Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Molecular Mechanisms Underlying Twin-to-Twin Transfusion Syndrome.

Twin-to-twin transfusion syndrome is a unique disease and a serious complication occurring in 10-15% of monochorionic multiple pregnancies with various placental complications, including hypoxia, anemia, increased oxidative stress, and ischemia-reperfusion injury. Fetoscopic laser photocoagulation, a minimally invasive surgical procedure, seals the placental vascular anastomoses between twins and dramatically improves the survival rates in twin-to-twin transfusion syndrome. However, fetal demise still occurs, suggesting the presence of causes other than placental vascular anastomoses. Placental insufficiency is considered as the main cause of fetal demise in such cases; however, little is known about its underlying molecular mechanisms. Indeed, the further association of the pathogenic mechanisms involved in twin-to-twin transfusion syndrome placenta with several molecules and pathways, such as vascular endothelial growth factor and the renin-angiotensin system, makes it difficult to understand the underlying pathological conditions. Currently, there are no effective strategies focusing on these mechanisms in clinical practice. Certain types of cell death due to oxidative stress might be occurring in the placenta, and elucidation of the molecular mechanism underlying this cell death can help manage and prevent it. This review reports on the molecular mechanisms underlying the development of twin-to-twin transfusion syndrome for effective management and prevention of fetal demise after fetoscopic laser photocoagulation.

Hipotiroidismo subclínico y pérdida de embarazo: una revisión de la literatura / Subclinical Hypothyroidism and Pregnancy Loss: A Literature Review

Existe una alta prevalencia de hipotiroidismo subclínico (SCH) en el embarazo. Está vinculado a una importante morbilidad y mortalidad materna y fetal. Los efectos de SCH sobre el embarazo incluyen mayores riesgos de hipertensión gestacional y ruptura prematura de membranas (PROM). Sus fetos y bebés tenían más probabilidades de sufrir de bajo peso al nacer (LBW) y retraso del crecimiento intrauterino (IUGR). El riesgo de aborto espontáneo se informa alto en varios estudios para SCH no tratado. SCH se asocia directamente con una mayor presencia de anti -cuerpos anti TPO en suero materno. La detección temprana y el tratamiento de SCH han sido testigos de mejores resultados en términos de resultado del embarazo. Esta revisión se centra para establecer la relación de una mayor prevalencia de SCH en los países en desarrollo, así como su asociación con el aumento de los cuerpos anti TPO en suero materna y sacar una conclusión que puede ayudar a reducir las razones y proporcionar una solución. Este estudio concluyó que SCH es más frecuente en los países en desarrollo, ya sea debido a la deficiencia de yodo, una disminución de la conciencia sobre este problema o menos acceso a las instalaciones médicas. Por lo tanto, se sugiere que las hembras con antecedentes de partos prematuros, IUGR anteriores o abortos involuntarios deben someterse a una detección de hipotiroidismo subclínico y niveles de anticuerpos anti TPO durante sus visitas prenatales

There is a high prevalence of subclinical hypothyroidism (SCH) in pregnancy. It is linked to significant maternal and fetal morbidity and mortality. SCH's effects on pregnancy include increased risks of gestational hypertension and premature rupture of membranes (PROM). Their fetuses and infants had been more likely to suffer from low birth weight (LBW) and intrauterine growth retardation (IUGR). The risk of miscarriage is reported high in various studies for untreated SCH. SCH is directly associated with increased presence of anti TPO anti bodies in maternal serum. Early detection and treatment of SCH have witnessed better results in terms of pregnancy outcome. This review focuses to establish the relationship of increased prevalence of SCH in the developing countries as well as its association with increased anti TPO anti bodies in maternal serum and draw a conclusion which can help narrow down the reasons and provide solution. This study concluded that SCH is more prevalent in developing countries, either due to iodine deficiency, decreased awareness about this problem or less access to medical facilities. Therefore, it is suggested that females with history of preterm deliveries, previous IUGRs, or miscarriages should undergo screening for subclinical hypothyroidism and Anti TPO antibody levels during their antenatal visits.

