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Prenatal diagnosis of fetal aneuploidy following second-trimester abortion for fetal aneuploidy
S50 SMFM Abstracts 145
THE POLYMORPHISMS OF 5, 10-METHYLENETHTRAHYDROFOLATE REDUCTASE (MTHFR C677T AND A1298C) AND METHIONINE SYNTHASE REDUCTASE (MTRR A66G) GENE AS MATERNAL RISK FACTORS FOR FETAL ANEUPLOIDY HYUNMEE RYU1, DO-JIN KIM2, MOON-YOUNG KIM1, SO-YEON PARK2, JIN-WOO KIM2, SHIN-YOUNG KIM2, JAE-HYUG YANG1, JOUNG-YEOL HAN1, JOO OH KIM1, JINHOON CHUNG1, 1Samsung Cheil Hospital and Women’s Healthcare Center, Sungkyunkwan University School of Medicien, Obstetrics and Gynecology, Seoul, Korea, South Korea, 2Samsung Cheil Hospital and Women’s Healthcare Center, Laboratory of Medical Genetics, Seoul, Korea, South Korea OBJECTIVE: The purpose of this study was to address the association of MTHFR (C677T/A1298C) and MTRR (A66G) polymorphisms as maternal risk factors for fetal aneuploidy. STUDY DESIGN: We studied the presence of MTHFR C677T/A1298C and MTRR A66G in an aneuploidy group (n = 30) who had fetal aneuploidy and in a control group (n = 78) who had given birth to at least two healthy children without a history of miscarriage or abnormal pregnancy. To determine the polymorphism of these enzymes, we performed PCR/RFLP (Restriction Fragment Length Polymorphism). RESULTS: There were no statistical differences in the prevalence of MTHFR 677 variant T allele (P = .519) and 1298 variant C allele (P = .051) in both groups. Frequency of MTRR G allele in aneuploidy group was higher than in control group. Mother with MTRR 66 A¨G mutation had a 2.9-fold higher risk of having a fetus with aneuploidy than mother without the G substitute (odds ratio: 2.9; 95% CI: 1.5-5.3; P = .001). CONCLUSION: This study suggests that there was an increased risk of fetal aneuploidy in mother carriers of MTRR G allele, not in MTHFR C677T and A1298C. The MTRR A66G variant may be a significant risk factor for producing a child with chromosome aneuploidy.
147
THE IMPACT OF NUCHAL TRANSLUCENCY SCREENING ON AMA PATIENTS’ UPTAKE OF INVASIVE TESTING ANDREA WRAY1, ALESSANDRO GHIDINI1, COLETTE ALVIS1, JONATHAN HODOR1, HELAIN LANDY1, SARAH POGGI1, 1Georgetown University Hospital, Obstetrics and Gynecology, Washington, District of Columbia OBJECTIVE: Although invasive prenatal diagnostic testing is routinely offered to women of advanced maternal age (AMA), both CVS and amniocentesis have risks. Nuchal translucency screening (NT) is a newer first trimester screening test which our Institution began offering in 2002. Our objective is to determine the effects of availability of NT on the referrals for diagnostic testing and on the attitude of candidate women in our population. STUDY DESIGN: Included in the study were AMA patients presenting for prenatal care at our Institution in 2001 (NT not available) and in 2003 (NT available). Excluded were patients with known fetal abnormality or genetic disease. A single genetic counselor discussed the available tests. Charts were reviewed for maternal age, gestational age, parity, previous SAB or TAB, history of CVS or amniocentesis, order of gestation, abnormal ultrasound findings and decision to proceed with invasive testing. The two groups were compared using Student’s t test and c2. RESULTS: In 2001, 552 AMA women enrolled in prenatal care; 68 presented for early genetic counseling (!13 weeks). In 2003, 728 AMA women enrolled in prenatal care; 172 presented for early genetic counseling. More counseled women chose genetic testing in 2003 than in 2001 (163/172, or 95% vs 54/68, or 79%, P ! .01). Women referred for early genetic counseling and testing were similar in the two study periods for maternal age (P = .3), parity (P = .5), previous SAB (P = .4), previous TAB (P = .8), race (P = .5), previous invasive test (P = .5), sonographic abnormality during the current pregnancy (P = 1.0) and rate of multiple gestation (P = .6), but differed in gestational age at presentation (10.5 +/1.4 weeks in 2001 vs. 11.4 +/1.1 weeks in 2003, P ! .01). In 2001, 72% of subjects elected an invasive procedure, whereas in 2003 only 19% did so (P ! .01). CONCLUSION: Availability of NT screening results in a higher rate of AMA women choosing early prenatal genetic counseling and some form of genetic testing. Such women are less likely to choose invasive tests than those without access to NT screening.
