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This study (FIS-PI21/01244 and PI21/01252) was supported by the Instituto de Salud Carlos III (grant no. Estatal de I + D + I 2020–2027) and co-financed by the European Development Regional Fund “A way to achieve Europe” and P2022/BMD-7321 (Comunidad de Madrid), and Halekulani S.L. and MJR., Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT–qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients., European Development Regional Fund “A way to achieve Europe”, Comunidad de Madrid, Instituto de Salud Carlos III, Halekulani S.L., MJR, Depto. de Medicina Legal, Psiquiatría y Patología, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Psychosis is a complex entity characterized by psychological, behavioral, and motor alterations resulting in a loss of contact with reality. Although it is not common, pregnancy can be a period in which a first episode of psychosis can manifest, entailing detrimental consequences for both the fetus and the mother. The pathophysiological basis and study of maternofetal wellbeing need to be further elucidated. Lipid peroxidation and ferroptosis are two phenomena that are tightly linked to the placental dysfunction commonly observed in different complications of pregnancy. In the present study, we aim to explore the histopathological and gene expression of different markers of lipid peroxidation and ferroptosis in the placentas of women who underwent a first episode of psychosis during their pregnancy (n = 22). The aim is to then compare them with healthy pregnant women (n = 20). In order to achieve this goal, iron deposits were studied using Prussian Blue staining. In addition, the protein/gene expression of a transferrin receptor (TFRC), as well as an acyl-CoA synthetase long-chain family member 4 (ACSL-4), arachidonate lipoxygenase-5 (ALOX-5), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4) were all analyzed through gene expression (RT-qPCR) and immunohistochemical procedures. Our results demonstrate an increased presence of iron deposits that are accompanied by a further expression of TFRC, ACSL-4, ALOX-5, MDA, and GPX4—all of which are observed in the placenta tissue of women who have suffered from a first episode of psychosis. Therefore, in our study, a histopathological increase in lipid peroxidation and ferroptosis markers in the affected women is suggested. However, further studies are needed in order to validate our results and to establish possible consequences for the reported alterations., Unión Europea, Comunidad de Madrid, Instituto de Salud Carlos III, Halekulani S.L, Depto. de Medicina Legal, Psiquiatría y Patología, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

This study (FIS-PI21/01244 and PI21/01252) was supported by the Instituto de Salud Carlos III (grant no. Estatal de I + D + I 2020–2027) and co-financed by the European Development Regional Fund “A way to achieve Europe” and P2022/BMD-7321 (Comunidad de Madrid), and Halekulani S.L. and M.J.R., Psychotic episodes represent one of the most complex manifestations of various mental illnesses, and these encompass a wide variety of clinical manifestations that together lead to high morbidity in the general population. Various mental illnesses are associated with psychotic episodes; in addition, although their incidence and prevalence rates have been widely described in the general population, their correct identification and treatment is a challenge for health professionals in relation to pregnancy. In pregnant women, psychotic episodes can be the consequence of the manifestation of a previous psychiatric illness or may begin during the pregnancy itself, placing not only the mother, but also the fetus at risk during the psychotic episode. In addition, we cannot forget that both pharmacological and nonpharmacological management are complex given the different teratogenic effects of various neuroleptic drugs or mood stabilizers; moreover, the recommendation is that patients should be followed together with different specialists to maintain close contact during puerperium given the high incidence of recurrence of psychotic episodes. In addition, we cannot forget that a large portion of these patients for whom the onset times of such episodes are during pregnancy have a greater probability of an unpredictable psychiatric illness that requires a postpartum follow up, in addition to the postpartum psychotic episodes, at some point in their lives. Therefore, the purpose of this review is to summarize the epidemiology of psychotic breaks during pregnancy related to the main mental illnesses that affect this population and to summarize the main pharmacological treatments available for their clinical management., European Development Regional Fund “A way to achieve Europe”, Comunidad de Madrid, Instituto de Salud Carlos III, Halekulani S.L., M.J.R., Depto. de Medicina Legal, Psiquiatría y Patología, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

The umbilical cord is a critical anatomical structure connecting the placenta with the foetus, fulfilling multiple functions during pregnancy and hence influencing foetal development, programming and survival. Histologically, the umbilical cord is composed of three blood vessels: two arteries and one vein, integrated in a mucous connective tissue (Wharton’s jelly) upholstered by a layer of amniotic coating. Vascular alterations in the umbilical cord or damage in this tissue because of other vascular disorders during pregnancy are worryingly related with detrimental maternofoetal consequences. In the present work, we will describe the main vascular alterations presented in the umbilical cord, both in the arteries (Single umbilical artery, hypoplastic umbilical artery or aneurysms in umbilical arteries) and the vein (Vascular thrombosis, aneurysms or varicose veins in the umbilical vein), together with other possible complications (Velamentous insertion, vasa praevia, hypercoiled or hypocoiled cord, angiomyxoma and haematomas). Likewise, the effect of the main obstetric vascular disorders like hypertensive disorders of pregnancy (specially pre-eclampsia) and chronic venous disease on the umbilical cord will also be summarized herein., Unión Europea, Comunidad de Madrid, Instituto de Salud Carlos III, Halekulani S.L, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients., Comunidad de Madrid, HALEKULANI, S.L., Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group., Unión Europea, Comunidad de Madrid, Instituto de Salud Carlos III, Halekulani S.L, Fundación Santiago Dexeus Font, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

