Assessment-based management of placenta-mediated pregnancy complications: Pragmatism until a precision medicine approach evolves.

The management of pregnant women with thrombophilia and a history of gestational vascular complications remains debatable. Treatment of the latter is often based on clinical outcome rather than disease mechanism. While the use of venous thromboembolism prophylaxis in pregnancy is recommended for those at increased risk, the ability of anticoagulant and/or antiplatelet agents to lower the risk of placenta-mediated complications in this clinical setting remains controversial. The available guidelines are inconsistent in some situations, which reflects the limited evidence base. This review critically discusses risk assessment models (RAMs) and management strategies of women with thrombophilia and pregnancy complications, using clinical vignettes. RAMs, taking into account obstetric and thrombotic history as well as thrombophilia status, could drive a precision medicine approach, based on disease mechanism, and guide individual therapeutic interventions in high-risk clinical settings.

Criteria for placental examination for obstetrical and neonatal providers.

Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach. These criteria include indications in which placental pathology has clinical relevance, such as pregnancy loss, maternal infection, suspected abruption, fetal growth restriction, preterm birth, nonreassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurologic compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta that is abnormal on gross examination undergo a complete pathology examination. In addition, we suggest practice criteria for placental pathology services, including a list of critical values to be used by the relevant provider. We hope that these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve its relevance to clinical care.

Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early-onset and late-onset preeclampsia.

AIM: To analyze the differential genetic expression and protein localization of thrombomodulin (THBD) and tissue factor (F3) in the placentas of pregnancies affected by preeclampsia. METHODS: We assessed the expression of THBD and F3 by immunohistochemistry and real-time polymerase chain reaction (PCR) in placentas from 20 PE cases: 10 early-onset PE placentas, 10 late-onset PE placentas, and 10 control cases (normal pregnancies). RESULTS: In cases, we found higher THBD and F3 RNA levels in placental tissue. Protein expression in controls differed from that in late-onset PE placentas, which had lower THBD levels in syncytiotrophoblasts and amniotic cells. Likewise, late-onset PE placentas exhibited comparatively lower F3 expression in the perivillous fibrin. In contrast, early-onset PE had high F3 expression in the subdecidual fibrin. We found no significant differences in the F3/THBD ratio between the groups. CONCLUSION: Our study supports evidence that shows the involvement of F3 and THBD in placental disorders. Furthermore, this finding contributes to a better understanding of the physio-pathological role that these molecules may play in the development of this heterogeneous disease.

Quality of life and sexual function after a pregnancy complicated by placenta accreta spectrum.

BACKGROUND AND AIMS: Little is known about the impact of Placenta Accreta Spectrum (PAS) on quality of life (QoL). This study aims to explore QoL and sexual function after a pregnancy complicated by PAS. METHODS: Women who experienced a pregnancy complicated by PAS were invited to complete an online survey. Two validated surveys were completed: Short Form 36 (SF-36) and Female Sexual Function Index (FSFI). The mean scores were calculated and were compared between women by pregnancy outcomes. Continuous variables were presented as mean (standard deviation (SD)) and were compared to assess for significance between groups using independent t-test and one-way analysis of variance. Categorical variables were compared using χ2 test. RESULTS: A total of 142 women responded to the survey. For the SF-36, physical health was significantly higher for women at 24-36 months postpartum compared to those from 0-6 months postpartum for physical functioning (mean difference 21.9 (95% confidence interval (CI) 10.2, 33.5), role limitation due to physical function (mean difference 32.1 (95% CI 9.4, 54.7)) and pain (mean difference 15.5 (95% CI 3.4, 30.9)). For the mental health domains, only vitality improved at 24-36 months compared to the first six months postpartum (mean difference 12.8 (95% CI 0.2, 25.5)). The mean FSFI score was 24.8 (±5.8), lower than the critical score of 26.5 indicating sexual dysfunction, and 56.8% (n = 75), scored less than 26.5. CONCLUSION: Women after a pregnancy complicated by PAS had high scores on the physical health domains of SF-36. The mental health scores were lower for all women regardless of time since birth.

Adverse maternal and neonatal outcomes among singleton pregnancies in women of very advanced maternal age: a retrospective cohort study.

