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Pregnancy outcomes after exposure to etanercept
260
Free communications and posters / Reproductive Toxicology 31 (2011) 255–268
Pregnancy outcomes after exposure to etanercept Stefanie fer
Hultzsch ∗ ,
Corinna Weber-Schoendorfer, Christof Schae-
Pharmakovigilanzzentrum Embryonaltoxikologie (Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), BBGes/Charité Universitätsmedizin Berlin, Germany Introduction: There is still uncertainty about the teratogenic potential of the TNF-␣ blocking substance etanercept especially after publication of a case with VACTERL association. Although pregnancy outcome was normal in most published cases it is unknown, whether or not the inhibition of TNF-␣ affects the development of the fetus. Etanercept is a fusion protein consisting of the soluble human tumour necrosis factor (TNF) receptor and the Fc component of human immunoglobulin 1. We have recorded an increasing number of consultations concerning inadvertent etanercept treatment in early pregnancy, reflecting the increasing use of this drug. As women of childbearing age are often affected by rheumatoid diseases we wanted to estimate the risk for birth defects and screen for a specific pattern of anomalies. Methods: Prospectively ascertained case series with pregnancy outcome after maternal etanercept exposure during the first trimester. Results: Out of 55 initiated follow-ups, 34 fulfilled the criteria, of which 26 are completed, 6 are still pending and 2 are lost for follow-up. In three pregnancies treatment duration expanded to the second trimester, two of them being exposed throughout pregnancy. Treatment indication was rheumatoid arthritis in 19, ankylosing spondylitis in six and psoriatic arthritis in one pregnancy. A majority of women also used other immunomodulatory or antiphlogistic drugs. There were two voluntary terminations of pregnancy and five early miscarriages. Of the 19 live births five were premature. Three infants had major birth defects: congenital renal agenesis in one, hypoplastic left heart and hypospadia glandis in another child and a third infant with Wolf–Parkinson–WhiteSyndrome which was detected 6–8 weeks after birth requiring cardioversion with adenosine followed by propafenone therapy. Conclusions: Etanercept remains suspect, although in our prospective case series no VACTERL association or other specific pattern of birth defects was observed. However, due to the limited number of cases, no definite risk estimation can be made.
able recommendations for daily practice. This study aimed at characterizing the risk perception associated with drug use during pregnancy in a sample of Swiss health care professionals. Methods: An online French and German survey was emailed to four Swiss professional societies (Gynecologists, Pediatricians, Mid-wives and Pharmacists). The questionnaire intended (a) to assess the population characteristics and the opinion of the professionals regarding the medication use pattern in their pregnant patients, (b) to evaluate the sources of information used during their practice and finally (c) to assess their risk perception linked to drugs use during pregnancy. Results were analyzed by descriptive statistics and robust linear regression. Results: A total of 1310 questionnaires were collected (18% response rate). Most interviewed health care professionals believe that 30–60% of their pregnant patients are taking at least one treatment during pregnancy and that 60% are adherent to their prescribed treatment. A large majority think, however, that women are anxious about medication use during pregnancy. More than 80% of health professionals commonly use the Swiss Drug Reference Book (Compendium) to assess the risk associated with drugs during pregnancy, despite the uniformly low level of credibility they express about this reference. Except for some gynecologists, the majority of professionals are not aware of or do not use specialized information sources (books, websites or information centers). The risk related to drug intake was overall misjudged. The majority of participants think wrongly that more than 30% of drugs are teratogenic. About 40% of them are not aware of the absence of risk associated with paracetamol intake during pregnancy. Several factors were associated with a higher rate of misperception: non-gynecologist professionals (p < 0.01), female gender (p < 0.01), older age (p < 0.05) and infrequent use of specialized sources of information (p < 0.05). Conclusion: Swiss professionals tend to misjudge the risk associated with drug use during pregnancy. The level of training and awareness of specialized sources offering a more realistic estimation of the risk may protect against this misperception. Further efforts are needed to expand the training and the tools for health care professionals to optimize drug use during pregnancy. 1 These
two authors equally contributed to the work.