The placenta is a central structure in pregnancy and has pleiotropic functions. This organ grows incredibly rapidly during this period, acting as a mastermind behind different fetal and maternal processes. The relevance of the placenta extends far beyond the pregnancy, being crucial for fetal programming before birth. Having integrative knowledge of this maternofetal structure helps significantly in understanding the development of pregnancy either in a proper or pathophysiological context. Thus, the aim of this review is to summarize the main features of the placenta, with a special focus on its early development, cytoarchitecture, immunology, and functions in non-pathological conditions. In contraposition, the role of the placenta is examined in preeclampsia, a worrisome hypertensive disorder of pregnancy, in order to describe the pathophysiological implications of the placenta in this disease. Likewise, dysfunction of the placenta in fetal growth restriction, a major consequence of preeclampsia, is also discussed, emphasizing the potential clinical strategies derived. Finally, the emerging role of the placenta in maternal chronic venous disease either as a causative agent or as a consequence of the disease is equally treated., Unión Europea, Comunidad de Madrid, Instituto de Salud Carlos III, Halekulani S.L., Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–2016) and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF) and B2017/BMD-3804 MITIC-CM and the Maternal-fetal medicine research grant (Santiago Dexeus Font Foundation)., Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases., Unión Europea, Comunidad de Madrid, Instituto de Salud Carlos III, Fundación Santiago Dexeus Font, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

The research was funded by the University of Alcalá (COVID-19 UAH 2019/00003/016/001/023) and by (FIS-PI18/00912) the Instituto de Salud Carlos III (Plan Estatal de I + D+I 2013-2016) and cofinanced by the European Development Regional Fund “A way to achieve Europe” (ERDF) and B2017/BMD-3804 MITIC-CM., SARS-CoV-2 is the novel member of coronavirus responsible for the worldwide pandemic COVID-19, affecting all types of people. In this context, established research identified pregnant women as a susceptible group of SARS-CoV-2 infection, although there is still limited data regarding the real impact of COVID-19 in this group. With that purpose, we conducted a systematic review describing the maternal-fetal results of pregnant women infected by SARS-CoV-2, in aim to analyze the profile of the obstetric patients according to the country of origin of the publication. A total of 38 articles were included in this systematic review with 2670 patients from 7 countries, with 20 works published from China (52.6%). We reported significative differences according to the median maternal age, with Spain as the country with the highest age (34.6 years); The percentage of tabaquism; proportion of symptomatic patients in the triage; type of radiological exam (China and France conduct CT scans on all their patients in comparison to the use of chest X-Ray in the rest of the countries studied); percentages of C-sections (83.9% in China; 35.9% Spain, p < 0.001); maternal mortality rate, proportion of patients who need treatments, the use of antivirals, antibiotics, and anticoagulants as well as measurements of the newborns. Perinatal results are favorable in the majority of countries, with very low rates of vertical transmission in the majority of works. The studies collected in this review showed moderate to high index of quality. The different works describe the affectation during the first wave of the pandemic, where the pregnant woman with SARS-CoV-2 infection is generally symptomatic during the third trimester of gestation along with other factors associated with worse prognosis of the disease, such as higher age, body mass index, and further comorbidities developed during pregnancy. In the obstetric patient, proportion of C-sections are elevated together with prematurity, increas, Unión Europea, Comunidad de Madrid, Universidad de Alcalá, Instituto de Salud Carlos III, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” (ERDF) and B2017/BMD-3804 MITIC-CM., Background: Postpartum haemorrhage (PPH) is an unpredictable obstetric emergency that requires a multidisciplinary approach. Bakri balloon tamponade (BBT) is recommended when PPH does not respond to medical treatment. Nowadays few published studies have performed a multivariate analysis to determine the variables independently associated with BBT failure. Methods: Our study purpose was to determine the variables independently associated with BBT failure: first, in a large single-centre cohort study between 2010 and 2020, and second, in a systematic literature review using Medline and the Cochrane Library. Maternal and perinatal variables, PPH characteristics, technique-related variables and complications were recorded in the case series study, comparing between successful and failed BBT patients. Study characteristic and variables significantly associated with BBT failure were recorded in the systematic review. All studies used a logistic regression test. Results: The case series included 123 patients. The profile of these patients were primiparous, with vaginal delivery and a full-term new-born. BBT was successful in 81.3% of cases. Five studies were included in the systematic review, providing data from 551 patients. BBT was successful in 79.5% of cases. Conclusions: Maternal age, caesarean delivery, ≥7 red blood cells units (RBCU) transfused and curettage before BBT insertion, history of caesarean section, pre-pregnancy obesity, anteriorly placed placenta, placenta accreta, caesarean delivery, estimated blood loss before insertion of BBT, long operation duration, and coagulopathy were independent factors for BBT failure., Unión Europea, Comunidad de Madrid, Instituto de Salud Carlos III, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub