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Fas and Fas ligand polymorphism in preterm labor
S48 SMFM Abstracts 137
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FAS AND FAS LIGAND POLYMORPHISM IN PRETERM LABOR ALEKSANDR FUKS1, LANCE PARTON2, SATYA POLAVARAPU1, DENISE NETTA3, SONYA STRASSBERG2, IOANA GODI2, CHAUR-DONG HSU1, 1New York Medical College - Westchester Medical Center, Obstetrics and Gynecology, Valhalla, New York, 2New York Medical College - Westchester Medical Center, Pediatrics, Valhalla, New York, 3 UMDNJ - Robert Wood Johnson Medical School / Robert Wood Johnson University Hospital, Obstetrics and Gynecology, New Brunswick, New Jersey OBJECTIVE: Fetal inflammatory response has been demonstrated to be involved in the pathogenesis of preterm birth (PTB). We have previously reported on the role of Fas/Fas ligand (FasL) signal pathway of apoptosis in PTB. Subsequently we investigated the association between polymorphisms at position -670 in the Fas gene and position -124 in the FasL gene demonstrated in neonatal oral mucosa cells and PTB. STUDY DESIGN: Thirty seven singleton pregnancies were studied. Nineteen pregnancies were complicated by PTB and eighteen were full-term controls. Buccal swabs were obtained from each neonate and extracted DNA was analyzed by polymerase chain reaction-based restriction fragment length polymorphism for an adenine (A) to guanine (G) substitution at position -670 in the Fas promoter gene and at position -124 in the FasL gene. Chi-square and Fisher’s exact tests were used for statistical analysis. RESULTS: There was no difference with respect to race, maternal age and parity between the two groups. Frequencies of Fas -670 AG, -AA, and -GG genotype in PTB group differed from those in controls, but not statistically significantly (P = .692). Similar findings were observed when frequencies of FasL -124 AG, -AA, and -GG genotypes in PTB group were compared to controls. Neonatal heterozygous AG genotype at position -124 of the FasL gene was observed in 31.6% of PTB patients, as opposed to 11.1% in controls. No cases of homozygous GG genotype at position -124 of the FasL gene were observed in either of the groups. CONCLUSION: Our data suggest that Fas promoter gene AG polymorphism at position -670 and FasL gene AG polymorphism at position -124 may not be significantly involved in the Fas / FasL signal pathway of apoptosis associated with PTB.
THE EFFECT OF MATERNAL PREDNISONE USE ON SECOND-TRIMESTER MATERNAL SERUM UNCONJUGATED ESTRIOL LEVELS—RESULTS FROM THE FASTER TRIAL SABRINA CRAIGO1, ADAM URATO1, JACOB CANICK2, GINA PELOSO3, FERGAL MALONE4, BRYAN OSHIRO5, DAVID LUTHY6, CHRISTINE H. COMSTOCK7, GARY HANKINS8, RICHARD BERKOWITZ9, SUSAN GROSS10, LORRAINE DUGOFF11, ILAN TIMOR12, STEPHEN CARR2, HONOR WOLFE13, MARY D’LTON4, 1Tufts University, Boston, Massachusetts, 2Brown University, Providence, Rhode Island, 3DM-Stat, Medford, Massachusetts, 4Columbia University, New York, New York, 5University of Utah Health Sciences Center, Salt Lake City, Utah, 6 Swedish Medical Center, Seattle, Washington, 7William Beaumont Medical Center, Royal Oak, Michigan, 8University of Texas Medical Branch at Galveston, Galveston, Texas, 9Mount Sinai Medical Center, New York, New York, 10Albert Einstein College of Medicine, Bronx, New York, 11University of Colorado Health Sciences Center, Denver, Colorado, 12New York University, New York, New York, 13University of North Carolina, Chapel Hill, North Carolina OBJECTIVE: Prednisone is a widely used medication among women of childbearing age. Prednisone is known to alter the hypothalamic-pituitary axis, thus affecting endogenous maternal hormone levels. This study sought to determine the association between maternal prednisone use and changes in the unconjugated estriol values measured during second-trimester maternal serum screening. STUDY DESIGN: Data were obtained from the FASTER trial. Upon entry into the trial, patients were asked if they were using prednisone / taking steroids. Quad tests were performed on women from 15 to 18 weeks’gestation and levels of unconjugated estriol were assessed. Multivariable linear and logistic regression were then used to assess the association between prednisone use and log-transformed unconjugated estriol levels and to estimate the screen positive rate, adjusting for relevant confounders. RESULTS: 283 women out of 35,231 (0.80%) patients in the trial were taking prednisone. After adjusting for age, race, diabetes, smoking, alcohol use, and the presence of aneuploidy, the ratio of the median MoM for prednisone users to the median MoM for non-users is 0.88 (P ! .0001.) The age-adjusted screen positive rate in prednisone users was 13.6% (9.9-17.3), versus 8.6% (8.3-8.9) in non-users (P = .002.) CONCLUSION: Maternal prednisone use is associated with a lower unconjugated estriol MOM value on maternal serum screening and a significantly higher screen positive rate. Further study is needed to determine whether these effects are dose dependent, and whether prednisone use should be taken into consideration when evaluating the serum Quad screen.
