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418: Risk factors associated with intrauterine fetal demise (IUFD) in patients with positive and negative thrombophilia workup
SMFM Abstracts 417
www.AJOG.org
FETAL ECHOCARDIOGRAPHY CAN HELP PREDICT NEED FOR BALLOON ATRIAL SEPTOSTOMY IN THE NEONATE WITH TRANSPOSITION OF THE GREAT ARTERIES MARSHA AYZEN1, JACK RYCHIK2, 1The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, 2Fetal Heart Program at The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania OBJECTIVE: Transposition of the great arteries (TGA) can cause severe cyanosis in the newborn. Urgent balloon atrial septostomy (BAS) is often required in order to increase mixing and improve oxygenation prior to surgical correction. The great arterial relationship of TGA is readily diagnosed on fetal echocardiography (FE), however no method is currently available for predicting need for a postnatal BAS. We sought to determine whether the degree of excursion of the atrial septum, or relative size of the ductus arteriosus on FE may predict severe cyanosis and need for BAS in TGA. STUDY DESIGN: Retrospective review of 3rd trimester FE and records of 20 fetuses with TGA, gestational age 29-38 weeks (median 36 weeks). Ratio of the diameter of maximal atrial septal excursion into the left atrium-to-the left atrial width (max ASE ratio) in the four chamber view, as well as ratio of the diameter of the mid-portion of the ductus arteriosus-to-the pulmonary annulus (DA/PA ratio) was measured, while blinded to postnatal course. Indices were compared between fetuses who received BAS after birth (group 1) and those who did not (group 2). RESULTS: 7/20 underwent BAS (group1). Lowest average pO2 in the 1st 24 hours of life was 25⫹4 mm Hg for group 1 vs 35⫹6 mm for group 2 (p⬍0.0002). Max ASE ratio on fetal echo was lower for group 1 than group 2 (0.4⫹0.11 vs 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) CONCLUSION: Limited excursion of the atrial septum on FE is associated with postnatal hypoxemia and the need for BAS in TGA. Analysis of the position of the fetal atrial septum in TGA may prove useful in counseling families as to the need for delivery at a center that can offer urgent BAS at birth.
419
0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.446
418
RISK FACTORS ASSOCIATED WITH INTRAUTERINE FETAL DEMISE (IUFD) IN PATIENTS WITH POSITIVE AND NEGATIVE THROMBOPHILIA WORKUP DIMITRIOS 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, Obstetrics & Gynecology, Philadelphia, Pennsylvania, 3Temple University School of Medicine, Obstetrics, Gynecology and Reproductive Sciences, Philadelphia, Pennsylvania OBJECTIVE: Still births occur in 1:200 pregnancies constituting almost half of the perinatal mortality while at least half are unexplained. Thrombophilia workup 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 collected. 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 disorders. CONCLUSION: Patients with recent IUFD positive for thrombophilia have different 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.
LIMK PHOSPHORYLATION MEDIATES MMP-INDUCED COLLAGEN REMODELING OF THE CHRONICALLY HYPOXIC FETAL HEART YAFENG DONG1, WEIJIAN HOU2, CARL P WEINER1, 1University of Kansas, Kansas City, Kansas, 2University of Kansas School of Medicine, Obstetrics and Gynecology, Kansas OBJECTIVE: Chronically hypoxemic fetuses are at increased risk for adult cardiovascular diseases, e.g. hypertension, coronary heart disease. Chronic hypoxia induced collagen remodeling in the fetal heart leads by an unknown mechanism to pathological cardiac remodeling, diastolic dysfunction and increased sensitivity to ischemic injury. We tested the hypothesis the functional integrity of the fetal heart depends on collagen remodeling mediated by LIMK phosphorylation. STUDY DESIGN: Guinea pigs (n⫽4 per group) were housed in 10.5% O2 from 0.6-0.8 gestation (HPX). Controls (NMX) were housed in room air. Dams were delivered at 0.8 gestation and the fetal hearts rapidly frozen in liquid N2. mRNA was quantified by RT PCR. Melt analysis confirmed PCR amplification specificity; the slope of the std curve was used to determine PCR efficiency. Gene quantification was calculated by the delta-delta CT (2-DDCt) method with the 18S rRNA subunit as the control. Proteins were quantified by Western blotting using a 7.5% polyacrylamide gel. Bands were quantified by densitometry. All results were compared byttest, and a P⬍0.05 considered significant. RESULTS: Collagens I, III and VI proteins were significantly increased to 54%, 9% and 27%, respectively. LIMK1/2 was also upregulated at both the mRNA and protein levels. Phosphorylated LIMK1/2 increased 116% during HPX. In addition, Rho GTPases (RhoA, Rac-1 and Cdc42), MMP family genes (MMP2, MMP8, MMP9) and MAPs (ERK1/2) were each significantly increased by HPX at the mRNA and protein levels. CONCLUSION: We identify a new mechanism by which chronic fetal hypoxia 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 of fetal adaptation to hypoxia that becomes maladaptive under certain circumstances. Pharmacological inhibitors that inactivate LIMK phosphorylation might prevent the remodeling and the long-term effects of chronic hypoxia. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.448
420
WITHDRAWN 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.449
Characteristics of positive and negative groups
Age (years) # 1 trimester losses ( 10 weeks) Stillbirth weight (gr) Hypertensive disorders Abruption Cocaine abuse
Group 1
Group 2
N⫽58 24 0.50 1660 7 1 16
N⫽31 28 2.55 949 11 6 2
