Physiopathology of late-onset fetal growth restriction.

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its potential for genetic determination. FGR can have several causes, including genetic syndromes, chromosomal diseases, and infections; however, a vast majority of cases are probably attributed to impaired uterine and placental circulation. The relationships between abnormal placental development and FGR are complex, and studies are generally few, presenting confounding factors. Damage to the uteroplacental circulation associated with vasculogenesis and villus angiogenesis dysfunction are the main factors involved in subsequent FGR. The main receptors involved in FGR include hypoxia-inducible factor (HIF 1, 2, and 3), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), vascular endothelial growth factor C (VEGF-C), soluble Flt-1, soluble endoglin (Seng), angiopoietin-1 and -2 (Ang-1 and Ang-2), tyrosine kinase receptor 1 (Flt-1), tyrosine kinase receptor 2 (Flt-2), vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3, kinase domain receptor (KDR), and vascular endothelial growth factor receptor A (VEGFR-A). Furthermore, failure in trophoblastic invasion and remodeling of spiral arteries has been associated with FGR owing to poor placental perfusion. There are several possible causes for poor remodeling of spiral arteries, which probably vary on a case-to-case basis. Changes in the placental form, macroscopic and microscopic vascular lesions, inflammation, and genetic changes are also related to FGR. Based on gestational age at diagnosis, FGR can be classified as early- (˂32 weeks) and late-onset (≥32 weeks). Moreover, there exist several theories regarding possible pathophysiological differences between early- and late-onset FGR, with some postulating that it the same disease but at different stages or severity. Another hypothesis suggests that the change in the trophoblastic invasion of spiral arteries would be milder. In this article, we address the main mechanisms described in the pathophysiology of FGR and, later, the specific findings in late-onset FGR.

Antenatal corticosteroid treatment for the prevention of peri-intraventricular haemorrhage in preterm newborns: a retrospective cohort study using transfontanelle ultrasonography.

OBJECTIVE: The objective of this study was to assess the correlation between antenatal corticosteroids and peri-intraventricular haemorrhage (PIVH) using transfontanelle ultrasonography, as well as to evaluate the risk factors for its incidence. METHODS: We performed a retrospective cohort study using medical records of preterm newborns. The protocol for maternal corticoid administration for foetal lung maturation included dexamethasone 4 mg (intramuscular) 8/8 hours per 48 hours, with one cycle per week. The diagnosis of periintraventricular haemorrhage was based on transfontanelle ultrasonography, using the Papile's classification. The following risk factors for peri-intraventricular haemorrhage were assessed: birth weight, gestational age at delivery, type of delivery, newborn's sex, surfactant administration, premature rupture of membranes and previous history of infection during the current pregnancy. The student's t-test and chi-square test were used for statistical analysis. RESULTS: Our sample population included 184 preterm newborns. Transfontanelle ultrasonography revealed peri-intraventricular haemorrhage in 32 (74.4%) and periventricular leukomalacia in 11 (25.6%) newborns. Grade I haemorrhage was found in 20 (62.5%), grade II in five (15.6%), and grade III in seven (21.8%) newborns, as in accordance with Papile's classification. Vaginal delivery (p = 0.010), birth weight <1500 g (p = 0.024), gestational age at delivery ≤32 weeks (p = 0.018), and previous history of infection during pregnancy (p = 0.013) were considered risk factors for peri-intraventricular haemorrhage in preterm newborns. CONCLUSION: Maternal corticoid administration for foetal lung maturation showed a protective effect against peri-intraventricular haemorrhage in preterm newborns. The risk factors for peri-intraventricular haemorrhage were determined.

Antenatal diagnosis of renal duplication by ultrasonography: report on four cases at a referral center.

Duplication of the renal collecting system is the commonest major congenital malformation of the urinary tract, with an incidence of 1% among live births. Antenatal diagnosing of renal duplication and an associated ureterocele is infrequent. We report four cases of prenatally diagnosed unilateral duplication of the renal collecting system. In two of them, the renal duplication was associated with an ectopic ureterocele.

RHD gene polymorphisms in alloimmunized RhD-negative individuals with high rate of racial admixture.

