Antidepressant use During Pregnancy and the Risk of Major Congenital Malformations in a Cohort of Depressed Pregnant Women: A Re-analysis of the Quebec Pregnancy Cohort

ObjectiveTo quantify the association between first-trimester antidepressant exposure and the risk of major congenital malformations (MCM) in a cohort of depressed women.MethodData were obtained from the Quebec pregnancy cohort. All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included. Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and other antidepressants), and types were individually compared to non-exposure during the first-trimester (depressed untreated). MCM overall and organ-specific malformations in the first year of life were identified.ResultEighteen thousand four hundred and eighty-seven depressed pregnant women were included. Citalopram use during the first-trimester was increasing the risk of MCM (aOR 1.36, 95%CI 1.08, 1.73; 88 exposed cases). Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) were increasing the risk of certain organ specific defects: paroxetine was increasing the risk of cardiac defects (aOR 1.45, 95%CI 1.12, 1.88), and ventricular/atrial septal defects (aOR 1.39, 95%CI 1.00. 1.93); citalopram was increasing the risk of musculoskeletal defects (aOR 1.92, 95%CI 1.40. 2.62), and cranyosynostosis (aOR 3.95, 95%CI 2.08, 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95%CI 1.05, 5.72), and digestive defects (aOR 2.55, 95%CI 1.40. 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95%CI 1.07, 4.38).ConclusionAntidepressants with effects on serotonin reuptake during embryogenesis are increasing the risk of some organ specific malformations in a cohort of pregnant women with depression.Disclosure of interestCOI: Disclosures and acknowledgments: AB is a consultant for plaintiffs in litigations involving antidepressants and birth defects. All other authors report no financial relationships with commercial interests. All authors have completed the ICMJE uniform disclosure form.

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Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort

BMJ Open ◽

10.1136/bmjopen-2016-013372 ◽

2017 ◽

Vol 7 (1) ◽

pp. e013372 ◽

Cited By ~ 54

Author(s):

Anick Bérard ◽

Jin-Ping Zhao ◽

Odile Sheehy

Keyword(s):

Pregnant Women ◽

Congenital Malformations ◽

Pregnancy Cohort ◽

Antidepressant Use ◽

Major Congenital Malformations

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Duration of antidepressant use during pregnancy and risk of major congenital malformations

The British Journal of Psychiatry ◽

10.1192/bjp.bp.107.042523 ◽

2008 ◽

Vol 192 (5) ◽

pp. 344-350 ◽

Cited By ~ 50

Author(s):

Élodie Ramos ◽

Martin St-André ◽

Évelyne Rey ◽

Driss Oraichi ◽

Anick Bérard

Keyword(s):

Psychiatric Disorders ◽

Congenital Malformation ◽

Congenital Malformations ◽

First Trimester ◽

Major Congenital Malformation ◽

Increased Risk ◽

First Trimester Of Pregnancy ◽

Antidepressant Use ◽

Major Congenital Malformations ◽

First Year Of Life

BackgroundAntidepressant use during the gestational period is a controversial topic.AimsTo determine whether duration of antidepressant use during the first trimester increases the risk of major congenital malformations in offspring of women diagnosed with psychiatric disorders.MethodA case-control study was performed among women who had been pregnant between January 1998 and December 2002. Data were obtained from a Medication and Pregnancy registry, built by linking three databases from the province of Quebec, and a self-administered questionnaire. Women eligible for this study had to be 15–45 years old at the beginning of pregnancy, have at least one diagnosis of psychiatric disorder before pregnancy, have used antidepressants for ≥ 30 days in the year prior to pregnancy and have a pregnancy ending with a delivery. Cases were defined as any major congenital malformation diagnosed in the offspring's first year of life. Odds ratios, adjusted for relevant confounders, were estimated using logistic regression.ResultsAmong the 2329 women meeting the inclusion criteria, 189 (8.1%) infants were born with a major congenital malformation. Duration of antidepressant use during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations: 1–30 days v. 0 day, adjusted OR=1.23 (95% CI 0.77–1.98); 31–60 days v. 0 day, adjusted OR=1.03 (95% CI 0.63–1.69); ≥ 61 days v. 0 day, adjusted OR=0.92 (95% CI 0.50–1.69).ConclusionsThese data do not support an association between duration of antidepressant use during the first trimester of pregnancy and major congenital malformations in the offspring of women with psychiatric disorders. These findings should help clinicians decide whether to continue antidepressant therapy during pregnancy.

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Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence

Frontiers in Pharmacology ◽

10.3389/fphar.2021.722511 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anick Bérard ◽

Odile Sheehy ◽

Jin-Ping Zhao ◽

Evelyne Vinet ◽

Caroline Quach ◽

...

