Open Access Research Antidepressant use during pregnancy ...

1 Antidepressant use during pregnancyand the risk of major congenitalmalformations in a cohort of depressedpregnant women: an updated analysisof the Quebec pregnancy CohortAnick B rard,1,2 Jin-Ping Zhao,1,2 Odile Sheehy1To cite:B rard A, Zhao J-P,Sheehy O. Antidepressantuse during pregnancy andthe risk of major congenitalmalformations in a cohort ofdepressed pregnant women:an updated analysis of theQuebec pregnancy ;7 Prepublication history andadditional material isavailable. To view please visitthe journal ( ).Previous presentationThis Research was presentedin part at the 55th AnnualScientific Meeting of theTeratology Society, Montreal,Canada, 27 June to 1 6 July 2016 Revised 28 November 2016 Accepted 9 December 20161 Research Center, CHUS ainte-Justine, Montreal,Quebec, Canada2 Faculty of Pharmacy,University of Montreal,Montreal, Quebec, CanadaCorrespondence toDr Anick B rard.

2 Use during gestation hasbeen associated with risk of major congenitalmalformations but estimates can lack statistical poweror be confounded by maternal depression. We aimedto determine the association between first-trimesterexposure to antidepressants and the risk of majorcongenital malformations in a cohort of depressed/anxious and participants:Data were obtained fromthe Quebec pregnancy Cohort (QPC). All pregnancieswith a diagnosis of depression or anxiety, or exposedto antidepressants in the 12 months before pregnancy ,and ending with a live-born singleton were measures: Antidepressant classes(selective serotonin reuptake inhibitors (SSRI),serotonin norepinephrine reuptake inhibitors (SNRI),tricyclic antidepressants (TCA) and otherantidepressants) and types were individually comparedwith non-exposure during the first trimester (depresseduntreated).

3 Major congenital malformations overall andorgan-specific malformations in the first year of lifewere :18 487 pregnant women were looking at the specific types of antidepressantused during the first trimester, only citalopram wasincreasing the risk of major congenital malformations(adjusted OR, (aOR) , 95% CI to ; 88exposed cases), although there was a trend towardsincreased risk for the most frequently usedantidepressants. Antidepressants with serotoninreuptake inhibition effect (SSRI, SNRI, amitriptyline(the most used TCA)) increased the risk of certainorgan-specific defects: paroxetine increased the risk ofcardiac defects (aOR , 95% CI to ), andventricular/atrial septal defects (aOR , 95% CI ); citalopram increased the risk ofmusculoskeletal defects (aOR , 95% CI ), and craniosynostosis (aOR , 95% CI ); TCA was associated with eye, ear, face and neckdefects (aOR , 95% CI to ), and digestivedefects (aOR , 95% CI to ).

4 Andvenlafaxine was associated with respiratory defects(aOR , 95% CI to ).Conclusions:Antidepressants with effects onserotonin reuptake during embryogenesis increased therisk of some organ-specific malformations in a cohortof pregnant women with is common during pregnancy ,1and the use of antidepressants during gesta-tion has increased at a steady rate over thepast 20 the use of selectiveserotonin reuptake inhibitors (SSRIs) hasrisen sharply, and it is the most used class ofantidepressants during pregnancy , anincrease in the usage of other antidepressantssuch as serotonin norepinephrine reuptakeinhibitors (SNRIs) has also been observed.

5 Tri-cyclic antidepressants (TCA) is also a treat-ment is essential forhealthy fetal development during cross the placental barrier andbloc serotonin reuptake transporter (SERT)sites, disturbing the free movement of sero-tonin during this critical phase of mechanism of action of SNRIs isStrengths and limitations of this study Used of large registers, administrative and clin-ical databases that provide population-basedcoverage of Quebec pregnant women, withlinkage of data on the individual level. Permitted analysis of a large number of pregnantwomen with detailed information regardingexposure, outcomes and potential confounders,limiting selection bias.

6 Data collected prospectively, limiting recall bias. Owing to the number of comparisons made,chance could explain some of the rard A, ;7:e013372. AccessResearch on October 16, 2019 by guest. Protected by Open: first published as on 12 January 2017. Downloaded from similar to SSRIs,4and some TCAs, namely, amitriptyline,also have serotonin inhibition studies concerning the adverse effects of anti-depressant exposure during gestation on the developingfetus have showed increased risk of various congenitalmalformations such as cardiac, musculoskeletal, respira-tory, craniosynostosis and craniofacial,5 10but variationsbetween study results 15 Underlying maternaldepression, unaccounted potential confounders.

7 Classeffect compared with Antidepressant type effect or lackof statistical power could potentially explain the current debate, and the public healthimpact and clinical implications of prescribing andusing antidepressants during pregnancy on the fetus, weaimed to study the association betweenfirst-trimesterexposure to antidepressants and the risk of major con-genital malformations in a cohort of depressed pregnantwomen. We further aimed to study Antidepressant classesand types specifically as well as to quantify the risk oforgan-specific defects.

8 As somefindings in other studieshave been dismissed due to comparisons with a generalpopulation of pregnant women, our design allowed usto assess whether the observed rate of malformationsamong women on antidepressants was conducted a register-based cohort study using datafrom the Quebec pregnancy Cohort (QPC). The QPC isdescribed in Berard and , the QPC is anongoing population-based cohort with prospective datacollection on all pregnancies that occurred betweenJanuary 1998 and December 2009 in the province ofQuebec. Data on the mothers and children after theend of pregnancy are also collected resulting in up to11 years of follow-up.

9 Individual-level information isobtained from province-wide databases and linked usingunique personal identifiers. The QPC wasfirst con-structed by identifying all pregnancies in the R gie del assurance maladie du Qu bec (RAMQ) and theQuebec Hospitalisation Archives (MedEcho) Databases;subsequently,first day of the last menstrual period (firstday of gestation) was defined using data on gestationalage, which was validated against ultrasound measures inpatients follow-up was availablefrom 1 year before thefirst day of gestation, during preg-nancy and until December QPC data sources for this study included themedical service database (RAMQ.)

10 Diagnoses, medicalprocedures, socioeconomic status (SES) of women andprescribers), the Quebec Public Prescription DrugInsurance Database (drug name, start date, dosage, dur-ation), the Hospitalisation Archive Database (MedEcho:in-hospital diagnoses and procedures) and the QuebecStatistics Database (Institut de la statistique du Qu bec(ISQ): patient socio-demographic information, birthweight).PopulationTo be eligible for this study, pregnancies from the QPCmeeting the following inclusion criteria were considered:(1) pregnancies with continuous prescription druginsurance coverage of at least 12 months before thefirstday of gestation and during pregnancy , (2) pregnancieswith a diagnosis of depression and/or anxiety with orwithout concomitant related disorders (see onlinesupplementary table S1), and exposed to antidepres-sants in the 12 months before pregnancy (see onlinesupplementary table S2) and (3) pregnancies endingwith a live-born singleton.