doi:10.1016/j.reprotox.2010.12.034 Nanotoxicity in the placenta
doi:10.1016/j.reprotox.2010.12.033 Evaluation of risk perception related to drug use during pregnancy: A Swiss survey A. Jaquet a , U. Winterfeld b , Y. Meyer c , T. Buclin b , C. Csajka a,1 , A. Panchaud b,∗,1 a
Department of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland b Swiss Teratogen Information Service, Division clinical Pharmacology and Toxicology, University Hospital Centre, University of Lausanne, Lausanne, Switzerland c School of Health Sciences – Midwifery Section, Lausanne, Switzerland Introduction: Health care professionals’ perception of risk may impact on the therapeutic management of women during pregnancy. Since the thalidomide tragedy, the use of drugs during pregnancy generates fear. This concern might affect the estimation of the risk associated with drug intake during pregnancy, leading to premature discontinuation of a required treatment, superfluous anxiety or pointless termination of a desired pregnancy. Although data regarding the security of drugs during pregnancy are still scarce, a few specialized information sources exist providing reli-
Herbert Juch a,∗ , Stefanie Krassnig a , Martin Holzapfel-Bauer b , Gottfried Dohr a
Gauster a , Margit
a
Institute for Cellbiology, Histology and Embryology, Medical University Graz, Austria b Department of Obstetrics and Gynaecology, Medical University Graz, Austria Introduction: Nanotechnology is a rapidly developing field. More and more nanomaterials are introduced in medicine, for diagnostic and therapeutic purposes. On the one hand, unique features of e.g. particles in the 1–100 nm dimension range (ultra small size, large surface area to mass ratio) provide novel perspectives for drug development. On the other hand, these specific “nano-properties” have raised concerns among toxicologists and adverse effects have been described. Nanotoxicology is still in its infancy and little is known about nanotoxic effects in the placenta. Our aim was to investigate the effects of SiO2 nanoparticles (Min-U-Sil5) described as toxic due to their size (5 nm) in the placenta explant culture model. Methods: Placenta explants from first trimester placenta (after elective termination of pregnancy) and from term placenta were cultivated for 42 h under physiological pO2 in the presence and
Free communications and posters / Reproductive Toxicology 31 (2011) 255–268
Pregnancy outcomes after exposure to etanercept Stefanie fer
Hultzsch ∗ ,
Corinna Weber-Schoendorfer, Christof Schae-
Pharmakovigilanzzentrum Embryonaltoxikologie (Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), BBGes/Charité Universitätsmedizin Berlin, Germany Introduction: There is still uncertainty about the teratogenic potential of the TNF-␣ blocking substance etanercept especially after publication of a case with VACTERL association. Although pregnancy outcome was normal in most published cases it is unknown, whether or not the inhibition of TNF-␣ affects the development of the fetus. Etanercept is a fusion protein consisting of the soluble human tumour necrosis factor (TNF) receptor and the Fc component of human immunoglobulin 1. We have recorded an increasing number of consultations concerning inadvertent etanercept treatment in early pregnancy, reflecting the increasing use of this drug. As women of childbearing age are often affected by rheumatoid diseases we wanted to estimate the risk for birth defects and screen for a specific pattern of anomalies. Methods: Prospectively ascertained case series with pregnancy outcome after maternal etanercept exposure during the first trimester. Results: Out of 55 initiated follow-ups, 34 fulfilled the criteria, of which 26 are completed, 6 are still pending and 2 are lost for follow-up. In three pregnancies treatment duration expanded to the second trimester, two of them being exposed throughout pregnancy. Treatment indication was rheumatoid arthritis in 19, ankylosing spondylitis in six and psoriatic arthritis in one pregnancy. A majority of women also used other immunomodulatory or antiphlogistic drugs. There were two voluntary terminations of pregnancy and five early miscarriages. Of the 19 live births five were premature. Three infants had major birth defects: congenital renal agenesis in one, hypoplastic left heart and hypospadia glandis in another child and a third infant with Wolf–Parkinson–WhiteSyndrome which was detected 6–8 weeks after birth requiring cardioversion with adenosine followed by propafenone therapy. Conclusions: Etanercept remains suspect, although in our prospective case series no VACTERL association or other specific pattern of birth defects was observed. However, due to the limited number of cases, no definite risk estimation can be made.
