Significant association between circumvallate placenta, placental abruption and acute chorioamnionitis in preterm birth:A 23-year retrospective cohort study

Aim:circumvallate placenta, placental abruption and acute chorioamnionitis separately are associated with unfavourable clinical outcomes. We aimed to determine the prevalence and define whether an association exists between the three abnormalities. Methods: 16,042 placenta pathology reports between 1997 and 2020 from a tertiary care centre in the Netherlands were retrospectively analysed. For the statistical analysis, the chi-square test and bootstrapping were used to evaluate an association. Results: In our cohort the prevalence of circumvallate placenta is 2.2 %, placental abruption cases 4.0 % and acute chorioamnionitis 20.6 %. We observed a statistically significant association between all three placental abnormalities: circumvallate placenta, placental abruption and acute chorioamnionitis. In addition, there was also an association between circumvallate placenta and acute chorioamnionitis. Conclusion: Our results show that combined presence of circumvallate placenta, placental abruption and acute chorioamnionitis are associated in preterm birth (p = 0.001). A remarkable finding is that the combination of all three abnormalities (circumvallate placenta, placental abruption and acute chorioamnionitis) was not observed in term pregnancies &gt;37 weeks.</p

Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68+ cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance. The pathophysiologic mechanism of CHI is unclear, but it appears to be immunologically driven. The aim of this study was to obtain a better understanding of the phenotype of the cellular infiltrate in CHI.Method: We used imaging mass cytometry to achieve in-depth visualization of the intervillous maternal immune cells and investigated their spatial orientation in situ in relation to the fetal syncytiotrophoblast.Results: We found three phenotypically distinct CD68+HLA-DR+CD38+ cell clusters that were unique for CHI. Additionally, syncytiotrophoblast cells in the vicinity of these CD68+HLA-DR+CD38+ cells showed decreased expression of the immunosuppressive enzyme CD39.Discussion: The current results provide novel insight into the phenotype of CD68+ cells in CHI. The identification of unique CD68+ cell clusters will allow more detailed analysis of their function and could result in novel therapeutic targets for CHI.Research into fetal development and medicin

Cardiovascular causes of sudden unexpected death in children and adolescents (0–17 years) : A nationwide autopsy study in the Netherlands

Background: Little is known about the causes of unexpected death in minors (0–17 years). In young adults an important cause is cardiovascular disease, with primary arrhythmogenic disorders, atherosclerotic events, cardiomyopathies and myocarditis as main contributors. The aim of this autopsy study was to determine the contribution of cardiovascular disease to unexpected death in minors. Methods and results: In the Netherlands, systematic investigation of all cases of unexplained death in minors was compulsory in a nationwide governmental project during a 15-month period. Autopsies were performed according to a standardised protocol (autopsy rate 85%). A cardiovascular cause of death was found in 13/56 cases (23%). In the group <1 year, the main cardiovascular causes were various congenital defects (n = 3) and myocarditis (n = 2). In the 1–9 year group, no cardiovascular causes were found. In the 10–14 year group, hypertrophic cardiomyopathy (n = 1) and ruptured ascending aortic aneurysm (n = 1) were among the observed cardiovascular causes. In 14/56 (25%) cases autopsy revealed no structural abnormalities that could explain the sudden death, mostly in the group <1 year. Conclusion: This national cohort with a high autopsy rate reveals a high incidence (23%) of cardiovascular diseases as the pathological substrate of sudden unexpected death in children. Another high percentage of minors (25%) showed no structural abnormalities, with the possibility of a genetic arrhythmia. These findings underline the importance of systematic autopsy in sudden death in minors, with implications for cardiogenetic screening of relatives

Placental Histology After Minor Trauma in Pregnancy : A Pilot Study

Objective: Trauma in pregnancy may cause placental abruption. Consequences of moderate placental injury on neurodevelopment are unknown. The aim was to evaluate placental histology after maternal trauma. Methods: A prospective study was conducted at 2 tertiary medical centers in the Netherlands. Placentas from women exposed to maternal trauma ≥ 20 weeks’ gestational age were histologically examined. Neurological follow-up of the infants was performed at 1 year of age by means of Alberta Infant Motor Scale. Histological findings were compared to placentas from pregnancies without trauma. Principal Results: Thirteen placentas were investigated in the trauma group. The control group consisted of 15 placentas. Placental pathology was seen more often in the trauma cases (11 of the 13) than in the controls (6 of the 15), P =.024. Neurological follow-up was normal. Conclusions: In this small population, majority of the placentas showed pathology after minor trauma in pregnancy without consequences for neurodevelopment at 1 year

Towards standardized criteria for diagnosing chronic intervillositis of unknown etiology : A systematic review

