- Email: [email protected]
403: Progesterone as a biomarker for intrauterine growth restriction in a rat model
www.AJOG.org
Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases
Poster Session III
with control (Figure). The other subunits NOX1-4, DUOX1, and p67phox were also upregulated in the alcohol group, but the difference did not reach significance. NOXA1 was downregulated in the placenta and p67phox was upregulated in the liver of alcohol exposed pups. There were no differences between alcohol and control in any of the other NOX subunits in the liver or placenta. CONCLUSION: The NOX enzyme system is upregulated in the brain of fetuses exposed to alcohol. This effect is specific to the brain. NOX enzymes appear to be central to the generation of brain ROS in FAS. These results identify the NOX system as a potential target for preventative approaches in FAS.
Relative quantity of mRNA for DUOX2, NOXA1, and NOXO1 for alcohol versus control groups
Outcome measures of patients undergoing FETO, categorized by either having a collagen plug or not at the time of the initial operation
Line represents median, boxes represent interquartile range, and whiskers represent min and max values. *P ⬍ .05 compared to control.
403 Progesterone as a biomarker for intrauterine growth restriction in a rat model Amanda Roman1, Neeraj Desai1, Madhu Gupta2, Malvika Solanki2, Xiangying Xue2, Prodyot Chatterjee2, Burton Rochelson1, Christine Metz2 1 Division of Maternal-Fetal Medicine, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, 2Center for Immunology and Inflammation, Feinstein Institute for Medical Research, Manhasset, NY
402 The role of NADPH oxidase enzymes in fetal alcohol syndrome Alexandria Hill1, Huazhi Yin1, Ester Tamayo1, Nathan Drever2, George Saade1, Egle Bytautiene1 1 University of Texas Medical Branch, Maternal-Fetal Medicine, Galveston, TX, 2Scott & White Healthcare, Maternal-Fetal Medicine, Temple, TX
OBJECTIVE: Fetal alcohol syndrome (FAS) is the most common cause of non-genetic preventable neurocognitive disability. Oxidative stress is one of the purported mechanisms. NADPH oxidase (NOX) is an enzyme that is involved in the production of reactive oxygen species (ROS). Our objective was to determine whether the NOX enzyme system is involved in FAS. STUDY DESIGN: A well-validated FAS animal model was used (Spong, et al). Timed, pregnant C57BL6/J mice were treated on gestational day 8 with a 0.03ml/g intraperitoneal injection of either 25% alcohol or saline. On gestational day 18, the mice were euthanized and fetuses removed. Fetal brains, livers, and placenta were collected for mRNA extraction (n ⫽ 20 in each group) and quantitative real-time PCR of NOX subunits (DUOX1, DUOX2, NOX1, NOX2, NOX3, NOX4, NOXA1, NOXO1, RAC1, p22phox, and p67phox) was performed. Groups were compared using Student’s t or Mann-Whitney test as appropriate (statistical significance: p⬍0.05). RESULTS: NOX subunits DUOX2, NOXA1, and NOXO1 were significantly upregulated in the fetal brain in the ethanol group compared
OBJECTIVE: Progesterone concentrations increase as pregnancy progresses and decrease close to delivery and postpartum. We hypothesized that intrauterine growth restriction (IUGR), could disrupt the placental steroid production, decreasing progesterone concentrations. STUDY DESIGN: Pregnant female Wistar rats (12 wks old, GD18) were anesthetized using inhaled isoflurane and underwent either bilateral uterine artery ligation (BL⫽6) or sham surgery (SH⫽5); litter size was identified at the time of surgery. Dams were euthanized on GD19; only live fetuses and accompanying placentas were weighed. Maternal plasma was analyzed for progesterone levels (ng/mL). Data was analyzed using student t-test. RESULTS: The average fetal and placental weights were significantly lower in BL when compared to SH (P⬍0.001) with moderate fetal mortality (Table). The incidence of IUGR (pup weight ⬍10th-ile) in BL was 86.3%. Maternal plasma progesterone levels were significantly decreased (P⬍0.05) in BL dams when compared with SH dams, and remained decreased after correcting for litter size (Figure). CONCLUSION: Progesterone in maternal plasma is decreased in a rat model of BL-induced IUGR, correlating directly with placental size. Our group previously showed an enhanced cytokine expression in
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S177
Poster Session III
Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases
amniotic fluid and placenta tissues in BL when compared to SH, without maternal systemic inflammation. Future studies will investigate whether maternal progesterone supplementation can prevent IUGR in a rat model and can modulate inflammatory responses within the feto-placental unit. Supported by Oxenhorn Family and The Feinstein Institute.
