The Expression of Neuropilin-1 in Human Placentas From Normal and Preeclamptic Pregnancies.

Preeclampsia (PET) is a hypertensive disorder that affects 2% to 8% of pregnant women. Recent observations support the hypothesis that upregulation of placental anti-angiogenic factors are responsible for the clinical manifestations of the disease. Neuropilin-1 (NP-1) is a transmembrane protein that acts as a coreceptor for vascular endothelial growth factor and as a regulatory protein in the immune system. The aim of the study was to evaluate the expression of NP-1 in PET and normal placentas. Nineteen placental specimens from severe PET pregnancies were compared with 20 placental specimens of women with low-risk pregnancy. All the specimens underwent immunohistochemical staining with anti-human NP-1 antibody. The degree of NP-1 staining was measured both for intensity and extent. Our study demonstrated NP-1 immunoreactivity mainly in the decidual cells, the intermediate trophoblast, and the syncytiotrophoblast, particularly in the areas in the syncytial knots and shed particles. The particles were strongly NP-1 immunoreactive. The expression of NP-1 in the syncytiotrophoblast was lower in placentas of PET compared with control (P=0.017). Shedding of syncytiotrophoblast particles from placenta to maternal blood occurs in normal pregnancies and is enhanced during PET and contributes to the maternal vascular injury that characterizes PET. Our new observation that shows strong NP-1 immunoreactivity of these particles, and decreased NP1 expression in syncytiotrophoblast of PET placentas in comparison to the control group, may imply a role of NP-1 in PET.

The role of fibrin matrices and tissue factor in early-term trophoblast proliferation and spreading.

INTRODUCTION: Fibrin deposition in placenta is a common phenomenon which can be triggered by villous injury and coagulation activation. Fibrin abnormalities (hypo/dysfibrinogenemia) and factor XIII deficiency are associated with infertility and pregnancy loss. While trophoblasts are known to grow on fibrin matrices, the role of this protein in trophoblast repair processes remains unclear. We hypothesize that fibrin may have an essential role in trophoblast remodeling. METHODS: Morphology and spreading of primary early-term human trophoblasts and villi explants were investigated on various fibrin components. Cross-linking of matrices was evaluated by D-dimer assay. TF procoaguant activity, protein and mRNA levels in cells and villi were determined by chromogenic assay, ELISA, immunohistochemistry and reverse-transcription PCR (RT-PCR). RESULTS: Fibrin but not fibrinogen, thrombin or fibronectin caused increased trophoblast proliferation and spreading. Trophoblasts cultured on factor XIII (FXIII) depleted fibrin caused their increased proliferation and spreading, associated with cross-linking. FXIII addition further increased this effect, while cell culturing on active FXIII without fibrin retained cellular proliferation. Decreased TF activity, antigen and RNA expression were demonstrated in fibrin-cultured trophoblasts and villi explants, compared to matrigel explants. CONCLUSION: Results obtained demonstrate distinct mechanisms underlying fibrin cross-linking, which can affect trophoblast proliferation. The excess of fibrin deposits may be limited by the decrease in TF levels, thus enabling adequate placental perfusion. These findings demonstrate fibrin importance for placental repair and may partly explain poor pregnancy outcome associated with certain fibrinogen/fibrin abnormalities and FXIII deficiency.

Effect of B-mode optimization techniques on fetal bowel echogenicity using computerized image analysis.

