Natural Killer Cell Education in Women With Recurrent Pregnancy Loss.

Problem: Natural killer (NK) cells undergo education for full functionality via interactions between killer immunoglobulin-like receptors (KIRs) or NKG2A and human leukocyte antigen (HLA) ligands. Presumably, education is important during early pregnancy as insufficient education has been associated with impaired vascular remodeling and restricted fetal growth in mice. NK cell education is influenced by receptor co-expression patterns, human cytomegalovirus (CMV), the HLA-E107 dimorphism, and HLA-B leader peptide variants.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction: results of a large multicenter cohort study (the OPTICORE study).

Background: Early-onset fetal growth restriction as consequence of placental insufficiency frequently requires iatrogenic preterm birth. Administration of antenatal corticosteroids reduces risks of neonatal morbidity and mortality following preterm birth and is most beneficial if the neonate is delivered within 2 weeks following treatment. International guidelines on fetal growth restriction pregnancies do not provide directives regarding the timing of antenatal corticosteroids, resulting in practice variation.

Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

Background: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction.

Methods: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies.

Optimizing the Comet Assay-Based In Vitro DNA Repair Assay for Placental Tissue: A Pilot Study with Pre-Eclamptic Patients.

The comet assay-based in vitro DNA repair assay has become a common tool for quantifying base excision repair (BER) activity in human lymphocytes or cultured cells. Here, we optimized the protocol for studying BER in human placental tissue because the placenta is a non-invasive tissue for biomonitoring of early-life exposures, and it can be used to investigate molecular mechanisms associated with prenatal disorders. The optimal protein concentration of placental protein extracts for optimal damage recognition and incision was 2 mg protein/mL.

The association between non-viral sexually transmitted infections and pregnancy outcome in Latin America and the Caribbean: A systematic review.

Introduction: Non-viral sexually transmitted infections are known to be associated with adverse pregnancy outcomes. For these pathogens, standard antenatal screening is not broadly performed in Latin America and the Caribbean. The aim of this study was to comprehensively review the association of non-viral sexually transmitted infections and neonatal outcomes among pregnant women in the region.

The association between adverse pregnancy outcomes and non-viral genital pathogens among women living in sub-Saharan Africa: a systematic review.

Adverse pregnancy outcomes are the main causes of maternal and neonatal morbidity and mortality, including long-term physical and psychological sequelae. These events are common in low- and middle-income countries, particularly in Sub Saharan Africa, despite national efforts. Maternal infections can cause complications at any stage of pregnancy and contribute to adverse outcomes.

Antibiotic Use in Pregnancy: A Global Survey on Antibiotic Prescription Practices in Antenatal Care.

Antibiotic prescription and use practices in the antenatal care setting varies across countries and populations and has the potential to significantly contribute to the global spread of antibiotic resistance. This study aims to explore how healthcare practitioners make decisions about antibiotic prescriptions for pregnant women and what factors play a role in this process. A cross-sectional exploratory survey consisting of 23 questions, including 4 free-text and 19 multiple-choice questions, was distributed online.

Which first-trimester risk assessment method for preeclampsia is most suitable? A model-based impact study.

Background: Low-dose aspirin treatment reduces the risk of preeclampsia among high-risk pregnant women. Internationally, several first-trimester risk-calculation methods are applied.

Objective: This study aimed to assess the costs and benefits of different first-trimester preeclampsia risk estimation algorithms: EXPECT (an algorithmic prediction model based on maternal characteristics), National Institute for Health and Care Excellence (a checklist of risk factors), and the Fetal Medicine Foundation (a prediction model using additional uterine artery Doppler measurement and laboratory testing) models, coupled with low-dose aspirin treatment, in comparison with no risk assessment.

Analysis of FCGR3A-p.176Val variants in women with recurrent pregnancy loss and the association with CD16a expression and anti-HLA antibody status.

Natural Killer (NK) cells have been implicated in recurrent pregnancy loss (RPL). The p.Val176Phe (or Val158Phe) Single Nucleotide Polymorphism (SNP) in the FCGR3A gene encoding the FcγRIIIA or CD16a receptor has been associated with an enhanced affinity for IgG and stronger NK-mediated antibody-dependent cellular cytotoxicity.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE): study protocol of a multicentre, retrospective cohort study.

Introduction: Early-onset fetal growth restriction (FGR) requires timely, often preterm, delivery to prevent fetal hypoxia causing stillbirth or neurologic impairment. Antenatal corticosteroids (CCS) administration reduces neonatal morbidity and mortality following preterm birth, most effectively when administered within 1 week preceding delivery. Optimal timing of CCS administration is challenging in early-onset FGR, as the exact onset and course of fetal hypoxia are unpredictable.

Effect of COVID-19 on antenatal care: experiences of medical professionals in the Netherlands.

Background: COVID-19 has greatly affected the delivery of all health care services globally. Antenatal care is one area of care that has been impacted, despite the fact that attending antenatal check-ups is essential for pregnant women and cannot be postponed. Little is known about how exactly ANC provision has changed in the Netherlands, or how the changes have impacted midwives and gynaecologists providing those services.

Definition and Quantification of Three-Dimensional Imaging Targets to Phenotype Pre-Eclampsia Subtypes: An Exploratory Study.

