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P96 The role of a low oxygen environment on the invasion of extravillous trophoblast from first trimester of pregnancy
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Poster Presentations / Pregnancy Hypertension 1, Supplement 1 (2010) S43–S76
P95
P97
Do we deliver too soon for preterm pre-eclampsia?
Profile of maternal deaths in an obstetric ICU in Brazil
Eric Njforfut, Helena Nik, Steve Walkinshaw. Liverpool Women’s Hospital, Merseyside, UK
Alex Souza 1 , Adriana Scavuzzi 1 , Leila Katz 1 , Isabela Coutinho 1 , Melania Amorim 1 , Larissa Moura 2 , Renata Bezerra 2 . 1 Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Pernambuco, Brazil; 2 Faculdade Pernambucana de Saúde, Brazil
Introduction: Presentation with pre-eclampsia before 34 weeks’ gestation presents challenges in decision making that balance risks of neonatal morbidity and mortality against maternal risks. Recent review of the literature undertaken as part of the development of national guidelines in the UK posed questions on the maternal and fetal grounds often used to make decisions to deliver, suggesting that some births may be unnecessary. Aim: To examine indication for pretem birth for PET against proposed draft national guidance to determine the likely scope of potential pregnancy prolongation. Setting: UK tertiary maternity unit Methods: Identification of births < 34 weeks’ gestation for PET. Data on presentation, clinical course, laboratory investigations, fetal surveillance and blood pressure control was extracted from the case records. The indication for birth was extracted from the records, either as stated by the clinician or by agreement of two investigators. Standards: Justified birth (from draft UK guidance): severe persistent hypertension despite standard treatment to lower, symptomatic severe PET, eclampsia, platelets less than 70,000, ALT > 200 iu/ml, abnormal computerised CTG (STV < 3.5 msecs or recurrent decelerations), abnormal fetal Doppler (arterial and venous). Results: 130 cases identified from May 2005, of which 35 have been analysed. Mean time from admission to birth 9.9 days. 19 of 35 cases were judged justified. The commonest indications judged unjustified were increasing proteinuria and fetal growth restriction without evidence of compromise. In a few cases it was not possible to determine why particular women were delivered. Conclusion: Though the analysis is only partly completed, there is evidence that some pregnancies are ended on both maternal and fetal grounds where safe prolongation may be possible, even in a service where the average prolongation is compatible with published studies. It is possible that new national guidance may improve outcomes, particularly for the infant.
P96 The role of a low oxygen environment on the invasion of extravillous trophoblast from first trimester of pregnancy Akira Onogi, Katsuhiko Naruse, Toshiyuki Sado, Taketoshi Noguchi, Satomi Komeda, Emi Koyama, Kazuhiro Nishioka, Takashi Kitanaka, Hidekazu Oi, Hiroshi Kobayashi. Nara Medical University, Nara, Japan Background: During early pregnancy, cytotrophoblast differentiate into extravillous trophoblast (EVT) cells and invade into decidua, myometrium and uterine spiral arteries. In hypertensive pregnancy, disorder of this physiological process is regarded as an initial pathological feature. On the other hand, a low-oxygen environment is reported to effect on an invasiveness of each cancer cell lines. Aims: In this study, we investigated proteolytic functions and invasiveness of primary EVTs in hypoxia, to show the early placental pathology lead to hypertensive pregnancy. Methods: Placental samples (5-15 weeks gestation) were obtained from women undergoing elective surgical termination of pregnancy with written informed consent. Cytotrophoblast was separated with Percoll-based method and cultured on invasion assay chamber and 24-well plate applied Matrigel. Migration of the invasive phenotype trophoblast was studied with wound healing assay. Activity and expression of matrix metalloproteinases (MMP2 and MMP9) and urokinase-type plasminogen activator (uPA) in cell culture supernatant were investigated by geratin gel zymography and ELISA. Expression of HIF1α was measured with Western Blot using cell lysate. All cultures were performed under 20% oxygen, 5%, and 5% that repeated three times of hypoxic stimulation for one hour (0.1%). Results: Cell viabilities and migrations between each oxygen concentration showed no difference. Invasion was significantly increased in 20% and decreased in 0.1%. Activities of MMP2, TIMP2, and uPA did not alter in 0.1% than 5%, but increased in 20% environment. MMP9 showed no significant difference between each oxygen conditions. HIF1α was increased in 0.1% stimulation and decreased in 20% oxygen environment. Conclusion: These results suggested that a relatively low oxygen environment suppressed excessive invasion of the EVT in the placental bed of early pregnancy. HIF1α seemed not participated in the invasiveness of EVT, which suggested that severe hypoxia induces poor invasion of EVT in early pregnancy and may lead to later preeclampsia.
