- Email: [email protected]
ORAL CONCURRENT SESSION D Fetus Friday, February 9, 2001, 1:15 pm – 3:30 pm
ORAL C O N C U R R E N T S E S S I O N D Fetus Friday, February 9, 2001 1:15 pm - 3:30 pm
Moderators:
KennethJ. Moise, Jr., MD Ronald J. Wapner, MD
Judges:
Susan M. Cox, MD Mary E. D'Alton, MD Robert Silver, MD
Carson Abstract Numbers 44-52
$22 SMFM Abstracts O044
INCREASED P O L Y M O R P H O N U C t , F A R INFILTRATION AND AMNIOTIC BAND AFTER CLOSURE OF FETOSCOPIC ACC,F~S SITES WITH A BIOACTIVE MEMBRANE IN A RABBIT M O D E L Roland Devlieger 1, J a n DePrest 2, Eduard Gratacos3, Hilko Ardon -~, Lut Verbist4, Robert Pijnenborg4; ICentre for Surgical Technologies, KU Leuven, Leuven; 2University, Hospital Gasthuisberg, Leuven; SCentre for Surgical Technologies, Kid Leuven, Leuveo; 4Laboratory Experimental Gynaecology, Dept Obstetrics Gynaecology, Leuven, Belgium OBJECTIVES: To evaluate the use of a porcine small intestine derived bioactive m e m b r a n e c o n t a i n i n g growth factors TGF-[~ a n d bFGF (BioSiS, Cook) for closure o f the fetoscopic access p o r t following experimental fetoscopy in the rabbit at midgestation. STUDY DESIGN: Needle fetoscopy was performed in 100 gestational sacs in 16 does at 23/31 days' gestation. In g r o u p I (:1 = 50) the fetoscopic access site was closed using a 5- to 10-mm patch of the bioactive membrane; 50 sacs were left o p e n (positive controls, g r o u p 2). Fifty-two n o n o p e r a t e d sacs were used as negative controls (group 3). Macroscopic a n d microscopic evaluation of the operation site was p e r f o r m e d for evaluation of m e m b r a n e integrity, polymorphonuclear (PN) infiltration, fetal weight, fetal lung weight, and fetal lung to body weight ratio (LWBWR). RESULTS: Membrane integrity was much more frequently restored using the b i o m e m b r a n e (Table). Infiltration of PN was more frequent. LWBWR was compatible with pulmonary hypoplasia in positive controls while normal in all o t h e r fetuses. In 1 animal o f g r o u p 1, a postoperative amniotic b a n d was observed, which never occurred in o u r large experience with this m o d e l CONCLUSION: The use of a bioacdve m e m b r a n e resulted in significant i m p r o v e m e n t o f fetal m e m b r a n e repair rates a n d a significant decrease of p u l m o n a r y hypoplasia, but increased p o l y m o r p h o n u c l e a r infiltration. O n e occasional case of iatrogenic amniotic b a n d was observed. Using m e m b r a n e sealing substances should be investigated further before clinical application.
Membrane integrity LWBWR PN infiltration
0045
J a n u a r y 2001 Gynecol
AmJ O b s t e t
GROUP 1
GROUP 2
2 8 / 4 0 (70%) 0.032 ± 0.0067 1 9 / 4 0 (48%)
13/32 (41%) 0.027 ± 0.0082 5 / 3 2 (16%)
0046
PERINATAL FACTORS PREDICTING SEVERE INTRACRANIAL HEMORRHAGE James A. T h o r p I, Philip G. Jones ~, Jordan H. Perlow"s, Reese Clark 4, Bannie TaborS; IObstetrix of KS & MO, University' of Missouri at Kansas City, St. Luke's Perinatal Center, Kansas City, MO; '2Analytic Consultants, Lee's Summit, MO; :~Obstetrix Medical G r o u p of Phoenix, Maternal Fetal Medicine, Phoenix, AZ; 4pedlatrix Medical Group, Director of Clinical Research, Sunrise, FL; 5Obstetrix Medical G r o u p of Texas, Maternal Fetal Medicine, Fort Worth, TX OBJECTIVE: To assess perinatal factors associated with severe intracranial h e m o r r h a g e (ICH). STUDY DESIGN: Data were prospectively captured in 100 tertiary centers t h r o u g h o u t 5 geographic regions between May 1997 a n d J a n u a r y 2000. Retrospective analysis of n o n a n o m a l o u s newborns admitted to the NICU between 20 a n d 35 weeks' gestation was accomplished by multiple logistic regression. Severe ICH w-as defined as grade III or grade IV ICH. A predictive model was constructed using stepwise variable selection from a pool of 30 antenatal and perinatal factors (Pvalue for entry = .2; Pvalue for retention =. 1). RESULTS: A total of 16,211 cases were available for analysis. Gestational age ~¢as the most important predictor of severe ICH (P < .0001). With 34 weeks' gestation as a reference, the odds ratios were 66 at 23 weeks; 65 at 24 weeks; 50 at 25 weeks; 34 at 26 weeks; 19 at 27 weeks; 17 at 28 weeks; 7.8 at 29 weeks; 5.5 at 31 weeks; and 2.8 at 83 weeks. O t h e r important predictors ofsevere ICH in order of importance were (odds ratio, P value): surfactant use (2.2, <.0001); 5-minute A p g a r score <7 (1.6, .0001); p o o r prenatal care (1.6, .0002); antenatal indomethacin use (1.7, .008); chorioamnionitis (1.4, .016); and presentation (P = .034). Cesarean birth a n d antenatal steroids were not associated with lower rates of severe ICH by univariate or by multivariate analysis (P > .1). The validated model c-statistic was 0.87. CONCLUSIONS: Gestational age was the most important predictor of severe ICH. Antenatal i n d o m e t h a c i n a n d chorioamnionitis were associated with increased risk of severe ICH. Cesarean birth and antenatal steroids were not associated with lower rates of severe ICH.
