Organization Of Teratology Information Specialists Research Articles

Paternal Valproate Treatment and Risk of Childhood Neurodevelopmental Disorders: Precautionary Regulatory Measures Are Insufficiently Substantiated.

On January 12, 2024 the safety committee of the European Medicines Agency (EMA) recommended precautionary measures over a potential risk of neurodevelopmental disorders in children born to men treated with valproate. These new measures recommend patient supervision by a specialist in the management of epilepsy, bipolar disorder, or migraine. In the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) issued a far more stringent precaution, warning against prescribing valproate to anyone under 55 years of age. We, members of the European Network of Teratology Information Services (ENTIS) and the Organization of Teratology Information Specialists (OTIS), believe that the EMA and MHRA warnings were premature. We are of the opinion that the underlying scientific data do not convincingly substantiate the inference of a paternally mediated risk from valproate to children, much less to an extent that justifies these far-reaching recommendations.

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.

The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs). Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible.

S751 The Vedolizumab Pregnancy Exposure Registry: An OTIS Pregnancy Study Update

Introduction: Vedolizumab is a gut-selective immunoglobulin (Ig) G1 monoclonal antibody that binds to α4β7 integrin; it is approved for the treatment of moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC) in the U.S. and elsewhere. Published studies on the effect of vedolizumab in human pregnancy are limited. Data from the ongoing Vedolizumab Pregnancy Exposure Registry (NCT02678052) in the U.S. and Canada have been collected by the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS). This prospective observational pregnancy cohort study planned to enroll and analyze the outcomes of 100 vedolizumab-exposed (Vedo) participants compared to 100 disease-matched (DM) and 100 healthy comparison (HC) participants. Methods: Pregnant women treated with vedolizumab for UC or CD with at least one dose in the first trimester were enrolled in the Vedo group. Pregnant women with UC or CD but no exposure to vedolizumab were enrolled in the DM group. Pregnant women with no exposure to any biologic during pregnancy and not diagnosed with an auto-inflammatory or other exclusionary disease were enrolled in the HC group. Data were collected from telephone interviews and maternal and pediatric medical records; live-born children were followed to one year of age with a dysmorphological examination and developmental screening. The Short Quality of Life in Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to women with CD or UC. Results: Between December 2015 and March 2022, outcomes were collected for 301 women, 98 in the Vedo group, 104 in the DM group, and 99 in the HC group. SIBDQ mean scores were similar in the Vedo group, 5.8 (SD 1.0) and the DM group, 5.9 (SD 1.0). Preliminary descriptive outcome data are shown in Table. In the Vedo group 7.3% of pregnancies resulted in a fetus or infant with a major birth defect, compared to 7.8% in the DM group, and 4.7% in the HC group. No pattern of major birth defects was identified in the Vedo group. Conclusion: The proportion of pregnancies with vedolizumab exposure resulting in a major birth defect are similar to proportions in the disease comparison group, and did not represent a specific pattern. The Vedolizumab Pregnancy Exposure Registry is ongoing with formal statistical analysis planned once the study is completed in 2023. Table 1. - Pregnancy Outcomes in the Study Cohort Vedo-Total(N=98) DM-Total(N=104) HC-Total(N=99) Pregnancies ending with live born infant - n/N (%) 93/98 (94.9) 99/104 (95.2) 85/99 (85.9) Spontaneous abortion – N (Left Truncation Accounted Rate a ) 3 (8.7%) 3 (6.1%) 1 (6.4%) Termination - n/N (%) 0/98 (0.0) 0/104 (0.0) 0/99 (0.0) Stillbirth - n/N (%) 0/98 (0.0) 1/104 (1.0) 0/99 (0.0) Lost to follow-up (LTFU) - n/N (%) 2/98 (2.0) 1/104 (1.0) 13/99 (13.1) Preterm delivery – N (Rate b ) 13 (14.5%) 6 (6.1%) 6 (7.2%) Birth weight full term infants – mean g (SD) 3410.4 (436.7) 3428.8 (454.0) 3308.1 (432.3) Number of pregnancies with major birth defects among all pregnancies excluding LTFU – n/N’ (%) 7/96 (7.3) 8/103 (7.8) 4/86 (4.7) Serious infections in live born infants up to 1 year of age – n/N’(%) c 3/97 (3.1) 2/99 (2.0) 1/88 (1.1) Ages and Stages Screening at 1 year of age with concern – n/N’ (%) c 10/66 (15.2) 20/87 (23.0) 11/59 (18.6) aSpontaneous abortion rate computed using Fleming-Harrington estimate at 20 weeks' gestation, accounting for left truncation because women can enroll at various times in gestation;bComputed using Fleming-Harrington estimate at 37 weeks' gestation;cIncludes twins; % = (n/N') * 100. N' at each category: Number of pregnancies meeting the criteria specified in the row title.