Pre-eclampsia is a severe placenta-related complication of pregnancy with limited early diagnostic and therapeutic options. Aetiological knowledge is controversial, and there is no universal consensus on what constitutes the early and late phenotypes of pre-eclampsia. Phenotyping of native placental three-dimensional (3D) morphology offers a novel approach to improve our understanding of the structural placental abnormalities in pre-eclampsia.

Cumulative effect of maternal vascular malperfusion types in the placenta on adverse pregnancy outcomes.

Introduction: Placental vascular disease, characterized by Maternal Vascular Malperfusion (MVM) lesions, is considered to be the underlying cause of pregnancy complications. Aim is to evaluate the relationship between the cumulative number of MVM lesion types, and adverse pregnancy- and neonatal outcomes.

Methods: This retrospective cohort study included 272 women with singleton gestations who gave birth at a Dutch tertiary hospital between 2017 and 2018 with available placental histopathology reports.

Natural killer cell profiles in recurrent pregnancy loss: Increased expression and positive associations with TACTILE and LILRB1.

Problem: NK cells are important for healthy pregnancy and aberrant phenotypes or effector functions have been associated with RPL. We compared expression of a broad panel of NK cell receptors, including immune checkpoint receptors, and investigated their clinical association with RPL as this might improve patient stratification and prediction of RPL.

Method Of Study: Peripheral blood mononuclear cells were isolated from 52 women with RPL and from 2 women with an uncomplicated pregnancy for flowcytometric analysis and plasma was used to determine anti-CMV IgG antibodies.

The association between decidual vasculopathy and abnormal uterine artery Doppler measurement.

Introduction: Placental syndrome is an umbrella term encompassing the clinical phenotypes of preeclampsia and fetal growth restriction, and is associated with high maternal and neonatal morbidity. In women with placental syndrome, histologicl examination of the uteroplacental unit commonly demonstrates pathological lesions, such as decidual vasculopathy. Decidual vasculopathy are pathological changes in the spiral arteries, which are associated with adverse outcome in preeclampsia and long-term maternal cardiovascular health.

Endometrial factors in the implantation failure spectrum: protocol of a MUltidisciplinary observational cohort study in women with Repeated Implantation failure and recurrent Miscarriage (MURIM Study).

Introduction: Women with repeated implantation failure (RIF) and unexplained recurrent miscarriage (RM) are proposed to be at opposite ends of the implantation spectrum, with RM representing an overly receptive endometrium (implantation of genetically aberrant or poor-quality embryos) versus RIF representing an overly selective endometrium (no implantation even with good quality embryos). In both cases, often no explanation for reproductive failure can be found and although promising add-on treatments have been introduced, therapeutic options are frequently limited to supportive care. Both RM and RIF are multifactorial and research indicates that the interplay between steroidogenesis, uterine natural killer (uNK) cells and the microbiome determine the capacity of the endometrium to be a biosensor for invading embryos.

Intravenous immunoglobulins improve live birth rate among women with underlying immune conditions and recurrent pregnancy loss: a systematic review and meta-analysis.

Intravenous immunoglobulin (IVIG) is increasingly used as a treatment for recurrent pregnancy loss (RPL) despite lack of clear evidence on efficacy. Recent data suggest IVIG might be more effective in a subgroup of women with an aberrant immunological profile. Therefore, a systematic review and meta-analysis of studies on the effectiveness of IVIG treatment on pregnancy outcome among women with RPL and underlying immunological conditions (e.

Preconceptional evaluation of women with recurrent pregnancy loss: the additional value of assessing vascular and metabolic status.

Background: A majority of recurrent pregnancy loss cases (RPL) remains unexplained. We hypothesized that complications in vascular and metabolic status may guide towards underlying problems that also predispose to RPL and that the number of pregnancy losses is related.

Methods: A retrospective study in 123 women with either a history of low-order RPL (2-3 pregnancy losses) or high-order RPL (≥ 4 pregnancy losses) and 20 women with a history of uncomplicated pregnancy (controls) was performed.

Understanding Host-Pathogen Interactions in Acute Chorioamnionitis Through the Use of Animal Models.

Inflammation of the chorion and/or amnion during pregnancy is called chorioamnionitis. Acute chorioamnionitis is implicated in approximately 40% of preterm births and has wide-ranging implications for the mother, fetus, and newborn. Large disease burden and lack of therapeutic approaches drive the discovery programs to define and test targets to tackle chorioamnionitis.

Screening of Chorioamnionitis Using Volatile Organic Compound Detection in Exhaled Breath: A Pre-clinical Proof of Concept Study.

Chorioamnionitis is a major risk factor for preterm birth and an independent risk factor for postnatal morbidity for which currently successful therapies are lacking. Emerging evidence indicates that the timing and duration of intra-amniotic infections are crucial determinants for the stage of developmental injury at birth. Insight into the dynamical changes of organ injury after the onset of chorioamnionitis revealed novel therapeutic windows of opportunity.

Ultrasound evaluation of the placenta in healthy and placental syndrome pregnancies: A systematic review.

Introduction: An antepartum screening method to determine normal and abnormal placental function is desirable in the prevention of maternal and fetal pregnancy complications. Placental appearance can easily be obtained and evaluated using 2D ultrasonography, but surprisingly little is known about the change in placental appearance during gestation. Aim of this systematic review was to describe the antepartum placental appearance in placenta syndrome (PS) pregnancies, and to compare this to the appearance in healthy pregnancies.

Placental Mitochondrial Abnormalities in Preeclampsia.

Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission.