What’s causing the huge rise in autism: From mother’s hormone levels to severe morning sickness, vitamin deficiency and even air pollution, we examine all the theories behind the 800% increase

Why would cases of autism rocket by almost 800 per cent in 20 years? It’s a question scientists are trying to answer – and already they are discovering some intriguing theories.

Once considered a rare condition, there are now around 700,000 people in the UK living with autism, according to the National Autistic Society. Indeed, there has been an astonishing 787 per cent rise in diagnoses between 1998 and 2018, according to UK research published in the Journal of Child Psychology and Psychiatry in 2021.

However, these numbers are likely to be an underestimate, with the latest data from the Centers for Disease Control and Prevention showing that one in 36 children in the US has autism.

The question is, why? And could this understanding help improve the lives of those living with the condition – including, controversially, with a drug derived from vitamin B9.

While some of the rise can be explained by better awareness of the condition, that’s not the only reason.

‘Autism starts prenatally [i.e. in the womb] and is partly genetic, but not 100 per cent,’ says Sir Simon Baron-Cohen, a world expert on the condition and a professor of developmental psychopathology at the University of Cambridge.

Autism is a neurological condition that affects how people communicate, behave and interact with others.

It’s thought to arise from differences in both the way the brain works and its structure.

For example, people with autism tend to have fewer synapses – connections that feed messages from one part of the brain to another – according to a study published in Molecular Psychiatry last year.

The extent to which someone is affected varies greatly. Some may not communicate at all, while others are gifted intellectually, highly creative and focused. Others find forming relationships difficult, while many have problems adjusting to unexpected change and prefer predictability and routine.

A proportion have learning disabilities such as dyslexia, too, and it can lead to challenges with independent living.

Some may also have mental health conditions such as anxiety or depression; as well as physical conditions such as seizures or gastrointestinal problems (constipation, diarrhoea, abdominal pain), possibly linked to inflammation caused by an overactive immune system.

One of the causes now being investigated is how a mother’s levels of androgens (male hormones such as testosterone, which women have in small quantities) may affect her child’s risk of autism.

If a growing baby is exposed to higher levels of androgens – as may be the case if, for example, the mother has polycystic ovary syndrome – ‘this may “masculinise” the body and contribute to the likelihood of a child being autistic,’ says Professor Baron-Cohen.

The fact that a growing male baby will produce more androgens than a female could explain why more boys are diagnosed as autistic, he says. However, he adds that ‘there are undoubtedly more such factors to be discovered’.

Several studies have linked autism to children of mothers who had hyperemesis gravidarum – a severe form of morning sickness which affects less than 5 per cent of pregnancies.

According to US research published in the American Journal of Perinatology in 2019, children were 53 per cent more likely to be diagnosed with autism if their mothers had hyperemesis gravidarum.

The theory is that a lack of nutrients passing from mother to baby in the womb may affect the brain.

Other pregnancy-related factors include gestational diabetes, where a mother develops diabetes during pregnancy. The mechanism is not fully understood, but one theory is that it’s because babies were exposed to high levels of sugar in the womb at a critical point in development.

Multiple studies have linked older parents to an increased risk of autism, with one finding that the chance of a child developing autism is 50 per cent higher when the parents are in their 40s or 50s, as reported in Jama Network Open in 2020. This may be increasingly relevant as more people have children later in life.

It’s thought this could be because older sperm or eggs have accumulated mutations or defects that are then passed on to children.

There are many other factors that may play a part during pregnancy whatever the age of the parents – including simply having a viral infection.

A 2010 study in Denmark found that severe viral infections during the first trimester of pregnancy led to a threefold increase in the risk of autism, with studies in mice suggesting that it may affect the development of the cortex (the outer section of the largest region of the brain).

Scientists are also looking into possible links to air pollution, with exposure to high levels during the third trimester of pregnancy or early childhood being linked to a significantly increased risk of autism in children, according to Environmental Research Letters in 2021.

While genetic links to autism have been known for some time, scientists are now pinpointing the actual genes involved. However, ‘genetic disorders only account for a minority of cases’, says Dr Richard Frye, a paediatric neurologist based at Rossignol Medical Centre in Arizona.

He is among those who have been looking into the possibility that autism may be linked to low levels of folate (vitamin B9).

He is leading the trial involving Mason Connor, a non-verbal autistic child in Arizona, who made headlines around the world recently when he uttered his first words days after taking leucovorin, a drug which is similar to folate.