Spatial patterns of fetal mortality: scenario before and after the implementation of surveillance / Padrões espaciais da mortalidade fetal: cenário anterior e posterior à implantação da vigilância

Abstract Objectives: to analyze the spatial distribution of fetal deaths before and after implementation of surveillance for this event in the city of Recife, in the Northeast Region of Brazil. Methods: an ecological study whose spatial analysis unit was the 94 neighborhoods. The gross fetal mortality rates were calculated and the local empirical Bayesian estimator was adopted to smooth out random fluctuations of such rates. To analyze the spatial autocorrelation, the Global Moran's Index was used, and spatial clusters were located by the Local Moran's Index. Results: during the period before implementation of death surveillance, 1,356 fetal deaths were reported, a coefficient of 9.9 deaths per thousand births. During the second period, 1,325 fetal deaths occurred, a coefficient of 9.6 deaths per thousand births. The Global Moran's Indexes (I) were I=0.6 and I=0.4 for the first and second periods, respectively, with statistical significance (p<0.05). For both periods analyzed, spatial clusters of high-risk neighborhoods were identified in the northern and eastern regions of the city. Conclusion: the spatial analysis indicated areas that persist as priorities for planning surveillance and health assistance actions to reduce fetal mortality.

Resumo Objetivos: analisar a distribuição espacial dos óbitos fetais, antes e após a implantação da vigilância deste evento, na cidade do Recife, Nordeste do Brasil. Métodos: estudo ecológico utilizando os 94 bairros existentes como unidade de análise espacial. Foram calculados os coeficientes de mortalidade fetal brutos e empregado o estimador bayesiano empírico local para a suavização de flutuações aleatórias desses coeficientes. A autocorrelação espacial foi analisada com a utilização do Índice de Moran Global e agregados espaciais foram identificados pelo Moran Local. Resultados: foram registrados 1.356 óbitos fetais (coeficiente de mortalidade de 9,9 óbitos por mil nascimentos) e 1.325 óbitos fetais (coeficiente de 9,6 óbitos por mil nascimentos), nos períodos anterior e posterior à implantação da vigilância do óbito, respectivamente. Houve diferença estatisticamente significante (p<0,05) entre os índices de Moran Global (I) dos períodos anterior (I=0,6) e posterior (I=0,4) à implantação da vigilância. Identificaram-se agregados espaciais nos bairros das regiões Norte e Leste da cidade, como maior risco de mortalidade fetal. Conclusão: a análise espacial apontou áreas que persistem como prioritárias para o planejamento de ações de vigilância e assistência à saúde para a redução da mortalidade fetal.

Implementation and evaluation of a quality improvement initiative to reduce late gestation stillbirths in Australia: Safer Baby Bundle study protocol.

BACKGROUND: In 2015, the stillbirth rate after 28 weeks (late gestation) in Australia was 35% higher than countries with the lowest rates globally. Reductions in late gestation stillbirth rates have steadily improved in Australia. However, to amplify and sustain reductions, more needs to be done to reduce practice variation and address sub-optimal care. Implementing bundles for maternity care improvement in the UK have been associated with a 20% reduction in stillbirth rates. A similar approach is underway in Australia; the Safer Baby Bundle (SBB) with five elements: 1) supporting women to stop smoking in pregnancy, 2) improving detection and management of fetal growth restriction, 3) raising awareness and improving care for women with decreased fetal movements, 4) improving awareness of maternal safe going-to-sleep position in late pregnancy, 5) improving decision making about the timing of birth for women with risk factors for stillbirth. METHODS: This is a mixed-methods study of maternity services across three Australian states; Queensland, Victoria and New South Wales. The study includes evaluation of 'targeted' implementer sites (combined total approximately 113,000 births annually, 50% of births in these states) and monitoring of key outcomes state-wide across all maternity services. Progressive implementation over 2.5 years, managed by state Departments of Health, commenced from mid-2019. This study will determine the impact of implementing the SBB on maternity services and perinatal outcomes, specifically for reducing late gestation stillbirth. Comprehensive process, impact, and outcome evaluations will be conducted using routinely collected perinatal data, pre- and post- implementation surveys, clinical audits, focus group discussions and interviews. Evaluations explore the views and experiences of clinicians embedding the SBB into routine practice as well as women's experience with care and the acceptability of the initiative. DISCUSSION: This protocol describes the evaluation of the SBB initiative and will provide evidence for the value of a systematic, but pragmatic, approach to strategies to reduce the evidence-practice gaps across maternity services. We hypothesise successful implementation and uptake across three Australian states (amplified nationally) will be effective in reducing late gestation stillbirths to that of the best performing countries globally, equating to at least 150 lives saved annually. TRIAL REGISTRATION: The Safer Baby Bundle Study was retrospectively registered on the ACTRN12619001777189 database, date assigned 16/12/2019.

