ABSTRACT
AIM: This qualitative focus group study aims to asses cerclage-related symptoms, the impact of a cerclage on daily functioning and patient perspectives of their healthcare experience. This study extends beyond the current focus on surgical and obstetric outcomes of a cerclage, thereby contributing to a more comprehensive understanding of the challenges faced by individuals in the context of extreme preterm birth and fetal loss and the impact of a cerclage on multiple facets in life. METHODS: Participants were recruited from the Amsterdam University Medical Center, Amsterdam, the Netherlands or via the website of a Dutch patient organization for (extreme) preterm birth. Eligible participants were ≥ 18 years old with a previous vaginal and/or abdominal cerclage with a subsequent delivery at ≥ 34 weeks of gestation with neonatal survival. Two focus group discussions (FGD) were performed. A predefined format was used, which was identical for both the vaginal and abdominal cerclage group. The International Classification of Functioning, Disability and Health (ICF-DH) was used to provide structure. Outcomes were a broad range of participants reported perspectives on physical, emotional, and social-related quality of life. RESULTS: In the Vaginal Cerclage Group (VCG) and Abdominal Cerclage Group (ACG), respectively, 11 and 8 participants were included. Fear for a subsequent pregnancy loss was the most limiting factor to perform daily activities during pregnancy in all participants with a cerclage. Fear to conceive again because of prior second-trimester fetal loss was experienced by 27% in the VCG and 13% in the ACG. The majority of participants experienced a reduction in anxiety after placement of their cerclage (VCG = 64%, ACG = 75%). Decreased mobility/bedrest (VCG = 100%, ACG = 75%) and blood loss (VCG = 55%, ACG = 13%) were frequently mentioned complaints during pregnancy with cerclage. Other aspects mentioned in both groups were social isolation, the lack of societal participation, and the perceived need to quit work and sports. All participants in the abdominal cerclage group reported a lack of comprehensible and unambiguous information about obstetric management and expectations during pregnancy in secondary care hospitals. Clear communication between secondary and tertiary care hospitals about obstetric management following an abdominal cerclage, for example, about the need for cervical length measurements by ultrasound, the need for bedrest or advice concerning sexual activity was missing (63%). Psychologic support was desired in half of all participants, but was not offered to them. CONCLUSIONS: The fear of a subsequent pregnancy loss was reported as the most limiting factor in daily life by all participants. Cerclage placement resulted in the reduction of anxiety. Participants mentioned a significant impact of bedrest and activity restriction during pregnancy with cerclage on social participation and daily activities. Unfortunately, no high level evidence is available on this matter. Patients might even benefit from appropriate levels of physical activity throughout their pregnancy to promote their overall well-being. More evidence is needed to determine the optimal level of physical activity. There is a need for clear and unambiguous patient information about obstetric management.
Subject(s)
Cerclage, Cervical , Focus Groups , Premature Birth , Qualitative Research , Quality of Life , Humans , Female , Pregnancy , Premature Birth/psychology , Adult , Netherlands , Quality of Life/psychology , Patient Preference/psychology , Young AdultABSTRACT
OBJECTIVE: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. DESIGN: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). SETTING: Nationwide, the Netherlands. POPULATION: All pregnant women between April 2016 and April 2018. METHODS: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. MAIN OUTCOME MEASURES: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. RESULTS: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. CONCLUSIONS: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality.
Subject(s)
Hemoperitoneum , Perinatal Death , Pregnancy Complications , Female , Humans , Pregnancy , Cohort Studies , Hemoperitoneum/diagnosis , Hemoperitoneum/epidemiology , Hemoperitoneum/etiology , Parturition , Perinatal Mortality , Pregnancy Complications/diagnosis , Pregnancy Complications/epidemiology , Pregnancy Complications/etiology , Infant, NewbornABSTRACT
Abdominal cerclage is an effective treatment for cervical incompetence in patients with a previously failed vaginal cerclage or with anatomic restrictions to a vaginal cerclage. Management of second trimester complications that warrant a delivery impose a complex clinical situation in patients with an abdominal cerclage. We report 3 cases of successful removal of an abdominal cerclage by posterior and anterior colpotomy in the second trimester of pregnancy. This new and minimally invasive surgical technique avoids the need for extensive dilation, laparoscopy, or laparotomy to remove the cerclage and allow a vaginal delivery.
