427: Risk factors for preterm delivery and uterine dehiscence following prenatal surgery for myelomeningocele

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Doppler Assessment, Fetus, Prematurity

Poster Session III

426 Adolescent cognitive and anxiety behavior in offspring following in utero exposure to increased trans unsaturated fatty acids through maternal diet

425 Improved detection of anomalies by CVS with fish analysis prior to multifetal reduction (MFPR) Mara Rosner1, Eugene Pergament2, Stephanie Andriole3, Pe’er Dar4, Rachel Greenbaum5, Mark Evans6 1

Montefiore Medical Center/Albert Einstein College of Medicine, Obstetrics & Gynecology and Women’s Health, Bronx, NY, 2Northwestern Reproductive Genetics PC, Genetics, Chicago, IL, 3Comprehensive Genetics, Genetic Counseling, New York, NY, 4Albert Einstein College of Medicine/ Montefiore Medical Center, Obstetrics & Gynecology and Women’s Health, Bronx, NY, 5Comprehensive Genetics, Ultrasound, New York, NY, 6Comprehensive Genetics & Mt. Sinai School of Medicine, Obstetrics & Gynecology, New York, NY

OBJECTIVE: Over 50% of patients undergoing IVF in the USA are ⬎35 years of age. When multiples, PGD, and ICSI are added, over 70% are at increased risk, yet most patients are not offered CVS prior to MFPR. We routinely offer CVS prior to MFPR. STUDY DESIGN: We retrospectively reviewed our last 470 CVS/MFPR patients. Abnormalities were categorized as structural, FISH, and abnormal karyotype. Our approach is generally not to test fetuses that are clearly abnormal and reduced such that the overall cytogenetic abnormality rate is artificially lowered. RESULTS: 94/470(20%) pregnancies and 96/1339(7.2%) fetuses had anomalies. 62/94(66%) were referred in the 1st trimester of which 24/62(39%) were identified or suggested by ultrasound(US). 27/ 62(43.5%) had an abnormal FISH that dictated MFPR. 21/27(77.7%) of the cytogenetic abnormalities had normal US. 5/21(24%) were T21, 2/21(10%) were T18/13, 13/21(62%) were sex chromosome mosaics, and one was a trisomy 13 mosaic. When final karyotype was available, FISH agreed with the karyotype in 702/728(96.4%) fetuses. Of the 26 discrepancies between FISH and karyotype, 18/26(69%) were sex chromosomes suggesting cross contamination or known innocuous findings such as tetraploidy or inherited inversions. Ultimately, there were 8/728(1%) potentially concerning karyotypic abnormalities discordant from FISH which included mosaic trisomies, one trisomy 8 and one chromosome 15p⫹ ⫺ 7/8 of which were confined placental mosaicisms. Final karyotype and subsequent amniocentesis confirmed one 46XX/46XY mosaic not seen on FISH. CONCLUSION: In our cohort, US alone identified only 39% of 1st trimester anomalies before MFPR. FISH identified another 32.8% and added value beyond US for 15/351 (4.3%) patients. 8/728(1%) required follow up amniocentesis for discrepancies. Given the risks of carrying multiples and published mistakes in reducing the wrong fetus by waiting for karyotype, our data suggest CVS, next day FISH and then MFPR as the optimal strategy. As a by-product, patients can then consider fetal sex when there are no other abnormalities.

Mark Alanis1, Claudia Umphlet2, Heather Boger2, Ann-Charlotte Granholm2 1 Medical University of South Carolina, Obstetrics and Gynecology, Charleston, SC, 2MUSC, Neurosciences, Charleston, SC

