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707: Mechanisms of telomere shortening in placentas from pregnancies complicated with intrauterine growth restriction
www.AJOG.org
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
termination, 103 (22.7%) were born alive (6% of them with Down’s syndrome), 67 (14.8%) miscarried before 24 weeks, 5 (1.1%) had fetal loss after 24 weeks and 2 (0.4%) suffered neonatal death. Of the electively terminated pregnancies we found that 76 (27.5%) had a normal karyotype, 148 (53.6%) had an abnormal karyotype, and no karyotype was available for 52 (18.8%) subjects. Of all genetic abnormalities, Trisomy 21 (32.4%) was the most frequently detected, followed by Monosomy X and Trisomy 18 (23.6% each). Trisomy 13 was detected in 8% while Mosaicism and Triploidies were both diagnosed in 2%. 8% had other abnormal karyotypes. CONCLUSIONS: Many pregnant women (60%) diagnosed with cystic hygroma terminate their pregnancy. A significant percentage (27.5%) of those terminations have a normal karyotype.
705 Neural tube defects and growth restriction: is there an association? Shayna Norman1, Anthony Odibo1, Ryan Longman1, Kimberly A. Roehl1, George Macones1, Alison Cahill1 1
Washington University in St. Louis, St. Louis, MO
OBJECTIVE: To estimate the association between neural tube defects
(NTD) and intrauterine growth restriction (IUGR). STUDY DESIGN: This was a retrospective cohort study of consecutive women undergoing ultrasound from 17-22 weeks for anatomic survey with a singleton gestation at one institution from 1990 to 2008. Presence or absence of a fetus with a NTD, excluding anencephaly, defined the two study groups. The primary outcomes were IUGR defined as birth weight ⬍ 10th percentile, and severe IUGR defined as birth weight ⬍ 5th percentile. Subgroup analysis was performed for isolated NTD to observe if the association with IUGR persisted. Univariate, bivariate, and multiple logistic regression analyses were performed. RESULTS: Among 66,956 women in the cohort, 170 were found to have fetal NTD. Of the 170 women with a NTD, 149 cases were isolated NTD with no other major anomalies. At baseline, the only characteristic that differed between the 2 study groups was maternal age; women found to have fetal NTD were significantly younger. Fetuses with a NTD were found to have a significantly increased risk for IUGR ⬍10th percentile and severe IUGR ⬍5th percentile, and the association persisted even when the finding of NTD was isolated. (Table 1) CONCLUSIONS: Women found to have a fetal NTD are at increased risk for IUGR even when the NTD is an isolated finding. The findings suggest that a policy of serial growth scans in cases with isolated NTD is justified. Table 1. Association between isolated NTD and IUGR
IUGR ⬍10%
Isolated† NTD Present (nⴝ149)
NTD Absent (nⴝ66786)
RR (95% CI)
aOR* (95% CI)
P value
18.1%
8.3%
2.2
2.4
⬍0.01
..........................................................................................................................................................................................
(n⫽5642) (1.6-3.1) (1.5-3.6) .......................................................................................................................................................................................... IUGR ⬍5% 14.1% 6.3% 2.2 2.3 ⬍0.01 .......................................................................................................................................................................................... (n⫽4265) (1.5-3.3) (1.5-3.7) ..........................................................................................................................................................................................
* Adjusted for advanced maternal age, African-American race, smoking, and chronic hypertension † No other major congenital anomalies identified
706 Electrical uterine myography (EUM) is as good as intra uterine pressure catheter (IUP) in measuring contractions Gabi Haran1, Moshe D Fejgin1, Tal Biron-Shental1 1
Meir Medical Center, Tel Aviv University, Kfar Saba
OBJECTIVE: Electrical uterine myography (EUM) enables noninvasive
measuring of uterine contractions. Unlike the external commonly used monitor, the EUM is capable of evaluating the intensity of the contractions. Nowadays, whenever this parameter is crucial during
Poster Session V
labor, intra uterine pressure catheter (IUP) is used. Since IUP is invasive, requires ruptured membranes and might increase infections and bleeding, an accurate noninvasive tool to measure contractions is beneficial. The aim of this study was to determine the accuracy of the EUM in evaluating contraction compared to IUP. STUDY DESIGN: EUM was measured prospectively on 10 women in different stages of labor. Subjects were monitored simultaneously by an IUP monitor. Myometrial electrical activity was measured using a multi-channel amplifier and a 3-dimensional non-invasive position sensor. Data evaluator was blinded to clinical parameters. Energy was presented in units of micro-Watts and was compared to IUP. We compared the intensity, the length and the frequency of uterine contractions between the two methods. Usage of IUP was made only according to clinical indications. RESULTS: Pearson analysis showed complete correlation between the EUM and the IUP in terms of timing, length and intensity of the contractions (P⬍0.0001). CONCLUSIONS: EUM is as good as IUP for evaluating contractions during labor. Since EUM is noninvasive, it might be even beneficial.
