Neonatal Hemochromatosis: Systematic Review of Prenatal Ultrasound Findings-Is There a Place for MRI in the Diagnostic Process?

Abstract

Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.

Keywords: gestational alloimmune liver disease; hemochromatosis; iron; liver failure; magnetic resonance imaging; prenatal; siderosis.

Figure 1

Details of the literature review—PRISMA diagram.

Figure 2

Prenatal findings in 74 cases evaluated in the literature review diagnosed with neonatal hemochromatosis and with confirmed extrahepatic siderosis, reported from 1993 to 2021.

Figure 3

Prenatal diagnosis algorithm proposal for suspected neonatal hemochromatosis in the first affected pregnancy.

Figure 4

Neonatal hemochromatosis in a hypotrophic fetus with idiopathic non-immune hydrops. (A) Ultrasound axial abdominal section depicting hepatosplenomegaly (arrow), ascites, and subcutaneous edema at 17 WGA. (B) Prenatal MRI 3T, T2 WI depicting fetoplacental anasarca and the liver with axial T2 hypersignal and (C) sagittal section (arrow) at 18 WGA. (D,E) Virtual autopsy using postmortem MRI, T2WI, and T1WI in the coronal plane depicting fetal liver with low signal (arrow), indicating the presence of iron at 21 WGA. (F) Hematoxylin–eosin staining (7×) showing two centrilobular veins and cords of hepatocytes. (G) Perls staining showing hemosiderin deposits (blue) in liver parenchyma (8×).