A Decade of Experience with the Ovine Model of Myelomeningocele: Risk Factors for Fetal Loss.

INTRODUCTION: The ovine model is the gold standard large animal model of myelomeningocele (MMC); however, it has a high rate of fetal loss. We reviewed our experience with the model to determine risk factors for fetal loss. METHODS: We performed a retrospective review from 2009 to 2018 to identify operative factors associated with fetal loss (early fetal demise, abortion, or stillbirth). Operative risk factors included gestational age at operation, operative time, reduction of multiple gestations, amount of replaced amniotic fluid, ambient temperature, and method of delivery. RESULTS: MMC defects were created in 232 lambs with an overall survival rate of 43%. Of the 128 fetuses that died, 53 (42%) had demise prior to repair, 61 (48%) aborted, and 14 (11%) were stillborn. Selective reduction of multiple gestations in the same uterine horn was associated with increased fetal demise (OR 3.03 [95% CI 1.29-7.05], p = 0.01). Later gestational age at MMC repair and Cesarean delivery were associated with decreased abortion/stillbirth (OR 0.90 [95% CI 0.83-0.90], p = 0.03, and OR 0.37 [95% CI 0.16-0.31], p = 0.02), respectively. CONCLUSION: Avoiding selective reduction, repairing MMC later in gestation, and performing Cesarean delivery decreases the rate of fetal loss in the ovine MMC model.

Tendências recentes dos óbitos fetais por malformações congênitas: um estudo descritivo / Recent trends in fetal death due to congenital malformations: a descriptive study / Tendencias recientes de los óbitos de fetos por malformaciones congénitas: un estudio descriptivo

Este artigo se baseia em um estudo de série temporal sobre os óbitos fetais por malformações congênitas no estado do Maranhão relativo ao período de 2006 a 2016. Foram construídos indicadores epidemiológicos para estimar o risco de morte fetal e sua tendência ao longo da série estudada. Os dados são provenientes do Departamento de Informática do SUS e sua análise realizada por modelos de regressão linear. Foram registrados 17.843 óbitos fetais no período abordado pelo estudo, 528 dos quais decorrentes de malformações congênitas (2,96%). Observou-se uma tendência significativa de aumento do coeficiente de mortalidade fetal geral, correspondente a 6,99% (ß1=0,17; p=0,004) e do específico por malformações congênitas, equivalente a 5,13% (ß1=0,01; p=0,04). Os resultados deste estudo corroboram a tendência histórica dos serviços de saúde negligenciarem os óbitos fetais. É importante destacar que parte destes óbitos são preveníveis e potencialmente evitáveis. Desse modo, a implementação dos comitês de investigação de óbitos fetais e infantis e a sua vigilância adequada poderiam melhorar a assistência prestada tanto no pré-natal quanto no parto.

This article bases on a time series study about fetal deaths due to congenital malformations in the state of Maranhão, Brazil, occurred from 2006 to 2016. Epidemiological indicators were constructed to estimate the risk of fetal death and its trend throughout the series studied. The data were obtained in the Department of Informatics of SUS and analyzed by linear regression models. There were 17,843 fetal deaths during the analysed period, from which 528 were a direct result of congenital malformations (2.96%). A significant tendency towards an increase in the coefficient of general fetal mortality corresponding to 6.99% (ß1=0.17; p=0.004) and in the coefficient of specific fetal mortality due to congenital malformations equivalent to 5.13% (ß1=0.01; p=0.04) were observed. The end results of this study corroborate the historical trend toward negligence in Brazilian health centres with regard to fetal deaths. It is important to remark that some of these deaths can be presumed and potentially preventable. Thus, the implementation of the fetal and infant death investigation committees and their adequate surveillance could improve care during prenatal and delivery.

