First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.

BACKGROUND:Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic...

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Main Authors: Lu Ban, Joe West, Jack E Gibson, Linda Fiaschi, Rachel Sokal, Pat Doyle, Richard Hubbard, Liam Smeeth, Laila J Tata
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4071000?pdf=render
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author Lu Ban
Joe West
Jack E Gibson
Linda Fiaschi
Rachel Sokal
Pat Doyle
Richard Hubbard
Liam Smeeth
Laila J Tata
author_facet Lu Ban
Joe West
Jack E Gibson
Linda Fiaschi
Rachel Sokal
Pat Doyle
Richard Hubbard
Liam Smeeth
Laila J Tata
author_sort Lu Ban
collection DOAJ
description BACKGROUND:Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic and hypnotic drugs taken in the first trimester of pregnancy, compared with children of mothers with depression and/or anxiety but not treated with medication and children of mothers without diagnosed mental illness during pregnancy. METHODS:We identified singleton children born to women aged 15-45 years between 1990 and 2010 from a large United Kingdom primary care database. We calculated absolute risks of MCAs for children with first trimester exposures of different anxiolytic and hypnotic drugs and used logistic regression with a generalised estimating equation to compare risks adjusted for year of childbirth, maternal age, smoking, body mass index, and socioeconomic status. RESULTS:Overall MCA prevalence was 2.7% in 1,159 children of mothers prescribed diazepam, 2.9% in 379 children with temazepam, 2.5% in 406 children with zopiclone, and 2.7% in 19,193 children whose mothers had diagnosed depression and/or anxiety but no first trimester drug exposures. When compared with 2.7% in 351,785 children with no diagnosed depression/anxiety nor medication use, the adjusted odds ratios were 1.02 (99% confidence interval 0.63-1.64) for diazepam, 1.07 (0.49-2.37) for temazepam, 0.96 (0.42-2.20) for zopiclone and 1.27 (0.43-3.75) for other anxiolytic/hypnotic drugs and 1.01 (0.90-1.14) for un-medicated depression/anxiety. Risks of system-specific MCAs were generally similar in children exposed and not exposed to such medications. CONCLUSIONS:We found no evidence for an increase in MCAs in children exposed to benzodiazepines and non-benzodiazepine hypnotics in the first trimester of pregnancy. These findings suggest that prescription of these drugs during early pregnancy may be safe in terms of MCA risk, but findings from other studies are required before safety can be confirmed.
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spelling doaj.art-f98cf5bff5594493a950a16fa250ca0a2022-12-22T01:31:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e10099610.1371/journal.pone.0100996First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.Lu BanJoe WestJack E GibsonLinda FiaschiRachel SokalPat DoyleRichard HubbardLiam SmeethLaila J TataBACKGROUND:Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic and hypnotic drugs taken in the first trimester of pregnancy, compared with children of mothers with depression and/or anxiety but not treated with medication and children of mothers without diagnosed mental illness during pregnancy. METHODS:We identified singleton children born to women aged 15-45 years between 1990 and 2010 from a large United Kingdom primary care database. We calculated absolute risks of MCAs for children with first trimester exposures of different anxiolytic and hypnotic drugs and used logistic regression with a generalised estimating equation to compare risks adjusted for year of childbirth, maternal age, smoking, body mass index, and socioeconomic status. RESULTS:Overall MCA prevalence was 2.7% in 1,159 children of mothers prescribed diazepam, 2.9% in 379 children with temazepam, 2.5% in 406 children with zopiclone, and 2.7% in 19,193 children whose mothers had diagnosed depression and/or anxiety but no first trimester drug exposures. When compared with 2.7% in 351,785 children with no diagnosed depression/anxiety nor medication use, the adjusted odds ratios were 1.02 (99% confidence interval 0.63-1.64) for diazepam, 1.07 (0.49-2.37) for temazepam, 0.96 (0.42-2.20) for zopiclone and 1.27 (0.43-3.75) for other anxiolytic/hypnotic drugs and 1.01 (0.90-1.14) for un-medicated depression/anxiety. Risks of system-specific MCAs were generally similar in children exposed and not exposed to such medications. CONCLUSIONS:We found no evidence for an increase in MCAs in children exposed to benzodiazepines and non-benzodiazepine hypnotics in the first trimester of pregnancy. These findings suggest that prescription of these drugs during early pregnancy may be safe in terms of MCA risk, but findings from other studies are required before safety can be confirmed.http://europepmc.org/articles/PMC4071000?pdf=render
spellingShingle Lu Ban
Joe West
Jack E Gibson
Linda Fiaschi
Rachel Sokal
Pat Doyle
Richard Hubbard
Liam Smeeth
Laila J Tata
First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.
PLoS ONE
title First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.
title_full First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.
title_fullStr First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.
title_full_unstemmed First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.
title_short First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study.
title_sort first trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies a united kingdom population based cohort study
url http://europepmc.org/articles/PMC4071000?pdf=render
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