BACKGROUND: There is an increasing prevalence of women who tend to delay childbirth until a very advanced age. However, there is sparse data regarding very advanced maternal age (vAMA) and the interplay between vAMA and assisted reproductive technology (ART) on adverse perinatal outcomes. The study aimed to assess the risk of adverse maternal and neonatal outcomes of vAMA women (≥43 years), and to investigate the effect of maternal age on adverse maternal and neonatal outcomes in ART pregnancies. METHODS: Data was obtained from a population-based retrospective cohort of women who delivered in Ontario, Canada, between April 1st, 2012 and March 31st, 2015. The adjusted relative risks (ARR) and 95% confidence intervals (CI) for adverse maternal and neonatal outcomes were estimated by using multivariate log-binomial regression models among age groups. All models were stratified by the utilization of ART (ART and spontaneous conceptions). RESULTS: Women at vAMA had a higher risk of composite outcome comprised of preeclampsia, intrauterine growth retardation, stillbirth, and placental abruption than the younger counterparts (ARR = 1.38, 95% CI: 1.23-1.55 compared to mothers aged 20-34; ARR = 1.26, 95% CI: 1.12-1.42 compared to mothers aged 35-42). Increased risk of the primary outcome in ART compared to spontaneous conception was only observed in women aged 20-34 years (ARR = 1.24, 95% CI: 1.14-1.35). For women conceived with ART, the risk for the primary outcome significantly increased in women at vAMA (ARR = 1.29, 95% CI: 1.01-1.65 compared to mothers aged 20-34; ARR = 1.36, 95% CI: 1.06-1.74 compared to mothers aged 35-42). CONCLUSION: Women at vAMA have higher risks of adverse maternal and neonatal outcomes. Although the utilization of ART may carry an independent role for adverse perinatal outcomes, it does not further enhance the adverse effect of vAMA.

Complications and adverse outcomes in pregnancy and childbirth among women who conceived by assisted reproductive technologies: a nationwide birth cohort study of Japan environment and children's study.

BACKGROUND: Although pregnancies conceived by assisted reproductive technology (ART) have a higher risk of maternal/perinatal complications, the overall risk of adverse outcomes necessitating advanced obstetric care has not been closely examined. The present study aimed to assess and compare the risk of maternal/perinatal complications and adverse outcomes in pregnancy and childbirth conceived by ART with those conceived naturally. METHODS: This study was conducted as a part of the Japan environment and children's study (JECS), an ongoing nationwide birth cohort study in Japan. The risk of maternal/perinatal complications and adverse outcomes was assessed by mode of conception (natural conception, ovulation induction [OI] without ART, conventional in vitro fertilization and embryo transfer [IVF-ET], or intracytoplasmic sperm injection [ICSI]) using logistic regression and generalized estimating equations controlling for potential confounders. RESULTS: The final dataset included women who conceived naturally (N = 90,506), by OI without ART (N = 3939), by conventional IVF-ET (N = 1476), and by ICSI (N = 1671). Compared with women who conceived naturally, those who conceived by conventional IVF-ET were at higher risk of placenta previa (adjusted OR 2.90 [95% CI 1.94, 4.34]), morbidly adherent placenta (6.85 [3.88, 12.13]), and pregnancy-induced hypertension (1.40 [1.10, 1.78]) whereas those who conceived by ICSI had a higher risk of placental abruption (2.16 [1.20, 3.88]) as well as placenta previa (2.01 [1.29, 3.13]) and morbidly adherent placenta (7.81 [4.56, 13.38]). Women who conceived by ART had a higher risk of blood transfusion (conventional IVF-ET: 3.85 [2.52, 5.88]; ICSI: 3.76 [2.49, 5.66]) and ICU admission (conventional IVF-ET: 2.58 [1.11, 6.01]; ICSI: 3.45 [1.68, 7.06]) even after controlling for potential confounders. Neonates conceived by ART had a higher risk of preterm birth (conventional IVF-ET: 1.42 [1.13, 1.78]; ICSI: 1.31 [1.05, 1.64]). CONCLUSIONS: Women who conceived by ART had a higher risk of maternal/perinatal complications necessitating advanced obstetric care. Obstetricians should be aware of the increased risk of adverse outcomes among this population.

[Placental pathology of uteroplacental vascular deficiency]. / Anatomie pathologique de l'insuffisance vasculaire utéroplacentaire.

The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.

The Impact of Oxidative Stress of Environmental Origin on the Onset of Placental Diseases.

