48 THYROID-STIMULATING HORMONE (TSH) VALUES IN TWIN VERSUSSINGLETON PREGNANCIES JODI DASHE1, BRIAN CASEY1, DONALDMCINTIRE1, C. EDWARD WELLS1, WILLIAM BYRD1, KENNETH LEVE-NO1, F. GARY CUNNINGHAM1, 1University of Texas Southwestern MedicalCenter, Obstetrics and Gynecology, Dallas, TX

OBJECTIVE: To compare TSH values in twin pregnancies with those ofsingleton pregnancies and non-pregnant adults.

STUDY DESIGN: Prospective observational study in which TSH wasassessed at the initial prenatal visit by using a third-generation chemi-luminescence assay (Immulite 2000, Diagnostic Products Corporation) between12/2000 and 11/2001. Singleton and twin pregnancies that resulted in liveborninfants weighing at least 500 grams were included. Pregnancies were grouped bymonth and trimester of gestation. TSH values were compared with the 2.5th and97.5th percentile values for non-pregnant adults provided by the manufacturer,0.4 mIU/mL and 4.0 mIU/mL, respectively. Analyses were performed by usingWilcoxon signed-rank test and chi-square.

RESULTS: Data are presented below for 13,719 singleton and 132 twinpregnancies. TSH suppression occurred in 30% of twin pregnancies and wasparticularly apparent between 9 and 16 weeks, when median TSH wassignificantly lower in twins than in singletons, P # 0.01. No twin pregnancyhad a TSH value above 4.0.

CONCLUSION: Screening for thyroid disease is problematic in twins, asTSH suppression is even more marked than that found in singletons. If non-pregnant reference ranges are applied to twin pregnancies, 30% will screenpositive for hyperthyroidism, and cases of hypothyroidism may be missed.

49 IN UTERO TRANSPLANTATION OF AUTOLOGOUS AND ALLOGENEICFETAL LIVER STEM CELLS IN FETAL SHEEP DANIEL SURBEK1,ANDREINA SCHOEBERLEIN1, LISBETH DUDLER1, WOLFGANG HOLZ-GREVE1, 1University of Basel, Obstetrics and Gynecology, Basel, Switzerland

OBJECTIVE: The fetus is believed to be immunologically naı̈ve in the firsttrimester of gestation. However, there is growing evidence that immunodefi-ciency in recipients is beneficial for a sustained engraftment of stem cells (SC) inthe fetus. The aim was to compare short-term engraftment of autologous andallogeneic SC in an immunocompetent large animal model.

STUDY DESIGN: Time-mated white alpine ewes were used. As donor SC,either allogeneic male fetal liver cells at 49 days’ gestation or autologous fetalliver cells were collected by using a previously described ultrasound-guidedtechnique. SC suspensions were labeled with PKH26 and cryopreserved untiltransplantation (Tx). SC grafts were transplanted into the fetal peritoneal cavityby using ultrasound guidance. Fetuses were sacrificed after 1-2 weeks. Donor cellengraftment was analyzed by FACS and real-time PCR targeting the SRY gene (inallo-Tx).

RESULTS: Allogeneic SC were transplanted into 14 fetuses (loss rate,21.4%). Donor cells engrafted preferentially in the spleen (1.14% ± 1.62%),followed by bone marrow (0.56% ± 0.54%), thymus (0.40% ± 0.69%), liver(0.23% ± 0.25%), and peripheral blood (0.11% ± 0.12%) by FACS. Real-timePCR data showed similar distribution at a lower rate. In the autologous Txgroup, 12 fetuses underwent in utero liver sampling of autologous SC, 8 fetuseswere transplantated, and 4 surviving fetuses were available for analysis of SCengraftment (loss rate 66%). Autologous donor cell levels and tissuedistribution were similar to the allogeneic Tx group.

CONCLUSION: Autologous in utero Tx of PKH26-stained donor fetal liverSC in the fetal sheep model as a two-step procedure is feasible but yields a highloss rate. Our data show no differences between homing and engraftmentcapacity of autologous and allogeneic SC, suggesting that in this sheep model,differences in the major histocompatibility complex (MHC) between donor andrecipient do not have a major impact on engraftment of SC transplanted early ingestation.

