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Genetic influence on dystocia
SMFM Abstracts S113
Volume 189, Number 6 Am J Obstet Gynecol 181
PREECLAMPSIA AND RISK FACTORS OF ANGIOTENSINOGEN, METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) AND FACTOR V GENE VARIANTS. ILWOON JI1, 1Chungbuk National University, Cheongju, South Korea OBJECTIVE: To determine the genotypic distributions of angiotensinogen, MTHFR, and factor V gene variants as risk factors for preeclampsia among Korean women. STUDY DESIGN: 113 preeclampsia patients and 70 normotensive pregnant patient controls were evaluated. DNA was extracted from peripheral leukocytes, then PCR and restriction assays were done with appropriate enzymes to identify the single nucleotide polymorphism (SNP). The genotypic distributions of preeclampsia and the control group were compared. RESULTS: Nineteen of 113 women (17%) with preeclampsia were heterozygous for the angiotensinogen T704C mutation, and 94 of 113 women (83%) with preeclampsia were homozygous; while 7/70 (10%) were heterozygous, and 59/70 (84%) were homozygous for the T704C mutation among the control subjects. The frequency of the MTHFR T677 allele was 36% in the preeclamptic group and 38% in the control group, and TT homozygosity was found in 26 preeclamptic women (23%) and in 13 controls (19%). No women were homozygous or heterozygous for the factor V Leiden mutation. CONCLUSION: Angiotensinogen T704C mutation is associated with preeclampsia in the study population. There was no association between the thermolabile variant of MTHFR and risk of preeclampsia in our study population. We observed no factor V Leiden mutation. The data also suggest that a person with angiotensinogen T704C mutation plus MTHFR C677T variant does not have a greater increase in risk for preeclampsia than having only the angiotensinogen T704C mutation.
183
CYSTIC FIBROSIS SCREENING: TO SCREEN OR NOT TO SCREEN? RAJIV GALA1, JOSEPH BIGGIO, JR1, PATRICK RAMSEY1, KATHARINE WENSTROM1, 1University of Alabama at Birmingham, Obstetrics/Gynecology, Birmingham, AL OBJECTIVE: To evaluate the cost-effectiveness of concurrent and sequential screening strategies vs no screening for cystic fibrosis (CF) in Caucasians in the U.S. STUDY DESIGN: Using a decision analysis model, two proposed neonatal screening strategies were compared in a hypothetical cohort of 1,000,000 women from the perspective of a third-party payer. With concurrent screening (CON), samples from both partners are tested and the couple is informed of the results of each partner. With sequential screening (SEQ), one partner is tested, and the second partner is tested only if the first partner is identified as a carrier. Baseline clinical and cost estimates were derived from the literature and local sources and included: screening acceptance 62%, carrier detection 88%, carrier rate 1/25, acceptance of invasive testing 91%, pregnancy termination rate 20%, cost of CF carrier screening per individual $215, and excess lifetime cost of care for CF $485k. Sensitivity analyses were performed on clinical parameters with imprecise point estimates. Outcome measures included total cost, cases detected, CF births averted, cost/case detected, and cost/case averted. Analyses were performed using DATA 3.5 (TreeAge Software). RESULTS: The baseline analysis is:
The costs of lifetime care of all children born with CF were less than the cost of screening unless screening cost less than $19 per person. Sequential screening became economically favorable only if the test cost less than $123 per individual and 100% of affected pregnancies were terminated. CONCLUSION: Both algorithms detect at-risk couples and CF neonates equally well. The most economically favorable strategy is no screening, but sequential screening is the best strategy allowing reproductive autonomy.
182
GENETIC INFLUENCE ON DYSTOCIA MICHAEL ALGOVIK1, EMMA ¨ LD3, SVEN CNATTINGIUS2, PAUL NILSSON2, AGNETA NORDENSKJO LICHTENSTEIN2, MAGNUS WESTGREN4, 1Karolinska Institute, Dept. of Clinical Sciences, Stockholm, Sweden 2Karolinska Institute, Dept. of Medical Epidemiology, Stockholm, Sweden 3Karolinska Institute, Dept. of Molecular Medicine, Stockholm, Sweden 4Huddinge University Hospital, Stockholm, Sweden OBJECTIVE: To quantify the genetic influence on dystocia, prolonged and difficult labor. STUDY DESIGN: A retrospective study where a total of 2,539,534 registered births in Sweden during the years 1973 through 1997 were analyzed. Data from the population-based Swedish Birth-, Twin- and National Family Registers were linked on individual basis, and relations between sibling, twin, and motherdaughter pairs were established. Relative risk of dystocia in sibling and motherdaughter pairs was calculated. Model fitting was used to estimate the relative contribution of genetic and environmental factors for liability to dystocia. RESULTS: A total of 190,747 births were diagnosed as dystocic, among whom there were 40 monozygotic twin pairs, 25 dizygotic twin pairs, 667 motherdaughter pairs, and 10,306 sibling pairs concordantly affected. Measures of familial similarity (relative risks and correlation of liability) for dystocia were higher in monozygotic twins than in dizygotic twins, other sibling pairs, and mother-daughter pairs. Correlation of liability was also higher in full sisters than in half sisters. Model fitting suggested that genetic effects accounted for 28% (95% confidence interval 21-32%) of the susceptibility for dystocia. CONCLUSION: Dystocia is a complex disorder of poor uterine action that is influenced by a significant genetic component as well as environmental factors. The amount of genetic influence makes it interesting to study the gene expression in these patients. Detection of the genes related to dystocia might lead to better pathophysiological understanding of this condition and detection of these mothers before parturition.
