Pre-eclampsia is associated with complement pathway activation in the maternal and fetal circulation, and placental tissue.

OBJECTIVES: Pre-eclampsia (PE) is a leading cause of obstetric morbidity, with no definitive therapy other than delivery. We aimed to compare complement markers in maternal and fetal circulation, and placental tissue, between women with PE and healthy pregnant controls. STUDY DESIGN: Maternal and umbilical cord blood was tested for iC3b, C3, C4, properdin, Ba and C5b-9, and placental tissue for C3d, C4d, C9 and C1q, from women with PE (n = 34) and healthy pregnant controls (n = 33). Maternal properdin and Ba tests were repeated in a separate validation cohort (PE n = 35; healthy pregnant controls n = 35). MAIN OUTCOME MEASURES: Complement concentrations in maternal and umbilical cord blood, and placental immunohistochemical complement deposition. RESULTS: Women with PE had significantly lower concentrations of properdin (mean: 4828 vs 6877 ng/ml, p < 0.001) and C4 (mean: 0.20 vs 0.31 g/l, p < 0.001), and higher Ba (median: 150 vs 113 ng/ml, p = 0.012), compared to controls. After controlling for gestational age at blood draw, average properdin concentration was 1945 ng/ml lower in PE vs controls (95 % CI: 1487-2402, p < 0.001). Of the cord blood markers assessed, only Ba differed significantly between PE and controls (median: 337 vs 233 ng/ml, p = 0.004). C4d staining of the syncytiotrophoblast membrane was increased in PE vs controls (median immunoreactivity score 3 vs 0, p < 0.001). Maternal properdin and C4 were significantly negatively correlated with placental C4d staining. CONCLUSIONS: Our data confirm excessive placental complement deposition associated with significant concurrent changes in maternal and fetal circulating complement biomarkers in PE. Inhibition of complement activation is a potential therapeutic target.

SARS-COV2 placentitis and pregnancy outcome: A multicentre experience during the Alpha and early Delta waves of coronavirus pandemic in England.

Background: Pregnant women with SARS-CoV-2 infection experience higher rates of stillbirth and preterm birth. A unique pattern of chronic histiocytic intervillositis (CHI) and/or massive perivillous fibrin deposition (MPFD) has emerged, coined as SARS-CoV-2 placentitis. Methods: The aim of this study was to describe a cohort of placentas diagnosed with SARS-CoV-2 placentitis during October 2020-March 2021. Cases with a histological diagnosis of SARS-CoV-2 placentitis and confirmatory immunohistochemistry were reported. Maternal demographic data, pregnancy outcomes and placental findings were collected. Findings: 59 mothers delivered 61 infants with SARS-CoV-2 placentitis. The gestational age ranged from 19 to 41 weeks with most cases (78.6%) being third trimester. 30 infants (49.1%) were stillborn or late miscarriages. Obese mothers had higher rates of pregnancy loss when compared with those with a BMI <30 [67% (10/15) versus 41% (14/34)]. 47/59 (79.7%) mothers had a positive SARS-CoV-2 PCR test either at the time of labour or in the months before, of which 12 (25.5%) were reported to be asymptomatic. Ten reported only CHI, two cases showed MPFD only and in 48 placentas both CHI and MPFD was described. Interpretation: SARS-CoV2 placentitis is a distinct entity associated with increased risk of pregnancy loss, particularly in the third trimester. Women can be completely asymptomatic and still experience severe placentitis. Unlike 'classical' MPFD, placentas with SARS-CoV-2 are generally normal in size with adequate fetoplacental weight ratios. Further work should establish the significance of the timing of maternal SARS-CoV-2 infection and placentitis, the significance of SARS-CoV2 variants, and rates of vertical transmission associated with this pattern of placental inflammation. Funding: There was not funding associated with this study.

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury.

CONTEXT.­: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.­: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.­: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.­: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.­: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Epigenetic Dysregulation of Trophoblastic Gene Expression in Gestational Trophoblastic Disease.

Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these subsets shared focal adhesion and actin cytoskeleton pathways in moles and choriocarcinoma. In moles, cell cycle and differentiation regulatory pathways, essential for trophoblast/placental development, were enriched. In choriocarcinoma cells, hormone biosynthetic, extracellular matrix-related, hypoxic gene regulatory, and differentiation-related signaling pathways were enriched. In moles, we found slight upregulation of DNMT3B protein, a developmentally important de novo DNA methylase, which is strongly overexpressed in choriocarcinoma cells that may partly be responsible for the large DNA methylation differences. Our findings provide new insights into the shared and disparate molecular pathways of disease in GTDs and may help in designing new diagnostic and therapeutic tools.

Proteomic identification of Placental Protein 1 (PP1), PP8, and PP22 and characterization of their placental expression in healthy pregnancies and in preeclampsia.

INTRODUCTION: Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications. METHODS: We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring. RESULTS: PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia. DISCUSSION: PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.

[Recommendation for the pathological examination of the placenta: practical aspects and indications. Methodological recommendation]. / A placenta vizsgálatának ajánlott módszertana és a vizsgálat javallatai. Módszertani javaslat.

Introduction: According to the Hungarian law, placental examination is not mandatory, although it is known from the international practice that it can give valuable information in cases of stillbirth or in conditions, where the neonate has difficulty in the postnatal adaptation. Aim: It can be useful in the early detection of diseases, which otherwise would have gone undetected until late in life. This article is unique in Hungary, as no similar guideline exists in Hungarian language. Method: The recommendation of the Royal College of Pathologists (United Kingdom) determines those conditions where essential information can be obtained from the placental examination in not normal pregnancies. It serves as a useful guide in the medical practice. The journal titled "Placenta", first published in 1980 with impact factor above two, just underlines this statement. Results: In this article, the authors present the recent guideline of the RCPath and finish with the presentation of established clinicopathological association that might help clinicians to get the most valuable information from placental examination. Conclusion: The present article aims to summarise updated recommendations and present clinicopathological correlations. Orv Hetil. 2019; 160(48): 1894-1903.

Proteomic identification of membrane-associated placental protein 4 (MP4) as perlecan and characterization of its placental expression in normal and pathologic pregnancies.

BACKGROUND: More than 50 human placental proteins were isolated and physico-chemically characterized in the 70-80s by Hans Bohn and co-workers. Many of these proteins turned to have important role in placental functions and diagnostic significance in pregnancy complications. Among these proteins was membrane-associated placental protein 4 (MP4), for which identity or function has not been identified yet. Our aim was to analyze the sequence and placental expression of this protein in normal and complicated pregnancies including miscarriage, preeclampsia and HELLP syndrome. METHODS: Lyophilized MP4 protein and frozen healthy placental tissue were analyzed using HPLC-MS/MS. Placental tissue samples were obtained from women with elective termination of pregnancy (first trimester controls, n = 31), early pregnancy loss (EPL) (n = 13), early preeclampsia without HELLP syndrome (n = 7) and with HELLP syndrome (n = 8), late preeclampsia (n = 8), third trimester early controls (n = 5) and third trimester late controls (n = 9). Tissue microarrays were constructed from paraffin-embedded placentas (n = 81). Slides were immunostained with monoclonal perlecan antibody and evaluated using light microscopy and virtual microscopy. Perlecan was also analyzed for its expression in placentas from normal pregnancies using microarray data. RESULTS: Mass spectrometry-based proteomics of MP4 resulted in the identification of basement membrane-specific heparan sulfate proteoglycan core protein also known as perlecan. Immunohistochemistry showed cytoplasmic perlecan localization in syncytiotrophoblast and cytotrophoblasts of the villi. Perlecan immunoscore decreased with gestational age in the placenta. Perlecan immunoscores were higher in EPL compared to controls. Perlecan immunoscores were higher in early preeclampsia without and with HELLP syndrome and lower in late preeclampsia than in respective controls. Among patients with preeclampsia, placental perlecan expression positively correlated with maternal vascular malperfusion and negatively correlated with placental weight. CONCLUSION: Our findings suggest that an increased placental perlecan expression may be associated with hypoxic ischaemic injury of the placenta in miscarriages and in early preeclampsia with or without HELLP syndrome.

Increased placental expression of Placental Protein 5 (PP5) / Tissue Factor Pathway Inhibitor-2 (TFPI-2) in women with preeclampsia and HELLP syndrome: Relevance to impaired trophoblast invasion?

