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Placental alterations caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) infection have already been described, but most studies used small sample groups and the difference according to the severity of the disease has not been verified. Our objective was to describe placental alterations in patients with coronavirus disease 2019 (COVID-19) and analyze the association of pathological placental findings with the clinical parameters of COVID-19 and perinatal results.This was a nested study within a prospective cohort study involving 109 symptomatic pregnant women with COVID-19. The prevalence of observed placental alterations was described, and the associations of pathological findings with the clinical parameters of COVID-19 severity and with perinatal outcomes were assessed.The frequency of types of placental features was poor maternal vascular perfusion in 45% of cases, poor fetal vascular perfusion in 33.9%, hematogenous origin infection in 32.1%, and morphological changes corresponding to ascending infection in 21.1%. Hematogenous infection differed significantly according to COVID-19 severity (p = 0.008), with a prevalence ratio (PR) of 1.74 (95% confidence interval, 1.02-2.98) in the moderate COVID-19 group compared to the mild COVID-19 group. Among the perinatal outcomes, there was an unexpected inverse association between prematurity and placental infection of hematogenous origin, with lower rates of prematurity among cases with inflammation of hematogenous origin (p = 0.029).Moderate SARS-Cov-2 infection presented a higher prevalence of placental pathological findings. There was no association of placental findings with adverse perinatal outcomes.

Introduction. Controlling the invasive activity of trophoblastic tissue has not been elucidated. In the accreta placenta, the invasion of placental tissue is directly related to the expression of CRIPTO-1 at the maternal-fetal interface. The aim of this study is to evaluate if the expression of the CRIPTO-1 is related to different degrees of trophoblast invasion into the tube wall in ampullary pregnancy. Methods. Prospective study with 21 patients with ampullary tubal pregnancy undergoing salpingectomy. Anatomopathological evaluation determined the degree of invasion of trophoblast tissues into the tubal wall and grouped the samples into invasive degrees I, II, or III. The groups were compared for tissue expression of CRIPTO-1 using the Kruskal-Wallis nonparametric test. p values lower than 0.05 were considered significant. Results. Quantitative expression of CRIPTO-1 differed in each of the three groups of trophoblast invasion in the tubal wall in ampullary pregnancies ( p < 0.001 ). There is a difference between groups when grade I + grade II versus grade III ( p < 0.001 ) and grade I versus grade II + grade III ( p < 0.001 ). The tissue expression of CRIPTO-1 in ectopic trophoblasts showed that deeper invasion of the tubal wall was associated with stronger expression than in shallow invasion ( p < 0.001 ). Discussion. In ampullary pregnancies, the depth of penetration of trophoblast tissue in the tubal wall is related to CRIPTO-1 tissue expression.

ObjectiveChronic pain is a prevalent and burdensome condition. Reboot Online was developed to address treatment barriers traditionally associated with accessing face-to-face chronic pain management programs. It is a comprehensive multidisciplinary online treatment program, based on an existing and effective face-to-face multidisciplinary pain program (the Reboot program).Design & ParticipantsA CONSORT-compliant randomized controlled trial was conducted, enrolling adults who had experienced pain for three months or longer.MethodsParticipants were randomly allocated to either an eight-lesson multidisciplinary pain management program, Reboot Online (N = 41), or to a usual care (UC) control group (N = 39). Clinical oversight was provided by a multidisciplinary team remotely, including physiotherapists and clinical psychologists. Participants were measured at baseline, post-treatment (week 16), and three-month follow-up (week 28).ResultsIntention-to-treat analyses revealed that Reboot Online was significantly more effective than UC at increasing pain self-efficacy (g = 0.69) at post-treatment, and these gains were maintained at follow-up. Similarly, Reboot Online was significantly more effective than UC on several secondary measures at post-treatment and follow-up, including movement-based fear avoidance and pain-related disability, but it did not significantly reduce pain interference or depression compared with UC. Clinician input was minimal, and adherence to Reboot Online was moderate, with 61% of participants (N = 25) completing all eight lessons.ConclusionsReboot Online presents a novel approach to multidisciplinary pain management and offers an accessible, efficacious alternative and viable treatment option for chronic pain management.