Oxidative stress (OS) plays a pivotal role in placental development; however, abnormal loads in oxidative stress molecules may overwhelm the placental defense mechanisms and cause pathological situations. The environment in which the mother evolves triggers an exposure of the placental tissue to chemical, physical, and biological agents of OS, with potential pathological consequences. Here we shortly review the physiological and developmental functions of OS in the placenta, and present a series of environmental pollutants inducing placental oxidative stress, for which some insights regarding the underlying mechanisms have been proposed, leading to a recapitulation of the noxious effects of OS of environmental origin upon the human placenta.

Twin to twin transfusion syndrome.

Twin to twin transfusion syndrome (TTTS) is a common complication that typically presents in the second trimester of pregnancy in 10-15% of monochorionic twins due to net transfer of volume and hormonal substances from one twin to the other across vascular anastomoses on the placenta. Without recognition and treatment, TTTS is the greatest contributor to fetal loss prior to viability in 90-100% of advanced cases. Ultrasound diagnosis of monochorionicity is most reliable in the first trimester and sets the monitoring strategy for this type of twins. The diagnosis of TTTS is made by ultrasound with the findings of polyhydramnios due to volume overload and polyuria in one twin and oligohydramnios due to oliguria of the co-twin. Assessment of bladder filling as well as arterial and venous Doppler patterns are required for staging disease severity. Assessment of fetal cardiac function also provides additional insight into the fetal cardiovascular impacts of the disease as well as help identify fetuses that may require postnatal follow up. Fetoscopic laser ablation of the communicating vascular anastomoses between the twins is the standard treatment for TTTS. It aims to cure the condition by interrupting the link between their circulations and making them independent of one another. Contemporary outcome data after laser surgery suggests survival for both fetuses can be anticipated in up to 65% of cases and survival of a single fetus in up to 88% of cases. However, preterm birth remains a significant contributor to postnatal morbidity and mortality. Long term outcomes of TTTS survivors indicate that up to 11% of children may show signs of neurologic impairment. Strategies to minimize preterm birth after treatment and standardized reporting by laser centers are important considerations to improve overall outcomes and understand the long-term impacts of TTTS.

Mirror syndrome with noncompaction cardiomyopathy in the mother and fetus. Case report / Síndrome en espejo con miocardiopatía no compactada en la madre y el feto. Reporte de caso

Objective: To report the case of a pregnant woman with mirror syndrome associated with non-compaction cardiomyopathy in the mother and the fetus, in which antenatal medical treatment provided to the mother resulted in a favorable perinatal maternal outcome. Case presentation: A 16-year old primigravida with 33 weeks of gestation referred from a Level I institution to a private Level IV center in Medellín, Colombia, because of a finding of fetal hydrops on obstetric ultrasound. During hospitalization, the patient showed clinical and ultrasonographic signs of heart failure (dyspnea, edema and hypoxemia), with the diagnosis of hydrops fetalis (mirror syndrome) also confirmed. Diuretic treatment with furosemide was initiated in the mother, with subsequent improvement of the maternal condition as well as of the fetal edema. During the subacute postpartum period in the hospital, the presence of non-compaction cardiomyopathy was confirmed on cardiac nuclear magnetic resonance imaging in both the mother and the newborn. After discharge in adequated condition, they were included in the cardiovascular follow-up program for heart failure and congenital heart disease, respectively. Conclusion: A case of mirror syndrome associated with maternal and fetal non-compaction cardiomyopathy is presented. There is a limited number of reports on mirror syndrome due to cardiac anomalies (maternal and fetal), with weak treatment descriptions, pointing to the need for research in this area. It would be important to consider the diagnosis of non-compaction cardiomyopathy in fetuses with hydrops unrelated to isoimmunization or cardiac dysfunction, and approach these cases from a multi-disciplinary perspective.