Subject(s)
Cerclage, Cervical , Colpotomy/methods , Device Removal/methods , Sutures , Uterine Cervical Incompetence/surgery , Abdomen/pathology , Abdomen/surgery , Adult , Cerclage, Cervical/adverse effects , Cerclage, Cervical/instrumentation , Cerclage, Cervical/methods , Colpotomy/instrumentation , Delivery, Obstetric , Female , Humans , Infant, Newborn , Laparoscopy/instrumentation , Laparoscopy/methods , Minimally Invasive Surgical Procedures/methods , Pregnancy , Pregnancy Complications/surgery , Pregnancy Trimester, Second , Sutures/adverse effects , Treatment OutcomeABSTRACT
OBJECTIVE: To perform a morphological evaluation of the ductus venosus, heart and jugular lymphatic sac (JLS) in first-trimester human fetuses with normal and abnormal ductus venosus flow velocity waveforms (DV-FVWs) and normal and increased nuchal translucency (NT). METHOD: Postmortem examination was performed on fetuses with increased NT or structural malformations with previous NT and DV-FVW measurements. Ductus venosus morphology was examined using markers for endothelium, smooth muscle actin (SMA), nerves and elastic fibers. Fetal hearts were studied by microscopy. The nuchal region was analyzed using markers for lymphatic vessels, endothelium, SMA and nerves. RESULTS: Two trisomy 21 and two trisomy 18 fetuses with increased NT and abnormal DV-FVWs were analyzed. As a control, one euploid anencephalic fetus with normal NT, cardiac anatomy and DV-FVWs was examined. Similar endothelial and SMA expression was observed in the ductus venosus in all fetuses. Nerve and elastic fiber expression were not detected. Three trisomic fetuses showed cardiac defects, one trisomic fetus demonstrated normal cardiac anatomy. The JLS was abnormally enlarged or contained red blood cells in all trisomic fetuses. The control fetus showed a normal JLS. CONCLUSION: Abnormal DV-FVWs are not justified by alterations in ductus venosus morphology. DV-FVWs most probably reflect intracardiac pressure. © 2016 John Wiley & Sons, Ltd.
Subject(s)
Blood Flow Velocity , Down Syndrome/diagnostic imaging , Fetal Heart/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Nuchal Translucency Measurement , Trisomy/diagnosis , Umbilical Veins/diagnostic imaging , Vena Cava, Inferior/diagnostic imaging , Abortion, Induced , Actins/metabolism , Anencephaly/diagnostic imaging , Autopsy , CD56 Antigen/metabolism , Chromosomes, Human, Pair 18 , Female , Humans , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Pregnancy , Pregnancy Trimester, First , Pulsatile Flow , Trisomy 18 Syndrome , Ultrasonography, Prenatal , Umbilical Veins/metabolism , Umbilical Veins/pathology , Veins/diagnostic imaging , Veins/metabolism , Veins/pathology , Vena Cava, Inferior/metabolism , Vena Cava, Inferior/pathologyABSTRACT
This overview provides insight into the underlying genetic mechanism of the high incidence of cardiac defects in fetuses with increased nuchal translucency (NT). Nuchal edema, the morphological equivalent of increased NT, is likely to result from abnormal lymphatic development and is strongly related to cardiac defects. The underlying genetic pathways are, however, unknown. This study aims to present a systematic overview of genes involved in both cardiac and lymphatic development in mouse embryos. A search of PubMed and the Mammalian Phenotype Browser was performed. Fifteen candidate genes involved in both cardiac and lymphatic development were identified: Adrenomedullin; Chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TFII); Cyp51; Ephrin-B2; Forkhead box protein C2 (Foxc2); Nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1); Neurofibromatosis type 1 (Nf1); Phosphoinositide 3-kinase encoding isoform p110α (Pik3ca); Podoplanin; Prospero-related homeobox 1 (Prox1); T-box 1 (Tbx1); Tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains 1 (Tie1); vascular endothelial growth factor (Vegf)-A; Vegf receptor-3 (Vegfr-3); and Vascular endothelial zinc finger 1 (Vezf1). Mutations in all but one gene (Pik3ca) resulted in both a cardiac defect and nuchal edema. Candidate genes - mainly encoding for endothelium - are involved in both cardiac and lymphatic development. Alterations in candidate genes are associated with the strong relation between increased NT and cardiac defects.