0047
PREVENTION OFALCOHOL-INDUCED PROINFLAMMATORY CYTOKINE B~I.FASE AND SPATIAL LEARNING DEFICITS WITH NOVEL PEPTIDES IN A M O U S E MODEL OF FETAL A L C O H O L SYNDROME C.Y Spongl,j. Auth I, J. Vink 2, D. T. Abebe 3, I. Gozes 4, D. E. Brenneman2; JNational Institutes of Health, SDMP, LDN, NICHD, Bethesda, MD; 2National Institutes of Health, SDMP, LDN, NICHD, Bethesda, MD; 3NIH, SDMP, LDN, NICHD, Bethesda, MD; 4Tel Aviv Univ., Biochem, Tel Aviv, Israel OBJECTIVE: To evaluate the release of proinflammatory cytoldnes in fetal alcohol syndrome (FAS) a n d the effect of the peptides, NAPVSIPQ (NAP) and SALLRSIPA (SAL) in modulating their release. Because cytokines have known effects on long-term potentiation, a model o f learning at the molecular level, we evaluated l e a r n i n g in adult offspring. Previously NAP+SAL prevented alcohobinduced fetal death, growth abnormalities, a n d oxidative damage in this FAS model. METHODS: A well-characterized FAS mouse model was used. O n day 8, p r e g n a n t mice were injected with alcohol (0.03 m L / k g ) or placebo. Pretreatment with the peptides NAP+SAL (20 lag) or placebo was given 30 minutes before alcohol. For cytokine analysis, embryos were removed after 6 h o u r s a n d analyzed (ELISA) for t u m o r necrosis factor ( T N F ~ ) a n d interleukin-6 (IL-6). To assess learning, adult male offspring were tested in the Morris watermaze evaluating latency to find a hidden platform. RESULTS: T N F ~ was significantly elevated in alcohol vs control (50.0 + 3.5 vs 32.7 + 2.4 p g / m L , P = .001). NAP + SAL pretreatment prevented the alcohobinduced increase (39.9 + 2.8 p g / m L , P = .01) with levels not different than control ( P = .1). Similarly, IL-6 was elevated in alcohol vs control (22.6 + 1.4 vs 17.3 + 0.6 p g / m L , P = .001); NAP + SAL prevented the alcohol-induced increase (19.1 + 1.0, P = .02), with levels similar to control (P = .2). In the Morris watermaze, the alcohol-treated litters exhibited no evidence of learning over the 7d trial. In contrast, the control litters decreased their latency 50% by the fifth day (P = .001). The learning curve of NAP + SAL + alcohol litters was not different than that of control at all time points tested. CONCLUSIONS: T h e peptides NAP + SAL attenuate alcohol-induced increases in p r o i n f l a m m a t o r y cytokines a n d prevent alcohol-induced performance deficits in a learning paradigm. These data suggest that NAP + SAL provide protective efficacy through cytokin~mediated mechanisms.
P <.02 <.05 <.005
NEURONAL NITRIC O ~ [ D E SYNTHASE (NNOS) REGULATES SPONTAN E O U S AND ANGIOTENSIN H (ANG ID-STIMULATED FETAL SWAI.,L O W I N G Mostafa El H a d d a d , Dr. 1, C o n r a d C h a t , Dr t, Michael ROSS2; IHarbor-UCLA, Obstetrics a n d Gynecology, Torrance, CA; 2University of California, Los Angeles, Obstetrics a n d Gynecology, Torrance, CA OBJECTIVE: Spontaneous fetal swallowing occurs at a markedly higher rate when c o m p a r e d with spontaneous adult drinking. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume. Central nitric oxide (NO) is critical for m a i n t a i n i n g n o r m a l rate o f fetal swallowing, as nonselective inhibition of N O (with central L-NAME) suppresses fetal swallowing. We sought to differentiate the contributions of central endothelial versus neuronal N O in the regulation o f s p o n t a n e o u s a n d stimulated fetal swallowing, using a selective nNOS inhibitor. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically p r e p a r e d with fetal vascular a n d intracerebroventricular (ICV) catheters, electrocorticogram (ECoG), a n d esophageal electromyogram electrodes a n d studied at 130 + 1 days' gestation. After an initial 2-hour baseline period, the selective nNOS inhibitor N-propyI-L-arginine (NPLA; 1 mL, 6 lag) was injected ICV. At time 4 hours, the dose of NPLA was repeated, together with Ang II ( 1 mL, 6.4 lag), a n d fetal swallowing was monitored for a final 2 hours. Four fetuses also received an identical control study (on an alternate day) in which NPLA was replaced with artificial cerebrospinal fluid (aCSF). RF~ULTS: Suppression o f nNOS by ICV NPLA significantly reduced mean (:~.SEM) spontaneous fetal swallowing (1.4 + 0.1 to 0.5 + 0.1 swallows/rain; P < .001). ICV injection of Ang lI in the presence o f NPLA h a d no dipsogenic effect o n fetal swallowing (0.7 + 0.1). In the control study ICV injection of aCSF p r o d u c e d n o changes in fetal swallowing, whereas ICV injection of Ang II resulted in a significant increase in the rate of fetal swallowing. CONCLUSION: T h e suppressive dipsogenic effects o f central NPLA indicate that spontaneous a n d Ang II-stimulated fetal swallowing is d e p e n d e n t o n central n N O S activity within dipsogenic neurons. We speculate that the increased rate of fetal swallowing n e a r term may be secondary to the induction of nNOS expression
SMFM Abstracts S23
V o l u m e 184, N u m b e r 1 AmJ Obstet Gvnecol 0048
0049
T H E MECHANISM OF O L I G O H Y D R A M N I O S IN POSTDATES PREGNANCY: A PROSPECTIVE D O P P L E R STUDY Ray Bahado-Singh I. Basia H o l n h e, L'tku Oz 3, Sang-lo,m (:hot t, (;iancarh) Mat+i:', Inci (,unev:+; Iyale University, Ohstetrics & (;ynecology, Maternal-Fetal Medicine Secticm, New Haven, CT: '-'~,tlc LTnivetsity School of Medicine, Ohstetrics and (;ynecologT, New Haveu, (;T; :~Mersin University, OB/(;YN, Mersin; I(]hosnn University Hospital, OB/(;YN, Kwangju (:it}'; :'University t)l'VA Iqealth Systems, OB/(;~ ~'N', Dirisiou of Maternal Fetal Medicine, (;harlottesville, VA OBJECTIVE: Oligohydramnios is tile nlost itnportant predictor t~f Ik'tal colnpronlisc iu postdales pregnanfy, yet its etiology is tutknown. Doppler stndies report cont]icting conclusions as to whether the oligoh,wh'ann'fios correlates with renal artery Doppler inclices. We perfi)rmed renal artery Doppler in a series of postdates pregnancies. METHODS: The renal artery end-diastolic velocity (EDV), resistance index (RI), and nmhilical artery RI were prospectively measured a n d couverted to MoM in singleton postdates pregnancies presentiug ti3r the standard biophysical profile testing. Stepwise logistic regression and the 2tailecl t test were osed to delerlnine whether the Doppler indices correlated with oligohydramuios (amniotic thfid index <5 cm). RESULTS: T h e r e were 147 study cases of which 21 (14.3%) had oligohydwnnnios. The mean (SD) gesta].ional age at Doppler was 41.4 (0.45) week.s and at delivery of 41.8 (0.47) weeks. Stepwise logistic regression ::sing the reual and tnnbilical arten'y Doppler indices finmd the renal RI to be the signilicant predictor of oligohydramnios (13 coefficient -10.42. P < .05). The reoal artery RI (MoM) ~ts signilicantly higher in the C~LSeSwith oligohydramnios mean (SD) = 0.88 ((I. 11) vs 0.86 ((I.05), P = .(14. A statistically significant correlation between a reduced renal artery Doppler EDV and the risk of oligohydramnios was also fin:nd. A renal artery EDV below the mean for gestation was associated with a RR (95% C1) of 1.5 (1.1 to 2.0) of oligohydmmnios. C O N C L U S I O N : O u r stncly, o n e of the largest series to date, f o u n d hemodynamic changes in the le'tal renal artery in postdate pregnancies with oligohydranmios. Renal artery Doppler was su[Jerior to the umbilical artery in predicting oligohydramnios. The association with reduced reual artery EDV indicates that increased arterial i m p e d a n c e occttrs resulting iu r e d n c e d nephron perl'nsicm and nriue productiou. This wot:ld explain the mechanfism of nligohydramnios in postdates pregnancies.
