SSRIS in pregnancy increase congenital abnormality risk

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Women who take selective serotonin reuptake inhibitor (SSRI) antidepressants in early pregnancy have a small but significantly greater risk of having babies with major birth defects or stillbirths, compared with those who did not take these antidepressants.

Professor Sue Jordan, of Swansea University, led the international research team1 of academics from the UK, Denmark and Norway. The study analysed data from more than 500,000 infants in Wales, Norway and Denmark and found that women who had been prescribed selective serotonin reuptake inhibitors, known as SSRIs, in the first trimester of pregnancy or 3 months before pregnancy were at a small but significantly greater risk of having infants with congenital anomalies, particularly severe heart defects or stillbirths compared with those who did not take SSRIs.

The study found that where SSRIs were not prescribed, 6 in 200 pregnancies had an adverse outcome of stillbirth or a baby with a major congenital anomaly, but when SSRIs were prescribed this rose to 7 in 200. The team say this risk is of public health importance due to the severity of the outcome and because SSRIs are prescribed to 5.5% of pregnant women in Wales, 2.1% in Denmark and 1.6% in Norway.

Now, the researchers are calling on health care professionals to take the following action: review all women requesting SSRI prescriptions and not just those who are planning pregnancy; consider women who misuse substances or alcohol as being at higher risk of adverse pregnancy outcomes when prescribed SSRIs; evaluate pre-pregnancy care when SSRIs are prescribed; consider offering at-risk women enhanced scans to detect serious heart defects; and ensure that appropriate levels of neonatal care are available to at-risk women at birth

Jordan said: “To our knowledge, this is the first dose-response analysis that shows the link between SSRI doses and congenital anomalies and stillbirths. While this extra risk may seem small, in my view, the outcomes are as serious as they can be.

“Women should not stop taking SSRIs without consulting their doctors, and we are not saying stop all medicines, but our message is that we want our health care professionals to be very mindful of this link and to take the appropriate action to ensure that women are given the right type of care before, during and after pregnancy to minimise the risks of congenital anomalies and stillbirths linked to SSRIs.”

Professor Helen Dolk, who led the EUROmediCAT project, said: “Women should not stop taking SSRIs without discussing with their doctor the benefits and risks of SSRIs and alternative non-pharmacological therapies, since good mental health is important for both mother and child.”

Abstract
Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP).
Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of ‘anomaly or stillbirth’ (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression.
Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care.

Authors
Sue Jordan, Joan K Morris, Gareth I Davies, David Tucker, Daniel S Thayer, Johannes M Luteijn, Margery Morgan, Ester Garne, Anne V Hansen, Kari Klungsøyr, Anders Engeland, Breidge Boyle, Helen Dolk

Swansea University material
PLOS One abstract


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