Progesterone maternal plasma levels (ng/mL) adjusted by litter size
www.AJOG.org
necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), length of total parenteral nutrition (TPN), length of ventilation and length of neonatal intensive care unit (NICU) stay. RESULTS: 73 neonates were in the early delivery group with mean gestational age (GA) of 34.3 weeks, and 70 were in the late with mean GA of 36.4 weeks. Mean weight of the early group was 2112g and for the late group 2436g (p⬍0.0001). The rate of primary closure was not significantly different between the two groups (72.8% in late group vs. 67.1% in early group (p⫽0.54)). Bowel atresia was more frequent in the early group (10.96% vs 7.1%) as well as NEC (5.5% vs 2.9%) but that difference wasn’t significant (p⫽0.42, and p⫽0.43 ). The percentage of RDS and mean length of ventilation wasn’t significantly different between groups (p⫽0.19, and p⫽0.2). The length of TPN and NICU stay were longer in the early group (37.6 vs 29.1 days and 45.7 vs 34.3 days respectively) and both were statistically significant (p⫽0.01). Based on the two variables that were significantly different between the groups (length of stay and TPN), we performed survival analysis to include 3 stillbirth cases. It predicted higher probability of discharge and discontinuation of TPN for the late delivery group. CONCLUSION: Delivery before 36weeks is associated with longer NICU stay and longer time of TPN feeding. At the same time there was no significant difference in rates of primary closure or intestinal complications among the two groups of gestation.
405 Termination rate and stillbirth in pregnancies affected by fetal Down syndrome Asha Rijhsinghani1, Chao Li1, Diedre Fleener1 1
University of Iowa Hospitals and Clinics, OB/GYN, Iowa City, IA
OBJECTIVE: Proportion of women that decide to terminate the preg-
Box plot: mean, 10th-ile, 90th-ile, minimum and maximum value Student t-test. BL, bilateral uterine artery ligation;SH, sham surgery.
Pup and placental outcomes
BL, bilateral uterine artery ligation;SH, sham surgery. * Student t test.
404 The impact of delivery timing on neonatal outcomes of infants with gastroschisis Anna Palatnik1, Matthew Loichinger1, Tana Kim1, Randall Kuhlmann1, Erica Peterson1 1 Medical College of Wisconsin, Department of Obstetrics and Gynecology, Milwaukee, WI
OBJECTIVE: To assess whether earlier delivery of infants with gastroschisis minimizes intestinal damage or improves neonatal outcomes STUDY DESIGN: A retrospective study of 143 newborns born with gastroschisis between 2000-2011 in a single tertiary center was performed. They were divided in two groups: those delivered ‘’early’’ (before 36 weeks) and those delivered “late” (after 36 weeks). These groups were compared in terms of neonatal outcomes, including weight at the time of delivery, rate of primary closure, bowel atresia,
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nancy with fetal Down syndrome (DS) is reported to be 71%-100%. In continuing pregnancies with fetal DS, the fetal loss rate is about 23% from the time diagnosis to delivery. Now, the pregnancies with fetal DS are diagnosed earlier and have close fetal surveillance. But IUFD still occurs. There are no recent studies regarding the outcomes of the pregnancies with fetal DS. STUDY DESIGN: Between 1990 and 2012 at the University of Iowa Hospitals and Clinics, 261 pregnancies were diagnosed with trisomy 21 by a genetic amniocentesis. Adequate follow up was available on 249 pregnancies. RESULTS: 146/249 (59 %) of the women were in the AMA group. The women in AMA group had amniocentesis earlier than those ⬍ 35 yrs of age. A total of 157 women chose to have pregnancy termination, of which 107 (73.3%) were in the AMA group. A total of 92 women continued the pregnancy including 51.5 % of younger women comparing to 26.7% of the women in the AMA group. Detailed information regarding the ongoing pregnancy and outcomes were available in 67/92 continuing pregnancies. IUFD occurred in 13/67 (19.4%) of continuing pregnancies of which 6 were under 20 weeks at the time of IUFD, 6 were after 20 weeks and in 1 patient there was inadequate information. The rate of stillbirth after 24 weeks gestation was 3/57 (5.3%). 2 of the 3 IUFD occurred at 24 and 37 weeks gestation with multiple fetal anomalies. One IUFD occurred at 34 weeks. CONCLUSION: Majority of the women diagnosed with fetal DS were AMA. Diagnosis was made at a later gestational age in younger women. The terminations were more frequent in the AMA group. IUFD occurred in 19.4% of the ongoing pregnancies and in 5.3% of those that progressed beyond 24 weeks.
