Dataset Information

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review.

ABSTRACT: Opioid use and abuse have increased dramatically in recent years, particularly among women.We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations.We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies.We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process.Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies.Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation.Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement.Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age.

SUBMITTER: Lind JN

PROVIDER: S-EPMC5561453 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review.

Lind Jennifer N JN Interrante Julia D JD Ailes Elizabeth C EC Gilboa Suzanne M SM Khan Sara S Frey Meghan T MT Dawson April L AL Honein Margaret A MA Dowling Nicole F NF Razzaghi Hilda H Creanga Andreea A AA Broussard Cheryl S CS

Pediatrics 20170601 6

<h4>Context</h4>Opioid use and abuse have increased dramatically in recent years, particularly among women.<h4>Objectives</h4>We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations.<h4>Data sources</h4>We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies.<h4>Study selection</h4>We included studies that were full-text journal articles and reported t ...[more]

PMID: 28562278

Similar Datasets

Project description:ImportanceProton pump inhibitors (PPIs) are increasingly used during pregnancy; however, several observational studies have raised concerns about an increased risk of specific types of congenital malformations.ObjectiveTo examine the association between PPI exposure during early pregnancy and the risk of congenital malformations.Design, setting, and participantsThis population-based cohort study used data from the National Health Insurance Service-National Health Information Database of South Korea (2010-2020); sibling-controlled analyses were conducted to account for familial factors. A total of 2 696 216 pregnancies in women aged 19 to 44 years between June 1, 2011, and December 31, 2019, and their live-born infants were identified. Pregnant women who were exposed to known teratogens or who delivered infants with chromosomal abnormalities or genetic syndromes were excluded. Data on participant race and ethnicity were not collected because the National Health Information Database does not report this information.ExposuresProton pump inhibitor use during the first trimester.Main outcomes and measuresPrimary outcomes were major congenital malformations, congenital heart defects, cleft palate, hydrocephalus, and hypospadias. The subtypes of major congenital malformations and congenital heart defects were evaluated as exploratory outcomes. Propensity score fine stratification was used to control for potential confounders, and a weighted generalized linear model was used to estimate relative risks with 95% CIs.ResultsOf 2 696 216 pregnancies (mean [SD] maternal age, 32.1 [4.2] years), 40 540 (1.5%; mean [SD] age, 32.4 [4.6] years) were exposed to PPIs during the first trimester. The absolute risk of major congenital malformations was 396.7 per 10 000 infants in PPI-exposed pregnancies and 323.4 per 10 000 infants in unexposed pregnancies. The propensity score-adjusted relative risks were 1.07 (95% CI, 1.02-1.13) for major congenital malformations, 1.09 (95% CI, 1.01-1.17) for congenital heart defects, 1.02 (95% CI, 0.72-1.43) for cleft palate, 0.94 (95% CI, 0.54-1.63) for hydrocephalus, and 0.77 (95% CI, 0.51-1.17) for hypospadias. In the sibling-controlled analyses, no associations were observed between PPI use and primary outcomes, including major congenital malformations (odds ratio, 1.05; 95% CI, 0.91-1.22) and congenital heart defects (odds ratio, 1.07; 95% CI, 0.88-1.30). A range of sensitivity analyses revealed results that were similar to the main findings.Conclusions and relevanceIn this cohort study, the use of PPIs during early pregnancy was not associated with a substantial increase in the risk of congenital malformations, although small increased risks were observed for major congenital malformations and congenital heart defects; findings from sibling-controlled analyses revealed that PPIs were unlikely to be major teratogens. These findings may help guide clinicians and patients in decision-making about PPI use in the first trimester.

Project description:BackgroundIn 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.MethodsThe study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).ResultsTwenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).ConclusionsThe evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.

Project description:BackgroundPregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis.MethodsMEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes).ResultsAfter screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not.ConclusionThe newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control.Systematic review registrationPROSPERO CRD42014008925.

Project description:BackgroundBiologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy.ObjectiveTo determine pregnancy outcomes in women with CID exposed to biologics during pregnancy.Search strategyPubMed and EMBASE databases were searched through January 1998-July 2021.Selection criteriaPeer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data.Data collection and analysisTwo authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence.Main resultsThirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; I2 = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I2 = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I2 = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I2 = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I2 = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I2 = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I2 = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I2 = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I2 = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I2 = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I2 = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I2 = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low.ConclusionWe demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.

Dataset Information

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review.

Publications

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets