"Children born after certain infertility treatments at higher risk of autism," reads the headline in The Independent. The news is based on a large long-term Swedish study.
Researchers looked at how children were conceived and how this might affect their risk of developing autism, a type of autistic spectrum disorder, or "mental retardation", a term used by researchers to describe a person with an IQ under 70 (average IQ is 100).
The Independent's headline is misleading, as the study in fact found there was no statistically significant increase in the risk of autism in children conceived through any form of in vitro fertilisation (IVF).
However, there was a statistically significant increase in the risk of mental retardation, but this increase was slight. The occurrence of mental retardation was 39.8 per 100,000 births in those conceived spontaneously, compared with 46.3 per 100,000 births in those conceived through IVF. This represents a difference of just 6.5 cases per 100,000 births.
This news should not cause alarm among those thinking about undergoing IVF treatment, but does highlight a potential association between IVF and mental development that warrants further study.
Where did the story come from?
The study was led by researchers from the Institute of Psychiatry, King's College London and was funded by Autism Speaks, a non-profit organisation that provides funding for autism spectrum disorder research, and the Swedish Research Council.
It was published in the peer-reviewed Journal of the American Medical Asssociation (JAMA).
Most of the UK media's reporting was balanced, including The Independent's coverage, which outlined important information on how "scientists stressed that the chances of an IVF baby being affected was tiny in real terms".
But many of the headline writers failed to make a similar distinction, with the exception of The Guardian and ITV News, which wrote that "IVF findings 'should not stop parents using fertility treatments'."
What kind of research was this?
This was a prospective cohort study designed to test whether the use of any IVF procedure (as well as specific types of IVF procedures) may be associated with an increased risk of autistic spectrum disorders (ASD) and mental retardation in children conceived this way.
IVF allows a woman's egg to be fertilised by sperm outside the body under controlled laboratory conditions. Different types of IVF have been developed over the years, and the researchers pointed towards previous research that suggests intracytoplasmic sperm injection (ICSI) might damage the egg when the sperm is inserted.
ICSI is usually used to treat male infertility (when the man has a low sperm count, or there are problems with the movement of sperm impeding natural conception, for instance) and involves injecting sperm directly into the egg.
The research group highlight that there is little research on how IVF, and different types of IVF, influence the brain development of children conceived using these techniques. Their study aimed to fill in this gap in our knowledge.
What did the research involve?
The researchers reviewed the records of more than 2.5 million infants born in Sweden between 1982 and 2007. They recorded how they were conceived and whether they were diagnosed with ASD or had "mental retardation" at the age of four.
Conception was categorised as being spontaneous (without IVF) or using IVF. The specific type of IVF used was also recorded, as was the source of the sperm (ejaculated or surgically extracted).
ASD is described as a deficit in social interaction and communication that also involves restricted, stereotypical or repetitive behaviour. Read more about the signs and symptoms of ASD. "Mental retardation" is defined as an IQ lower than 70, plus limitations in adaptive behaviour.
In Sweden, where the research took place, all infants and preschool children are regularly seen at "well-child" care clinics, and undergo routine medical and developmental screening. At the age of four, all children undergo a mandatory developmental assessment of their motor skills, language, and cognitive and social development. Children with a suspected developmental disorder are referred for further assessment by a specialised team.
The researchers used information from these assessments and the years that followed to categorise the children as having either infantile and childhood autism or mental retardation. They used diagnostic criteria from the International Classification of Diseases (ICD) ninth edition. These definitions did not include other forms of ASD such as Asperger syndrome, a higher-functioning form of ASD where intelligence is usually unaffected.
The researchers' main analysis compared the incidence of ASD and mental retardation, and whether the conditions differed depending on the method of conception.
The analysis was adjusted to take into account some confounders known to influence the risk of impaired child brain development, including:
- parental psychiatric history
- birth year
- multiple births
- preterm birth (less than 37 weeks)
What were the basic results?
Out of the approximately 2.5 million infants born, 30,959 (1.2%) were conceived by IVF. These were followed-up for an average of 10 years. Overall, 103 of 6,959 children (1.5%) with ASD and 180 of 15,830 (1.1%) with mental retardation were conceived by IVF.
The key results showed:
- There was no statistically significant difference between the risk of the child developing ASD in those conceived spontaneously and those using IVF (all types grouped together).
- There was a small and borderline significant increased risk of the child developing mental retardation if they were conceived using IVF (all types grouped together) compared with spontaneous conception. The occurrence of mental retardation was 39.8 per 100,000 births in those conceived spontaneously, compared with 46.3 per 100,000 births conceived through IVF.
- When the analysis was restricted to single births, the increased risk of mental retardation disappeared, so it only seemed relevant to multiple births from the same mother.
There were statistically significant differences in the risk of developing autism and mental retardation depending on the specific IVF techniques used to conceive.
Compared with IVF without ICSI, there were statistically significant increases in the risk of ASD and mental retardation following ICSI.
The relative risk increases when comparing IVF with and without ICSI were much larger than the overall relative risks reported when comparing IVF with spontaneous conception.
How did the researchers interpret the results?
The researchers concluded that, "compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significant increased risk of mental retardation".
For specific procedures, IVF with ICSI for paternal infertility was associated with a "small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI".
But the researchers do point out that "the prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small".
This large cohort study showed that compared with spontaneous conception, IVF treatment (all techniques combined) was not associated with autistic disorder but was associated with a small, borderline significant increase in the risk of mental retardation.
For specific IVF procedures, IVF with ICSI was associated with a small increase in the risk of ASD and mental retardation compared with IVF that did not involve ICSI.
This study benefits from a large sample size and robust data collection methods, and did well to address an issue few other studies have looked at. But it's worth noting that there may be other unrecorded factors – beyond the conception method – that influence the likelihood of a child developing autism or mental retardation.
While the researchers adjusted for some of these factors, there may be other factors that are also influencing the findings, such as parental socioeconomic status. As the researchers point out, the Swedish health authorities fund three cycles of IVF, so this may bias the results towards richer couples who have the means to pay for additional cycles that lead to more conceptions.
While the headlines may seem scary at first glance, it is important to highlight that the real risk increases are very small, a statement reiterated by the study authors themselves and, refreshingly, in some of the news coverage.
However, the influence of the specific type of IVF on the risk profiles for both developmental conditions is interesting and a worthy area of further research. It is hoped that further innovations can refine these techniques and lead to a reduction in the very low risk of complications.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 2 July 2013
Mail Online, 3 July 2013
The Independent, 2 July 2013
The Guardian, 2 July 2013
ITV News, 2 July 2013
Links to the science
JAMA. Published online July 3 2013