OBJECTIVES: The purpose of this study was to provide and compare measurable parameters for normal fetal bowel echogenicity under predefined B-mode scanning presets. METHODS: Forty healthy fetuses underwent 14- to 17-week ultrasound scans, and 40 underwent 21- to 25-week scans. Sagittal, coronal, and axial fetal abdominal images were tested using predefined B-mode presets. The presets differed from fundamental imaging by isolated activation of harmonic imaging, compound resolution imaging, speckle reduction imaging, focus and frequency composite imaging, and coded excitation imaging features. A transabdominal probe was used in all fetuses, and transvaginal images were added for the 14- to 17-week scans. The images were studied with custom-developed software, which provided a grayscale analysis of the pixels in the region of interest within the image. The mean brightness of the pixels from the fetal bowel area was calculated. RESULTS: The 14- to 17-week transabdominal scans showed significantly higher mean brightness on harmonic imaging compared to fundamental imaging (P < .01). Activation of coded excitation and compound resolution imaging in these scans resulted in a significant decrease in the mean brightness compared to fundamental imaging. Mean bowel brightness values on the 21- to 25-week transabdominal scans did not differ significantly with the use of the different imaging presets compared to fundamental imaging. CONCLUSIONS: Transabdominal harmonic imaging in the early second trimester may significantly increase the mean brightness of the fetal bowel tissue. Contrarily, compound resolution imaging and coded excitation imaging produce the opposite effect on bowel echogenicity.

Sonography of the fetal cochlea in the early second trimester of pregnancy.

OBJECTIVES: To examine the feasibility of imaging the fetal cochlea in the early second trimester. METHODS: This study included 42 healthy fetuses of low-risk pregnancies between 14 and 16 weeks. The coronal head sections via sagittal and lateral acoustic windows were used for cochlear visualization. The coronal plane was directed across the thalamus, oriented to the petrous part of the temporal bones. All fetuses were examined by 2-dimensional(2D) transvaginal sonography. Transabdominal scans were added in 11 fetuses at 16 weeks. Three-dimensional (3D) multiplanar reconstruction was used for coronal plane reformatting in cases with inappropriate head positioning for 2D scanning. RESULTS: Because of temporal bone hypomineralization in the early second trimester, sonographic depiction of the cochlear labyrinth was possible. On coronal imaging, the cochleas showed ringlike echogenic borders containing hypoechoic liquid content. The cochlear modiolus appeared as a central echogenic round spot ("cochlear target sign"). The cochleas were observed caudad to the temporal lobes, separated by the clivus. Shifting of the coronal plane showed progressive coiling of the basal cochlear turn toward the second turn ("cochlear whirlpool sign"). Two-dimensional transvaginal scanning showed at least 1 cochlea in 79% (33 of 42) of the cases. Adding 3D multiplanar reconstruction, at least 1 cochlear target sign was observed in 83% (35 of 42). The cochlear whirlpool sign on at least one side was shown in 57% (24 of 42). The maximal cochlear diameter was measured in fetuses with clear cochlear margin visualization. In this subgroup, the mean gestational age ± SD was 15.8 ± 0.5 weeks, and the mean maximal cochlear diameter was 6.4 ± 0.8 mm. CONCLUSIONS: Prenatal sonographic inner ear depiction was previously considered impossible. Using a unique time window in the early second trimester, we achieved feasible fetal cochlear imaging.

Pregnancy course and outcome in women traveling to developing countries.

BACKGROUND: The issue of travel to developing countries during pregnancy has not been sufficiently studied. The aim of this study is to investigate the rate, course, and outcome of pregnancies in women who traveled to developing countries while pregnant, or became pregnant during such travel. METHODS: Women visiting two major travel clinics in Israel for consultation within the years 2004 to 2009, who were pregnant or declared an intention of becoming pregnant during travel were contacted. This was followed by a telephone interview by an obstetrician with those women who were actually pregnant. Background characteristics, morbidity during travel, and pregnancy course and outcome were collected. RESULTS: Overall 52,430 travelers' records had been screened. Of these, we identified 49 women who were pregnant during their trip, but 3 declined participation. Of the remaining 46 women, 33 were pregnant at departure, and 13 conceived during travel. The incidence of pregnancy during travel was thus 0.93/1000 travelers. Thirty-three women traveled to East Asia, 8 to South and Central America, 5 to Africa. More than two thirds of women received pretravel vaccinations. Adherence to the World Health Organization recommendations regarding food and drink was high (87%) and travelers' diarrhea occurred in only 11% of women. Five of 22 women traveling to malarious areas had taken antimalarial prophylaxis. Six women required medical therapy during travel. Pregnancy outcome was not different from the normal population except for an unusually low rate of preterm delivery. CONCLUSIONS: In this cohort, travel to developing countries was not associated with adverse pregnancy outcome. Larger studies are needed to support these findings.