Objetivo: reportar el caso de una gestante con síndrome en espejo asociada a miocardiopatía no compactada, tanto en la madre como el feto, en los que el tratamiento médico antenatal en la madre llevó a un resultado materno perinatal favorable. Presentación del caso: se describe el caso de una primigestante de 16 años, con 33 semanas de embarazo, remitida desde una institución de primer nivel de atención a una institución privada de cuarto nivel en la ciudad de Medellín, Colombia, por presentar feto con hidropesía en ultrasonido obstétrico de control. Durante la hospitalización, la paciente presentó signos clínicos y ecocardiográficos de falla cardiaca (disnea, edema e hipoxemia), a la vez que se confirmó el diagnóstico de Hydrops fetalis (síndrome en espejo). Se instauró tratamiento diurético con furosemida en la madre, logrando mejoría del cuadro materno y del edema fetal. En el puerperio mediato hospitalario se confirmaron la presencia de miocardiopatía no compactada en la resonancia magnética nuclear cardiaca, tanto de la madre como del recién nacido. Ambos egresaron en adecuadas condiciones y fueron vinculados al programa de seguimiento cardiovascular: falla cardiaca y de cardiopatía congénitas, respectivamente. Conclusión: se presenta un caso de síndrome en espejo asociado a miocardiopatía no compactada materna y fetal. Es limitado el número de reportes de síndrome en espejo por anomalías cardiacas (maternas y fetales) y pobre la descripción de los tratamientos realizados que surgen como temas a investigar. Sería importante considerar el diagnóstico de MNC en fetos con hidropesía no asociados a isoinmunización y con disfunción cardiaca, así como su atención por equipos multidisciplinarios.

The limited knowledge of placental damage due to neglected infections: ongoing problems in Latin America.

The placenta works as a selective barrier, protecting the fetus from potential infections that may affect the maternal organism during pregnancy. In this review, we will discuss several challenging infections that are common within Latin American countries and that may affect the maternal-fetal interface and pose risks to fetal development. Specifically, we will focus on emerging infectious diseases including the arboviruses, malaria, leishmaniasis, and the bacterial foodborne disease caused by Shiga toxin-producing Escherichia coli. We will also highlight some topics of interest currently being studied by research groups that comprise an international effort aimed at filling the knowledge gaps in this field. These topics address the relationship between exposure to microorganisms and placental abnormalities, congenital anomalies, and complications of pregnancy. ABBREVIATIONS: ADE: antibody-dependent enhancement; CCL2: monocyte chemoattractant protein-1; CCL3: macrophage inflammatory protein-1 α; CCL5: chemokine (C-C motif) ligand 5; CHIKV: chikungunya virus; DCL: diffuse cutaneous leishmaniasis; DENV: dengue virus; Gb3: glycolipid globotriaosylceramyde; HIF: hypoxia-inducible factor; HUS: hemolytic uremic syndrome; IFN: interferon; Ig: immunoglobulins; IL: interleukin; IUGR: intrauterine growth restriction; LCL: localized cutaneous leishmaniasis; LPS: lipopolysaccharid; MCL: mucocutaneous leishmaniasis; NO: nitric oxide; PCR: polymerase chain reaction; PGF: placental growth factor; PM: placental malaria; RIVATREM: Red Iberoamericana de Alteraciones Vasculares em transtornos del Embarazo; sVEGFR: soluble vascular endothelial growth factor receptor; STEC: shiga toxin-producing Escherichia coli; stx: shiga toxin protein; TNF: tumor necrosis factor; TOAS: T cell original antigenic sin; Var2CSA: variant surface antigen 2-CSA; VEGF: vascular endothelial growth factor; VL: visceral leishmaniasis; WHO: world health organization; YFV: yellow fever virus; ZIKV: Zika virus.

Prediction of ischemic placental diseases during the first trimester combined test period: a retrospective cohort of low-risk pregnancies in search of the link between parity and disease.

Objective: To assess the predictive power of a multifactorial model established on maternal characteristics, placenta-associated plasma protein A (PAPPA), and the mean uterine artery pulsatility index (Ut A PI) levels for the development of ischemic placental diseases (IPD) during the first-trimester combined test (FTCT) period and to evaluate the strength of some generally accepted clinical risk factors.Method: The studied data were obtained from a retrospective cohort of low-risk singleton pregnancies in the FTCT between 1 August 2016 and 1 December 2017. After routine 11-13-week examinations for FTCT, the Ut A PI was measured and stored electronically. The PAPPA multiple of median (MoM) was obtained as a routine component of aneuploidy screening.Results: A sample of 2493 pregnancies with clearly documented outcomes was studied. Early-onset preeclampsia, late-onset preeclampsia and fetal growth restriction (FGR) were observed in 9 (0.36%), 27 (1.08%), and 41 (1.64%) cases, respectively. With optimum cut-off levels of 0.69 for PAPPA MoM and 2.05 for mean Ut A PI and a false positive rate of 4.9%, IPD cases could be predicted with 83.3% sensitivity and 73.7% specificity. Nulliparity, previous abortion in nulliparous women and first pregnancy from second marriage were not independent risk factors. Maternal age, an interval from the last delivery longer than 6 years, and body mass index were found to be independent risk factors.Conclusion: The IPD showed some common and distinct clinical, laboratory and Doppler findings during the FTCT and were predictable with the help of multifactorial analysis. Some widely accepted risk factors could be affected by various confounders. Because of the increased IPD frequencies, parous women with a time interval from the last delivery of 6 years or longer should be screened as a high-risk group for placental dysfunction-related diseases.

