Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 150

Many genetic conditions can be associated with FGR, but these are individually rare. The only relatively common known genetic cause of FGR is CPM, typically occurring as trisomy in some or most cells from the placenta, with a predominantly normal diploid fetus. CPM is present in approximately 10 percent of placentas associated with FGR pregnancies (after exclusion of constitutional chromosomal abnormalities).^53–56 In the past, CPM was generally only diagnosed prenatally when chorionic villus sampling (CVS) was performed, with trisomy 16 being one of the most common trisomies involved when there is poor fetal growth. CPM can also be detected by noninvasive prenatal testing (NIPT), which is based on genetic analysis of DNA that is largely derived from the placental trophoblast and increasingly used routinely in prenatal assessment.^{57, 58}

Although there is no identifiable placental pathology characteristic of placental (mosaic or nonmosaic) trisomy, certain features are more likely to be present. Placentas tend to be small, although fetal–placental weight ratio is often preserved.⁵⁹ In early gestation, there may be trophoblastic irregularities reminiscent of hyperplasia, with a lacey appearance, and increased invaginations or inclusions of trophoblastic epithelium.⁶⁰ In some cases of trisomy 16, ultrasound examination shows cystic changes, raising the clinical possibility of partial molar pregnancy but those changes are often not appreciated until after delivery of the placenta.⁶¹ Although not common, there are reports of other trisomies with a histological partial hydatidiform mole (PHM)‐like phenotype, including trisomies 7, 15, and 22.⁶²

The frequency with which CPM is identified as the explanation for FGR may be dependent on the criteria used to diagnose FGR and the prevalence of environmental risk factors for FGR (smoking, insufficient maternal nutrition, etc.) in the population. In addition, CPM would be considerably more likely when placental insufficiency occurs in the presence of older maternal age, a strong risk factor for trisomy. However, CPM and placental pathology can occur in the absence of IUGR, and further research is needed to clarify these relationships.

Amniocentesis for chromosome analysis in the second trimester may be recommended if fetal growth is discrepant for gestational age. Similarly, FGR detected in the third trimester would lead to serious consideration of an amniocentesis, since discovery, for example, of a trisomy, may well influence the mode and management of delivery. Chromosome analysis of the placenta at term may be warranted if there are concerns for the baby's development, especially if cord blood is not obtained. Placental mosaicism may be associated with fetal uniparental disomy or the trisomy may not be entirely confined to the placenta (i.e. low level fetal mosaicism can be present). For example, trisomy 7 in the placenta can be associated with fetal maternal uniparental disomy (UPD) 7, which can cause Silver–Russell syndrome (SRS),^{63, 64} a condition characterized by severe FGR and dysmorphic facial features. If placental investigation is undertaken, it is important that specimens from multiple sites of the placenta are tested to diagnose the underlying mosaicism, as it is often present in only a subset of sampled sites.^{53, 65}