Subject(s)
Edema/genetics , Genes, Developmental , Heart Defects, Congenital/genetics , Heart/embryology , Lymphatic System/embryology , Nuchal Translucency Measurement , Animals , Lymphatic System/abnormalities , MiceABSTRACT
OBJECTIVE: To assess whether cardiac failure, because of cardiac defects, and abnormal jugular lymphatic development are involved in nuchal edema (NE) - the morphological equivalent of increased nuchal translucency - in various euploid mutant mouse models. METHOD: Mouse embryos with lymphatic abnormalities and NE (Ccbe1(-/-)), with cardiac defects and NE (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+)) and with cardiac malformations without NE (Tbx2(-/-), Pitx2(-/-), Fgf10(-/-), Jarid2(-/-NE-)) were examined. Embryos were analyzed from embryonic day 11.5 to 15.5. Markers for lymphatic vessels, endothelium, smooth muscle cells and nerves were used to study the nuchal region. Hematoxylin-Azophloxine staining was performed to examine cardiac morphology. RESULTS: Mouse embryos with lymphatic abnormalities and NE (Ccbe1(-/-)) showed no formation of the jugular lymphatic sac but normal cardiac morphology. In mouse embryos with cardiac defects and NE (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+)) enlarged jugular lymphatic sacs or large nuchal cavities within the NE were found. In mouse embryos with a cardiac malformation without NE (Tbx2(-/-), Pitx2(-/-), Fgf10(-/-), Jarid2(-/-NE-)) normal jugular lymphatic sacs were observed. CONCLUSION: NE consistently coincides with abnormal jugular lymphatic development in euploid mouse embryos, independent of cardiac anatomy. NE is unlikely to be caused by temporary cardiac failure solely because of a cardiac defect.
Subject(s)
Heart Defects, Congenital/diagnostic imaging , Lymphatic Abnormalities/diagnostic imaging , Nuchal Translucency Measurement , Animals , Female , Mice, Knockout , PregnancyABSTRACT
OBJECTIVE: Increased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency. METHODS: Mouse embryos in which all NCCs were fluorescently labeled (Wnt1-Cre;Rosa26(eYfp) ), reporter embryos for in vivo RA activity (DR5-luciferase) and embryos with absent (Raldh2(-/-) ) or in utero inhibition of RA signaling (BMS493) were investigated. Immunofluorescence using markers for blood vessels, lymphatic endothelium and neurons was applied. Flow cytometry was performed to measure specific LEC populations. RESULTS: Cranial nerves were consistently close to the jugular lymph sac (JLS), in which NCCs were identified. In the absence of RA synthesis, enlarged JLS and nuchal edema were observed. Inhibiting RA signaling in utero resulted in a significantly higher amount of precursor-LECs at the expense of mature LECs and caused nuchal edema. CONCLUSIONS: Neural crest cells are involved in lymphatic development. RA is required for differentiation into mature LECs. Blocking RA signaling in mouse embryos results in abnormal lymphatic development and nuchal edema.
Subject(s)
Lymphatic Vessels/embryology , Neural Crest/physiology , Tretinoin/metabolism , Animals , Cell Differentiation , Endothelial Cells/cytology , Female , Lymphatic Vessels/cytology , Lymphatic Vessels/metabolism , Mice , Nuchal Translucency Measurement , PregnancyABSTRACT
OBJECTIVE: To evaluate spontaneous vaginal delivery and complication rates after induction of labor with a transcervical Foley catheter in women with a previous cesarean delivery. DESIGN: Retrospective cohort study. SETTING: Secondary teaching hospital in the second largest city of the Netherlands. POPULATION: Women with a history of cesarean delivery (n = 208), undergoing induction of labor with a Foley catheter in a subsequent pregnancy. MATERIAL AND METHODS: The women who had induction of labor with a transcervical Foley catheter in the Ikazia Hospital, Rotterdam, between January 2003 and January 2012, were identified in a computerized database. Patient's records were checked for accuracy. MAIN OUTCOME MEASURES: Vaginal delivery rate, cesarean section rate, uterine rupture and maternal and neonatal (infectious) morbidity. RESULTS: Of the women 60% had a spontaneous vaginal delivery and 11% were delivered by vacuum extraction. Uterine rupture occurred in one woman. Postpartum hemorrhage was the most common maternal complication (12%). Maternal intrapartum and postpartum infections occurred in 5% and 1%. Proven neonatal infection was found in 3% of the cases. Two perinatal deaths occurred (1%), of which one was related to uterine rupture. CONCLUSION: Induction of labor with a transcervical Foley catheter is an effective method to achieve vaginal delivery in women with a previous cesarean delivery. There is a low risk of uterine rupture and maternal and neonatal (infectious) morbidity in this cohort.
