Adverse outcomes during pregnancy and major congenital malformations in infants of patients with bipolar and schizoaffective disorders treated with antiepileptic drugs: a systematic review

ObjectivesTo investigate the association between paternal use of antiepileptic drugs (AEDs) and adverse neurodevelopmental outcomes and major congenital malformations (MCM) in the offspring.MethodsUsing nationwide Swedish registries, we included 1 144 795 births to 741 726 fathers without epilepsy and 4544 births to 2955 fathers with epilepsy. Of these, 2087 (45.9%) were born to fathers with epilepsy who had dispensed an AED during the conception period. Children who had both parents with epilepsy were excluded. The incidence rate of MCM, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and intellectual disability in offspring was analysed.ResultsOffspring of fathers exposed to AEDs did not show an increased risk of MCM (adjusted OR 0.9, 95% CI 0.7 to 1.2), autism (adjusted HR (aHR) 0.9, 95% CI 0.5 to 1.7), ADHD (aHR 1.1, 95% CI 0.7 to 1.9) or intellectual disability (aHR 1.3, 95% CI 0.6 to 2.8) compared with offspring of fathers with epilepsy not exposed to AEDs. Among offspring of fathers with epilepsy who used valproate in monotherapy during conception, rates of autism (2.9/1000 child-years) and intellectual disability (1.4/1000 child-years) were slightly higher compared with the offspring of fathers with epilepsy who did not use AEDs during conception (2.1/1000 child-years autism, 0.9/1000 child-years intellectual disability), but in the propensity-score adjusted analyses, no statistically significant increased risk of adverse outcomes was found.ConclusionsPaternal AED use during conception is not associated with adverse outcomes in the offspring.

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A systematic review and meta-analyses of pregnancy and fetal outcomes in women with multiple sclerosis: a contribution from the IMI2 ConcePTION project

Journal of Neurology ◽

10.1007/s00415-020-09913-1 ◽

2020 ◽

Vol 267 (9) ◽

pp. 2721-2731 ◽

Cited By ~ 2

Author(s):

Sandra Lopez-Leon ◽

Yvonne Geissbühler ◽

Meritxell Sabidó ◽

Moise Turkson ◽

Charlotte Wahlich ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Congenital Malformations ◽

Treatment Options ◽

Preterm Births ◽

Disease Modifying Drugs ◽

Pregnancy And Birth Outcomes ◽

Major Congenital Malformations ◽

Meta Analyses ◽

Pregnancy And Birth

Abstract Neurologists managing women with Multiple Sclerosis (MS) need information about the safety of disease modifying drugs (DMDs) during pregnancy. However, this knowledge is limited. The present study aims to summarize previous studies by performing a systematic review and meta-analyses. The terms “multiple sclerosis” combined with DMDs of interest and a broad profile for pregnancy terms were used to search Embase and Medline databases to identify relevant studies published from January 2000 to July 2019.1260 studies were identified and ten studies met our inclusion criteria. Pooled risk ratios (RR) of pregnancy and birth outcomes in pregnancies exposed to DMDs compared to those not exposed were calculated using a random effects model. For spontaneous abortion RR = 1.14, 95% CI 0.99–1.32, for preterm births RR = 0.93, 95% CI 0.72–1.21 and for major congenital malformations RR = 0.86, 95% CI 0.47–1.56. The most common major congenital malformations reported in MS patients exposed to MS drugs were atrial septal defect (ASD) (N = 4), polydactyly (N = 4) and club foot (N = 3), which are among the most prevalent birth defects observed in the general population. In conclusion, interferons, glatiramer acetate or natalizumab, do not appear to increase the risk for spontaneous abortions, pre-term birth or major congenital malformations. There were very few patients included that were exposed to fingolimod, azathioprine and rituximab; therefore, these results cannot be generalized across drugs. Future studies including internal comparators are needed to enable treating physicians and their patients to decide on the best treatment options.

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Risks of 23 specific malformations associated with prenatal exposure to 10 antiepileptic drugs

Neurology ◽

10.1212/wnl.0000000000007696 ◽

2019 ◽

Vol 93 (2) ◽

pp. e167-e180 ◽

Cited By ~ 14

Author(s):

Pierre-Olivier Blotière ◽

Fanny Raguideau ◽

Alain Weill ◽

Elisabeth Elefant ◽

Isabelle Perthus ◽

...

Keyword(s):

Health Care ◽

Valproic Acid ◽

Antiepileptic Drugs ◽

Congenital Malformations ◽

Cleft Lip ◽

Reference Group ◽

The Other ◽

Increased Risk ◽

Exact Confidence Intervals ◽

Major Congenital Malformations

ObjectiveTo assess the association between exposure to monotherapy with 10 different antiepileptic drugs (AEDs) during the first 2 months of pregnancy and the risk of 23 major congenital malformations (MCMs).MethodsThis nationwide cohort study, based on the French health care databases, included all pregnancies ≥20 weeks and ending between January 2011 and March 2015. Women were considered to be exposed when an AED had been dispensed between 1 month before and 2 months after the beginning of pregnancy. The reference group included pregnant women with no reimbursement for AEDs. MCMs were detected up to 12 months after birth (24 months for microcephaly, hypospadias, and epispadias). Odds ratios (ORs) were adjusted for potential confounders for MCMs with at least 5 cases. Otherwise, we calculated crude ORs with exact confidence intervals (CIs).ResultsThe cohort included 1,886,825 pregnancies, 2,997 of which were exposed to lamotrigine, 1,671 to pregabalin, 980 to clonazepam, 913 to valproic acid, 579 to levetiracetam, 517 to topiramate, 512 to carbamazepine, 365 to gabapentin, 139 to oxcarbazepine, and 80 to phenobarbital. Exposure to valproic acid was associated with 8 specific types of MCMs (e.g., spina bifida, OR 19.4, 95% CI 8.6–43.5), and exposure to topiramate was associated with an increased risk of cleft lip (6.8, 95% CI 1.4–20.0). We identified 3 other signals. We found no significant association for lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, and gabapentin.ConclusionsThese results confirm the teratogenicity of valproic acid and topiramate. Because of the small numbers of cases and possible confounding, the other 3 signals should be interpreted with appropriate caution.

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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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