Organization Of Teratology Information Services Research Articles

PREGNANCY OUTCOMES FROM TERIFLUNOMIDE CLINICAL STUDIES

Introduction Teriflunomide is a once-daily oral immunomodulator approved for treatment of relapsing–remitting multiple sclerosis. Teriflunomide is the active metabolite of leflunomide, approved for treatment of rheumatoid arthritis since 1998. Evidence from animal models suggests a potential for fetal risk from teriflunomide. Methods Reliable contraception was mandated during teriflunomide trials. Pregnant patients were to discontinue treatment and undergo an accelerated elimination procedure (cholestyramine or activated charcoal). Pregnancies were reported in the teriflunomide clinical database (cut-off October 2013). Results Eighty-three pregnancies were reported in female patients and 22 in partners of male patients; 26 live births occurred in teriflunomide-treated women and 16 occurred in partners of male patients receiving teriflunomide. Newborns whose parents received teriflunomide had no structural defects or functional deficits at birth. The spontaneous abortion rate for female patients was 18.6%–within the range reported in the general population. Conclusions Data from the clinical programme have shown no teratogenic signal for teriflunomide, consistent with findings of the Organization of Teratology Information Services (OTIS) registry, and >2.5 million patient-years of post-marketing data for leflunomide. Current pregnancy numbers are too small to draw firm conclusions. Additional data will be provided by teriflunomide pregnancy registries.

A safety assessment of tumor necrosis factor antagonists during pregnancy

Importance of the field: Disease modifying antirheumatic drugs are being increasingly utilized in the treatment of many autoimmune disorders. TNF-α antagonists have become the standard of care in treating many of these autoimmune diseases. Because these autoimmune disorders often affect women in their childbearing years, the safety of anti-TNF therapy in pregnancy becomes important.Areas covered in this review: We critically review the current literature on anti-TNF therapy safety in pregnancy. The available data regarding the anti-TNFs in the setting of pregnancy from 1999 to the present are reviewed.What the reader will gain: Case reports and small case series have produced conflicting results, yet their results should only be viewed with cautious interest. Two database reviews suggest little to no risk of congenital anomalies, whereas a much larger independent review of the FDA database reveals congenital anomalies born to mothers who were exposed to anti-TNFs during pregnancy. An ongoing prospective registry (Organization of Teratology Information Services) suggests that about 7 – 10% of children born to mothers taking a TNF antagonist during pregnancy are born with congenital anomalies.Take home message: Whether or not these data represent a significant increase, or if a definitive pattern of birth defects exists, remains in question. All these sources have limitations, which are discussed. Further studies are needed to definitively determine the safety and role of anti-TNFs in pregnancy.

Are we coming to terms with tumor necrosis factor inhibition in pregnancy?

