Background: Severe fetal anemias can cause high output cardiac failure. Mitochondria
are key regulators of cardiac function. However, the effects of an early phase of fetal anemia on the
fetal heart and cardiac mitochondrial function are not known.
Objective: The aim of this study is to compare mitochondrial function and cardiac biochemical
alterations in the fetal cardiac tissue between anemic and non-anemic fetuses.
Materials and Methods: A cross-sectional study was conducted in Fetuses affected by Hb Bart’s
disease (n=18) and non-anemic fetuses (n=10) at 17-20 weeks. Echocardiograms had been carried
out in all cases to assess prenatal cardiac function. Cardiac tissues were collected after pregnancy
termination for the determination of cardiac iron accumulation, mitochondrial function, including
mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling,
mitochondrial dynamics, inflammation, and apoptosis.
Results: Prenatal cardiac function evaluated by ultrasound was comparable between the Hb Bart’s
and non-anemic groups. In Bart’s group, the levels of cardiac mitochondrial depolarization and
swelling, and the TNF-α level were significantly higher, compared to the non-anemic group. On the
contrary, anti-inflammatory (IL-10) levels were significantly lower in the Hb Bart’s group.
Additionally, active caspase-3 and Bcl-2 expression were also significantly higher (P= 0.001,
P=0.035) in Bart’s group. The mitochondrial fission protein expression, including p-DRP1/total
DRP1, was significantly higher in Bart’s group. However, there was no difference in cardiac iron
accumulation levels between these two groups.
Conclusion: Despite equivalent prenatal cardiac function and comparable cardiac iron
accumulation in the Bart’s and non-anemic groups, fetal anemia is significantly associated with
cardiac mitochondrial dysfunction, increased mitochondrial fission, and increased inflammation and
apoptosis. These findings indicate that an early phase of fetal anemia without cardiac iron overload
can lead to cardiac mitochondrial dysfunction in fetuses with Hb Bart’s.