Etiopathogeny

Abstract

Fetal growth restriction (FGR) is defined as fetal growth beneath the 10th percentile for gestational age on a standardized population growth curve. In contrast to small for gestational age (SGA) fetuses, there is a pathology causing poor growth. Causes for FGR can be divided into fetal, maternal, and placental disorders. Fetal-caused FGR can develop because of genetic disorders or infections during pregnancy. These factors lead to an early-onset and symmetric FGR. Maternal causes are disorders like high blood pressure, preeclampsia, diabetes, or malnutrition that lead to FGR, mainly asymmetric leading to brain sparing of the fetus and manifesting later on during pregnancy. Decreased uteroplacental blood flow, reduced blood volume, and reduced oxygen transport capacity are responsible for placental insufficiency. Maternal and placental causes have a common final pathway and lead to placental insufficiency. Placental insufficiency is a risk factor for stillbirth . Fetal development is completely dependent on the placenta, which provides for immune protection, nutrient delivery, and endocrine function and limits harmful exposures, among other roles. Placental dysfunction impacting one or more of these processes can lead to preterm birth (PTB), poor fetal growth, and other complications associated with fetal/neonatal morbidity and mortality. Therefore, assessment of placental health during pregnancy is an important part of obstetric care. However, the number of tools in current use for assessing placental health is largely limited to placental imaging and a handful of maternal serum markers. Unlike the fetus, the placenta is in direct contact with maternal blood during pregnancy. As a consequence, a placenta-specific signature is easily detectable in maternal circulation due to passive release of large multinuclear structures, cells, and subcellular fragments, which all contain trophoblast-specific nucleic acids, or from actively secreted products, including hormones and growth factors, exosomes, or signal molecules. The utility of these placenta-derived products for the prenatal diagnosis of chromosome abnormalities has been well-demonstrated. Furthermore, recent advances in high-throughput approaches to biomarker identification provide many new avenues to pursue the improved prenatal assessment of fetal well-being. However, there are still gaps in our knowledge that need to be addressed before such approaches significantly impact the detection of perinatal and newborn health outcomes. These gaps include a need for improved characterization of (1) the normal variation in placental structure and gene expression, (2) the distinct etiologies that underlie the conditions we want to predict, and (3) the factors that influence the measured levels of these biomarkers in maternal fluids.