INTRODUCTION: Placental Protein 5 (PP5)/Tissue Factor Pathway Inhibitor-2 (TFPI-2) is an extracellular matrix-associated protein mainly expressed by the syncytiotrophoblast that may regulate trophoblast invasion. Our aim was to study placental PP5/TFPI-2 expression and its relation to placental pathology in various forms of preeclampsia and HELLP syndrome. METHODS: Placental and maternal blood specimens were collected at the time of delivery from the same women in the following groups: 1) early controls; 2) early preeclampsia; 3) early preeclampsia with HELLP syndrome; 4) late controls; and 5) late preeclampsia. After histopathological examination, placental specimens were immunostained with polyclonal anti-PP5/TFPI-2 antibody on Western blot and tissue microarray immunohistochemistry. Placental PP5/TFPI-2 immunoscores were assessed manually and with a semi-automated method. Maternal sera were immunoassayed for PP5/TFPI-2. RESULTS: PP5/TFPI-2 was localized to the cytoplasm of syncytiotrophoblast. Manual and semi-automated PP5/TFPI-2 immunoscores were higher in early preeclampsia with or without HELLP syndrome but not in late preeclampsia than in respective controls. In patients with preeclampsia, the correlation of placental PP5/TFPI-2 expression with maternal vascular malperfusion score of the placenta was positive while it was negative with birthweight and placental weight. Maternal serum PP5/TFPI-2 concentration was higher in early preeclampsia and it tended to be higher in early preeclampsia with HELLP syndrome than in early controls. DISCUSSION: Our findings suggest that an increased placental PP5/TFPI-2 expression may be associated with abnormal placentation in early preeclampsia, with or without HELLP syndrome.

Pathophysiological Mechanism of Extravasation via Umbilical Venous Catheters.

A rare complication of umbilical venous catheter (UVC) insertion is the extravasation of the infusate into the peritoneal cavity. We report 3 cases of abdominal extravasation of parenteral nutrition (PN) fluid via UVCs. Two of these cases presented as "acute abdomen" which were assumed to be necrotizing enterocolitis clinically; however, during postmortem, PN ascites and liver necrosis were found. A further case is described in an infant with congenital diaphragmatic hernia. While we were unable to ascertain direct vessel perforation by the catheter in any of these cases, based on pathological and histological examination, the proposed mechanism of PN fluid extravasation is leakage through microinjuries of liver vessel walls and necrotic parenchyma. PN extravasation should be considered as a differential diagnosis of acute abdomen when PN is infused via an UVC presumably as PN may have a direct irritant effect on the peritoneum.

Hippocampal Formation Maldevelopment and Sudden Unexpected Death across the Pediatric Age Spectrum.

Sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) are defined as sudden death in a child remaining unexplained despite autopsy and death scene investigation. They are distinguished from each other by age criteria, i.e. with SIDS under 1 year and SUDC over 1 year. Our separate studies of SIDS and SUDC provide evidence of shared hippocampal abnormalities, specifically focal dentate bilamination, a lesion classically associated with temporal lobe epilepsy, across the 2 groups. In this study, we characterized the clinicopathologic features in a retrospective case series of 32 children with sudden death and hippocampal formation (HF) maldevelopment. The greatest frequency of deaths was between 3 weeks and 3 years (81%, 26/32). Dentate anomalies were found across the pediatric age spectrum, supporting a common vulnerability that defies the 1-year age cutoff between SIDS and SUDC. Twelve cases (38%) had seizures, including 7 only with febrile seizures. Subicular anomalies were found in cases over 1 year of age and were associated with increased risk of febrile seizures. Sudden death associated with HF maldevelopment reflects a complex interaction of intrinsic and extrinsic factors that lead to death at different pediatric ages, and may be analogous to sudden unexplained death in epilepsy.

Elevated brain weight/liver weight ratio in normal body weight centile term perinatal deaths: an indicator of terminal intrauterine malnourishment.

