- Email: [email protected]
18: Maternal magnesium supplementation reduces incidence of intrauterine growth restriction in a rat model and modulates cytokine expression
Oral Concurrent Session 2
www. AJOG.org
Thursday, February 14, 2013 • 1:15 pm – 3:30 pm • Continental 1-4 FETUS/ULTRASOUND
Abstracts 18 – 26 Moderators: Honor Wolfe, MD; Karin Fuchs, MD 18 Maternal magnesium supplementation reduces incidence of intrauterine growth restriction in a rat model and modulates cytokine expression
Outcomes
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
OBJECTIVE: Intrauterine growth restriction (IUGR) increases the risk
of preterm birth and both are associated with enhanced inflammatory response. We sought to investigate whether magnesium attenuates inflammatory cytokines in a rat model of IUGR. STUDY DESIGN: Pregnant female Wistar rats (12 wks old, GD18) were divided in four groups: normal diet with bilateral uterine artery ligation (BL; n⫽6) or sham surgery (SH; n⫽5); and magnesium chloride 1% in drinking water throughout gestation ⫹ BL: MgBL (n⫽5) or sham: MgSH (n⫽5). Dams were euthanized 24 hrs postsurgery (GD19). We collected: maternal plasma, fetal plasma (pooled from a single dam), individual amniotic fluid samples, and placentas from live fetal pups only (BL⫽36; SH⫽20; MgBL⫽20; MgSH⫽20). All samples were analyzed for cytokines (IL-6, IL-1, CXCL1, CCL2 and TNF␣; sensitivity ⬍3pg/ml) using multiplex. Data was analyzed using ANOVA and t-test. RESULTS: The average fetal and placental weights were significantly lower in the BL dams when compared to SH dams (P⬍0.001) (Table 1). The overall fetal mortality was not significantly different for BL vs. MgBL. The incidence of IUGR (Pup weight ⬍10th) in BL vs. MgBL were 86.3% vs. 31% respectively [RR: 0.36 (CI:0.2-0.6) P ⬍0.0001]. IL-6, IL-1, TNF␣ (P⬍0.05) and CCL2 (P⬍0.001) levels were significantly increased in the BL amniotic fluids, while IL-6, IL-1, CCL2 and CXCL1 (P⬍0.001) and TNF␣ (P⬍0.05) were significantly increased in BL placental tissues when compared to SH, magnesium supplementation decreased the cytokine expression of IL-1, TNF␣ and CCL2 in amniotic fluid and IL1 in placental tissue of MgBL (P⬍0.001) (Fig. 1). Neither maternal nor fetal plasma showed differences in cytokine levels. CONCLUSION: Maternal oral magnesium supplementation reduced the incidence of BL-induced IUGR by 64% and modulated cytokine expression in amniotic fluid and placentas obtained from live IUGR fetuses in absence of maternal systemic inflammation. Supported by Oxenhorn Family.
Pup weight BL vs MgBL: P ⬍ .0001; placenta weight BL vs MgBL: P ⬍ .01. Pup and placenta weight: SH vs MgSH: P ⬍ .05 (Mann-Whitney Test). BL, bilateral uterine artery ligation; MgBL, magnesium chloride 1% ⫹ bilateral uterine artery ligation; MgSH, magnesium chloride 1% ⫹ sham surgery; SH, sham surgery.