Objective: To describe obstetrical deaths in an obstetrical intensive care unit (ICU). Methods: A cross-sectional study was conducted including all women admitted in the obstetrical ICU from September 2002 to August 2009. The study was approved by local Ethics Committee. Inclusion criteria were admission to obstetrical ICU. Frequency of death, cause of admission to ICU, age, admission before or after delivery, gestational age, parity, stillbirth and diagnosis established during ICU stay were the variables evaluated. When delivery occurred during ICU stay, weight of the newborn was studied. Epi-Info 3.5.1. was used for statistical analysis. Results: During the study period, 6307 women met inclusion criteria. 94 obstetrical deaths were analysed. Obstetrical deaths occurred 1.84% of ICU admissions, which corresponds to a maternal mortality ratio of 228. Mean age of patients who died was 26 years, 77% studied no more than seven years, and nearly 54% were referred to our institution from another health unit. 67% were admitted still pregnant and abdominal delivery was performed in 66%. Stillbirths occurred in 40% of the patients. The most common diagnosis established during ICU stay was hypertension (52%), septic shock (20%) and hemorrhage (12%). In women with hypertensive disorders, eclampsia occurred in 45% and HELLP syndrome in 29%. Conclusions: Our frequency of obstetrical deaths is similar to those seen in obstetrical ICU worldwide. The main diagnosis found in these women coincides with the main causes of obstetrical deaths in our country. Recognizing the profile of women who die in an obstetrical ICU may contribute to create strategies for the reduction of obstetrical deaths.
P98 Does supplementation of L-arginine plus folic acid improve reduced endothelial function seen in preeclampsia? Yoshikatsu Suzuki 1 , Tamao Yamamoto 2 , Takeo Itoh 2 . 1 Department of Obstetrics and Gynecology, West Medical Center Jouhoku Municipal Hospital, City of Nagoya, Aichi, Japan; 2 Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Japan Aim: Preeclampsia is characterized as an increase in vascular tone and permeability and blood coagulation due to activated endothelial function. It was found that either L-arginine (LARG, NO synthase substrate) or folic acid (FA) might improve the reduced endothelial function by adjustment between vascular superoxide production and nitric oxide (NO)-production in hypertensive disorders. In the present study, we investigated whether an oral supplementation of LARG plus FA improves endothelial dysfunction seen in preeclampsia. Methods: Change in brachial artery diameter by hyperemia (%FMD) was measured to evaluate endothelial function using ultrasound. 12 of 25 normal pregnant women seen reduced %FMD (<110) at less than 16 weeks of gestation were given the supplementation of FA 0.8mg+LARG1g daily throughout pregnancy. The concentrations of FA+LARG in erythrocyte, and cGMP (a second messenger of NO) and sFlt1 (anti-angiogenic factor) in serum were measured. Informed consent was obtained from each patient. Results: Reduced % FMD was seen in twenty-five pregnant women. One of 12 pregnant women in the supplementation group developed mild, late onset of preeclampsia, while 8 of 13 pregnant women in no supplement group developed onset preeclampsia (4 cases were severe). The concentration of sFlt-1 in preeclamptic women was increasing in both groups. Following the supplementation, %FMD had been increasing as well as the concentrations of FA and LARG in erythrocyte, although the concentration of cGMP in serum had no increase. Conclusions: The supplementation of FA+LARG might prevent preeclampsia due to improvement of the reduced endothelial function in high risk pregnant women.