Rheumatic diseases commonly affect women of childbearing age, who often receive immunosuppressive treatments that pose risks to the mother and/or fetus during pregnancy. Due to the benefits of early and aggressive treatment of inflammatory arthritis, rheumatologists prescribe tumor necrosis factor (TNF ) inhibitors early in disease and to a large number of patients. According to a recent survey, 44.2% of practicing US rheumatologists prescribe TNF inhibitors for at least half of their patients with rheumatoid arthritis (RA) (1). All commercially available TNF inhibitors are classified by the Food and Drug Administration as pregnancy risk category B: no adverse pregnancy effects have been observed in animal studies, but there have been insufficient controlled human studies. Given the lack of data in humans, it remains unclear how the practicing rheumatologist should manage TNF inhibitor therapy in women of childbearing age. Underscoring this uncertainty, 38–47% of practicing US rheumatologists recently surveyed believe that the TNF inhibitors etanercept and infliximab are contraindicated during pregnancy (2). However, many women taking TNF inhibitors become pregnant. According to an online survey of 1,023 practicing US rheumatologists, 454 patients with RA became pregnant while receiving anti-TNF therapy. Surprisingly, 31.3% of these patients continued taking TNF inhibitors throughout pregnancy (1). Despite the fact that disease severity tends to decrease in roughly three-fourths of pregnant patients with RA (3), rheumatologists may be reluctant to discontinue a medication that has proven effective. The published experience with TNF inhibition during pregnancy consists of a limited number of case reports, series, and ongoing registry data. Most reported exposures to TNF inhibitor therapy occurred prior to or at the time of conception or during the first trimester of pregnancy. In a retrospective study from the Infliximab Safety Database of 96 pregnancies in women (85% with Crohn’s disease) exposed to infliximab prior to or early in pregnancy, 67% resulted in a live birth, 15% in a miscarriage, and 19% in an elective termination (4). This finding is comparable with historical pregnancy outcomes in the general white population of the US reported by the National Center for Health Statistics (5). An interim data analysis by the Organization of Teratology Information Services compared pregnancy outcomes in 32 patients with RA exposed to etanercept or infliximab with outcomes in 74 patients with RA not exposed to anti-TNF therapy, and with 49 nondisease controls. Rates of miscarriage and fetal malformation did not differ significantly among these 3 groups, but there was a significant increase in the rates of preterm delivery and low-birth-weight infants in all patients with RA compared with controls (6), suggesting that the RA disease state rather than TNF inhibitor therapy predisposes patients to these adverse fetal outcomes. Whereas additional studies have also shown increased rates of adverse pregnancy outcomes among women with RA (7,8), including an increased incidence of low-birthweight infants (9), other investigators have failed to confirm these findings (3). In this issue of Arthritis & Rheumatism, Hyrich et al report data from the British Society for Rheumatology Biologics Register on pregnancy outcomes in a series of 32 women with rheumatic diseases (91% with RA) exposed to anti-TNF therapy (10). Of these women, 23 were exposed to TNF inhibitor therapy (74% to etanercept) at the time of conception, and 11 were also receiving either methotrexate or leflunomide. Overall, 69% of these 32 pregnancies resulted in a live birth, 22% in a miscarriage, and 9% in an elective termination, outcomes comparable with previously reJane E. Salmon, MD, Deborah Alpert, MD, PhD: Hospital for Special Surgery–Weill Medical College, Cornell University, New York, New York. Dr. Salmon has received consulting fees (less than $10,000 each) from Amgen and Genentech and owns stock in Amgen, Johnson and Johnson, and Biogen/Idec. Address correspondence and reprint requests to Jane E. Salmon, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail: salmonj@hss.edu. Submitted for publication March 21, 2006; accepted in revised form May 8, 2006.

Asthma medication use in pregnancy and fetal growth

Given the high prevalence of asthma in pregnancy, it is important to understand the relationship between asthma medications and fetal growth in the context of appropriate treatment. This study examines the effect of inhaled corticosteroids, systemic corticosteroids, and beta(2)-agonists on fetal growth in 654 infants born to women with asthma compared with 303 infants born to controls without asthma. Subjects for this prospective study were enrolled throughout North America between 1998 and 2003 and followed up by the Organization of Teratology Information Services. Incidence of small for gestational age (SGA) infants and mean birth size measures were compared among groups. Mean birth weight of full-term infants born to mothers who used systemic corticosteroids (3373 g) was lower than in the beta(2)-agonist group (3552 g) and controls without asthma (3540 g; P < .05) after adjustment for other risk factors. However, no differences in the incidence of SGA for weight were observed among groups. Adjusted mean birth length was slightly shorter in the systemic steroid group compared with controls (P=.02). Incidence of SGA for length and head circumference and mean head circumference did not vary among groups (P>.05). The treatment of asthma with systemic corticosteroids resulted in a deficit of about 200 g in birth weight compared with controls and exclusive beta(2)-agonist users and no increased incidence of SGA. These results suggest that asthma management with beta(2)-agonists and/or inhaled corticosteroids during pregnancy does not impair fetal growth, whereas systemic corticosteroids have a minimal effect which should be weighed against the necessity to control severe asthma.

18th International Conference of the Organization of Teratology Information Services (OTIS), June 24–28, 2005

Birth Defects Research Part A: Clinical and Molecular TeratologyVolume 73, Issue 5 p. 387-394 ProgramFree Access 18th International Conference of the Organization of Teratology Information Services (OTIS), June 24–28, 2005 First published: 11 May 2005 https://doi.org/10.1002/bdra.20159AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume73, Issue5Special Issue: 45th Annul Meeting of the Teratology Society, 29th Annual Meeting of the Neurobehavioral Teratology Society, 24th Annual Meeting of the Behavioral Toxicology Society, 18th International Conference of the Organization of Teratology Information ServicesMay 2005Pages 387-394 RelatedInformation

Postmarketing surveillance for drug safety in pregnancy: The Organization of Teratology Information Services Project