19 The optimal definition of intrauterine growth restriction based on perinatal morbidity and mortality—results of the National Multicenter Prospective PORTO trial Julia Unterscheider1, Sean Daly2, Michael Geary3, Mairead Kennelly4, Fionnuala McAuliffe5, Keelin O’Donoghue6, Alyson Hunter7, John Morrison8, Gerard Burke9, Patrick Dicker10, Elizabeth Tully1, Fergal Malone1 1 Royal College of Surgeons in Ireland, Obstetrics & Gynecology, Dublin, Ireland, 2Coombe Women and Infants University Hospital, Obstetrics & Gynecology, Dublin, Ireland, 3Rotunda Hospital, Obstetrics & Gynecology, Dublin, Ireland, 4Coombe Women and Infants University Hospital, UCD Center for Human Reproduction, Dublin, Ireland, 5National Maternity Hospital, UCD Obstetrics & Gynecology, School of Medicine and Medical Science, Dublin, Ireland, 6University College Cork, Cork University Maternity Hospital, Obstetrics & Gynecology, Cork, Ireland, 7Royal Jubilee Maternity Hospital, Obstetrics & Gynecology, Belfast, Ireland, 8National University of Ireland, Obstetrics & Gynecology, Galway, Ireland, 9MidWestern Regional Maternity Hospital, Obstetrics & Gynecology, Limerick, Ireland, 10Royal College of Surgeons in Ireland, Epidemiology & Public Health, Dublin, Ireland
OBJECTIVE: The PORTO Trial is a prospective study conducted at the seven largest Irish obstetric centers, whose goal is to study optimal IUGR management (defined as EFW ⬍10th centile). It is unclear however whether this definition is clinically significant. Our objective was to define which sonographic findings best predict perinatal morbidity and mortality. STUDY DESIGN: Over 1,000 consecutive singleton pregnancies with EFW⬍10th centile were recruited from January 2010 to June 2012. Definitions for significant IUGR included EFW or AC⬍10th, 5th or 3rd centiles, ⫹/⫺ oligohydramnios, ⫹/⫺ abnormal umbilical arterial (UA) Doppler (PI⬍95th centile or AEDF). Perinatal mortality, admission to NICU and a composite neonatal outcome of IVH, PVL, HIE, NEC, BPD and sepsis were documented for all cases. RESULTS: Of the 1,056 fetuses, 324 (31%) were admitted to NICU and 65 (6.2%) were affected by serious adverse outcome including 15 mortalities (1.4%). The only sonographic weight-related definition that consistently predicted adverse outcome was an EFW ⬍3rd centile (p⫽0.0034). The presence of oligohydramnios was only important when combined with an EFW ⬍3rd centile (p⫽0.0445). However the presence of abnormal umbilical Doppler was always associated with adverse outcomes, irrespective of the EFW or the AC measurement (Table). CONCLUSION: Abnormal UA Doppler is the strongest and most consistent predictor for adverse perinatal outcome with EFW⬍10th centile.
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S13
www. AJOG.org
Thursday, February 14, 2013 • 1:15 pm – 3:30 pm • Continental 1-4 FETUS/ULTRASOUND
Abstracts 18 – 26 Moderators: Honor Wolfe, MD; Karin Fuchs, MD 18 Maternal magnesium supplementation reduces incidence of intrauterine growth restriction in a rat model and modulates cytokine expression
Outcomes
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
OBJECTIVE: Intrauterine growth restriction (IUGR) increases the risk
of preterm birth and both are associated with enhanced inflammatory response. We sought to investigate whether magnesium attenuates inflammatory cytokines in a rat model of IUGR. STUDY DESIGN: Pregnant female Wistar rats (12 wks old, GD18) were divided in four groups: normal diet with bilateral uterine artery ligation (BL; n⫽6) or sham surgery (SH; n⫽5); and magnesium chloride 1% in drinking water throughout gestation ⫹ BL: MgBL (n⫽5) or sham: MgSH (n⫽5). Dams were euthanized 24 hrs postsurgery (GD19). We collected: maternal plasma, fetal plasma (pooled from a single dam), individual amniotic fluid samples, and placentas from live fetal pups only (BL⫽36; SH⫽20; MgBL⫽20; MgSH⫽20). All samples were analyzed for cytokines (IL-6, IL-1, CXCL1, CCL2 and TNF␣; sensitivity ⬍3pg/ml) using multiplex. Data was analyzed using ANOVA and t-test. RESULTS: The average fetal and placental weights were significantly lower in the BL dams when compared to SH dams (P⬍0.001) (Table 1). The overall fetal mortality was not significantly different for BL vs. MgBL. The incidence of IUGR (Pup weight ⬍10th) in BL vs. MgBL were 86.3% vs. 31% respectively [RR: 0.36 (CI:0.2-0.6) P ⬍0.0001]. IL-6, IL-1, TNF␣ (P⬍0.05) and CCL2 (P⬍0.001) levels were significantly increased in the BL amniotic fluids, while IL-6, IL-1, CCL2 and CXCL1 (P⬍0.001) and TNF␣ (P⬍0.05) were significantly increased in BL placental tissues when compared to SH, magnesium supplementation decreased the cytokine expression of IL-1, TNF␣ and CCL2 in amniotic fluid and IL1 in placental tissue of MgBL (P⬍0.001) (Fig. 1). Neither maternal nor fetal plasma showed differences in cytokine levels. CONCLUSION: Maternal oral magnesium supplementation reduced the incidence of BL-induced IUGR by 64% and modulated cytokine expression in amniotic fluid and placentas obtained from live IUGR fetuses in absence of maternal systemic inflammation. Supported by Oxenhorn Family.
