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1.
PLoS One ; 16(4): e0250983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33930082

RESUMO

OBJECTIVE: The aim was to explore the potential role of the placenta for the risk of stillbirth at term in pregnancies of obese women. METHODS: This was a case-control study comparing placental findings from term stillbirths with placental findings from live born infants. Cases were singleton term stillbirths to normal weight or obese women, identified in the Stockholm stillbirth database, n = 264 and n = 87, respectively. Controls were term singletons born alive to normal weight or obese women, delivered between 2002-2005 and between 2018-2019. Placentas were compared between women with stillborn and live-born infants, using logistic regression analyses. RESULTS: A long and hyper coiled cord, cord thrombosis and velamentous cord insertion were stronger risk factors for stillbirth in obese women compared to normal weight women. When these variables were adjusted for in the logistic regression analysis, also adjusted for potential confounders, the odds ratio for stillbirth in obese women decreased from 1.89 (CI 1.24-2.89) to 1.63 (CI 1.04-2.56). CONCLUSION: Approximately one fourth of the effect of obesity on the risk of stillbirth in term pregnancies is explained by umbilical cord associated pathology.

2.
Acta Obstet Gynecol Scand ; 99(12): 1649-1656, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32557543

RESUMO

INTRODUCTION: The prevalence of obesity in pregnancy is increasing worldwide. Maternal obesity increases risks of severe fetal and neonatal complications. The underlying pathophysiological mechanisms are unclear. One possible contributing factor could be chronic fetal hypoxia. The aim of this study was to compare placentas from women with and without obesity with respect to placental lesions, which could reflect compensatory mechanisms in response to chronic fetal hypoxia as well as lesions possibly leading to chronic fetal hypoxia. In addition, levels of erythropoietin in cord blood were compared between offspring of lean and obese women. MATERIAL AND METHODS: This cohort study included 180 women with uneventful, full-term, singleton pregnancies, out of which 91 lean women had a body mass index (BMI) of 18.5-24.9 kg/m2 and 89 women had obesity (BMI ≥30 kg/m2 ). Women were recruited at Södersjukhuset between 16 October 2018 and 2 December 2019. Placentas were investigated by two senior perinatal pathologists, who were blinded for maternal BMI. Cord blood was analyzed for levels of erythropoietin. RESULTS: Levels of erythropoietin in cord blood increased with maternal BMI (P = .01, ß = 0.97, 95% CI 0.27-1.68). There was no difference between placentas of obese and lean women in number of placental lesions reflecting chronic fetal hypoxia or in lesions that could possibly lead to chronic fetal hypoxia. CONCLUSIONS: This study of term and uneventful pregnancies demonstrated a positive association between maternal obesity and concentrations of erythropoietin in cord blood at birth. This finding supports the hypothesis of chronic fetal hypoxia as a risk factor for complications in the pregnancies of obese women. There were no differences in lesions associated with hypoxia between placentas of obese and lean women.

4.
J Exp Med ; 217(3)2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31914175

RESUMO

The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.


Assuntos
Receptor gp130 de Citocina/metabolismo , Exostose Múltipla Hereditária/metabolismo , Osteocondrodisplasias/metabolismo , Transdução de Sinais/fisiologia , Antígenos CD/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Interleucina-11/metabolismo , Interleucina-6/metabolismo , Fator Inibidor de Leucemia/metabolismo , Oncostatina M/metabolismo , Receptores de Citocinas/metabolismo
5.
Biomed Res Int ; 2019: 1315257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111043

RESUMO

Prenatal environmental exposures are considered to contribute to the development of allergic sensitization by epigenetic mechanisms. The role of histone acetylation in the placenta has not been examined yet. We hypothesized that placental histone acetylation at the promoter regions of allergy-related immune regulatory genes is associated with the development of sensitization to allergens in the child. Histones H3 and H4 acetylation at the promoter regions of 6 selected allergy-related immune regulatory genes was assessed by a chromatin immunoprecipitation assay in 173 term placentas collected in the prospective birth-cohort ALADDIN. The development of IgE sensitization to allergens in the children was followed from 6 months up to 5 years of age. We discovered significant associations of histone acetylation levels with decreased risk of allergic sensitization in 3 genes. Decreased risk of sensitization to food allergens was associated with higher H3 acetylation levels in placentas at the IFNG and SH2B3 genes, and for H4 acetylation in HDAC4. Higher HDAC4 H4 acetylation levels were also associated with a decreased risk of sensitization to aeroallergens. In conclusion, our results suggest that acetylation of histones in placenta has a potential to predict the development of sensitization to allergens in children.