Este artículo se basa en un estudio de serie temporal acerca de muertes de fetos por malformaciones congénitas en el estado de Maranhão, Brasil, concerniente al periodo de 2006 a 2016. Se construyeron indicadores epidemiológicos para estimar el riesgo de la muerte fetal y su tendencia a lo largo de la serie estudiada. Los datos son provenientes del Departamento de Informática del SUS y fueron analizados por modelos de regresión lineal. Se registraron 17.843 muertes de fetos en el período estudiado, de los cuales 528 fueron resultado de malformaciones congénitas (2,96%). Se observó una tendencia significativa al aumento del coeficiente de mortalidad fetal general correspondiente a 6.99% (ß1=0,17; p=0,004) y del específico, por malformaciones congénitas, equivalente a 5,13% (ß1=0,01; p=0,04). Los resultados del estudio corroboran la tendencia histórica a la negligencia de los centros de salud brasileños con respecto a las muertes de los fetos. Por su importancia debemos destacar que parte de esas muertes son presumibles y pueden ser evitadas. De ese modo, la implementación de los comités de investigación de muertes de fetos y infantiles y su vigilancia adecuada podrían mejorar la asistencia prestada en el prenatal y en el parto.

[Acute appendicitis during pregnancy]. / Ostryi appenditsit u beremennykh.

Acute appendicitis is the most frequent surgical disease complicating pregnancy. Accurate diagnosis is difficult due to atypical and misleading clinical manifestations. Surgeons frequently do not know about advantages and disadvantages of different diagnostic methods applied during pregnancy. Treatment of acute appendicitis in pregnant women remains the real challenge for surgeons. There are enough researches indicating on benefits and risks of both open and laparoscopic operations. The main risk is due to fetal loss after laparoscopic procedure. Safety of diagnostic techniques and laparoscopic procedures, surgical tactics and independent risk factors of pregnancy loss are touched in the article.

The Collaborative Improvement and Innovation Network (CoIIN) to Reduce Infant Mortality: An Outcome Evaluation From the US South, 2011 to 2014.

OBJECTIVES: To evaluate the impact of the Southern Public Health Regions' (Regions IV and IV) Collaborative Improvement and Innovation Network (CoIIN) to Reduce Infant Mortality, supported by the US Health Resources and Services Administration. METHODS: We examined pre-post change (2011-2014) for CoIIN strategies with available outcome data from vital records (early elective delivery, smoking) and the Pregnancy Risk Assessment Monitoring System (safe sleep) as well as preterm birth and infant mortality for Regions IV and VI relative to all other regions. RESULTS: For most outcomes, CoIIN improvements were greater in Regions IV and VI than in other regions. For example, early elective delivery decreased by 22% versus 14% in other regions, smoking cessation during pregnancy increased by 7% versus 2%, and back sleep position increased by 5% versus 2%. Preterm birth decreased by 4%, twice that observed in other regions, but infant mortality reductions did not differ significantly. CONCLUSIONS: The CoIIN approach to public health improvement shows promise in accelerating progress in intermediate outcomes and preterm birth. Impact on infant mortality may require additional strategies and sustained efforts.

Inhibition of gingipains prevents Porphyromonas gingivalis-induced preterm birth and fetal death in pregnant mice.

