Fetal hemoglobin Bart’s hydrops fetalis: pathophysiology, prenatal diagnosis and possibility of intrauterine treatment

Abstract

This review aimed at comprehensively summarizing current available reports regarding the ultrasound markers and biomarkers in predicting fetal Hb Bart's disease and evaluate the potential role of cardiac function assessment in a clinical practice. This review involves various methods in prenatal predicting fetal Hb Bart's disease or alpha-thalassemia major and attempts to provide valuable insights regarding the underlying mechanisms responsible for heart failure in Hb Bart's fetuses. Moreover, this information may be used to predict the cardiac function before the development of hydrops fetalis. Finally, the affected Hb Bart's fetus could be the best model of the study on cardiovascular response to fetal anemia, thus the cardiovascular ultrasound and molecular assessment may be helpful in predicting the prognosis or in making a choice in the management of the fetal anemia condition. In conclusion, ultrasound findings especially cardiomegaly and an increase in peak systolic velocity of the middle cerebral artery (MCA-PSV) are helpful in predicting the future hydrops fetalis and ultrasound assessment of fetal cardiac function is potentially helpful in clinical practice. Finally, this review highlights the pathogenesis of hydropic changes secondary to fetal anemia.

Nomograms of Fetal Cardiac Dimensions at 18–41 Weeks of Gestation

“…We have provided standardized and comprehensive reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. An accurate measurement of heart dimensions might be very useful to identify and monitor cardiac remodeling -change in shape, size, and structure -in response to pressure/volume overload or cardiac toxicity in many conditions, such as CHD [36,37], maternal diabetes [9], twin-to-twin transfusion syndrome [38], FGR [39], conception by ART [7], fetal anemia [40], congenital diaphragmatic hernia [41], or exposure to antiretroviral drugs [8]. A better understanding and follow-up of fetal cardiac adaptations could enable early interventions and minimize long-term cardiovascular consequences [42].…”

The best cutoff value of middle cerebral artery peak systolic velocity for the diagnosis of fetal homozygous alpha thalassemia‐1 disease

“…Currently, prenatal ultrasound screening of fetal anemia in pregnancy at risk for homozygous alpha thalassemia‐1 disease has played an important role in several high prevalence areas . Unfortunately, sonographic markers such as CTR, placental thickness, and MCA‐PSV are not sensitive enough for identifying all of the affected cases . Although MCA‐PSV has been accepted to be a gold standard for noninvasive screening of fetal anemia from other etiologies, the sensitivity of MCA‐PSV in screening of homozygous alpha thalassemia‐1 disease in the midtrimester was only 64.3% to 85.0% but with a high specificity of 98.6% to 100.0% .…”

“…Using MCA‐PSV above 1.5 multiples of the median (MoM) as a cutoff value, the sensitivity of MCA‐PSV for predicting fetal anemia from homozygous alpha thalassemia‐1 fetus at midtrimester was 64.3% to 85.0% with the specificity of 98.6% to 100.0% . Although highly effective, many authors proposed that the performance of MCA‐PSV was not as good for detecting all of the homozygous alpha thalassemia‐1 fetuses in contrast to anemia caused by other causes . In fact, MCA‐PSV > 1.5 MoM was responsible for identifying moderate to severe anemia but not mild anemia, suggesting that this may be one of the reasons .…”

Thalassemias: An Overview

“…This leads to severe hypoxia [19]. Intrauterine anemia leads to heart failure although the underlying mechanisms are still to be fully understood [20]. There are signs of pronounced fetal edema, hepatosplenomegaly and hydramnios.…”