717 The Vedolizumab Pregnancy Exposure Registry: An OTIS Pregnancy Study Update

INTRODUCTION: Vedolizumab is a gut-selective immunoglobulin (Ig) G1 monoclonal antibody that binds to α4β7 integrin; it is approved for the treatment of moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) in the U.S. and elsewhere. Published studies on the effect of vedolizumab during human pregnancy are limited. Data from the ongoing Vedolizumab Pregnancy Exposure Registry (NCT02678052) in the U.S. and Canada have been collected by the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS). This prospective observational cohort study intends to enroll and analyze the outcomes of 100 vedolizumab-exposed participants compared to 100 disease-matched (DM) comparison and 100 healthy comparison (HC) participants. This abstract describes progress of the study through March 1, 2019. METHODS: Pregnant women treated with vedolizumab for UC or CD for at least some part of the first trimester were enrolled in the vedolizumab-exposed group. Pregnant women with no exposure to vedolizumab were enrolled in a DM comparison group. Pregnant women with no exposure to any biologic during pregnancy and not diagnosed with an autoimmune disease or any other disease as defined by the OTIS Research Center were enrolled in a HC group. Pregnancy exposure and outcome data were collected from telephone interviews and medical records. The Short Quality of Life in Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to women with CD or UC at enrollment and 32 weeks' gestation. Follow-up of live born children included a dysmorphological exam, pediatric records review and developmental screening at one year of age. RESULTS: Between December 2015 and March 2019, outcomes were collected for 223 women, 53 in the vedolizumab group, 88 in the DM group, and 82 in the HC group. Preliminary descriptive data are shown in Table 1. No major structural birth defects were reported in the vedolizumab group, compared to 5 (5.7%) in the DM group, and 4 (5.3%) in the HC group. There was no evidence of a pattern of minor structural defects in the vedolizumab group. CONCLUSION: Updated data indicate pregnant women treated with vedolizumab in at least the 1st trimester have similar birth outcomes to disease-matched and healthy comparison women. The Vedolizumab Pregnancy Exposure Registry is ongoing with formal statistical analysis to be performed when the study is completed.

Oseltamivir use in pregnancy: Risk of birth defects, preterm delivery, and small for gestational age infants.

Influenza infection during pregnancy increases risks for adverse outcomes for both mother and fetus. For this reason, treatment for infection or postexposure prophylaxis with a neuraminidase inhibitor, such as oseltamivir, may be needed. Between 2009 and 2017, the Organization of Teratology Information Specialists (OTIS) MotherToBaby Pregnancy Studies enrolled pregnant women in the United States and Canada who were or were not treated with oseltamivir in a prospective cohort study. Data were collected on major birth defects, spontaneous abortion, preterm delivery, and small for gestational age birth size. Crude relative risks (RRs) or hazard ratios (HRs) were estimated together with 95% confidence intervals (CIs) for these outcomes. There were 716 subjects available for analysis; 112 were exposed to oseltamivir sometime in pregnancy and 604 were unexposed. 2/30 (6.7%) first-trimester-exposed pregnancies resulted in a fetus or infant with one or more major birth defects compared to 48/604 (7.9%) in the unexposed cohort (RR 0.84, 95% CI 0.19, 2.80). There were no spontaneous abortions reported. Risk of preterm delivery was not elevated in exposed versus comparison women (HR 0.65, 95% CI 0.26, 1.63). RRs for small for gestational age infants on weight, length, and head circumference following oseltamivir exposure anytime in pregnancy ranged from 0.70 to 1.30 with all 95% CIs including 1. We found no evidence of increased risks with oseltamivir for any of the outcomes evaluated. While numbers are small, these data are reassuring for pregnant women who need to be treated for infection or for postexposure prophylaxis.

Factors Associated With Preterm Delivery Among Women With Rheumatoid Arthritis and Women With Juvenile Idiopathic Arthritis.

