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838: Genome wide association study of spontaneous preterm delivery
Poster Session V
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
837 Serum and urinary neutrophil gelatinase-associated lipocalin evaluation through normal pregnancy versus pregnancies complicated by preeclampsia Alessandra Curti1, Giuliana Simonazzi2, Dalila Bernabini1, Francesca Lostritto1, Antonio Farina1, Letizia Ronchi1, Gaetano La Manna3, Sergio Stefoni3, Nicola Rizzo2 1
Department of Obstetrics and Gynecology, St. Orsola Malpighi Hospital, University of Bologna, Bologna, Italy, 2Departments of Obstetrics and Gynecology, Division of Prenatal Medicine, St. Orsola Malpighi General Hospital, University of Bologna, Bologna, Italy, 3Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy
OBJECTIVE: To compare serum (sNGAL) and urinary (uNGAL) concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in women affected by preeclampsia (PE) and in a control group, assessing the correlation with disease severity. STUDY DESIGN: This retropective case-control study enrolled 18 women affected by preeclampsia matched for gestational age with 22 uncomplicated pregnancies at term. NGAL assay was done with ELISA technique. Concentrations were expressed in multiple of median (MoM). The distribution within the groups was represented by Box whiskers plots. Detection rate (DR) was evaluated by ROC curve. Finally, likelihood ratio was calculated for severe PE versus controls. RESULTS: No differences were found in terms of distribution between cases and controls nor sNGAL nor uNGAL, although sNGAL values were found to be higher in case of severe PE with a DR of 28% at a false positive rate of 5%. Finally, the likelihood ratio ranged between 1,2 for 0,8 MoM to 6,2 for 3 MoM. CONCLUSIONS: A low DR of NGAL in discriminating different forms of PE was calculated. sNGAL tends to rise, especially in cases of severe PE, where the tissue damage linked to endothelial dysfunction is greater. Such lack of difference could be explained to the too advanced gestational age at the time of sampling.
838 Genome wide association study of spontaneous preterm delivery Bo Jacobsson1, Ronny Myhre2, Solveig Myking2, Per Magnus2, Aase Pay2, Ingrid Ostensen2 1
Sahlgrenska University Hospital/East, Goteborg, Norwegian Institute of Public Health, Oslo, IL
2
OBJECTIVE: Find single nucleotide polymorphism related to spontaneous preterm delivery. STUDY DESIGN: The study is a nested case - control study within the Norwegian Mother and Child Cohort Study (MoBa) initiated by and maintained at the Norwegian Institute of Public Health. In brief, MoBa is a nationwide pregnancy cohort that in the years from 1999 to 2008 have included more than 110,000 pregnancies. Pregnant women were invited to participate through a postal invitation after they signed up for routine ultrasound examination in their local hospital. In the genomics part of the project genotyping of 2000 samples is performed on the Human 660W-quad DNA chip (Illumina, San Diego, California, USA), consisting of 1000 case pregnancies with spontaneous preterm delivery and 1000 control pregnancies (gestational week 39 and 40). RESULTS: Analyses indicate several single nucleotide polymorphism in maternal DNA related to spontaneous preterm delivery. CONCLUSIONS: Single nucleotide polymorphisms indicate several new genes of interest to better understand spontaneous preterm delivery.
S326
www.AJOG.org
839 Value of MCA-PSV and of expected daily decrease in fetal hemoglobin for the timing of serial in utero transfusions in red-cell alloimmunization Bruno Carbonne1, Stephanie Friszer2, Guillaume Mace2, Vanina Castaigne-Meary2, Evelyne Cynober2, Agnes Mailloux3, Anne Cortey4 1 Department of Obstetrics and Gynecology and Centre National de Reference en Hemobiologie Perinatale, Hopital Saint Antoine, Paris, France, Paris, 2 Department of Obstetrics and Gynecology, Hopital Saint Antoine, Paris, France, 3Centre National de Reference en Hemobiologie Perinatale, Hopital Saint Antoine, Paris, 4Centre National de Reference en Hemobiologie Perinatal, Paris
OBJECTIVE: The accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) for the prediction of fetal anemia has been questioned after previous in utero transfusions (IUT). We assessed the detection and false positive rates of MCA-PSV in fetuses undergoing serial IUTs and searched for an effect of gestational age. Fetal hemoglobin level was also estimated from the expected daily decrease between transfusions. STUDY DESIGN: Doppler measurement of MCA-PSV was performed before cordocentesis at the time of the first (n⫽64), second (n⫽43) and third (n⫽29) in utero transfusions (IUT). We assessed the predictive value of MCA-PSV according to the rank of transfusion by comparing area under ROC curves (AUC). The effect of gestational age at the time of the first IUT was also assessed by AUC. Severe anemia was defined as hemoglobin⬍0.5 MoM. Daily decrease of fetal hemoglobin (Hb) after 1st, 2nd and 3rd IUT was estimated and expressed as MoM/day. RESULTS: The predictive value of MCA-PSV was almost similar before the first and the second IUT (AUC 0.85 and 0.86, respectively), but decreased before the 3rd IUT (AUC 0.72). The value of MCA-PSV decreased with gestational age at the time of the first IUT: AUC 0.92 before 28 weeks and 0.82 after 28 weeks. The mean daily decrease in fetal Hb was more important and had a higher variability after the 1st IUT (0.035 [0.019-0.064] MoM/day) than after the 2nd and 3rd IUTs (0.028 [0.020-0.039] and 0.025 [0.019-0.033] MoM/day, respectively). CONCLUSIONS: After one previous IUT, MCA PSV remains an accurate means to diagnose anemia whereas the expected decrease in fetal hemoglobin is very rapid and variable. After 2 or more IUTs, the predictive value of MCA PSV is decreased and even more so with increasing gestational age. After the 2nd and 3rd IUTs, expected decrease in fetal hemoglobin is less variable and allows more adequate decisions for the timing of the next IUTs.