Objective Chronic pain is a prevalent and disabling condition. Reboot Online was developed as a multidisciplinary and widely accessible online treatment program for chronic pain. It has been shown to be effective in clinical trials, but the effectiveness of this program in routine care settings remains unknown. This study aimed to examine program adherence and effectiveness in a real-world sample of participants completing Reboot Online in the community. Design and subjects A retrospective cohort study was conducted using real-world data from participants referred the Reboot Online program by clinicians as part of their routine care, from April 2017 to April 2019. Methods Routinely collected data on program adherence, participant demography and clinical outcomes were included in the analyses. Measures included the Pain Self Efficacy Questionnaire, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain-Disability Index, and Patient Health Questionnaire 9-item (depression). Logistic regression was used to investigate whether certain factors predict program adherence (completion versus noncompletion), and linear mixed models were used to examine effectiveness. Results In total, 867 participants were included in the analyses, and 583 engaged with at least one Reboot Online lesson. Of these, 42% (n = 247) completed the course in its entirety, with rurality and lower Tampa scores being significant predictors of adherence. Completers demonstrated significant improvements across all outcome measures (effect sizes ranging from 0.22 to 0.51). Conclusions Reboot Online is an effective treatment for chronic pain in the routine care setting. Adherence was variable (overall 42%), and could be predicted by rurality and less fear of movement at baseline.

Neuropsychologists are commonly asked practical questions about cognitive recovery in the first year following moderate-to-severe traumatic brain injury (TBI), however guiding evidence to provide answers is limited. The design of this longitudinal study rectifies methodological problems in the literature by taking serial assessments on a monthly basis from 3- to 12-months post-trauma in a severe TBI sample (

Objective This study investigated the qualitative and semi-quantitative expression of metalloproteinases (MMP) and their tissue inhibitors (TIMP) in trophoblastic tissue during ampullary ectopic pregnancies and correlated that expression with the degree of tubal invasion. Study design It is a prospective study that included 34 patients diagnosed with ampullary tubal pregnancy who underwent salpingectomy. A histological evaluation of the depth of trophoblastic invasion in the tubes obtained was performed. Subsequently, the expression of the MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 and TIMP-3 markers was qualitatively and semi-quantitatively evaluated by indirect immunohistochemistry. In addition, the degree of trophoblastic invasion was correlated with the expression of each marker and with the metalloproteinase/inhibitor ratios. Results MMP-2 (11.2 %; 3.6–17.9) was the marker with greater expression at the implantation site, both in the qualitative and semi-quantitative assessment, while MMP-9 (2.23 %; 0.2–5.4) and TIMP-3 (2.53 %; 0.1–15.3) were only weakly expressed. Conclusion There was wide variation in expression among the markers and metalloproteinase/inhibitor ratios studied compared to the degrees of invasion.

Background Internet-based treatment programs present a solution for providing access to pain management for those unable to access clinic-based multidisciplinary pain programs. Attrition from internet interventions is a common issue. Clinician-supported guidance can be an important feature in web-based interventions; however, the optimal level of therapist guidance and expertise required to improve adherence remains unclear. Objective The aim of this study is to evaluate whether augmenting the existing Reboot Online program with telephone support by a clinician improves program adherence and effectiveness compared with the web-based program alone. Methods A 2-armed, CONSORT (Consolidated Standards of Reporting Trials)–compliant, registered randomized controlled trial with one-to-one group allocation was conducted. It compared a web-based multidisciplinary pain management program, Reboot Online, combined with telephone support (n=44) with Reboot Online alone (n=45) as the control group. Participants were recruited through web-based social media and the This Way Up service provider network. The primary outcome for this study was adherence to the Reboot Online program. Adherence was quantified through three metrics: completion of the program, the number of participants who enrolled into the program, and the number of participants who commenced the program. Data on adherence were collected automatically through the This Way Up platform. Secondary measures of clinical effectiveness were also collected. Results Reboot Online combined with telephone support had a positive effect on enrollment and commencement of the program compared with Reboot Online without telephone support. Significantly more participants from the Reboot Online plus telephone support group enrolled (41/44, 93%) into the course than those from the control group (35/45, 78%; χ21=4.2; P=.04). Furthermore, more participants from the intervention group commenced the course than those from the control group (40/44, 91% vs 27/45, 60%, respectively; χ21=11.4; P=.001). Of the participants enrolled in the intervention group, 43% (19/44) completed the course, and of those in the control group, 31% (14/45) completed the course. When considering the subgroup of those who commenced the program, there was no significant difference between the proportions of people who completed all 8 lessons in the intervention (19/40, 48%) and control groups (14/27, 52%; χ21=1.3; P=.24). The treatment efficacy on clinical outcome measures did not differ between the intervention and control groups. Conclusions Telephone support improves participants’ registration, program commencement, and engagement in the early phase of the internet intervention; however, it did not seem to have an impact on overall course completion or efficacy. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12619001076167; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619001076167