HISTORY OF MISCARRIAGE AND INCREASED INCIDENCE OF FETAL ANEUPLOIDY IN SUBSEQUENT PREGNANCY KATHERINE BIANCO1, AARON B. CAUGHEY1, BRIAN SHAFFER1, REGINA BERGQUIST1, MARY NORTON1, 1University of California, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California OBJECTIVE: The purpose of this study was to examine history of spontaneous abortion (SAB) as a predictor of chromosomal abnormalities. STUDY DESIGN: This was a retrospective cohort study of all women that underwent fetal karyotype analysis with amniocentesis or CVS at a single prenatal diagnosis referral center. Information on SABs, parity, maternal age, and karyotype were assessed. Univariate and multivariate analyses were conducted. RESULTS: A total of 46,939 women were included. We found an increased risk of any aneuploidy (trisomy or monosomy) as the number of SABs increased
(P = .007). When we examined only the most common trisomies 13, 18, and 21, an increased risk is also seen with increasing number of SABs (Table). These differences persisted when controlling for maternal age, but were only statistical significant for 3 or more SABs. CONCLUSION: An increased risk of karyotypic abnormality is demonstrated in patients who have 3 or more SABs. This study provides novel information regarding this risk among patients who are presenting for prenatal diagnosis, and can be used to counsel such patients. These results need to be examined in low risk populations.
Number of SABs
Rate of tri 13, 18, or 21 P = .001
OR for tri 13, 18, or 21 (P value)
OR for any aneuploidy (P value)
0 1 2 3
1.10 1.45 1.56 1.70
— 1.17 (0.084) 1.28 (0.064) 1.44 (0.012)
— 1.08 (.081) 1.21 (.083) 1.48 (.027)
% % % %
All statistical comparisons are to patients with no prior SABs.
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FIRST AND SECOND TRIMESTER DOWN SYNDROME SCREENING MARKERS IN PREGNANCIES ACHIEVED THROUGH ASSISTED REPRODUCTIVE TECHNOLOGIES (ART): A FASTER TRIAL STUDY GERALYN LAMBERT-MESSERLIAN1, LORRAINE DUGOFF2, JOHN VIDAVER3, JACOB CANICK1, FERGAL MALONE4, FLINT PORTER5, CHRISTINE COMSTOCK6, DAVID LUTHY7, RADEK BUKOWSKI8, KEITH EDDLEMAN9, SUSAN GROSS10, SABRINA CRAIGO11, ILAN TIMOR12, STEPHEN CARR13, HONOR WOLFE14, MARY D’ALTON4, 1Brown University, Pathology and Laboratory Medicine, Providence, Rhode Island, 2University of Colorado Health Sciences Center, Denver, Colorado, 3DM-Stat, Medford, Massachusetts, 4Columbia University, New York, New York, 5University of Utah Health Sciences Center, Salt Lake City, Utah, 6William Beaumont Hospital, Royal Oak, Michigan, 7Swedish Medical Center, Seattle, Washington, 8University of Texas Medical Branch at Galveston, Galveston, Texas, 9Mount Sinai School of Medicine, New York, New York, 10Albert Einstein College of Medicine, Bronx, New York, 11Tufts University, Boston, Massachusetts, 12New York University, New York, New York, 13Women and Infants’ Hospital, Providence, Rhode Island, 14University of North Carolina, Chapel Hill, North Carolina OBJECTIVE: To determine whether first and second trimester Down syndrome screening markers and screen positive rates are altered in pregnancies achieved by assisted reproductive technologies (ART). STUDY DESIGN: ART pregnancies were identified as part of the FASTER Trial. Marker levels were expressed as multiple of the median (MoM) values and were evaluated for five types of ART: IVF with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), intrauterine insemination with OI (IUI-OI), or IUI without OI (IUI). Each group was compared to non-ART controls (n = 37,070) by Mann Whitney U analysis. RESULTS: PAPP-A was lower and free b-hCG was higher in ART pregnancies, but these trends were not significant and did not occur in ED pregnancies. Second trimester markers were significantly altered in IVF and IUI pregnancies, (lower uE3; higher hCG and inhA). ED pregnancies had higher AFP and inhA. Second, but not first trimester screen positive rates were significantly higher than expected, except when ED was used. First and second trimester median MoM levels and screen positive rates in ART patient groups IVF-OI (278) IUI-OI (323) IUI (247) IVF-OI-ED (59) IVF-ED (56) NT 1.03 PAPP-A 0.94 fB-hCG 1.13 1T+ (%) 8.6 Expected + (%) 5.5 AFP 1.05 uE3 0.94* hCG 1.10 inhA 1.12* 2T+ (%) 20.2# Expected + (%) 14.7
1.02 0.91* 1.06 3.4 4.2 1.04 0.91* 1.12* 1.10* 21.2# 11.9
1.97 0.98 1.08 6.1 4.3 0.96 0.94* 1.09 1.09* 19.1# 12.3
0.96 1.09 0.99 3.5 2.5 1.19* 0.95 1.09 1.35* 12.5 7.4
0.96 1.00 1.22 1.8 1.0 1.26* 0.93 1.15 1.33* 7.4 3.9
+ = screen positive. * P ! .005 versus control group levels. # P ! .05 versus expected positive rate. CONCLUSION: These data show for the first time that ART has a greater impact on second than first trimester screening, and that inhA levels are markedly increased in all types of ART. Adjustment for ART in the second trimester screening is warranted but complicated, depending on the type of ART used.
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FAS AND FAS LIGAND POLYMORPHISM IN PRETERM LABOR ALEKSANDR FUKS1, LANCE PARTON2, SATYA POLAVARAPU1, DENISE NETTA3, SONYA STRASSBERG2, IOANA GODI2, CHAUR-DONG HSU1, 1New York Medical College - Westchester Medical Center, Obstetrics and Gynecology, Valhalla, New York, 2New York Medical College - Westchester Medical Center, Pediatrics, Valhalla, New York, 3 UMDNJ - Robert Wood Johnson Medical School / Robert Wood Johnson University Hospital, Obstetrics and Gynecology, New Brunswick, New Jersey OBJECTIVE: Fetal inflammatory response has been demonstrated to be involved in the pathogenesis of preterm birth (PTB). We have previously reported on the role of Fas/Fas ligand (FasL) signal pathway of apoptosis in PTB. Subsequently we investigated the association between polymorphisms at position -670 in the Fas gene and position -124 in the FasL gene demonstrated in neonatal oral mucosa cells and PTB. STUDY DESIGN: Thirty seven singleton pregnancies were studied. Nineteen pregnancies were complicated by PTB and eighteen were full-term controls. Buccal swabs were obtained from each neonate and extracted DNA was analyzed by polymerase chain reaction-based restriction fragment length polymorphism for an adenine (A) to guanine (G) substitution at position -670 in the Fas promoter gene and at position -124 in the FasL gene. Chi-square and Fisher’s exact tests were used for statistical analysis. RESULTS: There was no difference with respect to race, maternal age and parity between the two groups. Frequencies of Fas -670 AG, -AA, and -GG genotype in PTB group differed from those in controls, but not statistically significantly (P = .692). Similar findings were observed when frequencies of FasL -124 AG, -AA, and -GG genotypes in PTB group were compared to controls. Neonatal heterozygous AG genotype at position -124 of the FasL gene was observed in 31.6% of PTB patients, as opposed to 11.1% in controls. No cases of homozygous GG genotype at position -124 of the FasL gene were observed in either of the groups. CONCLUSION: Our data suggest that Fas promoter gene AG polymorphism at position -670 and FasL gene AG polymorphism at position -124 may not be significantly involved in the Fas / FasL signal pathway of apoptosis associated with PTB.