0050
THE NEONATAL NUCLEATED RED B L O O D CELL INDEX: AN INDEPEND E N T P R O G N O S T I C I N D I C A T O R FOR DEATH IN GROWTH-RESTRICTED NEONATES Ahmet Baschad, UIIrich Gembruch, Prof-', Ludwig
0051
Gormen Prof ~, Carl Weiner 4, Christopher Harman4; IUniversity of Maryland at Baltimore, Obstetrics. Gynecology a n d Reproductive Sciences, Baltimore, MD; '-'Medical University LO.beck, Obstetrics & Gynecology, Lfibeck; 3Medical University Giessen, Pediatl-ics. Giessen; 4University of Maryland at Baltimore, Ohstetrics, Gynecology & Reproductive Sciences, Baltimore, MD OBJECTIVE: Fetal hypoxemia is associated with ele~-ated neonatal nucleated red blood cell (NRBC) cotmt and persistence of NRBC count elevation. We sought to determine ira NRBC index reflecting daese 2 factors is an independent risk factor lbr adverse outcome in growth-restricted neonates (IUGR). STUDY DESIGN: NRBC counts per 100 white blood cells (WBC) were determined fi'om a 2-hour postpartnm peripheral blood sample (NRBCI) in 235 IUGR neonates (birth weight <10th percentile). Persistence of NRBC count >10/100 WBC (NRBCP) in clays was deternained. An NRBC index (NRBCI + NRBC2 + NRBCN, where N = NRBCp in days) was calculated. Muhiple logistic regression was performed to deterufine the a.ssociation between NRBC parameters and otllConle. RESULTS: Complications included respiratory distress (RDS, n = 115, 51%). b r o n c h o p n h n o n a r y dysplasia (BPD, n = 29, 2.3%), intraventricular h e m o r r h a g e (IVH, n = 39, 16.6%), necrotizing enterocolitis (NEC, n = 15, 6.4%), a n d neonatal death (n = 10, 4.4%). Each NRBC p a r a m e t e r was significantly h i g h e r in the presence of complications (Table). Regression analysis identified the NRBC index ms an independent predictor of neonatal death (r2= 0.35, P < .001 ), and NEC 0.24, P< .05). C O N C L U S I O N : IUGR neonates with p o s t p a r t u m complications have significandy higher NRBC count and persistence of NRBC cotmt elevation. Only the NRBC index incorporating these 2 variables showed a significant relationship with neonatal death a n d NEC. NRBC1 (MEDIAN)
NRBCP (MEDIAN)
RDS ",s no RDS
11 vs 93*
BPD ,,,s no BPD IVH vs no 1VH NEC vs no NEC
23 vs 208* 23 vs 153" 26 ~ 339*
0.5 vs 3* 1 vs 4*
Dead vs alive
26 vs 2831"
"P < .0001. ~P < .005.
1 vs 41" 2 vs 5* 2 vs 61.
NRBC INDEX (MEDIAN) 11.6 vs 130.2"
27.6 vs 303.8* 27.7 vs 214" ,30.8 vs 484.5* 33 vs 409.8"t"
DOPPLER ULTRASONOGRAPHY FOR TIMING T H E SECOND TRANSFUSION IN FETAL ANEMIA FROM RED CELL ALLOIMMUNIZATION Laura
Detti 1, Utku Oz'-'. Raymond Bahado-Singh:*, Roland Z i m m e r m a n n 4, lnci Gtuley'2, Giancarlo Marl I; I University of Virginia, Obstetrics a n d Gynecology,, ('harlonesville, VA; 2University of Mersin, Obstetrics and Gynecology, Mersin; :~£alc Uuiversity, Obstetrics a n d Gynecology, New Haven, CT; "lUniversity Hospital of Zurich, Obstetrics and Gynecology, Zurich, Switzerland OBJEC'TIVE: The middle cerebral artery peak systolic velocity (MCA-Ic'SV) has heeu successfnlly nsed for timing the first cordocentesis in fetuses at risk for auemia becat:se of maternal red cell alloimmnnization. The objective of this study was to assess the feasibility of MCA-PSV for prediction of moderate and severe anemia in fetuses that had u n d e r g o n e a prior transfusion. STUDY DESIGN: Doppler m e a s u r e m e n t of MCA-PSV was p e r f o r m e d before cordocentesis in 5(.I fetuses. The timing of the second transfosion ~vas based on traditional criteria. The values of MCA-PSV a n d hemoglobin were expressed as multiples of the median (MoM). The threshold for performing a cordocentesis was MCA-PSV _> 1.5 MoM. Anemia was d e f n e d as mild (hemoglobin < 0.84 MoM for a given gestational age), moderate (hemoglobin < 0.65 MoM), a n d severe (hemoglobin < 0.55 MoM). RESULTS: Gestational age at Doppler stndy ranged from 19 to 36 weeks. Twenty-two fetuses (37%) had nol'mal hemoglobin concentration; 21 (36%) had mild anemia; 7 (12%) had moderate anemia; a n d 9 (15%) had severe anemia. MCA-PSV sensitivity was 100% for the detection of both severe a n d moderate anemia with a t'alse-positive rate of 6% and 37%, respectively. CONCLUSIONS: Previously, concerns have been expressed a b o u t the accnracy of Doppler prediction of anemia after a prior transfusion. We have demonstrated that MCA-PSV is an excellent tool to diagnose both severe a n d moderate anemia in fetuses with a prior transfusion. O u r findings expand the clinical situatioo in which Doppler can be nsed to monitor red cell alloimmunized pregnaucies.
