>> The JAMA Network.
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>> Hi, I'm Krista Huybrechts and I'm an epidemiologist within the division
of pharmacoepidemiology and pharmacoeconomics at the Brigham and Women's Hospital
and Assistant Professor of Medicine at Harvard Medical School.
In 2006 the FDA issued a public health advisory on a potential increase in the risk
of persistent pulmonary hypertension of the newborn associated with exposure
to SSRI antidepressants late in pregnancy.
This initial warning was based on evidence from one epidemiologic study
which found a six-fold increase of the risk of PPHN associated with SSRI exposure
after the 20th week of pregnancy.
Since then a number of additional studies have been conducted some
of which have found an increase in risk and some of which have not.
And this led the FDA to update its advisory in 2011 stating that it was premature
to reach a conclusion about a possible link.
Most of the studies that did not find an increase in risk tended to be small
which raises the possibility that they had insufficient power to detect an association
with an outcome that is very rare to begin with.
In order to try and shed some light on this controversy we decided to examine the risk
of PPHN associated with both SSRI and non-SSRI antidepressant exposure late in pregnancy
in a very large cohort of publically insured women.
We conducted a cohort study nested in the 2000 to 2010 Medicaid analytic extracts.
We identified a group of close to 3.8 million pregnant women who were publically insured
through the Medicaid program from a minimum of 2 months after the date
of the last menstrual period or fewer until at least 1 month after delivery.
We considered women to be exposed to antidepressant medications
if they either filled a prescription for an SSRI antidepressant during the last 90 days
of pregnancy or when they filled a prescription
for a non-SSRI antidepressant during that time period.
Women who did not use any antidepressant
at any time point during pregnancy were considered unexposed.
We defined the outcome as a recorded IDC9 diagnosis
of persistent pulmonary hypertension the newborn during the first 30 days following delivery.
Now to account for potential confounding variables and those are variables
that are associated with the exposure but that are also risk factors for PPHN,
we first restricted the cohort to women with a recorded diagnose of depression to account
for potential confounding by the underlying disease and factors associated with it.
And we stratified on propensity scores in the analysis.
Close to 3-1/2% of women in our cohort were exposed to antidepressants late in pregnancy
which we presents around 130,000 women.
And the large majority of them used SSRI antidepressants, about 80%.
The absolute risk of PPHN was 21 per 10,000 births in babies that were not exposed
to any antidepressant at any time point during pregnancy versus 32 per 10,000 in babies
that were exposed to an SSRI antidepressant and 29 per 10,000 births in babies
that were exposed to a non-SSRI antidepressant.
However, this 40 to 50% increase in risk was attenuated when we accounted
for potential confounding by depression,
its associated factors and other risk factors for PPHN.
The relative risk or the adjusted relative risk for SSRI antidepressants was 1.10
which was not statistically significant and for non-SSRI antidepressants, it was 1.02.
In sensitivity analysis where we used more stringent definitions of the exposure
and the outcome did not magnify the degree of observed risks.
Although we cannot entirely exclude the possibility that there might be a small increase
in the risk of PPHN associated with SSRI use late in pregnancy,
what our study has shown is that the absolute risk is small.
And any potential increase in risk if present is much more modest than some
of the previous studies have indicated.
Clinicians and their patients need to weigh this potential small increase in the risk
of PPHN along with other risks that have been attributed
to antidepressant use during pregnancy with the benefits that have been attributed
to these medications in improving maternal health and well-being.
There is important further research to be done in a couple of different directions.
First of all PPHN is only one of the possible adverse outcomes associated
with medication used during pregnancy.
Our group has already looked at a number
of other potential adverse outcomes and we will continue to do so.
The use of other psychotropic medications such as mood stabilizers, stimulants
and anti-psychotics is also increasing during pregnancy
and there is very limited information available on the safety of these medications.
So it will be important to study the safety of these other psychotropic medications
so that women have access to high quality evidence when they're trying to decide whether
to continue or initiate these medications during pregnancy.
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