Antenatal prevention of cerebral palsy and childhood disability: is the impossible possible?

Abstract

This review covers our current knowledge of the causes of perinatal brain injury leading to cerebral palsy-like outcomes, and argues that much of this brain damage is preventable. We review the experimental evidence that there are treatments that can be safely administered to women in late pregnancy that decrease the likelihood and extent of perinatal brain damage that occurs because of acute and severe hypoxia that arises during some births, and the additional impact of chronic fetal hypoxia, infection, inflammation, growth restriction and preterm birth. We discuss the types of interventions required to ameliorate or even prevent apoptotic and necrotic cell death, and the vulnerability of all the major cell types in the brain (neurons, astrocytes, oligodendrocytes, microglia, cerebral vasculature) to hypoxia/ischaemia, and whether a pan-protective treatment given to the mother before birth is a realistic prospect.

Embryonic cardioprotection by hydrogen sulphide: studies of isolated cardiac function and ischaemia‐reperfusion injury in the chicken embryo

“…Episodes of asphyxia or ischaemia occur in embryonic or fetal life and they remain an unfortunately common clinical concern (Vannucci & Perlman, 1997; Giussani, 2016; Bennet, 2017; Ellery et al . 2018). Moreover, compromised blood supply to the fetal heart has been shown to disrupt normal cardiac development and programme an increased risk of hypertension in the adult offspring (Patterson & Zhang, 2010; Giussani & Davidge, 2013).…”

Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury

“…In both cases, lives are saved and outcomes are improved, but the number needed to treat (NNT) for intrapartum use of magnesium sulfate is between 42 and 74 to see a significant reduction in rates of cerebral palsy (18,19), and the NNT is 7 for hypothermia to see a reduction in mortality and severe morbidity (20), meaning there are still many more infants that need help. This is despite considerable efforts to find adjunct therapies for use with hypothermia (21), and additional therapies for all infants. As such, there remains a strong unmet need for treatments that can be delivered easily and quickly, and over a wider window of time after birth.…”

Challenges and controversies in perinatal physiology

“…(), while Ellery and colleagues examine whether antenatal therapies such as melatonin, creatine, stem cells and magnesium sulphate could help prevent or reduce the risk for cerebral palsy (Ellery et al . ). Some of these antenatal treatments, such as magnesium sulphate, may have additional benefits.…”