146
PRENATAL DIAGNOSIS OF FETAL ANEUPLOIDY FOLLOWING SECOND-TRIMESTER ABORTION FOR FETAL ANEUPLOIDY STEPHEN CHASEN1, ROBIN B. KALISH1, MERUKA GUPTA1, FRANK A. CHERVENAK1, 1Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, New York OBJECTIVE: The perception that women prefer earlier abortion to later abortion is widespread, despite the lack of supporting data. Patients who have undergone second trimester abortion are well informed about this procedure. Our objective was to examine choices made by these women in pregnancies following D&E for fetal aneuploidy. STUDY DESIGN: Women who underwent D&E for fetal aneuploidy in our hospital from 1996–2003 and received subsequent prenatal care here were identified. All were referred for genetic counseling in subsequent pregnancies. Records from the D&E procedure and from subsequent pregnancies were reviewed. Categoric data were compared using Fisher’s exact test. Continuous data were compared using Student’s t test. RESULTS: 42 women met inclusion criteria. The mean maternal age at D&E was 34.5 G 4.4 years, and mean gestational age at D&E was 19.4 G 1.7 weeks. There were no complications associated with D&E. The median interval between D&E and EDC of subsequent pregnancy was 16 months (range 12-36). The indication for D&E was Trisomy 21 in 18 cases (42.9%), other Trisomy in 10 cases (23.8%), sex chromosome aneuploidy in 12 cases (28.6%), and other abnormalities in 2 cases (4.8%). In the next pregnancy, 23 women underwent CVS (54.8%), and 16 women (38.1%) underwent amniocentesis. Those who underwent D&E for sex chromosome aneuploidy, which is not associated with higher rates of recurrence, were less likely to undergo CVS than those undergoing D&E for other forms of aneuploidy (25.0% vs. 66.7%; P = .02). There was no difference in age between those who had CVS and those who declined this procedure (36.3 G 4.6 vs. 35.8 G 4.1 years; P = .73). CONCLUSION: The majority of these patients, who had undergone D&E without medical complications, opted to undergo CVS. This was especially true of those who were at higher risk of recurrent aneuploidy. These women, who had no reason to doubt the safety of D&E, had a strong interest in first trimester diagnosis. This suggests that second trimester abortion, while medically safe, is less acceptable for women than early abortion.
148
PLACENTAL GENE EXPRESSION LOUISE LAURENT1, THOMAS MOORE1, 1University of California, San Diego, Reproductive Medicine, San Diego, California OBJECTIVE: Located at the interface between mother and fetus, the placenta represents the site at which the bulk of biochemical maternal-fetal interactions occur. The placenta’s unique role in gestation makes it a logical organ to study in the quest to understand a number of critical problems in perinatal medicine. Up to this point, studies have focused on defining the functions or expression patterns of small numbers of genes, many of which have previously been postulated to be important in physiologic or pathophysiologic processes. We wished to move beyond these types of experiments, and utilize current microarray technologies find genes differentially expressed according to gestational age or the presence or absence of clinically important factors. STUDY DESIGN: This is a pilot study examining placental gene expression between 23 and 43 weeks of gestation. We performed quantitative measurements of the expression of all currently described human genes in placental RNA samples sorted into four pools according to gestational age. We selected genes that were differentially expressed between the pools, and performed quantitative PCR experiments on individual RNA samples. RESULTS: The resulting data was examined in two ways. First, genes that are expressed at progressively higher MHC II and calgranulin A) or lower (bHCG and EFEMP1) levels with advancing gestational age were sought. Next, we looked for genes differentially expressed according to the presence or absence of factors such as labor, premature rupture of membranes, chorioamnionitis, preeclampsia, and diabetes. These genes included calgranulin A (lower levels with premature rupture of membranes), EFEMP1 (lower levels with labor), and the frizzled-related protein (lower levels with pre-eclampsia). CONCLUSION: Further investigation of genes identified in this pilot study, and comprehensive microarray experiments on large numbers of individual samples are necessary utilize the full potential of these types of experiments in clarifying the mechanisms underlying normal and complicated pregnancies.