Subject(s)
Cervical Ripening/physiology , Labor, Induced/methods , Obstetric Labor Complications , Urinary Catheterization/methods , Vaginal Birth after Cesarean/methods , Catheter-Related Infections , Cohort Studies , Cross Infection , Female , Humans , Labor, Induced/adverse effects , Logistic Models , Netherlands , Pregnancy , Retrospective Studies , Risk , Urinary Catheterization/statistics & numerical data , Uterine Rupture/etiology , Vaginal Birth after Cesarean/statistics & numerical dataABSTRACT
BACKGROUND: Cervical incompetence is an important cause of extremely preterm delivery. Without specialized treatment, cervical incompetence has a 30% chance of recurrence in a subsequent pregnancy. Recently, the first randomized controlled trial showed significant superiority of abdominal cerclage compared with both high and low vaginal cerclage in preventing preterm delivery at <32 weeks of gestation and fetal loss in patients with a previous failed vaginal cerclage. OBJECTIVE: This study aimed to assess surgical and obstetrical outcomes in patients with pre- and postconceptional laparoscopic abdominal cerclage placement. Furthermore, it also aimed to perform subgroup analysis based on the indication for cerclage placement in order to identify patients who benefit the most from an abdominal cerclage. STUDY DESIGN: A retrospective multicenter cohort study with consecutive inclusion of all eligible patients from 1997 onward in the Dutch cohort (104 patients) and from 2007 onward in the Boston cohort (169 patients) was conducted. Eligible patients had at least 1 second- or third-trimester fetal loss due to cervical incompetence and/or a short or absent cervix after cervical surgery. This includes loop electrosurgical excision procedure, conization, or trachelectomy. Patients were divided into the following subgroups based on the indication for cerclage placement: (1) previous failed vaginal cerclage, (2) previous cervical surgery, and (3) other indications. The third group consisted of patients with a history of multiple second- or early third-trimester fetal losses due to cervical incompetence (without a failed vaginal cerclage) and/or multiple dilation and curettage procedures. The primary outcome measure was delivery at ≥34 weeks of gestation with neonatal survival at hospital discharge. Secondary outcome measures included surgical and obstetrical outcomes, such as pregnancy rates after preconceptional surgery, obstetrical complications, and fetal survival rates. RESULTS: A total of 273 patients were included (250 in the preconceptional and 23 in the postconceptional cohort). Surgical outcomes of 273 patients were favorable, with 6 minor complications (2.2%). In the postconceptional cohort, 1 patient (0.4%) had hemorrhage of 650 mL, resulting in conversion to laparotomy. After preconceptional laparoscopic abdominal cerclage (n=250), the pregnancy rate was 74.1% (n=137) with a minimal follow-up of 12 months. Delivery at ³34 weeks of gestation occurred in 90.5% of all ongoing pregnancies. Four patients (3.3%) had a second-trimester fetal loss. The indication for cerclage in all 4 patients was a previous failed vaginal cerclage. The other subgroups showed fetal survival rates of 100% in ongoing pregnancies, with a total fetal survival rate of 96%. After postconceptional placement, 94.1% of all patients with an ongoing pregnancy delivered at ³34 weeks of gestation, with a total fetal survival rate of 100%. Thus, second-trimester fetal losses did not occur in this group. CONCLUSION: Pre- and postconceptional laparoscopic abdominal cerclage is a safe procedure with favorable obstetrical outcomes in patients with increased risk of cervical incompetence. All subgroups showed high fetal survival rates. Second-trimester fetal loss only occurred in the group of patients with a cerclage placed for the indication of previous failed vaginal cerclage, but was nevertheless rare even in this group.