OBJECTIVES: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia. METHODS: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins. RESULTS: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024). CONCLUSION: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p

OBJECTIVE: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy. METHODS: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity. RESULTS: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798. CONCLUSIONS: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies.

Objective To assess the association between ultrasound images and serum concentrations of vascular endothelial growth factor (VEGF) in ampullary pregnancies. Design Prospective study. Setting University hospital. Patient(s) Fifty patients with ampullary pregnancy. Intervention(s) Criteria for inclusion in the study were: singleton pregnancy from spontaneous conception; diagnosis of tubal pregnancy in the ampullary region; radical surgical treatment (salpingectomy); and measurement of serum VEGF, human chorionic gonadotropin, and progesterone on the day of surgery. An additional criterion was description of an ectopic mass by transvaginal ultrasound, as follows: [1] ectopic gestational sac containing an embryo with cardiac activity; and [2] tubal ring: a paraovarian formation similar to a gestational sac, not containing a viable embryo (an anechoic structure surrounded by a peripheral hyperechogenic halo); an empty ectopic gestational sac; a sac containing an embryo without cardiac activity; or a vitelline vesicle. Main Outcome Measure(s) Association between ultrasound images and serum concentrations of VEGF. Result(s) An association was found between ultrasonographic images and VEGF serum concentrations. Ectopic embryos with cardiac activity were associated with higher levels of serum VEGF. Conclusion(s) In ampullary pregnancy, higher serum levels of VEGF are associated with the finding of an embryo with cardiac activity on transvaginal ultrasound. Greater production of VEGF likely creates development conditions more conducive to ectopic embryos.

Objectives. Chronic pain causes significant disability and psychological distress, but barriers often prevent people with pain from engaging in traditional face-to-face pain management programs. Accessible, feasible, and effective alternative treatment options are needed. Methods. A prospective, feasibility pilot study was conducted to trial a novel, multidisciplinary online pain management program: the “Reboot Online” program. Twenty participants experiencing pain of at least three months duration were recruited. All participants were enrolled in the “Reboot Online” program, consisting of eight online lessons completed over 16 weeks. Lessons incorporated multidisciplinary input from medical pain specialists, physiotherapists, and psychologists. Participants were assessed at pretreatment, posttreatment, and follow-up using a suite of outcome measures examining pain, disability, catastrophising, self-efficacy, mood, and psychological distress. Results. 13 participants completed the program (65% adherence). Following treatment, the participants had significantly improved scores on measures of pain-related disability, self-efficacy, catastrophising thoughts, acceptance of pain, symptoms of depression, and general psychological distress. These findings were retained at three months posttreatment. Participants also reported high levels of acceptability and satisfaction with the program. Discussion. This study provides pilot evidence for the feasibility, acceptability, and effectiveness of an online, multidisciplinary pain program: “Reboot Online.” Future investigations will focus on conducting a randomised controlled trial of this innovative and promising treatment for chronic pain. This trial is registered with ACTRN12615000660583.

Background— Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results— Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n=40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate ≤120 bpm, and a ventricular rate ≤55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death ( P Conclusions— This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of >90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents.

Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITE). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical appraisal of single-subject designs, thereby assisting to improve standards of single-case methodology.

