The risk of congenital malformations associated with exposure to ?-blockers early in pregnancy: a meta-analysis.
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ABSTRACT:
SUBMITTER: Yakoob MY
PROVIDER: S-EPMC4086784 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
The risk of congenital malformations associated with exposure to β-blockers early in pregnancy: a meta-analysis.
Yakoob Mohammad Y MY Bateman Brian T BT Ho Eugenia E Hernandez-Diaz Sonia S Franklin Jessica M JM Goodman Julie E JE Hoban Rebecca A RA
Hypertension (Dallas, Tex. : 1979) 20130610 2
β-blockers are commonly used during the first trimester of pregnancy. Data about risks of congenital anomalies in offspring have not been summarized. We performed a meta-analysis to determine teratogenicity of β-blockers in early pregnancy. A systematic literature search was performed using PubMed, EMBASE, Cochrane Clinical Trials, and hand search. Meta-analyses were performed using random-effects models based on odds ratios (ORs). Prespecified subgroup analyses were performed to explore heterog ...[more]
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Project description:ObjectiveThe aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations.MethodsA meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case-control studies, prospective cohort studies, and retrospective cohort studies.ResultsTwelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI)/carbimazole (CMZ) only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004). No differences were observed between propylthiouracil (PTU) exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24). Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001).ConclusionFor pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure.
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Project description:ObjectiveTo assess whether first-trimester exposure to pregabalin is associated with an increased risk of major congenital malformations, as recently suggested in a pregnancy registry study.MethodsWe performed a cohort study nested in the US Medicaid Analytic eXtract (MAX). The study population included 1,323,432 pregnancies resulting in a live-born infant between 2000 and 2010. We examined the risk of major congenital malformations among infants born to women exposed to pregabalin during the first trimester compared with women unexposed to anticonvulsants. We used propensity score fine stratification to control for >50 potential confounders, and we estimated relative risks (RRs) and 95% confidence intervals (CIs) in generalized linear models. The analyses were replicated in the Truven Health MarketScan Commercial Database (MarketScan). Pooled estimates based on the adjusted RR produced in MAX, MarketScan, and the previous registry study were calculated.ResultsOf 477 infants exposed to pregabalin during the first trimester in MAX, 28 (5.9%) had malformations compared to 3.3% in nonexposed infants. The crude RR of major congenital malformations for pregabalin was 1.80 (95% CI 1.26-2.58). After propensity score adjustment, the RR moved to 1.16 (95% CI 0.81-1.67). Restriction to pregabalin monotherapy and sensitivity analyses produced similar results. The adjusted RR for major congenital malformations for the 174 infants exposed in MarketScan was 1.03 (95% CI 0.56-1.90). The pooled RR was 1.33 (95% CI 0.83-2.15) for pregabalin any use and 1.02 (95% CI 0.69-1.51) for pregabalin monotherapy.ConclusionsFindings did not confirm the suggested teratogenic effects of pregabalin, although they cannot rule out the possibility of a small effect.
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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.
| S-EPMC9856708 | biostudies-literature
Project description:OBJECTIVE:To evaluate the association between increased exposure to airborne fine particulate matter (PM2.5) during the periconception period with risk of congenital anomalies. STUDY DESIGN:Using birth certificate data from the Ohio Department of Health (2006-2010) and PM2.5 data from the US Environmental Protection Agency's 57 monitoring stations located throughout Ohio, the geographic coordinates of the mother's residence for each birth were linked to the nearest PM2.5 monitoring station and monthly exposure averages were calculated. The association between congenital anomalies and increased PM2.5 levels was estimated, with adjustment for coexistent risk factors. RESULTS:After adjustment for coexisting risk factors, exposure to increased levels of PM2.5 in the air during the periconception period was modestly associated with risk of congenital anomalies. Compared with other periconception exposure windows, increased exposure during the 1 month before conception was associated with the highest risk increase at lesser distances from monitoring stations. The strongest influences of PM2.5 on individual malformations were found with abdominal wall defects and hypospadias, especially during the 1-month preconception. CONCLUSIONS:Increased exposure to PM2.5 in the periconception period is associated with some modest risk increases for congenital malformations. The most susceptible time of exposure appears to be the 1 month before and after conception. Although the increased risk with PM2.5 exposure is modest, the potential impact on a population basis is noteworthy because all pregnant women have some degree of exposure.
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Project description:PurposeTo study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM).MethodsA population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models.ResultsUse of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results.ConclusionsOlanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.
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Project description:BackgroundAntiretroviral therapy (ART) decreases perinatal HIV transmission, but concerns exist regarding maternal and infant safety. We compared the incidence of congenital malformations and other adverse outcomes in pregnancies exposed to integrase inhibitor (INSTI) versus non-INSTI ART.SettingSingle-site review of all pregnancies among women living with HIV between 2008 and 2018.MethodsWe used binomial family generalized estimating equations to model the relationship of congenital anomalies and pregnancy outcomes with exposure to INSTI or dolutegravir (DTG) versus non-INSTI ART.ResultsAmong 257 pregnancies, 77 women received ≥1 INSTI (54 DTG, 14 elvitegravir, 15 raltegravir), 167 received non-INSTI, and 3 had missing data. Fifty congenital anomalies were identified in 36 infants. Infants with first-trimester DTG or any first-trimester INSTI exposure had higher odds of congenital anomalies than infants with first-trimester non-INSTI exposure (OR = 2.55; 95%CI = 1.07-6.10; OR = 2.61; 95%CI = 1.15-5.94, respectively). Infants with INSTI exposure after the second trimester had no increased odds of anomalies. Women with INSTI exposure had higher odds of preeclampsia (OR = 4.73; 95%CI = 1.70-13.19). Among women who received INSTI, grade ≥3 laboratory abnormalities were noted in 2.6% while receiving the INSTI and 3.9% while not receiving the INSTI, versus 16.2% in women who received non-INSTI. There was no association between INSTI exposure and other pregnancy outcomes.ConclusionIn our cohort, first-trimester INSTI exposure was associated with increased rates of congenital anomalies and use of INSTI during pregnancy was associated with preeclampsia. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy.
