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745: Determinants of cardiovascular deterioration in fetal growth restriction (FGR)
SMFM Abstracts
www.AJOG.org 742
THE HUMAN FETUS MAINTAINS NORMAL RENAL ARTERY BLOOD FLOW REGARDLESS OF INFLAMMATION HUMBERTO AZPURUA1, MERT O. BAHTIYAR1, EDMUND F. FUNAI1, ANTONETTE T. DULAY1, SONYA S. ABDEL-RAZEQ1, STEPHEN F. THUNG1, GUOYANG LUO1, IRINA A. BUHIMSCHI1, JOSHUA A. COPEL1, CATALIN S. BUHIMSCHI1, 1Yale University, Ob./Gyn.&Reprod.Sci, New Haven, Connecticut OBJECTIVE: A systemic fetal inflammatory response is initiated when infection gains access to the fetus and stimulates the production of cytokines. Multiple organ dysfunction including that of the kidneys is expected. This study was conducted to evaluate fetal renal artery hemodynamics in the context of inflammation-induced preterm birth (PTB). STUDY DESIGN: Fetal renal artery Dopplers were performed in 50 singleton fetuses (median [range], GA: 28[22-34]wks) of women with signs or symptoms of PTB (48% PPROM) who had an amniocentesis to rule out infection. GA reference ranges were generated based on fetuses with uncomplicated pregnancies (n⫽20). Appropriate low filter (50-75Hz) was used. Renal artery pulsatility index (PI), resistance index (RI), systolic/diastolic (S/D) ratio, and presence or absence of enddiastolic blood flow were assessed. Intra-amniotic inflammation (IAI) was assessed by proteomic profiling. Velocities were interpreted in relation to: IAI, AFI and cord blood IL-6 measured by ELISA. RESULTS: 1) 94% (47/50) of fetuses were born preterm (GA: 31 [22-40]wks) and 32% (16/50) in the context of IAI; 2) There was no relationship between Doppler indices and GA or EFW in either normal pregnancies or those complicated by PTB. 3) Cord blood IL-6 was higher in IAI (p⬍0.001); 4) The degree of fetal inflammation by cord IL-6, did not impact on either renal artery PI, RI, S/D ratio or end-diastolic blood flow; 5) A significant inverse relationship between renal artery RI and AFI remained after correcting for membrane status (r⫽ -0.33, p⫽0.02) (Figure). CONCLUSION: This is the first study to demonstrate that the fetus is capable of sustaining normal renal artery hemodynamics regardless of inflammation. We also demonstrate that the resistance of the fetal renal artery impacts on urine output independent of inflammation.
744
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.773
745
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.771
743
MID-TRIMESTER MATERNAL MIDDLE CEREBRAL ARTERY (MCA) DOPPLER FOR PREDICTION OF PREECLAMPSIA IN A LOW RISK POPULATION MICHAEL BELFORT1, GEORGE SAADE2, STEVEN CLARK3, GARY DILDY3, JANALEE ALLRED3, SEAN LUDLOW4, 1 Hospital Corporation of America and the University of Utah, Obstetrics and Gynecology, Salt Lake City, Utah, 2UTMB, Galveston, OB-GYN MATERNAL FETAL MEDICINE, Galveston, Texas, 3Hospital Corporation of America, Salt Lake City, Utah, 4Hospital Corporation of America, Utah OBJECTIVE: To determine whether second trimester MCA Doppler parameters can predict the subsequent development of preeclampsia in a low risk population. STUDY DESIGN: Prospective longitudinal cohort study in a community hospital. Low risk pregnant women at 16 - 24 weeks were enrolled. Blood pressure and MCA Doppler systolic, diastolic and mean velocity were recorded. All patients were normotensive and had negative urine protein at the time of screening. After delivery patients were divided into normal uncomplicated