Hemolytic disease of fetus and newborn

Mechanism of oxygen deprivation in HDF

The pathogenesis of hemolytic disease is based on an immunological conflict, which acts as one of the main causes of chronic fetal hypoxia. Due to the constant destruction of red blood cells, anemia develops, triggering a specific mechanism of oxygen insufficiency.

According to the classification by mechanism of development, hemic hypoxia is observed in HDF. It is characterized by the fact that oxygen may be present in sufficient quantities in the uteroplacental blood flow, but the fetal blood loses its ability to transport it. In its pure form, this type is rare: as reserves become depleted, it is joined by secondary tissue hypoxia, in which fetal cells lose the ability to assimilate oxygen due to enzymatic system breakdown.

In domestic terminology, it is important to distinguish periods: while the child is in utero, the term "fetal hypoxia" is used (foreign equivalents are distress or asphyxia). If the baby is born with signs of oxygen deprivation, the term "neonatal asphyxia" is applied.

How the fetus resists hypoxia (Compensation stage)

Evolutionarily, the fetus possesses powerful defense mechanisms against oxygen deprivation. In the initial stages of hemolytic disease, the medullary and cortical layers of the adrenal glands are activated, and catecholamines are released.

Stability is ensured by the following factors:

• Hemodynamic features: cardiac output reaches 198 ml/kg (in adults — only 70 ml/kg), and the baseline heart rate stays at 120–160 beats per minute.
• Fetal hemoglobin: constitutes up to 70% of all fetal hemoglobin. It has a unique affinity for oxygen, instantly binding it and easily releasing it to the tissues.
• Anaerobic glycolysis: the fetus actively uses glycogen reserves, and the resulting metabolic acidosis paradoxically increases resistance to hypoxia.
• Centralization of blood circulation: peripheral vessels constrict, while blood flow in the brain, adrenal glands, and placenta increases.

Note: due to intestinal vessel spasm, the anal sphincter may relax, leading to the release of meconium into the amniotic fluid. The presence of three arteriovenous shunts (ductus venosus, ductus arteriosus, and foramen ovale) results in almost all organs receiving mixed blood, which slows down the drop in $pO_2$.

Decompensation stage and severe consequences

If the immunological conflict is not stopped, prolonged severe hypoxia leads to adrenal exhaustion. Cortisol levels drop, vital centers are suppressed: bradycardia develops and blood pressure decreases.

Catastrophic changes occur at the microcirculatory level:

1. Arteriolar tone drops, the vascular bed dilates, and blood flow slows down to stasis.
2. Against the background of acidosis, blood viscosity increases, cells aggregate, and DIC syndrome is triggered.
3. The production of nitric oxide (NO) by the endothelium, which normally prevents platelet adhesion, is disrupted.
4. Vessel walls lose their tone and become permeable. The liquid part of the blood leaks into the tissues, causing edema, hypovolemia, and massive hemorrhages.

At the cellular level, lipid peroxidation (LPO) is activated. Potassium is released from cells, provoking hyperkalemia, which together with acidosis causes overexcitation of the parasympathetic nervous system. The outcome is necrosis in the central nervous system, intrauterine growth restriction (IUGR), and in severe cases — stillbirth or death in the early neonatal period.

Diagnostics of fetal condition

A pregnant woman can suspect a deterioration in the condition herself: first, fetal movements become more frequent, and then they weaken. A critical sign is 3 movements or fewer in 1 hour. An indirect symptom of chronic hypoxia is lagging of the fundal height (due to IUGR and oligohydramnios).

Instrumental methods are used for accurate assessment:

• Dopplerometry: allows the problem to be detected earlier than other methods. The main marker is a decrease in diastolic velocity in the umbilical artery (systolic-diastolic ratio SD ratio > 3.0). As the disorder progresses, abnormalities are recorded in the aorta and middle cerebral artery.
• Cardiotocography (CTG): in the initial stages (5–7 points), tachycardia up to 180 bpm and short-term monotony are visible. With pronounced distress (≤ 4 points), the rhythm becomes persistently monotonous, and the heart rate drops below 100 bpm. A paradoxical reaction appears — non-reactive non-stress test (decelerations instead of accelerations in response to movement).
• Biophysical profile: a score of 5 points and below indicates severe intrauterine hypoxia (absence of breathing movements and tone).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Assessment of acid-base balance (ABB) of cord blood by cordocentesis
• The role of nitric oxide (NO) in the regulation of vascular tone of the amnion and umbilical cord
• Mechanisms of development of DIC syndrome against the background of metabolic acidosis
• Paradoxical reactions on CTG: late decelerations and non-reactive test
• Effect of hyperkalemia on the parasympathetic nervous system of the fetus

Other topics in the "Obstetrics" section

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