Subject(s)
Cerclage, Cervical , Laparoscopy , Premature Birth , Uterine Cervical Incompetence , Pregnancy , Female , Infant, Newborn , Humans , Cerclage, Cervical/adverse effects , Cerclage, Cervical/methods , Cohort Studies , Laparoscopy/adverse effects , Premature Birth/epidemiology , Premature Birth/etiology , Premature Birth/prevention & control , Cervix Uteri , Uterine Cervical Incompetence/diagnosis , Uterine Cervical Incompetence/epidemiology , Uterine Cervical Incompetence/surgeryABSTRACT
BACKGROUND: A "Menstruatie Educatie Kalender" application (Menstruation Education Calendar, (MEK-APP)) was developed for adults to evaluate menstrual complaints. The future aim of this app is to use it as a self-diagnostic instrument for menstrual abnormalities for both adults and adolescents. Early identification of the potential of an application for future use by both user groups would increase implementation success and adoption of the application. OBJECTIVE: To compare differences in experienced usability by adults versus adolescents and to identify factors influencing future use for both age groups in one mHealth application (in this study the MEK-APP). METHODS: This study consisted of three phases: (1) usability testing of the MEK-APP for iOS and Android by think-aloud method, (2) two-month daily use and (3) in-depth individual interview. During the think-aloud sessions, twelve tasks were performed in the application while they were thinking aloud. Usability problems were rated for their severity with Nielsen' Severity Scale. Both the think-aloud sessions and in-depth interviews were verbatim transcribed and thematically analyzed to determine the factors influencing future use for both groups. In addition, the System Usability Scale (SUS) and Intrinsic Motivation Inventory (IMI) questionnaires were filled out during the interviews. RESULTS: Seven adults (>18 years) and seven adolescents (14-18 years) evaluated the MEK-APP. There were 14 usability issues and 16 bugs in both groups. There were no differences between adults and adolescents. In the thematic qualitative analysis, the following future use factors were identified: user-expectation, motivation, privacy, understandability, and user-experience. The user-expectation, motivation and privacy differed between both groups but did not influence usage. No differences were observed in SUS and IMI scores between both groups. CONCLUSIONS: There are five factors influencing the future use of a menstrual-related mHealth application for both adults and adolescents. It is possible to serve different age groups with a single application.
Subject(s)
Mobile Applications , Telemedicine , Adult , Female , Humans , Adolescent , Menstruation , Telemedicine/methods , Motivation , Mitogen-Activated Protein Kinase KinasesABSTRACT
STUDY OBJECTIVE: The aim of this review was to create an overview of available instruments used to evaluate the menstrual complaints of dysmenorrhea and heavy menstrual bleeding (HMB) in adolescents. METHODS: The search was conducted in PubMed, Web of Science, Embase, and PsycINFO on December 1, 2022. Studies published in English reporting on menstrual complaints among girls aged 10-19 were included. The quality and bias risk was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Of 8994 identified studies, 57 were included. In these studies, 19 instruments were described, of which 8 were validated in adolescents. One was difficult to use in daily practice, 1 had low sensitivity and specificity in the detection of HMB, 2 were validated by face validity, and 2 were not specifically developed to evaluate (the impact of) menstrual complaints. Therefore, only 2 were validated and feasible to measure adolescent menstrual complaints: the Period ImPact and Pain Assessment (PIPPA) and the Adolescent Menstrual Bleeding Questionnaire (aMBQ). Remarkably, the Pictorial Blood Loss Assessment Chart (PBAC) was the most frequently used instrument in adolescents. There was one modified version of the PBAC for adolescents, which had a lower cutoff value for HMB and low sensitivity and specificity. CONCLUSION: We found that the PIPPA and aMBQ are suitable for assessing menstrual complaints and their impact on daily activities and health-related quality of life in adolescents. The PBAC, which is used frequently in adults, needs to be further assessed specifically for adolescents. In particular, the clinical relevance of the PBAC cutoff value for HMB should be determined for this age group. Considering the different interpretations, experiences, and limited knowledge of menstrual complaints, instruments suitable for adults may not be suitable for adolescents.
Subject(s)
Dysmenorrhea , Menorrhagia , Humans , Adolescent , Female , Dysmenorrhea/diagnosis , Menorrhagia/diagnosis , Surveys and Questionnaires , Young Adult , Pain Measurement , ChildABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the effectiveness of laparoscopic abdominal cerclage placement in the prevention of recurrent preterm birth. STUDY DESIGN: We conducted a multicenter cohort study with retrospective Dutch (32 patients) and Boston (34 patients) cohorts who had undergone preconceptional laparoscopic abdominal cerclage placement. Eligible patients had at least 1 second/third trimester fetal loss or delivered at <34 weeks of gestation because of cervical insufficiency and/or a short or absent cervix. Primary outcome was delivery of an infant at ≥ 34 weeks of gestation with neonatal survival. Secondary outcome measures included surgical and pregnancy outcomes and patients' satisfaction (Dutch cohort). RESULTS: Surgical outcomes of 66 patients were excellent, with 3 minor complications. After preconceptional laparoscopic abdominal cerclage, 35 pregnancies were evaluated. Twenty-five patients (71.4%) delivered at ≥ 34 weeks of gestation; 3 patients (8.6%) experienced a second-trimester fetal loss. The total fetal survival rate was 90.0%. CONCLUSION: Preconceptional laparoscopic abdominal cerclage shows encouraging and favorable perinatal outcomes in patients with a poor obstetric history.