707 Mechanisms of telomere shortening in placentas from pregnancies complicated with intrauterine growth restriction Tal Biron-Shental1, Rivka Sukenik-Halevy2, Moshe D Fejgin1, Reuven Sharony1, Dvora Kidron3, Aliza Amiel4 1
Meir Medical Center, Tel Aviv University, Kfar Saba, 2Meir Medical Center, Kfar Saba, 3Meir Medical Center, Tel Aviv Uniersity, Kfar Saba, 4Genetic Institute, Meir Medical Center, Bar Ilan University, Kfar saba
OBJECTIVE: Intrauterine Growth Restriction (IUGR) correlates with placental telomere shortening and senescence. Telomerase is an enzyme complex that elongates telomeres. Telomerase RNA component (TERC) gene serves as the RNA template for the addition of telomeric repeats. Telomerase reverse transctiptase (TERT) is the catalytic component of telomerase. We studies mechanisms of telomere shortening in IUGR placentas. STUDY DESIGN: We estimated the copy number of the TERC gene using FISH and the expression of TERT mRNA using RT-PCR, in placental biopsies from six pregnancies complicated with IUGR and from six gestational age matched controls. RESULTS: Lower TERC gene copy number was observed in IUGR trophoblasts (p⬍0.05). TERT mRNA was found to be diminished in IUGR placentas compared to control samples (mean fold of 0.5⫾0.2 and 0.96⫾0.1 respectively, p⫽0.0005). CONCLUSIONS: These results support and explain the observations of telomere shortening and decreased telomerase activity in IUGR placentas. We suggest that these findings may play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.
708 Maternal tobacco use and maternal obesity alter mitochondrial DNA in placental tissue Adi Abramovici1, Lauren Patterson1, Behrouz Zand1, Cynthia Shope1, Min Hu1, Lori Showalter1, Melissa Suter1, Kjersti Aagaard1 1
Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX
OBJECTIVE: Maternal adipose tissue contributes to an inflammatory
response, providing a potential source of oxidative stress on the placenta. Maternal smoking leads to the activation of phase I enzymes in the placenta, which process xenobiotics into reactive unstable intermediates and expose the cell to increased oxidative stress. We hypothesized that increased oxidative stress related to maternal tobacco use or obesity may lead to associative altered mitochondrial DNA (mtDNA) copy number, as well as the highly variant D-loop segment of the mitochondrial genome (Figure). STUDY DESIGN: Placentas were stored at ⫺80°C within 30 minutes of delivery until use. Nuclear DNA, RNA, and mtDNA was extracted from each of three nested cohorts: smokers (SP, N⫽20), class II/III obese(OP, n⫽18), and their 1:1 matched controls (matched by ma-
Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology
S279
Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging
termination, 103 (22.7%) were born alive (6% of them with Down’s syndrome), 67 (14.8%) miscarried before 24 weeks, 5 (1.1%) had fetal loss after 24 weeks and 2 (0.4%) suffered neonatal death. Of the electively terminated pregnancies we found that 76 (27.5%) had a normal karyotype, 148 (53.6%) had an abnormal karyotype, and no karyotype was available for 52 (18.8%) subjects. Of all genetic abnormalities, Trisomy 21 (32.4%) was the most frequently detected, followed by Monosomy X and Trisomy 18 (23.6% each). Trisomy 13 was detected in 8% while Mosaicism and Triploidies were both diagnosed in 2%. 8% had other abnormal karyotypes. CONCLUSIONS: Many pregnant women (60%) diagnosed with cystic hygroma terminate their pregnancy. A significant percentage (27.5%) of those terminations have a normal karyotype.
705 Neural tube defects and growth restriction: is there an association? Shayna Norman1, Anthony Odibo1, Ryan Longman1, Kimberly A. Roehl1, George Macones1, Alison Cahill1 1
Washington University in St. Louis, St. Louis, MO
OBJECTIVE: To estimate the association between neural tube defects
(NTD) and intrauterine growth restriction (IUGR). STUDY DESIGN: This was a retrospective cohort study of consecutive women undergoing ultrasound from 17-22 weeks for anatomic survey with a singleton gestation at one institution from 1990 to 2008. Presence or absence of a fetus with a NTD, excluding anencephaly, defined the two study groups. The primary outcomes were IUGR defined as birth weight ⬍ 10th percentile, and severe IUGR defined as birth weight ⬍ 5th percentile. Subgroup analysis was performed for isolated NTD to observe if the association with IUGR persisted. Univariate, bivariate, and multiple logistic regression analyses were performed. RESULTS: Among 66,956 women in the cohort, 170 were found to have fetal NTD. Of the 170 women with a NTD, 149 cases were isolated NTD with no other major anomalies. At baseline, the only characteristic that differed between the 2 study groups was maternal age; women found to have fetal NTD were significantly younger. Fetuses with a NTD were found to have a significantly increased risk for IUGR ⬍10th percentile and severe IUGR ⬍5th percentile, and the association persisted even when the finding of NTD was isolated. (Table 1) CONCLUSIONS: Women found to have a fetal NTD are at increased risk for IUGR even when the NTD is an isolated finding. The findings suggest that a policy of serial growth scans in cases with isolated NTD is justified. Table 1. Association between isolated NTD and IUGR
IUGR ⬍10%
Isolated† NTD Present (nⴝ149)
NTD Absent (nⴝ66786)
RR (95% CI)
aOR* (95% CI)
P value
18.1%
8.3%
2.2
2.4
⬍0.01
..........................................................................................................................................................................................