THE EFFECT OF MATERNAL PREDNISONE USE ON SECOND-TRIMESTER MATERNAL SERUM UNCONJUGATED ESTRIOL LEVELS—RESULTS FROM THE FASTER TRIAL SABRINA CRAIGO1, ADAM URATO1, JACOB CANICK2, GINA PELOSO3, FERGAL MALONE4, BRYAN OSHIRO5, DAVID LUTHY6, CHRISTINE H. COMSTOCK7, GARY HANKINS8, RICHARD BERKOWITZ9, SUSAN GROSS10, LORRAINE DUGOFF11, ILAN TIMOR12, STEPHEN CARR2, HONOR WOLFE13, MARY D’LTON4, 1Tufts University, Boston, Massachusetts, 2Brown University, Providence, Rhode Island, 3DM-Stat, Medford, Massachusetts, 4Columbia University, New York, New York, 5University of Utah Health Sciences Center, Salt Lake City, Utah, 6 Swedish Medical Center, Seattle, Washington, 7William Beaumont Medical Center, Royal Oak, Michigan, 8University of Texas Medical Branch at Galveston, Galveston, Texas, 9Mount Sinai Medical Center, New York, New York, 10Albert Einstein College of Medicine, Bronx, New York, 11University of Colorado Health Sciences Center, Denver, Colorado, 12New York University, New York, New York, 13University of North Carolina, Chapel Hill, North Carolina OBJECTIVE: Prednisone is a widely used medication among women of childbearing age. Prednisone is known to alter the hypothalamic-pituitary axis, thus affecting endogenous maternal hormone levels. This study sought to determine the association between maternal prednisone use and changes in the unconjugated estriol values measured during second-trimester maternal serum screening. STUDY DESIGN: Data were obtained from the FASTER trial. Upon entry into the trial, patients were asked if they were using prednisone / taking steroids. Quad tests were performed on women from 15 to 18 weeks’gestation and levels of unconjugated estriol were assessed. Multivariable linear and logistic regression were then used to assess the association between prednisone use and log-transformed unconjugated estriol levels and to estimate the screen positive rate, adjusting for relevant confounders. RESULTS: 283 women out of 35,231 (0.80%) patients in the trial were taking prednisone. After adjusting for age, race, diabetes, smoking, alcohol use, and the presence of aneuploidy, the ratio of the median MoM for prednisone users to the median MoM for non-users is 0.88 (P ! .0001.) The age-adjusted screen positive rate in prednisone users was 13.6% (9.9-17.3), versus 8.6% (8.3-8.9) in non-users (P = .002.) CONCLUSION: Maternal prednisone use is associated with a lower unconjugated estriol MOM value on maternal serum screening and a significantly higher screen positive rate. Further study is needed to determine whether these effects are dose dependent, and whether prednisone use should be taken into consideration when evaluating the serum Quad screen.
HISTORY OF MISCARRIAGE AND INCREASED INCIDENCE OF FETAL ANEUPLOIDY IN SUBSEQUENT PREGNANCY KATHERINE BIANCO1, AARON B. CAUGHEY1, BRIAN SHAFFER1, REGINA BERGQUIST1, MARY NORTON1, 1University of California, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, California OBJECTIVE: The purpose of this study was to examine history of spontaneous abortion (SAB) as a predictor of chromosomal abnormalities. STUDY DESIGN: This was a retrospective cohort study of all women that underwent fetal karyotype analysis with amniocentesis or CVS at a single prenatal diagnosis referral center. Information on SABs, parity, maternal age, and karyotype were assessed. Univariate and multivariate analyses were conducted. RESULTS: A total of 46,939 women were included. We found an increased risk of any aneuploidy (trisomy or monosomy) as the number of SABs increased
(P = .007). When we examined only the most common trisomies 13, 18, and 21, an increased risk is also seen with increasing number of SABs (Table). These differences persisted when controlling for maternal age, but were only statistical significant for 3 or more SABs. CONCLUSION: An increased risk of karyotypic abnormality is demonstrated in patients who have 3 or more SABs. This study provides novel information regarding this risk among patients who are presenting for prenatal diagnosis, and can be used to counsel such patients. These results need to be examined in low risk populations.