OBJECTIVE: The developing brain is potentially susceptible to inflammatory diets, such as trans unsaturated fatty acids (TFA). STUDY DESIGN: Fisher 344 virgin rats were randomized to isocaloric experimental (TFA) or study (AIN93) diets for 4 weeks, mated, and then maintained on their study diets until weaning. On postnatal day 23 (P23) offspring were further randomized into 1 of 4 prenatal/postnatal dietary arms (N ⫽ 16 litters): TFA/TFA, TFA/AIN, AIN/AIN, and AIN/TFA. Adolescent male and female rats (P36-38) underwent anxiety assessment using the elevated plus maze paradigm. Decreased % time and entry into open arms indicate increased anxiety. Adolescent male rats (P40-45) underwent cognitive behavioral performance testing using the water radial arm maze (WRAM) over 12 consecutive days. Spatial working and reference memory errors were averaged across litters during learning (days 1-3) and asymptotic phases (days 4-7, 6-9, and 10-12). Group comparisons were performed using 2-way analysis of variance (ANOVA) with repeated measures. Equality of variance was assessed by the F-test. Two-tailed p values ⬍.05 were considered significant. RESULTS: Females demonstrated greater anxiety than males based on the number of entries into open arms (10.5 0.9 versus 16.9 1.6, p ⫽ .001), but not % open time (40% versus 53% open time, respectively, p ⫽ .05). Diet did not demonstrate a significant relationship with anxiety (p ⫽ .52). Rats in all 4 diet arms showed similar improvement over the 12 day WRAM test (Figure). When collapsing the analysis to 2 groups (prenatal TFA versus AIN), prenatal TFA rats committed more total working memory errors compared to prenatal AIN rats during the day 10-12 phase (6.1 .6 vs. 3.3 1.2 errors, respectively; p ⫽ .03). Variance was not significantly different between the 4 groups (p ⬎ .05 for all F-tests). CONCLUSION: Prenatal and postnatal dietary exposure of TFA did not demonstrate a major impact on either anxiety or hippocampal-dependent cognitive behavior, which may be explained by a true absence of effect or variance in the sample set (Type II error).

427 Risk factors for preterm delivery and uterine dehiscence following prenatal surgery for myelomeningocele Mark Johnson1 1

For the Eunice Kennedy Shriver NICHD, MOMS Trial Group, Bethesda, MD

OBJECTIVE: Prenatal repair for myelomeningocele (MMC) has been

shown to improve outcome in children with spina bifida. However, the surgery is also associated with significant morbidity especially preterm delivery and uterine dehiscence at delivery. The objective is to identify risk factors for early preterm birth (PTD) and non-intact hysterotomy (NH) at delivery in women undergoing fetal MMC repair. Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology

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Doppler Assessment, Fetus, Prematurity

STUDY DESIGN: Secondary analysis of maternal and surgical risk factors from a RCT comparing pre and postnatal surgery for MMC. PTD was defined as delivery ⱕ 34.0 weeks. NH was defined as a very thin area, or partial or complete dehiscence of the prior hysterotomy site. RESULTS: 89 patients underwent prenatal surgery; PTD occurred in 38(43%). The hysterotomy site was evaluated in 88; NH was reported in 31 women (35%) with complete or partial dehiscence in 10 of them. Surgery times, both total (skin incision to closure) and uterine, were longer in those with PTD than those who delivered later. Use of Duragen in fetal repair, oligohydramnios and spontaneous membrane rupture (SROM) were also associated with an increased risk for PTD. In a logistic regression, surgery time but not Duragen use remained significant, with an increase in odds of 20% for each 10 minute increase in surgery time (adjusted OR 1.02, 95% CI 1.00, 1.04). Total surgery time was also longer in those with subsequent oligohydramnios (119.3 vs 100.9 minutes, p⫽0.04) and SROM (112.5 vs 98.6 minutes, p⫽0.01) than those without, suggesting a causal pathway to PTD. NH occurred over twice as often in nulliparous as in multiparous patients and was associated with the need for longer duration of post operative MgSO4. Excluding the very thin cases, partial/complete dehiscence was also associated with these factors, and with oligohydramnios (p⫽0.03). CONCLUSION: Longer surgical time is associated with the development of SROM and subsequent early preterm delivery. Development of oligohydramnios also places patients at increased risk for preterm delivery. Nulliparous patients should be counseled about the higher risk of hysterotomy complications.

428 Intracranial stem cell transplantation with and without erythropoietin facilitates motor recovery in a perinatal rat brain injury model Martin Mueller1, Andreina Schoeberlein1, Ursula Reinhart1, Ruth Sager1, Marianne Messerli1, Daniel Surbek2 1

University of Bern, Obstetrics and Gynecology, Bern, Switzerland, University Hospital of Bern, Obstetrics and Gynecology, Bern, Switzerland