Mason, five, started taking leucovorin aged three. The drug is licensed in the US to help reduce the toxicity of a form of chemotherapy, but is available off-label for autism and costs around £2 a tablet.

Mason’s mother Caroline told CBS News that she thought the drug had helped her son start speaking. He is now due to attend a mainstream nursery school in September.

The drug has yet to be approved for autism in the US or here – and experts believe its benefits remain in question.

Dr Frye says leucovorin overcomes a problem that, according to his own unpublished research in 2012, affects up to seven in ten autistic children: folate receptor autoantibodies.

These antibodies damage the machinery that transports folate into the brain (where folate helps with many essential processes).

Leucovorin can pass into the brain because it uses an alternate route, says Dr Frye.

‘The low folate level we’ve found in children is isolated to the brain,’ he says.

‘We believe the folate improves the function of neurons [nerve cells] so they can communicate with each other better,’ he explains, adding that leucovorin is not a cure for autism, but ‘could really have a substantial impact on a very good percentage’ of children with autism.

Dr Frye says: ‘The drug could make a substantial difference. There are now four blinded, placebo-controlled trials showing that leucovorin can improve speech and autism symptoms, so it’s definitely not a one-off.’

He hopes to get funding for the necessary studies to get it approved in the US.

Leucovorin – which is not available for autism in the UK, even off-label – joins a long list of potential therapies for autism, with varying amounts of evidence to support their use.

For example, magnetic e-resonance therapy (MeRT) – brain stimulation approved in the US for depression and obsessive compulsive disorder – has been widely publicised as a treatment for autism.

The theory is that it generates magnetic waves that stimulate targeted areas of the brain, to reshape brain waves said to have been disrupted.

Multiple researchers are examining whether it may help, but so far there are no studies to support its use.

Despite that, there are many people in the US prepared to pay thousands for a six-week course.

Professor Baron-Cohen urges caution when it comes to newer treatments.

‘Parents should be wary of treatments for autism that have not been in a randomised controlled trial. They should check if there are unwanted side-effects and that the investigators have no conflicts of interest,’ he says.

What’s more, he adds: ‘There is a place for treating symptoms that cause distress in autistic people – such as anxiety, gastrointestinal pain and epilepsy – but not autism per se, since autism is part of the person’s identity. A person should be accepted and respected for being autistic, rather than feeling pressured to be “normalised” or to hide their autism.’

And there are therapies that have been shown to help improve quality of life. Speech therapy, occupational therapy and educational support in schools can be beneficial.

Meanwhile, faster and more accurate ways to diagnose autism are being developed.

Currently, diagnosis is based on professionals observing and identifying abnormal behaviour, ‘which can be time-consuming and difficult’, says Dr Frye.

Researchers at Nottingham Trent University, working with a team at the Kennedy Krieger Institute in the US, have developed a one-minute video game which, according to a recent study, can correctly identify children with autism with an 80 to 90 per cent success rate.

The tool, called the Computerised Assessment of Motor Imitation (CAMI), uses motion-tracking technology to detect differences in imitation skills.

Autistic people find it harder to imitate others – imitating others’ actions is central to the development of social skills.

For the study, published in the British Journal of Psychiatry in January, 183 children were asked to copy the dance-like movements of a video avatar for one minute, while their imitation performance was measured using CAMI.

‘Autism is traditionally seen as a social-communication disorder, but we now know sensory-motor difficulties, like motor imitation, play a key role in shaping social and communication skills,’ said Dr Bahar Tuncgenç, a social development expert at Nottingham Trent University and one of the co-authors of the study.

The video game also differentiated autism from ADHD, which causes a lack of focus and impulsive behaviour, with 70 per cent accuracy. This is a particular challenge because ADHD and autism often co-occur, and it can be hard to identify the diagnoses.

Meanwhile, it’s hoped that biomarkers can be identified so that in future children who are at risk could be diagnosed at birth, or even before.

‘Biomarkers that identify children at risk before there are any symptoms, or even before a child is born, could help make diagnoses much more accurate and faster, and would be a great advance,’ says Dr Frye.

Professor Baron-Cohen is part of a team supporting and fundraising for a new hospital, Cambridge Children’s Hospital. The collaborative venture between three partners is due to open in 2029 and could help to ensure that autism diagnoses are made earlier.

‘Cambridge Children’s Hospital will hopefully accelerate early diagnosis and early intervention – and evidence shows that children who receive their autism diagnosis earlier have better mental health in adolescence and adulthood,’ he says.