Pregnant women with inflammatory arthritis may be at increased risk for preterm delivery (PTD), yet it is unclear what drives this risk. This aim of this prospective cohort study of pregnant women with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), or healthier comparison women was to analyze the independent effects of maternal disease activity, medication use, and comorbid pregnancy conditions on PTD risk. Women were enrolled before 19 weeks completed gestation as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project. Data on pregnancy events, medications, disease activity, and outcomes were obtained by maternal report and validated by medical records. Poisson regression with robust standard errors estimated risk ratios (RR), multivariable adjusted risk ratios (ARRs), and 95% confidence intervals (95% CIs). A total of 657 women with RA, 170 with JIA, and 564 comparison women without autoimmune disease who delivered live born infants, from 2004 to 2017 were included for analysis. Both the RA and JIA groups had an increased risk of PTD versus the comparison group (RR 2.09 [95% CI 1.50-2.91] and RR 1.81 [95% CI 1.14-2.89], respectively). Active RA at enrollment (ARR 1.58 [95% CI 1.10-2.27]) and any time during pregnancy (ARR 1.52 [95% CI 1.06-2.18]) was associated with PTD. Corticosteroid use in every trimester was associated with an approximate 2- to 5-fold increased risk for PTD for both arthritis groups, independent of disease activity. Women with RA and women with JIA are at increased risk for PTD. Maternal disease activity and corticosteroid use may contribute to some of this excess risk.

No Association of Discontinuing Tumor Necrosis Factor Inhibitors Before Gestational Week Twenty in Well-Controlled Rheumatoid Arthritis and Juvenile Idiopathic Arthritis With a Disease Worsening in Late Pregnancy.

To investigate whether the discontinuation of tumor necrosis factor inhibitors (TNFi) during pregnancy is associated with any changes of the disease course in women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Pregnant women with RA and JIA from the US and Canada were enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project, a prospective cohort study. Information about medication and disease activity (patient-reported outcome measures) was collected prior to gestational week 20 and at gestational week 32. Associations between patterns of TNFi continuation or discontinuation and disease activity changes were tested in unadjusted and multivariate analyses. Among 490 women (397 with RA, 93 with JIA) enrolled between 2005 and 2017, 122 (24.9%) discontinued a TNFi before gestational week 20, 201 (41.0%) received a TNFi beyond week 20, and 167 (34.1%) did not receive a TNFi during pregnancy. At the time of enrollment, disease activity was low to minimal in 72.9% of women. TNFi discontinuation was not associated with a clinically important worsening of patient reported outcome measures at the third trimester. Univariate but not multivariate analysis showed that women receiving TNFi beyond week 20 were more likely to experience improved disease activity scores at the third trimester. Discontinuing TNFi before gestational week 20 seems feasible in women with RA and JIA who enter pregnancy with well-controlled disease.

388. Characteristics and outcomes of prospectively reported pregnancies exposed to certolizumab pegol from a safety database

Introduction Anti-tumour necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNFs are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF approved for treatment of rheumatic diseases and/or Crohn’s disease, has no active placental transfer. Objective/Hypothesis To provide information on pregnancy outcomes in women receiving CZP, especially those with early pregnancy exposure. Methods Prospective and retrospective data on maternal CZP exposure, including timing and duration, outcomes, comorbidities, and major malformations were extracted from the UCB Pharma safety database through 6 March 2017. This analysis was limited to prospective reports to avoid bias associated with retrospective submissions. Numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained. Results From a total of 1541 maternal CZP-exposed pregnancies, 1137 were reported prospectively, of which 528 pregnancies (including 10 twins) had 538 known outcomes: 459 live births (85%), 47 miscarriages (9%), 27 elective abortions (5%), and 5 stillbirths (1%). Of the 459 live births, 8 (2%) cases of major congenital malformations were reported. Of the 528 prospective pregnancies with known outcomes, 436 (83%) were exposed to CZP during the 1st trimester, when most organogenesis occurs; 201 (45%) pregnancies were exposed during all 3 trimesters. Discussion This analysis represents the largest published cohort of pregnant women exposed to an anti-TNF for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a malformative effect of CZP compared to the EU general population (2–3%), nor an increased risk of foetal death. These data are reassuring for women of childbearing age considering treatment with CZP, however, the ongoing collection of post-marketing surveillance data, including the ongoing MotherToBaby study from the Organization of Teratology Information Specialists, will provide further important information.