Adrenalectomy for adrenocortical adenoma causing Cushing's syndrome in pregnancy: a case report and review of literature.

We present a case of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome diagnosed in a patient in the third trimester of her pregnancy, with an adrenal mass observed on imaging studies. Laparoscopic adrenalectomy was performed successfully at 32 weeks. To the best of our knowledge, this is the latest gestational age at which laparoscopic adrenalectomy has been reported. We present the various considerations for determining the surgical approach and the optimal timing for surgery. Adrenalectomy during pregnancy for the treatment of Cushing's syndrome caused by adrenocortical adenoma has been reported in 23 patients in the English-language medical literature to date and seems safe and beneficial. According to the data, surgical treatment has led to a reduction in perinatal mortality and maternal morbidity rates, but has not affected the occurrence of preterm birth and intrauterine growth restriction. The best outcome can be achieved by a multidisciplinary approach, with a team comprising a maternal-fetal medicine specialist, an endocrinologist and a surgeon. The timing of surgery and the surgical approach need to be determined according to the surgeon's expertise, the severity of the condition, the patient's preferences, and gestational age. Laparoscopy may prove to be the preferred surgical approach. The small number of cases precludes providing evidence-based recommendations.

Oral naproxen versus oral tramadol for analgesia after cesarean delivery.

OBJECTIVE: To compare the efficacies of oral naproxen and oral tramadol for pain relief after cesarean delivery, and to evaluate administration at fixed intervals versus on request. METHODS: In a prospective study, 120 women were randomized into 4 groups receiving either oral naproxen or oral tramadol at fixed intervals or on request. Pain was assessed at 6, 12, 24, and 48hours after delivery, and adverse effects, mobility, breastfeeding, and the need for additional drugs for breakthrough pain were recorded. RESULTS: No difference in pain scores was observed at 6, 12, 24, or 48hours among the 4 groups, between the 2 drugs, or between the 2 methods of administration. Women randomized to receive oral tramadol requested additional drugs for breakthrough pain more frequently. In addition, adverse effects were twice as common in the tramadol group as in the naproxen group, and more women in the tramadol group abandoned the study. CONCLUSION: Although similar in terms of pain scores, oral naproxen might be more effective than oral tramadol for pain relief after cesarean delivery. Naproxen seemed to have a better adverse-effects profile, and therefore might be more suitable for mothers. Administration at fixed intervals might be more efficacious than administration on request.

Haptoglobin phenotype in women with preeclampsia.

In pre-eclampsia, poor placentation causes both oxidative and endoplasmic reticulum stress of the placenta. The anti-oxidative protein Haptoglobin has three phenotypes: 1-1, 1-2, and 2-2. Haptoglobin 1-1 is a more potent antioxidant. Our objective was to determine whether haptoglobin 1-1 was less common in women with preeclampsia which is a disease with an oxidatives-stress component, compared to the healthy population. Haptoglobin phenotype was compared in 240 healthy and 120 preeclamptic gravida in a case-control study. Statistical analysis was performed using Chi square test. The prevalence of haptoglobin 1-1 was 13% among healthy women and 6% among preeclamptic women (P=0.049). Secondary analysis was also performed. The prevalence of haptoglobin 1-1 is higher in healthy compared to preeclamptic subjects, a finding compatible with a protective role. Haptoglobin 1-1 might have a protective role in preeclampsia. Further work is needed with more Hp 1-1 subjects before we can conclude on the possible use of Haptoglobin phenotype to assess the risk of preeclampsia.

The association between supra-physiological levels of estradiol and response patterns to experimental pain.

