Uterine artery pulsatility index in hypertensive pregnancies: When does the index normalize in the puerperium?

OBJECTIVE: To investigate whether the uterine artery pulsatility index (UtA PI) of hypertensive pregnancies is higher than that of normal pregnancies in the puerperium, as well as in the antepartum period. METHODS: The UtA PI was measured in hypertensive (group 1) and normal pregnancies (group 2) during antepartum, immediate postpartum or late postpartum periods. Using the transvaginal approach, the bilateral uterine artery indices were measured. RESULTS: One hundred twenty-two women were enrolled: group 1, hypertensive disease in pregnancy (11 cases in antepartum, 13 cases in immediate postpartum and 10 cases in late postpartum period); group 2, normal pregnancies (32 cases in antepartum, 29 cases in immediate postpartum and 27 cases in late postpartum). In antepartum and immediate postpartum periods, the mean UtA PI and the proportion of cases with an early diastolic notch were higher in group 1 than in group 2 (antepartum mean UtA PI, 1.14 in group 1 vs. 0.68 in group 2, P<0.001; early diastolic notch, 46% vs. 9%, P<0.05; immediate postpartum mean UtA PI, 1.30 vs. 1.08, P<0.05; early diastolic notch, 85% vs. 48%, P<0.05). In late postpartum period, the mean value of UtA PI of group 1 was still higher than that of group 2, although the proportion of cases with an early diastolic notch was not different (mean UtA PI, 1.43 vs. 1.20, P<0.05; early diastolic notch, 60% vs. 52%, P=0.73). CONCLUSION: The UtA PI in hypertensive pregnancies was still higher than normal pregnancies in puerperal periods, suggesting that more than several weeks are required to resolve increased uterine artery vascular impedance.

Proteomic biomarkers in second trimester amniotic fluid that identify women who are destined to develop preeclampsia.

OBJECTIVES: This study investigated whether proteomic analysis of amniotic fluid (AF) in the early second trimester can be used to predict the development of preeclampsia. METHODS: Amniotic fluid samples were collected at the time of genetic amniocentesis (15-19 weeks of gestation) from women who subsequently developed preeclampsia and from gestational age-matched normotensive controls (n = 10 for each). Amniotic fluid samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulfate polyacrylamide gel coupled with in-gel tryptic digestion, electrospray ionization tandem mass spectrometry (MS/MS), immunodepletion assays, and enzyme-linke immunosorbent assay. RESULTS: Five proteomic biomarkers were identified, which were differentially expressed in women who subsequently developed preeclampsia compared with those women who did not; four of these peaks were significantly upregulated (mass-to-charge ratio of 9080 [P = .006], 14 045 [P = .010], 14 345 [P = .049], and 28 087 [P = .006]) and one was significantly downregulated (mass-to-charge ratio of 4679 [P = .014]) in women who subsequently developed preeclampsia. Using electrospray ionization MS/MS and immunodepletion assays, two protein peaks were identified as albumin fragment and apolipoprotein A-I. CONCLUSIONS: Using proteomic technology, this study identified protein biomarkers that are differentially expressed in the early second trimester AF from women who subsequently develop preeclampsia compared with women who remained normotensive. Early identification of women at risk of developing preeclampsia will allow clinicians to better optimize maternal and perinatal outcomes.

Angiopoietin-2: a promising indicator for the occurrence of severe preeclampsia.

BACKGROUND: The known connection between placental hypoxia and the development of preeclampsia suggests that angiogenic factors in the placenta would be changed and affect the maternal and/or umbilical cord plasma levels in patients with preeclampsia. OBJECTIVE: The aim of this study was to determine the difference and correlation of placental mRNA expression and maternal/umbilical cord plasma concentrations of vascular endothelial growth factor A (VEGF-A), angiopoietin-1, and angiopoietin-2 between women with severe preeclampsia and normal pregnancies. METHODS: Sixteen patients with severe preeclampsia and 29 normotensive pregnant women were studied. The placental mRNA expression was assessed using real-time quantitative RT-PCR analysis. Maternal/umbilical cord plasma levels were measured using an enzyme-linked immunoassay. Nonparametric methods were applied for statistical analysis. RESULTS: . Placental mRNA expression of angiopoietin-2 was significantly increased in patients with severe preeclampsia (p < 0.001). The maternal plasma angiopoietin-2 protein level was also significantly increased in women with severe preeclampsia (p < 0.05) and showed a positive correlation with the placental mRNA expression of angiopoietin-2 (r = 0.54, p < 0.005). For VEGF-A and angiopoietin-1, there were no significant differences between the two groups. A maternal plasma angiopoietin-2 concentration of 8.4 ng/mL had a sensitivity of 63% and a specificity of 83% for predicting severe preeclampsia. CONCLUSION: Placental angiopoietin-2 mRNA expression was increased and correlated with the maternal plasma angiopoietin-2 protein concentration in women with severe preeclampsia. This suggests that the plasma angiopoietin-2 protein level may be a candidate marker for severe preeclampsia.