Poster Presentations / Pregnancy Hypertension 1, Supplement 1 (2010) S43–S76
P95
P97
Do we deliver too soon for preterm pre-eclampsia?
Profile of maternal deaths in an obstetric ICU in Brazil
Eric Njforfut, Helena Nik, Steve Walkinshaw. Liverpool Women’s Hospital, Merseyside, UK
Alex Souza 1 , Adriana Scavuzzi 1 , Leila Katz 1 , Isabela Coutinho 1 , Melania Amorim 1 , Larissa Moura 2 , Renata Bezerra 2 . 1 Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Pernambuco, Brazil; 2 Faculdade Pernambucana de Saúde, Brazil
Introduction: Presentation with pre-eclampsia before 34 weeks’ gestation presents challenges in decision making that balance risks of neonatal morbidity and mortality against maternal risks. Recent review of the literature undertaken as part of the development of national guidelines in the UK posed questions on the maternal and fetal grounds often used to make decisions to deliver, suggesting that some births may be unnecessary. Aim: To examine indication for pretem birth for PET against proposed draft national guidance to determine the likely scope of potential pregnancy prolongation. Setting: UK tertiary maternity unit Methods: Identification of births < 34 weeks’ gestation for PET. Data on presentation, clinical course, laboratory investigations, fetal surveillance and blood pressure control was extracted from the case records. The indication for birth was extracted from the records, either as stated by the clinician or by agreement of two investigators. Standards: Justified birth (from draft UK guidance): severe persistent hypertension despite standard treatment to lower, symptomatic severe PET, eclampsia, platelets less than 70,000, ALT > 200 iu/ml, abnormal computerised CTG (STV < 3.5 msecs or recurrent decelerations), abnormal fetal Doppler (arterial and venous). Results: 130 cases identified from May 2005, of which 35 have been analysed. Mean time from admission to birth 9.9 days. 19 of 35 cases were judged justified. The commonest indications judged unjustified were increasing proteinuria and fetal growth restriction without evidence of compromise. In a few cases it was not possible to determine why particular women were delivered. Conclusion: Though the analysis is only partly completed, there is evidence that some pregnancies are ended on both maternal and fetal grounds where safe prolongation may be possible, even in a service where the average prolongation is compatible with published studies. It is possible that new national guidance may improve outcomes, particularly for the infant.
P96 The role of a low oxygen environment on the invasion of extravillous trophoblast from first trimester of pregnancy Akira Onogi, Katsuhiko Naruse, Toshiyuki Sado, Taketoshi Noguchi, Satomi Komeda, Emi Koyama, Kazuhiro Nishioka, Takashi Kitanaka, Hidekazu Oi, Hiroshi Kobayashi. Nara Medical University, Nara, Japan Background: During early pregnancy, cytotrophoblast differentiate into extravillous trophoblast (EVT) cells and invade into decidua, myometrium and uterine spiral arteries. In hypertensive pregnancy, disorder of this physiological process is regarded as an initial pathological feature. On the other hand, a low-oxygen environment is reported to effect on an invasiveness of each cancer cell lines. Aims: In this study, we investigated proteolytic functions and invasiveness of primary EVTs in hypoxia, to show the early placental pathology lead to hypertensive pregnancy. Methods: Placental samples (5-15 weeks gestation) were obtained from women undergoing elective surgical termination of pregnancy with written informed consent. Cytotrophoblast was separated with Percoll-based method and cultured on invasion assay chamber and 24-well plate applied Matrigel. Migration of the invasive phenotype trophoblast was studied with wound healing assay. Activity and expression of matrix metalloproteinases (MMP2 and MMP9) and urokinase-type plasminogen activator (uPA) in cell culture supernatant were investigated by geratin gel zymography and ELISA. Expression of HIF1α was measured with Western Blot using cell lysate. All cultures were performed under 20% oxygen, 5%, and 5% that repeated three times of hypoxic stimulation for one hour (0.1%). Results: Cell viabilities and migrations between each oxygen concentration showed no difference. Invasion was significantly increased in 20% and decreased in 0.1%. Activities of MMP2, TIMP2, and uPA did not alter in 0.1% than 5%, but increased in 20% environment. MMP9 showed no significant difference between each oxygen conditions. HIF1α was increased in 0.1% stimulation and decreased in 20% oxygen environment. Conclusion: These results suggested that a relatively low oxygen environment suppressed excessive invasion of the EVT in the placental bed of early pregnancy. HIF1α seemed not participated in the invasiveness of EVT, which suggested that severe hypoxia induces poor invasion of EVT in early pregnancy and may lead to later preeclampsia.