2

OBJECTIVE: Peripartal brain injury in the premature infant leads to a large spectrum of clinical problems including lifelong neurodevelopmental deficits. We examined intracranial mesenchymal stem cells (MSC) transplantation as a promising therapy to facilitate motor recovery after perinatal hypoxic-ischemic brain damage with inflammatory component in a perinatal rat model. STUDY DESIGN: The study was conducted in a sham controlled design. Subcutaneous administration of LPS from E. coli followed by ligation of the left carotid artery and hypoxia (8% O2, 30min) was performed on rats on postnatal d4. On postnatal d11 mesenchymal stem cells (MSC) were injected into the left lateral ventricle and administration of erythropoietin (1000 U/kg bw, ip) on postnatal d11, d12 and d13 was conducted in separate therapy group. In brain sections, donor human MSC were detected and evaluated by histology and immuno-

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histochemistry (postnatal d25 and d40). Spastic paresis (SP) was evaluated by footprint and walking pattern (postnatal d40). RESULTS: Injected donor-derived cells were detected in the lateral ventricle by immunohistochemistry in both therapeutic groups. Migration in the ventricle and parenchyma was also present. MSC’s with unaltered morphology were detected in the cortex cerebri. Application of MSC’s and MSC’s and EPO resulted in alleviation of SP. CONCLUSION: This study demonstrates that intracerebral transplantation of human mesenchymal stem cells in a complex rat model of perinatal brain damage results in incorporation of MSCs in the lesioned brain area an reduction of cerebral palsy.

429 Programming of offspring adaptive immune response following maternal inflammation Michael Ross1, Nizar Khatib2, Zeev Weiner3, Yuval Ginsberg2, Nibal Awad2, Shay Arison2, Israel Thaler2, Joseph Itskovitz-Eldor2, Ron Beloosesky1 1 LABioMed at Harbor-UCLA Med. Ctr., Obstetrics and Gynecology, Torrance, CA, 2Rambam Medical Center, Obstetrics and Gynecology, Haifa, Israel, 3Rambam Medical Center, Technion Israel Institute of Technology, Obstetrics and Gynecology, Haifa, Israel

OBJECTIVE: Prenatal infection with gram negative bacteria is common during pregnancy. We have shown previously that acute maternal LPS exposure at E18 programs significant decrease the offspring innate immune response. The adaptive immune response is composed of B and T lymphocytes. T helper (CD4⫹, CD8-) and T Cytotoxic (CD8⫹, CD4-) compose the majority of T cells, and are essential for adequate immune responses. While T helper cells play an important role in establishing and maximizing the capabilities of the immune system, T Cytotoxic destroy virally infected cells and tumor cells. We sought to determine whether the adaptive immune response is programmed by maternal inflammation. STUDY DESIGN: Pregnant Sprague Dawley rats (n⫽4) at 18 days gestation received intraperitoneal (i.p.) injections of LPS (500 ug/kg) or saline (control). Male and female pups were delivered spontaneously y (e21) and allowed to mature until postnatal day 24 (p24). CD⫹4 and CD⫹8 lymphocytes, granulocytes, and macrophages expressing Toll like receptor 4 (TLR4) were characterized in the blood, spleen, and thymus of offspring pups by flow cytometry. RESULTS: Pups of LPS treated dams had significantly lower blood T Cytotoxic lymphocytes than pups of saline treated dams, though the same number of T helper lymphocytes. Pups of LPS dams had significantly higher counts of blood CD4⫹ TLR4⫹ and CD8⫹ TLR4⫹ lymphocytes, TLR4⫹ granulocytes, and a trend towards higher TLR4⫹ macrophages. The same pattern was demonstrated in the spleen and thymus. CONCLUSION: The decrease in the T Cytotoxic lymphocyte in the offspring of LPS exposed dams may increase their ability to cope with viral infection and potential tumor development. The increase in CD4⫹ TLR4⫹ lymphocytes may aid in anti-inflammatory responses and may explain the decrease in the proinflammatory cytokines previously demonstrated in these offspring following exposure to LPS. These results suggest that maternal inflammation during the antenatal period may induce long term sequelae in the offspring innate immune response which may predispose to adult disease.

430 Natural history for pregnancies complicated by obstructive uropathy and normal amniotic fluid volume Nahla Khalek1, Mark Johnson1 1 The Children’s Hospital of Philadelphia, The Center for Fetal Diagnosis and Treatment, Philadelphia, PA

OBJECTIVE: There is a paucity of literature documenting the outcome of fetuses prenatally diagnosed with obstructive uropathy and normal amniotic fluid volume. Current practice excludes these fetuses as candidates for vesicoamniotic shunt placement. The aim of this interim analysis is to provide data up to delivery of affected neonates.

American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012