pregancy (NORM) or preeclampsia (PRE) groups confirmed by chart review by an investigator who was blinded to the cerebral perfusion pressure (CPP) results. Clinical providers were also blinded to the Doppler data. CPP, resistance index (RI), and pulsatility index (PI) were calculated. Data, both unadjusted and adjusted for gestational age using multiples of the median (MoM), were analyzed with Student’s t test, and ROC curves as appropriate (significance: p ⬍ 0.05). RESULTS: 181 patients participated. Eight women (4.4%) developed preeclampsia. Demographics (age, weight, height, parity) and 2nd trimester mean arterial pressure (MAP) for NORM and PRE respectively [Mean(SD): 82(8) vs. 85(6) mmHg; p ⫽ 0.4] were not significantly different. Screen-to-delivery interval was similar for NORM and PRE [19.0(3.6) vs. 18.2(2.3) weeks; p ⫽ NS). Despite the fact that the MAP of the two groups was similar, the CPP was higher at the screening measurement in the women who subsequently developed preeclampsia [48(10) vs. 41(11) mmHg; p ⫽ 0.06). CPP at 16 - 24 weeks was predictive of preeclampsia (area under the curve 0.69; p ⫽ 0.02). CPP ⬎ 46 mmHg at 16-24 weeks had a sensitivity of 63% and specificity of 73% for prediction of preeclampsia at term. A CPP ⬎ 1 MoM was 63% sensitive and 79% specific. CONCLUSION: A middle cerebral artery perfusion pressure greater than 46 mmHg between 16 and 24 weeks may be useful in predicting women who will ultimately develop preeclampsia. This easily performed measurement may have signifiacnt implications for both researchers and clinicians.
PREDICTORS OF ADVERSE PERINATAL AND MATERNAL OUTCOMES IN SEVERE PRETERM PREECLAMPSIA MADDALENA INCERTI1, SILVIA MALBERTI1, ANNA LOCATELLI1, ILARIA POZZI1, MASSIMILIANO GRECO1, ALESSANDRO GHIDINI1, 1University of Milano-Bicocca, Department of Obstetrics and Gynecology, Monza, Italy OBJECTIVE: To asses the variables predicting maternal complications and perinatal outcomes in women with severe preeclampsia (SPE) at 24-33 weeks’ gestation. STUDY DESIGN: From a cohort of 130 women with singleton pregnancies admitted over a 6-year period for SPE at 24-33 weeks= gestation managed expectantly, we selected those with Doppler findings available. Demographic variables, Doppler findings, laboratory test results and relevant obstetric variables were related to occurrence of maternal complications (abruptio placentae, need of transfusion, eclampsia, DIC, pulmonary edema, and renal failure) or adverse neonatal outcome (death or severe complications) using one-way ANOVA, chi-square test, and logistic regression with P⬍0.05 considered significant. RESULTS: During the study period 71/130 women (54%) with SPE had Doppler findings available. Thirteen women developed maternal complications and 21 neonates had adverse outcome. The only variables significantly associated with maternal complications were AST and ALT values (p⫽0.05 and p⫽0.004). At univariate analysis neonatal adverse outcome was associated with abnormal uterine artery (p⫽0.029), birth weight (p⬍.001), gestational age at delivery (31 vs 28 weeks, p⬍0.001), and latency from admission to hospital to delivery (p⬍0.001). At logistic regression analysis only gestational age at delivery was significantly associated with adverse neonatal outcome (p⬍0.001). CONCLUSION: In women SPE at 24-33 weeks’ gestation, only liver function tests predict maternal complications and only gestational age at delivery predicts occurrence of adverse neonatal outcome.