Identification of proteomic biomarkers in maternal plasma in the early second trimester that predict the subsequent development of gestational diabetes.

INTRODUCTION: This study is designed to identify proteomic biomarkers that predict the subsequent development of gestational diabetes mellitus (GDM). METHODS: Maternal blood was obtained prospectively from healthy pregnant women in the early second trimester (16-20 weeks). Twelve women subsequently diagnosed with GDM at 24 to 28 weeks were selected as cases; an equal number of normoglycemic women as controls. Proteomic analysis of the previously stored plasma was performed by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. RESULTS: Three peaks (9122 Da, 9412 Da, and 9701 Da) that were increased in cases were characterized as isoforms of apolipoprotein CIII. Another discriminatory peak (17 105 Da) that was decreased in cases was matched to apolipoprotein AII. Enzyme-linked immunosorbent assay (ELISA) confirmed that women who subsequently developed GDM had significantly higher levels of apolipoprotein CIII than controls did. Levels of apolipoprotein AII failed to reach statistical significance. CONCLUSION: Our data suggest that there already exist biomarkers in the maternal circulation at 16 to 20 weeks in women who subsequently develop GDM.

Characterization of discriminatory urinary proteomic biomarkers for severe preeclampsia using SELDI-TOF mass spectrometry.

OBJECTIVE: To analyze the proteomic pattern in urine for distinguishing severe preeclampsia from mild preeclampsia and normotensive controls using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). STUDY DESIGN: Urine samples were collected from women with severe preeclampsia (n=11 [sPE]), mild preeclampsia (n=7 [mPE]), and normotensive controls (n=8) and analyzed by SELDI-TOF-MS to identify discriminatory protein peaks in the sPE cohort. A scoring system was constructed--designated as Preeclampsia Proteomic Score of Urine (PPSU)--to differentiate sPE from mPE and normotensive controls. RESULTS: Four discriminatory protein peaks were identified (m/z ratio: 4155, 6044, 6663, and 7971), all of which were down-regulated in women with sPE. PPSU scores in women with sPE were significantly lower than that in both mPE and controls (sPE 0 [0-4] vs. mPE 3 [0-4] vs. controls 4 [2-4]; median [range]; P<0.05). PPSU<2 had a sensitivity of 90.9% and specificity of 93.3% in discriminating patients with sPE from mPE and controls. CONCLUSION: Proteomic analysis of urine can accurately distinguish sPE from mPE and normotensive controls.

Successful vaginal delivery of a pregnant woman with Cantrell's Pentalogy.

Cantrell's Pentalogy is a rare condition that consists of defects involving the abdominal wall, lower sternum, anterior diaphragm, pericardium, and heart. In the literature to date, pregnant women with Cantrell's Pentalogy have not been discussed. We performed successful vaginal delivery of a 23-yr-old nulliparous, primigravid woman who had been diagnosed with this condition. Diagnosis was based on cardiac catheterization, angiography, and echocardiogram, and abdominopelvic CT. Vaginal delivery may be an option for women with Cantrell's Pentalogy and may be attempted with caution.

Self-reported smoking and urinary cotinine levels among pregnant women in Korea and factors associated with smoking during pregnancy.