Number of SABs
Rate of tri 13, 18, or 21 P = .001
OR for tri 13, 18, or 21 (P value)
OR for any aneuploidy (P value)
0 1 2 3
1.10 1.45 1.56 1.70
— 1.17 (0.084) 1.28 (0.064) 1.44 (0.012)
— 1.08 (.081) 1.21 (.083) 1.48 (.027)
% % % %
All statistical comparisons are to patients with no prior SABs.
140
FIRST AND SECOND TRIMESTER DOWN SYNDROME SCREENING MARKERS IN PREGNANCIES ACHIEVED THROUGH ASSISTED REPRODUCTIVE TECHNOLOGIES (ART): A FASTER TRIAL STUDY GERALYN LAMBERT-MESSERLIAN1, LORRAINE DUGOFF2, JOHN VIDAVER3, JACOB CANICK1, FERGAL MALONE4, FLINT PORTER5, CHRISTINE COMSTOCK6, DAVID LUTHY7, RADEK BUKOWSKI8, KEITH EDDLEMAN9, SUSAN GROSS10, SABRINA CRAIGO11, ILAN TIMOR12, STEPHEN CARR13, HONOR WOLFE14, MARY D’ALTON4, 1Brown University, Pathology and Laboratory Medicine, Providence, Rhode Island, 2University of Colorado Health Sciences Center, Denver, Colorado, 3DM-Stat, Medford, Massachusetts, 4Columbia University, New York, New York, 5University of Utah Health Sciences Center, Salt Lake City, Utah, 6William Beaumont Hospital, Royal Oak, Michigan, 7Swedish Medical Center, Seattle, Washington, 8University of Texas Medical Branch at Galveston, Galveston, Texas, 9Mount Sinai School of Medicine, New York, New York, 10Albert Einstein College of Medicine, Bronx, New York, 11Tufts University, Boston, Massachusetts, 12New York University, New York, New York, 13Women and Infants’ Hospital, Providence, Rhode Island, 14University of North Carolina, Chapel Hill, North Carolina OBJECTIVE: To determine whether first and second trimester Down syndrome screening markers and screen positive rates are altered in pregnancies achieved by assisted reproductive technologies (ART). STUDY DESIGN: ART pregnancies were identified as part of the FASTER Trial. Marker levels were expressed as multiple of the median (MoM) values and were evaluated for five types of ART: IVF with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), intrauterine insemination with OI (IUI-OI), or IUI without OI (IUI). Each group was compared to non-ART controls (n = 37,070) by Mann Whitney U analysis. RESULTS: PAPP-A was lower and free b-hCG was higher in ART pregnancies, but these trends were not significant and did not occur in ED pregnancies. Second trimester markers were significantly altered in IVF and IUI pregnancies, (lower uE3; higher hCG and inhA). ED pregnancies had higher AFP and inhA. Second, but not first trimester screen positive rates were significantly higher than expected, except when ED was used. First and second trimester median MoM levels and screen positive rates in ART patient groups IVF-OI (278) IUI-OI (323) IUI (247) IVF-OI-ED (59) IVF-ED (56) NT 1.03 PAPP-A 0.94 fB-hCG 1.13 1T+ (%) 8.6 Expected + (%) 5.5 AFP 1.05 uE3 0.94* hCG 1.10 inhA 1.12* 2T+ (%) 20.2# Expected + (%) 14.7
1.02 0.91* 1.06 3.4 4.2 1.04 0.91* 1.12* 1.10* 21.2# 11.9
1.97 0.98 1.08 6.1 4.3 0.96 0.94* 1.09 1.09* 19.1# 12.3
0.96 1.09 0.99 3.5 2.5 1.19* 0.95 1.09 1.35* 12.5 7.4
0.96 1.00 1.22 1.8 1.0 1.26* 0.93 1.15 1.33* 7.4 3.9
+ = screen positive. * P ! .005 versus control group levels. # P ! .05 versus expected positive rate. CONCLUSION: These data show for the first time that ART has a greater impact on second than first trimester screening, and that inhA levels are markedly increased in all types of ART. Adjustment for ART in the second trimester screening is warranted but complicated, depending on the type of ART used.