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417 FETAL ECHOCARDIOGRAPHY CAN HELP PREDICT NEED FOR BALLOON ATRIAL 419 LIMK PHOSPHORYLATION MEDIATES MMP-INDUCED COLLAGEN REMODELING OF THE
SEPTOSTOMY IN THE NEONATE WITH TRANSPOSITION OF THE GREAT CHRONICALLY HYPOXIC FETAL HEART YAFENG DONG1, WEIJIAN HOU2, CARL P
ARTERIES MARSHA AYZEN1, JACK RYCHIK2, 1The Children’s Hospital of Philadel- WEINER1, 1University of Kansas, Kansas City, Kansas, 2University of Kansas School
phia, Philadelphia, Pennsylvania, 2Fetal Heart Program at The Children’s Hospital of Medicine, Obstetrics and Gynecology, Kansas
of Philadelphia, Philadelphia, Pennsylvania OBJECTIVE: Chronically hypoxemic fetuses are at increased risk for adult car-
OBJECTIVE: Transposition of the great arteries (TGA) can cause severe cyanosis diovascular diseases, e.g. hypertension, coronary heart disease. Chronic hypoxia
in the newborn. Urgent balloon atrial septostomy (BAS) is often required in order induced collagen remodeling in the fetal heart leads by an unknown mechanism to
to increase mixing and improve oxygenation prior to surgical correction. The great pathological cardiac remodeling, diastolic dysfunction and increased sensitivity to
arterial relationship of TGA is readily diagnosed on fetal echocardiography (FE),
however no method is currently available for predicting need for a postnatal BAS. ischemic injury. We tested the hypothesis the functional integrity of the fetal heart
We sought to determine whether the degree of excursion of the atrial septum, or depends on collagen remodeling mediated by LIMK phosphorylation.
relative size of the ductus arteriosus on FE may predict severe cyanosis and need for STUDY DESIGN: Guinea pigs (n⫽4 per group) were housed in 10.5% O2 from
BAS in TGA. 0.6-0.8 gestation (HPX). Controls (NMX) were housed in room air. Dams were
STUDY DESIGN: Retrospective review of 3rd trimester FE and records of 20 delivered at 0.8 gestation and the fetal hearts rapidly frozen in liquid N2. mRNA was
fetuses with TGA, gestational age 29-38 weeks (median 36 weeks). Ratio of the quantified by RT PCR. Melt analysis confirmed PCR amplification specificity; the
diameter of maximal atrial septal excursion into the left atrium-to-the left atrial slope of the std curve was used to determine PCR efficiency. Gene quantification
width (max ASE ratio) in the four chamber view, as well as ratio of the diameter of was calculated by the delta-delta CT (2-DDCt) method with the 18S rRNA subunit
the mid-portion of the ductus arteriosus-to-the pulmonary annulus (DA/PA ratio) as the control. Proteins were quantified by Western blotting using a 7.5% polyacryl-
was measured, while blinded to postnatal course. Indices were compared between amide gel. Bands were quantified by densitometry. All results were compared byt-
fetuses who received BAS after birth (group 1) and those who did not (group 2). test, and a P⬍0.05 considered significant.
RESULTS: 7/20 underwent BAS (group1). Lowest average pO2 in the 1st 24 RESULTS: Collagens I, III and VI proteins were significantly increased to 54%,
hours of life was 25⫹4 mm Hg for group 1 vs 35⫹6 mm for group 2 (p⬍0.0002). 9% and 27%, respectively. LIMK1/2 was also upregulated at both the mRNA and
Max ASE ratio on fetal echo was lower for group 1 than group 2 (0.4⫹0.11 vs protein levels. Phosphorylated LIMK1/2 increased 116% during HPX. In addition,
0.6⫹0.25, p⫽ 0.03). No difference was noted in DA/PA ratio between group 1 and
group 2 (0.47⫹0.1 vs 0.45⫹0.15, p⫽NS) Rho GTPases (RhoA, Rac-1 and Cdc42), MMP family genes (MMP2, MMP8,
CONCLUSION: Limited excursion of the atrial septum on FE is associated with MMP9) and MAPs (ERK1/2) were each significantly increased by HPX at the
postnatal hypoxemia and the need for BAS in TGA. Analysis of the position of the mRNA and protein levels.
fetal atrial septum in TGA may prove useful in counseling families as to the need for CONCLUSION: We identify a new mechanism by which chronic fetal hypoxia
delivery at a center that can offer urgent BAS at birth. causes cardiac injury. Chronic hypoxia triggers fetal cardiac collagen remodeling by
LIMK phosphorylation through RhoGTPase, MMPs and MAP kinase activation.
The LIMK dephosphorylation-phosphorylation axis appears yet another example
0002-9378/$ - see front matter of fetal adaptation to hypoxia that becomes maladaptive under certain circum-
doi:10.1016/j.ajog.2008.09.446 stances. Pharmacological inhibitors that inactivate LIMK phosphorylation might
prevent the remodeling and the long-term effects of chronic hypoxia.