Assuntos
Hipersensibilidade Alimentar/genética , Histona Desacetilases/genética , Interferon gama/genética , Proteínas/genética , Proteínas Repressoras/genética , Acetilação , Proteínas Adaptadoras de Transdução de Sinal , Alérgenos/efeitos adversos , Pré-Escolar , Cromatina/genética , Epigênese Genética/genética , Epigênese Genética/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/patologia , Histona Desacetilases/imunologia , Histonas/genética , Histonas/imunologia , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Lactente , Recém-Nascido , Interferon gama/imunologia , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Placenta/imunologia , Placenta/patologia , Gravidez , Regiões Promotoras Genéticas/genética , Proteínas/imunologia , Proteínas Repressoras/imunologia
6.
Environ Int ; 124: 482-492, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30684806

RESUMO

BACKGROUND: The persistent environmental contaminants perfluoroalkyl substances (PFASs) have gained attention due to their potential adverse health effects, in particular following early life exposure. Information on human fetal exposure to PFASs is currently limited to one report on first trimester samples. There is no data available on PFAS concentrations in fetal organs throughout all three trimesters of pregnancy. METHODS: We measured the concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorohexane sulfonic acid (PFHxS) in human embryos and fetuses with corresponding placentas and maternal serum samples derived from elective pregnancy terminations and cases of intrauterine fetal death. A total of 78 embryos and fetuses aged 7-42 gestational weeks were included and a total of 225 fetal organs covering liver, lung, heart, central nervous system (CNS), and adipose tissue were analyzed, together with 71 placentas and 63 maternal serum samples. PFAS concentrations were assayed by liquid chromatography/triple quadrupole mass spectrometry. RESULTS: All evaluated PFASs were detected and quantified in maternal sera, placentas and embryos/fetuses. In maternal serum samples, PFOS was detected in highest concentrations, followed by PFOA > PFNA > PFDA = PFUnA = PFHxS. Similarly, PFOS was detected in highest concentrations in embryo/fetal tissues, followed by PFOA > PFNA = PFDA = PFUnA. PFHxS was detected in very few fetuses. In general, PFAS concentrations in embryo/fetal tissue (ng/g) were lower than maternal serum (ng/ml) but similar to placenta concentrations. The total PFAS burden (i.e. the sum of all PFASs) was highest in lung tissue in first trimester samples and in liver in second and third trimester samples. The burden was lowest in CNS samples irrespective of fetal age. The placenta:maternal serum ratios of PFOS, PFOA and PFNA increased across gestation suggesting bioaccumulation in the placenta. Further, we observed that the ratios were higher in pregnancies with male fetuses compared to female fetuses. CONCLUSIONS: Human fetuses were intrinsically exposed to a mixture of PFASs throughout gestation. The compounds were detected in all analyzed tissues, suggesting that PFASs reach and may affect many types of organs. Collectively, our results demonstrate that PFASs pass the placenta and deposit to embryo and fetal tissues, calling for risk assessment of gestational exposures.


Assuntos
Poluentes Ambientais/química , Feto/química , Fluorcarbonetos/química , Placenta/química , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Exposição Materna , Gravidez , Espectrometria de Massas em Tandem , Adulto Jovem
7.
PLoS One ; 14(1): e0210017, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30615648

RESUMO

The incidence of stillbirth in Sweden has essentially remained constant since the 1980's, and despite thorough investigation, many cases remain unexplained. It has been suggested that a proportion of stillbirth cases is caused by heart disease, mainly channelopathies. The aim of this study was to analyze DNA from 290 stillbirth cases without chromosomal abnormalities for pathogenic single nucleotide variants (SNVs) in 70 genes associated with cardiac channelopathies and cardiomyopathies. The HaloPlex Target Enrichment System (Agilent Technologies) was utilized to prepare sequencing libraries which were sequenced on the Illumina NextSeq platform. We found that 12.1% of the 290 investigated stillbirth cases had one (n = 31) or two (n = 4) variants with evidence supporting pathogenicity, i.e. loss-of-function variants (nonsense, frameshift, splice site substitutions), evidence from functional studies, or previous identification of the variants in affected individuals. Regarding identified putative pathogenic variants in genes associated with channelopathies, the prevalence was significantly higher in the stillbirth cohort (n = 23, 7.93%) than the corresponding prevalence of the same variants in the non-Finnish European population of the Exome Aggregation Consortium (2.70%, p<0.001) and SweGen, (2.30%, p<0.001). Our results give further support to the hypothesis that cardiac channelopathies might contribute to stillbirth. Screening for pathogenic SNVs in genes associated with heart disease might be a valuable complement for stillbirth cases where today's conventional investigation does not reveal the underlying cause of fetal demise.


Assuntos
Predisposição Genética para Doença/genética , Cardiopatias/genética , Mutação com Perda de Função , Polimorfismo de Nucleotídeo Único , Natimorto/genética , Cardiomiopatias/genética , Canalopatias/genética , Códon sem Sentido , Estudos de Coortes , Feminino , Mutação da Fase de Leitura , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Incidência , Natimorto/epidemiologia , Suécia/epidemiologia
8.
Acta Paediatr ; 108(5): 927-932, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30338564

RESUMO

AIM: To investigate (i) whether maternal sensitisation to allergens, and lifestyle can influence the risk of acute and chronic inflammation of the placenta, in the forms of chorioamnionitis and villitis, respectively, and (ii) whether these placental inflammations are associated with the outcome of sensitisation for the child during preschool age. METHODS: Placentas from term uncomplicated pregnancies (n = 275) in the assessment of lifestyle and allergic disease during infancy study were analysed for the presence of acute chorioamnionitis and chronic villitis. Stepwise logistic regression was performed to estimate the relative risk of placental inflammation in relation to maternal allergic sensitisation and lifestyle, and the association between placental inflammation and sensitisation of the child up to five years of age. RESULTS: Parity and delivery at home were independently associated with chorioamnionitis, home delivery only with the low grade. Maternal allergic sensitisation was associated with increased risk of villitis in the bivariable model, however, not in the multivariable model. No significant associations were detected between placental inflammation and the outcome of sensitisation to allergens at five years of age. CONCLUSION: Our data do not support the hypothesis that the increased risk for sensitisation of a child when the mother is allergic is mediated via placental inflammation.


Assuntos
Corioamnionite/epidemiologia , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Estilo de Vida , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Gravidez , Fatores de Risco , Inquéritos e Questionários
9.
Pediatr Dev Pathol ; 22(3): 236-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30428272

RESUMO

INTRODUCTION: Chorangioma (CA) is the most common nontrophoblastic, vascular tumor-like lesion of the placenta with a reported incidence of 0.5% to 1% in all examined placentas. The underlying molecular mechanisms of CAs are still poorly elucidated, and a systematic investigation of the genetic background of CAs has not previously been done. MATERIALS AND METHODS: Tissue biopsies from 8 large (>40 mm) histologically confirmed CAs and 8 unaffected matched placenta controls, along with standard control DNA samples were analyzed for large genomic deletions and duplications using array comparative genomic hybridization (array-CGH) method. RESULTS: Array-CGH analysis revealed no rare or novel copy number variants in the CA samples compared with either standard control DNA or unaffected placenta DNA from the same individual. DISCUSSION: In this study, a systematic genetic investigation of 8 large CAs failed to demonstrate any large-scale pathogenic genetic changes. This lack of association might support a nongenetic, nontumorous origin of these lesions; however, additional genetic studies focusing on smaller genomic alterations are required to fully assess any possible genetic contribution.


Assuntos
Variações do Número de Cópias de DNA/genética , Hemangioma/genética , Hibridização Genômica Comparativa , Feminino , Testes Genéticos , Idade Gestacional , Hemangioma/patologia , Humanos , Placenta/patologia , Gravidez , Duplicações Segmentares Genômicas/genética , Deleção de Sequência
10.
Scand J Gastroenterol ; 53(12): 1535-1540, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572730

RESUMO

OBJECTIVE: Lynch syndrome (LS) has an autosomal dominant inheritance pattern and is associated with increased risk for colorectal cancer (CRC) and other cancers. Various strategies are used to identify patients at risk and offer surveillance and preventive programs, the cost effectiveness of which is much dependent on the prevalence of LS in a population. Universal testing (UT) is proposed as an effective measure, targeting all newly diagnosed CRC patients under a certain age. MATERIALS AND METHODS: LS cases were identified in a cohort of 572 consecutive CRC patients. Immunohistochemistry was performed in 539 cases, using antibodies against mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. Microsatellite instability and gene mutation screening were performed in 57 cases. RESULTS: In total 11 pathogenic variants were detected, identifying LS in 1.9% of new CRC cases. Comparing the results with current clinical methods, 2 pathogenic variants were found with Amsterdam criteria and 9 when using either Bethesda guidelines or our institution's prior clinical criteria. Pathogenic variants in MSH6 were the most common in our series. We also found different outcomes using different age cut offs. CONCLUSION: Our study demonstrates that UT of tumors before age on onset at 75 years would most likely be cost-efficient and essentially equivalent to applying the Bethesda guidelines or our institution's prior clinical criteria on all new CRC.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Predisposição Genética para Doença , Programas de Rastreamento , Instabilidade de Microssatélites , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/mortalidade , Metilação de DNA , Proteínas de Ligação a DNA/genética , Feminino , Testes Genéticos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Morbidade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Suécia/epidemiologia
11.
Acta Oncol ; 57(8): 1094-1099, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29451409

RESUMO

BACKGROUND: Reported incidence rates of hydatidiform mole (HM) show wide geographic and temporal variations, making reliable international comparisons difficult. The aim of the current study was to examine temporal trends in the incidence of HM and post-molar gestational trophoblastic neoplasia (GTN) in Stockholm County. MATERIAL AND METHODS: Data of all women with a diagnosis of HM in Stockholm County 1991-2010 was collected. The incidence of HM was assessed both in relation to number of births and viable conceptions (births and pregnancy terminations). The risk of post-molar GTN was analysed for all HM, as well as for the subtypes complete (CHM) and partial hydatidiform mole (PHM). Temporal trends were analysed by stratifying the study period into five-year intervals. RESULTS: The overall incidence rate of HM was 2.08/1000 deliveries and 1.48/1000 viable conceptions. A significant temporal increase in the incidence rate of HM, as well as in the total number and proportion of PHM, was seen. Among 956 women with HM, 77 (8%) progressed into post-molar GTN. There was evidence of a slight, but non-significant increase in the risk of malignancy in the two last five-year periods under study. CONCLUSIONS: We found evidence of a significant temporal increase in the incidence rate of HM, which could not fully be explained by an increase in maternal age over time. Changes in diagnostic methods probably contributed to the increased incidence rate of PHM. The risk of post-molar GTN remained constant over time.


Assuntos
Mola Hidatiforme/epidemiologia , Neoplasias Uterinas/epidemiologia , Adulto , Estudos de Coortes , Feminino , Doença Trofoblástica Gestacional/epidemiologia , Doença Trofoblástica Gestacional/patologia , Humanos , Mola Hidatiforme/patologia , Incidência , Gravidez , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Neoplasias Uterinas/patologia
12.
Knee Surg Sports Traumatol Arthrosc ; 26(1): 79-87, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28255657

RESUMO

PURPOSE: The purpose of the present study was to analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with shoulder impingement syndrome (SAIS) and compare them with samples from male patients with post-traumatic recurrent shoulder instability. The hypothesis of the study was that patients with SAIS would have more histologic and ultrastructural degenerative changes in their subscapularis tendon and joint capsule than patients with post-traumatic recurrent shoulder instability. METHODS: Male patients scheduled for surgery, with either subacromial decompression or Bankart reconstruction, were included. Four biopsies from each patient were obtained from the capsule and four from the subscapularis tendon during arthroscopic surgery. The histologic characteristics and the presence of glycosaminoglycans were assessed using the light microscope, and the ultrastructure was assessed using a transmission electron microscope. RESULTS: Eight patients, median age 53 (45-74) years (p < 0.0001), were included in the impingement group, and 12 patients, median age 27 (22-48) years, were included in the instability group. The histologic assessment revealed significantly higher cellularity and total degeneration score in the capsule (p = 0.016 and p = 0.014 respectively) in patients with subacromial impingement compared with the instability patients. The corresponding finding was not made for the subscapularis tendon. The ultrastructural evaluation revealed that the instability patients had more fibrils with a large diameter (indicating less degeneration) in both the subscapularis tendon and the capsule compared with the impingement patients (p < 0.0001). CONCLUSION: Male patients with subacromial impingement have more histologic and ultrastructural degenerative changes in their shoulder compared with patients with post-traumatic recurrent shoulder instability. CLINICAL RELEVANCE: It appears that in patients with subacromial impingement, the whole shoulder joint is affected and not only the subacromial space. It is the opinion of the authors that intra-articular therapeutic injections could be tried more often in these patients. LEVEL OF EVIDENCE: III.


