Physiology of the Fetus

1. Introduction
2. Maternal-Fetal Exchange in Outline
3. Fetal Cardiovascular Physiology
   • The Three Shunts
   • Circulation and Streaming
   • Fetal Haemoglobin
4. Fetal Respiratory Physiology
   • Stages of Lung Development
   • Surfactant
   • Fetal Breathing Movements
5. Fetal Renal and Gastrointestinal Physiology
6. Fetal Endocrine and Metabolic Physiology
7. Fetal Immune Physiology
8. Fetal CNS and Sensory Physiology
9. Transition at Birth
10. Summary
11. Quiz

• The fetus exists in an oxygen-poor, glucose-rich, immunologically protected environment supplied by the placenta. Its physiology is built around maximising oxygen extraction from a blood supply with a low oxygen tension (the pressure of oxygen dissolved in the blood). It also bypasses the lungs and, in part, the liver until they are needed at birth.
• The fetal circulation has three shunts (channels that let blood bypass an organ). The ductus venosus is a venous bypass of the liver. The foramen ovale (a hole between the two atria) and the ductus arteriosus (a vessel joining the pulmonary artery to the aorta) are the other two shunts. Both are right-to-left cardiac shunts that bypass the lungs. Streaming (blood from different sources staying in separate layers as it flows) directs the most oxygenated blood to the brain and myocardium and the most desaturated (least oxygenated) blood to the placenta.
• Fetal haemoglobin (HbF, α₂γ₂, meaning two alpha and two gamma chains) binds 2,3-bisphosphoglycerate (2,3-BPG, a molecule that helps haemoglobin release oxygen) poorly. It therefore has a higher oxygen affinity (it holds on to oxygen more tightly) than adult haemoglobin. This shifts the oxygen dissociation curve (the graph of haemoglobin's oxygen saturation against oxygen pressure) to the left and supports placental gas exchange.
• Three transitions begin at birth. The first is aeration of the lungs (the lungs filling with air), helped by surfactant, which is produced from about 24 weeks. The second is a fall in pulmonary vascular resistance (the resistance to blood flow through the lungs). The third is closure of the fetal shunts. The foramen ovale closes functionally as left atrial pressure rises above right. The ductus arteriosus constricts, within about 24 to 48 hours in healthy term babies, in response to a rising arterial oxygen tension and falling placental prostaglandins (chemical messengers that keep the duct open). The ductus venosus closes over the first days as umbilical flow ceases. Failure of these transitions underlies many neonatal emergencies (emergencies in the first 28 days of life).

Introduction

Fetal physiology is unusual in that it is preparation for a life that has not yet started. The fetus must support its own metabolism, growth and development inside a tightly regulated maternal environment. At the same time it must build organs that will only function fully after birth: the lungs, kidneys, gut and immune system. The fetus makes several trade-offs. Its oxygen-poor blood is handled by haemoglobin that binds oxygen tightly. Its lungs are filled with fluid and bypassed by the circulation. Its kidneys make urine that adds to the amniotic fluid (the fluid surrounding the fetus) rather than clearing waste. Understanding these trade-offs explains both healthy fetal growth and many of the early neonatal emergencies.

This article focuses on the physiology of the fetus at term (a full-length pregnancy, from 37 weeks) and the changes at birth. The architecture of the placenta is covered next in The Placenta. Embryology of organ formation is in Development of the Reproductive System. The system-specific embryology articles are in Embryology. The maternal cardiovascular and respiratory adaptations in pregnancy are in Physiology of the Mother.