Objective: To describe obstetrical deaths in an obstetrical intensive care unit (ICU). Methods: A cross-sectional study was conducted including all women admitted in the obstetrical ICU from September 2002 to August 2009. The study was approved by local Ethics Committee. Inclusion criteria were admission to obstetrical ICU. Frequency of death, cause of admission to ICU, age, admission before or after delivery, gestational age, parity, stillbirth and diagnosis established during ICU stay were the variables evaluated. When delivery occurred during ICU stay, weight of the newborn was studied. Epi-Info 3.5.1. was used for statistical analysis. Results: During the study period, 6307 women met inclusion criteria. 94 obstetrical deaths were analysed. Obstetrical deaths occurred 1.84% of ICU admissions, which corresponds to a maternal mortality ratio of 228. Mean age of patients who died was 26 years, 77% studied no more than seven years, and nearly 54% were referred to our institution from another health unit. 67% were admitted still pregnant and abdominal delivery was performed in 66%. Stillbirths occurred in 40% of the patients. The most common diagnosis established during ICU stay was hypertension (52%), septic shock (20%) and hemorrhage (12%). In women with hypertensive disorders, eclampsia occurred in 45% and HELLP syndrome in 29%. Conclusions: Our frequency of obstetrical deaths is similar to those seen in obstetrical ICU worldwide. The main diagnosis found in these women coincides with the main causes of obstetrical deaths in our country. Recognizing the profile of women who die in an obstetrical ICU may contribute to create strategies for the reduction of obstetrical deaths.
P98 Does supplementation of L-arginine plus folic acid improve reduced endothelial function seen in preeclampsia? Yoshikatsu Suzuki 1 , Tamao Yamamoto 2 , Takeo Itoh 2 . 1 Department of Obstetrics and Gynecology, West Medical Center Jouhoku Municipal Hospital, City of Nagoya, Aichi, Japan; 2 Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Japan Aim: Preeclampsia is characterized as an increase in vascular tone and permeability and blood coagulation due to activated endothelial function. It was found that either L-arginine (LARG, NO synthase substrate) or folic acid (FA) might improve the reduced endothelial function by adjustment between vascular superoxide production and nitric oxide (NO)-production in hypertensive disorders. In the present study, we investigated whether an oral supplementation of LARG plus FA improves endothelial dysfunction seen in preeclampsia. Methods: Change in brachial artery diameter by hyperemia (%FMD) was measured to evaluate endothelial function using ultrasound. 12 of 25 normal pregnant women seen reduced %FMD (<110) at less than 16 weeks of gestation were given the supplementation of FA 0.8mg+LARG1g daily throughout pregnancy. The concentrations of FA+LARG in erythrocyte, and cGMP (a second messenger of NO) and sFlt1 (anti-angiogenic factor) in serum were measured. Informed consent was obtained from each patient. Results: Reduced % FMD was seen in twenty-five pregnant women. One of 12 pregnant women in the supplementation group developed mild, late onset of preeclampsia, while 8 of 13 pregnant women in no supplement group developed onset preeclampsia (4 cases were severe). The concentration of sFlt-1 in preeclamptic women was increasing in both groups. Following the supplementation, %FMD had been increasing as well as the concentrations of FA and LARG in erythrocyte, although the concentration of cGMP in serum had no increase. Conclusions: The supplementation of FA+LARG might prevent preeclampsia due to improvement of the reduced endothelial function in high risk pregnant women.