Mean gestational age of diagnosis of DS and termination rate
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013
Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases
Poster Session III
with control (Figure). The other subunits NOX1-4, DUOX1, and p67phox were also upregulated in the alcohol group, but the difference did not reach significance. NOXA1 was downregulated in the placenta and p67phox was upregulated in the liver of alcohol exposed pups. There were no differences between alcohol and control in any of the other NOX subunits in the liver or placenta. CONCLUSION: The NOX enzyme system is upregulated in the brain of fetuses exposed to alcohol. This effect is specific to the brain. NOX enzymes appear to be central to the generation of brain ROS in FAS. These results identify the NOX system as a potential target for preventative approaches in FAS.
Relative quantity of mRNA for DUOX2, NOXA1, and NOXO1 for alcohol versus control groups
Outcome measures of patients undergoing FETO, categorized by either having a collagen plug or not at the time of the initial operation
Line represents median, boxes represent interquartile range, and whiskers represent min and max values. *P ⬍ .05 compared to control.
403 Progesterone as a biomarker for intrauterine growth restriction in a rat model Amanda Roman1, Neeraj Desai1, Madhu Gupta2, Malvika Solanki2, Xiangying Xue2, Prodyot Chatterjee2, Burton Rochelson1, Christine Metz2 1 Division of Maternal-Fetal Medicine, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY, 2Center for Immunology and Inflammation, Feinstein Institute for Medical Research, Manhasset, NY
402 The role of NADPH oxidase enzymes in fetal alcohol syndrome Alexandria Hill1, Huazhi Yin1, Ester Tamayo1, Nathan Drever2, George Saade1, Egle Bytautiene1 1 University of Texas Medical Branch, Maternal-Fetal Medicine, Galveston, TX, 2Scott & White Healthcare, Maternal-Fetal Medicine, Temple, TX
OBJECTIVE: Fetal alcohol syndrome (FAS) is the most common cause of non-genetic preventable neurocognitive disability. Oxidative stress is one of the purported mechanisms. NADPH oxidase (NOX) is an enzyme that is involved in the production of reactive oxygen species (ROS). Our objective was to determine whether the NOX enzyme system is involved in FAS. STUDY DESIGN: A well-validated FAS animal model was used (Spong, et al). Timed, pregnant C57BL6/J mice were treated on gestational day 8 with a 0.03ml/g intraperitoneal injection of either 25% alcohol or saline. On gestational day 18, the mice were euthanized and fetuses removed. Fetal brains, livers, and placenta were collected for mRNA extraction (n ⫽ 20 in each group) and quantitative real-time PCR of NOX subunits (DUOX1, DUOX2, NOX1, NOX2, NOX3, NOX4, NOXA1, NOXO1, RAC1, p22phox, and p67phox) was performed. Groups were compared using Student’s t or Mann-Whitney test as appropriate (statistical significance: p⬍0.05). RESULTS: NOX subunits DUOX2, NOXA1, and NOXO1 were significantly upregulated in the fetal brain in the ethanol group compared
OBJECTIVE: Progesterone concentrations increase as pregnancy progresses and decrease close to delivery and postpartum. We hypothesized that intrauterine growth restriction (IUGR), could disrupt the placental steroid production, decreasing progesterone concentrations. STUDY DESIGN: Pregnant female Wistar rats (12 wks old, GD18) were anesthetized using inhaled isoflurane and underwent either bilateral uterine artery ligation (BL⫽6) or sham surgery (SH⫽5); litter size was identified at the time of surgery. Dams were euthanized on GD19; only live fetuses and accompanying placentas were weighed. Maternal plasma was analyzed for progesterone levels (ng/mL). Data was analyzed using student t-test. RESULTS: The average fetal and placental weights were significantly lower in BL when compared to SH (P⬍0.001) with moderate fetal mortality (Table). The incidence of IUGR (pup weight ⬍10th-ile) in BL was 86.3%. Maternal plasma progesterone levels were significantly decreased (P⬍0.05) in BL dams when compared with SH dams, and remained decreased after correcting for litter size (Figure). CONCLUSION: Progesterone in maternal plasma is decreased in a rat model of BL-induced IUGR, correlating directly with placental size. Our group previously showed an enhanced cytokine expression in
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S177
Poster Session III
Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases
amniotic fluid and placenta tissues in BL when compared to SH, without maternal systemic inflammation. Future studies will investigate whether maternal progesterone supplementation can prevent IUGR in a rat model and can modulate inflammatory responses within the feto-placental unit. Supported by Oxenhorn Family and The Feinstein Institute.
