Davor Jurkovic

Placenta accreta: Pathogenesis of a 20th century iatrogenic uterine disease

Placenta accreta refers to different grades of abnormal placental attachment to the uterine wall, which are characterised by invasion of trophoblast into the myometrium. Placenta accreta has only been described and studied by pathologists for less than a century. The fact that the first detailed description of a placenta accreta happened within a couple of decades of major changes in the caesarean surgical techniques is highly suggestive of a direct relationship between prior uterine surgery and abnormal placenta adherence. Several concepts have been proposed to explain the abnormal placentation in placenta accreta including a primary defect of the trophoblast function, a secondary basalis defect due to a failure of normal decidualization and more recently an abnormal vascularisation and tissue oxygenation of the scar area. The vast majority of placenta accreta are found in women presenting with a previous history of caesarean section and a placenta praevia. Recent epidemiological studies have also found that the strongest risk factor for placenta praevia is a prior caesarean section suggesting that a failure of decidualization in the area of a previous uterine scar can have an impact on both implantation and placentation. Ultrasound studies of uterine caesarean section scar have shown that large and deep myometrial defects are often associated with absence of re-epithelialisation of the scar area. These findings support the concept of a primary deciduo-myometrium defect in placenta accreta, exposing the myometrium and its vasculature below the junctional zone to the migrating trophoblast. The loss of this normal plane of cleavage and the excessive vascular remodelling of the radial and arcuate arteries can explain the in-vivo findings and the clinical consequence of placenta accreta. Overall these data support the concept that abnormal decidualization and trophoblastic changes of the placental bed in placenta accreta are secondary to the uterine scar and thus entirely iatrogenic.

Umbilical cord cysts in early pregnancy

Objective To assess the prevalence, morphologic characteristics, and natural history of umbilical cord cysts detected by ultrasound in the first trimester of pregnancy. Methods This was an ultrasound screening study for the presence of umbilical cord cysts in 859 pregnant women with singleton live fetuses at 7–13 weeks gestation. In all cases of cord cysts the scan was repeated fortnightly until the cyst resolved or a fetal abnormality was detected. All patients with ongoing pregnancies had detailed scans at 20 weeks. Infants and umbilical cords were examined after delivery for the presence of structural abnormalities. Results Umbilical cord cysts were present in 29 (3.4%) of the 859 pregnancies. Fetal abnormalities were found in seven (26%) of the 27 cases with ongoing pregnancies. The fetus was more likely to be abnormal if the cyst was located near the placental or fetal extremity of the cord (relative risk [RR] 3.3; 95% confidence interval [CI] 1.3, 8.5) or paraxially (RR 3.8; 95% CI 1.2, 12.0) or if it persisted beyond 12 weeks gestation (RR 7.7; 95% CI 3.2, 18.6). Conclusions The prevalence of umbilical cord cysts at 7–13 weeks gestation is approximately 3%, and in more than 20% of cases there are fetal chromosomal or structural defects.

Selection and identification of standard cardiac views from three-dimensional volume scans of the fetal thorax.

The feasibility of fetal echocardiographic examination using three-dimensional ultrasonography was investigated in 54 healthy pregnant women with uncomplicated pregnancies between 17 and 37 weeks of gestation. In 46 cases (85.2%), good quality three-dimensional volumes of the fetal heart were obtained from both apical and lateral four-chamber views. By reslicing apical volumes, the reformatted sections of the long axis view of the left ventricle and the aortic crest were seen in 40 (87%) and 38 (83%) of 46 cases, respectively. The short axis was seen in 26 (57%) and ductal arch in 30 (65%) cases. The examination of lateral volumes was much less successful. The short axis was seen in 11 (24%) cases, and the aortic crest in 22 (48%), whereas the analysis of the longitudinal views was not possible. The best results were obtained at a gestational age between 22 and 27 weeks. Three-dimensional fetal echocardiography allowed the examination of the four chambers of the heart and left outflow tract during the late second trimester. The technique may become useful for the screening and diagnosis of congenital cardiac defects in the future.