Background and objective Salivary gland development entails co-ordinated processes involving complex molecular interactions in which integrins have a fundamental role. The integrins are a family of heterodimeric transmembrane receptors comprising alpha and beta subunits that mediate intercellular and extracellular signals involved in the organisation of cells in tissues and organs during development. The beta-1 integrin in particular have been implicated in proliferation and differentiation of cells involved in the development of epithelial tissues. To understand the role of beta-1 integrin in salivary gland development we have studied its expression in human foetal tissues. Design In situ hybridisation was used to compare the expression and localisation of integrin beta-1 with differentiation markers in developing human salivary glands obtained from foetuses of 8–24 weeks gestation. Results Integrin beta-1 first appeared during bud stage in a few cells and its distribution increased as salivary gland morphogenesis progressed. This increased pattern of beta-1 integrin expression was coincident with the appearance of the differentiation markers CK14, CK low MW and smooth-muscle actin. Conclusions The developmentally regulated expression of integrin beta-1 in association with the establishment of a mature phenotype indicated by salivary gland tissue differentiation markers is suggestive of its role in salivary gland morphogenesis.

Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations.

Purpose The aim of this study was to compare pregnancy outcome and pathologic findings in cases of placental lake visualized on sonography in pregnancies without concurrent fetal or maternal disease. Methods Placental aspect was evaluated sonographically in 4,106 singleton pregnancies without maternal or fetal disease at between 15 and 34 weeks3 gestation. Fifty-nine cases presenting with placental lakes were followed through the end of pregnancy. Obstetric outcome was compared with that of cases with sonographically normal placental aspects (n = 37). Macroscopic and microscopic examinations for pathology were also performed in a few cases in both groups. Results Placental lakes were present in 2.2% (92/4,106) of the cases. No statistically significant difference was observed in birth weight, gestational age at delivery, adverse obstetric outcome, and macroscopic or microscopic results between the control and study groups. Conclusion Our findings do not seem to indicate an increase in the risk for an adverse pregnancy outcome in cases presenting with placental lakes. © 2005 Wiley Periodicals, Inc. J Clin Ultrasound 33:67–71, 2005

We report on the ultrasound features and natural history of trisomy 10. At 12 weeks' gestation in a routine scan examination, the fetus presented with increased nuchal translucency thickness, mild skin oedema, bilateral pleural effusion, marked micrognathia, cardiomegaly, unilateral talipes and reversed A-wave in the ductus venosus blood flow. Karyotyping on chorionic villus sampling (CVS) led to the diagnosis of trisomy 10, which was confirmed by fetal blood sampling at 22 weeks' gestation. As the parents opted to continue with the pregnancy, the natural history and following ultrasound features are described. This is the third case of trisomy 10 in the literature reporting on the physical features. The most frequent ultrasound findings presented in trisomy 10 are increased nuchal translucency, micrognathia, renal agenesis, facial cleft, limbabnormalities, cardiac defects and early severe growth retardation.

Epithelioid trophoblastic tumor is a distinctive but rare trophoblastic tumor. It derives from intermediate trophoblastic cells of the chorion laeve and is usually associated with a previous gestational event. We report the case of a patient who had undergone dilatation and curettage for a missed miscarriage. Three months later gestational trophoblastic disease was suspected because of persistent vaginal bleeding and high levels of beta-human chorionic gonadotropin (beta-hCG). Transvaginal ultrasound revealed irregular echolucent lacunae within the myometrium, some of them filled with low-resistance, turbulent blood flow on Doppler examination, emphasizing the diagnosis of gestational trophoblastic disease. The patient was treated with 12 courses of multiagent chemotherapy. After a 2-year remission, a low rise in serum beta-hCG was observed. Transvaginal ultrasound revealed a well-circumscribed echogenic lesion with a diameter of 1.8 cm in the uterine fundus, with no detectable blood flow on Doppler imaging. A diagnosis of tumor of intermediate trophoblastic cells was suspected and total hysterectomy was performed. On pathological examination, the histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. Most reported cases of epithelioid trophoblastic tumor have solitary nodules with sharp margins, which is consistent with our ultrasound findings. Ultrasound may be helpful in differentiating epithelioid trophoblastic tumor from placental-site trophoblastic tumor, another tumor of intermediate trophoblastic cells, which shows infiltrative growth insinuating between muscle fibers.