50

Volume 189, Number 6Am J Obstet Gynecol

SMFM Abstracts S75

FETAL THROMBOPHILIC POLYMORPHISMS ARE NOT A RISK FACTORFOR CEREBRAL PALSY CATHERINE GIBSON1, ALASTAIR MA-CLENNAN1, BILL HAGUE2, ZBIGNIEW RUDZKI3, PHILLIPA SHARPE4,ANNABELLE CHAN5, GUSTAAF DEKKER1, 1Adelaide University, Obstetricsand Gynaecology, Adelaide, South Australia, Australia 2Women’s andChildren’s Hospital, Adelaide, Obstetrics and Gynaecology, North Adelaide,South Australia, Australia 3Institute of Medical and Veterinary Sciences,Molecular Pathology, Adelaide, South Australia, Australia 4Women’s andChildren’s Hospital, South Australian Clinical Genetics Service, Adelaide,South Australia, Australia 5Department of Human Services, PregnancyOutcomes Unit, Adelaide, South Australia, Australia

OBJECTIVE: To investigate the association between cerebral palsy andinherited fetal thrombophilias.

STUDY DESIGN: Genomic DNA from the Guthrie card blood spots of 354consecutive cerebral palsy cases and 708 controls (all Caucasian, 1986-1999)were tested for four thrombophilic polymorphisms—factor V Leiden (G1691A),prothrombin gene (G20210A), methylenetetrahydrofolate reductase (MTHFR)C677T, and MTHFR A1298G. Odds ratios were calculated by using EpiInfo 6 inunivariate analysis.

RESULTS: Individually, none of the thrombophilic polymorphisms in-vestigated were significantly increased in the cerebral palsy cases whencompared with controls. Heterozygous factor V Leiden and homozygousMTHFR 1298 were negatively associated with cerebral palsy (OR 0.55 [0.31-0.98]and 0.61 [0.37-0.98], respectively). Further analysis of the major subtypes ofcerebral palsy (spastic diplegia, hemiplegia, and quadriplegia [data not shownin Table]) also showed some negative associations with these thrombophilicpolymorphisms.

CONCLUSION: In contrast to most of the existing literature (small samplesizes), the data derived from this large population sample of Caucasian cerebralpalsy cases reject the presence of a direct link between these four thrombophilicpolymorphisms individually (commonly found in Caucasians) and cerebralpalsy.

CP(n = 354)

Control(n = 708)

Odds Ratio(95% CI)

Factor V Leiden Homoor Hetero

22 (6.3%) 69 (9.8%) 0.62 (0.37-1.05)

Factor V Leiden Homo 4 (1.1%) 6 (0.8%) 1.35 (0.28-5.74)Factor V Leiden Hetero 18 (5.1%) 63 (8.9%) 0.55 (0.31-0.98)Prothrombin gene Homo

or Hetero18 (5.2%) 33 (4.7%) 1.11 (0.59-2.06)

Prothrombin gene Homo 2 (0.6%) 2 (0.3%) 2.02 (0.15-28.00)Prothrombin gene Hetero 16 (4.6%) 31 (4.4%) 1.04 (0.51-2.01)MTHFR 677 Homo

or Hetero183 (54.1%) 331 (48.2%) 1.27 (0.97-1.66)

MTHFR 677 Homo 49 (14.5%) 84 (12.2%) 1.22 (0.82-1.81)MTHFR 677 Hetero 134 (39.6%) 247 (36%) 1.17 (0.89-1.54)MTHFR 1298 Homo

or Hetero160 (47.1%) 338 (49.5%) 0.91 (0.69-1.19)

MTHFR 1298 Homo 26 (7.6%) 82 (12.0%) 0.61 (0.37-0.98)MTHFR 1298 Hetero 134 (39.4%) 256 (37.5%) 1.08 (0.82-1.43)MTHFR 677 + 1298Compound Heterozygotes

60 (17.2%) 106 (15.1%) 1.18 (0.82-1.69)