Hemoglobin is a protein in red blood cells that carries oxygen throughout the body. While adults primarily produce adult hemoglobin (HbA), fetal hemoglobin (HbF) is the main oxygen transporter in a developing fetus. This unique protein is crucial for sustaining life in the womb, ensuring the fetus receives adequate oxygen for growth and development.
The Role of Fetal Hemoglobin in Development
Fetal hemoglobin is essential for a developing baby due to its distinct properties. HbF possesses a higher affinity for oxygen, allowing the fetus to efficiently extract oxygen from the mother’s bloodstream. Oxygen transfers across the placenta, where maternal and fetal blood circulate in close proximity. The stronger pull of HbF ensures the fetus can effectively “draw” oxygen from the maternal circulation, which has a lower oxygen tension than in the lungs. This capability helps meet the high oxygen demands of a growing fetus in the womb’s relatively low-oxygen environment.
The Gradual Shift to Adult Hemoglobin
The body undergoes a programmed change to transition from producing fetal to adult hemoglobin, beginning during late pregnancy (32-36 weeks gestation) with decreasing HbF and increasing HbA. After birth, this transition accelerates as the newborn enters an oxygen-rich environment. Increased oxygen availability signals the body to switch genetic expression from gamma-globin chains (HbF) to beta-globin chains (HbA). This response ensures the infant’s red blood cells are equipped with the hemoglobin type best suited for oxygen transport in the postnatal world. While the exact signal for the complete switch is not fully known, it involves transcriptional repressors that silence gamma-globin gene expression.
Typical Timeline of Fetal Hemoglobin Disappearance
Fetal hemoglobin levels decline rapidly after birth as the infant’s body adjusts to independent respiration. At birth, HbF typically accounts for 50% to 98% of a newborn’s total hemoglobin, reducing by approximately 5% per week or 10% per fortnight during the initial months. Fetal hemoglobin is largely replaced by adult hemoglobin by 6 months of age, with HbA becoming the predominant type. By one year old, HbF levels are expected to be very low, often less than 1% of total hemoglobin, approximating adult levels. However, trace amounts, typically less than 1%, may persist throughout adulthood in some individuals.
When Fetal Hemoglobin Levels Remain High
In some circumstances, fetal hemoglobin levels remain elevated into adulthood, not following the typical decline after infancy. One scenario is Hereditary Persistence of Fetal Hemoglobin (HPFH), a rare genetic condition where HbF production continues beyond the usual shutoff point. HPFH is often considered benign, typically not causing health problems on its own. People with HPFH can have HbF percentages ranging from less than 1% to as high as 30% of their total hemoglobin, with homozygotes potentially reaching 100%.
High HbF levels can also be advantageous in certain blood disorders, particularly sickle cell disease and beta-thalassemia. In sickle cell disease, HbF helps compensate for dysfunctional adult hemoglobin (HbS) by inhibiting red blood cell sickling, which reduces symptom severity. Similarly, in beta-thalassemia, where adult hemoglobin production is insufficient, elevated HbF can improve oxygen-carrying capacity. For individuals with these conditions, continued fetal hemoglobin production is either a genetic anomaly offering protection or a therapeutic target to alleviate symptoms. Drugs like hydroxyurea are used to stimulate HbF production in these patients.