BACKGROUND: The D-negative phenotype is the result of the total RHD gene deletion in almost all Caucasians, but it accounts for only about 20% in Africans and 70% in Asians. In Africans the RHDΨ that is one of the most important causes of the D-negative phenotype. We investigated the RHD polymorphisms in D-negative phenotype mixed Brazilians who have anti-D alloantibody. STUDY DESIGN AND METHODS: Blood samples from 130 individuals previously typed as D-negative were phenotyped again using: (a) two tube reagents (Anti-D blend reagent, Cellular line TH-28, MS-26; and Anti-D polyclonal); (b) one gel test ID-Card for Rh subgroups including C(w) and K antigen; and (c) ABO/Rh (Anti-D blend reagent, Cellular line 175-2, LDM3). The method used for RHD screening detected the presence of RHD exon 10 and intron 4. Sequence analysis was performed on PCR products amplified from genomic DNA for all 10 exons RHD gene. RESULTS: We found that 118/130 (90.8%) of D-negative tested individuals had total RHD gene deletion, while 12/130 (9.2%) showed RHD gene polymorphisms. The RHDΨ was found in 10 (7.7%) individuals, one sample (0.77%) hybrid RHD-CE-D(s) /RHDΨ, and another (0.77%) weak D type 4.2. CONCLUSIONS: The results showed that the RHD gene was present in 9.2% of racially mixed Brazilians who produced usually clinically significant anti-D alloantibodies. Therefore, the data showed that careful attention is necessary for clinicians in applying RhD genotyping to transfusion medicine in populations with high rate of racial admixture.

Prenatal Diagnosis of EEC Syndrome with "Lobster Claw" Anomaly by 3D Ultrasound.

THE EEC SYNDROME IS A GENETIC ANOMALY CHARACTERIZED BY THE TRIAD: ectodermal dysplasia (development of anomalies of the structures derived from the embryonic ectodermal layer), ectrodactyly (extremities, hands and feet malformations) and cleft lip and/or palate; these malformations can be seen together or in isolation. The prenatal diagnosis can be made by two-dimensional ultrasonography (2DUS) that identifies the facial and/or limb anomalies, most characteristic being the "lobster-claw" hands. The three-dimensional ultrasonography (3DUS) provides a better analysis of the malformations than the 2DUS. A 25-year-old primigravida, had her first transvaginal ultrasonography that showed an unique fetus with crow-rump length of 47 mm with poorly defined hands and feet,. She was suspected of having sporadic form of EEC syndrome. The 2DUS performed at 19 weeks confirmed the EEC syndrome, showing a fetus with lobster-claw hands (absence of the 2(nd) and 3(rd) fingers), left foot with the absence of the 3rd toe and the right foot with syndactyly, and presence of cleft lip/palate. The 3DUS defined the anomalies much better than 2DUS including the lobster-claw hands.

Fetal thigh and upper arm volumes by 3D-sonography: comparison between multiplanar and XI VOCAL methods.

OBJECTIVE: To compare fetal upper arm and thigh volume measurements acquired by three-dimensional (3D) ultrasound using the multiplanar and the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) methods with different number of sectional planes. METHODS: This study enrolled 40 healthy pregnant women between 20 and 40 weeks of gestation. The volume of fetal limbs was calculated using the multiplanar (with 5.0 mm intervals) and the XI VOCAL (with 5, 10, 15, and 20 slice planes) methods. Comparison between the techniques was made by analysis of variance and Bonferroni statistical tests. RESULTS: Mean fetal upper arm volume measured by the 15 sectional planes XI VOCAL method was lower than the same method using 5 and 10 planes instead (p = 0.025 and 0.039, respectively). Fetal thigh volume showed no statistically significant differences among all studied methods. CONCLUSION: The XI VOCAL using 15 sectional planes method underestimated the fetal upper arm volume by 5 and 10 planes XI VOCAL techniques.

Delineation of vertebral area on the coronal plane using three-dimensional ultrasonography advanced volume contrast imaging (VCI) Omni view: intrarater reliability and agreement using standard mouse, high definition mouse, and pen-tablet.

OBJECTIVE: To assess the fetal lumbosacral spine by three-dimensional (3D) ultrasonography using volume contrast imaging (VCI) omni view method and compare reproducibility and agreement between three different measurement techniques: standard mouse, high definition mouse and pen-tablet. METHODS: A comparative and prospective study with 40 pregnant women between 20 and 34 + 6 weeks was realized. 3D volume datasets of the fetal spine were acquired using a convex transabdominal transducer. Starting scan plane was the coronal section of fetal lumbosacral spine by VCI-C function. Omni view manual trace was selected and a parallel plane of fetal spine was drawn including interest region. Intraclass correlation coefficient (ICC) was used for reproducibility analysis. The relative difference between three used techniques was compared by chi-square test and Fischer test. RESULTS: Pen-tablet showed better reliability (ICC=0.987). In the relative proportion of differences, this was significantly higher for the pen-tablet (82.14%; p<0.01). In paired comparison, the relative difference was significantly greater for the pen-tablet (p<0.01). CONCLUSION: The pen-tablet showed to be the most reproductive and concordant method in the measurement of body vertebral area of fetal lumbosacral spine by 3D ultrasonography using the VCI.