The authors report a prospective study of correlation between histopathological alterations of the placenta, risk factors and early-onset bacterial infections in 224 premature newborns. They used a mathematical model for evaluation and prediction of neonatal bacterial infection according to the localization in chorioamniotic tissues (chorioamniotic plate, amniotic membranes and umbilical cord) invaded by leukocytes. Septicemia, pneumonia or omphalitis were documented in 45 (20%) infected premature newborns and inflammatory lesions in the placenta were observed in all of them. In order of statistical significance, the most important variables for early-onset bacterial neonatal infection were invasion of the chorioamniotic plate, amniotic membranes and umbilical cord tissues by PMNL (P < 0.0000), premature rupture of membranes (P < 0.0000), birthweight lower than 1500 g (P < 0.0000), gestational age under 34 weeks (P < 0.0001), foul smell (P < 0.0038), no antibiotics before delivery (P < 0.0066) and intrapartum fever (P < 0.0087). By logistic stepwise multiple regression analysis, invasion of fetal chorioamniotic plate and of amniotic membranes by leukocytes were the only statistically significant variables. The probability of neonatal infection in premature newborns, when polymorphonuclear neutrophils were present in chorioamniotic plate and in amniotic membranes, was 62.5%, while the probability was 0.5% when these tissues were normal. These data suggest that histological chorioamnionitis has to be considered as an important risk factor for early-onset infection in premature newborns.

CRIPTO-(CR)1 is a protein associated with tumorigenesis and metastasis. Here we demonstrate that CR-1 expression in normal and creta placentas is associated with various degrees of uterine invasion. Cytokeratin (CK) and CR-1 protein expression was visualized by immunohistochemical staining of formalin-fixed, paraffin-embedded placental specimens (control placentas,n=9; accreta,n=6; increta,n=10; percreta,n=15). The pattern of extravillous trophoblast (EVT) cell morphology was distinctive in creta placentas: densely-compacted cell columns and large star-shaped cells with a typically migratory phenotype, not common among third trimester control placentas. Quantification revealed higher CR-1 immunoreactivities in accreta(P=0.001), increta(P=0.0002), and percreta placentas(P=0.001)than in controls. In contrast to controls, there was a significant positive relationship between CR-1 and CK reactivity in all creta placentas (accreta,P=0.02; increta,P=0.0001, and percreta,P=0.025). This study demonstrated CR-1 expression in the placental bed, its increased expression in creta placentas, and EVT cells as the main CR-1-producing cell type. Morphological examination revealed an immature and invasive trophoblast profile in creta placentas, suggesting impairment of the trophoblast differentiation pathway. These findings provide important new insights into the pathophysiology of abnormal creta placentation and its gestational consequences.

The prenatal diagnosis of congenital transmission of Chagas' disease in a pregnant woman with the indeterminate form of the disease is reported. Sonography revealed fetal hydrops at 31 weeks' gestation. Anti-Trypanosoma cruzi IgM and IgG antibodies were negative in the fetal blood sampled by cordocentesis, but T. cruzi trypomastigotes were found in its buffy coat. Owing to anemia, in utero exchange transfusion was undertaken, but fetal demise ensued. Labor was induced and a stillborn infant weighing 2030 g was delivered. The pathological examination revealed placentitis and meningoencephalitis, myocarditis and splenitis in the stillborn fetus. Amastigotes were found in the myocardium, brain and placenta.

Background The aim of this study was to determine the accuracy of prenatal echocardiography in the diagnosis of intracardiac malformations and the degree of cardiac fusion in conjoined twins presenting to a single center over a 25-year period. Methods The study group included 53 sets of conjoined twins from 1987 to 2012, including 38 thoracopagus, six parapagus, six omphalo-ischiopagus, two omphalopagus, and one cephalopagus. Twins were classified according to the degree of cardiac fusion: separate hearts and pericardium (group A, n = 10), separated hearts and common pericardium (group B, n = 2), fused atria and separated ventricles (group C, n = 2), and fused atria and ventricles (group D, n = 39). Postmortem examination was possible in 68 individual cases (98 deaths [69.3%]). Results Cardiac defects were diagnosed in 47 sets of twins (88.6%). In 10 (18.8%), only one fetus was affected, and in 37 (69.8%), both fetuses were affected ( n = 84/106 [79.2%]). There was a high predominance of right-sided lesions (63.0% [53 fetuses in 84 affected]) including pulmonary atresia or stenosis (35.7%), tricuspid atresia (11.9%), and hypoplastic or small right ventricle (21.4%). Autopsy findings added information to fetal echocardiographic findings in nine sets of twins (25.7%). Three pairs classified antenatally in groups A, B, and D were confirmed by autopsy in groups B, C, and C, respectively. Conclusions This study demonstrates that specialized fetal echocardiography is not a perfect diagnostic tool but is sensitive enough to establish prognosis in the counseling process. Because of complexity, such evaluations should be performed only at tertiary centers by specialists who are familiar with the peculiarities of this rare malformation. The predominance of right-sided lesions is not only an interesting finding, but this information has essential importance in terms of shortening examination times, allowing a more focused analysis of the fetal heart.