able recommendations for daily practice. This study aimed at characterizing the risk perception associated with drug use during pregnancy in a sample of Swiss health care professionals. Methods: An online French and German survey was emailed to four Swiss professional societies (Gynecologists, Pediatricians, Mid-wives and Pharmacists). The questionnaire intended (a) to assess the population characteristics and the opinion of the professionals regarding the medication use pattern in their pregnant patients, (b) to evaluate the sources of information used during their practice and finally (c) to assess their risk perception linked to drugs use during pregnancy. Results were analyzed by descriptive statistics and robust linear regression. Results: A total of 1310 questionnaires were collected (18% response rate). Most interviewed health care professionals believe that 30–60% of their pregnant patients are taking at least one treatment during pregnancy and that 60% are adherent to their prescribed treatment. A large majority think, however, that women are anxious about medication use during pregnancy. More than 80% of health professionals commonly use the Swiss Drug Reference Book (Compendium) to assess the risk associated with drugs during pregnancy, despite the uniformly low level of credibility they express about this reference. Except for some gynecologists, the majority of professionals are not aware of or do not use specialized information sources (books, websites or information centers). The risk related to drug intake was overall misjudged. The majority of participants think wrongly that more than 30% of drugs are teratogenic. About 40% of them are not aware of the absence of risk associated with paracetamol intake during pregnancy. Several factors were associated with a higher rate of misperception: non-gynecologist professionals (p < 0.01), female gender (p < 0.01), older age (p < 0.05) and infrequent use of specialized sources of information (p < 0.05). Conclusion: Swiss professionals tend to misjudge the risk associated with drug use during pregnancy. The level of training and awareness of specialized sources offering a more realistic estimation of the risk may protect against this misperception. Further efforts are needed to expand the training and the tools for health care professionals to optimize drug use during pregnancy. 1 These
two authors equally contributed to the work.
doi:10.1016/j.reprotox.2010.12.034 Nanotoxicity in the placenta
doi:10.1016/j.reprotox.2010.12.033 Evaluation of risk perception related to drug use during pregnancy: A Swiss survey A. Jaquet a , U. Winterfeld b , Y. Meyer c , T. Buclin b , C. Csajka a,1 , A. Panchaud b,∗,1 a
Department of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland b Swiss Teratogen Information Service, Division clinical Pharmacology and Toxicology, University Hospital Centre, University of Lausanne, Lausanne, Switzerland c School of Health Sciences – Midwifery Section, Lausanne, Switzerland Introduction: Health care professionals’ perception of risk may impact on the therapeutic management of women during pregnancy. Since the thalidomide tragedy, the use of drugs during pregnancy generates fear. This concern might affect the estimation of the risk associated with drug intake during pregnancy, leading to premature discontinuation of a required treatment, superfluous anxiety or pointless termination of a desired pregnancy. Although data regarding the security of drugs during pregnancy are still scarce, a few specialized information sources exist providing reli-
Herbert Juch a,∗ , Stefanie Krassnig a , Martin Holzapfel-Bauer b , Gottfried Dohr a
Gauster a , Margit
a
Institute for Cellbiology, Histology and Embryology, Medical University Graz, Austria b Department of Obstetrics and Gynaecology, Medical University Graz, Austria Introduction: Nanotechnology is a rapidly developing field. More and more nanomaterials are introduced in medicine, for diagnostic and therapeutic purposes. On the one hand, unique features of e.g. particles in the 1–100 nm dimension range (ultra small size, large surface area to mass ratio) provide novel perspectives for drug development. On the other hand, these specific “nano-properties” have raised concerns among toxicologists and adverse effects have been described. Nanotoxicology is still in its infancy and little is known about nanotoxic effects in the placenta. Our aim was to investigate the effects of SiO2 nanoparticles (Min-U-Sil5) described as toxic due to their size (5 nm) in the placenta explant culture model. Methods: Placenta explants from first trimester placenta (after elective termination of pregnancy) and from term placenta were cultivated for 42 h under physiological pO2 in the presence and