DETERMINANTS OF CARDIOVASCULAR DETERIORATION IN FETAL GROWTH RESTRICTION (FGR) OZHAN TURAN1, SIFA TURAN2, BERG CHRISTOPH3, ULRICH GEMBRUCH4, KYPROS NICOLAIDES5, CHRISTOPHER HARMAN1, AHMET BASCHAT1, 1University of Maryland at Baltimore, Baltimore, Maryland, 2University of Maryland, Baltimore, Maryland, 3Friedrich-Wilhelm University, , Germany, 4Friedrich Wilhelm University, Bonn, Obstetrics & Prenatal MEdicine, Bonn, Germany, 5King’s College Hospital, London, United Kingdom OBJECTIVE: Identify factors that determine progression of cardiovascular deterioration in FGR. STUDY DESIGN: Prospective longitudinal observational study of singleton FGR (abdominal circumference ⬍5th %ile). Serial standardized Doppler included umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV). Temporal characteristics and degree of cardiovascular deterioration were related to Doppler parameters and gestational age. RESULTS: 104 fetuses had 688 longitudinal exams, identifying 3 patterns of progression. Sequence of deterioration (Figure:X axis is days before delivery not gestational age) was determined by degree of UA Doppler abnormality at onset and progression during initial monitoring. All who progressed rapidly (onset 27w, delivery by30w, upper curve) had UA PI ⬎ 3SD, and deteriorated in 6-day increments. Rate did vary, but all showed at least two further increments in the first 2.5w of monitoring. Those who ultimately progressed more slowly (onset 29w, delivery 33w, mid curve) had UA PI ⬍2SD but worsened in 2.5w to UA PI ⬎3, MCA centralized, worsening venous abnormality. Mild group (lower curve) changed gradually, with no increments in first 2.5w (onset 32w, delivery 35w). Mild and progressive groups initially similar, diverged by the 2.5w point. Rate of deterioration in UA, MCA and DV all significantly related to gestation at onset, and ultimately predicted severity of growth delay, condition at birth.
CONCLUSION: In longitudinal FGR monitoring, temporal sequence and progression of Doppler deterioration are determined by gestational age at onset, degree of UA abnormality, and changes over first 2.5 weeks of monitoring. These observations have critical implications for selection of monitoring intervals and modalities in these challenging pregnancies. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.774
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.772
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
S211
www.AJOG.org 742
THE HUMAN FETUS MAINTAINS NORMAL RENAL ARTERY BLOOD FLOW REGARDLESS OF INFLAMMATION HUMBERTO AZPURUA1, MERT O. BAHTIYAR1, EDMUND F. FUNAI1, ANTONETTE T. DULAY1, SONYA S. ABDEL-RAZEQ1, STEPHEN F. THUNG1, GUOYANG LUO1, IRINA A. BUHIMSCHI1, JOSHUA A. COPEL1, CATALIN S. BUHIMSCHI1, 1Yale University, Ob./Gyn.&Reprod.Sci, New Haven, Connecticut OBJECTIVE: A systemic fetal inflammatory response is initiated when infection gains access to the fetus and stimulates the production of cytokines. Multiple organ dysfunction including that of the kidneys is expected. This study was conducted to evaluate fetal renal artery hemodynamics in the context of inflammation-induced preterm birth (PTB). STUDY DESIGN: Fetal renal artery Dopplers were performed in 50 singleton fetuses (median [range], GA: 28[22-34]wks) of women with signs or symptoms of PTB (48% PPROM) who had an amniocentesis to rule out infection. GA reference ranges were generated based on fetuses with uncomplicated pregnancies (n⫽20). Appropriate low filter (50-75Hz) was used. Renal artery pulsatility index (PI), resistance index (RI), systolic/diastolic (S/D) ratio, and presence or absence of enddiastolic blood flow were assessed. Intra-amniotic inflammation (IAI) was assessed by proteomic profiling. Velocities were interpreted in relation to: IAI, AFI and cord blood IL-6 measured by ELISA. RESULTS: 1) 94% (47/50) of fetuses were born preterm (GA: 31 [22-40]wks) and 32% (16/50) in the context of IAI; 2) There was no relationship between Doppler indices and GA or EFW in either normal pregnancies or those complicated by PTB. 3) Cord blood IL-6 was higher in IAI (p⬍0.001); 4) The degree of fetal inflammation by cord IL-6, did not impact on either renal artery PI, RI, S/D ratio or end-diastolic blood flow; 5) A significant inverse relationship between renal artery RI and AFI remained after correcting for membrane status (r⫽ -0.33, p⫽0.02) (Figure). CONCLUSION: This is the first study to demonstrate that the fetus is capable of sustaining normal renal artery hemodynamics regardless of inflammation. We also demonstrate that the resistance of the fetal renal artery impacts on urine output independent of inflammation.
744
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.773
745
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.771
743
MID-TRIMESTER MATERNAL MIDDLE CEREBRAL ARTERY (MCA) DOPPLER FOR PREDICTION OF PREECLAMPSIA IN A LOW RISK POPULATION MICHAEL BELFORT1, GEORGE SAADE2, STEVEN CLARK3, GARY DILDY3, JANALEE ALLRED3, SEAN LUDLOW4, 1 Hospital Corporation of America and the University of Utah, Obstetrics and Gynecology, Salt Lake City, Utah, 2UTMB, Galveston, OB-GYN MATERNAL FETAL MEDICINE, Galveston, Texas, 3Hospital Corporation of America, Salt Lake City, Utah, 4Hospital Corporation of America, Utah OBJECTIVE: To determine whether second trimester MCA Doppler parameters can predict the subsequent development of preeclampsia in a low risk population. STUDY DESIGN: Prospective longitudinal cohort study in a community hospital. Low risk pregnant women at 16 - 24 weeks were enrolled. Blood pressure and MCA Doppler systolic, diastolic and mean velocity were recorded. All patients were normotensive and had negative urine protein at the time of screening. After delivery patients were divided into normal uncomplicated pregancy (NORM) or preeclampsia (PRE) groups confirmed by chart review by an investigator who was blinded to the cerebral perfusion pressure (CPP) results. Clinical providers were also blinded to the Doppler data. CPP, resistance index (RI), and pulsatility index (PI) were calculated. Data, both unadjusted and adjusted for gestational age using multiples of the median (MoM), were analyzed with Student’s t test, and ROC curves as appropriate (significance: p ⬍ 0.05). RESULTS: 181 patients participated. Eight women (4.4%) developed preeclampsia. Demographics (age, weight, height, parity) and 2nd trimester mean arterial pressure (MAP) for NORM and PRE respectively [Mean(SD): 82(8) vs. 85(6) mmHg; p ⫽ 0.4] were not significantly different. Screen-to-delivery interval was similar for NORM and PRE [19.0(3.6) vs. 18.2(2.3) weeks; p ⫽ NS). Despite the fact that the MAP of the two groups was similar, the CPP was higher at the screening measurement in the women who subsequently developed preeclampsia [48(10) vs. 41(11) mmHg; p ⫽ 0.06). CPP at 16 - 24 weeks was predictive of preeclampsia (area under the curve 0.69; p ⫽ 0.02). CPP ⬎ 46 mmHg at 16-24 weeks had a sensitivity of 63% and specificity of 73% for prediction of preeclampsia at term. A CPP ⬎ 1 MoM was 63% sensitive and 79% specific. CONCLUSION: A middle cerebral artery perfusion pressure greater than 46 mmHg between 16 and 24 weeks may be useful in predicting women who will ultimately develop preeclampsia. This easily performed measurement may have signifiacnt implications for both researchers and clinicians.
