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Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.d8012 (Published 12 January 2012) Cite this as: BMJ 2012;344:d8012

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Re: Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

I read this article with interest given the increasing number of women we are seeing on SSRIs during pregnancy.

Taken at face value, the study appears to show a significantly increased incidence of PPHN amongst infants born to mothers taking SSRIs late in pregnancy.

However, I have a number of concerns with the data interpretation.

At the start of the article, the authors note recognised risks factors for PPHN as “maternal overweight, smoking, diabetes and use of NSAIDs during pregnancy”. They then go on to state “As smoking and BMI in an analysis in a subset did not confound results we precluded these variables from further analyses”. Since other potential confounders such as maternal age were accounted for when calculating odds ratios, I cannot see why smoking and BMI were not treated as confounders within the whole dataset. This concern is further deepened when reading the statement “The mothers who had filled a prescription for an SSRI were generally older and more often smokers”.

Another concern is why the analysis only looks at exposure before 8 weeks and after 20 weeks gestation. Were these cut offs decided before analysis and with what rationale? Since cardiac development occurs between the 3rd and 20th week after fertilisation (gestational weeks 5-22), it seems strange to look for the effects of a potential teratogen largely outside of these times.

My final question to the authors is regarding NSAID use. In the UK, most NSAIDs are bought over the counter. I note the authors acknowledgement of the limitations of using filled prescriptions as a marker of medications taken but what about any women who may have taken over the counter NSAIDs in addition?

Testing a hypothesis with retrospective data is never going to be perfect and there will always be confounders but I wonder whether other readers shared my concerns.

Competing interests: No competing interests

16 February 2012
Lauren Newcomb
ST1 O+G
Prince Charles Hospital, Merthyr Tydfil
Prince Charles Hospital, Merthyr Tydfil