The authors report a prospective study of the correlation between histopathological alterations in the placenta and the umbilical cord and neonatal infection in 223 newborns. The pathological studies were specifically concerned with the presence of infection as shown by a polymorphonuclear infiltrate at these sites. Inflammatory lesions were demonstrated in 26.9% of specimens and were highest in those with prolonged premature rupture of membranes and in the least mature placentas. Among the cases of histological chorioamnionitis, only 23.3% of infants had documented infection. Neonatal infection was diagnosed in 7.2% of the newborns and was 10 times more frequent in preterm newborns. Among the cases of infected newborns, 87.5% of placentas had histological chorioamnionitis. Pneumonia and septicemia were the most frequent conditions found among infected newborns. There was a strong correlation between histological chorioamnionitis and neonatal infection. The data obtained in this investigation suggest that histological chorioamnionitis is an important indicator of neonatal infection.

The incidence of CRS and CRI has decreased markedly worldwide with the implementation of efficient vaccination programs. We report a congenital rubella case with fetal death occurred at 29th week of gestation. RV was confirmed in placenta. The results of phylogenetic analysis showed that the RVs/SaoPaulo01.- BRA/08.CRI belongs to the genotype 2B of RV.

We present a case of an advanced invasive mole with a metastatic thrombus in the inferior vena cava in which sonography clearly showed vesicles in the myometrium, ovaries, and metastatic thrombus leading to a diagnosis of invasive mole rather than choriocarcinoma. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2013.

The aim of this study was to analyze conjoined twins in terms of antenatal, delivery and postnatal aspects.A retrospective descriptive analysis of prenatally diagnosed conjoined twins. Prenatal ultrasound and echocardiography, delivery details, postnatal follow-up, surgical separation and post mortem data were reviewed. The twins were classified according to the type of fusion between fetal structures. The following data were analyzed: ultrasound and echocardiographic findings, antenatal lethality and possibility of surgical separation, delivery details and survival rates.Forty cases of conjoined twins were included in the study. There were 72.5% cases of thoracophagus, 12.5% of paraphagus, 7.5% of omphalo-ischiophagus, 5.0% of omphalophagus, and 2.5% of cephalophagus. Judicial termination of pregnancy was requested in 58.8% of the cases. Cesarean section was performed in all cases in which pregnancy was not terminated. The mean gestational age at delivery was 35 weeks; all twins were live births with a mean birth weight of 3,860 g and 88% died postnatally. Ten percent of the live borns were submitted to surgical separation with a 60% survival rate. The total survival rate was 7.5% and postnatal survival was 12%. Antenatal evaluation of lethality and possibility of surgical separation were precise. There were no maternal complications related to delivery.Conjoined twins present a dismal prognosis mainly related to the complex cardiac fusion present in the majority of cases with thoracic sharing. At referring centers, prenatal ultrasound and echocardiographic evaluation accurately delineate fetal prognosis and the possibility of postnatal surgical separation.

Myoepithelial cells are important components of salivary gland structure, aiding the expulsion of saliva from acinar lobules. The aim was to evaluate the expression of smooth muscle actin (SMA), calponin, caldesmon, CD10, CD29, S100 protein, glial fibrillary acidic protein (GFAP) and p63 in myoepithelial cells during salivary gland morphogenesis to understand the maturation process of these cells and their possible use in the diagnosis of salivary gland lesions.Major and minor human salivary glands at various stages of development, derived from fetuses at 8-26 weeks of gestation, were studied immunohistochemically. Fully developed salivary glands were used as controls. The protein p63 was present in all stages of salivary gland morphogenesis from initial bud to terminal bud stage. CD29, S100 and calponin were detected increasingly as salivary gland structure matured and in fully developed salivary gland. Proteins GFAP, CD10 and caldesmon were not observed in myoepithelial cells of salivary glands.The proteins SMA, calponin, CD29, S100 and p63, which are present from the earliest stages of salivary gland maturation, are valuable myoepithelial markers but, although very specific, are not exclusive markers for this cell type.

