of energy in the context of PA. It can serve as energy supply not only for the brain but for the myocardium as well (2,109). Multiple experimental studies using maternal diet supplementation with creatine show positive results, mainly on the diaphragm, but recent data indicate cardioprotective effects through HIF-1 activation (110).…”

“…Although the majority of the studies have concentrated on the hypoxic brain injury, and how to diminish its impact, the effects on the cardiovascular system are equally important. Some studies report that 78% out of the total number of babies with severe PA suffered cardiac complications (2); in others, the value varies between 25 and 60% of cases (8,9). The most extensive range is between 25 and 82% of the cases of neonatal asphyxia, comprising mild, moderate, and severe cardiac dysfunction (10)(11)(12).…”

“…A limited degree of asphyxia is standard during childbirth (1). However, when prolonged or severe, fetal asphyxia may have harmful effects first and foremost on the fetal brain, but also other organs, like the heart, lungs, or the kidneys (2). Despite the efforts to reduce its incidence and consequences, perinatal asphyxia (PA) continues to occur globally in about 4 million babies every year (2) and accounts for 23% of all neonatal deaths and 8% of childhood deaths (3).…”

Early‐life N‐arachidonoyl‐dopamine exposure increases antioxidant capacity of the brain tissues and reduces functional deficits after neonatal hypoxia in rats

“…In the neonatal brain HI triggers a cascade of biological processes culminating in cell death (Griva et al, 2017; Sukhanova et al, 2016). Studies of the development of HI brain damage in animal models have shown that oxidative stress plays an important role in causing organ injury in the compromised fetus and neonate (LaRosa et al, 2017; Millar et al, 2017). The immature brain is known to be particularly susceptible to oxidative stress‐mediated ischemia/reperfusion injury compared to the mature brain.…”