Progesterone maternal plasma levels (ng/mL) adjusted by litter size
www.AJOG.org
necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), length of total parenteral nutrition (TPN), length of ventilation and length of neonatal intensive care unit (NICU) stay. RESULTS: 73 neonates were in the early delivery group with mean gestational age (GA) of 34.3 weeks, and 70 were in the late with mean GA of 36.4 weeks. Mean weight of the early group was 2112g and for the late group 2436g (p⬍0.0001). The rate of primary closure was not significantly different between the two groups (72.8% in late group vs. 67.1% in early group (p⫽0.54)). Bowel atresia was more frequent in the early group (10.96% vs 7.1%) as well as NEC (5.5% vs 2.9%) but that difference wasn’t significant (p⫽0.42, and p⫽0.43 ). The percentage of RDS and mean length of ventilation wasn’t significantly different between groups (p⫽0.19, and p⫽0.2). The length of TPN and NICU stay were longer in the early group (37.6 vs 29.1 days and 45.7 vs 34.3 days respectively) and both were statistically significant (p⫽0.01). Based on the two variables that were significantly different between the groups (length of stay and TPN), we performed survival analysis to include 3 stillbirth cases. It predicted higher probability of discharge and discontinuation of TPN for the late delivery group. CONCLUSION: Delivery before 36weeks is associated with longer NICU stay and longer time of TPN feeding. At the same time there was no significant difference in rates of primary closure or intestinal complications among the two groups of gestation.
405 Termination rate and stillbirth in pregnancies affected by fetal Down syndrome Asha Rijhsinghani1, Chao Li1, Diedre Fleener1 1
University of Iowa Hospitals and Clinics, OB/GYN, Iowa City, IA
OBJECTIVE: Proportion of women that decide to terminate the preg-
Box plot: mean, 10th-ile, 90th-ile, minimum and maximum value Student t-test. BL, bilateral uterine artery ligation;SH, sham surgery.
Pup and placental outcomes
BL, bilateral uterine artery ligation;SH, sham surgery. * Student t test.
404 The impact of delivery timing on neonatal outcomes of infants with gastroschisis Anna Palatnik1, Matthew Loichinger1, Tana Kim1, Randall Kuhlmann1, Erica Peterson1 1 Medical College of Wisconsin, Department of Obstetrics and Gynecology, Milwaukee, WI
OBJECTIVE: To assess whether earlier delivery of infants with gastroschisis minimizes intestinal damage or improves neonatal outcomes STUDY DESIGN: A retrospective study of 143 newborns born with gastroschisis between 2000-2011 in a single tertiary center was performed. They were divided in two groups: those delivered ‘’early’’ (before 36 weeks) and those delivered “late” (after 36 weeks). These groups were compared in terms of neonatal outcomes, including weight at the time of delivery, rate of primary closure, bowel atresia,
S178
nancy with fetal Down syndrome (DS) is reported to be 71%-100%. In continuing pregnancies with fetal DS, the fetal loss rate is about 23% from the time diagnosis to delivery. Now, the pregnancies with fetal DS are diagnosed earlier and have close fetal surveillance. But IUFD still occurs. There are no recent studies regarding the outcomes of the pregnancies with fetal DS. STUDY DESIGN: Between 1990 and 2012 at the University of Iowa Hospitals and Clinics, 261 pregnancies were diagnosed with trisomy 21 by a genetic amniocentesis. Adequate follow up was available on 249 pregnancies. RESULTS: 146/249 (59 %) of the women were in the AMA group. The women in AMA group had amniocentesis earlier than those ⬍ 35 yrs of age. A total of 157 women chose to have pregnancy termination, of which 107 (73.3%) were in the AMA group. A total of 92 women continued the pregnancy including 51.5 % of younger women comparing to 26.7% of the women in the AMA group. Detailed information regarding the ongoing pregnancy and outcomes were available in 67/92 continuing pregnancies. IUFD occurred in 13/67 (19.4%) of continuing pregnancies of which 6 were under 20 weeks at the time of IUFD, 6 were after 20 weeks and in 1 patient there was inadequate information. The rate of stillbirth after 24 weeks gestation was 3/57 (5.3%). 2 of the 3 IUFD occurred at 24 and 37 weeks gestation with multiple fetal anomalies. One IUFD occurred at 34 weeks. CONCLUSION: Majority of the women diagnosed with fetal DS were AMA. Diagnosis was made at a later gestational age in younger women. The terminations were more frequent in the AMA group. IUFD occurred in 19.4% of the ongoing pregnancies and in 5.3% of those that progressed beyond 24 weeks.
Mean gestational age of diagnosis of DS and termination rate
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013