Risk of infantile hemangiomas in the offspring of women with autoimmune disease and the pathogenic implications of these lesions.

The purpose of this study was to analyze the risk of maternal autoimmune disease or associated treatments on infantile hemangiomas (IHs), a common benign vascular tumor in infants, and to better understand how maternal chronic inflammation may play a factor in the pathogenesis of these lesions. Eligible women from the United States and Canada who enrolled before 19 weeks' gestation and delivered at least one live born infant were recruited as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project from 2004-2013. A total of 51/969 (5.3%) and 8/240 (3.3%) infants with IH were born to mothers with and without autoimmune disease, respectively (OR 1.61; 95%CI, 0.75-.44). The presence of ulcerative colitis (UC) in the mother was significantly associated with IH in the child (OR 3.46; 95%CI, 1.29-9.26). The five largest IH occurred within the autoimmune disease cohort and to women taking a biologic medication. These results imply that UC may be a risk factor for IH development, and that chronic inflammation may influence the development of these lesions. This potential link between IH and autoimmune disease warrants further investigation.

Association between CYP2D6 Genotypes and the Risk of Antidepressant Discontinuation, Dosage Modification and the Occurrence of Maternal Depression during Pregnancy.

Importance: Polymorphic expression of drug metabolizing enzymes affects the metabolism of antidepressants, and thus can contribute to drug response and/or adverse events. Pregnancy itself can affect CYP2D6 activity with profound variations determined by CYP2D6 genotype.Objective: To investigate the association between CYP2D6 genotype and the risk of antidepressant discontinuation, dosage modification, and the occurrence of maternal CYP2D6, Antidepressants, Depression during pregnancy.Setting: Data from the Organization of Teratology Information Specialists (OTIS) Antidepressants in Pregnancy Cohort, 2006–2010, were used. Women were eligible if they were within 14 completed weeks of pregnancy at recruitment and exposed to an antidepressant or having any exposures considered non-teratogenic.Main Outcomes and Measures: Gestational antidepressant usage was self-reported and defined as continuous/discontinued use, and non-use; dosage modification was further documented. Maternal depression and anxiety were measured every trimester using the telephone interviewer-administered Edinburgh Postnatal Depression Scale and the Beck Anxiety Inventory, respectively. Saliva samples were collected and used for CYP2D6 genotype analyses. Logistic regression models were used to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals.Results: A total of 246 pregnant women were included in the study. The majority were normal metabolizers (NM, n = 204, 83%); 3.3% (n = 8) were ultrarapid metabolizers (UM), 5.7% (n = 14) poor metabolizers (PM), and 8.1% (n = 20) intermediate metabolizers (IM). Among study subjects, 139 women were treated with antidepressants at the beginning of pregnancy, and 21 antidepressant users (15%) discontinued therapy during pregnancy. Adjusting for depressive symptoms, and other potential confounders, the risk of discontinuing antidepressants during pregnancy was nearly four times higher in slow metabolizers (poor or intermediate metabolizers) compared to those with a faster metabolism rate (normal or ultrarapid metabolizers), aOR = 3.57 (95% CI: 1.15-11.11). Predicted CYP2D6 metabolizer status did not impact dosage modifications. Compared with slow metabolizers, significantly higher proportion of women in the fast metabolizer group had depressive symptom in the first trimester (19.81 vs. 5.88%, P = 0.049). Almost 21% of treated women remained depressed during pregnancy (14.4% NM-UM; 6.1% PM-IM).Conclusions and Relevance: Prior knowledge of CYP2D6 genotype may help to identify pregnant women at greater risk of antidepressant discontinuation. Twenty percent of women exposed to antidepressants during pregnancy remained depressed, indicating an urgent need for personalized treatment of depression during pregnancy.