418 RISK FACTORS ASSOCIATED WITH INTRAUTERINE FETAL DEMISE (IUFD) IN PATIENTS 0002-9378/$ - see front matter
WITH POSITIVE AND NEGATIVE THROMBOPHILIA WORKUP DIMITRIOS doi:10.1016/j.ajog.2008.09.448
MASTROGIANNIS1, JENNIFER COX2, VANI DANDOLU3, 1Temple University School of
Medicine, Obstetrics and Gynecology and Reproductive Science, Philadelphia,
Pennsylvania, 2Temple University School of Medicine, Temple University, Obstet-
rics & Gynecology, Philadelphia, Pennsylvania, 3Temple University School of Med- 420 WITHDRAWN
icine, Obstetrics, Gynecology and Reproductive Sciences, Philadelphia, Pennsylva-
nia
OBJECTIVE: Still births occur in 1:200 pregnancies constituting almost half of 0002-9378/$ - see front matter
the perinatal mortality while at least half are unexplained. Thrombophilia workup doi:10.1016/j.ajog.2008.09.449
has become an integral part of the evaluation of patients with IUFD. In this study,
we compared risk factors associated with IUFD in patients with recent stillbirths
with positive and negative thrombophilia workup.
STUDY DESIGN: Retrospective review of 89 patients following an IUFD for
evaluation between 2001-2007. The patients underwent thrombophilia workup as
part of their evaluation (consisting of the following tests: anticardiolipin antibodies,
lupus anticoagulant, factor V Leiden mutation, prothrombin mutation, protein S,
C, antithrombin III deficiencies and fasting serum homocysteine). Demographic,
social, obstetrical, pathological and autopsy, along with medical data were col-
lected. Two groups were identified based on positive (defined as any positive) or
negative thrombophilia workup (defined as all negative tests).
RESULTS: 58 patients were found to have negative (group 1) while 31 had
positive (group 2) thrombophilia workup. The negative group was younger with
more cocaine use, less hypertensive disorders and abruption, but higher stillbirth
weight. The positive group had more first trimester losses and hypertensive disor-
ders.
CONCLUSION: Patients with recent IUFD positive for thrombophilia have dif-
ferent characteristics (probably due to early placental compromise) than patients
who were negative justifying a different approach for counseling, management and
follow up in future pregnancies.
Characteristics of positive and negative groups
Group 1 Group 2
N⫽58 N⫽31 P value
Age (years) 24 28 P⫽.002
# 1 trimester losses ( 10 weeks) 0.50 2.55 P⫽0.00
Stillbirth weight (gr) 1660 949 P⫽0.004
Hypertensive disorders 7 11 P⫽0.006
Abruption 1 6 P⫽0.003
Cocaine abuse 16 2 P⫽0.019

0002-9378/$ - see front matter


doi:10.1016/j.ajog.2008.09.447

S126 American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008

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