Chronic intervillositis of unknown etiology (CIUE) is a poorly understood, relatively rare condition characterized histologically by the intervillous infiltration of mononuclear cells in the placenta. Clinically, CIUE is associated with poor pregnancy outcome (e.g., impaired fetal growth, preterm birth, fetal death) and high risk of recurrence in subsequent pregnancies. Because CIUE is not defined consistently, it is essential to clearly define this condition. We therefore review the published definitions of CIUE. In addition, we provide an overview of the reviewed histopathological and maternal characteristics, obstetric features, and pregnancy outcomes. Medical publication databases were searched for articles published through February 2017. Eighteen studies were included in our systematic review. The sole inclusion criterion used in all studies was the presence of intervillous infiltrates. Overall, CIUE was characterized by adverse pregnancy outcome. Miscarriage occurred in 24% of cases, with approximately half of these miscarriages defined as late. Impaired growth was commonly observed, 32.4% of pregnancies reached term, and the live birth rate was 54.9%. The high recurrence rate (25.1%) of the intervillous infiltrates in subsequent pregnancies underscores the clinical relevance of CIUE, the need for increased awareness among pathologists and clinicians, and the need for further research. Criteria for the diagnosis of CIUE are proposed and a Delphi study could be used to resolve any controversy regarding these criteria. Future studies should be designed to characterize the full clinical spectrum of CIUE

Clinical outcomes in chronic intervillositis of unknown etiology

Introduction: Chronic intervillositis of unknown etiology (CIUE) is a histopathological lesion of the placenta that is frequently accompanied by unfavourable pregnancy outcomes, e.g. miscarriage, fetal growth restriction (FGR) and intrauterine fetal death. Earlier described case series and cohorts have been based on diverse diagnostic criteria of CIUE. To improve our understanding of clinical outcomes associated with CIUE, we report the obstetric and perinatal outcomes in a cohort based on the recently described diagnostic criteria. Methods: CIUE is defined as an infiltrate occupying 5% or more of the intervillous space with approximately 80% of mononuclear cells positive for CD68 in the absence of an infection. Thirty-eight cases were included. Also previous and subsequent pregnancies were described. Results: Pregnancies accompanied by CIUE frequently resulted in FGR (51.6%) and pre-term birth (55.3%). Twenty-nine out of 38 pregnancies (76.3%) with CIUE resulted in a living baby. Women with CIUE frequently have had a miscarriage (16/38; 42%). Four-teen subsequent pregnancies in 8 women resulted in 2 miscarriages, 2 terminations of pregnancy for FGR, 1 early neonatal death and 9 living babies (9/14; 64.3%). Histopathologically confirmed CIUE recurred in 5 out of 10 subsequent pregnancies. Two pregnancies with recurrent CIUE were terminated, one pregnancy ended in a late miscarriage and another resulted in term birth complicated by FGR. Recurrent CIUE can also be accompanied by an uncomplicated pregnancy (1/5; 20%). Conclusion: This study provides additional insight into the clinical phenotype of CIUE and emphasises the need for further research to understand the pathophysiology behind different pregnancy outcomes in CIUE

In vivo fluorescence kinetics and localisation of aluminium phthalocyanine disulphonate in an autologous tumour model

Sulphonated phthalocyanines are studied as photosensitisers for photodynamic therapy of cancer. Their strong fluorescence and tumour-localising properties make them also potentially useful for detection of cancer by fluorescence. For this purpose, we have studied the fluorescence kinetics and localisation of aluminium phthalocyanine disulphonate (AlPcS2) in 4-nitroquinoline 1-oxide (4NQO)-induced dysplasia and invasive cancer of the oral mucosa of the hard palate in Wistar albino rats. Twenty-two rats were divided into six groups. Five groups were subjected to a 4NQO application period of 8, 12, 16, 20 or 26 weeks and one was a control group. The dysplasia varied from slight to severe and was correlated with the duration of the application period. All animals received a dose of 1 μmol kg-1 AlPcS2 i.v. Fluorescence images were recorded via a specially designed 'palatoscope' with excitation at 460 ± 20 nm for autofluorescence, 610 ± 15 nm for AlPcS2 fluorescence and detection of emission at 675 ± 15 nm. After subtraction of the two images the specific AlPcS2 fluorescence remained. AlPcS2-mediated fluorescence increased significantly when the severity of dysplasia increased (P &lt; 0.04). Also the phenomenon of strong fluorescent spots on the fluorescence images was observed. This always occurred within the first 10 h after injection of AlPcS2. Histological analysis showed a local alteration to the mucosa in 67% of these spots, which was either invasive cancer (29%) or inflammation (38%). These results suggest two different mechanisms of AlPcS2 uptake in tissue, one associated with the presence of generalised dysplasia and another associated with local changes of the epithelial/connective tissue, which is not necessarily specific for tumours.</p