P value P⫽.002 P⫽0.00 P⫽0.004 P⫽0.006 P⫽0.003 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
www.AJOG.org
FETAL ECHOCARDIOGRAPHY CAN HELP PREDICT NEED FOR BALLOON ATRIAL SEPTOSTOMY IN THE NEONATE WITH TRANSPOSITION OF THE GREAT ARTERIES MARSHA AYZEN1, JACK RYCHIK2, 1The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, 2Fetal Heart Program at The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania OBJECTIVE: Transposition of the great arteries (TGA) can cause severe cyanosis in the newborn. Urgent balloon atrial septostomy (BAS) is often required in order to increase mixing and improve oxygenation prior to surgical correction. The great arterial relationship of TGA is readily diagnosed on fetal echocardiography (FE), however no method is currently available for predicting need for a postnatal BAS. We sought to determine whether the degree of excursion of the atrial septum, or relative size of the ductus arteriosus on FE may predict severe cyanosis and need for BAS in TGA. STUDY DESIGN: Retrospective review of 3rd trimester FE and records of 20 fetuses with TGA, gestational age 29-38 weeks (median 36 weeks). Ratio of the diameter of maximal atrial septal excursion into the left atrium-to-the left atrial width (max ASE ratio) in the four chamber view, as well as ratio of the diameter of the mid-portion of the ductus arteriosus-to-the pulmonary annulus (DA/PA ratio) was measured, while blinded to postnatal course. Indices were compared between fetuses who received BAS after birth (group 1) and those who did not (group 2). RESULTS: 7/20 underwent BAS (group1). Lowest average pO2 in the 1st 24 hours of life was 25⫹4 mm Hg for group 1 vs 35⫹6 mm for group 2 (p⬍0.0002). Max ASE ratio on fetal echo was lower for group 1 than group 2 (0.4⫹0.11 vs 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) CONCLUSION: Limited excursion of the atrial septum on FE is associated with postnatal hypoxemia and the need for BAS in TGA. Analysis of the position of the fetal atrial septum in TGA may prove useful in counseling families as to the need for delivery at a center that can offer urgent BAS at birth.
419
0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.446
418
RISK FACTORS ASSOCIATED WITH INTRAUTERINE FETAL DEMISE (IUFD) IN PATIENTS WITH POSITIVE AND NEGATIVE THROMBOPHILIA WORKUP DIMITRIOS 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, Obstetrics & Gynecology, Philadelphia, Pennsylvania, 3Temple University School of Medicine, Obstetrics, Gynecology and Reproductive Sciences, Philadelphia, Pennsylvania OBJECTIVE: Still births occur in 1:200 pregnancies constituting almost half of the perinatal mortality while at least half are unexplained. Thrombophilia workup 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 collected. 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 disorders. CONCLUSION: Patients with recent IUFD positive for thrombophilia have different 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.
LIMK PHOSPHORYLATION MEDIATES MMP-INDUCED COLLAGEN REMODELING OF THE CHRONICALLY HYPOXIC FETAL HEART YAFENG DONG1, WEIJIAN HOU2, CARL P WEINER1, 1University of Kansas, Kansas City, Kansas, 2University of Kansas School of Medicine, Obstetrics and Gynecology, Kansas OBJECTIVE: Chronically hypoxemic fetuses are at increased risk for adult cardiovascular diseases, e.g. hypertension, coronary heart disease. Chronic hypoxia induced collagen remodeling in the fetal heart leads by an unknown mechanism to pathological cardiac remodeling, diastolic dysfunction and increased sensitivity to ischemic injury. We tested the hypothesis the functional integrity of the fetal heart depends on collagen remodeling mediated by LIMK phosphorylation. STUDY DESIGN: Guinea pigs (n⫽4 per group) were housed in 10.5% O2 from 0.6-0.8 gestation (HPX). Controls (NMX) were housed in room air. Dams were delivered at 0.8 gestation and the fetal hearts rapidly frozen in liquid N2. mRNA was quantified by RT PCR. Melt analysis confirmed PCR amplification specificity; the slope of the std curve was used to determine PCR efficiency. Gene quantification was calculated by the delta-delta CT (2-DDCt) method with the 18S rRNA subunit as the control. Proteins were quantified by Western blotting using a 7.5% polyacrylamide gel. Bands were quantified by densitometry. All results were compared byttest, and a P⬍0.05 considered significant. RESULTS: Collagens I, III and VI proteins were significantly increased to 54%, 9% and 27%, respectively. LIMK1/2 was also upregulated at both the mRNA and protein levels. Phosphorylated LIMK1/2 increased 116% during HPX. In addition, Rho GTPases (RhoA, Rac-1 and Cdc42), MMP family genes (MMP2, MMP8, MMP9) and MAPs (ERK1/2) were each significantly increased by HPX at the mRNA and protein levels. CONCLUSION: We identify a new mechanism by which chronic fetal hypoxia 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 of fetal adaptation to hypoxia that becomes maladaptive under certain circumstances. Pharmacological inhibitors that inactivate LIMK phosphorylation might prevent the remodeling and the long-term effects of chronic hypoxia. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.448
420
WITHDRAWN 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.449
Characteristics of positive and negative groups
Age (years) # 1 trimester losses ( 10 weeks) Stillbirth weight (gr) Hypertensive disorders Abruption Cocaine abuse
Group 1
Group 2
N⫽58 24 0.50 1660 7 1 16
N⫽31 28 2.55 949 11 6 2
P value P⫽.002 P⫽0.00 P⫽0.004 P⫽0.006 P⫽0.003 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