Diagnóstico prenatal de displasia mesenquimal placentaria / Prenatal diagnosis of placental mesenchymal dysplasia

RESUMEN La displasia mesenquimal placentaria es una anomalía placentaria benigna y rara. Está caracterizada por placentomegalia con múltiples lesiones quísticas de las vellosidades troncales y anomalías vasculares junto con el aumento de las concentraciones séricas maternas de alfafetoproteína. Es una entidad clínica desconocida y puede confundirse con enfermedad trofoblástica gestacional debido a los hallazgos ecográficos similares en ambas entidades; pero, el manejo y la resultante perinatal son diferentes. Debe incluirse en el diagnóstico diferencial de los hallazgos ecográficos que muestran feto de apariencia normal y placenta con lesiones quísticas. No obstante, la displasia mesenquimal placentaria está asociada a complicaciones como restricción del crecimiento intrauterino y muerte fetal intrauterina. Debido al alto número de complicaciones y patologías asociadas, es necesario aumentar las evaluaciones ecográficas para disminuir la morbimortalidad fetal. Se presenta un caso de diagnóstico prenatal de displasia mesenquimal placentaria con feto normal.

ABSTRACT Placental mesenchymal dysplasia is a rare and benign placental abnormality. It is characterized by placentomegaly with multiple cystic lesions of the villous tree and vascular abnormalities along with increased maternal serum alpha-fetoprotein concentrations. It is an unknown clinical entity and can be confused with gestational trophoblastic disease due to the similar ultrasound findings in both entities; but the management and the perinatal outcome are different. It should be included in the differential diagnosis of ultrasound findings showing a normal-appearing fetus and a placenta with cystic lesions. However, placental mesenchymal dysplasia is associated with complications such as intrauterine growth restriction and intrauterine fetal death. Due to the high number of complications and associated pathologies, it is necessary to increase ultrasound evaluations to reduce fetal morbidity and mortality. A case of prenatal diagnosis of placental mesenchymal dysplasia with normal fetus is presented.

Síndrome en espejo con miocardiopatía no compactada en la madre y el feto. Reporte de caso / Mirror syndrome with noncompaction cardiomyopathy in the mother and fetus. Case report

Objetivo: reportar el caso de una gestante con síndrome en espejo asociada a miocardiopatía no compactada (MNC), tanto en la madre como el feto, en los que el tratamiento médico antenatal en la madre llevó a un resultado materno perinatal favorable. Presentación del caso: se describe el caso de una primigestante de 16 años, con 33 semanas de embarazo, remitida desde una institución de primer nivel de atención a una institución privada de cuarto nivel en la ciudad de Medellín, Colombia, por presentar feto con hidropesía en ultrasonido obstétrico de control. Durante la hospitalización, la paciente presentó signos clínicos y ecocardiográficos de falla cardiaca (disnea, edema e hipoxemia), a la vez que se confirmó el diagnóstico de Hydrops fetalis (síndrome en espejo). Se instauró tratamiento diurético con furosemida en la madre, logrando mejoría del cuadro materno y del edema fetal. En el puerperio mediato hospitalario se confirmaron la presencia de miocardiopatía no compactada en la resonancia magnética nuclear cardiaca, tanto de la madre como del recién nacido. Ambos egresaron en adecuadas condiciones y fueron vinculados al programa de seguimiento cardiovascular: falla cardiaca y de cardiopatía congénitas, respectivamente. Conclusión: se presenta un caso de síndrome en espejo asociado a miocardiopatía no compactada materna y fetal. Es limitado el número de reportes de síndrome en espejo por anomalías cardiacas (maternas y fetales) y pobre la descripción de los tratamientos realizados que surgen como temas a investigar. Sería importante considerar el diagnóstico de MNC en fetos con hidropesía no asociados a isoinmunización y con disfunción cardiaca, así como su atención por equipos multidisciplinarios.