Transvaginal grey scale histogram of the cervix at 20-25 weeks of pregnancy.

AIM: To assess the echogenicity of the cervical stroma and area surrounding the cervical canal (cervical gland area - CGA) using grey scale histogram (GSH) in pregnancies between 20 and 25 weeks. METHODS: Cross-sectional study involving 149 pregnancies in the second trimester. Transvaginal sonography was performed to measure cervical length (biometric evaluation), assess the CGA and detect cervical funnelling (morphologic evaluation). The GSH was used for the objective assessment of the cervical stroma and CGA in the mid portion of the cervix. Mean, minimum, maximum and standard deviation measurements were obtained on the GSH and the CGA/stroma ratio was calculated. Intra-observer and inter-observer reproducibility were assessed using the intraclass correlation coefficient (ICC). RESULTS: Mean cervical length was 42.37 ± 7.05 mm (range 12-54 mm). Funnelling was detected in four women (2.7%) and one of these also had absent CGA. The mean GSH stroma value was 103 ± 25 (53-160) and the mean CGA value was 64.5 ± 23 (13-167). The mean CGA/stroma ratio was 0.62 ± 0.14 (0.24-1.29). Intra- and inter-observer reproducibility was excellent with ICC of 0.975 and 0.922 respectively. CONCLUSION: There are large differences in the texture of the cervical stroma and CGA on GSH allowing the objective differentiation of the two areas. The CGA/stroma ratio allows the objective assessment of the absence or presence of the CGA.

Reproducibility of fetal heart volume by 3D-sonography using the XI VOCAL method.

BACKGROUND: To assess the reliability of fetal heart volume measurement by three-dimensional sonography (3DUS) using the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) method. METHODS: This reliability study enrolled 30 pregnant women with singleton healthy pregnancies between 19 and 34 weeks of gestation. All volume acquirements were performed with a convex volumetric transducer (C3-7ED) coupled to an Accuvix XQ sonography device (Medison, Korea). The XI VOCAL 10 planes was the method of choice for volumetric measurement. 3D datasets were analyzed by two observers (EQSB and HJFM); fetal heart volume was measured twice by the first and once by the second observer to calculate intra and interobserver reproducibility. Statistical analysis used pareated Student's t test (p) and calculated Intraclass correlation coefficients (ICC). Bland-Altman plots were also constructed. RESULTS: We observed an excellent intra- and interobserver reliability for fetal cardiac volume assessed by XI VOCAL. For the intraobserver the ICC was 0.998 (95% CI: 0.997; 0.999), with mean of differences of 0.12 cm3 (95% limits of agreement: -0.84; +0.84; p = 0.130). For interobserver the ICC was 0.899 (95%CI: 0.996; 0.998), mean of differences 0.05 cm3 (95% limits of agreement: -0.84; +0.84; p = 0.175). CONCLUSION: Fetal cardiac volume assessed by 3DUS using XI VOCAL method is highly reproducible between 19 to 34 gestational weeks.

Diagnosis of ovarian torsion by three-dimensional power Doppler in first trimester of pregnancy.

Three-dimensional ultrasonography in power Doppler mode (3D power Doppler) allows the appropriate quantitative assessment of the ovarian tissue vascularization. The present case is of an ovarian torsion in a pregnant woman at 6.5 weeks with ovarian hyperstimulation syndrome due to in vitro fertilization. Gray-scale images of endovaginal two-dimensional ultrasonography revealed enlargement of the right ovary and multiple peripheral follicles. Two-dimensional ultrasonography in color Doppler mode revealed the absence of venous flow and reduction in arterial flow to the impaired ovary. 3D power Doppler allowed the appropriate quantitative assessment of tissue vessel density of the impaired ovary, which greatly influenced the decision for conservative surgical treatment. The 3D power Doppler assessment performed after the surgery confirmed the integrity of the ovarian tissue. 3D power Doppler can help in the selection of patients with ovarian torsion for conservative surgical treatment.