Consistency of maternal telephone administration of the asthma control test using postpartum recall compared to repeated measures during pregnancy

ABSTRACTBackground: Suboptimal asthma control during pregnancy may impact perinatal outcomes. U.S. guidelines recommend questionnaires to assess asthma control including the Asthma Control Test (ACT). It is unknown in a research setting to what extent recall differs by the time between symptom occurrence and the administration of the questionnaire. Methods: Between 2009–2014, 196 pregnant asthmatic women were recruited by the Organization of Teratology Information Specialists (OTIS) MotherToBaby Pregnancy Studies. Participants were administered the ACT at enrollment, gestational weeks 20 and 32, and shortly after delivery. The same women were also administered the ACT retrospectively at approximately 6 months postpartum. Results: The Pearson correlation coefficients between the in-pregnancy and retrospective continuous ACT scores for the 1st, 2nd and 3rd trimesters were: 0.67 (95% CI: 0.58, 0.74), 0.61 (0.52, 0.70) and 0.65 (0.56, 0.72), respectively. When dichotomized into well-controlled asthma (ACT score ≥ 20) versus otherwise, the chi-square test for all three trimesters resulted in p values <0.0001. Cohen's Kappa statistics for the same dichotomized scores were 0.51, 0.45 and 0.40 for each trimester respectively. There was no evidence that adverse outcome of pregnancy (recall bias) influenced postpartum responses. Conclusions: The retrospectively recalled ACT score obtained postpartum was substantially different compared to in-pregnancy administration of the same questionnaire which could reflect test-retest variability as well as attenuation of recall. Documentation of the magnitude and direction of these differences could be useful in interpretation of the impact of asthma control when the ACT is used in retrospective case-control studies for pregnancy outcomes.

Pregnancy and lactation advice: How does Australian Product Information compare with established information resources?

Product information is a popular medicines information resource; however, there is some evidence that its pregnancy and lactation information is overconservative, which can lead to inadequate treatment of pregnant and lactating women. A thorough analysis of pregnancy and lactation information within Australian Product Information and Consumer Medicines Information was performed. The statements within these resources were compared with established clinical resources: Australian Medicines Handbook, Therapeutic Guidelines, South Australian Perinatal Practice Guidelines, Organization of Teratology Information Specialists, LactMed, Motherisk and the Pregnancy and Breastfeeding Medicines Guide published by the Royal Women's Hospital Melbourne. Product Information was found to be the most cautious resource, with 44.5% of pregnancy recommendations and 69% of lactation recommendations reviewed being more conservative than other resources. Product Information is an imperfect and often overconservative reference for pregnant and lactating women. Health professionals are urged to review established clinical resources to inform decision making.

The ASQ and R-PDQ telephone-administered validation within the OTIS antidepressant in pregnancy study.

This study aimed to assess the telephone administration of the 12-month Ages and Stages Questionnaire (ASQ) and the 9- to 24-month Revised Prescreening Denver Questionnaire (R-PDQ) using the Antidepressants in Pregnancy Study cohort from the Organization of Teratology Information Specialists. The ASQ includes five domains (communication, gross motor, fine motor, problem-solving, and personal-social). The R-PDQ tests four areas of development (gross motor, fine motor, personal-social, and language). Both instruments were self and telephone-administered to mothers at 12 months postpartum. Concordance between the telephone and self-administration was assessed with intraclass correlation coefficients (ICCs) with 95% CIs. For the ASQ, concordance between test scores was substantial for the communication scale (ICC = 0.76, 95% CI [0.63, 0.85]), almost perfect for the gross motor scale (ICC = 0.83, 95% CI [0.73, 0.89]), and moderate for the fine motor, problem-solving, and personal-social scales (ICC = 0.43, 95% CI [0.19, 0.61]; ICC = 0.42, 95% CI [0.19, 0.61]; and ICC = 0.50, 95% CI [0.29, 0.67], respectively). Regarding the R-PDQ, concordance between test scores was as follows: gross motor (ICC = 0.90, 95% CI [0.83, 0.94]), language (ICC = 0.57, 95% CI [0.36, 0.73]), and personal-social scales (ICC = 0.26, 95% CI [0.00, 0.49]). For the fine motor scale, the correlation between both modes was 100%. The 12-month ASQ telephone administration could be an alternative for children developmental screening. Except the personal-social scale, the 9- to 24-month R-PDQ could be telephone-administered for prescreening development.

Influenza vaccine safety in pregnancy: can we identify exposures?