Assuntos
Cápsula Articular/patologia , Instabilidade Articular/patologia , Manguito Rotador/patologia , Síndrome de Colisão do Ombro/patologia , Articulação do Ombro/patologia , Tendões/patologia , Adulto , Idoso , Artroscopia , Biópsia , Glicosaminoglicanos/análise , Humanos , Cápsula Articular/química , Cápsula Articular/cirurgia , Cápsula Articular/ultraestrutura , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Recidiva , Manguito Rotador/química , Manguito Rotador/cirurgia , Manguito Rotador/ultraestrutura , Ombro/patologia , Ombro/cirurgia , Síndrome de Colisão do Ombro/cirurgia , Articulação do Ombro/química , Articulação do Ombro/cirurgia , Articulação do Ombro/ultraestrutura , Tendões/química , Tendões/cirurgia , Tendões/ultraestrutura , Ferimentos e Lesões/complicações , Adulto Jovem
13.
J Matern Fetal Neonatal Med ; 31(17): 2265-2270, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28605945

RESUMO

OBJECTIVE: To examine whether different grades of placenta inflammation are associated with risk for spontaneous preterm birth, taking into consideration maternal and delivery factors. Placentas from spontaneous preterm births were compared with a control group from full-term deliveries. METHODS: Placentas from 98 full-term, 71 late preterm (gestational week 34-37), and 65 early preterm (gestational week 22-33) singleton deliveries were analysed from the Karolinska University Hospital in Stockholm. The placentas were examined for histologic chorioamnionitis (HCA) grade 1 (low) and 2 (high). Mother, child, and delivery parameters were collected from maternity centre and delivery forms. RESULTS: There was a relatively low incidence of HCA in the preterm groups (26.7% and 38.5% in the late and early preterm groups, respectively). HCA 2 was most common in the early preterm group and HCA 1 was most common in the full-term group. The odds of early preterm birth was lower for placentas with HCA 1 compared to HCA 2 (OR = 0.17) and higher for placentas with HCA 2 compared to no HCA (OR = 2.17). CONCLUSIONS: Despite a relatively low incidence of HCA in the preterm groups, HCA 2 seems to be associated with early preterm birth whereas HCA 1 seems to be part of the full-term delivery.


Assuntos
Corioamnionite/epidemiologia , Corioamnionite/patologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Adulto , Estudos de Coortes , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Ruptura Prematura de Membranas Fetais/etiologia , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Trabalho de Parto Prematuro/epidemiologia , Trabalho de Parto Prematuro/etiologia , Gravidez , Fatores de Risco , Índice de Gravidade de Doença , Suécia/epidemiologia
14.
Hum Mutat ; 39(4): 495-505, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29285825

RESUMO

Congenital malformations affecting the neural tube can present as isolated malformations or occur in association with other developmental abnormalities and syndromes. Using high-resolution copy number screening in 66 fetuses with neural tube defects, we identified six fetuses with likely pathogenic mutations, three aneuploidies (one trisomy 13 and two trisomy 18) and three deletions previously reported in NTDs (one 22q11.2 deletion and two 1p36 deletions) corresponding to 9% of the cohort. In addition, we identified five rare deletions and two duplications of uncertain significance including a rare intragenic heterozygous in-frame WDR63 deletion in a fetus with occipital encephalocele. Whole genome sequencing verified the deletion and excluded known pathogenic variants. The deletion spans exons 14-17 resulting in the expression of a protein missing the third and fourth WD-repeat domains. These findings were supported by CRISPR/Cas9-mediated somatic deletions in zebrafish. Injection of two different sgRNA-pairs targeting relevant intronic regions resulted in a deletion mimicking the human deletion and a concomitant increase of abnormal embryos with body and brain malformations (41%, n = 161 and 62%, n = 224, respectively), including a sac-like brain protrusion (7% and 9%, P < 0.01). Similar results were seen with overexpression of RNA encoding the deleted variant in zebrafish (total abnormal; 46%, n = 255, P < 0.001) compared with the overexpression of an equivalent amount of wild-type RNA (total abnormal; 3%, n = 177). We predict the in-frame WDR63 deletion to result in a dominant negative or gain-of-function form of WDR63. These are the first findings supporting a role for WDR63 in encephalocele formation.


Assuntos
Encefalocele/genética , Éxons/genética , Deleção de Genes , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Animais , Proteína 9 Associada à CRISPR , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Feto , Marcação de Genes , Testes Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Íntrons/genética , Masculino , Peixe-Zebra/genética
15.
Acta Obstet Gynecol Scand ; 97(1): 74-81, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28981981

RESUMO

INTRODUCTION: Mothers at risk of preterm birth are treated with antenatal corticosteroids, which have advantageous effects for prematurely born infants. Accelerated villous maturation in the placenta is also associated with improved perinatal outcome. The primary aim of this study was to examine the association between antenatal corticosteroids and accelerated villous maturation. The secondary aim was to study associations with other placental pathologies. MATERIAL AND METHODS: A retrospective cohort study including 105 women who had (n = 75) or had not (n = 30) been treated with antenatal corticosteroids. The women gave birth between 22+0 and 26+6  weeks of gestation in Stockholm County between 1 April 2004 and 31 March 2007. A pathologist blinded to all clinical data except gestational age examined the placental slides to identify pathology parameters. The outcomes were correlated with antenatal corticosteroid treatment, and confounding factors were adjusted using logistic regression. RESULTS: Accelerated villous maturation was significantly higher in the group treated with corticosteroids (odds ratio 16, 95% CI 2.4-690, p = 0.0005). After adjustment for gestational age and preeclampsia, the difference remained significant (odds ratio 8.9, 95% CI 1.2-389, p = 0.021). No significant associations were found regarding the secondary outcome variables, after adjusting for possible confounders. CONCLUSIONS: Antenatal corticosteroid treatment before preterm birth is associated with accelerated villous maturation. This could be one of the pathways by which corticosteroids are beneficial for preterm infants.


Assuntos
Vilosidades Coriônicas , Glucocorticoides , Doenças Placentárias , Placenta/patologia , Nascimento Prematuro/prevenção & controle , Adulto , Vilosidades Coriônicas/efeitos dos fármacos , Vilosidades Coriônicas/crescimento & desenvolvimento , Feminino , Idade Gestacional , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Recém-Nascido , Doenças Placentárias/diagnóstico , Doenças Placentárias/etiologia , Doenças Placentárias/prevenção & controle , Gravidez , Nascimento Prematuro/epidemiologia , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Estatística como Assunto , Suécia/epidemiologia
16.
BMJ Open ; 7(9): e015539, 2017 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-28871010

RESUMO

OBJECTIVES: Placenta or placental chorangioma could be the origin site of infantile haemangioma since they share various histochemical and genetic characteristics with placental vascular tissue. The aim of the current study was to investigate the association between chorangiomas and infantile haemangiomas in singleton and multiple pregnancies. MATERIALS AND METHODS: An informative questionnaire enquiring about the presence or not of infantile haemangioma and including illustrative photos of haemangioma was sent to 469 (153 cases with chorangioma and 316 controls) mothers of 323 singleton (104 cases and 219 controls) and 146 multiple (49 cases and 97 controls) liveborn neonates registered in Sweden. Overall, 310 mothers (66.1%) from 216 singleton and 94 multiple pregnancies (96 cases and 214 controls) provided feedback and their consent to participate in the current case-control study. RESULTS: The incidence of infantile haemangioma showed no statistically significant differences between cases and controls (18.8% vs 18.2%) or between singleton and multiple pregnancies (18.9% vs 17.0%). The frequency of pre-eclampsia was significantly higher in cases with chorangioma compared with controls (41.7% vs 24.3%, OR=2.22, 95% CI 1.33 to 3.71, p=0.0022) and in singleton compared with multiple pregnancies (33.3% vs 21.3%, OR=1.85, 95% CI 1.04 to 3.26, p=0.034), whereas there were no significant differences in the incidence of infantile haemangioma in neonates of mothers with or without pre-eclampsia or in neonates of mothers with multiple compared with singleton pregnancies. CONCLUSION: There was no association between placental chorangiomas and infantile haemangiomas. Multiple pregnancies or pre-eclampsia were not significantly related to higher incidence of infantile haemangioma.