Keyword(s):

Real World ◽

Lupus Erythematosus ◽

Time Window ◽

First Trimester ◽

Pregnancy Cohort ◽

Real World Evidence ◽

Increased Risk ◽

Organ Specific ◽

Adverse Pregnancy ◽

Major Congenital Malformations

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence.Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998–2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations.Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84–2.30), LBW (aOR 1.11, 95%CI 0.59–2.06), or MCM (aOR 1.01, 95%CI 0.67–1.52).Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.

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Antidepressant use during first trimester not associated with risk of major congenital malformations

Evidence-Based Mental Health ◽

10.1136/ebmh.12.1.28 ◽

2009 ◽

Vol 12 (1) ◽

pp. 28-28

Author(s):

L. Howard

Keyword(s):

Congenital Malformations ◽

First Trimester ◽

Antidepressant Use ◽

Major Congenital Malformations

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Use of Selective Serotonin Reuptake Inhibitors During Pregnancy and Prevalence of Congenital Malformations: A Protocol for Systematic Review and Meta-analysis of Observational Studies from 2009-2020.

10.21203/rs.3.rs-102876/v1 ◽

2020 ◽

Author(s):

Ayodele Lucy Fela-Thomas ◽

Emmanuel Okechukwu Nna ◽

Nnaemeka Anyahara ◽

Oluwafemi T Ojo ◽

Olugbemi Motilewa ◽

...

Keyword(s):

Pregnant Women ◽

Serotonin Reuptake ◽

Congenital Malformations ◽

Observational Studies ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Cochrane Library ◽

Duration Of Treatment ◽

In Pregnancy

Abstract Background: The effect of antidepressants on the foetus is of great public concern on account of teratogenicity. However, evidence on this is quite controversial. This study aims to determine the risk of congenital malformations in offsprings of pregnant women placed on Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy compared to the offsprings of pregnant women not on SSRIs. It also aims to assess if significant increase in risk occurs across trimesters. METHODS AND ANALYSIS:A search strategy is developed using MeSH, text words and entry terms. Nine databases will be searched: PubMed, Embase, CINAHL, AJOL, Google Scholar, Web of Science, Cochrane Library, Research gate and Scopus. Only Observational studies from 2009-2020, retrievable in the English Language will be included. The primary measurable outcome is risk of teratogenicity with SSRI use in pregnancy. All identified studies, imported into End note version 9, will be screened based on the inclusion/exclusion criteria; data will be exported into Microsoft excel. Extractable data will include first author’s name and year of publication, proportion of congenital malformations in women on SSRIs and women without SSRIs, trimester, time of initiation and duration of treatment. Pedro quality scores and Cochrane risk of bias for individual study will be reported. All studies will be assessed for methodological, clinical and statistical heterogeneity. Publication bias will be assessed using the funnel plot. Subgroup analysis will be performed. The different trimesters and time of initiation of treatment will be used as moderators. Meta-regression will be done using duration of treatment. The CMA version 3 will be used for statistical analysis and forest plots. Discussion:The study will require no ethical approval, it is based on published data. The results obtained from this review will provide relevant information on the use of SSRIs in pregnancy and the risk of congenital malformations. Furthermore, it will provide vital information on the levels and trend of risk at each trimester. The final report will be made available to mental health experts providing care to pregnant women.Trial Registration Number: This protocol is registered in PROSPERO, with number CRD42020213505

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Safety of selective serotonin reuptake inhibitors in pregnancy

Psychiatric Bulletin ◽

10.1192/pb.bp.106.012898 ◽

2007 ◽

Vol 31 (5) ◽

pp. 183-186 ◽

Cited By ~ 2

Author(s):

Allison Donnelly ◽

Carol Paton

Keyword(s):

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Clinical Excellence ◽

First Trimester ◽

Serotonin Reuptake Inhibitors ◽

Selective Serotonin ◽

Joint Decision ◽

Increased Risk ◽

Major Congenital Malformations ◽

In Pregnancy

Aims and MethodSelective serotonin reuptake inhibitors (SSRIs) are recommended by the National Institute for Clinical Excellence as first-line drugs for the treatment of depression, but there is emerging evidence that they might not be entirely safe in pregnancy. We reviewed the literature in this area.ResultsSome data indicate an association between first-trimester SSRI exposure, particularly with paroxetine, and an increased risk of some major congenital malformations. Stronger evidence supports an association with small reductions in gestational age and neonatal withdrawal symptoms.Clinical ImplicationsRisks and benefits of using SSRIs during pregnancy should be discussed with the patient, and a joint decision made between prescriber and patient regarding treatment. Limited data suggest that other SSRIs are safer than paroxetine in pregnancy.

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