Subject(s)
Cerclage, Cervical , Cervix Uteri/surgery , Laparoscopy , Obstetric Labor, Premature/prevention & control , Premature Birth/prevention & control , Adult , Cohort Studies , Female , Follow-Up Studies , Humans , Obstetric Labor, Premature/surgery , Pregnancy , Premature Birth/surgery , Retrospective Studies , Secondary Prevention , Treatment OutcomeABSTRACT
BACKGROUND: In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac function or are caused by local morphological alterations in the ductus venosus. AIM: The aim of this study was to investigate if the observed increased nuchal translucency, cardiac defects and abnormal lymphatic development in the examined mouse models are associated with local changes in ductus venosus morphology. STUDY DESIGN: Mouse embryos with anomalous lymphatic development and nuchal edema (Ccbe1(-/-) embryos), mouse embryos with cardiac defects and nuchal edema (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+) embryos) and mouse embryos with cardiac defects without nuchal edema (Tbx2(-/-), Fgf10(-/-), Jarid2(-/-NE-) embryos) were examined. Embryos were analyzed from embryonic day (E) 11.5 to 15.5 using markers for endothelium, smooth muscle actin, nerve tissue and elastic fibers. RESULTS: All mutant and wild-type mouse embryos showed similar, positive endothelial and smooth muscle cell expression in the ductus venosus at E11.5-15.5. Nerve marker and elastic fiber expression were not identified in the ductus venosus in all investigated mutant and wild-type embryos. Local morphology and expression of the used markers were similar in the ductus venosus in all examined mutant and wild-type embryos. CONCLUSIONS: Cardiac defects, nuchal edema and abnormal lymphatic development are not associated with morphological changes in the ductus venosus. Ductus venosus flow velocity waveforms most probably reflect intracardiac pressure.
Subject(s)
Edema/pathology , Heart Defects, Congenital/pathology , Lymphatic System/abnormalities , Nuchal Cord/pathology , Umbilical Veins/pathology , Actins/genetics , Actins/metabolism , Animals , Blood Flow Velocity , Calcium-Binding Proteins/genetics , Female , Fibroblast Growth Factor 10/genetics , Heart Defects, Congenital/genetics , Lymphatic System/pathology , Mice , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Nuchal Cord/genetics , Nuchal Translucency Measurement , Polycomb Repressive Complex 2/genetics , T-Box Domain Proteins/genetics , Tacrolimus Binding Protein 1A/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
BACKGROUND: Doppler flow velocities of the ductus venosus are increasingly used to assess fetal increased nuchal translucency, growth-restriction and monochorionic twins, and might contribute to screening for cardiac defects. It is disputed whether a sphincter at the ductus venosus inlet actively regulates blood flow. AIMS: This study aims to define the morphogenesis of the developing mouse and human ductus venosus and to address the existence of a sphincter. STUDY DESIGN: The presence of endothelium, smooth muscle, elastic fibers and nerves in the ductus venosus of E10.5-15.5 mouse embryos and in three corresponding human embryos (CS16, CS19 and CS23) was examined using immunohistochemistry. Three-dimensional reconstructions of the ductus venosus of E11.5-15.5 mouse and CS14-23 human embryos were generated and examined. RESULTS: The ductus venosus lumen was narrowed from ventral-caudal to dorsal-cranial in E13.5-15.5 mouse and CS16-23 human embryos. Mouse embryos showed positive endothelial Pecam1 expression from E11.5-15.5 and smooth muscle actin staining in the ventral-caudal part of the ductus venosus from E12.5-15.5. At all developmental stages, elastic fiber and nerve marker expression was not detected in the ductus venosus (Fig. 2). In human embryos endothelial Pecam1 and smooth muscle actin expression was found in the ductus venosus from CS16 and CS19 onwards. Elastic fiber and nerve marker expression was not detected in all stages (Fig. 4). Morphogenesis and staining results of the ductus venosus were similar in both species. CONCLUSIONS: The ductus venosus lacks a sphincter at its inlet as no accumulation of smooth muscle cells, elastic fibers or nerve innervation was found in mouse embryos from E11.5-15.5 and in human embryos from CS14-23.