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CONCLUSION: Our analysis does not support neuroprotective effects of prolonged nifedipine in women with threatened preterm birth. 183 Human Wharton’s jelly-derived mesenchymal stem cells express neurotrophic factors in vitro Marianne Messerli 1 , Martin Müller 2 , Andreina Schoeberlein 1 , Ruth Sager 1 , Daniel Surbek 2 1 University of Bern, Department of Clinical Research, Bern, Switzerland, 2 University Women’s Hospital Bern, Obstetrics & Feto-Maternal Medicine, Bern, Switzerland OBJECTIVE: Perinatal brain damage is a major neurological problem in surviving premature infants. Transplantation experiments in various animal models suggest a neuro-regenerative potential of multipotent mesenchymal stem cells (MSC). The curative effect of MSC might be due to their production of neurotrophic factors. The Wharton’s jelly represents a promising source of MSC. Thus, the aim of the study is to assess the expression and release of neurotrophic factors by human Wharton’s jelly-derived MSC and induced neural progenitor cells in vitro. STUDY DESIGN: MSC from Wharton’s jelly of term and pre-term (gesta- tional age 37 weeks) pregnancies were evaluated. Adaptations of pre- viously published multistep protocols (Portmann-Lanz et al, AJOG 2010; Fu et al, Acta Neurobiol Exp 2007; Zhang et al, Differentiation 2010) were used to produce neural progenitors (neurospheres). The transcription of neurotrophic factors was assessed by real-time PCR. The release of neural growth factors into the cell culture medium was measured by a mem- brane-based cytokine antibody array. RESULTS: At passage five MSC from term and preterm pregnancies were expressing key neurotrophic factors, such as brain-derived neu- rotrophic factor (BDNF), neurotrophin 3 (NTF3) and glial cell-de- rived neurotrophic factor (GDNF), and the cytokine interleukin (IL)-6, at the mRNA level. BDNF and IL-6 were detected in the cell culture supernatant after 48h of cultivation. The transcription of BDNF and NTF3 were significantly reduced in neurospheres relative to MSC, independent of gestational age. However, the gene expression of GDNF was up-regulated in neurospheres compared to the non- induced MSC derived from term pregnancies. CONCLUSION: MSC derived from Wharton’s jelly of term and preterm pregnancies, and the induced neural progenitor cells produce neu- rotrophic factors in vitro. The role of the released factors in neurogenesis and neuro-regeneration is currently analyzed in co-culture experiments with neural stem cells. Financial support by Cryosave Switzerland. 184 Neonatal MRI brain following fetoscopic laser surgery for twin-twin transfusion syndrome: implications for clinical practice Michael Boyle 1 , Aisling Lyons 1 , Stephanie Ryan 2 , Fergal Malone 3 , Adrienne Foran 1 1 Rotunda Hospital, Neonatology, Dublin, Ireland, 2 The Children’s University Hospital, Radiology, Dublin, Ireland, 3 Rotunda Hospital, Fetal Medicine, Dublin, Ireland OBJECTIVE: To date, neonatal outcome studies of TTTS survivors fol- lowing fetoscopic laser surgery (FLS) have relied upon cranial ultra- sound (CUS) to confirm normality. Our objective was to evaluate intracranial abnormalities in surviving twins following FLS using term-corrected MRI. STUDY DESIGN: For this prospective, blinded, case-control study, term-corrected MRI brain scans were performed on 3 groups; (A) survivors of TTTS who had undergone FLS (n14), (B) MCDA twins without TTTS (n12) and (C) dichorionic twins (n8). Each scan was graded blindly as either normal, minor abnormality or an abnor- mality likely to be of clinical significance. The primary study outcome was abnormal findings on MRI brain or fetal demise. RESULTS: The primary outcome occurred in 9/14 (64.3%) within the TTTS group, versus 4/12 (33.3%) in the MCDA group. No primary outcome occurred in the DC group.There was a significant difference across all study groups for the primary outcome [p(1,2) 0.01; 2 9.1]. 2/7 (28.6%) of the abnormal MRI’s in the TTTS group were deemed to be of immediate clinical significance (Figure) and in both cases CUS were normal. Cranial ultrasound as the sole imaging mo- dality yielded an abnormality in 1/12(8.3%) in TTTS group versus 2/12(16.7%) in the MCDA group. The primary outcome was present in 5/26 (19.2%) of study participants when CUS was analysed as the sole imaging modality. With MRI the primary outcome was present in 13/26 (50%) of the study participants; P 0.041; 2 5.44. Sensitivity analysis was performed comparing the two imaging modalities and referencing MRI with a sensitivity of 100%. Against this MRI bench- mark CUS had a significantly poorer sensitivity of 37.9% (22.6, 56.0). CONCLUSION: CUS as the sole imaging modality in TTTS survivors can miss significant abnormalities and under-states the true rate of abnor- mality as shown using MRI. This has implications for how patients are counseled prior to FLS and methods of neonatal surveillance following delivery. Table Figure Top row; T1 (right) and T2 (left) images of Twin A (1) focal cortical migration abnormality (arrow). Bottom row; Twin G (2) Periventicular leukomalacia (arrow). Poster Session I Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity www.AJOG.org S88 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013

184: Neonatal MRI brain following fetoscopic laser surgery for twin-twin transfusion syndrome: implications for clinical practice

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CONCLUSION: Our analysis does not support neuroprotective effects ofprolonged nifedipine in women with threatened preterm birth.

