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dc.contributor.authorJordan, Sueen_US
dc.contributor.authorMorris, Joan Ken_US
dc.contributor.authorDavies, Gareth I.en_US
dc.contributor.authorTucker, Daviden_US
dc.contributor.authorThayer, Daniel Sen_US
dc.contributor.authorLuteijn, Johannes Michielen_US
dc.contributor.authorMorgan, Margeryen_US
dc.contributor.authorGarne, Esteren_US
dc.contributor.authorHansen, Anne Vinkelen_US
dc.contributor.authorKlungsøyr, Karien_US
dc.contributor.authorEngeland, Andersen_US
dc.contributor.authorBoyle, Breidgeen_US
dc.contributor.authorDolk, Helenen_US
dc.PublishedJordan S, Morris JK, Davies, Tucker D, Thayer DS, Luteijn JM, Morgan M, Garne E, Hansen AV, Klungsøyr K, Engeland A, Boyle B, Dolk H. Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants in pregnancy and congenital anomalies: Analysis of linked databases in Wales, Norway and Funen, Denmark. PLoS ONE. 2016;11(12):e0165122eng
dc.description.abstractBackground: 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.en_US
dc.rightsAttribution CC BYeng
dc.titleSelective Serotonin Reuptake Inhibitor (SSRI) antidepressants in pregnancy and congenital anomalies: Analysis of linked databases in Wales, Norway and Funen, Denmarken_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2016 The Author(s)
dc.source.journalPLoS ONE

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