To assess the feasibility of identifying influenza vaccine exposure in pregnancy. Two study designs were used. (i) Women who contacted the Organization of Teratology Information Specialists (OTIS) network and were referred to their research center or contacted the center directly were invited to participate. (ii) Vaccine exposure information was gathered within an ongoing case-control surveillance program, the Slone Birth Defects Study (BDS). To confirm vaccine exposure and obtain details (e.g., brand name, presence of thimerosal), we requested medical records. If records were not available, we contacted the provider for information regarding the vaccine product used in that setting. If the provider used only one vaccine product during the reported exposure period, we assumed those vaccine details applied to the reported exposure. Otherwise, no details could be inferred. Between September 2006 and February 2008, OTIS enrolled 106 women who reported influenza vaccine exposure during pregnancy. Vaccine was confirmed for 100 (94.3%); brand was confirmed for 87 (82.1%). Among 2177 BDS interviews completed during the same period, 462 (20.8%) reported influenza vaccine exposure; brand and formulation were available for 314 (69.5%). Over one quarter of the BDS women (29%) received their vaccine in nontraditional settings, where influenza vaccine exposure would not likely be recorded in their medical record. We demonstrated the capacity both to identify influenza vaccine exposure in pregnancy and to obtain important details of the specific vaccine administered. Many women receive influenza vaccines outside of typical health care settings, which has important implications for influenza vaccine studies that rely on medical records.

Pregnancy outcome in women exposed to leflunomide before or during pregnancy

Findings from animal studies have suggested that leflunomide may be a human teratogen. In the only human cohort study published to date, an increase in adverse outcomes in pregnancies after exposure to leflunomide was not detected. The aim of the present analysis was to expand on the previously published data with a description of birth outcomes among women who did not meet the previous cohort study criteria but who were exposed to leflunomide either during pregnancy or prior to conception. Data on pregnancy exposures and outcomes were collected from 45 pregnant women who had contacted counseling services of the Organization of Teratology Information Specialists in the US or Canada between 1999 and 2009. Sixteen women were exposed to leflunomide during the first trimester of pregnancy and 29 women were exposed preconception. All 16 of the pregnancies with leflunomide exposure during pregnancy and 27 (93%) of the pregnancies with exposure prior to conception resulted in liveborn infants. There were 2 infants with major malformations from mothers who were exposed during pregnancy, and no malformations reported in the preconception group. There was a potential known alternative etiology for at least some of the defects observed. These data provide additional reassurance to women who inadvertently become pregnant while taking leflunomide and who undergo the washout procedure, as well as women who discontinue the medication prior to conception but have no prepregnancy documentation of drug clearance. However, until more conclusive data become available, women receiving leflunomide should be advised to use contraceptive methods and avoid pregnancy.

Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis

Data on pregnancy outcomes among women with psoriasis are lacking. However, there are several known comorbidities of psoriasis, including obesity, smoking and depression, each of which increases the risk for negative birth outcomes. To determine if pregnant women with psoriasis have an excess of potentially modifiable risk factors for adverse pregnancy outcomes. Prospectively collected data from the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project were analysed to compare the prevalence of selected risk factors between 170 pregnant women with psoriasis and 158 nondiseased controls. Women with psoriasis were more likely to be overweight/obese prior to pregnancy (P < 0.0001), to smoke (P < 0.0001), or to have a diagnosis of depression (P = 0.03), and were less likely to have been taking preconceptional vitamin supplements (P = 0.004). After controlling for race/ethnicity and socioeconomic status, women with psoriasis were 2.37 (95% confidence interval 1.45-3.87) times more likely to be overweight/obese as women without psoriasis. Duration of disease, age at onset, measures of disease impact during pregnancy, or use of biologics in pregnancy were not significant predictors of overweight/obesity in the subset of psoriatic women. Pregnant women with psoriasis may be at increased risk for adverse pregnancy outcomes due to comorbidities or other health behaviours associated with the disease. These should be taken into consideration during clinical treatment of women with psoriasis who are in their childbearing years.

Use of biological therapy during pregnancy in the treatment of IBD

Ulcerative colitis and Crohn′s disease often occur in the younger population, which means they are likely to affect women of child-bearing age. Infliximab and adalimumab, both biological therapies, are being increasingly used to treat moderate-to-severe inflammatory bowel disease (IBD) when response to conventional therapy has been lost. Current practice contraindicates their use during pregnancy, as teratogenic effects are not fully known. Incidental use and the ongoing Crohn′s Therapy, Resource, Evaluation and Assessment Tool (TREAT) registry and Organization of Teratology Information Specialists (OTIS) studies provide evidence to support their use. This article reviews available literature to provide an insight for healthcare professionals into the risks and benefits of the use of biological therapy during pregnancy for the IBD patient, thus allowing for thorough and thoughtful counselling.