Accreta placentation: a systematic review of prenatal ultrasound imaging and grading of villous invasiveness

BACKGROUNDnDetermining the depth of villous invasiveness before delivery is pivotal in planning individual management of placenta accreta. We have evaluated the value of various ultrasound signs proposed in the international literature for the prenatal diagnosis of accreta placentation and assessment of the depth of villous invasiveness.nnnOBJECTIVEnWe undertook a PubMed and MEDLINE search of the relevant studies published from the first prenatal ultrasound description of placenta accreta in 1982 through March 30, 2016, using key words placenta accreta, placenta increta, placenta percreta, abnormally invasive placenta, morbidly adherent placenta, and placenta adhesive disorder as related to sonography, ultrasound diagnosis, prenatal diagnosis, gray-scale imaging, 3-dimensional ultrasound, and color Doppler imaging.nnnSTUDY DESIGNnThe primary eligibility criteria were articles that correlated prenatal ultrasound imaging with pregnancy outcome. A total of 84 studies, including 31 case reports describing 38 cases of placenta accreta and 53 series describing 1078 cases were analyzed. Placenta accreta was subdivided into placenta creta to describe superficially adherent placentation and placenta increta and placenta percreta to describe invasive placentation.nnnRESULTSnOf the 53 study series, 23 did not provide data on the depth of villous myometrial invasion on ultrasound imaging or at delivery. Detailed correlations between ultrasound findings and placenta accreta grading were found in 72 cases. A loss of clear zone (62.1%) and the presence of bridging vessels (71.4%) were the most common ultrasound signs in cases of placenta creta. In placenta increta, a loss of clear zone (84.6%) and subplacental hypervascularity (60%) were the most common ultrasound signs, whereas placental lacunae (82.4%) and subplacental hypervascularity (54.5%) were the most common ultrasound signs in placenta percreta. No ultrasound sign or a combination of ultrasound signs were specific of the depth of accreta placentation.nnnCONCLUSIONnThe wide heterogeneity in terminology used to describe the grades of accreta placentation and differences in study design limits the evaluation of the accuracy of ultrasound imaging in the screening and diagnosis of placenta accreta. This review emphasizes the need for further prospective studies using a standardized evidence-based approach including a systematic correlation between ultrasound signs of placenta accreta and detailed clinical and pathologic examinations at delivery.

Biochemical investigation of fetal renal maturation in early pregnancy

The objective of this study was to evaluate the biochemical indices of normal fetal kidney maturation in early pregnancy. Urea, creatinine,γ-glutamyltransferase, and β2-microglobulin levels were measured on paired samples of amniotic and coelomic fluids and maternal serum collected at the time of pregnancy termination in a group of woman with pregnancies between 8 and 11 wk, or on paired samples of amniotic fluid and maternal serum collected from woman undergoing early transabdominal amniocentesis between 11 and 16 wk. Before 11 wk of gestation (n = 12), significantly lower concentrations of creatinine andβ2-microglobulin, and higher concentration ofγ-glutamyltransferase were found in amniotic fluid compared with both maternal serum and coelomic fluid. Significant positive correlations were found between gestational age (8-16 wk) and amniotic fluid (n = 47) levels of urea (r = 0.45; p < 0.01), creatinine(r = 0.68; p < 0.001), γ-glutamyltransferase(r = 0.71; p < 0.001), and β2-microglobulin(r = 0.69; p < 0.001). The maternal serum levels of the corresponding variables did not varied significantly. The abrupt increase in creatinine, γ-glutamyltransferase, and β2-microglobulin amniotic fluid concentrations after 10 wk of gestation provides biochemical evidence for the maturation of the fetal renal glomerular function at a time when the reabsorption capacity of the proximal tubular cells is not established. We suggest that this important variation in the amniotic fluid composition, unrelated to any comparable changes in the maternal serum, reflects the fetal kidney development from the mesonephros to the metanephros.

Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6–10 weeks from women presenting with TM (nu200a=u200a40), from asymptomatic controls (nu200a=u200a32) and from non- pregnant women in their luteal phase (nu200a=u200a14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF (∼2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (∼25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss.

Investigation of placental circulations by color Doppler ultrasonography

The placental circulations of 25 normal and five complicated pregnancies were studied by color Doppler ultrasonography. Flow velocity waveforms were obtained in all 30 pregnancies and could discriminate between fetal and maternal intraplacental blood flow. We believe that color Doppler ultrasonography will improve our understanding of the pathophysiology of various pregnancy disorders that alter the placental circulations and that color ultrasonography is useful for the prenatal differential diagnosis of intrauterine masses.