The precise mechanism by which gonadal hormones influence pain perception is still obscure. However, no studies have examined experimental pain responses at supra-physiological hormone levels. This study explored the influence of pharmacological estradiol (E2) levels on the stability of pain perception obtained via quantitative sensory testing. A repeated measures design was used with 31 women, treated by a same In Vitro Fertilization (IVF) protocol. Patterns of experimental pain response were assessed in three different sessions (baseline, down regulation, maximal ovarian stimulation). Correlations between hormonal levels (E2, progesterone, luteinizing hormone (LH)) and pain perceptions were assessed at each session. While in the entire sample the pattern of response to pain stimulations remained unchanged regardless of hormonal manipulations, a greater pain sensitivity was associated with supra-physiological levels of E2 during the maximal ovarian stimulation session (for 47 degrees C stimulation: r=.383, p=0.044). Mixed model repeated measures ANOVA indicated that participants who over-responded to the ovarian stimulation session (E2 > 10,500 pmol/l) showed significant enhanced pain responses under this condition (p=0.004). No correlations between progesterone, LH and experimental pain perception were found in any of the study sessions. Although pain perceptions at different E2 levels remained constant, the enhancement of pain scoring at supra-physiological E2 levels, underscore the possible role of sex hormones in pain modulation and experience.

Variations of the origin of renal arteries in the fetus identified on power Doppler and 3D sonography.

PURPOSE: To investigate anatomic variations of renal arteries (RAs) using 2-dimensional (2D)/3D power Doppler sonography (PDUS) in normal fetuses and in fetuses with renal anomalies. METHODS: The origin, direction, and distribution of RAs were studied in 120 fetuses without renal malformations using 2D/3D PDUS. Studies were performed between 14 and 17 weeks of gestation age on 64 male and 56 female fetuses. PDUS of the RAs was also performed in 12 fetuses with renal anomalies. RESULTS: In 117/120 fetuses, a single RA was found to originate from each side of the abdominal aorta. The origin of the right RA from the abdominal aorta was superior to, at the same level as, and inferior to that of the left RA in 47% (55/117), 25.5% (30/117), and 27.5% (32/117) of the cases, respectively. An accessory right RA was found in 3 cases. Bifurcation of the right RA was found in 2 cases. There were no variations of the origin of renal vessels in 69% of the cases (83/120), whereas the remaining 31% (37/120) had 1 or several variation patterns. Variations in renal vessels were found in 8 of the 12 fetuses with renal malformations: accessory artery in 3 cases, origin of the right RA from the iliac artery in horseshoe kidney and in 2 cases with pelvic kidney, and bifurcation in 2 of the fetuses with double collecting system. CONCLUSIONS: Variations in origin and distribution of fetal RAs are frequently observed in normal pregnancies. The majority of renal malformations are associated with such vascular variations.

Expectant management of pregnancy-related high-velocity uterine arteriovenous shunt diagnosed after abortion.

OBJECTIVE: To assess sonographic and clinical outcome in women with pregnancy-related uterine arteriovenous malformations (AVMs) diagnosed after abortion. METHOD: Twelve patients diagnosed as having AVMs after abortion were followed-up until resolution of the lesions. RESULTS: The 9 asymptomatic patients were managed expectantly for 4 to 10 weeks without further complications. None of the 12 required aggressive interventions such as transcatheter arterial embolization, and 6 had uncomplicated pregnancies after resolution of the lesions. CONCLUSION: Expectant management is an option in many women with pregnancy-related uterine AVMs.

How reliable is the determination of cervical dilation? Comparison of vaginal examination with spatial position-tracking ruler.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of clinical measurement of cervical dilation with a position-tracking system during vaginal examination. STUDY DESIGN: This prospective study that was conducted in Poissy, France, Brooklyn, NY, and Haifa, Israel, included 333 measurements that were performed in 188 women with term singleton vertex uncomplicated pregnancies during the active stage of labor. Ninety measurements with clinical diagnosis of full dilation were excluded from analysis. Measurements were performed with a sensor attached to the midwife's index fingertip and a position-tracking system that was based on a low magnetic field. Evaluations were done when cervical examinations were clinically indicated. RESULTS: Results were similar in all centers. Mean error was 10.2 +/- 8.4 mm and ranged from 7.5 +/- 7.3 mm, when cervical dilation was > 8 cm, to 12.5 +/- 8.7 mm when cervical dilation was between 6.1 and 8 cm. CONCLUSION: This first evaluation of cervical assessment accuracy during vaginal examination with a position-tracking system shows limited precision.

