Placentas from Women with Late-Onset Preeclampsia Exhibit Increased Expression of the NLRP3 Inflammasome Machinery.

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1ß, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients.

COVID-19 pandemic in prisons in Spain: characteristics of cases and implemented control measures, March 2020-June 2022.

OBJECTIVES: Our aim was to describe the epidemiological characteristics of COVID-19 cases in prison inmates in Spain and the control measures implemented to response to this public health challenge. STUDY DESIGN: Retrospective observational study. METHODS: All COVID-19-confirmed cases reported to the Spanish information system in prisons between March 2020 and June 2022 were analyzed. Prevention plans and protocols established by penitentiary and health authorities were reviewed. Likewise, information on vaccines administered to prison inmates was described. RESULTS: A total of 8500 COVID-19 cases were reported to penitentiary public health surveillance. The overall cumulative incidence (CI) was 2054.18 cases per 10,000 inmate population. By epidemic periods, the average weekly CI was 1.15 per 10,000 inmate population during the first period, 6.91 during the second, 25.18 during the third, 3.53 during the fourth, 23.27 during the fifth, 34.72 during the sixth and 25.68 during the seventh period. The median age of cases was 49.2 years, 69.1% was born in Spain, 64.1% was asymptomatic and 16 cases died. Ninety-four percent were vaccinated. Control measures such as lockdown, suspending visitation rights and confining inmates in their cells were adopted at the beginning of the pandemic. These measures changed in accordance with the COVID-19 situation in the general population with a view to restoring the inmates' rights. CONCLUSION: The COVID-19 pandemic has had a moderate incidence in Spanish prisons. Hospitalization and CFR were lower than the general population. The control measures adopted against COVID-19 have contributed to preventing and controlling the number of cases in prisons.

The NDDG criteria versus the IADPSG or the ADA criteria for diagnosing early-onset gestational diabetes mellitus or abnormal glucose tolerance.

OBJECTIVE: To analyze the effects of substituting the National Diabetes Data Group (NDDG) criteria with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) or American Diabetes Association (ADA) criteria for the diagnosis of early-onset gestational diabetes mellitus (Early-GDM) or first trimester abnormal glucose tolerance (1 t-AGT). METHODS: A retrospective cohort study was conducted of 3200 women: 400 with Early-GDM, 800 with GDM, and 2000 with Non-GDM, according to the NDDG criteria. Rates of women with missed and new Early-GDM according to the IADPSG or ADA criteria were calculated. Multivariate logistic regression analysis was used to compare perinatal outcomes between groups. RESULTS: Using the IADPSG criteria, 61.6% of women with Early-GDM according to the NDDG were undiagnosed (Missed-Early-GDM group), and 25.9% of women with GDM and 15.7% of women with Non-GDM were diagnosed with Early-GDM (New-Early-GDM groups). Perinatal outcomes were worse in Missed-Early-GDM than in Non-GDM and better in New-Early-GDM groups than in the Early-GDM group. According to the ADA recommendations, only 11.8% of women with Early-GDM according to the NDDG criteria were diagnosed. CONCLUSION: Replacing the NDDG recommendations for the diagnosis of Early-GDM with the IADPSG or ADA criteria would mean depriving a large number of women with AGT and higher risk of adverse perinatal outcomes from early treatment and treating others with lower risk.

Fasting Glucose for the Diagnosis of Gestational Diabetes Mellitus (GDM) during the COVID-19 Pandemic.

Background: During the COVID-19 pandemic, different non-validated tests were proposed to simplify the diagnosis of gestational diabetes (GDM). Aim: To analyse the effects of replacing the two-step approach for Early-GDM and GDM diagnosis, with a fasting plasma glucose test. Material and Methods: This is a cohort study consisting of 3200 pregnant women: 400 with Early-GDM, 800 with GDM and 2000 with Non-GDM diagnosed using the two-step approach. Using fasting plasma glucose for Early-GDM and GDM diagnosis, according to the recommendations of Spain, Australia, Italy and the UK during the pandemic, the rates of missed and new Early-GDM and GDM were calculated and perinatal outcomes were analysed. Results: Using fasting plasma glucose in the first trimester >100 mg/dL for Early-GDM diagnosis, the rates of post-COVID missed and new Early-GDM were 79.5% and 3.2%, respectively. Using fasting plasma glucose at 24−28 weeks <84 or >92, 95 or 100 mg/dL for GDM diagnosis, the rates of missed GDM were 50.4%, 78%, 82.6% and 92.4%, respectively, and 8.6%, 5.6% and 2.3% women with Non-GDM were diagnosed with new GDM. Conclusion: Fasting plasma glucose is not a good test for the diagnosis of GDM either in the first trimester or at 24−28 weeks.