Although medications are frequently used during pregnancy, premarketing studies exclude pregnant women, with the result that maternal and fetal risks of medications are largely unknown prior to marketing. To demonstrate the feasibility of using Teratology Information Services (TISs) to identify potential subjects who may participate in postmarketing surveillance studies regarding medications taken during pregnancy, maternal characteristics and pregnancy exposure data routinely collected from callers to member agencies of the Organization of Teratology Information Services (OTIS) were pooled for two one-month periods. A total of 3536 calls inquiring about 7746 different agents were received from pregnant women. Of the 40 medications about which pregnant women most frequently asked, the top two were nonprescription acetaminophen and pseudoephedrine, three were prescription drugs with a U.S. Food and Drug Administration pregnancy label category D designation, and five were prescription antidepressants. TISs are well positioned to prospectively ascertain medication exposures in large numbers of pregnant women and may be an exceptional resource for conducting postmarketing surveillance for the safety of medications taken during pregnancy.

17th International Conference of the Organization of Teratology Information Services (OTIS), June 25–28, 2004

17^th International Conference of the Organization of Teratology Information Services (OTIS), June 25–28, 2004

16th International Conference of the Organization of Teratology Information Services

Birth Defects Research Part B: Developmental and Reproductive ToxicologyVolume 68, Issue 3 p. 288-298 Program and AbstractsFree Access 16th International Conference of the Organization of Teratology Information Services First published: 13 May 2003 https://doi.org/10.1002/bdrb.10026Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume68, Issue3Special Issue: 43rd Annual Meeting of the Teratology Society, 27th Annual Meeting of the Neurobehavioral Teratology Society, 22nd Annual Meeting of the Behavioral Teratology Society, 16th International Conference of the Organization of Teratology Information ServicesJune 2003Pages 288-298 RelatedInformation

16th International Conference of the Organization of Teratology Information Services (OTIS), June 20–24, 2003

Birth Defects Research Part A: Clinical and Molecular TeratologyVolume 67, Issue 5 p. 384-394 ProgramFree Access 16th International Conference of the Organization of Teratology Information Services (OTIS), June 20–24, 2003 First published: 28 May 2003 https://doi.org/10.1002/bdra.10069AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume67, Issue5Special Issue: 43rd Annual Meeting of the Teratology Society, 27th Annual Meeting of the Neurobehavioral Teratology Society, 22nd Annual Meeting of the Behavioral Teratology Society, 16th International Conference of the Organization of Teratology Information ServicesMay 2003Pages 384-394 RelatedInformation

Fifteenth International Conference of the Organization of Teratology Information Services (OTIS): Program and Abstracts

Fifteenth International Conference of the Organization of Teratology Information Services (OTIS): Program and Abstracts

Postmarketing surveillance for human teratogenicity: a model approach.

Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a single major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this report is to outline a complementary approach that can be used in addition to other more established methods to provide the most comprehensive evaluation of prenatal exposures with respect to teratogenicity. We describe a multicenter prospective cohort study design involving dysmorphological assessment of liveborn infants. This design uses the Organization of Teratology Information Services, a North American network of information providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed. The focused cohort study design allows for evaluation of a spectrum of adverse pregnancy outcomes ranging from spontaneous abortion to functional deficit. While sample sizes are typically inadequate to identify increased risks for single major malformations, the use of dysmorphological examinations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants. As the known human teratogens are generally associated with patterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an acceptable level of confidence regarding the risk or safety of specific exposures during pregnancy.

Use of Psychoactive Medication During Pregnancy and Possible Effects on the Fetus and Newborn

To the Editor. We would like to commend the AAP's Committee on Drugs for a very thorough review, in your April 2000 issue, of the use of psychoactive medications during pregnancy. We were also pleased to see an informative review of the difficulties in using the FDA “Use-in-Pregnancy Ratings” as a guide to prescribing and counseling families with these exposures.However, a few points require clarification. OTIS (Organization of Teratology Information Services) is a 40-member organization of Teratology Information Services (TIS) in the United States and Canada. TIS consists of 3 components: service, education, and research. TIS provides information concerning exposures before and during pregnancy to over 50 000 health care providers and consumers annually. Individual services generally provide didactic presentations in their area of service. Many TIS have become involved in research projects looking at outcomes of pregnancies exposed to numerous agents such as angiotensin-converting enzyme inhibitors, maternal varicella infection, asthma medications, and Arava (a new drug used for rheumatoid arthritis). Most TIS are funded with state-specific monies and are accessible via toll-free phone lines. For information on the TIS in a specific area, please contact the OTIS national headquarters at 1-888-285-3410 or the web site located at www.ucsd.edu/otis.Additionally, OTIS does not coordinate subscriptions to TERIS, although the web site address (http://weber.u.washington.edu/terisweb/teris/index.html) listed is accurate. It should be mentioned that a similar database is also available, REPROTOX, which can be subscribed to at the following web site: http://www.reprotox.org. We would also like to stress that TIS are comprehensive and multidisciplinary resources for consultation regarding prenatal exposures, available to both health care providers and consumers.