Determination of fetal head station and position during labor: a new technique that combines ultrasound and a position-tracking system.

OBJECTIVE: The purpose of this study was to compare the ultrasound-based LaborPro (Trig Medical Ltd, Yokneam, Israel) system determination of fetal head station and position with routine vaginal examination. STUDY DESIGN: This prospective study, which was conducted in 3 centers included 311 measurements that were performed in 166 singleton term pregnancies during the active phase of vertex, uncomplicated labor. Ultrasound-based position-tracking system calculations of fetal head station and position were compared with routine vaginal examination measurements. RESULTS: Comparison of vaginal examination with the system head station results revealed a mean absolute difference of 5.5 +/- 6.1 mm (n = 311). Vaginal examination head-position evaluation, within a 45 degrees interval, complied with the system in 35 of 87 cases (40.2%). CONCLUSION: Our data show that an ultrasound-based system can determine fetal head station and position during labor, when compared with vaginal examination, and requires minimal ultrasound skills. The limits of vaginal examination assessment of the head position are in agreement with published data.

Effectiveness of a novel home-based testing device for the detection of rupture of membranes.

We evaluated the ability of a testing panty liner (TPL) embedded with a pH/ammonia indicator polymer to differentiate amniotic fluid leakage from urine. A multicenter, open-label study in which 339 pregnant women (age 18 to 45 years, minimum 16 weeks' gestation, presenting with unexplained vaginal wetness) were enrolled. The TPL was worn and the results read by the subject and a health care provider (HCP) who was blinded to the subject's reading. Results were compared with the standard clinical diagnosis, as determined by direct visualization of vaginal pooling, crystallization (ferning), and nitrazine tests, performed by a second blinded HCP. Subject experience with the test was assessed with a brief questionnaire. The TPL accurately detected 154 of the 161 subjects found to have amniotic fluid leakage by the standard diagnosis; thus, the sensitivity of the TPL was 95.65%. The specificity was 84.46% (% true negative readings), as the TPL demonstrated a negative result for 125 of the 148 subjects whose clinical diagnosis was negative for amniotic fluid leakage. The overall agreement between the TPL readings of the clinician and that of the subject was 97.40%. The TPL is a reliable test to determine the presence of amniotic fluid leakage.

Modulation of heart rate variability by estrogen in young women undergoing induction of ovulation.

Estrogens are involved in the modulation of the cardiovascular system, yet their effects in young women remains largely unknown. Women who undergo ovulation induction treatments attain extremely high estrogen concentrations during a very short time period. The aim of the present study was to evaluate the effects of an acute increase in estrogens on the autonomic nervous system modulation of heart rate variability (HRV). A total of 27 women undergoing ovulation induction and 14 normally menstruating women were prospectively studied. HRV was assessed during nadir and peak estrogen using time domain and power spectral density analyses. A significant increase in high-frequency spectral power (243 +/- 77 vs. 188 +/- 73 ms(2)/Hz, P < 0.01) with a significant decrease in the ratio of low to high-frequency power was observed during estrogen peak in women undergoing induction of ovulation. The acute increase in estrogen in women undergoing ovulation induction was associated with vagal activation and altered sympathovagal balance.

Fetal weight estimation for prediction of fetal macrosomia: does additional clinical and demographic data using pattern recognition algorithm improve detection?