(n⫽5642) (1.6-3.1) (1.5-3.6) .......................................................................................................................................................................................... IUGR ⬍5% 14.1% 6.3% 2.2 2.3 ⬍0.01 .......................................................................................................................................................................................... (n⫽4265) (1.5-3.3) (1.5-3.7) ..........................................................................................................................................................................................
* Adjusted for advanced maternal age, African-American race, smoking, and chronic hypertension † No other major congenital anomalies identified
706 Electrical uterine myography (EUM) is as good as intra uterine pressure catheter (IUP) in measuring contractions Gabi Haran1, Moshe D Fejgin1, Tal Biron-Shental1 1
Meir Medical Center, Tel Aviv University, Kfar Saba
OBJECTIVE: Electrical uterine myography (EUM) enables noninvasive
measuring of uterine contractions. Unlike the external commonly used monitor, the EUM is capable of evaluating the intensity of the contractions. Nowadays, whenever this parameter is crucial during
Poster Session V
labor, intra uterine pressure catheter (IUP) is used. Since IUP is invasive, requires ruptured membranes and might increase infections and bleeding, an accurate noninvasive tool to measure contractions is beneficial. The aim of this study was to determine the accuracy of the EUM in evaluating contraction compared to IUP. STUDY DESIGN: EUM was measured prospectively on 10 women in different stages of labor. Subjects were monitored simultaneously by an IUP monitor. Myometrial electrical activity was measured using a multi-channel amplifier and a 3-dimensional non-invasive position sensor. Data evaluator was blinded to clinical parameters. Energy was presented in units of micro-Watts and was compared to IUP. We compared the intensity, the length and the frequency of uterine contractions between the two methods. Usage of IUP was made only according to clinical indications. RESULTS: Pearson analysis showed complete correlation between the EUM and the IUP in terms of timing, length and intensity of the contractions (P⬍0.0001). CONCLUSIONS: EUM is as good as IUP for evaluating contractions during labor. Since EUM is noninvasive, it might be even beneficial.
707 Mechanisms of telomere shortening in placentas from pregnancies complicated with intrauterine growth restriction Tal Biron-Shental1, Rivka Sukenik-Halevy2, Moshe D Fejgin1, Reuven Sharony1, Dvora Kidron3, Aliza Amiel4 1
Meir Medical Center, Tel Aviv University, Kfar Saba, 2Meir Medical Center, Kfar Saba, 3Meir Medical Center, Tel Aviv Uniersity, Kfar Saba, 4Genetic Institute, Meir Medical Center, Bar Ilan University, Kfar saba
OBJECTIVE: Intrauterine Growth Restriction (IUGR) correlates with placental telomere shortening and senescence. Telomerase is an enzyme complex that elongates telomeres. Telomerase RNA component (TERC) gene serves as the RNA template for the addition of telomeric repeats. Telomerase reverse transctiptase (TERT) is the catalytic component of telomerase. We studies mechanisms of telomere shortening in IUGR placentas. STUDY DESIGN: We estimated the copy number of the TERC gene using FISH and the expression of TERT mRNA using RT-PCR, in placental biopsies from six pregnancies complicated with IUGR and from six gestational age matched controls. RESULTS: Lower TERC gene copy number was observed in IUGR trophoblasts (p⬍0.05). TERT mRNA was found to be diminished in IUGR placentas compared to control samples (mean fold of 0.5⫾0.2 and 0.96⫾0.1 respectively, p⫽0.0005). CONCLUSIONS: These results support and explain the observations of telomere shortening and decreased telomerase activity in IUGR placentas. We suggest that these findings may play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.
708 Maternal tobacco use and maternal obesity alter mitochondrial DNA in placental tissue Adi Abramovici1, Lauren Patterson1, Behrouz Zand1, Cynthia Shope1, Min Hu1, Lori Showalter1, Melissa Suter1, Kjersti Aagaard1 1
Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX
OBJECTIVE: Maternal adipose tissue contributes to an inflammatory
response, providing a potential source of oxidative stress on the placenta. Maternal smoking leads to the activation of phase I enzymes in the placenta, which process xenobiotics into reactive unstable intermediates and expose the cell to increased oxidative stress. We hypothesized that increased oxidative stress related to maternal tobacco use or obesity may lead to associative altered mitochondrial DNA (mtDNA) copy number, as well as the highly variant D-loop segment of the mitochondrial genome (Figure). STUDY DESIGN: Placentas were stored at ⫺80°C within 30 minutes of delivery until use. Nuclear DNA, RNA, and mtDNA was extracted from each of three nested cohorts: smokers (SP, N⫽20), class II/III obese(OP, n⫽18), and their 1:1 matched controls (matched by ma-
Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology
S279