RAPID T R A N S I T I O N O F FRESH H U M A N UMBILICAL CORD B L O O D M O N O N U C L E A R Cl~l.l.g T O FETAL B L O O D FOLLOWING INJECTION I N T O THE EXOCELOMIC CAVITY OF T H E RABBIT Jun Wu I, Greet Bries 2,
Eduard Gratacos3, W e m e r Scheers 4, Marc Boogaerts4, J a n DePrestS; ICentre for Surgical Technologies, KU Leuven, Leuven; 2UZ Leuven, Dept o f Haemotology, Leuven; ~Cenu'e for Surgical Technologies, Dept of Obstetrics Gynaecology, Leuven; 4UZ Leuven, Dept of Haematulogy, Leuven; 5University Hospital Gasthuisberg, Leuven, Belgium OBJECTIVES: The window of opportunity for in uteru transplantation of stem cells is prior to 14 weeks. At that time extraembryonic spaces are still well discernible a n d accessible. In the present study we investigated the potential of transition of injected h u m a n umbilical cord blood m o n o n u c l e a r cells (HMNC) from the exocelomic cavity to the fetal blood circulation in a rabbit model. STUDY DESIGN: After collection of fresh h u m a n umbilical cord blood, m o n o n u c l e a r cells were isolated by Ficoll density separation a n d resuspended at 16 x 106/mL in culture medium and 5% rabbit serum. Fetuses from timedated p r e g n a n t New Zealand rabbits were injected with 250 I.tL (6 x 1061 HMNC cells u n d e r the operation microscope, either in the exocelomic cavity (EEC, n = 9) or in file fetal abdominal cavity (AC, n = 6). Twenty-four hours later the animals were sacrificed to harvest EEC fluid, fetal blood, a n d fetal liver, which were homogenized. Samples were analyzed by flow cytometry after incubation with FITC-labeled anti-CD45 monoclonal antibodies, to detect the presence of h u m a n leucocytes. RESULTS: Twenty-four hours after injection into the EEC, HMNC cells were found in 7 of 9 (78%) fetuses, while this s~as 100% after intra-abdominal injection. HMNC represented 3.4% -¢-5.7% of fetal peripheral blood cells in the EEC group, while 12% :l: 17.4% in the AC group. In the EEC g r o u p no HMNC could be detected in the liver homogenate within the 94 hours of the experiment. In all cases in the AC group, HMNC cells were present in the liver homogenates at a mean percentage of 0.5% 4- 0.4%. CONCLUSION: This study provides first evidence that injection of HMNC into the EEC is associated with a rapid transition of a proportion of these cells to fetal peripheral blood. This warrants further investigation into the dynamics of this process a n d the fate of cells injected into the EEC.
S24 SMFM Abstracts 0052
J a n u a ~ , 2001 AmJ Obstet Gynecol
DOPPLER VELOCIMETRY O F T H E DISTAL R I G H T PULMONARY ARTERY AND T H E DEVELOPMENT OF LUNG HYPOPLASIA Luis Medina l, Ricardo Gomez I, Adela Camus 2, Veronica Saez I, Gonzalo Galleguillos2, Rogelio Gonzalez I, Percy Pacora s, Ivan Rojas I, Greggory DeVote 3, Roberto Romero:~; ICEDIP, Sotero del Rio Hospital, OB/Gyn, Univ Catolica de Chile, Pnente Alto, Santiago; 2CEDIP, Sotero del Rio Hospital, Puente Alto, Santiago. Chile; SPerinatology Research Branch, NICHD. Bethesda, MD OBJECTIVE: L u n g hypoplasia (LH) is a major cause of perinatal death in patients with preterm PROM a n d in disorders characterized by restrictive h m g disease. Pulmonary hypertension is frequently present in LH. The objective of this study was to d e t e r m i n e if there is a relationship between the fetal pulmonary vascular bed impedance to flow a n d the subsequent development of LH. STUDY DESIGN: A case-control study was designed including 16 fetuses who died at birth because of LH (cases) a n d 185 control patients. Controls were fetuses with normal outcome. Measurements were performed in the distal branch of the right pulmonary artery (DRPA) with an angle close to 0 degrees. Parameters o b t a i n e d were pulsatility index (PI), peak velocity (PV), a n d velocity time integral (VTI). Regression analysis and nonparametric procedures were used for analysis. RESULTS: A reference range for Doppler indices of the DRPA was constructed based on the control population. DRPA PI and VTI c h a n g e d with gestadonal age (GA) but PV did not. For comparisons, delta values (mean-actual value) were obtained when PIj ". • the variable c h a n g e d with GA. Cases with LH h a d a higher delta DRPA PI a n d a lower delta DRPA VTI than controls (delta PI: median 2.76 [1.00 to 5.15] vs median -0.03 [-1.24 to 7 • 1.72], P < .001; delta VTI: m e d i a n - 0 . 0 1 1 [-0.03 to 0.01] vs median -0.002 .=It l'It'... ,,. . I * ".--'I [-0.03 to 0.06], P < .001, respectively). All cases with LH (triangles in the Figure) had a DRPA PI above the 95% confidence limit 18 24 30 36 40 for GA. There were no differences for DRPA PV beGestational age (wks) tween groups. CONCLUSION: Fetuses with LH had significandy higher impedance to flow in the pulmonary circulation. This parameter may be of clinical value in the risk assessment of fetal pulmonary hypoplasia.