Pup weight BL vs MgBL: P ⬍ .0001; placenta weight BL vs MgBL: P ⬍ .01. Pup and placenta weight: SH vs MgSH: P ⬍ .05 (Mann-Whitney Test). BL, bilateral uterine artery ligation; MgBL, magnesium chloride 1% ⫹ bilateral uterine artery ligation; MgSH, magnesium chloride 1% ⫹ sham surgery; SH, sham surgery.
19 The optimal definition of intrauterine growth restriction based on perinatal morbidity and mortality—results of the National Multicenter Prospective PORTO trial Julia Unterscheider1, Sean Daly2, Michael Geary3, Mairead Kennelly4, Fionnuala McAuliffe5, Keelin O’Donoghue6, Alyson Hunter7, John Morrison8, Gerard Burke9, Patrick Dicker10, Elizabeth Tully1, Fergal Malone1 1 Royal College of Surgeons in Ireland, Obstetrics & Gynecology, Dublin, Ireland, 2Coombe Women and Infants University Hospital, Obstetrics & Gynecology, Dublin, Ireland, 3Rotunda Hospital, Obstetrics & Gynecology, Dublin, Ireland, 4Coombe Women and Infants University Hospital, UCD Center for Human Reproduction, Dublin, Ireland, 5National Maternity Hospital, UCD Obstetrics & Gynecology, School of Medicine and Medical Science, Dublin, Ireland, 6University College Cork, Cork University Maternity Hospital, Obstetrics & Gynecology, Cork, Ireland, 7Royal Jubilee Maternity Hospital, Obstetrics & Gynecology, Belfast, Ireland, 8National University of Ireland, Obstetrics & Gynecology, Galway, Ireland, 9MidWestern Regional Maternity Hospital, Obstetrics & Gynecology, Limerick, Ireland, 10Royal College of Surgeons in Ireland, Epidemiology & Public Health, Dublin, Ireland
OBJECTIVE: The PORTO Trial is a prospective study conducted at the seven largest Irish obstetric centers, whose goal is to study optimal IUGR management (defined as EFW ⬍10th centile). It is unclear however whether this definition is clinically significant. Our objective was to define which sonographic findings best predict perinatal morbidity and mortality. STUDY DESIGN: Over 1,000 consecutive singleton pregnancies with EFW⬍10th centile were recruited from January 2010 to June 2012. Definitions for significant IUGR included EFW or AC⬍10th, 5th or 3rd centiles, ⫹/⫺ oligohydramnios, ⫹/⫺ abnormal umbilical arterial (UA) Doppler (PI⬍95th centile or AEDF). Perinatal mortality, admission to NICU and a composite neonatal outcome of IVH, PVL, HIE, NEC, BPD and sepsis were documented for all cases. RESULTS: Of the 1,056 fetuses, 324 (31%) were admitted to NICU and 65 (6.2%) were affected by serious adverse outcome including 15 mortalities (1.4%). The only sonographic weight-related definition that consistently predicted adverse outcome was an EFW ⬍3rd centile (p⫽0.0034). The presence of oligohydramnios was only important when combined with an EFW ⬍3rd centile (p⫽0.0445). However the presence of abnormal umbilical Doppler was always associated with adverse outcomes, irrespective of the EFW or the AC measurement (Table). CONCLUSION: Abnormal UA Doppler is the strongest and most consistent predictor for adverse perinatal outcome with EFW⬍10th centile.
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S13