Antidepressant use in pregnancy 'linked to childhood autism'

"Taking antidepressants during pregnancy almost doubles the risk of children developing autism," The Daily Telegraph reports. Researchers say it is possible that chemicals present in antidepressants could interfere with child development.

However, when looked at in its overall context, the study found only a small increased risk of a child developing autism spectrum disorder (ASD) – estimated to be less than 1 in 100 (0.72% of all births in this study).

Researchers tracked just under 150,000 pregnancies and found the use of antidepressants in the second and/or third trimester of pregnancy was linked to an almost doubled risk of a child developing ASD. No link was found for antidepressant use in the first trimester (first 12 weeks) of pregnancy.

The study was well designed, but this type of study cannot prove that the drugs were causing ASD. The reason why the pregnant mothers were prescribed antidepressants, rather than the drug itself, may have contributed to the risk of ASD, although the researchers did try to account for the effect of maternal depression in their analysis. Other genetic and unknown factors may also have influenced the results.

In conclusion, pregnant mothers using antidepressants shouldn't be overly alarmed by this headline. If you are prescribed antidepressants during pregnancy, it is likely to be because the benefit you get from taking them is considered to outweigh any risks.

You should not stop taking any prescribed medicines without first consulting your GP. You could also discuss any concerns you have about the possible effect of antidepressants with them.  

Where did the story come from?

The study was carried out by researchers from universities in Canada, and was funded by the Canadian Institutes of Health Research and the Quebec Training Network in Perinatal Research.

It was published in the peer-reviewed medical journal JAMA Pediatrics.

The Daily Telegraph and the Mail Online reported the story accurately. Encouragingly, both recognised some of the study's limitations, including some good advice: "Women should not stop their medication suddenly and, if they are concerned about continuing the antidepressant in pregnancy, they should discuss the options with their doctor." 

What kind of research was this?

This was a cohort study examining the risk of ASD in children born to mothers taking antidepressants during pregnancy, taking into account maternal depression.

ASD is a condition that affects social interaction, communication, interests and behaviour. In children with ASD, the symptoms are present before the age of three, although a diagnosis can sometimes be made when they are older.

It's estimated about 1 in every 1,000 people in the UK has ASD. More boys are diagnosed with the condition than girls.

The study's authors explain that the association between the use of antidepressants during pregnancy and the risk of ASD in childhood is controversial, partly because the causes of ASD itself are unclear.

Studies to date have suggested that genetic and environmental factors may play a role, including maternal depression. 

What did the research involve?

The researchers analysed the Quebec Pregnancy/Children Cohort, which included data on all pregnancies and children in Quebec from January 1 1998 to December 31 2009.

However, they didn't use the entire database. Their work focused on a sample of 145,456 full-term single babies born to mothers covered by medical insurance, meaning their prescription drug use – including antidepressant use – was available for study.

The effects of antidepressant use was examined by when they were taken (first, second and/or third trimester) and the different antidepressant drug types.

Children with ASD were defined as those with at least one diagnosis of ASD between their date of birth and the last date of follow-up – the average was about six years.

The analysis took account of the influence of a major confounder for ASD: underlying maternal depression. Other confounders that were taken into account in the analysis include:

• maternal sociodemographic characteristics – age at conception, living alone, receiving social welfare, educational level
• history of maternal psychiatric characteristics 
• history of chronic physical conditions
• infant characteristics – gender, year of birth 

What were the basic results?

ASD was diagnosed in 1,054 infants in the full cohort (0.72%), with four times as many boys diagnosed as girls.

The study found 3.2% (4,724) of infants were exposed to antidepressants during pregnancy. Of these, the majority were exposed during the first trimester (88.9%), with 53.6% exposed during the second and/or third trimester. There were 40 ASD diagnoses among those exposed during the first trimester (1%), and 31 among those exposed during the second and/or third (1.2%).

Putting this together, the use of antidepressants during the second and/or third trimester was linked to an 87% increased risk of ASD compared with no use (31 infants, hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.15 to 3.04). This stayed stable after adjusting for history of maternal depression (HR 1.75, 95% CI 1.03 to 2.97).

When divided by the type of antidepressant used, a significant risk increase was only found for selective serotonin reuptake inhibitors (SSRIs). Almost two-thirds of those taking an antidepressant during the second and third trimester were taking an SSRI.

Their use during the second or third trimester was linked to a more than doubling of risk of ASD compared with no use (22 infants, HR 2.17 95% CI 1.20 to 3.93).

There were only a handful of cases among people taking other types of antidepressants, and no significant links with ASD were found for other groups. However, there was an increased risk for those taking more than one type of antidepressant during this time (five infants, HR 4.39 95% CI 1.44 to 13.32).

Before we jump to the conclusion that certain SSRIs carry a risk for pregnant women having children with ASD, it must be noted that SSRIs are by far the most common antidepressants prescribed.

As not many women were taking other types of antidepressant and ASD is rare, the numbers may not have been large enough to detect associations in these groups, making these findings a lot less reliable.

The use of antidepressants in the first trimester was not linked to any increase in risk of ASD compared with no exposure to the drugs. 

How did the researchers interpret the results?

The research authors concluded: "Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression.

"Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy." 

Conclusion

This cohort study, based on almost 150,000 infant records, showed that the use of antidepressants called SSRIs in the second and/or third trimester of pregnancy was linked to a more than doubled risk of ASD. No such link was found for antidepressant use in the first trimester of pregnancy or using other antidepressant classes.

The study was well designed, but this type of study cannot prove the drugs were causing ASD. There are a number of explanations for the results:

There were few ASD diagnoses

Only 31 children exposed during the second and third trimester developed ASD. And while SSRIs were the only group found to significantly increase the risk of ASD, they were by far the most common type used.

With smaller numbers exposed in other groups and few ASD cases overall, it may be the smaller groups are less reliable for seeing whether there is a link.

It could be that SSRIs have distinct biochemical properties that increase risk, while other types do not, but we would need other study types to find out.

An example of this would be comparing the risk of ASD in children born to the same mothers, first in one pregnancy using antidepressants and in another not using them. This would reduce the influence of any genetic factors that might be involved.

Underlying genetic factors

Underlying genetics may predispose a mother to depression and use of antidepressants, and make it more likely for the infant to develop ASD. In this case, antidepressant use isn't the cause of the link, it's merely a symptom of something else.

Unknown confounders and biases

The researchers take into account many physical and mental health factors that could influence any association between antidepressant use and ASD.

However, their analyses may not have been able to fully account for all of these factors, and other unmeasured factors could have had an effect.

Mums-to-be prescribed antidepressants during the second and third trimester of pregnancy may be more at risk of having a child with ASD than women who are not, for reasons we don't yet know about. It may not be the drugs themselves.

We need more studies to confirm the truth, so mothers should not be overly alarmed by these findings. While the headlines correctly reported that the relative risk of ASD had doubled, it is important to recognise that the overall risk of ASD is quite low: less than 1 in 100, and 0.72% of all births in this study.

Antidepressants are prescribed for a variety of important reasons. If you are prescribed antidepressants during pregnancy, it is likely to be because the benefit you get from taking them is considered to outweigh any risks.

You should not stop taking any prescribed medicines without first consulting your GP. It is advisable to discuss any concerns you have about the possible effect of antidepressants with them.

Find out more in the pregnancy and baby guide.