184
THE FACTOR V LEIDEN AND PROTHROMBIN GENE MUTATIONS AND FETAL DEMISE AMY E. SULLIVAN1, LESA NELSON1, M. SEAN ESPLIN1, D. WARE BRANCH1, ROBERT M. SILVER1, 1University of Utah, Obstetrics and Gynecology, Salt Lake City, UT OBJECTIVE: Women with thrombophilias are thought to be at an increased risk for thrombosis and impaired uteroplacental circulation. Several recent studies have reported an association between inherited thrombophilias and adverse perinatal outcomes. However, other studies report no association. Several thrombophilias are common and frequently diagnosed in the general population. Currently, there is confusion as to the optimal management of these cases. Thus, we sought to determine whether the two most commonly inherited thrombophilias, the factor V Leiden mutation (FV) and the G20210A prothrombin mutation (PT), are associated with fetal death. STUDY DESIGN: We used a case-control study to compare the frequencies of the FV and PT mutations between women with a history of fetal demise (pregnancy loss >10 weeks’ gestation) and controls (at least one live birth, no miscarriages, and no fetal demises). The gestational ages of fetal demises were confirmed by ultrasound, fetal evaluation, or both. Results were compared using chi-square. P > 0.05 was significant. RESULTS: The mean number of fetal demises in cases was 1.8 (range 1-6). The mean gestational age at the time of fetal demise was 12.3 weeks (range 1022). One hundred thirty-nine cases and 74 controls were tested for FV. One hundred twenty cases and 88 controls were tested for PT. Eight of 139 cases (5.8%) and 3 of 74 controls (4.1%) were heterozygous for FV (P > 0.05). Three of 120 cases (2.5%) and 1 of 88 controls (1.1%) were heterozygous for PT (P > 0.05). Thirty male partners were also tested for FV and PT. None were heterozygous for either mutation. No cases or controls were homozygous for the mutations. CONCLUSION: In our population, the FV and the PT mutations were only present in a small proportion of patients. The precise role of these common, heritable thrombophilias remains to be determined.
Volume 189, Number 6 Am J Obstet Gynecol 181
PREECLAMPSIA AND RISK FACTORS OF ANGIOTENSINOGEN, METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) AND FACTOR V GENE VARIANTS. ILWOON JI1, 1Chungbuk National University, Cheongju, South Korea OBJECTIVE: To determine the genotypic distributions of angiotensinogen, MTHFR, and factor V gene variants as risk factors for preeclampsia among Korean women. STUDY DESIGN: 113 preeclampsia patients and 70 normotensive pregnant patient controls were evaluated. DNA was extracted from peripheral leukocytes, then PCR and restriction assays were done with appropriate enzymes to identify the single nucleotide polymorphism (SNP). The genotypic distributions of preeclampsia and the control group were compared. RESULTS: Nineteen of 113 women (17%) with preeclampsia were heterozygous for the angiotensinogen T704C mutation, and 94 of 113 women (83%) with preeclampsia were homozygous; while 7/70 (10%) were heterozygous, and 59/70 (84%) were homozygous for the T704C mutation among the control subjects. The frequency of the MTHFR T677 allele was 36% in the preeclamptic group and 38% in the control group, and TT homozygosity was found in 26 preeclamptic women (23%) and in 13 controls (19%). No women were homozygous or heterozygous for the factor V Leiden mutation. CONCLUSION: Angiotensinogen T704C mutation is associated with preeclampsia in the study population. There was no association between the thermolabile variant of MTHFR and risk of preeclampsia in our study population. We observed no factor V Leiden mutation. The data also suggest that a person with angiotensinogen T704C mutation plus MTHFR C677T variant does not have a greater increase in risk for preeclampsia than having only the angiotensinogen T704C mutation.
