Sophie Grigoriadis1,2,3,4, Lisa Graves5, Miki Peer2, Lana Mamisashvili2, Myuri Ruthirakuhan6, Parco Chan6, Mirna Hennawy3, Supriya Parikh3, Simone Natalie Vigod4,7, Cindy-Lee Dennis8, Meir Steiner9, Cara Brown4, Amy Cheung1,3,4, Hiltrud Dawson10, Neil Rector1,3,4, Melanie Guenette2,11, Margaret Richter1,3,4. 1. Department of Psychiatry, 71545Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada. 2. Evaluative Clinical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada. 3. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Ontario, Canada. 4. Department of Psychiatry, University of Toronto, Ontario, Canada. 5. Department of Family and Community Medicine, Homer Stryker MD School of Medicine, 4175Western Michigan University, Kalamazoo, MI, USA. 6. Department of Pharmacology and Toxicology, 282299Sunnybrook Research Institute, University of Toronto, Ontario, Canada. 7. Department of Psychiatry, 7985Women's College Hospital, University of Toronto, Ontario, Canada. 8. Lawrence S. Bloomberg Faculty of Nursing, 7938University of Toronto, Ontario, Canada. 9. Department of Psychiatry & Behavioural Neurosciences, St. Joseph's Healthcare Hamilton, McMaster University, Ontario, Canada. 10. 67136Health Nexus, Toronto, Ontario, Canada. 11. Division of Neurology, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Abstract
OBJECTIVE: Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes. DATA SOURCES: Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018. STUDY SELECTION: English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included. DATA EXTRACTION: Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure. RESULTS: There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: -151.35 g; 95% CI, -329.73 to 27.03), gestational age (-0.49 weeks; 95% CI, -1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes. CONCLUSIONS: Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.
OBJECTIVE: Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes. DATA SOURCES: Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018. STUDY SELECTION: English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included. DATA EXTRACTION: Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure. RESULTS: There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: -151.35 g; 95% CI, -329.73 to 27.03), gestational age (-0.49 weeks; 95% CI, -1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes. CONCLUSIONS: Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.
Authors: Marlene P Freeman; Lina Góez-Mogollón; Kathryn A McInerney; Abigail C Davies; Taylor R Church; Alexandra Z Sosinsky; Olivia B Noe; Adele C Viguera; Lee S Cohen Journal: Gen Hosp Psychiatry Date: 2018-05-29 Impact factor: 3.238
Authors: Lori E Ross; Sophie Grigoriadis; Lana Mamisashvili; Emily H Vonderporten; Michael Roerecke; Jürgen Rehm; Cindy-Lee Dennis; Gideon Koren; Meir Steiner; Patricia Mousmanis; Amy Cheung Journal: JAMA Psychiatry Date: 2013-04 Impact factor: 21.596
Authors: Sophie Grigoriadis; Lisa Graves; Miki Peer; Lana Mamisashvili; George Tomlinson; Simone N Vigod; Cindy-Lee Dennis; Meir Steiner; Cara Brown; Amy Cheung; Hiltrud Dawson; Neil A Rector; Melanie Guenette; Margaret Richter Journal: J Clin Psychiatry Date: 2018-09-04 Impact factor: 4.384
Authors: Jacqueline M Cohen; Mollie E Wood; Sonia Hernandez-Diaz; Hedvig Nordeng Journal: Pharmacoepidemiol Drug Saf Date: 2018-02-28 Impact factor: 2.890
Authors: William V Bobo; Robert L Davis; Sengwee Toh; De-Kun Li; Susan E Andrade; T Craig Cheetham; Pamala Pawloski; Sascha Dublin; Simone Pinheiro; Tarek Hammad; Pamela E Scott; Richard A Epstein; Patrick G Arbogast; James A Morrow; Judith A Dudley; Jean M Lawrence; Lyndsay A Avalos; William O Cooper Journal: Paediatr Perinat Epidemiol Date: 2012-11 Impact factor: 3.980
Authors: Richard A Epstein; William V Bobo; Richard C Shelton; Patrick G Arbogast; James A Morrow; Wei Wang; Rameela Chandrasekhar; William O Cooper Journal: Pharmacoepidemiol Drug Saf Date: 2012-11-05 Impact factor: 2.890
Authors: Ludvig D Bjørndal; Fatima Tauqeer; Kristin S Heiervang; Hanne K Clausen; Kristine Heitmann; Angela Lupattelli Journal: BMJ Open Date: 2022-09-30 Impact factor: 3.006