Accumulating epidemiological evidence indicates that infection with Porphyromonas gingivalis which is a major periodontal pathogen, causes preterm birth and low birth weight. However, virulence factors of P. gingivalis responsible for preterm birth/low birth weight remain to be elucidated. In this study, using P. gingivalis-infected pregnant mice as an in vivo model, we investigated whether gingipains-cysteine proteinases produced by P. gingivalis-affect preterm birth and low birth weight. We found that intravenous infection of pregnant mice with P. gingivalis induced higher accumulation of the bacterium in the placenta than that in other organs. Compared to infection with P. gingivalis wild-type, infection with a gingipain-deficient P. gingivalis mutant KDP136 led to significant reduction in preterm birth and pregnancy loss. Although repetitive low-level infections of P. gingivalis failed to induce preterm birth and fetal death, it induced suppressive effects on IFN-γ production. Therapeutically, treatment with ginginpain inhibitors prevented fetal death and preterm birth caused by P. gingivalis infection and resulted in recovery of IFN-γ suppression caused by repetitive chronic P. gingivalis infection. These results indicate that gingipains are major virulence factors of P. gingivalis responsible for preterm birth/low birth, and gingipain inhibitors may be useful not only as a therapeutic agent for periodontal diseases, but also as a preventive medicine for preterm birth/low birth weight.

Cesación de tabaquismo en embarazo / Smoking cessation in pregnancy

Resumen En Chile, las mujeres en edad fértil y las embarazadas presentan una alta prevalencia de tabaquismo. El consumo de tabaco durante el embarazo tiene efectos prenatales (por ejemplo, aborto espontáneo, mortinatalidad) y es un factor de riesgo de morbilidad y mortalidad infantil. Todas las mujeres en edad fértil deben ser alentadas a dejar de fumar, y las mujeres que ya están embarazadas deben ser alentadas a dejar de fumar continuamente durante todo el embarazo, desde el momento más precoz posible hasta el período posterior al parto. Se presenta un conjunto de antecedentes y recomendaciones para la cesación de tabaquismo en embarazadas, basadas en guías internacionales sobre este tema.

In Chile, women of childbearing age and pregnant women have a high prevalence of smoking. Tobacco use during pregnancy has antenatal effects (spontaneous abortion, stillbirth) and it is a risk factor for infant morbidity and mortality. All women of childbearing age should be encouraged to quit smoking, and women who are already pregnant should be encouraged to stop smoking continuously throughout the pregnancy, from the earliest possible moment to the postpartum period. We present a set of background information and recommendations for smoking cessation in pregnant women, based on international guidelines on this topic.

Atividades desenvolvidas pelos comitês de prevenção do óbito infantil e fetal: revisão integrativa / Actividades desarrolladas por los comités de prevención de la muerte infantil y fetal: revisión integradora / Activities developed by the committees of prevention of infant and fetal deaths: integrative review

RESUMO Objetivo Sistematizar o conhecimento sobre as atividades desenvolvidas por comitês que atuam com a prevenção do óbito infantil e fetal. Método Revisão integrativa de literatura, realizada no mês de novembro de 2015, nas bases de dados PubMed, CINAHL, Scopus, LILACS, BDEnf e SciELO, utilizando as palavras-chave e descritores mortalidade infantil, óbito infantil, óbitos infantis, óbito fetal, óbitos fetais, mortalidade fetal, mortalidade neonatal, comitê de profissionais, comissão, comissões, comitês consultivos. Os 34 estudos selecionados foram organizados e analisados com auxílio do Microsoft Excel®. Resultados Há comitês de âmbito internacional, nacional, regional, estadual e municipal que analisam óbitos e realizam atividades para qualificar a assistência materno-infantil e alimentar os sistemas de informação em saúde. Conclusão Os comitês de prevenção do óbito infantil e fetal desenvolvem atividades de coleta, produção, análise e divulgação de informações relacionadas ao óbito com a finalidade de reduzir taxas de mortalidade infantil e fetal.