Maternal-Fetal Exchange in Outline

The placenta does much of the work that the lungs, gut, kidneys and liver do after birth. Practical points relevant to fetal physiology:

• Oxygen exchange. Maternal arterial blood entering the placenta has a P_O2 (partial pressure of oxygen, also called oxygen tension) of about 95 mmHg. The blood emerging in the umbilical vein has a P_O2 of only 30-35 mmHg. Fetal physiology functions at this oxygen tension throughout intrauterine life (life inside the womb). This fall in oxygen pressure between mother and fetus is offset by HbF's higher oxygen affinity, the higher haemoglobin concentration, and the higher cardiac output per kilogram in the fetus.
• Glucose crosses the placenta down its concentration gradient via GLUT1 transporters (carrier proteins in the cell membrane that move glucose across). Glucose is the principal fetal fuel.
• Amino acids are actively transported across the placenta against a concentration gradient, by Na⁺-coupled cotransporters (carrier proteins that move an amino acid across the membrane together with sodium).
• Free fatty acids cross more slowly. They need fatty acid transport and binding proteins in the placental cell membranes, so passive diffusion alone does not explain their transfer.
• CO₂ diffuses readily. The fetal P_CO2 (partial pressure of carbon dioxide) is slightly higher than the maternal value.
• Waste (urea, creatinine and bilirubin) is cleared by the maternal liver and kidneys.

Fetal Cardiovascular Physiology

The Three Shunts

The fetal circulation looks complicated at first glance because it must achieve two goals at the same time. It must deliver oxygenated placental blood to the body, and it must bypass the lungs (which do not yet exchange gas) and part of the liver. It does both with three shunts: one venous bypass of the liver and two right-to-left cardiac shunts that bypass the lungs. All three close after birth.

1. Ductus venosus. Connects the umbilical vein (carrying the most oxygenated blood in the fetus) to the inferior vena cava, bypassing part of the liver. In the human fetus, about 30% of umbilical venous blood takes this short cut at 18 to 20 weeks of pregnancy, falling to about 18% by 31 weeks. The rest perfuses the liver. The short cut lets well-oxygenated blood reach the heart without first passing through the liver.
2. Foramen ovale. An opening between the right and left atria, with a flap (the septum primum) acting as a one-way valve. Inferior vena caval blood arriving at the right atrium is preferentially streamed across the foramen ovale into the left atrium, again bypassing the lungs.
3. Ductus arteriosus. Connects the pulmonary artery directly to the descending aorta just beyond the origin of the great vessels (the large arteries that supply the head and upper limbs). Pulmonary vascular resistance in the fetus is high, because the lungs are unexpanded and hypoxic (low in oxygen). Most of the right ventricular output therefore takes this route into the systemic circulation, bypassing the lungs once again.

Diagram: the fetal circulation, showing the three shunts: the ductus venosus, which bypasses part of the liver, and the foramen ovale and ductus arteriosus, which are right-to-left shunts that bypass the lungs. The colour gradient highlights how the most oxygenated blood is streamed preferentially to the brain and myocardium.

Creative commons source by OpenStax College, CC BY 3.0.

Circulation and Streaming

The path of fetal blood, traced from the placenta:

1. Oxygenated blood enters the fetus via the single umbilical vein.
2. Between about 18% and 30% of this blood (depending on the stage of pregnancy) passes through the ductus venosus into the inferior vena cava. There it joins less-oxygenated blood from the lower body. Anatomical streaming inside the right atrium directs this oxygen-rich stream preferentially across the foramen ovale into the left atrium and on to the left ventricle.
3. From the left ventricle, blood is ejected into the ascending aorta and supplies the brain and myocardium: the two organs that need the highest oxygen tension.
4. Meanwhile, less-oxygenated blood returning from the upper body via the superior vena cava passes through the right atrium into the right ventricle and then into the pulmonary artery.
5. Most of this passes through the ductus arteriosus into the descending aorta. It is now mixed with the residual oxygenated blood from the left ventricle, supplies the lower body, and returns to the placenta via the two umbilical arteries.