Screening of inmates transferred to Spain reveals a Peruvian prison as a reservoir of persistent Mycobacterium tuberculosis MDR strains and mixed infections.

It is relevant to evaluate MDR-tuberculosis in prisons and its impact on the global epidemiology of this disease. However, systematic molecular epidemiology programs in prisons are lacking. A health-screening program performed on arrival for inmates transferred from Peruvian prisons to Spain led to the diagnosis of five MDR-TB cases from one of the biggest prisons in Latin America. They grouped into two MIRU-VNTR-clusters (Callao-1 and Callao-2), suggesting a reservoir of two prevalent MDR strains. A high-rate of overexposure was deduced because one of the five cases was coinfected by a pansusceptible strain. Callao-1 strain was also identified in 2018 in a community case in Spain who had been in the same Peruvian prison in 2002-5. A strain-specific-PCR tailored from WGS data was implemented in Peru, allowing the confirmation that these strains were currently responsible for the majority of the MDR cases in that prison, including a new mixed infection.

Maternal and perinatal outcomes in external cephalic version: prognostic factors for the success of the technique.

Background We aimed to analyze the success rate of external cephalic version (ECV) for breech presentations performed in our center between March 2011 and March 2016. We evaluated factors related to a successful ECV, delivery mode, complications and newborn status after ECV. Methods Analysis of assembled data of 327 consecutive ECVs in the third trimester was done. Results The total success rate was 56.6%. After a successful ECV, 85.9% of the fetuses were delivered vaginally. Logistic regression analysis of background factors leading to a successful ECV showed that tocolysis with ritodrine and anterior placenta were each significantly correlated with the rate of successful version. No severe complications were registered during the ECVs, and all babies had normal Apgar scores at delivery. Conclusion These findings suggest that attempting an ECV in breech presentations, once or even twice, seems to be an appropriate management given that a successful ECV decreases the rate of cesarean section in this group of patients and by doing so, it might also decrease the risk of cesarean sections in future pregnancies.

Breast cancer during pregnancy: results of maternal and perinatal outcomes in a single institution and systematic review of the literature.

To compare the maternal and the perinatal variables of the patients with pregnancy associated breast cancer (PABC) and the pregnant patients without breast cancer (PNABC), we retrospectively included 13 PABC cases and 66.265 PNABC patients. The PABC patients presented a lower mean gestational age at their delivery and had higher induction of labour and prematurity rates. A diagnosis was performed before stage III in 77% of the cases. The overall survival was 90%; moreover, we collected 16 manuscripts when gathering data from 1581 patients with PABC. The mean follow-up time was 70 ± 8 months. The mean maternal age at diagnosis was 34 years old. Most of the patients were at their second trimester of pregnancy. The gestational age at delivery was 35 weeks. A mastectomy was the most frequently used surgical approach. PABC should be managed by a multidisciplinary team, ensuring there is a rigorous oncological treatment, with foetal well-being. IMPACT STATEMENT What is already known on this subject? The malignant breast tumours diagnosed during pregnancy, or 1 year after a delivery are increasing, there is evidence supporting the treatment during a pregnancy with maternal and foetal safety. A PABC should be managed by a multidisciplinary team in a referral centre, ensuring that there is a rigorous oncological treatment with foetal well-being. What do the results of this study add? Our results show that the PABC patients in our centre had a mean maternal age older than the PNABC women, as well as a higher percentage of the induction of labour and prematurity. 48 Cancer was usually diagnosed in early stages, and the most common type was ductal infiltrating, with positive hormonal receptors. For those patients continuing their pregnancies, a mastectomy plus a lymphadenectomy was the most frequent chemotherapy, and was usually administered in the third trimester of pregnancy. What are the implications of these findings for future clinical practice and/or further research? Moreover, the number of publications concerning PABC has grown, series are still scarce. We understand the limitations of the low number of the cases on our population, but this study is the first which compare the PABC with the PNABC patients, allowing to describe and compare the obstetrical and perinatal variables. Finally, we consider it is of a paramount importance to create an international database to register in a prospective way all of the cases of PABC to increase our knowledge in this field.

