Design of a Phase 3, Global, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn.

Objective:  Nipocalimab is a neonatal fragment crystallizable (Fc) receptor (FcRn)-blocking monoclonal antibody that inhibits placental immunoglobulin G (IgG) transfer and lowers circulating maternal IgG levels. In an open-label, single-arm, phase 2 study, nipocalimab demonstrated evidence of safety and efficacy that support further investigation in a pivotal phase 3 trial of recurrent hemolytic disease of the fetus and newborn (HDFN). The phase 3 AZALEA study aims to evaluate the efficacy and safety of nipocalimab in a larger population at risk for severe HDFN, defined as HDFN associated with poor fetal outcomes or neonatal death.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn.

Background: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.

Methods: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN.

Hemolytic disease of the fetus and newborn: rapid review of postnatal care and outcomes.

Background: Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research.

Live birth prevalence of hemolytic disease of the fetus and newborn in the United States from 1996 to 2010.

Background: Hemolytic disease of the fetus and newborn (HDFN) is mediated by maternal alloantibodies, a consequence of immune sensitization during pregnancy with maternal-fetal incompatibility with ABO, Rhesus factor (Rh), and/or other red blood cell antigens. RhD, Kell, and other non-ABO alloantibodies are the primary cause of moderate to severe HDFN, whereas ABO HDFN is typically mild. HDFN live birth prevalence owing to Rh alloimmunization among newborns in the United States was last estimated to be 106 per 100,000 births in 1986.

Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.

Background: Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research.

Methods: We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.

[More focus on prevention in the health care system? Acknowledge the need for a programmatic approach].

Objective: A sustainable healthcare system calls for strengthening the focus on prevention. In general, there is no articulated demand for preventive interventions by an individual. Prevention therefore requires a programmatic approach.

Global proteomic characterization of microdissected estrogen receptor positive breast tumors.

We here describe two proteomic datasets deposited in ProteomeXchange via PRIDE partner repository [1] with dataset identifiers PXD000484 (defined as "training") and PXD000485 (defined as "test") that have been used for the development of a tamoxifen outcome predictive signature [2]. Both datasets comprised 56 fresh frozen estrogen receptor (ER) positive primary breast tumor specimens derived from patients who received tamoxifen as first line therapy for recurrent disease. Patient groups were defined based on time to progression (TTP) after start of tamoxifen therapy (6 months cutoff): 32 good and 24 poor treatment outcome patients were comprised in the training set, respectively.

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer.

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM).

First-trimester follistatin-like-3 levels in pregnancies complicated by subsequent gestational diabetes mellitus.

OBJECTIVE To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM (> or =2 abnormal values on a 100-g glucose tolerance test at approximately 28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy.

Antibodies to trophoblast antigens HLA-G, placenta growth factor, and neuroD2 do not improve detection of circulating trophoblast cells in maternal blood.

Objectives: Non-invasive prenatal diagnosis using circulating fetal trophoblast cells has been challenging due to lack of a reproducible trophoblast-specific antibody. We investigated the use of three trophoblast cell-specific antibodies, HLA-G, placenta growth factor, and neuroD2, for the isolation of trophoblast cells from the maternal circulation.

Methods: Trophoblast cells were isolated by density centrifugation from maternal blood samples (gestational age 10-20 weeks, n = 9).

Angiogenic factors and preeclampsia.

Preeclampsia is a major cause of maternal and neonatal morbidity and mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, hypertension and proteinuria, may be due to an excess of circulating anti-angiogenic growth factors, most notably soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng). sFlt1 is an endogenous protein that is produced by the placenta.

Fetal nucleic acids in maternal body fluids: an update.

Our laboratory continues to be actively involved in the development of new biomarkers for prenatal diagnosis using maternal blood and amniotic fluid. We have also developed a mouse model that demonstrates that cell-free fetal (cff) DNA is detectable in the pregnant maternal mouse. In human maternal plasma and serum we have analyzed factors that are important in the clinical interpretation of cff DNA levels.

Trophoblastic oxidative stress and the release of cell-free feto-placental DNA.

Considerable quantities of cell-free fetal DNA circulate in the maternal blood during human pregnancy, but the origin of the DNA remains uncertain. Circumstantial evidence suggests the placenta is the principal source, so we tested the hypothesis that release occurs from the syncytiotrophoblast after the induction of apoptotic changes. Villous explants from normal placentas delivered by elective caesarean section were cultured under normoxic conditions (10% oxygen) for up to 20 hours or exposed to hypoxia (0.

Circulating cell-free fetal messenger RNA levels after fetoscopic interventions of complicated pregnancies.

Objective: The aim of this study was to examine fetal gene expression in maternal plasma after fetoscopic intervention for twin-twin transfusion syndrome or congenital diaphragmatic hernia.