PREDICTORS OF ADVERSE PERINATAL AND MATERNAL OUTCOMES IN SEVERE PRETERM PREECLAMPSIA MADDALENA INCERTI1, SILVIA MALBERTI1, ANNA LOCATELLI1, ILARIA POZZI1, MASSIMILIANO GRECO1, ALESSANDRO GHIDINI1, 1University of Milano-Bicocca, Department of Obstetrics and Gynecology, Monza, Italy OBJECTIVE: To asses the variables predicting maternal complications and perinatal outcomes in women with severe preeclampsia (SPE) at 24-33 weeks’ gestation. STUDY DESIGN: From a cohort of 130 women with singleton pregnancies admitted over a 6-year period for SPE at 24-33 weeks= gestation managed expectantly, we selected those with Doppler findings available. Demographic variables, Doppler findings, laboratory test results and relevant obstetric variables were related to occurrence of maternal complications (abruptio placentae, need of transfusion, eclampsia, DIC, pulmonary edema, and renal failure) or adverse neonatal outcome (death or severe complications) using one-way ANOVA, chi-square test, and logistic regression with P⬍0.05 considered significant. RESULTS: During the study period 71/130 women (54%) with SPE had Doppler findings available. Thirteen women developed maternal complications and 21 neonates had adverse outcome. The only variables significantly associated with maternal complications were AST and ALT values (p⫽0.05 and p⫽0.004). At univariate analysis neonatal adverse outcome was associated with abnormal uterine artery (p⫽0.029), birth weight (p⬍.001), gestational age at delivery (31 vs 28 weeks, p⬍0.001), and latency from admission to hospital to delivery (p⬍0.001). At logistic regression analysis only gestational age at delivery was significantly associated with adverse neonatal outcome (p⬍0.001). CONCLUSION: In women SPE at 24-33 weeks’ gestation, only liver function tests predict maternal complications and only gestational age at delivery predicts occurrence of adverse neonatal outcome.
DETERMINANTS OF CARDIOVASCULAR DETERIORATION IN FETAL GROWTH RESTRICTION (FGR) OZHAN TURAN1, SIFA TURAN2, BERG CHRISTOPH3, ULRICH GEMBRUCH4, KYPROS NICOLAIDES5, CHRISTOPHER HARMAN1, AHMET BASCHAT1, 1University of Maryland at Baltimore, Baltimore, Maryland, 2University of Maryland, Baltimore, Maryland, 3Friedrich-Wilhelm University, , Germany, 4Friedrich Wilhelm University, Bonn, Obstetrics & Prenatal MEdicine, Bonn, Germany, 5King’s College Hospital, London, United Kingdom OBJECTIVE: Identify factors that determine progression of cardiovascular deterioration in FGR. STUDY DESIGN: Prospective longitudinal observational study of singleton FGR (abdominal circumference ⬍5th %ile). Serial standardized Doppler included umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV). Temporal characteristics and degree of cardiovascular deterioration were related to Doppler parameters and gestational age. RESULTS: 104 fetuses had 688 longitudinal exams, identifying 3 patterns of progression. Sequence of deterioration (Figure:X axis is days before delivery not gestational age) was determined by degree of UA Doppler abnormality at onset and progression during initial monitoring. All who progressed rapidly (onset 27w, delivery by30w, upper curve) had UA PI ⬎ 3SD, and deteriorated in 6-day increments. Rate did vary, but all showed at least two further increments in the first 2.5w of monitoring. Those who ultimately progressed more slowly (onset 29w, delivery 33w, mid curve) had UA PI ⬍2SD but worsened in 2.5w to UA PI ⬎3, MCA centralized, worsening venous abnormality. Mild group (lower curve) changed gradually, with no increments in first 2.5w (onset 32w, delivery 35w). Mild and progressive groups initially similar, diverged by the 2.5w point. Rate of deterioration in UA, MCA and DV all significantly related to gestation at onset, and ultimately predicted severity of growth delay, condition at birth.
CONCLUSION: In longitudinal FGR monitoring, temporal sequence and progression of Doppler deterioration are determined by gestational age at onset, degree of UA abnormality, and changes over first 2.5 weeks of monitoring. These observations have critical implications for selection of monitoring intervals and modalities in these challenging pregnancies. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.774
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.772
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
S211