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.

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.

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.

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.

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.

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.

Ehlers-Danlos syndrome: insights on obstetric aspects.

UNLABELLED: Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperelasticity, tissue fragility, easy bruising, and poor healing of wounds. The clinical manifestations vary depending on the type of disease. The syndrome may be associated with a number of pregnancy and peripartum complications. Because of the multiorgan involvement and varied presentation of this disease, no uniform or routine obstetric and anesthetic recommendations can be made for the perinatal care of these patients. We present a review of the literature on EDS with emphasis on the obstetric, anesthetic, and perinatal consequences. We also report our experience with this syndrome: an uneventful term vaginal delivery in a 32-year-old woman diagnosed with hypermobility type of EDS. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the potentially severe nature of Ehlers-Danlos Syndrome (EDS) in both pregnant and nonpregnant patients, summarize the wide range of signs and symptoms and its genetic inheritance, and explain the difficulty in recommending obstetric and anesthesia procedures to avoid complications.

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

Results of a well-defined protocol for a trial of labor after prior cesarean delivery.

OBJECTIVE: It has been claimed that a trial of labor after cesarean carries higher maternal and fetal risks than planned cesarean delivery. Because the management of such patients in our department differs from that described in some studies, and is perhaps more cautious, we hypothesized that the outcome may be better. METHODS: We identified women with 1 previous low uterine segment cesarean who had delivered a cephalic singleton infant at gestational age 34 weeks or more from January 2000 through May 2005. Our policy is to encourage such women to undergo a trial of labor unless cesarean delivery is indicated. Unless otherwise indicated, our policy is to wait for spontaneous labor. We do not use prostaglandins, and recommend cesarean delivery if the cervix is unripe.(Bishop score < 6). We compared the outcome between women who underwent a trial of labor and women who underwent planned cesarean delivery. RESULTS: A trial of labor was attempted by 841 women (80% successful), and 467 underwent planned cesarean delivery. Uterine rupture was observed in 1 woman 18 hours after vaginal delivery. There was no difference in major or minor maternal morbidity. There was no serious neonatal morbidity. Among the planned cesarean patients, hospital stay was longer, and there were more admissions to the neonatal intensive care unit. CONCLUSION: With our well-defined protocol, a trial of labor after cesarean seems to be as safe for the mother and infant as planned cesarean delivery, and the hospital stay is shorter. LEVEL OF EVIDENCE: II-2.

Maternal complications associated with multiple cesarean deliveries.

OBJECTIVE: The claim that a planned repeat cesarean delivery is safer than a trial of labor after cesarean may not be applicable to women who desire larger families. The aim of this study was to assess maternal complications after multiple cesarean deliveries. METHODS: The records of women who underwent two or more planned cesarean deliveries between 2000 and 2005 were reviewed. We compared maternal complications occurring in 277 women after three or more cesarean deliveries (multiple-cesarean group) with those occurring in 491 women after second cesarean delivery (second-cesarean group). RESULTS: Excessive blood loss (7.9% versus 3.3%; P < .005), difficult delivery of the neonate (5.1% versus 0.2%; P < .001), and dense adhesions (46.1% versus 25.6%; P < .001) were significantly more common in the multiple-cesarean group. Placenta accreta (1.4%) and hysterectomy (1.1%) were more common, but not significantly so, in the multiple-cesarean group. The proportion of women having any major complication was higher in the multiple-cesarean group, 8.7% versus 4.3% (P = .013), and increased with the delivery index number: 4.3%, 7.5%, and 12.5% for second, third, and fourth or more cesarean delivery, respectively (P for trend = .004). CONCLUSION: Multiple cesarean deliveries are associated with more difficult surgery and increased blood loss compared with a second planned cesarean delivery. The risk of major complications increases with cesarean delivery number. LEVEL OF EVIDENCE: II-2.

Early versus late initiation of epidural analgesia in labor: does it increase the risk of cesarean section? A randomized trial.

