New insights into the causes of cerebral palsy are opening pathways to prevention and treatment, write Nadia Badawi and John Keough.
Cerebral palsy affects one in every 500 people. It refers to a range of movement-related conditions diagnosed in childhood and involving one or both sides of the body. This may cause impaired mobility, muscle stiffness or weakness and/or abnormal or uncontrolled movements.
Children with cerebral palsy often have other neurological impairments such as epilepsy, visual impairment, hearing loss and intellectual disability.
Around half of children with cerebral palsy have normal or high intelligence, and the degree of physical disability varies widely. Most will live full lives. But some are so profoundly affected they will never walk or speak and will be wheelchair-dependent. They will often be in chronic pain.
The underlying causes of cerebral palsy are varied and still poorly understood, but we’ve learnt a lot in recent decades.
In the 19th century, British orthopaedic surgeon William Little, who performed operations to help the skeletal deformities seen in these children, attributed cerebral palsy to problems in labour. He had no evidence to support this hypothesis. But his “expert opinion” remained largely unchallenged until the late 20th century.
At this time, Karen Nelson, a paediatric neurologist from the United States' National Institute of Health, and then Australian researchers Fiona Stanley and Eve Blair began to use modern research techniques in the field of epidemiology (the origins of disease) to explore this idea. They found, somewhat to their surprise, that only around one in 10 cases was linked to labour.
Sigmund Freud had come to the same view much earlier when he asked why, with 280 days in pregnancy, we would assume that all the damage occurred on the last day: at birth.
Nonetheless, by the time these questions were being asked, a large industry had evolved around preventing the intrapartum asphyxia – poor oxygen supply to the baby’s brain in labour – that was assumed to cause cerebral palsy in labour.
Large legal settlements in the 1980s onwards led to defensive medicine, soaring caesarean section rates and medical indemnity insurance costs, which kept the focus on labour. The theory was that if poor oxygen supply caused cerebral palsy, then surely identifying abnormalities early and delivering by caesarean section would avoid the disability.
Cardiotocography or CTG monitors, which continuously recorded the fetal heart rate, became standard equipment in labour wards around the world from the 1980s onwards but were never shown to prevent cerebral palsy.
Attributing cerebral palsy to “birth issues” turned out to be a gross oversimplification. The single diagnosis of cerebral palsy covers a wide range of conditions with many different contributing factors that interact in complex ways.
A mother can bring a number of risk factors to the pregnancy. Maternal poverty, age, infertility, birth order, pre-existing medical conditions such as high blood pressure and thyroid disease, and a family history of neurological disease all increase risk of CP.
Once pregnant, the risk increases if the woman has a multiple pregnancy, pre-eclampsia (dangerously high blood pressure and protein in her urine), poor fetal growth or birth defects. In fact, prematuriuty is the main factor behind 40 percent of cases of cerebral palsy.
So while it’s true that problems in labour can cause cerebral palsy, they rarely act alone and can only be reasonably identified in one in ten cases.
Over the past 20 years, researchers have made important progress in the search for ways to prevent or ameliorate cerebral palsy. One such step was the agreement by in-vitro fertilisation (IVF) clinics in Australia to transfer only a single embryo per cycle in most cases, decreasing the chance of twins. Multiple embryos were previously transferred to improve the chance of pregnancy, but multiple pregnancies were common.
Antenatal care in Western countries aims to detect and, where possible, treat problems such as pre-eclampsia and growth restriction early in pregnancy.
The care of preterm infants has gone through something of a revolution and is preventing neurological damage in premature infants. Magnesium sulphate, given to mothers delivering a very preterm baby in the few hours before birth, can prevent up to 30 percent of cerebral palsy in this group.
Cooling the heads of babies at term who do asphyxiate during labour has been shown to decrease cerebral palsy. It turns out that most of the damage happens in the 72 hours after the oxygen deprivation occurs. If we can slow down the brain’s metabolic needs after the injury, we can decrease cell damage and death in this subgroup of cases.
Intramuscular steroids given to women at high risk of delivery before 34 weeks has prevented cerebral haemorrhage (bleeding into the brain). Further research into the use of stem cells, and the hormones erythropoietin and melatonin, also shows promise.
Nearly one-third of children with cerebral palsy have a birth defect. This provides a strong clue that many causes are genetic in origin. However, since these birth defects vary widely – from congenital heart conditions and intestinal blockages to extra toes or fingers and occasionally and, not surprisingly, brain defects – it is difficult to know how to identify and address the common causes behind them.
New techniques such as whole-exome sequencing – which looks at the protein-coding part of the genome – have facilitated research into genetic causes of cerebral palsy. Gai McMichael from the University of Adelaide and her team found that in 14 percent of cerebral palsy cases where DNA was available for study from both parents and the child, there was a gene variant (mutation) that could conceivably explain the condition.
The finding is just the beginning of this story. It has opened up a whole new area of research into the causes of cerebral palsy and possible pathways to prevention and treatment.
Genetic research also has the potential to help answer questions about the origins of other important neuro-developmental conditions. These include autism, epilepsy and intellectual disability and even adult neurological conditions such as Parkinson’s and multiple sclerosis.
Hopefully, we will soon be able to answer parents much more fully when they ask why their child has cerebral palsy and will one day see this condition increasingly consigned to history.
Professor Nadia Badawi is an expert on newborn encephalopathy and cerebral palsy and is the Macquarie Foundation Chair of Cerebral Palsy at the Cerebral Palsy Alliance Research Institute.
Dr John Keogh is a consultant obstetrician and gynaecologist at the Sydney Adventist Hospital and Associate Professor at the University of Sydney.
This article was originally published in The Conversation.