ABSTRACT Objective: To report the case of a pregnant woman with mirror syndrome associated with noncompaction cardiomyopathy in the mother and the fetus, in which antenatal medical treatment provided to the mother resulted in a favorable perinatal maternal outcome. Case presentation: A 16-year old primigravida with 33 weeks of gestation referred from a Level I institution to a private Level IV center in Medellín, Colombia, because of a finding of fetal hydrops on obstetric ultrasound. During hospitalization, the patient showed clinical and ultrasonographic signs of heart failure (dyspnea, edema and hypoxemia), with the diagnosis of hydrops fetalis (mirror syndrome) also confirmed. Diuretic treatment with furosemide was initiated in the mother, with subsequent improvement of the maternal condition as well as of the fetal edema. During the subacute postpartum period in the hospital, the presence of non-compaction cardiomyopathy was confirmed on cardiac nuclear magnetic resonance imaging in both the mother and the newborn. After discharge in adequated condition, they were included in the cardiovascular follow-up program for heart failure and congenital heart disease, respectively. Conclusion: A case of mirror syndrome associated with maternal and fetal non-compaction cardiomyopathy is presented. There is a limited number of reports on mirror syndrome due to cardiac anomalies (maternal and fetal), with weak treatment descriptions, pointing to the need for research in this area. It would be important to consider the diagnosis of non-compaction cardiomyopathy in fetuses with hydrops unrelated to isoimmunization or cardiac dysfunction and approach these cases from a multidisciplinary perspective.

Fetal death: obstetric, placental and fetal necroscopic factors / Óbito fetal: fatores obstétricos, placentários e necroscópicos fetais

ABSTRACT Introduction: Fetal death is defined as the death of the product of conception, regardless of gestational age. Objectives: The objective of this study was to investigate the maternal (obstetrical and placental) risk factors and the necropsy findings associated with fetal death, based on data obtained from the Verification of Death Service [Serviço de Verificação de Óbito (SVO)] in Florianópolis, Santa Catarina, Brazil. Material and method: This is an observational, cross-sectional study using secondary data. Were included the reports released between 2010 and 2015, with a diagnosis of fetal deaths at gestational age of 20 weeks or more. Results: During the period evaluated, 210 autopsies were performed. From these, 15.2% (n = 32) presented umbilical cord abnormalities, 22.4% (n = 47) placental abnormalities, 49.5%(n = 104) maternal health problem related to pregnancy, and 10% (n = 21) previous maternal disease. Among the fetal characteristics involved, it was observed that 6.7% (n = 14) presented meconium aspiration and 5.2% (n = 11) fetal malformations. In this study, 21.9%(n = 46) did not have their causa mortis defined. Discussion: The findings of this study show a statistically significant association (p <0.05) between meconium aspiration and full term pregnancy, hospital origin and normal birth weight. Such information is in agreement with the literature, which shows signs of intrauterine hypoxia, such as the presence of meconium, which are more prevalent in full term pregnancy. Conclusion: Among the causes of fetal death, ascending infection was the most prevalent; the maternal death related to pregnancy were the ones that stood out the most.

RESUMEN Introducción: Muerte fetal se define como muerte del producto de la concepción independientemente de la duración del embarazo. Objetivos: El objetivo de este trabajo fue investigar los factores de riesgo maternos (obstétricos y placentarios) y los hallazgos de la autopsia asociados a muerte fetal con base en los datos obtenidos en el Servicio de Verificación de Muerte [Serviço de Verificação de óbitos (SVO)] de Florianópolis, Santa Catarina, Brasil. Materialy método: Este es un estudio observacional, de diseno transversal, que utilizó datos secundarios. Se incluyeron informes de autopsia de fetos con edadgestacional de 20 semanas o más, practicadas entre 2010 y 2015. Resultados: En el período evaluado se realizaron 210 autopsias. Entre estas, 15,2% (n = 32)presentaron alteraciones de cordón umbilical; 22,4% (n = 47), de placenta; 49,5% (n = 104), enfermedades maternas relacionadas con el embarazo; y 10% (n = 21), enfermedades maternas previas. Entre las características fetales implicadas, se encontróque 6,7% (n = 14) presentaron aspiración meconialy 5,2% (n = 11), malformaciones fetales. En este estudio, 21,9% (n = 46) no tuvieron sus causas de muerte determinadas. Discusión: Los hallazgos de esta investigación muestran una relación estadísticamente significativa (p < 0,05) entre aspiración meconial y gestación a término, procedencia hospitalaria y peso adecuado al nacimiento. Estas informaciones están de acuerdo con la literatura, que trae senales de hipoxia intrauterina, como la presencia de meconio, más frecuentes en los embarazos a término. Conclusión: Entre las causas de muerte fetal, infección ascendente fue la más común; las causas de muerte materna relacionadas con el embarazo fueron las que más se destacaron.