S1
"
"; .
Moderators:
KennethJ. Moise, Jr., MD Ronald J. Wapner, MD
Judges:
Susan M. Cox, MD Mary E. D'Alton, MD Robert Silver, MD
Carson Abstract Numbers 44-52
$22 SMFM Abstracts O044
INCREASED P O L Y M O R P H O N U C t , F A R INFILTRATION AND AMNIOTIC BAND AFTER CLOSURE OF FETOSCOPIC ACC,F~S SITES WITH A BIOACTIVE MEMBRANE IN A RABBIT M O D E L Roland Devlieger 1, J a n DePrest 2, Eduard Gratacos3, Hilko Ardon -~, Lut Verbist4, Robert Pijnenborg4; ICentre for Surgical Technologies, KU Leuven, Leuven; 2University, Hospital Gasthuisberg, Leuven; SCentre for Surgical Technologies, Kid Leuven, Leuveo; 4Laboratory Experimental Gynaecology, Dept Obstetrics Gynaecology, Leuven, Belgium OBJECTIVES: To evaluate the use of a porcine small intestine derived bioactive m e m b r a n e c o n t a i n i n g growth factors TGF-[~ a n d bFGF (BioSiS, Cook) for closure o f the fetoscopic access p o r t following experimental fetoscopy in the rabbit at midgestation. STUDY DESIGN: Needle fetoscopy was performed in 100 gestational sacs in 16 does at 23/31 days' gestation. In g r o u p I (:1 = 50) the fetoscopic access site was closed using a 5- to 10-mm patch of the bioactive membrane; 50 sacs were left o p e n (positive controls, g r o u p 2). Fifty-two n o n o p e r a t e d sacs were used as negative controls (group 3). Macroscopic a n d microscopic evaluation of the operation site was p e r f o r m e d for evaluation of m e m b r a n e integrity, polymorphonuclear (PN) infiltration, fetal weight, fetal lung weight, and fetal lung to body weight ratio (LWBWR). RESULTS: Membrane integrity was much more frequently restored using the b i o m e m b r a n e (Table). Infiltration of PN was more frequent. LWBWR was compatible with pulmonary hypoplasia in positive controls while normal in all o t h e r fetuses. In 1 animal o f g r o u p 1, a postoperative amniotic b a n d was observed, which never occurred in o u r large experience with this m o d e l CONCLUSION: The use of a bioacdve m e m b r a n e resulted in significant i m p r o v e m e n t o f fetal m e m b r a n e repair rates a n d a significant decrease of p u l m o n a r y hypoplasia, but increased p o l y m o r p h o n u c l e a r infiltration. O n e occasional case of iatrogenic amniotic b a n d was observed. Using m e m b r a n e sealing substances should be investigated further before clinical application.
Membrane integrity LWBWR PN infiltration
0045
J a n u a r y 2001 Gynecol
AmJ O b s t e t
GROUP 1
GROUP 2
2 8 / 4 0 (70%) 0.032 ± 0.0067 1 9 / 4 0 (48%)
13/32 (41%) 0.027 ± 0.0082 5 / 3 2 (16%)
0046
PERINATAL FACTORS PREDICTING SEVERE INTRACRANIAL HEMORRHAGE James A. T h o r p I, Philip G. Jones ~, Jordan H. Perlow"s, Reese Clark 4, Bannie TaborS; IObstetrix of KS & MO, University' of Missouri at Kansas City, St. Luke's Perinatal Center, Kansas City, MO; '2Analytic Consultants, Lee's Summit, MO; :~Obstetrix Medical G r o u p of Phoenix, Maternal Fetal Medicine, Phoenix, AZ; 4pedlatrix Medical Group, Director of Clinical Research, Sunrise, FL; 5Obstetrix Medical G r o u p of Texas, Maternal Fetal Medicine, Fort Worth, TX OBJECTIVE: To assess perinatal factors associated with severe intracranial h e m o r r h a g e (ICH). STUDY DESIGN: Data were prospectively captured in 100 tertiary centers t h r o u g h o u t 5 geographic regions between May 1997 a n d J a n u a r y 2000. Retrospective analysis of n o n a n o m a l o u s newborns admitted to the NICU between 20 a n d 35 weeks' gestation was accomplished by multiple logistic regression. Severe ICH w-as defined as grade III or grade IV ICH. A predictive model was constructed using stepwise variable selection from a pool of 30 antenatal and perinatal factors (Pvalue for entry = .2; Pvalue for retention =. 1). RESULTS: A total of 16,211 cases were available for analysis. Gestational age ~¢as the most important predictor of severe ICH (P < .0001). With 34 weeks' gestation as a reference, the odds ratios were 66 at 23 weeks; 65 at 24 weeks; 50 at 25 weeks; 34 at 26 weeks; 19 at 27 weeks; 17 at 28 weeks; 7.8 at 29 weeks; 5.5 at 31 weeks; and 2.8 at 83 weeks. O t h e r important predictors ofsevere ICH in order of importance were (odds ratio, P value): surfactant use (2.2, <.0001); 5-minute A p g a r score <7 (1.6, .0001); p o o r prenatal care (1.6, .0002); antenatal indomethacin use (1.7, .008); chorioamnionitis (1.4, .016); and presentation (P = .034). Cesarean birth a n d antenatal steroids were not associated with lower rates of severe ICH by univariate or by multivariate analysis (P > .1). The validated model c-statistic was 0.87. CONCLUSIONS: Gestational age was the most important predictor of severe ICH. Antenatal i n d o m e t h a c i n a n d chorioamnionitis were associated with increased risk of severe ICH. Cesarean birth and antenatal steroids were not associated with lower rates of severe ICH.