183
CYSTIC FIBROSIS SCREENING: TO SCREEN OR NOT TO SCREEN? RAJIV GALA1, JOSEPH BIGGIO, JR1, PATRICK RAMSEY1, KATHARINE WENSTROM1, 1University of Alabama at Birmingham, Obstetrics/Gynecology, Birmingham, AL OBJECTIVE: To evaluate the cost-effectiveness of concurrent and sequential screening strategies vs no screening for cystic fibrosis (CF) in Caucasians in the U.S. STUDY DESIGN: Using a decision analysis model, two proposed neonatal screening strategies were compared in a hypothetical cohort of 1,000,000 women from the perspective of a third-party payer. With concurrent screening (CON), samples from both partners are tested and the couple is informed of the results of each partner. With sequential screening (SEQ), one partner is tested, and the second partner is tested only if the first partner is identified as a carrier. Baseline clinical and cost estimates were derived from the literature and local sources and included: screening acceptance 62%, carrier detection 88%, carrier rate 1/25, acceptance of invasive testing 91%, pregnancy termination rate 20%, cost of CF carrier screening per individual $215, and excess lifetime cost of care for CF $485k. Sensitivity analyses were performed on clinical parameters with imprecise point estimates. Outcome measures included total cost, cases detected, CF births averted, cost/case detected, and cost/case averted. Analyses were performed using DATA 3.5 (TreeAge Software). RESULTS: The baseline analysis is:
The costs of lifetime care of all children born with CF were less than the cost of screening unless screening cost less than $19 per person. Sequential screening became economically favorable only if the test cost less than $123 per individual and 100% of affected pregnancies were terminated. CONCLUSION: Both algorithms detect at-risk couples and CF neonates equally well. The most economically favorable strategy is no screening, but sequential screening is the best strategy allowing reproductive autonomy.
182
GENETIC INFLUENCE ON DYSTOCIA MICHAEL ALGOVIK1, EMMA ¨ LD3, SVEN CNATTINGIUS2, PAUL NILSSON2, AGNETA NORDENSKJO LICHTENSTEIN2, MAGNUS WESTGREN4, 1Karolinska Institute, Dept. of Clinical Sciences, Stockholm, Sweden 2Karolinska Institute, Dept. of Medical Epidemiology, Stockholm, Sweden 3Karolinska Institute, Dept. of Molecular Medicine, Stockholm, Sweden 4Huddinge University Hospital, Stockholm, Sweden OBJECTIVE: To quantify the genetic influence on dystocia, prolonged and difficult labor. STUDY DESIGN: A retrospective study where a total of 2,539,534 registered births in Sweden during the years 1973 through 1997 were analyzed. Data from the population-based Swedish Birth-, Twin- and National Family Registers were linked on individual basis, and relations between sibling, twin, and motherdaughter pairs were established. Relative risk of dystocia in sibling and motherdaughter pairs was calculated. Model fitting was used to estimate the relative contribution of genetic and environmental factors for liability to dystocia. RESULTS: A total of 190,747 births were diagnosed as dystocic, among whom there were 40 monozygotic twin pairs, 25 dizygotic twin pairs, 667 motherdaughter pairs, and 10,306 sibling pairs concordantly affected. Measures of familial similarity (relative risks and correlation of liability) for dystocia were higher in monozygotic twins than in dizygotic twins, other sibling pairs, and mother-daughter pairs. Correlation of liability was also higher in full sisters than in half sisters. Model fitting suggested that genetic effects accounted for 28% (95% confidence interval 21-32%) of the susceptibility for dystocia. CONCLUSION: Dystocia is a complex disorder of poor uterine action that is influenced by a significant genetic component as well as environmental factors. The amount of genetic influence makes it interesting to study the gene expression in these patients. Detection of the genes related to dystocia might lead to better pathophysiological understanding of this condition and detection of these mothers before parturition.
184
THE FACTOR V LEIDEN AND PROTHROMBIN GENE MUTATIONS AND FETAL DEMISE AMY E. SULLIVAN1, LESA NELSON1, M. SEAN ESPLIN1, D. WARE BRANCH1, ROBERT M. SILVER1, 1University of Utah, Obstetrics and Gynecology, Salt Lake City, UT OBJECTIVE: Women with thrombophilias are thought to be at an increased risk for thrombosis and impaired uteroplacental circulation. Several recent studies have reported an association between inherited thrombophilias and adverse perinatal outcomes. However, other studies report no association. Several thrombophilias are common and frequently diagnosed in the general population. Currently, there is confusion as to the optimal management of these cases. Thus, we sought to determine whether the two most commonly inherited thrombophilias, the factor V Leiden mutation (FV) and the G20210A prothrombin mutation (PT), are associated with fetal death. STUDY DESIGN: We used a case-control study to compare the frequencies of the FV and PT mutations between women with a history of fetal demise (pregnancy loss >10 weeks’ gestation) and controls (at least one live birth, no miscarriages, and no fetal demises). The gestational ages of fetal demises were confirmed by ultrasound, fetal evaluation, or both. Results were compared using chi-square. P > 0.05 was significant. RESULTS: The mean number of fetal demises in cases was 1.8 (range 1-6). The mean gestational age at the time of fetal demise was 12.3 weeks (range 1022). One hundred thirty-nine cases and 74 controls were tested for FV. One hundred twenty cases and 88 controls were tested for PT. Eight of 139 cases (5.8%) and 3 of 74 controls (4.1%) were heterozygous for FV (P > 0.05). Three of 120 cases (2.5%) and 1 of 88 controls (1.1%) were heterozygous for PT (P > 0.05). Thirty male partners were also tested for FV and PT. None were heterozygous for either mutation. No cases or controls were homozygous for the mutations. CONCLUSION: In our population, the FV and the PT mutations were only present in a small proportion of patients. The precise role of these common, heritable thrombophilias remains to be determined.