RESUMO Introdução: Óbito fetal se define como morte do produto da concepção independente do tempo da gestação. Objetivos: O objetivo deste estudo foi investigar os fatores de risco maternos (obstétricos e placentários) e os achados de necropsia associados ao óbito fetal a partir de dados obtidos no Serviço de Verificação de Óbito (SVO) de Florianópolis, Santa Catarina, Brasil. Material e método: Trata-se de um estudo observacional, com delineamento transversal, que utilizou dados secundários. Foram incluídos laudos com diagnóstico de óbito fetal e idade gestacional de 20 semanas ou mais, realizados entre 2010 e 2015. Resultados: No período avaliado, foram realizadas 210 autópsias. Destas, 15,2% (n = 32) apresentaram alterações de cordão; 22,4% (n = 47), de placenta; 49,5% (n = 104), doenças maternas relacionadas com a gestação; e 10% (n = 21), doenças maternas prévias. Entre as características fetais implicadas, observou-se que 6,7% (n = 14) apresentaram aspiração meconial e 5,2% (n = 11), malformações fetais. Neste estudo, 21,9% (n = 46) não tiveram sua causa mortis definida. Discussão: Os achados desta pesquisa mostram associação estatisticamente significativa (p < 0,05) entre aspiração meconial e gestação a termo, procedência hospitalar e peso adequado ao nascer. Tais informações estão em concordância com a literatura, que traz sinais de hipóxia intraútero, como a presença de mecônio, mais prevalentes em gestação a termo. Conclusão: Entre as causas de óbito fetal, a infecção ascendente foi a maisprevalente; as causas de morte materna relacionadas com a gestação foram as que mais se destacaram.

Trophoblasts, invasion, and microRNA.

MicroRNAs (miRNAs) have recently become essential actors in various fields of physiology and medicine, especially as easily accessible circulating biomarkers, or as modulators of cell differentiation. To this respect, terminal differentiation of trophoblasts (the characteristic cells of the placenta in Therian mammals) into syncytiotrophoblast, villous trophoblast, or extravillous trophoblast constitutes a good example of such a choice, where miRNAs have recently been shown to play an important role. The aim of this review is to provide a snapshot of what is known today in placentation mechanisms that are mediated by miRNA, under the angles of materno-fetal immune dialog regulation, trophoblast differentiation, and angiogenesis at the materno-fetal interface. Also, two aspects of regulation of these issues will be highlighted: the part played by oxygen concentration and the specific function of imprinted genes in the developing placenta.

Fetal thrombotic vasculopathy: A case report and literature review / Vasculopatia trombótica fetal: relato de caso e revisão da literatura

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

Resumo Introdução: a vasculopatia trombótica fetal é uma alteração placentária recentemente descrita, com espectro variado de acometimento e, muitas vezes, associada a resultado perinatal adverso. Trata-se de diagnóstico histopatológico e, portanto, pós-natal, o que a torna um desafio para a prática clínica. Método: apresentação de um relato de caso e revisão da literatura. Resultados: o caso apresentado é de uma gestante com restrição do crescimento fetal, encaminhada tardiamente ao serviço, com histórico obstétrico ruim. Apesar da avaliação semanal da vitalidade fetal (perfil biofísico fetal e dopplervelocimetria) e dos cuidados pré-natais, o caso evoluiu a óbito fetal com 36 semanas e 1 dia. Não houve associação com trombofilias hereditárias e adquiridas. O anatomopatológico da placenta revelou vasculopatia trombótica fetal. Conclusão: sabe-se que a vasculopatia trombótica fetal pode estar associada a resultado perinatal adverso, incluindo óbito fetal. Ainda há muito a ser estudado acerca de sua etiopatogenia. Não é possível o diagnóstico durante a gestação e não existe ainda qualquer tratamento comprovado para essa condição. Estudos futuros são necessários para que estratégias que minimizem o impacto da vasculopatia trombótica fetal sejam desenvolvidas.