This study examined urinary cotinine levels and self-reported smoking among pregnant women in Korea and the factors associated with smoking during pregnancy. The subjects were selected from pregnant women who visited 30 randomly sampled obstetric clinics and prenatal care hospitals in Korea in 2006. Smoking status was determined by self-reporting and urinary cotinine measurement. A total of 1,090 self-administered questionnaires and 1,057 urine samples were analyzed. The percentage of smoking revealed by self-reporting was 0.55% (95% confidence interval [CI], 0.11-0.99) and that revealed by urinary cotinine measurement (>100 ng/mL) was 3.03% (95% CI, 1.99-4.06). The kappa coefficient of agreement between self-reported smoking status and urinary cotinine measurement was 0.20 (95% CI, 0.03-0.37). Multiple logistic regression analysis revealed that early gestational period, low educational level, and being married to a smoker were significant risk factors for smoking during pregnancy. Smoking among pregnant women in Korea is not negligible, and those who are concerned to maternal and child health should be aware of this possibility among pregnant women in countries with similar cultural background.

Identification and characterization of proteins in amniotic fluid that are differentially expressed before and after antenatal corticosteroid administration.

OBJECTIVE: We sought to examine changes in the intraamniotic proteomic environment after the administration of antenatal corticosteroids to women with impending preterm delivery. STUDY DESIGN: Amniotic fluid samples were collected at the time of clinically indicated amniocentesis before and within 7 days of administration of antenatal corticosteroids for impending preterm delivery (n = 12). Proteins differentially expressed before and after corticosteroids were identified by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. They were isolated, characterized, and quantified by fast protein liquid chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in-gel tryptic digestion, immunodepletion assays, enzyme-linked immunosorbent assay, and electrospray ionization tandem mass spectrometry. RESULTS: Five protein peaks of interest were identified and characterized, all of which were significantly decreased after antenatal corticosteroid administration. These included 2 isoforms of transthyretin, albumin, prothrombin fragment 2, and lumican. CONCLUSION: Four proteins, identified and characterized in amniotic fluid, were differentially expressed with antenatal corticosteroid administration. These data may provide additional insight into the molecular mechanisms by which antenatal corticosteroids prevent neonatal complications.

Identification of proteomic biomarkers of preeclampsia in amniotic fluid using SELDI-TOF mass spectrometry.

OBJECTIVE: To identify proteomic biomarkers in amniotic fluid (AF) that can distinguish preeclampsia (PE) from chronic hypertension (CHTN) and normotensive controls (CTR). METHODS: AF from women with PE, CHTN, and CTR were subjected to proteomic analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Proteomic profiling of AF identified 2 biomarkers: peak X (17399.11 Da), which distinguished PE from CTR, and peak Y (28023.34 Da), which distinguished PE and CHTN from CTR. High performance liquid chromatography fractions containing the biomarkers were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in-gel tryptic digestion. The biomarkers were matched to proapolipoprotein A-I (peak Y) and a functionally obscure peptide, SBBI42 (peak X). Western blot analysis confirmed that AF from PE and CHTN had higher proapolipoprotein A-I levels than CTR. CONCLUSION: Proteomic analysis of AF can distinguish PE from CHTN and CTR. The discriminatory proteins were identified as proapolipoprotein A-I and SBBI42.

Relationship between twin-to-twin delivery interval and umbilical artery acid-base status in the second twin.

The purpose of this study was to determine the effect of twin-to-twin delivery interval on umbilical artery acid-base status of the second twin at birth. This was a retrospective cohort study of all live-born twins with measured acid-base status in umbilical arterial blood who were delivered after 34 weeks' gestation from June 2003 to February 2006. Twins with any maternal or fetal complications were excluded. Subjects were divided into two groups based on the mode of delivery of the first twin: normal cephalic vaginal deliveries (n=40) or cesarean deliveries (n=67). The inter-twin differences in umbilical arterial blood pH, PCO(2), PO(2), and base excess in twin newborns born vaginally were significantly greater than the corresponding differences in those born by cesarean section. A significant positive correlation was found between twin-to-twin delivery interval and inter-twin difference in umbilical arterial blood pH in twin newborns born vaginally. The umbilical arterial blood pH of the second twin was less than 7.0 in 14% (2/14) in cases delivered more than 20 min after the first twin. The umbilical arterial blood gas status of the second twin worsened with increasing twin-to-twin delivery interval, and pathologic fetal acidemia (pH<7.0) might develop in the second twin when the twin-to-twin delivery interval was greater than 20 min.

Pregnancy outcomes in women with mechanical heart valves.