RESUMEN Objetivo Para sistematizar el conocimiento de las actividades desarrolladas por los comités que trabajan con la prevención del trabajo infantil y la muerte fetal. Método Revisión integrada de la literatura, que se celebró en noviembre de 2015, de las bases de datos PubMed, CINAHL, Scopus, LILACS, BDEnf y SciELO, usando las palabras clave y descriptores de mortalidad infantil,mortalidad fetal intrauterina, mortinatos, mortalidad fetal, la mortalidad neonatal, del comité profesional, comisiones, comités de asesoramiento. Se organizaron los 34 estudios seleccionados y se los analizó utilizando Microsoft Excel®. Resultados Existen internacionalmente comités, nacional, regional, estatal y actividades escénicas locales para calificar los sistemas de información de salud materna e infantil y de los alimentos. Conclusión Los comités de prevención de la mortalidad infantil y fetal se desarrollan las actividades de recolección, producción, análisis y difusión de información relacionada con la muerte, a fin de reducir las tasas de mortalidad infantil y fetal.

ABSTRACT Objective To systematize knowledge on the activities developed by the committees involved in the prevention of infant and fetal deaths. Method Integrated literature review conducted in November 2015 at PubMed, CINAHL, Scopus, LILACS, BDEnf and SciELO databases using keywords and descriptors of infant mortality, infant death, infant deaths, fetal death, fetal deaths, fetal mortality, neonatal mortality, professional committee, committee, committees, advisory committees. The 34 selected studies were organized and analyzed using Microsoft Excel®. Results International, national, regional, state and local committees analyze the deaths and conduct activities aimed to qualify maternal and childcare and feed the health information systems. Conclusion The committees for the prevention of infant and fetal mortality collect, produce, analyze and disseminate information related to these deaths in order to reduce infant and fetal mortality rates.

Further evidence of the etiology of prune belly syndrome provided by a transient massive intraabdominal cyst in a female.

We present a female neonate born with prune belly syndrome (PBS) in whom a large intraabdominal cyst was diagnosed at 12weeks of gestation. Rapid and exponential growth of the cyst caused pressure effects on the intraabdominal organs and stretching of the anterior abdominal wall by 19weeks of gestation. This led to drainage of the massive cyst at 20weeks of gestation to prevent fetal demise. This case provides further clues to the likely etiology of PBS: transient stretching and attenuation of the fetal abdominal wall secondary to gross fetal abdominal distension - from any cause.

Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy.

Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface.

Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation.

Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 µg/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-α, interleukin (Il)-1ß, Il-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation.

Prediction of single fetal demise after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: Single fetal demise (SFD) occurs in up to 20% of monochorionic pregnancies treated with laser coagulation for twin-twin transfusion syndrome (TTTS). We aimed to determine the independent factors associated with SFD to improve outcome in the care of TTTS pregnancies in the future. METHODS: This was a case-control study on twin pregnancies treated for TTTS between 2007 and 2013. Data on ultrasound, laser surgery and outcome were retrieved from our monochorionic twin database. We analyzed separately cases of SFD in donor and recipient twins, and compared them with treated pregnancies that resulted in two live births. RESULTS: Of the 273 TTTS pregnancies treated with laser coagulation, SFD occurred in 30 donors (11.0%) and 27 recipients (9.9%). In 67% of pregnancies with SFD, the death occurred within 1 week after laser treatment. For SFD in donors, absent/reversed end-diastolic flow in the umbilical artery was the strongest predictor (odds ratio (OR), 3.0 (95% CI, 1.1-8.0); P = 0.01), followed by the presence of an arterioarterial anastomosis (OR, 4.2 (95% CI, 1.4-13.1); P = 0.03) and discordance in estimated fetal weight (OR, 1.0 (95% CI, 1.0-1.1); P = 0.04). For SFD in recipients, independent predictors were absent/reversed A-wave in the ductus venosus (OR, 3.6 (95% CI, 1.2-10.5); P = 0.02) and the absence of recipient-to-donor arteriovenous anastomoses (OR, 10.6 (95% CI, 1.8-62.0); P < 0.01). CONCLUSIONS: Our findings confirm earlier reports that suggest that abnormal blood flow is associated with SFD after laser treatment for TTTS. The association of SFD with the type of anastomoses is a new finding. We speculate that the type of anastomoses present determines the degree of hemodynamic change during laser therapy. Future strategies should aim at stabilizing fetal circulation before laser therapy to decrease the vulnerability to acute preload and afterload changes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.