840 Is diabetes related to subclinical thyroid disease identified during pregnancy? Carmen M. Tudela1, Brian M. Casey1, Donald D. McIntire1, Lisa M. Halvorson1, F. Gary Cunningham1 1
University of Texas Southwestern Medical Center, Dallas, TX
OBJECTIVE: There is a well-known relationship between overt hypo-
thyroidism and diabetes. Insulin resistance is also a common finding in hyperthyroidism. Our purpose was to evaluate the prevalence of diabetes in women identified with either subclinical hypothyroidism or subclinical hyperthyroidism during pregnancy. STUDY DESIGN: Between November 2000 and April 2003, all women who presented for prenatal care had TSH levels measured using a chemiluminescent assay. Blood samples from women whose TSH levels were either greater than 3.0 or less than 0.2 mU/L were prospectively assayed for fT4. These TSH thresholds represent the 95th and the 5th percentiles based on 1,000 pregnant women screened in October 2000. If the reflexive fT4 fell outside the normal range, women were referred to a special obstetrics clinic for evaluation and treatment. All other women screened were eligible for this study. For the purposes of this analysis, women who had an elevated TSH and a normal fT4 were designated to have subclinical hypothyroidism and those who had a
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2011
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
837 Serum and urinary neutrophil gelatinase-associated lipocalin evaluation through normal pregnancy versus pregnancies complicated by preeclampsia Alessandra Curti1, Giuliana Simonazzi2, Dalila Bernabini1, Francesca Lostritto1, Antonio Farina1, Letizia Ronchi1, Gaetano La Manna3, Sergio Stefoni3, Nicola Rizzo2 1
Department of Obstetrics and Gynecology, St. Orsola Malpighi Hospital, University of Bologna, Bologna, Italy, 2Departments of Obstetrics and Gynecology, Division of Prenatal Medicine, St. Orsola Malpighi General Hospital, University of Bologna, Bologna, Italy, 3Nephrology Dialysis and Renal Transplantation Unit, S. Orsola University Hospital, Bologna, Italy
OBJECTIVE: To compare serum (sNGAL) and urinary (uNGAL) concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in women affected by preeclampsia (PE) and in a control group, assessing the correlation with disease severity. STUDY DESIGN: This retropective case-control study enrolled 18 women affected by preeclampsia matched for gestational age with 22 uncomplicated pregnancies at term. NGAL assay was done with ELISA technique. Concentrations were expressed in multiple of median (MoM). The distribution within the groups was represented by Box whiskers plots. Detection rate (DR) was evaluated by ROC curve. Finally, likelihood ratio was calculated for severe PE versus controls. RESULTS: No differences were found in terms of distribution between cases and controls nor sNGAL nor uNGAL, although sNGAL values were found to be higher in case of severe PE with a DR of 28% at a false positive rate of 5%. Finally, the likelihood ratio ranged between 1,2 for 0,8 MoM to 6,2 for 3 MoM. CONCLUSIONS: A low DR of NGAL in discriminating different forms of PE was calculated. sNGAL tends to rise, especially in cases of severe PE, where the tissue damage linked to endothelial dysfunction is greater. Such lack of difference could be explained to the too advanced gestational age at the time of sampling.