Three key points to remember:

• The umbilical vein carries oxygenated blood. Most other veins carry deoxygenated blood. The exception is the pulmonary veins, which bring oxygenated blood from the lungs to the left atrium.
• The two ventricles work in parallel, not in series (both ventricles pump blood onwards to the body at the same time, rather than the right ventricle sending its blood through the lungs to the left). They share a single combined cardiac output, and in late pregnancy the right ventricle contributes about 60% of it.
• Streaming is partial, not complete. There is mixing at every step, so even the ‘best’ blood reaching the brain has a P_O2 of only about 25-30 mmHg. This is much lower than arterial values after birth.

Fetal Haemoglobin

The fetus copes with this low-oxygen environment by using fetal haemoglobin (HbF, α₂γ₂) instead of adult HbA (α₂β₂). The two γ chains differ from β chains in their interaction with 2,3-bisphosphoglycerate (2,3-BPG). 2,3-BPG normally stabilises the deoxygenated (T, or tense) state of haemoglobin, which releases oxygen. Because HbF binds 2,3-BPG poorly, this state is less stable and HbF holds on to oxygen more tightly. The oxygen dissociation curve is therefore shifted to the left compared with HbA. At any given P_O2, fetal blood holds more oxygen.

HbF is the dominant haemoglobin in the fetus. It is made from about 10 to 12 weeks of pregnancy until about 6 months after birth. The switch from γ-chain to β-chain synthesis begins late in the third trimester (the last three months of pregnancy) and is largely complete by 6 months after birth. The principles of oxygen transport are explained in Protein Function in Oxygen Transport; the genetic basis of haemoglobinopathies (inherited disorders of haemoglobin) is in Haemoglobinopathies.

Fetal blood also carries a higher haemoglobin concentration (around 17 g/dL at term) and a higher cardiac output per kilogram, both of which add to oxygen delivery despite the low P_O2.

Fetal Respiratory Physiology

Stages of Lung Development

The lungs develop in five overlapping stages, all of which are commonly tested:

1. Embryonic (weeks 3-7): the lung bud arises from the foregut (the front part of the embryonic gut tube) and the main bronchi form.
2. Pseudoglandular (weeks 5-17): the conducting airway tree is laid down, looking like a branching gland under the microscope. No respiratory exchange surface yet.
3. Canalicular (weeks 16-26): respiratory bronchioles (the first small airways with alveoli in their walls) develop and become vascularised (gain a blood supply). From around 24 weeks, type II pneumocytes (the lung cells that make surfactant) start producing surfactant. Surfactant is only one factor in whether a baby can survive. UK guidance from the British Association of Perinatal Medicine (BAPM, 2026) says that survival-focused care (care aimed at helping the baby to survive) should not be offered for babies born before 22 weeks. For babies born from 22 weeks up to 27 weeks, decisions are based on the baby's overall risk profile and not on the number of weeks of pregnancy alone.
4. Saccular (weeks 24-38): terminal sacs form and thin out their walls.
5. Alveolar (week 36 to about 8 years after birth in classical teaching, although a recent review reports that alveoli keep forming until young adulthood): mature alveoli appear and multiply. Most alveolar formation happens after birth.

Surfactant

Surfactant is a phospholipid-protein mixture that lowers alveolar surface tension, preventing alveolar collapse at end-expiration. It is produced by type II pneumocytes from approximately 24 weeks of gestation (24 weeks into the pregnancy), with production rising rapidly through the third trimester. The principal phospholipid is dipalmitoylphosphatidylcholine (DPPC); the surfactant proteins SP-A through SP-D contribute to organisation and host defence.

Without sufficient surfactant, alveoli collapse on each expiration and the work of breathing becomes overwhelming. This is respiratory distress syndrome (RDS) of the newborn. Two measures target surfactant deficiency, one to help prevent RDS and one to treat it:

• Antenatal maternal corticosteroids (steroid medicines given before birth, typically betamethasone or dexamethasone) are given to women at risk of preterm delivery (birth before 37 weeks). They accelerate type II pneumocyte maturation and surfactant production.
• Exogenous surfactant replacement (surfactant given from outside the body): animal-derived surfactant given to the preterm neonate after birth to treat established RDS. It is given alongside respiratory support, most commonly continuous positive airway pressure (CPAP, a steady gentle pressure that keeps the airways open).