Comparison of two- and three-dimensional ultrasonography in the evaluation of fetal heart: image quality and time spent in the exam.

OBJECTIVES: To compare fetal heart evaluation done through two-dimensional (2DUS) and three-dimensional ultrasonography (3DUS) as to optimal plane imaging, image quality, and time needed to perform the examination. METHODS: Prospective study involving 12 normal pregnant women, with gestational ages ranging from 22 to 26 weeks, scanned with a VOLUSON 730 with a convex 4.0-7.0 MHz transducer, in both two- and three-dimensional modes. In each case, three basic view planes were obtained: four-chambers view, right, and left ventricular outflow tracts. Each view was subjectively evaluated by three different examiners as to image quality, and graded from 0 (minimum) to 4 (maximum) cross-marks (+). The sum of all grades obtained for each case was used to classify the quality of the exam as unsatisfactory (0 to 1+), poor (2 to 4+), regular (5 to 7+), and good (8 to 12+). The time taken to obtain the views was recorded for each case, starting with the acquisition of the first view on the 2D exam and with the identification and opening of the volume blocks on the three-dimensional software. RESULTS: The number of three-dimensional blocks with good, regular, poor, and unsatisfactory grades were, respectively, 6, 15, 9, and 10. The average in cross-marks of the cases graded good in each group without the worst result for each plane was 8. 2DUS was superior to 3DUS regarding the quality of the images obtained by the three pattern view planes and the average time to obtain high quality view planes was longer for 3DUS when compared to 2DUS. 2DUS offered better quality images and in less time than 3DUS. CONCLUSIONS: Three-dimensional ultrasound is an advancement in fetal heart evaluation; however two-dimensional ultrasound remains the best screening method in diagnosing cardiac malformations, due to the good quality of its images and the lesser time needed to perform the exam.

Diagnosis of uteroperitoneal fistula through color Doppler hysterosonography.

INTRODUCTION: Uterine fistulas are infrequent pathologic entities characterized by abnormal communication of the uterus with any other organ or structure through a perforation formed due to traumatic and infectious conditions among others. The use of hysterosonography as method of diagnosis for that pathologic entity has few descriptions in medical literature. MEDLINE search resulted in only two cases reporting the use of HS in the diagnosis of uterine fistula. OBJECTIVE: Our objective is to report a case of uteroperitoneal fistula caused by uterine trauma during curettage, diagnosed by color Doppler hysterosonogrphy. The importance of our report lies on HS as a simple, safe and low cost method, which can be used for the diagnosis of fistulous processes involving the uterus.

Validation of fetal cerebellar volume by three-dimensional ultrasonography in Brazilian population.

BACKGROUND: To validate the prediction equation of the volume of fetal cerebellum by three-dimensional ultrasonography determined for Taiwan's population in Brazilian population. METHODS: A longitudinal prospective study was performed with 52 normal pregnant women between 20 and 32 weeks. The measurement of fetal cerebellar volume was done by virtual organ computer-aided analysis (VOCAL) method, with a rotation angle of 30 degrees. To establish the correlation of fetal cerebellar volume with gestational age, a polynomial regression analysis was performed, with cerebellar volume as dependent variable and gestational age as independent variable. To compare the prediction equation of the volume of fetal cerebellum in Taiwan's population and the equation established in this study, with the values obtained from Brazilian population (referential), we used the intraclass correlation coefficient, with the averages compared by paired Student's t test. RESULTS: The volume of fetal cerebellum was highly correlated with gestational age, and the best prediction equation obtained was of the second degree. The equation established in this study predicted cerebellar volumes more accurately than the equation established for Taiwan's population, since the average values of fetal cerebellar volume were more similar to the average values of reference. CONCLUSIONS: The equation established for Taiwan's population presented less accuracy in Brazilian population, possibly due to the strong ethnical differences between both populations.

Sirenomelia sequence: early prenatal diagnosis of one rare case associated with acardiac malformation.

Sirenomelia sequence is a very rare congenital malformation, with incidence of around 1.5-4.2 per 100,000 births. Prenatal diagnosis of sirenomelia in the first trimester is rare; there are only five cases reported for the present, and the association of sirenomelia with acardiac malformation is even rarer. We present a rare case of sirenomelia associated with acardiac malformation detected in the first trimester through combined two-dimensional, three-dimensional and color Doppler sonographies.

Prenatal diagnosis of a large fetal cervical teratoma by three-dimensional ultrasonography: a case report.