0047
PREVENTION OFALCOHOL-INDUCED PROINFLAMMATORY CYTOKINE B~I.FASE AND SPATIAL LEARNING DEFICITS WITH NOVEL PEPTIDES IN A M O U S E MODEL OF FETAL A L C O H O L SYNDROME C.Y Spongl,j. Auth I, J. Vink 2, D. T. Abebe 3, I. Gozes 4, D. E. Brenneman2; JNational Institutes of Health, SDMP, LDN, NICHD, Bethesda, MD; 2National Institutes of Health, SDMP, LDN, NICHD, Bethesda, MD; 3NIH, SDMP, LDN, NICHD, Bethesda, MD; 4Tel Aviv Univ., Biochem, Tel Aviv, Israel OBJECTIVE: To evaluate the release of proinflammatory cytoldnes in fetal alcohol syndrome (FAS) a n d the effect of the peptides, NAPVSIPQ (NAP) and SALLRSIPA (SAL) in modulating their release. Because cytokines have known effects on long-term potentiation, a model o f learning at the molecular level, we evaluated l e a r n i n g in adult offspring. Previously NAP+SAL prevented alcohobinduced fetal death, growth abnormalities, a n d oxidative damage in this FAS model. METHODS: A well-characterized FAS mouse model was used. O n day 8, p r e g n a n t mice were injected with alcohol (0.03 m L / k g ) or placebo. Pretreatment with the peptides NAP+SAL (20 lag) or placebo was given 30 minutes before alcohol. For cytokine analysis, embryos were removed after 6 h o u r s a n d analyzed (ELISA) for t u m o r necrosis factor ( T N F ~ ) a n d interleukin-6 (IL-6). To assess learning, adult male offspring were tested in the Morris watermaze evaluating latency to find a hidden platform. RESULTS: T N F ~ was significantly elevated in alcohol vs control (50.0 + 3.5 vs 32.7 + 2.4 p g / m L , P = .001). NAP + SAL pretreatment prevented the alcohobinduced increase (39.9 + 2.8 p g / m L , P = .01) with levels not different than control ( P = .1). Similarly, IL-6 was elevated in alcohol vs control (22.6 + 1.4 vs 17.3 + 0.6 p g / m L , P = .001); NAP + SAL prevented the alcohol-induced increase (19.1 + 1.0, P = .02), with levels similar to control (P = .2). In the Morris watermaze, the alcohol-treated litters exhibited no evidence of learning over the 7d trial. In contrast, the control litters decreased their latency 50% by the fifth day (P = .001). The learning curve of NAP + SAL + alcohol litters was not different than that of control at all time points tested. CONCLUSIONS: T h e peptides NAP + SAL attenuate alcohol-induced increases in p r o i n f l a m m a t o r y cytokines a n d prevent alcohol-induced performance deficits in a learning paradigm. These data suggest that NAP + SAL provide protective efficacy through cytokin~mediated mechanisms.
P <.02 <.05 <.005
NEURONAL NITRIC O ~ [ D E SYNTHASE (NNOS) REGULATES SPONTAN E O U S AND ANGIOTENSIN H (ANG ID-STIMULATED FETAL SWAI.,L O W I N G Mostafa El H a d d a d , Dr. 1, C o n r a d C h a t , Dr t, Michael ROSS2; IHarbor-UCLA, Obstetrics a n d Gynecology, Torrance, CA; 2University of California, Los Angeles, Obstetrics a n d Gynecology, Torrance, CA OBJECTIVE: Spontaneous fetal swallowing occurs at a markedly higher rate when c o m p a r e d with spontaneous adult drinking. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume. Central nitric oxide (NO) is critical for m a i n t a i n i n g n o r m a l rate o f fetal swallowing, as nonselective inhibition of N O (with central L-NAME) suppresses fetal swallowing. We sought to differentiate the contributions of central endothelial versus neuronal N O in the regulation o f s p o n t a n e o u s a n d stimulated fetal swallowing, using a selective nNOS inhibitor. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically p r e p a r e d with fetal vascular a n d intracerebroventricular (ICV) catheters, electrocorticogram (ECoG), a n d esophageal electromyogram electrodes a n d studied at 130 + 1 days' gestation. After an initial 2-hour baseline period, the selective nNOS inhibitor N-propyI-L-arginine (NPLA; 1 mL, 6 lag) was injected ICV. At time 4 hours, the dose of NPLA was repeated, together with Ang II ( 1 mL, 6.4 lag), a n d fetal swallowing was monitored for a final 2 hours. Four fetuses also received an identical control study (on an alternate day) in which NPLA was replaced with artificial cerebrospinal fluid (aCSF). RF~ULTS: Suppression o f nNOS by ICV NPLA significantly reduced mean (:~.SEM) spontaneous fetal swallowing (1.4 + 0.1 to 0.5 + 0.1 swallows/rain; P < .001). ICV injection of Ang lI in the presence o f NPLA h a d no dipsogenic effect o n fetal swallowing (0.7 + 0.1). In the control study ICV injection of aCSF p r o d u c e d n o changes in fetal swallowing, whereas ICV injection of Ang II resulted in a significant increase in the rate of fetal swallowing. CONCLUSION: T h e suppressive dipsogenic effects o f central NPLA indicate that spontaneous a n d Ang II-stimulated fetal swallowing is d e p e n d e n t o n central n N O S activity within dipsogenic neurons. We speculate that the increased rate of fetal swallowing n e a r term may be secondary to the induction of nNOS expression
SMFM Abstracts S23
V o l u m e 184, N u m b e r 1 AmJ Obstet Gvnecol 0048
0049
T H E MECHANISM OF O L I G O H Y D R A M N I O S IN POSTDATES PREGNANCY: A PROSPECTIVE D O P P L E R STUDY Ray Bahado-Singh I. Basia H o l n h e, L'tku Oz 3, Sang-lo,m (:hot t, (;iancarh) Mat+i:', Inci (,unev:+; Iyale University, Ohstetrics & (;ynecology, Maternal-Fetal Medicine Secticm, New Haven, CT: '-'~,tlc LTnivetsity School of Medicine, Ohstetrics and (;ynecologT, New Haveu, (;T; :~Mersin University, OB/(;YN, Mersin; I(]hosnn University Hospital, OB/(;YN, Kwangju (:it}'; :'University t)l'VA Iqealth Systems, OB/(;~ ~'N', Dirisiou of Maternal Fetal Medicine, (;harlottesville, VA OBJECTIVE: Oligohydramnios is tile nlost itnportant predictor t~f Ik'tal colnpronlisc iu postdales pregnanfy, yet its etiology is tutknown. Doppler stndies report cont]icting conclusions as to whether the oligoh,wh'ann'fios correlates with renal artery Doppler inclices. We perfi)rmed renal artery Doppler in a series of postdates pregnancies. METHODS: The renal artery end-diastolic velocity (EDV), resistance index (RI), and nmhilical artery RI were prospectively measured a n d couverted to MoM in singleton postdates pregnancies presentiug ti3r the standard biophysical profile testing. Stepwise logistic regression and the 2tailecl t test were osed to delerlnine whether the Doppler indices correlated with oligohydramuios (amniotic thfid index <5 cm). RESULTS: T h e r e were 147 study cases of which 21 (14.3%) had oligohydwnnnios. The mean (SD) gesta].ional age at Doppler was 41.4 (0.45) week.s and at delivery of 41.8 (0.47) weeks. Stepwise logistic regression ::sing the reual and tnnbilical arten'y Doppler indices finmd the renal RI to be the signilicant predictor of oligohydramnios (13 coefficient -10.42. P < .05). The reoal artery RI (MoM) ~ts signilicantly higher in the C~LSeSwith oligohydramnios mean (SD) = 0.88 ((I. 11) vs 0.86 ((I.05), P = .(14. A statistically significant correlation between a reduced renal artery Doppler EDV and the risk of oligohydramnios was also fin:nd. A renal artery EDV below the mean for gestation was associated with a RR (95% C1) of 1.5 (1.1 to 2.0) of oligohydmmnios. C O N C L U S I O N : O u r stncly, o n e of the largest series to date, f o u n d hemodynamic changes in the le'tal renal artery in postdate pregnancies with oligohydranmios. Renal artery Doppler was su[Jerior to the umbilical artery in predicting oligohydramnios. The association with reduced reual artery EDV indicates that increased arterial i m p e d a n c e occttrs resulting iu r e d n c e d nephron perl'nsicm and nriue productiou. This wot:ld explain the mechanfism of nligohydramnios in postdates pregnancies.