Maternal and perinatal outcomes in pregnancy-associated melanoma. Report of two cases and a systematic literature review.

OBJETIVES: Melanoma is one of the most frequent malignancies during gestation. However, oncological and perinatal management is still challenging. Our first objective is to describe the cases of pregnancy-associated melanoma (PAM) diagnosed in our centre between January-2004 and May-2015. Secondly, to perform a systematic review of the published articles analysing the maternal-perinatal outcomes of patients diagnosed with PAM. DESIGN, POPULATION AND METHODS: Obstetrical, oncological and perinatal variables were recorded in the case series. For the systematic review we include all published articles assessing the obstetric and neonatal outcomes in PAM cases in Pubmed, Web of Knowledge and Cochrane Library. The search was restricted to articles published in English, between January-2004 and May-2015. Study characteristics, oncological and maternal-perinatal variables were recorded in the systematic review. RESULTS: Two patients were found: the first case presents a newly diagnosed metastatic melanoma at 26-weeks of gestation with fatal maternal and neonatal outcome. The second case presents a patient with metastatic melanoma who got pregnant during her treatment. For the systematic review we found 25 articles, providing data from 489 patients. Maternal-perinatal outcomes, including termination of pregnancy rates, vary depending on the country, gestational age and tumour stage at diagnosis. PAM is usually detected at advanced stages, even with metastasis affecting the placenta and the foetus. CONCLUSIONS: When diagnosed at early stages, melanoma does not seem to alter the evolution of gestation, whereas patients with advanced stages of melanoma frequently deliver prematurely, by caesarean section, with lower neonatal weight, higher neonatal morbidity and mortality rates.

Reference ranges for the pulsatility index of the fetal aortic isthmus in singleton and twin pregnancies.

OBJECTIVES: The purpose of this study was to estimate reference ranges for the pulsatility index (PI) of the fetal aortic isthmus in uncomplicated singleton and twin pregnancies during the second half of pregnancy. METHODS: We conducted a cross-sectional observational study involving 543 healthy fetuses: 361 singleton pregnancies and 182 twin pregnancies between 19 and 36 weeks' gestation. The aortic isthmus PI was measured in 2 sonographic planes: the longitudinal aortic arch view and the 3-vessel and trachea view. We evaluated the reproducibility of aortic isthmus PI measurements between these planes by calculating intraclass correlation coefficients and limits of agreement. Scans were performed by 2 physicians, and intraobserver agreement was also measured. Regression analysis was used to estimate gestational age reference values for the aortic isthmus PI. RESULTS: The aortic isthmus PI was significantly correlated with gestational age in singletons and twins during the second half of pregnancy (P < .01). We did not find significant differences between reference ranges in singletons and twins or between the sonographic views. CONCLUSIONS: This study offers reference ranges for the aortic isthmus PI during the second half of gestation in singleton and twin pregnancies. Mean aortic isthmus PI values were similar in both types of gestations as well as both sonographic views. The aortic isthmus PI may be reliably obtained from either sonographic view.

Fetal MRI as a complementary technique after prenatal diagnosis of persistent vitelline artery in an otherwise normal fetus.

Prenatal ultrasound is the standard for the diagnosis of fetal anomalies. However, fetal MRI has emerged as a valuable diagnosis tool to complete the study of fetal malformations. Type II single umbilical artery results from the absence of both umbilical arteries and persistence of the vitelline artery. It has been described only in fetuses with sirenomelia or caudal regression syndrome. We report a favorable outcome in a normal fetus in which prenatal ultrasound and MRI showed a single umbilical artery arising from the aorta. The etiology of such a finding and its possible consequences are discussed.

Obstetric and perinatal outcome in women with twin pregnancy and gestational diabetes.