OBJECTIVE: To determine whether early initiation of epidural analgesia in nulliparous women affects the rate of cesarean sections and other obstetric outcome measures. STUDY DESIGN: A randomized trial in which 449 at term nulliparous women in early labor, at less than 3 cm of cervical dilatation, were assigned to either immediate initiation of epidural analgesia at first request (221 women), or delay of epidural until the cervix dilated to at least 4 cm (228 women). RESULTS: At initiation of the epidural the mean cervical dilatation was 2.4 cm in the early epidural group and 4.6 cm in the late group (P < 0.0001). The rates of cesarean section were not significantly different between the groups--13% and 11% in the early and late groups, respectively (P = 0.77). The mean duration from randomization to full dilatation was significantly shorter in the early compared to the late epidural group--5.9 hours and 6.6 hours respectively (P = 0.04). When questioned after delivery regarding their next labor, the women indicated a preference for early epidural. CONCLUSION: Initiation of epidural analgesia in early labor, following the first request for epidural, did not result in increased cesarean deliveries, instrumental vaginal deliveries, and other adverse effects; furthermore, it was associated with shorter duration of the first stage of labor and was clearly preferred by the women.

Subendometrial arterial spectral doppler assessment during IVF cycles and its correlation with treatment outcome.

The influence of blood flow impedance in subendometrial arteries on embryo implantation rate was investigated by transvaginal sonographic examination in in vitro fertilization (IVF) cycles. A total of 39 women undergoing IVF treatment were evaluated along the treatment cycle. Power and spectral Doppler studies of subendometrial arteries were performed to calculate the pulsatility index (PI), resistance index (RI) and systolic:diastolic ratio (S:D). The correlation between these parameters and pregnancy achievement was analyzed. Patients were grouped according to whether pregnancy was achieved or not. RI and S:D did not differ between the groups along the course of treatment. In pregnant patients, the PI was significantly lower in the beginning of the cycle than on the preovulation day and ovum pickup day. PI in the beginning of the treatment was significantly lower in pregnancy cycles than in nonpregnancy ones. A lower PI on day 1 was correlated with a better chance for pregnancy.

Severe pregnancy complication (preeclampsia) is associated with greater periodontal destruction.

BACKGROUND: Preeclampsia is a pregnancy-specific disease which is one of the leading causes of maternal and fetal morbidity and mortality. The etiology of preeclampsia remains elusive. The underlying pathology may be related to a generalized intravascular hyperinflammatory state. Since the placental histopathologic lesions of acute atherosis, seen in preeclampsia, bear resemblance to those seen in atherosclerosis, and recent evidence links atherosclerosis with chronic infection, we decided to investigate a possible link between preeclampsia and chronic periodontal infection. METHODS: Thirty primigravidas, 15 suffering from preeclampsia, had full mouth periodontal examinations. Gingival crevicular fluid samples were taken for laboratory immunological assessment. Similar examination and sampling were performed in 15 age- and maternal status-matched controls. RESULTS: Significantly higher periodontal probing depth and clinical attachment level scores were found in the preeclamptic group compared with controls (2.98 versus 2.11 and 3.33 versus 2.30, respectively). Plaque index, gingival index, and mean gingival overgrowth scores were very similar in both groups. Furthermore, prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta levels were all significantly higher in the preeclamptic group (247.4 ngr/sample versus 89.1 ngr/sample, 8.03 pgr/sample versus 4.03 pgr/sample, and 175.7 pgr/sample versus 62.2 pgr/sample, respectively). CONCLUSION: The above results suggest a possible association between periodontal inflammation and preeclampsia.

Common oral manifestations during pregnancy: a review.

UNLABELLED: Pregnancy has far-reaching systemic effects extending beyond the reproductive system. Oral and masticatory changes during pregnancy have been documented for many years; however, their magnitude and frequency have not been stressed. This review highlights the major oral complications during pregnancy. Pregnancy gingivitis and pregnancy tumor are described and presented, and possible preventive strategies are suggested. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to summarize the major oral complications during pregnancy, to outline the etiologic factors associated with each of these conditions, and to explain the role of dental treatment during pregnancy.

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.

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.

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.