0050
THE NEONATAL NUCLEATED RED B L O O D CELL INDEX: AN INDEPEND E N T P R O G N O S T I C I N D I C A T O R FOR DEATH IN GROWTH-RESTRICTED NEONATES Ahmet Baschad, UIIrich Gembruch, Prof-', Ludwig
0051
Gormen Prof ~, Carl Weiner 4, Christopher Harman4; IUniversity of Maryland at Baltimore, Obstetrics. Gynecology a n d Reproductive Sciences, Baltimore, MD; '-'Medical University LO.beck, Obstetrics & Gynecology, Lfibeck; 3Medical University Giessen, Pediatl-ics. Giessen; 4University of Maryland at Baltimore, Ohstetrics, Gynecology & Reproductive Sciences, Baltimore, MD OBJECTIVE: Fetal hypoxemia is associated with ele~-ated neonatal nucleated red blood cell (NRBC) cotmt and persistence of NRBC count elevation. We sought to determine ira NRBC index reflecting daese 2 factors is an independent risk factor lbr adverse outcome in growth-restricted neonates (IUGR). STUDY DESIGN: NRBC counts per 100 white blood cells (WBC) were determined fi'om a 2-hour postpartnm peripheral blood sample (NRBCI) in 235 IUGR neonates (birth weight <10th percentile). Persistence of NRBC count >10/100 WBC (NRBCP) in clays was deternained. An NRBC index (NRBCI + NRBC2 + NRBCN, where N = NRBCp in days) was calculated. Muhiple logistic regression was performed to deterufine the a.ssociation between NRBC parameters and otllConle. RESULTS: Complications included respiratory distress (RDS, n = 115, 51%). b r o n c h o p n h n o n a r y dysplasia (BPD, n = 29, 2.3%), intraventricular h e m o r r h a g e (IVH, n = 39, 16.6%), necrotizing enterocolitis (NEC, n = 15, 6.4%), a n d neonatal death (n = 10, 4.4%). Each NRBC p a r a m e t e r was significantly h i g h e r in the presence of complications (Table). Regression analysis identified the NRBC index ms an independent predictor of neonatal death (r2= 0.35, P < .001 ), and NEC 0.24, P< .05). C O N C L U S I O N : IUGR neonates with p o s t p a r t u m complications have significandy higher NRBC count and persistence of NRBC cotmt elevation. Only the NRBC index incorporating these 2 variables showed a significant relationship with neonatal death a n d NEC. NRBC1 (MEDIAN)
NRBCP (MEDIAN)
RDS ",s no RDS
11 vs 93*
BPD ,,,s no BPD IVH vs no 1VH NEC vs no NEC
23 vs 208* 23 vs 153" 26 ~ 339*
0.5 vs 3* 1 vs 4*
Dead vs alive
26 vs 2831"
"P < .0001. ~P < .005.
1 vs 41" 2 vs 5* 2 vs 61.
NRBC INDEX (MEDIAN) 11.6 vs 130.2"
27.6 vs 303.8* 27.7 vs 214" ,30.8 vs 484.5* 33 vs 409.8"t"
DOPPLER ULTRASONOGRAPHY FOR TIMING T H E SECOND TRANSFUSION IN FETAL ANEMIA FROM RED CELL ALLOIMMUNIZATION Laura
Detti 1, Utku Oz'-'. Raymond Bahado-Singh:*, Roland Z i m m e r m a n n 4, lnci Gtuley'2, Giancarlo Marl I; I University of Virginia, Obstetrics a n d Gynecology,, ('harlonesville, VA; 2University of Mersin, Obstetrics and Gynecology, Mersin; :~£alc Uuiversity, Obstetrics a n d Gynecology, New Haven, CT; "lUniversity Hospital of Zurich, Obstetrics and Gynecology, Zurich, Switzerland OBJEC'TIVE: The middle cerebral artery peak systolic velocity (MCA-Ic'SV) has heeu successfnlly nsed for timing the first cordocentesis in fetuses at risk for auemia becat:se of maternal red cell alloimmnnization. The objective of this study was to assess the feasibility of MCA-PSV for prediction of moderate and severe anemia in fetuses that had u n d e r g o n e a prior transfusion. STUDY DESIGN: Doppler m e a s u r e m e n t of MCA-PSV was p e r f o r m e d before cordocentesis in 5(.I fetuses. The timing of the second transfosion ~vas based on traditional criteria. The values of MCA-PSV a n d hemoglobin were expressed as multiples of the median (MoM). The threshold for performing a cordocentesis was MCA-PSV _> 1.5 MoM. Anemia was d e f n e d as mild (hemoglobin < 0.84 MoM for a given gestational age), moderate (hemoglobin < 0.65 MoM), a n d severe (hemoglobin < 0.55 MoM). RESULTS: Gestational age at Doppler stndy ranged from 19 to 36 weeks. Twenty-two fetuses (37%) had nol'mal hemoglobin concentration; 21 (36%) had mild anemia; 7 (12%) had moderate anemia; a n d 9 (15%) had severe anemia. MCA-PSV sensitivity was 100% for the detection of both severe a n d moderate anemia with a t'alse-positive rate of 6% and 37%, respectively. CONCLUSIONS: Previously, concerns have been expressed a b o u t the accnracy of Doppler prediction of anemia after a prior transfusion. We have demonstrated that MCA-PSV is an excellent tool to diagnose both severe a n d moderate anemia in fetuses with a prior transfusion. O u r findings expand the clinical situatioo in which Doppler can be nsed to monitor red cell alloimmunized pregnaucies.