OBJECTIVE: The aim of this study was to test whether pattern recognition classifiers with multiple clinical and sonographic variables could improve ultrasound prediction of fetal macrosomia over prediction which relies on the commonly used formulas for the sonographic estimation of fetal weight. METHODS: THE SVM ALGORITHM WAS USED FOR BINARY CLASSIFICATION BETWEEN TWO CATEGORIES OF WEIGHT ESTIMATION: >4000gr and <4000gr. Clinical and sononographic input variables of 100 pregnancies suspected of having LGA fetuses were tested. RESULTS: Thirteen out of 38 features were selected as contributing variables that distinguish birth weights of below 4000gr and of 4000gr and above. Considering 4000gr. as a cutoff weight the pattern recognition algorithm predicted macrosomia with a sensitivity of 81%, specificity of 73%, positive predictive value of 81% and negative predictive value of 73%. The comparative figures according to the combined criteria based on two commonly used formulas generated from regression analysis were 88.1%, 34%, 65.8%, 66.7%. CONCLUSIONS: The SVM algorithm provides a comparable prediction of LGA fetuses as other commonly used formulas generated from regression analysis. The better specificity and better positive predictive value suggest potential value for this method and further accumulation of data may improve the reliability of this approach.

The outcome and cumulative morbidity associated with the second and third postcesarean delivery.

The purpose of this study was to compare the outcome and cumulative morbidity among women who delivered twice after a cesarean delivery (CD), and who underwent in the second delivery either a trial of labor (TOL) or planned cesarean delivery (PCD). Eligible women (N = 399) were divided into two groups based on first post-CD: a TOL (n = 304) or PCD (n = 95). Women attempting a TOL were successful in 70 and 75% in the first and second post-CD, respectively. All participants undergoing a PCD subsequently had a third PCD. The overall morbidity was 8.4 and 5.3% among PCD and TOL groups, respectively ( P = 0.258). Women attempting a TOL after a previous CD had a 70 and 53% likelihood for at least one successful or two successful vaginal births in the two subsequent deliveries, respectively. No significant difference was documented between the groups regarding the cumulative morbidity.

Immediate versus delayed umbilical cord clamping in premature neonates born < 35 weeks: a prospective, randomized, controlled study.

The purpose of this study was to test whether delayed versus immediate cord clamping would result in higher blood pressure (BP) and hematocrit (Hct), and to assess its clinical effects on the neonatal course in premature neonates (< 35 weeks). This was a prospective, masked, randomized, controlled study. Prior to delivery, 35 neonates were randomly assigned to immediate cord clamping (ICC) at 5 to 10 seconds, and a comparable group of 30 neonates were randomly assigned to delayed cord clamping (DCC) at 30 to 45 seconds. Intention-to-treat analyses revealed that the DCC group tended to have higher initial diastolic BP and higher Hct (especially in vaginally delivered neonates). Infants weighing < 1500 g with DCC tended to have higher mean BP, and needed less mechanical ventilation and surfactant compared with ICC neonates. Infants with DCC did not experience more polycythemia (Hct > 60%), but had a trend toward higher bilirubin levels with no differences in the phototherapy needs. DCC seems to be safe and may be beneficial when compared with ICC in premature neonates. However, the differences between the two methods were modest and the clinical relevance needs to be assessed further by larger studies and additional meta-analysis of randomized trials.

Evidence of periopathogenic microorganisms in placentas of women with preeclampsia.

BACKGROUND: Periodontal disease is a chronic inflammatory infectious disease that may act as a focus of infection. Preeclampsia is a pregnancy-specific hypertensive disorder that often leads to maternal morbidity and mortality. Acute atherosis, the placental lesion of preeclampsia, shares many histopathological features with atherosclerosis. Recently, chronic infection was linked to the initiation of atherosclerosis. Oral pathogens have been detected in atherosclerotic plaques, where they may play a role in the development and progression of atherosclerosis. The purpose of the present study was to explore the possibility that periopathogenic bacteria may translocate into the placental tissues of women with preeclampsia. METHODS: Samples were taken from 16 placentas obtained from cesarean sections of women with preeclampsia and from 14 age-matched healthy pregnant women. Polymerase chain reaction was used to detect Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum ssp., Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, and Treponema denticola. RESULTS: Eight of the 16 (50%) placenta specimens were positive for one or more periopathogenic bacteria in the preeclampsia group, compared to only two of the 14 samples (14.3%) from controls. Bacterial counts were statistically significantly higher in the preeclampsia group for all of the periopathogenic bacteria examined (P