Assuntos
Hemangioma/epidemiologia , Pré-Eclâmpsia/epidemiologia , Complicações Neoplásicas na Gravidez/epidemiologia , Gravidez Múltipla/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Placenta/patologia , Gravidez , Fatores de Risco , Suécia/epidemiologia , Centros de Atenção Terciária
17.
Anticancer Res ; 37(4): 1831-1835, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28373448

RESUMO

BACKGROUND/AIM: Most known cancer syndromes confer an increased risk of more than one tumour types, and families with more than one colorectal cancer often segregate other cancers as well. The aim of this study was to examine if there is a general increased risk of other cancers in colorectal cancer families, which are defined as having two or more cases of colorectal cancer in close relatives. MATERIALS AND METHODS: The study used a detailed family history of cancer diagnoses in a cohort of more than 3,000 consecutive colorectal cancer cases. A comparison was made between families with sporadic and those with familial colorectal cancer cases. Detailed morphology data were used to find further support for putative syndromes. RESULTS: There were significantly more non-colorectal cancers in the family history of the familial CRC cases (p<0.001), with significantly more gastric cancers (p<0.001), prostate cancers (p<0.001), urinary bladder cancers (p<0.001) and melanomas (p=0.002), leukaemia/lymphomas (p=0.004), gynaecological cancers (p=0.007) and breast cancers (p=0.023). There was also some support for different morphological profiles for four of the five tested syndromes. CONCLUSION: This study found support for a general increased risk of one or more different cancer syndromes involving families with colorectal cancer and other cancers. Further studies will define the different possible syndromes and determine the genetic background.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Idoso , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Suécia/epidemiologia , Síndrome
18.
PLoS One ; 11(11): e0166562, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27835686

RESUMO

INTRODUCTION: Chorangiomas (CAs) are the most common non-trophoblastic tumor-like-lesions of the placenta. Although the clinical significance of small CAs is unknown, the large lesions are often associated with maternal and fetal complications. The aim of our study was to assess the maternal clinical characteristics and neonatal outcome in singleton and multiple pregnancies with placental CA. MATERIALS AND METHODS: Among 15742 selected placentas 170 CAs were diagnosed. Pregnancy and neonatal outcomes were analyzed in singleton (n = 121) and multiple (n = 49) pregnancy groups including 121 and 100 neonates, respectively. RESULTS: The frequency of APGAR score <7 at 5 minutes (p = 0,012), abnormal pulsatility index (p = 0,034), and abnormal blood flow class (p = 0,011) were significantly higher in neonates from singleton compared to multiple pregnancies. Significantly smaller CAs in singleton pregnancies were related to small for gestational age neonates (p = 0,00040) and neonates admitted to the neonatal care unit (p = 0,028). In singleton pregnancies, significantly smaller CAs were associated to maternal preeclampsia (p = 0,039) and larger CAs to multiparity (p = 0,005) and smoking (p = 0,001) groups. The frequency of preeclampsia was high in both singleton and multiple pregnancy groups (41,32% vs 26,53%, respectively), however, the difference did not reach the level of statistical significance. DISCUSSION: A high incidence of preeclampsia in cohort of placental CA might lead to a possible recognition of CAs as potential morphologic indicator of placental hypoxia. CONCLUSION: A more favorable pregnancy outcome in multiple gestations compared to the singleton gestations with CAs might reflect an adaptive mechanism for increased demand of oxygen and associated placental tissue hypoxia in this group.


