Antidepressants and pregnancy

BBC News said today that “children born to women taking anti-depressants in early pregnancy have a small but important increased risk of heart defects”. It reported on a Danish study that looked at over 400,000 children born between 1996 and 2003.

This research investigated whether taking antidepressants called selective serotonin re-uptake inhibitors (SSRIs) in the first trimester of pregnancy affected the rate of malformations. It found that defects in the wall separating the left and right chambers of the heart were 0.4% more common in the children of women taking SSRIs. No other malformations were associated with SSRI use.

Although this study suggests that SSRI use in early pregnancy may increase the risk of septal heart defects in the baby, it is important to note that the absolute risk of it happening is small (less than 1%).

In general, doctors try to avoid prescribing drugs for women who are pregnant because they may have an effect on the baby. However, depression is a serious illness and in some cases, the benefits of antidepressant treatment may be considered to outweigh the potential risks.

Where did the story come from?

Dr Lars Henning Pedersen and colleagues from Aarhus University in Denmark and the UCLA School of Public Health in the US carried out this research. The study was funded by the Lundbeck Foundation, the National Danish Research Foundation, Aarhus University, the Danish Society of Obstetrics and Gynaecology, the Ville Heise Foundation, and the Rosalie Petersen Foundation. The study was published in the peer-reviewed British Medical Journal .

What kind of scientific study was this?

This cohort study investigated the effects of taking selective serotonin re-uptake inhibitors (SSRIs) during pregnancy on the risk of major malformations in a newborn. SSRIs are a type of drug used to treat depression and certain other conditions.

The researchers collected data on mothers and newborns from Danish nationwide registers on prescriptions filled at pharmacies, births and hospital diagnoses.

The database data could be linked using personal identification numbers assigned at birth to all Danish citizens. Information was collected on maternal age, maternal smoking during pregnancy, number of children, delivery date, gestational age, birth weight and sex of newborn, and whether the pregnancy was a multiple pregnancy. Women having multiple pregnancies (e.g. twins) were excluded.

They then examined SSRI prescriptions filled 28 days before the estimated date of conception to 112 days after conception. Women were considered exposed if they had two SSRI prescriptions in this period.

Women who had prescriptions for insulin or high blood pressure medicines in the three months before the estimated date of conception were excluded. So were women who took other psychiatric medications during pregnancy, such as antiepileptic medication, antipsychotics and anti-anxiety medication.

Antidepressants other than SSRIs, such as tricyclic antidepressants and venlafaxine, were excluded from the main analyses but were assessed in subsidiary analyses.

These researchers looked at all live births between January 1 1996 and December 31 2003. After exclusions, 496,881 children were available for analysis. The researchers categorised malformations in these children according to a standard categorisation system. They then used statistical methods to look at the effect of maternal SSRI use on risk of malformations. They took into account various factors that could affect the outcome, including maternal age, year of birth, marital status, income and smoking.

What were the results of the study?

Of the 496,881 children, 15,573 (3.1%) had major malformations, and 1,370 (0.3%) had mothers who were exposed to SSRIs in early pregnancy. Women taking SSRIs were more likely to be older, living alone, unmarried and smokers.

Receiving SSRIs during early pregnancy did not affect the overall risk of malformations (odds ratio [OR] 1.21, 95% confidence interval [CI] 0.91 to 1.62), or the risk of malformations not affecting the heart (OR 1.12, 95% CI 0.79 to 1.59).

However, it was associated with an increased risk of defects of the septum, the wall separating the left and right chambers of the heart (0.9% compared with 0.5% of children not exposed to SSRIs; OR 1.99, 95% CI 1.13 to 3.53). These figures meant that for every 246 mothers taking SSRIs during early pregnancy, there would be one extra child with a septal heart defect.

Of the individual SSRI drugs, sertraline (1.5% affected) and citalopram (1.1% affected) were associated with an increased risk of septal heart defects, but not fluoxetine (0.6%). The numbers of women taking the SSRI paroxetine were too small for reliable analysis, as were the numbers of women taking non-SSRI antidepressants (tricyclic antidepressants or venlafaxine).

Women taking more than one SSRI in early pregnancy were at even greater risk of having a child with septal heart defects, with 2.1% of children affected (OR 4.70, 95% CI 1.74 to 12.7). These figures meant that for every 62 mothers taking more than one SSRI during early pregnancy, there would be one extra child with a septal heart defect.

What interpretations did the researchers draw from these results?

The researchers concluded that septal heart defects are more common in children whose mothers take an SSRI in early pregnancy, particularly sertraline and citalopram. The greatest risk is from taking more than one type of SSRI.

What does the NHS Knowledge Service make of this study?

This large study has shown an association between SSRI prescriptions in early pregnancy and one type of birth defect affecting the wall between the chambers of the heart. There are a number of points to note:

• As with all studies of this type (observational studies), there is the possibility that these differences may be due to factors other than the one tested. The researchers took measures to reduce this likelihood by taking potential confounding factors into account, but this may not totally have removed this effect. Due to ethical concerns, it is unlikely that a randomised controlled trial testing the effects of SSRIs in pregnancy would be carried out. In addition, because these events are so rare, studies would have to be very large to be able to detect them. This means that large population-based observation studies such as this one are likely to be the best forms of evidence available about this question.
• This study was not able to remove the possible effects of depression itself, as it was not able to identify and compare pregnant women with depression who were not taking antidepressants.
• The study was based on national databases of records about prescriptions, births and medical diagnoses. Some of the information in these databases may have been misrecorded or missed.
• It is possible that the newborns of those women known to be taking prescription drugs may have been more thoroughly examined for defects at birth, which would tend to bias towards finding more defects in this group. However, the overall proportion of malformations found in exposed and unexposed children suggests that this is not the case.
• The women categorised as exposed had collected at least two prescriptions for SSRIs in early pregnancy. However, this information does not tell us whether the women took the drugs or how much they took. The inclusion of only women who filled at least two prescriptions for the medication should increase the likelihood that they were in fact taking the drug, making these findings more robust.

In general, doctors try to avoid prescribing drugs for women who are pregnant in case they have effects on the baby. However, depression is a serious illness and, in some cases, the benefits of antidepressant treatment may be considered to outweigh the potential risks.

Although this study suggests that SSRI use in early pregnancy may increase the risk of septal heart defects in the baby, it is important to note that the absolute increase in the risk of a child being affected is small, i.e. less than 1%.