A comparison of intratumoural indices of blood flow velocity and impedance for the diagnosis of ovarian cancer

The aim was to assess the value of blood flow velocity indices in an ultrasound-based test to discriminate between malignant and benign adnexal tumours. Fifty-one women (35 premenopausal and 16 postmenopausal) with persistent adnexal masses were scanned prior to surgery using transvaginal sonography with colour Doppler imaging. Intratumoural flow velocity waveforms obtained by pulsed Doppler sonography were used to determine the time averaged maximum velocity (TAMXV), peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI). The tumours were classified by histologic criteria (42 benign, 1 borderline and 8 malignant tumours). Two of the malignant and the single borderline tumour were stage I, five were stage III and one was stage IV. Detectable blood flow signals were found in all malignant and borderline tumours and in 33 of 42 (78.6%) of the benign tumours. TAMXV was the best parameter for discrimination of benign and malignant adnexal pathology and at a cut-off value of TAMXV > or = 12 cm/s to indicate malignancy, the sensitivity and specificity were 88.9% and 81.0%, respectively. At the same sensitivity level, this gave a better specificity than the PI < or = 0.90 (specificity 61.9%, P = 0.036), RI < or = 0.60 (specificity 54.8%, P = 0.010) and PSV > or = 16 cm/s (specificity 71.4%, P = 0.121). Discrimination between benign and malignant tumours was improved further by using two criteria rather than one. When the two criteria of a TAMXV of > or = 12 cm/s and a PI < or = 1.0 were applied simultaneously, the tumours could be characterised with a sensitivity of 88.9% and a specificity of 88.1%. Therefore, intratumoural PSV and TAMXV could be used to discriminate between benign and malignant adnexal tumours better than values for PI and RI. The best discrimination was achieved by using a combination of cut-off values for velocity and impedance parameters as two criteria to define malignancy.

The origin of α-fetoprotein in first-trimester anembryonic pregnancies

Abstract OBJECTIVE: Our purpose was to evaluate the origin of α-fetoprotein in the maternal circulation and coelomic fluid of pregnancies with an empty gestational sac on first-trimester ultrasonographic examinatin. STUDY DESIGN: The α-fetoprotein level and the affinity of α-fetoprotein for concanavalin A Sepharose was measured between 8 and 11 weeks of gestation in the maternal serum and coelomic fluid of nine pregnancies complicated by an empty gestational sac and of 27 normal pregnancies. RESULTS: The maternal serum α-fetoprotein level in patients with an empty gestational sac was high in seven cases and normal in two cases. In these cases the median level was significantly ( p 50% of α-fetoprotein molecules in the coelomic fluid were of the concanavalin A nonreactive fraction, whereas in one case the coelomic fluid sample contained CONCLUSION: Normal or high maternal serum AFP levels and α-fetoprotein molecules predominantly of yolk sac origin in the coelomic fluid of pregnancies with an empty gestational sac on ultrasonography provide further evidence that the most likely explanation for this feature is the early death of the embryo with persistence of the placental tissue.

Color flow mapping in obstetrics.

Blood flow studies are now used extensively in evaluating fetal peripheral circulation. By using continuous and pulsed Doppler ultrasonic equipment the raw Doppler shifts caused by blood moving in the vessels can be analyzed in different ways. Spectral data can be used to estimate blood velocity and volume in the vessel, and pulsatility characteristics and turbulence. All these data are obtained from very restricted areas within the body so that aiming of the probe is critical, and obtaining data from an area requires long and tedious effort. Color flow mapping which has recently been introduced into clinical practice provides an overview of flow velocities and directions within an area. Color coded flow can be displayed by applying the moving target identification principle (as in radar) to an ultrasonic diagnostic instrument where sound waves are used instead of radio waves. The value of flow mapping has already been recognized in the diagnosis of congenital and acquired heart disease in adults and children. Direct visualization of intracardiac flow provides for a fast and accurate diagnosis of various cardiac defects, such as the ventricular septal defect, without cardiac catheterization. In the present study we have investigated the potential of color flow mapping in obstetrics. 211 pregnant women were examined between the 15th and 40th weeks of pregnancy. 193 of them had normal pregnancies; 18 were abnormal, including 11 cases of insulin dependent diabetes, 2 cases of Rh-immunization, 2 cases of nonimmunologic fetal hydrops, 2 cases of fetal cardiac structural defects and 1 case of intrauterine growth retardation. Intracardiac flow was clearly seen in 78% (35/45) of cases at the gestational age between the 20th and 24th weeks. After the 24th week the heart flow visualization rate gradually decreased to 31% (11/36) before term. In 2 cases of congenital heart abnormality flow mapping enabled clear visualization of reverse flow through the tricuspid valve and diagnosis of valvular insufficiency. The best results in studies of flow in peripheral vessels were obtained from umbilical vessels which were seen in all cases after the 15th week. The flow visualization rate was much lower when the fetal aorta, intrahepatic umbilical vein and internal carotid artery were studied. The comparison between the diameter of the umbilical vein measured on the B-scan and flow width in the same vessel showed no significant difference (t = 0.26; p less than 0.01; N = 209).(ABSTRACT TRUNCATED AT 400 WORDS)