Decidual macrophages and Hofbauer cells in fetal growth restriction

Placental macrophages, which include maternal decidual macrophages and fetal Hofbauer cells, display a high degree of phenotypical and functional plasticity. This provides these macrophages with a key role in immunologically driven events in pregnancy like host defense, establishing and maintaining maternal-fetal tolerance. Moreover, placental macrophages have an important role in placental development, including implantation of the conceptus and remodeling of the intrauterine vasculature. To facilitate these processes, it is crucial that placental macrophages adapt accordingly to the needs of each phase of pregnancy. Dysregulated functionalities of placental macrophages are related to placental malfunctioning and have been associated with several adverse pregnancy outcomes. Although fetal growth restriction is specifically associated with placental insufficiency, knowledge on the role of macrophages in fetal growth restriction remains limited. This review provides an overview of the distinct functionalities of decidual macrophages and Hofbauer cells in each trimester of a healthy pregnancy and aims to elucidate the mechanisms by which placental macrophages could be involved in the pathogenesis of fetal growth restriction. Additionally, potential immune targeted therapies for fetal growth restriction are discussed

Building consensus and standards in fetal growth restriction studies

Fetal growth restriction is a pathologic condition in which the fetus fails to reach its biologically based growth potential. There is inconsistency in terminology, definition, monitoring, and management, both in clinical practice and in the existing literature. This hampers interpretation and comparison of cohorts and studies. Standardization is essential. With the lack of a golden standard, or the opportunity to come to empirical evidence, consensus procedures can help to establish standardization. Consensus procedures provide no new information but formulate an agreement (as second best in the absence of robust evidence) for clinical and/or research practice on the basis of existing data. Consensus agreements need to be updated when new evidence becomes available and can change over time. In this chapter, we address the different issues that lack uniformity in FGR studies and management. Furthermore, we discuss several consensus methods and recent consensus procedures regarding fetal growth restriction

Practice variation in diagnosis, monitoring and management of fetal growth restriction in the Netherlands

Objectives: Fetal growth restriction (FGR) is a condition characterized by its complexity in diagnosis and management. There is a need for early accurate diagnosis, evidence-based monitoring and management of FGR to improve neonatal outcomes. This study evaluated differences and similarities in protocols of Dutch hospitals in the approach of (suspected) FGR in the context of the national guideline. Study design: FGR protocols were collected from Dutch hospitals between November 2019 and June 2020. Collected data were coded for further analysis and categorized in eight predetermined key domains of definition, preventive measures, testing, referral, monitoring strategies, interventions, mode of delivery and pathologic placenta examination. Results: 55 of 71 approached hospitals (78 %) responded to the request and 54 protocols (76 %) were obtained. Protocols used variable definitions of FGR, and management was mostly based on fetal biometry results in combination with Doppler results (n = 47, 87 %). In pregnancies with an abdominal circumference (AC) or an estimated fetal weight (EFW) 95th percentile, (preterm) labour induction was recommended in the majority of the protocols regardless of fetal size (≥36 weeks: n = 2, 4 %; ≥37 weeks: n = 41, 76 %, not stated: n = 11, 20 %). Conclusion: This study found practice variation in all predetermined domains of FGR protocols of Dutch hospitals, underscoring the complexity of the condition. The differences found in this study feed the research agenda that informs the process of improving obstetric care by better identification of the fetus at risk for consequences of FGR, improving evidence-based monitoring strategies to identify (imminent) fetal hypoxia, and more accurate timing of delivery

Correction: Perinatal mortality rate and adverse perinatal outcomes presumably attributable to placental dysfunction in (near) term gestation: A nationwide 5-year cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0285096.]

Perinatal mortality rate and adverse perinatal outcomes presumably attributable to placental dysfunction in (near) term gestation: A nationwide 5-year cohort study.

IntroductionPlacental dysfunction can lead to perinatal hypoxic events including stillbirth. Unless there is overt severe fetal growth restriction, placental dysfunction is frequently not identified in (near) term pregnancy, particularly because fetal size is not necessarily small. This study aimed to evaluate, among (near) term births, the burden of hypoxia-related adverse perinatal outcomes reflected in an association with birth weight centiles as a proxy for placental function.Material and methodA nationwide 5-year cohort of the Dutch national birth registry (PeriNed) including 684,938 singleton pregnancies between 36+0 and 41+6 weeks of gestation. Diabetes, congenital anomalies, chromosomal abnormalities and non-cephalic presentations at delivery were excluded. The main outcome was antenatal mortality rate according to birthweight centiles and gestational age. Secondary outcomes included perinatal hypoxia-related outcomes, including perinatal death and neonatal morbidity, analyzed according to birthweight centiles.ResultsBetween 2015 and 2019, 1,074 perinatal deaths (0.16%) occurred in the study population (n = 684,938), of which 727 (0.10%) antenatally. Of all antenatal- and perinatal deaths, 29.4% and 27.9% occurred in birthweights below the 10th centile. The incidence of perinatal hypoxia-related outcomes was highest in fetuses with lowest birthweight centiles (18.0%), falling gradually up to the 50th and 90th centile where the lowest rates of hypoxia-related outcomes (5.4%) were observed.ConclusionPerinatal hypoxia-related events have the highest incidence in the lowest birthweight centiles but are identifiable throughout the entire spectrum. In fact, the majority of the adverse outcome burden in absolute numbers occurs in the group with a birthweight above the 10th centile. We hypothesize that in most cases these events are attributable to reduced placental function. Additional diagnostic modalities that indicate placental dysfunction at (near) term gestation throughout all birth weight centiles are eagerly wanted