Workshop report179th ENMC international workshop: Pregnancy in women with neuromuscular disorders: 5–7 November 2010, Naarden, The Netherlands
Introduction
Sixteen doctors and scientists met in Naarden, The Netherlands, from 5 to 7 November 2010 to review current knowledge in the field of pregnancy in women with neuromuscular disease. The group was joined by three patients and their families. Participants were from eight countries, namely Belgium, Finland, France, Germany, Italy, Norway, The Netherlands and the United Kingdom. A variety of disciplines were represented, including neurology, clinical genetics, cardiology, respiratory medicine, obstetrics and gynaecology, epidemiology, ethics, a nurse specialist, and a representative from the ENMC research committee.
Parenthood is a highly desirable aim in life for many couples, and increasingly this also applies to women affected by neuromuscular disorders (NMDs). Little is known about the effect of individual NMD on the course of pregnancy and delivery and conversely the effect of pregnancy on muscles themselves [1]. In the past, many patients have been discouraged from undertaking pregnancy for a variety of reasons.
The overarching aim of the workshop was to harness knowledge about pregnancy in NMD with the intention of improving maternal and fetal outcomes. The workshop was structured to first review existing knowledge in the field, and second to propose practical recommendations for each stage of pregnancy, both in general terms and also specific to individual or groups of conditions, for use by all the specialists involved in a woman’s care. The third aim was to stimulate research and collaborative studies in this area.
Section snippets
Physiological changes in pregnancy and obstetric risks in the general population
Mandish Dhanjal, UK, gave an overview of physiological changes during normal pregnancy. These include (a) haematological effects such as a dilutional anaemia, reduction in total plasma proteins and an increased thromboembolic risk due to increased clotting (and venous stasis), (b) cardiological changes such as a rise in heart rate, stroke volume and thus a rise in cardiac output by 50%, (c) respiratory changes including a rise in tidal volume and oxygen consumption, (d) immunological changes
Metabolic and mitochondrial myopathies and their impact on pregnancy
Marianne de Visser, The Netherlands, discussed metabolic muscle disorders of glycogen and lipid metabolism. She focussed on Pompe disease which has a prevalence of about 1 in 50.000 in Holland and where the late onset form typically presents as a progressive proximal myopathy with respiratory involvement [3]. Anecdotal accounts suggest an exacerbation of weakness associated with delivery. In a larger study of patients with McArdle’s disease, no adverse effects of pregnancy and delivery were
Patient introduction and discussion
Sabine Rudnik-Schöneborn, Germany, introduced two German patients and summarised their experiences with pregnancy. The first patient has a form of LGMD and found that she became weaker from the 6th month of gestation with no subsequent recovery. The second patient was affected by SMA type II and had an uneventful pregnancy with stable motor and lung function [13]. A Dutch patient with SMA type II was introduced by Lieve Page-Christiaens, The Netherlands, and presented a powerful firsthand
Pregnancy and delivery complications and their management
Lieve Page-Christiaens, The Netherlands, addressed important NMDs for which the literature data are available regarding pregnancy: DM1, DM2, SMA, CMT neuropathy, DMD and BMD carriers, FSHD and limb girdle muscular dystrophy (LGMD). She emphasised the process of decision making when contemplating pregnancy. This should start with the alternatives in the preconception planning phase, in particular, when the life span of the mother is reduced, the risk of a pregnancy is high or genetic risks are
Myotonic dystrophies, non-dystrophic myotonias
Catharina Faber, The Netherlands, gave an overview about the obstetric risks in DM1 which are specifically high when the fetus is affected. The combination of fetal clubfeet and polyhydramnios is indicative of congenital DM1 in the fetus and associated with a high risk of blood loss in the mother at delivery. The condition is complex in its multiorgan involvement and genetic mechanism of anticipation. Well-known complications are polyhydramnios, preterm delivery, placental anomalies and a high
Influence of pregnancy on the disease course
Corrado Angelini, Italy, addressed the question of exacerbation of muscle weakness in different NMDs and the factors that might be related to it. According to his own experience, about two thirds of patients with LGMD and DMD symptomatic carriers show worsening in pregnancy [37]. Triggering factors are increasing body weight, metabolic changes and mechanical influences, e.g. diaphragmatic elevation. The depletion of vitamin D stores can aggravate osteoporosis. After delivery muscle weakness may
Hereditary NMDs: genetic risks and reproductive attitudes
Willem Verpoest, Belgium, discussed the possible reproductive options in couples with infertility problems, which is not an issue in most NMDs apart from DM1. He presented data from the long-standing experience with preimplantation genetic diagnosis (PGD) in Belgium. Decision making for PGD includes cognitive appraisal (financial risks, misdiagnosis, success rates and time line), emotional response (pain, physical and psychological burden) and moral judgements regarding the rights and status of
Pregnancy in MND: a pro- and retrospective study in Germany
Sabine Rudnik-Schöneborn and Carina Awater, Germany, introduced the study design in Germany where a pro- and retrospective assessment of pregnancy and delivery in patients with various hereditary NMDs has been conducted since the early 1990s. It requires active participation of patients and has been successfully applied to many different conditions. Meanwhile the study group includes 180 patients of five major disease categories (myotonic dystrophy, muscular dystrophy, CMT disease, SMA,
Recommendations and future work
A major part of the workshop was devoted to recommendations to women with NMD who wish to have children. It was stressed that further research is necessary to improve knowledge and medical advice in indivdual conditions. International platforms like TREAT-NMD can be helpful to stipulate patient registries and international studies.
Participants
Corrado Angelini, Padua, Italy
Carina Awater, Aachen, Germany
Annelien Bredenoord, Utrecht, The Netherlands
Mandish Dhanjal, London, UK
Catharina Faber, Maastricht, The Netherlands
Nicholas Hart, London, UK
Louise Hastings, Newcastle, UK
Anne Kjersti Daltveit, Bergen, Norway
Hanns Lochmüller, Newcastle, UK
Fiona Norwood, London, UK
Lieve Page-Christiaens, Utrecht, The Netherlands
Sabine Rudnik-Schöneborn, Aachen, Germany
Willem Verpoest, Brussels, Belgium
Marianne de Visser, Amsterdam, The Netherlands
Karim
Acknowledgements
This workshop was made possible by the financial support of The European Neuromuscular Centre (ENMC) and ENMC main sponsors: Muskelsvindfonden (Denmark), Deutsche Gesellschaft für Muskelkranke (Germany), Telethon Foundation (Italy), Schweizerische Stiftung für die Erforschung der Muskelkrankheiten (Switzerland), Prinses Beatrix Fonds (The Netherlands), Vereniging Spierziekten Nederland (The Netherlands), Muscular Dystrophy Campaign (UK), and associated members: Association Francaise Contre les
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