Objective To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and β-hCG and to assess its predictive value. Design Prospective study. Setting Tertiary care university hospital. Patient(s) Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. Intervention(s) Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. Main Outcome Measure(s) The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and β-hCG serum concentrations on the day of surgery. Result(s) An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and β-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. Conclusion(s) Maternal serum VEGF and β-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall.

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonography (TVS) in women with ampullary pregnancy. Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 85 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity had been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Lymphangioma is a rare benign tumor characterized by proliferating lymph vessels and composed of large cyst spaces with endothelium-lined channels of varying dimensions. The incidence of lymphangioma is approximately one in 6000 pregnancies. Less than 1% of lymphangiomas are purely mediastinal. The great majority of cases are of cystic lymphangioma, but very rarely there is a mixed lesion consisting of multiple cysts of dilated capillary and lymph vessels. We report a case of posterior mediastinal lymphangioma diagnosed at 28 weeks' gestation, in which three-dimensional ultrasonography was helpful in determining the precise location of the tumor. A Cesarean section was performed at 39 weeks and the tumor was resected on the 5(th) day postdelivery; histological examination revealed a mixed cystic lymphangioma.

BACKGROUND: Predictive factors of damage to the Fallopian tube may guide the treatment for patients with tubal pregnancy. The aim of this study was to assess the predictive value of the following parameters: gestational age, serum b-hCG concentrations and ultrasound findings. METHODS: A total of 105 patients with ampullary pregnancy undergoing salpingectomy were analysed. Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer and stage III in the case of complete tubal wall infiltration. We correlated the depth of trophoblastic infiltration into the tubal wall with gestational age, b-hCG concentration on the day of surgery and the type and size of the ectopic mass upon ultrasound. RESULTS: No association was observed between the depth of trophoblastic invasion and gestational age (P = 0.53) or tubal mass diameter (P = 0.43). Trophoblastic invasion was, however, associated with b-hCG concentration (P < 0.001) and with the type of ultrasonographic image (P = 0.001). b-hCG levels of 2400 mIU/ml showed 82.8% sensitivity and 85.5% specificity for stage I, and levels of 5990 mIU/ml showed 82.6% sensitivity and 74.6% specificity for stage III. CONCLUSIONS: Depth of trophoblastic penetration into the tubal wall of the ampullary region of Fallopian tube is correlated with b-hCG concentration and the type of ultrasonographic image; serum b-hCG is the best predictor of the depth of penetration.

The classic sonographic appearance of the kidneys in fetuses with autosomal recessive polycystic kidney disease (ARPKD) has been well described. We report a case of enlarged kidneys with pyramidal hyperechogenicity quite similar to medullary nephrocalcinosis found in a fetus at 34 weeks' gestation. At 39 weeks, a female neonate was delivered and died after 22 h due to pulmonary insufficiency secondary to severe oligohydramnios. On pathological analysis, the gross and microscopic findings were typical of ARPKD with diffuse dilatation of tubules throughout. The fetal renal lobulation was prominent and on section, the pyramids were delineated within each lobule, accounting for the clear image of the pyramids observed on sonography.

Previous studies had shown a correlation between infection with the human adeno-associated virus (AAV) and spontaneous abortion in early pregnancy. Furthermore, AAV DNA had been detected in cells of the human trophoblast lines, Jeg-3, JAr, and BeWo, in cells of the human amnion line, FL, and in trophoblasts from amnion fluids. Infectious AAV virions could be isolated from amnion fluids. To further analyse AAV infection during pregnancy, we tested material from Gestational Trophoblastic Disease for the presence of AAV DNA. With 63 tissue samples from patients from Brazil, including 49 hydatiform moles and 14 choriocarcinomas, nested PCR was performed to detect the presence of AAV DNA. In addition, 15 samples from spontaneous abortions were analysed. AAV DNA was found in 43 samples (28/49 hydatiform moles, 4/14 choriocarcinomas, 11/15 miscarriage material). These findings confirm AAV infection of embryo-derived tissue in humans and further suggest a role of AAV in miscarriage and trophoblastic disease.