838 Genome wide association study of spontaneous preterm delivery Bo Jacobsson1, Ronny Myhre2, Solveig Myking2, Per Magnus2, Aase Pay2, Ingrid Ostensen2 1
Sahlgrenska University Hospital/East, Goteborg, Norwegian Institute of Public Health, Oslo, IL
2
OBJECTIVE: Find single nucleotide polymorphism related to spontaneous preterm delivery. STUDY DESIGN: The study is a nested case - control study within the Norwegian Mother and Child Cohort Study (MoBa) initiated by and maintained at the Norwegian Institute of Public Health. In brief, MoBa is a nationwide pregnancy cohort that in the years from 1999 to 2008 have included more than 110,000 pregnancies. Pregnant women were invited to participate through a postal invitation after they signed up for routine ultrasound examination in their local hospital. In the genomics part of the project genotyping of 2000 samples is performed on the Human 660W-quad DNA chip (Illumina, San Diego, California, USA), consisting of 1000 case pregnancies with spontaneous preterm delivery and 1000 control pregnancies (gestational week 39 and 40). RESULTS: Analyses indicate several single nucleotide polymorphism in maternal DNA related to spontaneous preterm delivery. CONCLUSIONS: Single nucleotide polymorphisms indicate several new genes of interest to better understand spontaneous preterm delivery.
S326
www.AJOG.org
839 Value of MCA-PSV and of expected daily decrease in fetal hemoglobin for the timing of serial in utero transfusions in red-cell alloimmunization Bruno Carbonne1, Stephanie Friszer2, Guillaume Mace2, Vanina Castaigne-Meary2, Evelyne Cynober2, Agnes Mailloux3, Anne Cortey4 1 Department of Obstetrics and Gynecology and Centre National de Reference en Hemobiologie Perinatale, Hopital Saint Antoine, Paris, France, Paris, 2 Department of Obstetrics and Gynecology, Hopital Saint Antoine, Paris, France, 3Centre National de Reference en Hemobiologie Perinatale, Hopital Saint Antoine, Paris, 4Centre National de Reference en Hemobiologie Perinatal, Paris
OBJECTIVE: The accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) for the prediction of fetal anemia has been questioned after previous in utero transfusions (IUT). We assessed the detection and false positive rates of MCA-PSV in fetuses undergoing serial IUTs and searched for an effect of gestational age. Fetal hemoglobin level was also estimated from the expected daily decrease between transfusions. STUDY DESIGN: Doppler measurement of MCA-PSV was performed before cordocentesis at the time of the first (n⫽64), second (n⫽43) and third (n⫽29) in utero transfusions (IUT). We assessed the predictive value of MCA-PSV according to the rank of transfusion by comparing area under ROC curves (AUC). The effect of gestational age at the time of the first IUT was also assessed by AUC. Severe anemia was defined as hemoglobin⬍0.5 MoM. Daily decrease of fetal hemoglobin (Hb) after 1st, 2nd and 3rd IUT was estimated and expressed as MoM/day. RESULTS: The predictive value of MCA-PSV was almost similar before the first and the second IUT (AUC 0.85 and 0.86, respectively), but decreased before the 3rd IUT (AUC 0.72). The value of MCA-PSV decreased with gestational age at the time of the first IUT: AUC 0.92 before 28 weeks and 0.82 after 28 weeks. The mean daily decrease in fetal Hb was more important and had a higher variability after the 1st IUT (0.035 [0.019-0.064] MoM/day) than after the 2nd and 3rd IUTs (0.028 [0.020-0.039] and 0.025 [0.019-0.033] MoM/day, respectively). CONCLUSIONS: After one previous IUT, MCA PSV remains an accurate means to diagnose anemia whereas the expected decrease in fetal hemoglobin is very rapid and variable. After 2 or more IUTs, the predictive value of MCA PSV is decreased and even more so with increasing gestational age. After the 2nd and 3rd IUTs, expected decrease in fetal hemoglobin is less variable and allows more adequate decisions for the timing of the next IUTs.
840 Is diabetes related to subclinical thyroid disease identified during pregnancy? Carmen M. Tudela1, Brian M. Casey1, Donald D. McIntire1, Lisa M. Halvorson1, F. Gary Cunningham1 1
University of Texas Southwestern Medical Center, Dallas, TX
OBJECTIVE: There is a well-known relationship between overt hypo-
thyroidism and diabetes. Insulin resistance is also a common finding in hyperthyroidism. Our purpose was to evaluate the prevalence of diabetes in women identified with either subclinical hypothyroidism or subclinical hyperthyroidism during pregnancy. STUDY DESIGN: Between November 2000 and April 2003, all women who presented for prenatal care had TSH levels measured using a chemiluminescent assay. Blood samples from women whose TSH levels were either greater than 3.0 or less than 0.2 mU/L were prospectively assayed for fT4. These TSH thresholds represent the 95th and the 5th percentiles based on 1,000 pregnant women screened in October 2000. If the reflexive fT4 fell outside the normal range, women were referred to a special obstetrics clinic for evaluation and treatment. All other women screened were eligible for this study. For the purposes of this analysis, women who had an elevated TSH and a normal fT4 were designated to have subclinical hypothyroidism and those who had a
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2011