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• Pregnant women are increasingly exposed to newer antiseizure medication like lacosamide although their safety has not been evidenced yet. • Preliminary data indicate no increased risk for spontaneous abortion or major birth defects related to lacosamide during pregnancy. • Effects of newer antiseizure medication on pregnancy outcome are difficult to specify, because of limited numbers of well documented pregnancies, frequent antiseizure co-medication and a high rate of terminated pregnancies. Epilepsy is a common neurological disease requiring long-term therapy also during pregnancy. Most studies on pregnancy outcomes in women with epilepsy are based on antiseizure medication (ASM) in monotherapy. However, about 20–30% of epilepsy patients require polytherapy and newer ASMs are an option, when seizure control is not achieved with first line ASMs. Observational study evaluating the use of newer ASMs with marketing authorization since 2005 reported to the Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy between 2004 and 2019. In addition, course and outcome of lacosamide exposed pregnancies were analysed. Our study confirms the increasing use of newer ASMs also in pregnant women. This is especially true for lacosamide, eslicarbazepine and brivaracetam with rising numbers of exposed pregnancies soon after marketing authorization. Analysis of 55 prospectively and 10 retrospectively ascertained lacosamide exposed pregnancies does not indicate increased risks of major birth defects or spontaneous abortion. However, bradycardia observed in 3 neonates might be related to prenatal lacosamide exposure. Available data do not support the assumption of lacosamide being a major teratogen. The increasing use of newer ASMs during pregnancy underscores the need for more studies to guide preconception counselling, especially for lacosamide, eslicarbazepine and brivaracetam. [ABSTRACT FROM AUTHOR]

A whole-genome scan of families affected by Emery-Dreifuss muscular dystrophy (EDMD) is conducted and its linkage to Xq26.3 locus containing the FHL1 gene is identified, along with seven mutations in the distal exons of FHL1. The reduced levels of FHL1 proteins in EDMD patients, which are associated with a severe delay in myotube formation, suggest that FHL1 gene is associated with both the X-linked EDMD phenotype and hypertrophic myopathy.

Objectives Analyze the cumulative evidence for pregnancy outcomes after maternal exposure to tocilizumab, an anti-interleukin-6-receptor monoclonal antibody used for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. At present, published experience on tocilizumab use during pregnancy is very limited. Methods We have analyzed all pregnancy-related reports documented in the Roche Global Safety Database until December 31, 2014 ( n = 501). Results After exclusion of ongoing pregnancies, duplicates, and cases retrieved from the literature, 399 women were found to have been exposed to tocilizumab shortly before or during pregnancy, with pregnancy outcomes being reported in 288 pregnancies (72.2%). Of these 288 pregnancies, 180 were prospectively reported resulting in 109 live births (60.6%), 39 spontaneous abortions (21.7%), 31 elective terminations of pregnancy (17.2%), and 1 stillbirth. The rate of malformations was 4.5%. Co-medications included methotrexate in 21.1% of the prospectively ascertained cases. Compared to the general population, an increased rate of preterm birth (31.2%) was observed. Retrospectively reported pregnancies ( n = 108) resulted in 55 live births (50.9%), 31 spontaneous abortions (28.7%), and 22 elective terminations (20.4%). Three infants/fetuses with congenital anomalies were reported in this group. No increased risks for adverse pregnancy outcomes were observed after paternal exposure in 13 pregnancies with known outcome. Conclusions No indication for a substantially increased malformation risk was observed. Considering the limitations of global safety databases, the data do not yet prove safety, but provide information for physicians and patients to make informed decisions. This is particularly important after inadvertent exposure to tocilizumab, shortly before or during early pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: There are only few studies with conflicting results on pregnancy outcome after paternal exposure to azathioprine or 6-mercaptopurine. In our study, pregnancy outcome of 115 prospectively followed pregnancies after paternal exposure to azathioprine or 6-mercaptopurine is compared to a control group of 341 pregnancies. The rate of major malformations was not increased (3.0% in exposed versus 2.2% in the control group). There was no specific pattern of birth defects and no indication for chromosomal aberrations in the exposed group. We observed a higher rate of elective terminations of pregnancy in the exposed group and a non-significant increase of spontaneous abortions (cumulative incidence 19% versus 13%, respectively). Further prospective studies are required to address the question of a possibly increased risk for spontaneous abortion. [Copyright &y& Elsevier]

Analysis of linkage intervals from 125 unrelated families with nonsyndromic X-linked mental retardation (NS-XLMR) has revealed that the respective gene defects are conspicuously clustered in defined regions of the human X-chromosome, with approximately 30% of all mutations being located on the proximal Xp. In 83% of these families, underlying gene defects are not yet known. Our observations should speed up the search for mutations that are still missing and pave the way for the molecular diagnosis of this common disorder. [Copyright &y& Elsevier]