Teratogenicity of antiepileptic dual therapy

ObjectiveTo determine the relative risk (RR) of major congenital malformations (MCMs) in infants with antenatal exposure to antiepileptic drug (AED) dual therapy and to explore the influence of specific AEDs vs dose.MethodsAll completed pregnancies prospectively enrolled in the Kerala Registry of Epilepsy and Pregnancy from 1998 until December 2013 on AED dual therapy exposure during the first trimester were analyzed for the outcome, MCMs. Dose was expressed as ratio of prescribed to daily defined dose (PDD/DDD), and the RR for malformation was referenced to lamotrigine monotherapy.ResultsOf 1,688 completed pregnancies, 368 women were on dual therapy. The risk of MCM with dual therapy was 1.6 times more than with monotherapy (p = 0.0015). The frequency of renal, alimentary, and skeletal malformations was higher with dual therapy, while cardiac malformations were more common with monotherapy. The risk of MCM was highest with topiramate dual therapy (14.82, 95% confidence interval [CI] 1.88–113.83). No MCMs were seen with levetiracetam or lamotrigine dual therapy. There was a marked reduction in the risk of MCM when dual therapies involving topiramate or valproate were excluded (RR 1.78, 95% CI 1.00–3.15). The risk of MCM with dual therapy was higher even at lower doses (8.2%, PDD/DDD 0.5–1), and the subsequent dose-dependent increment was less profound than with monotherapy.ConclusionsOur data indicate that the excess risk of dual therapy over monotherapy is contributed largely by topiramate or valproate. The complex pharmacokinetic and pharmacodynamic effects of dual therapy adversely influence MCM risk.

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Faculty Opinions recommendation of Major congenital malformations after first-trimester exposure to ACE inhibitors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14201.501141 ◽

2006 ◽

Author(s):

Laura Magee

Keyword(s):

Ace Inhibitors ◽

Congenital Malformations ◽

First Trimester ◽

Trimester Exposure ◽

Major Congenital Malformations

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Herbal Medicines Used During the First Trimester and Major Congenital Malformations

Drug Safety ◽

10.2165/00002018-200629060-00006 ◽

2006 ◽

Vol 29 (6) ◽

pp. 537-548 ◽

Cited By ~ 43

Author(s):

Chao-Hua Chuang ◽

Pat Doyle ◽

Jung-Der Wang ◽

Pei-Jen Chang ◽

Jung-Nien Lai ◽

...

Keyword(s):

Congenital Malformations ◽

Herbal Medicines ◽

First Trimester ◽

Major Congenital Malformations

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P07 Roxithromycin in early pregnancy and the risk of major congenital malformation: a register based nationwide cohort study

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.46 ◽

2019 ◽

Vol 104 (6) ◽

pp. e20.1-e20

Author(s):

RH Olsen ◽

HE Poulsen ◽

JT Andersen

Keyword(s):

Cohort Study ◽

Congenital Malformation ◽

Congenital Malformations ◽

Safety Data ◽

First Trimester ◽

Adverse Outcomes ◽

Sensitivity Analyses ◽

Multiple Birth ◽

Major Congenital Malformation ◽

Major Congenital Malformations

BackgroundMedicine use during pregnancy often causes concern for fetal harm. Roxithromycin, a macrolide antibiotic, is regarded as inadvisable to use during pregnancy due to lack of safety data. However, alternative macrolides have been associated with adverse outcomes in pregnancy. We conducted a register-based nationwide cohort study testing the hypothesis that use of roxithromycin in the first trimester is associated with major congenital malformations.MethodsWe included all Danish women giving live birth from 1997 to 2012. Women with at least one redeemed receipt of roxithromycin during first trimester were regarded as exposed. Multivariable logistic regression adjusting for maternal age, multiple birth, parity, year of conception, smoking, educational length, and household income was performed, supplemented by sensitivity analyses comparing unexposed with exposure to increasing accumulated doses of roxithromycin.ResultsThe study included 966,372 pregnancies of which 2,430 children were born to an exposed mother, 78 (3.34%) of the exposed children were diagnosed with a major congenital malformation compared with 33,609 (3.49%) among children born to unexposed mothers. The odds ratio for the occurrence of a major congenital malformation after exposure to roxithromycin was 0.96 (95% CI 0.76–1.20) and multifactorially adjusted 0.94 (0.74–1.18). Sensitivity analyses comparing unexposed with exposure to increasing accumulated doses of roxithromycin showed no dose response relationship. Further, no differences in the type of major malformation according to the EUROCAT subgrouping system were seen.ConclusionsWe found no association between exposure to roxithromycin in the first trimester of pregnancy and major congenital malformations.Disclosure(s)Nothing to disclose

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Major Congenital Malformations after First-Trimester Exposure to ACE Inhibitors

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70072-9 ◽

2007 ◽

Vol 2007 ◽

pp. 98-99

Author(s):

J.S. Dungan

Keyword(s):

Ace Inhibitors ◽

Congenital Malformations ◽

First Trimester ◽

Trimester Exposure ◽

Major Congenital Malformations

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Birth outcomes following antiretroviral exposure during pregnancy: Initial results from a pregnancy exposure registry in South Africa

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v20i1.971 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Ushma C. Mehta ◽

Cari Van Schalkwyk ◽

Prineetha Naidoo ◽

Arthi Ramkissoon ◽

Otty Mhlongo ◽

...