Organization of Teratology Information Services (OTIS) Fourteenth Annual Meeting, June 23–June 26, 2001 Program

TeratologyVolume 63, Issue 6 p. 321-324 ProgramFree Access Organization of Teratology Information Services (OTIS) Fourteenth Annual Meeting, June 23–June 26, 2001 Program First published: 17 May 2001 https://doi.org/10.1002/tera.1041Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume63, Issue6June 2001Pages 321-324 RelatedInformation

Mini-review: history of organized teratology information services in North America.

A history of the Organization of Teratology Information Services (OTIS) is presented in context of the history of teratology information services. During the late 1970s, teratology information services grew out of the need for current and accurate information about fetal effects of environmental exposures in pregnancy. Over the next decade, teratology information services networked and collaborated, developing their own professional organization. A description of the activities of OTIS is described.

Organization of Teratology Information Services (OTIS) abstracts

TeratologyVolume 61, Issue 6 p. 520-522 Abstracts Organization of Teratology Information Services (OTIS) abstracts First published: 01 June 2000 https://doi.org/10.1002/1096-9926(200006)61:6<520::AID-TERA8>3.0.CO;2-0Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume61, Issue6June 2000Pages 520-522 RelatedInformation

The Teratology Society 39th annual meeting, June 29-July 4, 1999 and the 11th International Conference of the Organization of Teratology Information Services (OTIS), June 28-July 1, 1999. Keystone, Colorado, USA. Abstracts.

TeratologyVolume 59, Issue 6 p. 375-389 Abstracts Teratology Society Platform Sessions Abstracts First published: 02 June 1999 https://doi.org/10.1002/(SICI)1096-9926(199906)59:6<375::AID-TERA3>3.0.CO;2-4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume59, Issue6June 1999Pages 375-389 RelatedInformation

The Organization of Teratology Information Services (OTIS) Registry Study

Some population-based studies of the risks of gestational medication use are limited by differential recall or enrollment of mothers of children with abnormalities. Prospective acquisition of exposure information, before knowledge of pregnancy outcome, is the most unbiased manner in which to obtain denominator-based outcome information. The Organization of Teratology Information Services (OTIS) Registry Study will prospectively evaluate pregnancy outcomes in relation to exposures to asthma medications. Patients will be enrolled by participating Teratology Information Services. Information regarding medication exposure, asthma severity, and other important medical events will be assessed during pregnancy by means of standardized interviews, supplemented by medical records. Outcome information will be obtained from copies of the pediatric records. Data analysis will evaluate relative risks of adverse outcomes in exposed compared with unexposed asthmatic and nonasthmatic subjects. (J Allergy Clin Immunol 1999;103:S373-6.)

Eleventh International Conference of the Organization of Teratology Information Services (OTIS), June 19‐21, 1998: Program and Abstracts

TeratologyVolume 57, Issue 4-5 p. 277-284 Free Access Eleventh International Conference of the Organization of Teratology Information Services (OTIS), June 19-21, 1998: Program and Abstracts First published: 07 December 1998 https://doi.org/10.1002/(SICI)1096-9926(199804/05)57:4/5<277::AID-TERA13>3.0.CO;2-%23AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume57, Issue4-5April ‐ May 1998Pages 277-284 RelatedInformation

Eleventh International Conference of the Organization of Teratology Information Services (OTIS), June 19-21, 1998: Program and Abstracts

Eleventh International Conference of the Organization of Teratology Information Services (OTIS), June 19-21, 1998: Program and Abstracts

Eleventh International Conference of the Organization of Teratology Information Services (OTIS), June 19‐21, 1998: Program and Abstracts

Eleventh International Conference of the Organization of Teratology Information Services (OTIS), June 19‐21, 1998: Program and Abstracts