THE POLYMORPHISMS OF 5, 10-METHYLENETHTRAHYDROFOLATE REDUCTASE (MTHFR C677T AND A1298C) AND METHIONINE SYNTHASE REDUCTASE (MTRR A66G) GENE AS MATERNAL RISK FACTORS FOR FETAL ANEUPLOIDY HYUNMEE RYU1, DO-JIN KIM2, MOON-YOUNG KIM1, SO-YEON PARK2, JIN-WOO KIM2, SHIN-YOUNG KIM2, JAE-HYUG YANG1, JOUNG-YEOL HAN1, JOO OH KIM1, JINHOON CHUNG1, 1Samsung Cheil Hospital and Women’s Healthcare Center, Sungkyunkwan University School of Medicien, Obstetrics and Gynecology, Seoul, Korea, South Korea, 2Samsung Cheil Hospital and Women’s Healthcare Center, Laboratory of Medical Genetics, Seoul, Korea, South Korea OBJECTIVE: The purpose of this study was to address the association of MTHFR (C677T/A1298C) and MTRR (A66G) polymorphisms as maternal risk factors for fetal aneuploidy. STUDY DESIGN: We studied the presence of MTHFR C677T/A1298C and MTRR A66G in an aneuploidy group (n = 30) who had fetal aneuploidy and in a control group (n = 78) who had given birth to at least two healthy children without a history of miscarriage or abnormal pregnancy. To determine the polymorphism of these enzymes, we performed PCR/RFLP (Restriction Fragment Length Polymorphism). RESULTS: There were no statistical differences in the prevalence of MTHFR 677 variant T allele (P = .519) and 1298 variant C allele (P = .051) in both groups. Frequency of MTRR G allele in aneuploidy group was higher than in control group. Mother with MTRR 66 A¨G mutation had a 2.9-fold higher risk of having a fetus with aneuploidy than mother without the G substitute (odds ratio: 2.9; 95% CI: 1.5-5.3; P = .001). CONCLUSION: This study suggests that there was an increased risk of fetal aneuploidy in mother carriers of MTRR G allele, not in MTHFR C677T and A1298C. The MTRR A66G variant may be a significant risk factor for producing a child with chromosome aneuploidy.
147
THE IMPACT OF NUCHAL TRANSLUCENCY SCREENING ON AMA PATIENTS’ UPTAKE OF INVASIVE TESTING ANDREA WRAY1, ALESSANDRO GHIDINI1, COLETTE ALVIS1, JONATHAN HODOR1, HELAIN LANDY1, SARAH POGGI1, 1Georgetown University Hospital, Obstetrics and Gynecology, Washington, District of Columbia OBJECTIVE: Although invasive prenatal diagnostic testing is routinely offered to women of advanced maternal age (AMA), both CVS and amniocentesis have risks. Nuchal translucency screening (NT) is a newer first trimester screening test which our Institution began offering in 2002. Our objective is to determine the effects of availability of NT on the referrals for diagnostic testing and on the attitude of candidate women in our population. STUDY DESIGN: Included in the study were AMA patients presenting for prenatal care at our Institution in 2001 (NT not available) and in 2003 (NT available). Excluded were patients with known fetal abnormality or genetic disease. A single genetic counselor discussed the available tests. Charts were reviewed for maternal age, gestational age, parity, previous SAB or TAB, history of CVS or amniocentesis, order of gestation, abnormal ultrasound findings and decision to proceed with invasive testing. The two groups were compared using Student’s t test and c2. RESULTS: In 2001, 552 AMA women enrolled in prenatal care; 68 presented for early genetic counseling (!13 weeks). In 2003, 728 AMA women enrolled in prenatal care; 172 presented for early genetic counseling. More counseled women chose genetic testing in 2003 than in 2001 (163/172, or 95% vs 54/68, or 79%, P ! .01). Women referred for early genetic counseling and testing were similar in the two study periods for maternal age (P = .3), parity (P = .5), previous SAB (P = .4), previous TAB (P = .8), race (P = .5), previous invasive test (P = .5), sonographic abnormality during the current pregnancy (P = 1.0) and rate of multiple gestation (P = .6), but differed in gestational age at presentation (10.5 +/1.4 weeks in 2001 vs. 11.4 +/1.1 weeks in 2003, P ! .01). In 2001, 72% of subjects elected an invasive procedure, whereas in 2003 only 19% did so (P ! .01). CONCLUSION: Availability of NT screening results in a higher rate of AMA women choosing early prenatal genetic counseling and some form of genetic testing. Such women are less likely to choose invasive tests than those without access to NT screening.