Study Design: Twelve women with pregnancies that were complicated by twin-twin transfusion syndrome and 10 women carrying fetuses with congenital diaphragmatic hernia were sampled before and sequentially after treatment. Levels of glyceraldehyde-3-phosphate dehydrogenase, human placental lactogen, and gamma globin messenger RNA were measured by real-time reverse transcriptase polymerase chain reaction amplification.

A fusion-based clinical decision support for disease diagnosis from endoscopic images.

This paper presents an intelligent decision support system designed on a decision fusion framework coupled with a priori knowledge base for abnormality detection from endoscopic images. Sub-decisions are made based on associated component feature sets derived from the endoscopic images and predefined algorithms, and subsequently fused to classify the patient state. Bayesian probability computations are employed to evaluate the accuracies of sub-decisions, which are utilized in estimating the probability of the fused decision.

Markers for presymptomatic prediction of preeclampsia and intrauterine growth restriction.

Preeclampsia and intrauterine growth restriction are both characterized by placental malfunction. The pathological processes of abnormal trophoblast invasion, partial absence of maternal spiral artery modification, increased apoptosis of trophoblast cells, and placental ischemia are all associated with the release of specific molecules. These proteins, as well as cell-free fetal DNA and RNA might be detected in the maternal peripheral circulation, quantified, and used for early identification and prediction of preeclampsia and intrauterine growth restriction, prior to the appearance of the clinical symptoms.

Neurokinin B levels in maternal circulation during early pregnancy.

Neurokinin B levels were measured between the 10th-20th weeks of pregnancy, i.e., prior to the development of clinical symptoms, in women who developed preeclampsia or delivered a growth-restricted baby.

Plasma hepatocyte growth factor as a marker for small-for-gestational age fetuses.

Objective: To study the association between hepatocyte growth factor (HGF) levels and pregnancy outcome.

Study Design: Hepatocyte growth factor levels were measured in 42 plasma samples between weeks 14 and 21 of gestation using an enzyme-linked immunosorbent assay (ELISA). Results were correlated to pregnancy outcome and Mann-Whitney U-test applied to study the differences.

Elevated C-reactive protein levels during first trimester of pregnancy are indicative of preeclampsia and intrauterine growth restriction.

C-reactive protein (CRP) is a marker of tissue damage and inflammation. Maternal levels of CRP are elevated in overt preeclampsia, but there is still debate about its use as a predictive marker for preeclampsia during the first and second trimesters of pregnancy. In this study, we measured CRP levels during the first trimester of pregnancy in women who later developed preeclampsia or gave birth to a growth-restricted baby.

Feature extraction for the analysis of colon status from the endoscopic images.

Background: Extracting features from the colonoscopic images is essential for getting the features, which characterizes the properties of the colon. The features are employed in the computer-assisted diagnosis of colonoscopic images to assist the physician in detecting the colon status.

Methods: Endoscopic images contain rich texture and color information.

Circulating trophoblast in maternal blood.

This review describes the status of circulating trophoblast, but is considered in the perspective that only a specific subset of trophoblast cells circulates in the maternal blood. The consequences for isolation, identification and clinical potential are described.

Identification of triploid trophoblast cells in peripheral blood of a woman with a partial hydatidiform molar pregnancy.

In a woman with a partial hydatidiform molar pregnancy with 69,XXY karyotype, the presence of male fetal cells of trophoblastic origin was demonstrated in maternal blood by X/Y-chromosome specific PCR and by immunostaining combined with FISH on two cell populations isolated from maternal blood. Blood was obtained three weeks prior to the detection of fetal demise, at 13 weeks' gestation. Results were confirmed on formalin-fixed paraffin-embedded molar tissue, removed at 16 weeks' gestational age for therapeutic reasons.

Plasma placenta growth factor levels in midtrimester pregnancies.

Objective: Previous studies have shown decreased levels of placenta growth factor in serum of pregnant women with preeclampsia. The aim of this study was to investigate whether levels of placenta growth factor are decreased before the clinical onset of preeclampsia, and whether placenta growth factor levels are decreased in pregnancies complicated by intrauterine growth restriction.

Methods: From an ongoing longitudinal study, 101 plasma samples were collected from 72 pregnant women at weeks 11-21 of gestation.

HLA-G expression in trophoblast cells circulating in maternal peripheral blood during early pregnancy.

Objective: The aim of this study was to assess the use of circulating trophoblast cells in maternal peripheral blood for noninvasive prenatal diagnosis of numeric chromosomal aberrations.

Study Design: A combined procedure for immunocytochemical identification and deoxyribonucleic acid fluorescence in situ hybridization was used after a single enrichment step consisting of density gradient centrifugation. A specific HLA-G monoclonal antibody was used in combination with X and Y chromosome specific probes in deoxyribonucleic acid fluorescence in situ hybridization to confirm fetal identity of cells bearing HLA-G in the case of a male fetus.