OBJECTIVE: To evaluate maternal complications and perinatal outcomes in women with mechanical heart valves treated with warfarin and heparin during pregnancy. STUDY DESIGN: A retrospective chart review was performed on 45 pregnancies in 28 women who were previously fitted with mechanical valve prostheses and treated between 1991 and 2005 at Seoul National University Hospital. Outcome parameters were maternal complications and perinatal outcomes. RESULTS: Overall, there were 27 live births (60%), 7 stillbirths (15.6%), 2 therapeutic terminations in the second trimester (4.4%), 9 first-trimester spontaneous abortions (20%) and 2 neonatal deaths after preterm delivery. After excluding 9 first-trimester spontaneous abortions and 3 pregnancies administered warfarin throughout pregnancy, there were significantly more live births among patients administered heparin only after a diagnosis of pregnancy than among those administered warfarin from the second trimester (11 of 11 vs. 13 of 22, p = 0.015). One patient with mitral valve thrombosis during heparinization in the first trimester received valve replacement surgery and then aborted. Late postpartum hemorrhage occurred in 1 patient. All stillbirths and therapeutic terminations occurred in women being administered warfarin. CONCLUSION: Warfarin use from the second trimester in combination anticoagulation regimens increases the risk of an adverse perinatal outcome.

Angiotensinogen G(-6)A polymorphism is associated with the elevation of blood pressure in the hypertensive disorders of pregnancy.

The objective of the present study was to determine whether angiotensinogen G(-6)A polymorphism is associated with the elevation of blood pressure (BP) in the hypertensive disorders of pregnancy in Korean population. The subjects included 201 cases with the hypertensive disorders of pregnancy and 160 healthy controls. The medical records of subjects were reviewed. Cases were classified into the four subtypes (transient hypertension, preeclampsia, chronic hypertension, and preeclampsia superimposed on chronic hypertension) by the diagnostic criteria suggested by the National High Blood Pressure Education Program Working Group. Cases were also divided into the high and low BP group by the elevation of BP (diastolic BP greater than or equal to 110 mmHg). Maternal angiotensinogen G(-6)A polymorphism was determined by restriction fragment length polymorphism. Frequencies of AA genotype were significantly higher in the high than in the low BP group in the preeclampsia, superimposed preeclampsia, and the combined group (N = 201), suggesting that the angiotensinogen G(-6)A allele was significantly associated with the elevation of BP in the hypertensive disorders of pregnancy among South Korean women. The present findings imply that the elevation of BP can serve as an endophenotype for a spectrum of hypertensive conditions in pregnancy.

Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in preterm labor.

BACKGROUND: Our purpose was to determine whether amniotic fluid concentrations of tumor necrosis factor-alpha are of value in the prediction of early-onset neonatal sepsis (proven or suspected) in patients with preterm labor and intact membranes. METHODS: The relationship between amniotic fluid tumor necrosis factor-alpha concentrations and early-onset neonatal sepsis was examined in 59 consecutive patients with preterm labor and intact membranes who delivered preterm neonates within 72 h after transabdominal amniocentesis. Early-onset neonatal sepsis was defined either as the presence of a positive blood culture or as suspected sepsis within 72 h of delivery. Tumor necrosis factor-alpha was determined by enzyme-linked immunosorbent assays. RESULTS: Patients delivering neonates with early-onset neonatal sepsis had significantly higher median amniotic fluid TNF-alpha concentrations than patients delivering neonates without early-onset neonatal sepsis (p < 0.0005). An amniotic fluid tumor necrosis factor-alpha concentration > or =41 pg/ml had a sensitivity of 82% (23/29) and specificity of 79% (38/48) in the prediction of early-onset neonatal sepsis. Multiple logistic regression indicated that elevated amniotic fluid tumor necrosis factor-alpha (> or =41 pg/ml) was the only independent predictor of early-onset neonatal sepsis (odds ratio 12.9, 95% confidence interval 1.3-125.3, p=0.01) after correction for known confounding variables. CONCLUSIONS: (1) Amniotic fluid tumor necrosis factor-alpha is a marker for the prediction of early-onset neonatal sepsis in patients with preterm labor and intact membranes. (2) Amniotic fluid tumor necrosis factor-alpha is a better independent predictor of early-onset neonatal sepsis than placental histologic finding or amniotic fluid culture.