RAPID T R A N S I T I O N O F FRESH H U M A N UMBILICAL CORD B L O O D M O N O N U C L E A R Cl~l.l.g T O FETAL B L O O D FOLLOWING INJECTION I N T O THE EXOCELOMIC CAVITY OF T H E RABBIT Jun Wu I, Greet Bries 2,
Eduard Gratacos3, W e m e r Scheers 4, Marc Boogaerts4, J a n DePrestS; ICentre for Surgical Technologies, KU Leuven, Leuven; 2UZ Leuven, Dept o f Haemotology, Leuven; ~Cenu'e for Surgical Technologies, Dept of Obstetrics Gynaecology, Leuven; 4UZ Leuven, Dept of Haematulogy, Leuven; 5University Hospital Gasthuisberg, Leuven, Belgium OBJECTIVES: The window of opportunity for in uteru transplantation of stem cells is prior to 14 weeks. At that time extraembryonic spaces are still well discernible a n d accessible. In the present study we investigated the potential of transition of injected h u m a n umbilical cord blood m o n o n u c l e a r cells (HMNC) from the exocelomic cavity to the fetal blood circulation in a rabbit model. STUDY DESIGN: After collection of fresh h u m a n umbilical cord blood, m o n o n u c l e a r cells were isolated by Ficoll density separation a n d resuspended at 16 x 106/mL in culture medium and 5% rabbit serum. Fetuses from timedated p r e g n a n t New Zealand rabbits were injected with 250 I.tL (6 x 1061 HMNC cells u n d e r the operation microscope, either in the exocelomic cavity (EEC, n = 9) or in file fetal abdominal cavity (AC, n = 6). Twenty-four hours later the animals were sacrificed to harvest EEC fluid, fetal blood, a n d fetal liver, which were homogenized. Samples were analyzed by flow cytometry after incubation with FITC-labeled anti-CD45 monoclonal antibodies, to detect the presence of h u m a n leucocytes. RESULTS: Twenty-four hours after injection into the EEC, HMNC cells were found in 7 of 9 (78%) fetuses, while this s~as 100% after intra-abdominal injection. HMNC represented 3.4% -¢-5.7% of fetal peripheral blood cells in the EEC group, while 12% :l: 17.4% in the AC group. In the EEC g r o u p no HMNC could be detected in the liver homogenate within the 94 hours of the experiment. In all cases in the AC group, HMNC cells were present in the liver homogenates at a mean percentage of 0.5% 4- 0.4%. CONCLUSION: This study provides first evidence that injection of HMNC into the EEC is associated with a rapid transition of a proportion of these cells to fetal peripheral blood. This warrants further investigation into the dynamics of this process a n d the fate of cells injected into the EEC.
S24 SMFM Abstracts 0052
J a n u a ~ , 2001 AmJ Obstet Gynecol
DOPPLER VELOCIMETRY O F T H E DISTAL R I G H T PULMONARY ARTERY AND T H E DEVELOPMENT OF LUNG HYPOPLASIA Luis Medina l, Ricardo Gomez I, Adela Camus 2, Veronica Saez I, Gonzalo Galleguillos2, Rogelio Gonzalez I, Percy Pacora s, Ivan Rojas I, Greggory DeVote 3, Roberto Romero:~; ICEDIP, Sotero del Rio Hospital, OB/Gyn, Univ Catolica de Chile, Pnente Alto, Santiago; 2CEDIP, Sotero del Rio Hospital, Puente Alto, Santiago. Chile; SPerinatology Research Branch, NICHD. Bethesda, MD OBJECTIVE: L u n g hypoplasia (LH) is a major cause of perinatal death in patients with preterm PROM a n d in disorders characterized by restrictive h m g disease. Pulmonary hypertension is frequently present in LH. The objective of this study was to d e t e r m i n e if there is a relationship between the fetal pulmonary vascular bed impedance to flow a n d the subsequent development of LH. STUDY DESIGN: A case-control study was designed including 16 fetuses who died at birth because of LH (cases) a n d 185 control patients. Controls were fetuses with normal outcome. Measurements were performed in the distal branch of the right pulmonary artery (DRPA) with an angle close to 0 degrees. Parameters o b t a i n e d were pulsatility index (PI), peak velocity (PV), a n d velocity time integral (VTI). Regression analysis and nonparametric procedures were used for analysis. RESULTS: A reference range for Doppler indices of the DRPA was constructed based on the control population. DRPA PI and VTI c h a n g e d with gestadonal age (GA) but PV did not. For comparisons, delta values (mean-actual value) were obtained when PIj ". • the variable c h a n g e d with GA. Cases with LH h a d a higher delta DRPA PI a n d a lower delta DRPA VTI than controls (delta PI: median 2.76 [1.00 to 5.15] vs median -0.03 [-1.24 to 7 • 1.72], P < .001; delta VTI: m e d i a n - 0 . 0 1 1 [-0.03 to 0.01] vs median -0.002 .=It l'It'... ,,. . I * ".--'I [-0.03 to 0.06], P < .001, respectively). All cases with LH (triangles in the Figure) had a DRPA PI above the 95% confidence limit 18 24 30 36 40 for GA. There were no differences for DRPA PV beGestational age (wks) tween groups. CONCLUSION: Fetuses with LH had significandy higher impedance to flow in the pulmonary circulation. This parameter may be of clinical value in the risk assessment of fetal pulmonary hypoplasia.
S1
"
"; .