Fetal Breathing Movements

The fetus performs fetal breathing movements from about the end of the first trimester. The lungs are filled with lung fluid, not air, and gas exchange does not occur, but the diaphragm contracts rhythmically. These movements are essential for normal lung development, particularly the stretch-driven proliferation of pneumocytes. Conditions that suppress fetal breathing or restrict thoracic (chest) expansion cause pulmonary hypoplasia (underdeveloped lungs). Examples are oligohydramnios (too little amniotic fluid), congenital diaphragmatic hernia (a hole in the diaphragm that lets abdominal organs move into the chest) and neuromuscular disease.

Most of the lung fluid produced during pregnancy is dealt with in two ways at birth. First, its production falls, triggered by the rise in adrenaline during labour. Second, the same adrenaline surge drives active sodium absorption through ENaC channels (epithelial sodium channels, which move sodium out of the airspaces into the cells of the lung lining). Mechanical squeezing of the chest during vaginal delivery contributes to the final clearance. Elective caesarean delivery (without labour) misses out on part of this process, which is one of the reasons why it is associated with transient tachypnoea of the newborn (TTN). TTN is fast breathing in the first hours of life caused by delayed clearance of lung fluid.

Fetal Renal and Gastrointestinal Physiology

The fetal kidneys begin producing urine from about 10 weeks. By the third trimester, fetal urine is the principal contributor to amniotic fluid volume. The fetus does not need its kidneys to clear waste, because the placenta does this. Even so, adequate fetal urine output is essential. It maintains the amniotic fluid volume, which in turn is essential for normal lung development and protects the umbilical cord from compression.

This explains the link between renal anomalies and lung problems in the neonate. Bilateral renal agenesis (absence of both kidneys; Potter sequence) produces severe oligohydramnios, pulmonary hypoplasia, and a characteristic facial appearance. Posterior urethral valves (folds of tissue that block the male urethra) and bilateral severe hydronephrosis (swelling of both kidneys from backed-up urine) can produce a similar picture through obstructive renal failure. Some medicines can also damage the fetal kidneys. ACE inhibitors (angiotensin-converting enzyme inhibitors, a class of blood pressure medicines) are not for use in pregnancy. In the second and third trimesters they carry a known risk of fetotoxicity (harm to the fetus), including decreased fetal kidney function and oligohydramnios. They also carry a risk of kidney failure, low blood pressure and high potassium in the newborn.

The fetal gastrointestinal tract develops motility (the ability to move its contents along) from mid-gestation. The fetus swallows amniotic fluid, and this swallowing is essential for normal gut development. Conditions that impair fetal swallowing cause polyhydramnios (too much amniotic fluid). Examples are anencephaly (absence of most of the brain and skull vault), gross neurological abnormality and oesophageal atresia (an oesophagus that does not connect to the stomach). The fetal bowel accumulates meconium: a sticky greenish-black mixture of swallowed amniotic-fluid debris, intestinal cells, bile and gut-derived enzymes. Meconium is normally retained until birth. Its release into the amniotic fluid (meconium-stained liquor; liquor means amniotic fluid) can indicate fetal compromise (a fetus that is not coping, for example because of too little oxygen). Meconium also reflects gastrointestinal maturity, so it is more common at term and post-term (42 weeks or more). On its own it does not prove that the fetus is stressed. In labour, however, NICE advises that its presence should still trigger a full risk assessment and a discussion with the woman about the option of CTG (cardiotocography, a recording of the fetal heart rate) monitoring. Meconium that the baby breathes into the lungs (aspirates) at delivery can lead to meconium aspiration syndrome.

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