Clinical outcomes in chronic intervillositis of unknown etiology

Introduction: Chronic intervillositis of unknown etiology (CIUE) is a histopathological lesion of the placenta that is frequently accompanied by unfavourable pregnancy outcomes, e.g. miscarriage, fetal growth restriction (FGR) and intrauterine fetal death. Earlier described case series and cohorts have been based on diverse diagnostic criteria of CIUE. To improve our understanding of clinical outcomes associated with CIUE, we report the obstetric and perinatal outcomes in a cohort based on the recently described diagnostic criteria. Methods: CIUE is defined as an infiltrate occupying 5% or more of the intervillous space with approximately 80% of mononuclear cells positive for CD68 in the absence of an infection. Thirty-eight cases were included. Also previous and subsequent pregnancies were described. Results: Pregnancies accompanied by CIUE frequently resulted in FGR (51.6%) and pre-term birth (55.3%). Twenty-nine out of 38 pregnancies (76.3%) with CIUE resulted in a living baby. Women with CIUE frequently have had a miscarriage (16/38; 42%). Four-teen subsequent pregnancies in 8 women resulted in 2 miscarriages, 2 terminations of pregnancy for FGR, 1 early neonatal death and 9 living babies (9/14; 64.3%). Histopathologically confirmed CIUE recurred in 5 out of 10 subsequent pregnancies. Two pregnancies with recurrent CIUE were terminated, one pregnancy ended in a late miscarriage and another resulted in term birth complicated by FGR. Recurrent CIUE can also be accompanied by an uncomplicated pregnancy (1/5; 20%). Conclusion: This study provides additional insight into the clinical phenotype of CIUE and emphasises the need for further research to understand the pathophysiology behind different pregnancy outcomes in CIUE

In vivo fluorescence kinetics and localisation of aluminium phthalocyanine disulphonate in an autologous tumour model

Sulphonated phthalocyanines are studied as photosensitisers for photodynamic therapy of cancer. Their strong fluorescence and tumour-localising properties make them also potentially useful for detection of cancer by fluorescence. For this purpose, we have studied the fluorescence kinetics and localisation of aluminium phthalocyanine disulphonate (AlPcS2) in 4-nitroquinoline 1-oxide (4NQO)-induced dysplasia and invasive cancer of the oral mucosa of the hard palate in Wistar albino rats. Twenty-two rats were divided into six groups. Five groups were subjected to a 4NQO application period of 8, 12, 16, 20 or 26 weeks and one was a control group. The dysplasia varied from slight to severe and was correlated with the duration of the application period. All animals received a dose of 1 μmol kg-1 AlPcS2 i.v. Fluorescence images were recorded via a specially designed 'palatoscope' with excitation at 460 ± 20 nm for autofluorescence, 610 ± 15 nm for AlPcS2 fluorescence and detection of emission at 675 ± 15 nm. After subtraction of the two images the specific AlPcS2 fluorescence remained. AlPcS2-mediated fluorescence increased significantly when the severity of dysplasia increased (P &lt; 0.04). Also the phenomenon of strong fluorescent spots on the fluorescence images was observed. This always occurred within the first 10 h after injection of AlPcS2. Histological analysis showed a local alteration to the mucosa in 67% of these spots, which was either invasive cancer (29%) or inflammation (38%). These results suggest two different mechanisms of AlPcS2 uptake in tissue, one associated with the presence of generalised dysplasia and another associated with local changes of the epithelial/connective tissue, which is not necessarily specific for tumours.</p

Mutated PET117 causes complex IV deficiency and is associated with neurodevelopmental regression and medulla oblongata lesions

The genetic basis of the many progressive, multi systemic, mitochondrial diseases that cause a lack of cellular ATP production is heterogeneous, with defects found both in the mitochondrial genome as well as in the nuclear genome. Many different mutations have been found in the genes encoding subunits of the enzyme complexes of the oxidative phosphorylation system. In addition, mutations in genes encoding proteins involved in the assembly of these complexes are known to cause mitochondrial disorders. Here we describe two sisters with a mitochondrial disease characterized by lesions in the medulla oblongata, as demonstrated by brain magnetic resonance imaging, and an isolated complex IV deficiency and reduced levels of individual complex IV subunits. Whole exome sequencing revealed a homozygous nonsense mutation resulting in a premature stop codon in the gene encoding Pet117, a small protein that has previously been predicted to be a complex IV assembly factor. PET117 has not been identified as a mitochondrial disease gene before. Lentiviral complementation of patient fibroblasts with wild-type PET117 restored the complex IV deficiency, proving that the gene defect is responsible for the complex IV deficiency in the patients, and indicating a pivotal role of this protein in the proper functioning of complex IV. Although previous studies had suggested a possible role of this protein in the insertion of copper into complex IV, studies in patient fibroblasts could not confirm this. This case presentation thus implicates mutations in PET117 as a novel cause of mitochondrial disease