A proportion of antepartum/intrapartum intrauterine deaths (IUDs) with normal or elevated body weight (BW) centile also show an elevated brain weight/liver weight (BLR) ratio. We postulate that this may be an indication of intrauterine malnourishment/incipient intrauterine growth restriction (IUGR), which may have a bearing on the cause of death. Searching our departmental postmortem database, we identified 331 IUD/intrapartum deaths (254; 77%) or early neonatal deaths (77; 23%), ≥37/40 weeks gestation in a 4-year period. The customized BW centile, BLR, brain weight/thymus weight ratio (BTR), fetus weight/placenta weight ratio (FPR), and maternal body mass index were calculated. A BLR >4.0 and a BTR >60 were regarded as abnormal. Of the 331 cases, the BLR was >4.0 in 71 (21.4%). Nineteen (26.7%) of the 71 had a BW above the 25th centile, and these were all IUDs. Eight deaths were explained. In the 11 unexplained deaths, the BTR was raised in 5 and FPR was elevated in 7. Three of these 11 mothers had impaired glucose tolerance, and 7 were overweight or obese. In the absence of a definitive cause, a raised BLR in an IUD with a normal BW centile is likely to indicate nutritional impairment/incipient IUGR. The majority of these deaths are associated with maternal obesity, with or without impaired glucose tolerance. Recognition of features of IUGR in IUDs of normal BW may help us understand the death. In these cases, placental growth may be insufficient to support a macrosomic fetus, leading to late nutritional impairment and death.

Implementation and experience of an alternative QF-PCR and MLPA diagnostic strategy to detect chromosomal abnormalities in fetal and neonatal pathology samples.

Chromosomal abnormalities are a significant cause of pregnancy loss. Solid tissue fetal and neonatal pathology samples are routinely examined by karyotype analysis after cell culture. However, there is a high failure rate, and this approach is expensive and labor intensive. We have therefore evaluated a new molecular strategy involving quantitative fluorescent polymerase chain reaction (QF-PCR) and subtelomere multiplex ligation-dependent probe amplification (MLPA) analysis. A retrospective audit showed that less than 4% of abnormal cases may not be detected by this molecular strategy. We validated this strategy in parallel with cytogenetic analysis on 110 patient samples, which included cases of fetal loss, still birth, neonatal death, termination of pregnancy, recurrent miscarriage, and sudden unexpected death in infancy. This validation showed that 55 of the 57 samples that gave a result for both strategies were concordant. During the 1st year of diagnostic testing, we analyzed 382 samples by the molecular strategy. A 16% abnormality rate was observed. These included trisomies 13, 18, 21, monosomy X, and triploidy detected by QF-PCR (77%), and 23% were other trisomies and subtelomere imbalances detected by MLPA. This strategy had a 92% success rate in contrast to the 20%-30% failure rate observed with cell culture and cytogenetic analysis. We conclude that QF-PCR and subtelomere MLPA is a suitable strategy for analysis of the majority of fetal and neonatal pathology samples, with many advantages over conventional cytogenetic analysis.

Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome.

Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia and HELLP syndrome.

Prenatally diagnosed fetal brain injuries with known antenatal etiologies.

Periventricular leukomalacia of pre- or postnatal onset is responsible for severe neurological and intellectual impairment and cerebral palsy later in life. The etiology is multifactorial, involving hypoxic-ischemic insults of various origin. The disorder is characterized by multiple necrotic foci of the white matter found most frequently adjacent to the lateral ventricles. In the past, intrapartum factors were thought to be the major cause of neonatal brain damage, but recent investigations highlighted the role of antenatal risk factors. We present 4 cases of antenatally diagnosed brain injury with known and unusual etiology.

Trisomy 20 mosaicism and nonmosaic trisomy 20: a report of 2 cases.

BACKGROUND: Together with chromosome 19, chromosome 20 belongs to group F, the group of small metacentric chromosomes. Trisomy 20 mosaicism is one of the most frequent chromosomal mosaicisms, representing approximately 16% of prenatally diagnosed cases. In nonmosaic trisomy 20, the usual findings are severe and manifold. Only 3 cases in the literature involved fetuses surviving past the first trimester. CASES: In case 1, a 42-year-old woman presented in her sixth pregnancy; she had had 4 vaginal deliveries of term infants and a miscarriage. Both her familial and personal genetic histories were unremarkable. Genetic amniocentesis was performed in the 18th gestational week for advanced maternal age. Sample analysis revealed a normal, male karyotype in 27 mitoses, while 4 were trisomy 20 (46,XY [27]/47,XY, +20 [4]). In the 37th gestational week a live, immature, male infant weighing 1,730 g was delivered. Chromosomal investigation of the newborn's blood sample did not reveal trisomy 20 but a normal male karyotype. In case 2, a healthy 37-year-old nullipara underwent amniocentesis at the 18th week of pregnancy for advanced maternal age. Amniotic fluid cell karyotype revealed trisomy 20 (47,XX, +20). Ultrasonography performed simultaneously with genetic amniocentesis showed slightly shortened fetal long bones, detectable narrowing of the cranium in the region of the frontal bone, lateral ventricles of 10 mm in width bilaterally, echogenic bowel and polyhydramnios. Abortion was induced in the 23rd week of pregnancy, and a 490-g female fetus was delivered. CONCLUSION: Based on these 2 well-documented, prenatally diagnosed cases, as far as genetic counseling is concerned, nonmosaic trisomy 20 is much less challenging than its mosaic form since the prognosis is uniformly poor in the former.