OBJECTIVE: The aim of this study was to evaluate pregnancy complications and obstetric and perinatal outcomes in women with twin pregnancy and GDM. STUD DESIGN: An observational multicentre retrospective study was performed and 534 pregnant woman and 1068 twins infants allocated into two groups, 257 with GDM and 277 controls, were studied. MAIN OUTCOME MEASURES: Pregnant women characteristics, hypertensive complications, preterm delivery rate, mode of delivery and birthweight were analysed. RESULTS: Pregnant women with GDM were older (p < 0.001) and had higher body mass index (p < 0.001) than controls. GDM was associated with higher risk of prematurity in twin pregnancy (odds ratio 1.64, 95% confidence interval [1.14-2.32], p = 0.005). This association was based on the association with other pregnancy complications. Birthweight Z-scores were significantly higher in the GDM group (p = 0.02). The rate of macrosomia was higher in the GDM group (p = 0.002) and small for gestational age (SGA) babies were significantly less frequent (p = 0.03). GDM was an independent predictor of macrosomia (p = 0.006). CONCLUSION: The presence of GDM in twin pregnancy was associated with a higher risk of hypertensive complications, prematurity and macrosomia, but significantly reduces the risk of SGA infants. Prematurity was related to the presence of other associated pregnancy complications.

Sonographic thymic measurements in Down syndrome fetuses.

OBJECTIVE: Children with Down syndrome (DS) can have hypoplastic thymuses with an impaired capacity to liberate newly generated T cells. We sought to determine if the size of the thymus in DS fetuses is different from control fetuses. METHODS: We performed comprehensive prenatal sonographic evaluation that included measurements of the thymus in 874 control fetuses and in 12 DS fetuses. We used graphic comparisons between thymic measurements obtained from the two groups of fetuses and a nested case-control validation study in which DS fetuses were matched for gestational age with control fetuses using a 2-to-1 ratio to make group comparisons. RESULTS: The plot analysis showed that more than two-thirds of DS fetuses had sonographic signs of thymic hypoplasia. The nested case-control study confirmed that the thymus of DS fetuses was statistically smaller than the thymus of control fetuses [DS transverse diameter 12.3 mm, interquartile range (IQR) 6.2 vs. control 18.1 mm, IQR 4.4; p < 0.001 and, DS perimeter 30.9 mm, IQR 20.1 vs. control 48.6 mm, IQR 20.4; p < 0.01]. CONCLUSIONS: Our findings suggest that the majority of DS fetuses have smaller thymuses than control. Prenatal measurements of the thymus may be clinically useful in the management of DS pregnancies.

Comparison of measurements of the transverse diameter and perimeter of the fetal thymus obtained by magnetic resonance and ultrasound imaging.

PURPOSE: To compare measurements of the fetal thymus obtained by magnetic resonance imaging (MRI) and ultrasound (US). MATERIALS AND METHODS: Written informed consent was obtained from the patients that participated in this Institutional Review Board-approved observational study. The study population consisted of 17 pregnant women carrying fetuses between 21 and 34 weeks of gestation with suspected abnormalities. The transverse diameter and perimeter of the thymus were measured in these fetuses at the level of an axial view of the thorax that includes the pulmonary, aorta, and superior vena cava. The degree of agreement between MRI and US measurements was determined using Lin's concordance correlation coefficient and Bland-Altman analysis. RESULTS: The mean (standard deviation, SD) gestational age at the time of the prenatal evaluation was 28.4 weeks (3.6). The thymus was measured by MRI and US in all cases. Comparison of the measurements from these two imaging modalities demonstrated a relatively good reproducibility with no evidence of systematic error. CONCLUSION: MRI and US measurements of the fetal thymus during the second half of pregnancy are comparable. This finding suggests that MRI can become a useful adjuvant to US for assessment of the fetal thymus.

Sonographic measurements of the thymus in male and female fetuses.

OBJECTIVE: The purpose of this study was to determine whether the size of the thymus is different in male and female fetuses. METHODS: In this prospective study, the transverse diameter and perimeter of the thymus were measured in healthy fetuses between 24 and 37 weeks' gestation. The means of the study variables from male and female fetuses were compared by the Student t test, and the relationships between the transverse diameter and perimeter of the thymus and gestational age and other common fetal biometric parameters were determined by linear regression modeling. RESULTS: No differences were noted between male and female fetuses for the means of the study variables. After the relationship between the transverse diameter and perimeter of the thymus and gestational age was confirmed (R(2) = 0.8 and 0.75, respectively; both P < .01), the 95% confidence interval-predicted changes were calculated, and the scatterplots of the measurements suggested that sex did not affect the size of the thymus. Bland-Altman plots were used to analyze intraobserver variability and showed good agreement for both of these thymic measurements for male and female fetuses. CONCLUSIONS: These results suggest that fetal sex does not affect the size of the thymus and, together with previous reports, support the hypothesis that a quantitative reduction in fetal thymus size could serve as an indirect marker of abnormal thymopoiesis and congenital thymic insufficiency.