Keyword(s):

Birth Outcomes ◽

Congenital Malformations ◽

First Trimester ◽

First Year ◽

Increased Risk ◽

Bivariable Analysis ◽

Major Congenital Malformations ◽

Clinical Records ◽

Surface Examination ◽

The Impact

Background: In 2013, a pregnancy exposure registry and birth defects surveillance (PER/BDS) system was initiated in eThekwini District, KwaZulu-Natal (KZN), to assess the impact of antiretroviral treatment (ART) on birth outcomes.Objectives: At the end of the first year, we assessed the risk of major congenital malformations (CM) and other adverse birth outcomes (ABOs) detected at birth, in children born to women exposed to ART during pregnancy.Method: Data were collected from women who delivered at Prince Mshiyeni Memorial Hospital, Durban, from 07 October 2013 to 06 October 2014, using medicine exposure histories and birth outcomes from maternal interviews, clinical records and neonatal surface examination. Singleton births exposed to only one ART regimen were included in bivariable analysis for CM risk and multivariate risk analysis for ABO risk.Results: Data were collected from 10 417 women with 10 517 birth outcomes (4013 [38.5%] HIV-infected). Congenital malformations rates in births exposed to Efavirenz during the first trimester (T1) (RR 0.87 [95% CI 0.12–6.4; p = 0.895]) were similar to births not exposed to ART during T1. However, T1 exposure to Nevirapine was associated with the increased risk of CM (RR 9.28 [95% CI 2.3–37.9; p = 0.002]) when compared to the same group. Other ABOs were more frequent in the combination of HIV/ART-exposed births compared to HIV-unexposed births (29.9% vs. 26.0%, adjusted RR 1.23 [1.14–1.31; p 0.001]).Conclusion: No association between T1 use of EFV-based ART regimens and CM was observed. Associations between T1 NVP-based ART regimen and CM need further investigation. HIV- and ART-exposed infants had more ABOs compared to HIV-unexposed infants.

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Methimazole Has a Dose-Dependent Association With Congenital Malformations, but Switching to PTU in the First Trimester Seems Too Late

Clinical Thyroidology ◽

10.1089/ct.2018;30.104-107 ◽

2018 ◽

Vol 30 (3) ◽

pp. 104-107 ◽

Cited By ~ 1

Author(s):

Tim I.M. Korevaar

Keyword(s):

Congenital Malformations ◽

First Trimester ◽

Dose Dependent

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Major Congenital Malformations After First-Trimester Exposure to ACE Inhibitors

Survey of Anesthesiology ◽

10.1097/sa.0b013e3180336519 ◽

2007 ◽

Vol 51 (2) ◽

pp. 91

Author(s):

&NA;

Keyword(s):

Ace Inhibitors ◽

Congenital Malformations ◽

First Trimester ◽

Trimester Exposure ◽

Major Congenital Malformations

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Risk of Major Congenital Malformations after First Trimester Exposure to Topical Azoles

Clinical Therapeutics ◽

10.1016/j.clinthera.2017.05.047 ◽

2017 ◽

Vol 39 (8) ◽

pp. e15

Author(s):

R. Rotem ◽

B. Fishman ◽

G. Koren ◽

S. Daniel ◽

E. Lunenfeld ◽

...

Keyword(s):

Congenital Malformations ◽

First Trimester ◽

Trimester Exposure ◽

Major Congenital Malformations

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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

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2019 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S155-S155

Author(s):

A. Bérard ◽

J.P. Zhao ◽

O. Sheehy

Keyword(s):

Pregnant Women ◽

Serotonin Reuptake ◽

Congenital Malformations ◽

Selective Serotonin Reuptake Inhibitors ◽

First Trimester ◽

Pregnancy Cohort ◽

Organ Specific ◽

Antidepressant Use ◽

Major Congenital Malformations ◽

First Year Of Life

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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Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study

10.2337/figshare.14769912 ◽

2021 ◽

Author(s):

Elisabeth R. Mathiesen ◽

Norsiah Ali ◽

Amra C. Alibegovic ◽

Eleni Anastasiou ◽

Katarzyna Cypryk ◽

...

Keyword(s):

Congenital Malformations ◽

Neonatal Death ◽

Insulin Detemir ◽

First Trimester ◽

Risk Difference ◽

Adjusted Risk ◽

Adverse Pregnancy ◽

Major Congenital Malformations ◽

Design And Methods ◽

Similar Risk

OBJECTIVE: To compare the risk of severe adverse pregnancy complications in women with pre-existing diabetes. RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations, perinatal or neonatal death (primary endpoint) following treatment with insulin detemir (detemir) vs other basal insulins. RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations, perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01,0.04]; adjusted risk difference −0.003 [95% CI −0.03,0.03]). The crude prevalence of ≥1 congenital malformation (major + minor) was 9.4% vs 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064,0.000]) and after (−0.036 [95% CI –0.081,0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs 6.7% [48 vs 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300,−0.062]) and the second trimester (6.1% vs 6.3% [43 vs 45 mmol/mol]; −0.139 [95% CI −0.232,−0.046]), and a lower prevalence of major hypoglycemia (6.0% vs 9.0%; risk difference −0.030 [95% CI −0.058,−0.002]), pre-eclampsia (6.4% vs 10.0%; −0.036 [95% CI −0.064,−0.007]), and stillbirth (0.4% vs 1.8%; −0.013 [95% CI −0.024,−0.002],) with detemir compared to other basal insulins. However, differences were not significant post-adjustment. CONCLUSION: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, pre-eclampsia and stillbirth.

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