Oxygen is carried from the environment to the fetus by maternal and fetal blood along a pathway that invariably includes the maternal lungs, heart, vasculature, uterus, placenta and umbilical cord. Interruption of oxygen transfer can occur at any or all the points along the oxygen pathway.

External environment

In inspired air, the partial pressure exerted by oxygen gas is approximately 150 mmHg. As oxygen is transferred from the environment to the fetus, the partial pressure steadily declines. By the time oxygen reaches fetal umbilical venous blood, the partial pressure is as low as 30–35 mmHg. After oxygen is delivered to fetal tissues, the PO2 of deoxygenated blood in the umbilical arteries returning to the placenta is in the range of 15–25 mmHg [1-4]. The sequential transfer of oxygen from the environment to the fetus and potential causes of interruption at each step are described below.

Maternal lungs

Inspiration carries oxygenated air from the external environment to the distal air sacs of the lung – the alveoli. Normal alveolar PO2 is in the region of 105 mmHg. Interruption of normal oxygen transfer from the environment to the alveoli can result from upper airway obstruction or from interruption of breathing caused by depression of central respiratory control (narcotics, magnesium, seizure). From the alveoli, oxygen diffuses into maternal pulmonary capillary blood across a thin “blood–gas” barrier consisting of a single-cell layer of alveolar epithelium, an interstitial collagen layer and a single-cell layer of pulmonary capillary endothelium. Interruption of normal oxygen transfer from the alveoli to the pulmonary capillary blood can be caused by a number of factors including ventilation-perfusion mismatch and diffusion defects. Pulmonary causes of interrupted oxygenation may include respiratory depression due to medication or seizure, pulmonary embolus, pulmonary edema, pneumonia, asthma, atelectasis or adult respiratory distress syndrome.

Maternal blood

In maternal arterial blood, more than 98% of oxygen combines with hemoglobin in maternal red blood cells. Approximately 1–2% remains dissolved in the blood and is measured by the partial pressure of dissolved oxygen (PaO2). A normal adult PaO2 value of 95–100 mmHg results in hemoglobin saturation of approximately 95–98%. A number of factors affect the affinity of hemoglobin for oxygen. In general, the tendency for hemoglobin to release oxygen is increased by factors that signal an increased requirement for oxygen such as anaerobic glycolysis (reflected by increased 2, 3-DPG concentration), production of hydrogen ions (reflected by decreased pH) and heat. Interruption of oxygen transfer from the environment to the fetus due to abnormal maternal oxygen-carrying capacity can result from severe anemia or from hereditary or acquired abnormalities affecting oxygen binding (hemoglobinopathies or methemoglobinemia). Reduced maternal oxygen-carrying capacity is an uncommon cause of reduced fetal oxygenation.

Maternal heart

From the lungs, pulmonary veins carry oxygenated maternal blood to the heart. Blood enters the left atrium with a PaO2 of approximately 95 mmHg. Oxygenated blood passes from the left atrium, through the mitral valve into the left ventricle and out the aorta for systemic distribution. Interruption of oxygen transfer from the environment to the fetus at the level of the maternal heart can be caused by any condition that reduces cardiac output, including altered heart rate (arrhythmia), reduced preload (hypovolemia, compression of the inferior vena cava), impaired contractility (ischemic heart disease, diabetes, cardiomyopathy, congestive heart failure) and increased afterload (hypertension). In addition, structural abnormalities of the heart and/or great vessels may impede the normal ability to pump blood (valvular stenosis, valvular insufficiency, pulmonary hypertension, coarctation of the aorta). In a healthy obstetric patient, the most common cause of reduced cardiac output is reduced preload (hypovolemia, compression of the inferior vena cava).

Maternal vasculature

Oxygenated blood leaving the heart is carried by the systemic vasculature to the uterus. The path includes the aorta, common iliac artery, internal iliac artery, anterior division of the internal iliac artery and the uterine artery. From the uterine artery, oxygenated blood travels through the arcuate arteries, the radial arteries and finally the spiral arteries before exiting the maternal vasculature and entering the intervillous space of the placenta. Interruption of normal oxygen transfer from the environment to the fetus at the level of the maternal vasculature commonly results from hypotension (for example, regional anesthesia, hypovolemia, impaired venous return, impaired cardiac output, medications). Alternatively, it may result from vasoconstriction of distal arterioles in response to endogenous vasoconstrictors or medications. Conditions associated with chronic vasculopathy, such as chronic hypertension, long-standing diabetes, collagen vascular disease, thyroid disease and renal disease, may result in chronic suboptimal transfer of oxygen and nutrients to the fetus. Pre-eclampsia is associated with abnormal vascular remodeling at the level of the spiral arteries and can impede normal perfusion of the intervillous space. Catastrophic vascular injury (trauma, aortic dissection) is rare.

Uterus

Between the maternal uterine arteries and the intervillous space of the placenta, the arcuate, radial and spiral arteries traverse the muscular wall of the uterus. Interruption of normal oxygen transfer from the environment to the fetus at the level of the uterus commonly results from uterine contractions that compress intramural blood vessels and impede the flow of blood. Excessive uterine activity and uterine injury (rupture, trauma) are the most common causes of acute interruption of fetal oxygenation at this level.

Placenta