183 Human Wharton’s jelly-derived mesenchymalstem cells express neurotrophic factors in vitroMarianne Messerli1, Martin Müller2, Andreina Schoeberlein1,Ruth Sager1, Daniel Surbek2

1University of Bern, Department of Clinical Research, Bern, Switzerland,2University Women’s Hospital Bern, Obstetrics & Feto-Maternal Medicine,Bern, SwitzerlandOBJECTIVE: Perinatal brain damage is a major neurological problem insurviving premature infants. Transplantation experiments in variousanimal models suggest a neuro-regenerative potential of multipotentmesenchymal stem cells (MSC). The curative effect of MSC might bedue to their production of neurotrophic factors. The Wharton’s jellyrepresents a promising source of MSC. Thus, the aim of the study is toassess the expression and release of neurotrophic factors by humanWharton’s jelly-derived MSC and induced neural progenitor cells invitro.STUDY DESIGN: MSC from Wharton’s jelly of term and pre-term (gesta-tional age � 37 weeks) pregnancies were evaluated. Adaptations of pre-viously published multistep protocols (Portmann-Lanz et al, AJOG 2010;Fu et al, Acta Neurobiol Exp 2007; Zhang et al, Differentiation 2010) wereused to produce neural progenitors (neurospheres). The transcription ofneurotrophic factors was assessed by real-time PCR. The release of neuralgrowth factors into the cell culture medium was measured by a mem-brane-based cytokine antibody array.RESULTS: At passage five MSC from term and preterm pregnancieswere expressing key neurotrophic factors, such as brain-derived neu-rotrophic factor (BDNF), neurotrophin 3 (NTF3) and glial cell-de-rived neurotrophic factor (GDNF), and the cytokine interleukin(IL)-6, at the mRNA level. BDNF and IL-6 were detected in the cellculture supernatant after 48h of cultivation. The transcription ofBDNF and NTF3 were significantly reduced in neurospheres relativeto MSC, independent of gestational age. However, the gene expressionof GDNF was up-regulated in neurospheres compared to the non-induced MSC derived from term pregnancies.CONCLUSION: MSC derived from Wharton’s jelly of term and pretermpregnancies, and the induced neural progenitor cells produce neu-rotrophic factors in vitro. The role of the released factors in neurogenesisand neuro-regeneration is currently analyzed in co-culture experimentswith neural stem cells. Financial support by Cryosave Switzerland.

184 Neonatal MRI brain following fetoscopic lasersurgery for twin-twin transfusion syndrome: implicationsfor clinical practiceMichael Boyle1, Aisling Lyons1, Stephanie Ryan2, Fergal Malone3,Adrienne Foran1

1Rotunda Hospital, Neonatology, Dublin, Ireland, 2The Children’sUniversity Hospital, Radiology, Dublin, Ireland, 3Rotunda Hospital, FetalMedicine, Dublin, IrelandOBJECTIVE: To date, neonatal outcome studies of TTTS survivors fol-lowing fetoscopic laser surgery (FLS) have relied upon cranial ultra-sound (CUS) to confirm normality. Our objective was to evaluateintracranial abnormalities in surviving twins following FLS usingterm-corrected MRI.STUDY DESIGN: For this prospective, blinded, case-control study,term-corrected MRI brain scans were performed on 3 groups; (A)

survivors of TTTS who had undergone FLS (n�14), (B) MCDA twinswithout TTTS (n�12) and (C) dichorionic twins (n�8). Each scanwas graded blindly as either normal, minor abnormality or an abnor-mality likely to be of clinical significance. The primary study outcomewas abnormal findings on MRI brain or fetal demise.RESULTS: The primary outcome occurred in 9/14 (64.3%) within theTTTS group, versus 4/12 (33.3%) in the MCDA group. No primaryoutcome occurred in the DC group.There was a significant differenceacross all study groups for the primary outcome [p(1,2) � 0.01; �2 �9.1]. 2/7 (28.6%) of the abnormal MRI’s in the TTTS group weredeemed to be of immediate clinical significance (Figure) and in bothcases CUS were normal. Cranial ultrasound as the sole imaging mo-dality yielded an abnormality in 1/12(8.3%) in TTTS group versus2/12(16.7%) in the MCDA group. The primary outcome was presentin 5/26 (19.2%) of study participants when CUS was analysed as thesole imaging modality. With MRI the primary outcome was present in13/26 (50%) of the study participants; P � 0.041; �2 �5.44. Sensitivityanalysis was performed comparing the two imaging modalities andreferencing MRI with a sensitivity of 100%. Against this MRI bench-mark CUS had a significantly poorer sensitivity of 37.9% (22.6, 56.0).CONCLUSION: CUS as the sole imaging modality in TTTS survivors canmiss significant abnormalities and under-states the true rate of abnor-mality as shown using MRI. This has implications for how patients arecounseled prior to FLS and methods of neonatal surveillance followingdelivery.

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Figure

Top row; T1 (right) and T2 (left) images of Twin A (1) focal cortical migration abnormality (arrow).Bottom row; Twin G (2) Periventicular leukomalacia (arrow).

Poster Session I Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity www.AJOG.org

S88 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013