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elp us better understand the molecular mechanisms that are asso-iated with DM induced birth defects.

upported by the RW & MS Goode Trust, US–Israel BiNational Foun-ation (0374352), and the Israeli Science Foundation (0394193).

oi:10.1016/j.reprotox.2010.12.049

he molecular biology of Valproic Acid in the etiology of autism:vidence from molecular genetic studies in a rat model ofutism

.J. Stodgell a, G. Glazko b

Department of Obstetrics/Gynecology, University of Rochester Schoolf Medicine and Dentistry, Rochester, NY 14618, USADepartment of Biostatistics/Computational Biology, University ofochester School of Medicine and Dentistry, Rochester, NY 14618, USA

Valproic Acid (VPA) has long been an effective treatment forertain seizure disorders. More recently, the indications for useave increased to include mania associated with bipolar disorder,igraine headaches and as a chemotherapeutic agent for cancer.PA has long been known to be teratogenic in both humans andnimal models with variable presentation of terata ranging fromrofound neural tube defects, to delays in developmental and learn-

ng milestones, as well as developmental behavioral disorders suchs autism spectrum disorders (ASDs). Some have recommendedhat women of reproductive age on VPA cease taking VPA if theyish to become pregnant. However, this may not be practical in all

ases, especially if VPA is effective in its treatment of the conditionsor which it is prescribed.

The risk for autism spectrum disorders (ASDs) is increased asuch as 20-fold when the fetus is exposed to VPA. Further, evidence

upporting VPA’s role in ASD’s stems from the neuroanatomicalnd behavioral similarities seen between cases of ASDs, and ratsxposed to VPA in utero. Having a better understanding of theolecular and genetic and molecular mechanisms that are affected

n the embryo and fetus may provide important information aboutPA’s teratogenicity. This may, in turn, allow for the developmentf better alternatives of VPA. This presentation will discuss the evi-ence for VPA’s involvement in ASDs, and how we are using rodentodels to understand the molecular genetic events that lead to the

euroanatomical and behavioral deficits seen after exposure.

upported in part by RW & MS Goode Trust.

oi:10.1016/j.reprotox.2010.12.050

regnancy outcome after in-utero exposure toethylphenidate: A prospective comparative cohort study

ebecka Wajnberg a, Orna Diav-Citrin a, Svetlana Shechtman a,sher Ornoy a,b,∗

The Israeli Teratology Information Service, Israel Ministry of Health,erusalem, IsraelThe Hebrew University Hadassah Medical School, Jerusalem, Israel

Introduction: Methylphenidate is a central nervous systemtimulant medicinally used in the treatment of attention deficitisorder with or without hyperactivity (ADD/ADHD). The preva-

ence rate of ADD/ADHD is estimated to be 5–8% of school-agedhildren. In recent years, methylphenidate is increasingly pre-

cribed in children and young adults. Pregnancy human experienceith methylphenidate is scant and partly derived from womenho abused it. In a study examining IV pentazocine andethylphenidate abuse there was a high rate of preterm deliver-

es, growth restriction and withdrawal symptoms after birth. The

ctive Toxicology 31 (2011) 255–268 267

primary objective of the present study was to evaluate the risk ofmajor anomalies after pregnancy exposure to methylphenidate formedical indications.

Methods: Callers who contacted the Israeli teratology infor-mation service (TIS) between 2005 and 2009 in regard tomethyphenidate exposure during pregnancy were prospectivelycollected and followed-up.

Results: We followed-up 54 methylphenidate-exposed preg-nancies [52/54 (96%) in the first trimester]. The outcome wascompared to that of 54 pregnancies who contacted the IsraeliTIS in regard to exposure not known to be teratogenic, matchedby maternal age, gestational age at initial contact, and year. Therate of major congenital anomalies was comparable between thegroups [0/46 (0%) in the methylphenidate first trimester exposedgroup vs. 2/51 (3.9%), p = 0.496]. Genetic or cytogenetic anoma-lies were excluded from the analysis. There were no significantdifferences in the rate of live-births, miscarriages, or elective termi-nations of pregnancy between the groups. The median gestationalage at delivery [39 (38–40) in both groups, p = 0.310] and birthweight [3293 (2990–3500) methylphenidate vs. 3300 (3000–3600),p = 0.879] were also comparable.

Conclusion: The present study suggests that treatment withmethylphenidate in pregnancy does not seem to be a major humanteratogen and does not adversely affect the gestational age atdelivery or neonatal birth weight. Further studies are required toestablish its pregnancy safety.

doi:10.1016/j.reprotox.2010.12.051

Pregnancy outcomes in women exposed to adalimumab orinfliximab: The experience of the Berlin Institute for ClinicalTeratology and Drug Risk Assessment in Pregnancy

Corinna Weber-Schoendorfer ∗, Juliane Fritzsche, Christof Schaefer

Pharmakovigilanzzentrum Embryonaltoxikologie BBGes/Charité Uni-versitätsmedizin Berlin, Germany

Introduction: Infliximab and adalimumab are TNF-� blocking,IgG1 monoclonal antibodies (mabs) mainly used in the treatmentof severe rheumatoid arthritis, Crohn’s disease, and other autoim-mune diseases. Women of reproductive age are often affected, butexperience of mabs in pregnancy is still limited, although their usehas been steadily increasing. This is reflected by an increasing num-ber of inquiries to our institute: 0.04% of all consultations in 1999,and 1.3% in 2010. IgGs are large molecules that can hardly reachthe embryo during the 1st trimester. This is consistent with theexperience with infliximab during the 1st trimester not suggestingteratogenicity so far. Later in pregnancy, transplacental transfer iswell documented for infliximab. However, it is unknown, whetheror not the inhibition of TNF-� affects the development of the fetus.Experience with adalimumab during the 1st trimester is scarce andtransplacental transfer has been assumed but not been demon-strated by now. The aim of our study is to screen for teratogenicsignals and for possible effects after long-term exposure.

Methods: Prospectively ascertained case series with pregnancyoutcome after infliximab or adalimumab exposure during preg-nancy.

Results: In 85 cases we could initiate the follow-up procedure,which has been completed in 28 adalimumab and in 25 inflix-imab exposed pregnancies. There were 2 miscarriages each and2 voluntary terminations of pregnancy in the adalimumab and 1

in the infliximab cohort. Four of 24 live born infants exposed toadalimumab, and 4 of 22 exposed to infliximab were premature.There were 1 infant after intrauterine adalimumab exposure withan autosomal dominant disease inherited from his father and 2after infliximab exposure with a major birth defect (ventricular