CONTEXT: The cervical teratomas are rare, benign tumors, they are formed by the three embryonic layers, and they represent only 6% of teratomas. The prognosis depends mainly on the size and location of the lesion, on the tumor growth rate, and on the level of tracheal compression. Prenatal diagnosis is usually reached with the aid of a two-dimensional ultrasonography (2DUS) after the 15th week of gestation, which shows a large heterogeneous mass in the cervical region, plus a polyhydramnios, on the Doppler mode which also shows the vascularization of the tumor. CASE REPORT: We report a case of cervical teratoma diagnosed on the 31st week of gestation with the aid of a 2DUS and color Doppler mode. We focus on the main findings obtained with the three-dimensional ultrasonography in surface mode, and we highlight the importance of this methodology for the indirect evaluation of the neonatal prognosis.

Treatment of twin reversed arterial perfusion sequence by septostomy and amniodrainage: a case report.

INTRODUCTION: An acardiac fetus is the most severe malformation seen in humans. It is an extremely rare complication, occurring in approximately 1% of all monozygotic twin gestations, with an incidence of about 1 in 35,000 births. This malformation happens as a result of the syndrome of reversed arterial perfusion of the acardiac twin from the other normal fetus (pump twin), due to the presence of arterio-arterial anastomoses in a monochorionic placenta. Several obstetric and perinatal complications have been associated to this anomaly and several treatments have been proposed to reduce the morbimortality of the pump twin. There's no report in MEDLINE about the treatment of twin gestations with acardiac fetus through septostomy. CASE REPORT: The present article reports a case of reversed arterial perfusion sequence complicated by polyhydramnios diagnosed at 19th week of pregnancy, treated with septostomy and serial amniodrainage. DISCUSSION: This case presented it demonstrate favorable development of the gestation, with labor happening at 35 weeks gestation and pump twin presenting good vitality conditions. In cases with no major factors of bad prognosis, septostomy combined with amniodrainage could be an interesting therapeutic option for a safe and efficacious management of selected cases of TRAP sequence.

Prevalence of uterine defects in habitual abortion patients attended on at a university health service in Brazil.

OBJECTIVES: Assessment of the prevalence and types of uterine defects in patients with recurrent pregnancy loss (RPL) through hysteroscopy (HTC). PATIENTS AND METHODS: Sixty non pregnant patients with history of three or more consecutive spontaneous abortions were evaluated through HTC. The findings were separated into three groups: synechias, polypoids lesions (endometrial polyps and submucous myomas), and alterations of the cavity shape (mullerian anomalies). The findings were gathered and tabulated according to the presence of each defect. RESULTS: Uterine anomalies were observed in 23 (38.3%) patients, with 16 (26.7%) synechias, 3 (5.0%) polypoids lesions and 8 (13.3%) shape alterations. CONCLUSIONS: The results obtained here suggest that the uterine factor has high prevalence in patients with a RPL history, and for this reason it should be systematically assessed in patients with a RPL history.

Comparison of hysterosalpingography, hysterosonography and hysteroscopy in evaluation of the uterine cavity in patients with recurrent pregnancy losses.

AIM: To evaluate the accuracy and acceptability of hysterosonography (HS) in the diagnosis of uterine anomalies in patients with recurrent pregnancy loss. METHOD: Sixty non-pregnant patients with a history of at least three previous recurrent miscarriages were submitted to the HS, HSG and hysteroscopy (HTC) exams. The findings fall into three categories: synechiae, polypoid lesions and abnormal uterine cavity shape. The HTC exam was used as the gold standard. The findings of the HS and the HSG were compared to the HTC's and the agreement was evaluated using the Kappa coefficient. Significance was established at < 0.05. Sensitivity, specificity, positive and negative predictive values were determined for each method. RESULT: Uterine anomalies were present in 38.3% (23) of the patients: 16 (26.7%) with synechiae, 3 (5.0%) with polypoid lesions and 8 (13.3%) with abnormal uterine cavity shape. Accuracy of the HS and the HSG was 90.9 and 85.2%. General sensitivity of the HS was superior to the HSG (90.5 vs. 75.0%). It also had a higher degree of agreement with the HTC (Kappa = 0.81 vs. 0.68). The HS caused significantly less pain than the other two methods. CONCLUSIONS: The HS had higher diagnostic accuracy in the detection of uterine cavity anomalies and it was better tolerated by the patients when compared to hysterosalpingography and hysteroscopy.