Human brain of preterm infants after hypoxic-ischaemic injuries: no evidence of a substantial role for apoptosis by using a fine-tuned ultrasound-guided neuropathological analysis.

Preterm birth may be associated with hypoxic-ischaemic encephalopathy (HIE) showing a well recognised number of patterns, including neuronal karyorrhexis/eosinophilia mostly at the diencephalon and brain stem and leukomalacia at the periventricular white matter. To investigate whether programmed cell death or apoptosis plays a role in HIE, we examined human brains of preterm infants. Brain tissue samples from 12 consecutive infants (24-34 weeks of gestation) were available at post-mortem examination (1998-2000) after approval of the Ethics Committee. Two tissue sections were stereologically localised after brain fixation, slice preparation, and comparison with ultrasound imaging. We studied the periventricular white matter and the corresponding cortical region in each brain. Conventional histological stains were used. In addition, apoptosis was detected using a neuronal-specific terminal deoxynucleotidyl transferase-mediated nick end-labelling (TUNEL) method (NeuroTACS). A semiquantitative evaluation was performed to compare regions close to brain lesions with injury-free areas. Neuronal apoptosis was low in both cortical and in periventricular regions. No glial apoptosis was detected. Apoptosis in neurones was, however, detected in preterm brains with bacterial or mycotic infection. These results point out to the ambiguity of the TUNEL-reactive neurons in the diseased premature infants using fine-tuned ultrasound-guided neuropathological analysis, support the probable coexistence of neuronal TUNEL-reactivity and infection, and suggest that the association between apoptosis and HIE should overall be viewed with more caution.

[Fetal examination of first trimester abortions]. / Az elsó trimesterbeli vetélések morfológiai háttere.

INTRODUCTION: Rather few papers are about first trimesters pathology. The reason of this roots in the technical difficulties. The first trimesters pathology can not be separated from prenatal diagnostics. OBJECTIVES: The authors summarized the molecular basis of embryology, malformations, and published cases that had been diagnosed prenatally. MATERIALS AND METHODS: In the I. Department of Obstetrics and Gynecology, Semmelweis University in Budapest between 1995. and 2000. altogether sixty embryos 70 gms or smaller were examined. RESULTS: Malformations included neural tube defects, disorders of twinning, body stalk defect, chromosome aberrations, hydrops, omphalocele and gastroschisis. CONCLUSIONS: Examination of early embryos may discover many results on the fields of prenatal diagnosis and the pathomechanism of developmental abnormalities.

[Heterotaxy syndrome, analysis of 13 cases and review of the literature]. / Heterotaxia syndroma: 13 foetopathologiai eset elemzése és irodalmi áttekintés.

INTRODUCTION: Heterotaxy syndrome (Ivemark syndrome, or asplenia-polysplenia syndrome) is a heterogeneous group of disease with disturbed body symmetry and malposition of internal organs. Heterotaxy syndrome is caused by the disturbance of the left/right axis in the early embryonic period. AIM OF THE STUDY: The most frequency of heterotaxy syndrome's concomitant anomalies during a five year period in own fetopathology material. MATERIALS AND METHODS: Data of fetopathologic examination of 13 fetuses suffering from prenatally diagnosed heterotaxy syndrome. RESULTS: Situs ambiguus was detected in 9 cases out of 13. In the remaining 4 cases situs inversus totalis was diagnosed. The most frequent and important associated malformation included congenital heart disease was AV channel (10/13) and great vessel anomaly (10/13). CONCLUSION: In cases with prenatally detected complex cardiac anomalies (especially AV channel cases) heterotaxy anomaly must be taken into consideration, with main consequences in prenatal counselling.