We have studied two groups of pregnant women 939 adults and 246 adolescents whose first prenatal visit was prior to 14 weeks of gestation. These women belong to a low socioeconomic group attending public obstetric outpatient services of the National Health System (NHS) of Santiago-Chile and the Adolescent Reproductive Medicine Center Medical School University of Chile. The seroprevalence of Cytomegalovirus (CMV) infection was established in the first trimester through an enzymelinked immunosorbent assay test being quite high in both groups: 95% in adults and 89.9% in adolescents. All seronegative women were followed prospectively to document the occurrence of primary CMV infection during pregnancy and the presence of congenital infection in their newborns. We found that 4 of 25 seronegative adolescents acquired CMV during pregnancy as compared to 1 of 47 adult women. Of the babies born to the 4 adolescent mothers two had congenital infections one was not evaluated and the remaining baby had neither clinical nor laboratory findings consistent with CMV as was the case with the child born to the adult mother with primary CMV infection. (excerpt)

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, neonatally lethal developmental disorder of the lung with defining histologic abnormalities typically associated with multiple congenital anomalies (MCA). Using array CGH analysis, we have identified six overlapping microdeletions encompassing the FOX transcription factor gene cluster in chromosome 16q24.1q24.2 in patients with ACD/MPV and MCA. Subsequently, we have identified four different heterozygous mutations (frameshift, nonsense, and no-stop) in the candidate FOXF1 gene in unrelated patients with sporadic ACD/MPV and MCA. Custom-designed, high-resolution microarray analysis of additional ACD/MPV samples revealed one microdeletion harboring FOXF1 and two distinct microdeletions upstream of FOXF1, implicating a position effect. DNA sequence analysis revealed that in six of nine deletions, both breakpoints occurred in the portions of Alu elements showing eight to 43 base pairs of perfect microhomology, suggesting replication error Microhomology-Mediated Break-Induced Replication (MMBIR)/Fork Stalling and Template Switching (FoSTeS) as a mechanism of their formation. In contrast to the association of point mutations in FOXF1 with bowel malrotation, microdeletions of FOXF1 were associated with hypoplastic left heart syndrome and gastrointestinal atresias, probably due to haploinsufficiency for the neighboring FOXC2 and FOXL1 genes. These differences reveal the phenotypic consequences of gene alterations in cis.

Summary Introduction: Fetal thrombotic vasculopathy is a recently described placental alteration with varying degrees of involvement and often associated with adverse perinatal outcomes. The diagnosis is made histologically and therefore is postnatal, which makes it a challenge in clinical practice. Method: Case report and review of literature on the subject. Results: The present case refers to a pregnant woman presenting fetal growth restriction, with poor obstetrical past, and sent late to our service. Even with weekly assessments of fetal vitality (fetal biophysical profile and Doppler velocimetry) and prenatal care, the patient progressed with fetal death at 36 weeks and 1 day. There was no association with inherited and acquired thrombophilia. Pathological examination of the placenta revealed fetal thrombotic vasculopathy. Conclusion: The fetal thrombotic vasculopathy may be associated with adverse perinatal outcomes including fetal death, but much remains to be studied regarding its pathogenesis. Diagnosis during pregnancy is not possible and there is still no proven treatment for this condition. Future studies are needed so that strategies can be developed to minimize the impact of fetal thrombotic vasculopathy.

In order to determination if an interdependence exists between the well-known maturational disturbances in placentas of diabetics and the quality of metabolic adjustment, a morphometric study covering 7,500 terminal villi of 50 placentas was performed. The diabetic mothers were divided into two groups according to satisfactory or unsatisfactory blood glucose values. Significant differences in placental retardation were observed between both diabetic groups and a normal control group. Although outcomes did not differ greatly between the two diabetic groups, macrosomia and the ratio of malformations in the newborns correlate with unsatisfactory metabolic management. Small-for-date babies, the need for early termination of pregnancy as well as pre-eclampsia are related to the severity and duration of the disease.