Better data needed from pregnancy registries

This article is a consensus position statement from the Research Committee of the Organization of Teratology Information Specialists (OTIS). The Committee believes that more specific information on the timing and dose of drug exposures from pregnancy birth defect registries sponsored by pharmaceutical companies (herein called pregnancy registries) would improve the estimation of risk for developmental toxicity (i.e., growth alteration, structural anomalies, functional/neurobehavioral deficits, or death). Specifically, the Committee believes that the exposure timing should be stated in gestational weeks and days rather than simply weeks. In addition, the Committee believes that the exposure dose should be stated in patient-specific terms, such as body weight (mg/kg) or body surface area (mg/m(2)) rather than simply dose strength. Although the focus of this position is pregnancy registries, it also is applicable to any source of medication-induced embryo-fetal toxicity.

Pregnancy Outcomes in Women Exposed to Adalimumab

Purpose: The fully human, anti-tumor necrosis factor monoclonal antibody adalimumab is approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and psoriasis in the United States, Europe, and elsewhere, as well as for juvenile idiopathic arthritis in the United States. Methods: This report describes preliminary outcomes from an ongoing study of the safety of adalimumab in RA patients during pregnancy conducted by the Organization of Teratology Information Specialists (OTIS). Through a prospective cohort design, women with RA treated with adalimumab during the first trimester of pregnancy were followed for 1-year postpartum. Pregnancy outcomes were compared with those from a disease-matched group of pregnant women with RA who had not been treated with adalimumab during their pregnancies, and a non-diseased group of women who neither had RA nor had been treated with adalimumab. In addition to conducting the cohort study, the OTIS investigators also collected information on adalimumab-exposed pregnancies that did not meet the cohort criteria, but were followed as a case series. The case-series pregnancies are presented separately as they have no comparison group. They include patients treated for diseases other than RA, as well as retrospectively reported outcomes. Results: As of May 15, 2008 (4 years of the study), pregnancy outcomes were available for 126 women in the cohort (Table). Two major structural defects (6.6%) had been reported for 30 women with adalimumab exposure during their first trimesters for whom pregnancy outcomes were known: 1 with undescended testicle and 1 with microcephaly. For 51 pregnancies in the disease-matched comparison group for which pregnancy outcomes were known, 1 fetus (2.0%) was diagnosed with chromosomal abnormalities. Two major structural defects (5.1%) have been reported via 39 pregnancies with known outcomes in the healthy comparison group. In the case-series group (data not included in the Table), of the 66 known outcomes, 7 (10.6%) resulted in major congenital defects — 3 chromosomal anomalies, 1 spina bifida with hydrocephalus, 1 ventricular septal defect, 1 congenital hip dysplasia with inguinal hernia, and 1 congenital hypothyroidism. Of these 66 known outcomes in the case series, 23 had a diagnosis of Crohn's disease.Table: Pregnancy Outcomes in the OTIS Cohort StudyConclusion: Based on these preliminary data, no concerns have been raised regarding increased risks for adverse pregnancy outcomes associated with early pregnancy exposure to adalimumab in the treatment of RA. Firm conclusions await accumulation of sufficient sample size in this prospective cohort study. In Fall 2008, the OTIS cohort study will expand enrollment to include patients with Crohn's disease.

Addressing Concerns of Pregnant and Lactating Women After the 2005 Hurricanes

Natural disasters are devastating for anyone affected, but pregnant and breastfeeding women often have specific concerns about the effects of certain exposures (such as infections, chemicals, medications, and stress) on their fetus or breastfed child. For this reason, the Organization of Teratology Information Specialists (OTIS) and the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention partnered to provide information for women and healthcare professionals about the effects of exposures on pregnancy and breastfeeding after the hurricanes of 2005. This service expanded on OTIS's existing telephone counseling and fact sheets. Through this project, fact sheets were created to address specific potential concerns regarding exposures after the hurricanes. The OTIS national toll-free telephone number also was modified to accommodate questions regarding hurricane-related exposures, and several strategies were used to publicize this number as a resource for obtaining hurricane-related exposure information related to pregnancy and breastfeeding. This article describes OTIS's response after the 2005 hurricanes, the challenges encountered in implementing the response, and lessons learned that might be useful to improve the response to the unique needs of this special population after any disaster or public health emergency.