Assuntos
Hemangioma/patologia , Placenta/patologia , Pré-Eclâmpsia/patologia , Gravidez Múltipla , Adulto , Índice de Apgar , Feminino , Idade Gestacional , Hemangioma/complicações , Hemangioma/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Paridade , Pré-Eclâmpsia/diagnóstico , Gravidez , Resultado da Gravidez , Fatores de Risco , Fumar/fisiopatologia , Carga Tumoral
19.
Placenta ; 41: 39-44, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27208406

RESUMO

INTRODUCTION: Retained placenta is a potentially fatal obstetric disorder due to postpartum hemorrhage, its pathophysiology is however unknown. We aimed to assess if retained placenta was associated with increased macroscopic and histological signs of placental maternal underperfusion, a pattern otherwise seen in preeclampsia and other disorders of defective placentation. METHODS: This was a case-control study of retained (n = 49) and non-retained (n = 47) placentas, collected from full-term singleton and otherwise healthy pregnancies, carried out at a tertiary level obstetric department. Macroscopic and histological analysis was performed. Signs of maternal placental underperfusion and signs of placental inflammation, fetal vascular thrombo-occlusive disease and increased placental attachment were recorded in a primary and secondary analysis respectively. Variables were compared groupwise using unconditional logistic regression or comparison of median or mean values. RESULTS: Compared to non-retained placentas retained placentas had a significantly smaller surface area (p = 0.05), were more oblong in shape (OR 5.24 95% CI:1.34-20.21) and showed overall more signs of maternal underperfusion (OR 2.52 95% CI: 1.07-5.87). There was no significant difference in signs of placental inflammation, fetal vascular thrombo-occlusive disease or placenta accreta but basal plate myometrial fibers were more common among retained placentas. CONCLUSION: In regard to shape, surface area and histological signs of maternal placental underperfusion, retained placentas showed a histological pattern similar to that seen in preeclamptic placentas.


Assuntos
Placenta Retida/patologia , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Masculino , Miométrio/patologia , Placenta/irrigação sanguínea , Placenta/patologia , Placenta Acreta/patologia , Doenças Placentárias/patologia , Pré-Eclâmpsia/patologia , Gravidez , Estudos Prospectivos
20.
Placenta ; 39: 154-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26992689

RESUMO

INTRODUCTION: Chorangiomas (CAs) are the most frequent non-trophoblastic tumor-like-lesions of the placenta, and since they occur with an unusual frequency in pregnancies at high altitude, they are considered as a part of a spectrum of hypoxia-related vascular lesions of the placenta. The aim of our study is to describe the morphological features of the CAs and to show associations between CAs and other hypoxia related morphological changes in placentas of singleton and multiple pregnancies. MATERIALS AND METHODS: Placentas from singleton (121 vs 242) and multiple (49 vs 98) pregnancies, with and without CAs, respectively, were selected from a cohort of 15,742 placentas and enrolled into a case control study. RESULTS: Singleton placentas with CAs showed increased incidence of hypoxia-related placental changes including accelerated maturation of chorionic villi (OR = 2.40, p < 0.001), infarction (OR = 2.89, p < 0.001), decidual arteriopathy (OR = 3.24, p < 0.001), fetal thrombosis (OR = 4.05, p < 0.001) and hypercoiled umbilical cords (OR = 5.55, p < 0.001). The incidence of CAs in multiple placentas was higher in our studied cohort and a significant associated change was shown with fetal thrombosis (OR = 4.58, p = 0.017). There were no significant morphological changes between CAs in singleton compared to multiple pregnancies. DISCUSSION: In singleton placentas, CA is associated with several placental changes related to hypoxia, whereas in multiple pregnancies this relationship is not present. We speculate that CAs in multiple pregnancies might reflect an adaptive mechanism for relative hypoxia per se in these pregnancies. CONCLUSION: Our study provides evidence that CAs are associated with an increased rate of hypoxia related changes in singleton placentas.


Assuntos
Hemangioma/epidemiologia , Hipóxia/epidemiologia , Doenças Placentárias/epidemiologia , Placenta/patologia , Gravidez Múltipla , Adulto , Estudos de Casos e Controles , Feminino , Hemangioma/patologia , Humanos , Hipóxia/patologia , Doenças Placentárias/patologia , Gravidez
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