146
PRENATAL DIAGNOSIS OF FETAL ANEUPLOIDY FOLLOWING SECOND-TRIMESTER ABORTION FOR FETAL ANEUPLOIDY STEPHEN CHASEN1, ROBIN B. KALISH1, MERUKA GUPTA1, FRANK A. CHERVENAK1, 1Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, New York OBJECTIVE: The perception that women prefer earlier abortion to later abortion is widespread, despite the lack of supporting data. Patients who have undergone second trimester abortion are well informed about this procedure. Our objective was to examine choices made by these women in pregnancies following D&E for fetal aneuploidy. STUDY DESIGN: Women who underwent D&E for fetal aneuploidy in our hospital from 1996–2003 and received subsequent prenatal care here were identified. All were referred for genetic counseling in subsequent pregnancies. Records from the D&E procedure and from subsequent pregnancies were reviewed. Categoric data were compared using Fisher’s exact test. Continuous data were compared using Student’s t test. RESULTS: 42 women met inclusion criteria. The mean maternal age at D&E was 34.5 G 4.4 years, and mean gestational age at D&E was 19.4 G 1.7 weeks. There were no complications associated with D&E. The median interval between D&E and EDC of subsequent pregnancy was 16 months (range 12-36). The indication for D&E was Trisomy 21 in 18 cases (42.9%), other Trisomy in 10 cases (23.8%), sex chromosome aneuploidy in 12 cases (28.6%), and other abnormalities in 2 cases (4.8%). In the next pregnancy, 23 women underwent CVS (54.8%), and 16 women (38.1%) underwent amniocentesis. Those who underwent D&E for sex chromosome aneuploidy, which is not associated with higher rates of recurrence, were less likely to undergo CVS than those undergoing D&E for other forms of aneuploidy (25.0% vs. 66.7%; P = .02). There was no difference in age between those who had CVS and those who declined this procedure (36.3 G 4.6 vs. 35.8 G 4.1 years; P = .73). CONCLUSION: The majority of these patients, who had undergone D&E without medical complications, opted to undergo CVS. This was especially true of those who were at higher risk of recurrent aneuploidy. These women, who had no reason to doubt the safety of D&E, had a strong interest in first trimester diagnosis. This suggests that second trimester abortion, while medically safe, is less acceptable for women than early abortion.
148
PLACENTAL GENE EXPRESSION LOUISE LAURENT1, THOMAS MOORE1, 1University of California, San Diego, Reproductive Medicine, San Diego, California OBJECTIVE: Located at the interface between mother and fetus, the placenta represents the site at which the bulk of biochemical maternal-fetal interactions occur. The placenta’s unique role in gestation makes it a logical organ to study in the quest to understand a number of critical problems in perinatal medicine. Up to this point, studies have focused on defining the functions or expression patterns of small numbers of genes, many of which have previously been postulated to be important in physiologic or pathophysiologic processes. We wished to move beyond these types of experiments, and utilize current microarray technologies find genes differentially expressed according to gestational age or the presence or absence of clinically important factors. STUDY DESIGN: This is a pilot study examining placental gene expression between 23 and 43 weeks of gestation. We performed quantitative measurements of the expression of all currently described human genes in placental RNA samples sorted into four pools according to gestational age. We selected genes that were differentially expressed between the pools, and performed quantitative PCR experiments on individual RNA samples. RESULTS: The resulting data was examined in two ways. First, genes that are expressed at progressively higher MHC II and calgranulin A) or lower (bHCG and EFEMP1) levels with advancing gestational age were sought. Next, we looked for genes differentially expressed according to the presence or absence of factors such as labor, premature rupture of membranes, chorioamnionitis, preeclampsia, and diabetes. These genes included calgranulin A (lower levels with premature rupture of membranes), EFEMP1 (lower levels with labor), and the frizzled-related protein (lower levels with pre-eclampsia). CONCLUSION: Further investigation of genes identified in this pilot study, and comprehensive microarray experiments on large numbers of individual samples are necessary utilize the full potential of these types of experiments in clarifying the mechanisms underlying normal and complicated pregnancies.