| S-EPMC10259792 | biostudies-literature
Project description:ImportanceWomen with epilepsy (WWE) require treatment with antiseizure medications (ASMs) during pregnancy, which may be associated with an increased risk of major congenital malformations (MCMs) in their offspring.ObjectiveTo investigate the prevalence of MCMs after prenatal exposure to 8 commonly used ASM monotherapies and changes in MCM prevalence over time.Design, setting, and participantsThis was a prospective, observational, longitudinal cohort study conducted from June 1999 to October 2022. Since 1999, physicians from more than 40 countries enrolled ASM-treated WWE before pregnancy outcome was known and followed up their offspring until 1 year after birth. Participants aged 14 to 55 years who were exposed to 8 of the most frequently used ASMs during pregnancy were included in this study. Data were analyzed from April to September 2023.ExposureMaternal use of ASMs at conception.Main outcomes and measuresMCMs were assessed 1 year after birth by a committee blinded to type of exposure. Teratogenic outcomes across exposures were compared by random-effects logistic regression adjusting for potential confounders and prognostic factors.ResultsA total of 10 121 prospective pregnancies exposed to ASM monotherapy met eligibility criteria. Of those, 9840 were exposed to the 8 most frequently used ASMs. The 9840 pregnancies occurred in 8483 women (mean [range] age, 30.1 [14.1-55.2] years). MCMs occurred in 153 of 1549 pregnancies for valproate (9.9%; 95% CI, 8.5%-11.5%), 9 of 142 for phenytoin (6.3%; 95% CI, 3.4%-11.6%), 21 of 338 for phenobarbital (6.2%; 95% CI, 4.1%-9.3%), 121 of 2255 for carbamazepine (5.4%; 95% CI, 4.5%-6.4%), 10 of 204 for topiramate (4.9%; 95% CI, 2.7%-8.8%), 110 of 3584 for lamotrigine (3.1%; 95% CI, 2.5%-3.7%), 13 of 443 for oxcarbazepine (2.9%; 95% CI, 1.7%-5.0%), and 33 of 1325 for levetiracetam (2.5%; 95% CI, 1.8%-3.5%). For valproate, phenobarbital, and carbamazepine, there was a significant increase in the prevalence of MCMs associated with increasing dose of the ASM. Overall prevalence of MCMs decreased from 6.1% (153 of 2505) during the period 1998 to 2004 to 3.7% (76 of 2054) during the period 2015 to 2022. This decrease over time was significant in univariable logistic analysis but not after adjustment for changes in ASM exposure pattern.Conclusions and relevanceOf all ASMs with meaningful data, the lowest prevalence of MCMs was observed in offspring exposed to levetiracetam, oxcarbazepine, and lamotrigine. Prevalence of MCMs was higher with phenytoin, valproate, carbamazepine, and phenobarbital, and dose dependent for the latter 3 ASMs. The shift in exposure pattern over time with a declining exposure to valproate and carbamazepine and greater use of lamotrigine and levetiracetam was associated with a 39% decline in prevalence of MCMs, a finding that has major public health implications.
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Project description:There is inconsistent evidence that zidovudine use during pregnancy increases overall, cardiac, and male genital malformations.We conducted a systematic review and meta-analysis of zidovudine use and malformations and, using Bayesian methods, combined it with data from a cohort study of mother-infant pairs in the nationwide Medicaid Analytic eXtract (MAX).Using MAX data (2000-2010), we identified pregnant women with HIV treated with antiretroviral therapy (ART). Women with at least one zidovudine dispensing during the first trimester were compared to women receiving ART without zidovudine in the first trimester. Malformation outcomes were defined using diagnosis/procedure codes. To adjust for confounding, we performed 1?:?1 propensity score matching. Bayesian methods require specification of a prior, which we developed in the meta-analysis. Logistic regression models combined MAX data with the prior, estimating odds ratios (ORs) and 95% credible intervals.Fourteen articles contributed information on overall malformations, seven on cardiac malformations, and five on male genital malformations. In MAX, matching led to a sample of 735 women each in the zidovudine and comparator groups. When comparing first trimester zidovudine use to other ART, the Bayesian procedure yielded OR estimates slightly above the null for overall [OR?=?1.11, 95% credible interval (0.80-1.55)] and cardiac [OR?=?1.30 (0.63-2.71)] malformations. There were no zidovudine-exposed cases of male genital malformations in MAX, but the meta-analysis yielded elevated OR estimates [OR?=?2.57 (1.26-5.24)].For most malformations, first-trimester zidovudine was not associated with increased risk. The potential increase in male genital malformations was small in absolute terms, and should be evaluated further.
| S-EPMC5534355 | biostudies-literature
Project description:BackgroundThe prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths.Methods and findingsA population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates.ConclusionsBased on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.
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