Prenatal and postnatal physiology

Last updated: November 14, 2022

Summary

Fetal and neonatal physiology differ. Prenatally, nutrient and gas exchange occur via the fetoplacental unit. Blood flows from the placenta to the fetus through the umbilical vein, while deoxygenated blood is removed through the umbilical arteries and directed back into the maternal circulation. The fetal circulation has three bypass shunts. Oxygenated blood bypasses both the liver (through the ductus venosus) and the lungs (via the foramen ovale of the fetal heart). The ductus arteriosus allows the deoxygenated blood to bypass the lungs by connecting the aorta and pulmonary trunk. Postnatally, the circulatory system and fetal organs must adapt to the new environment. All three shunts, as well as the umbilical arteries and the umbilical vein, obliterate. The obliterated vessels form ligaments, while the foramen ovale forms the fossa ovalis. Interruption of placental blood supply at birth (i.e., cutting of the umbilical cord) initiates changes in metabolism as well as respiratory adaptation of the neonate. Neonatal temperature regulation occurs via lipolysis of brown adipose tissue and peripheral vasoconstriction.

Fetal physiology

The fetal period begins at week 9 of gestation and continues until birth. After the rudimentary structure of the organs is established during the embryonic period (weeks 1–8), the organs begin to grow and differentiate. In many cases, the fine structure and function of individual organs develop slowly. Some organs do not develop completely until after birth. Fetal circulation and fetal organ function differ considerably from that of a child or adult. Intrauterine conditions ensure that nutrient and gas exchange occurs via the fetoplacental unit. The metabolism and hormones are also provided by the mother, especially at the beginning of development.

Fetal length can be determined on ultrasound starting from week 9 of development by measuring the crown-rump length (CRL). The CRL in centimeters is roughly equal to the square of the month of gestation.

The fetal period

All of the tissues and organs that develop during the embryonic period grow and differentiate during the fetal period (week 9 of development until birth). This period is initially characterized by an increase in fetal size and, from the sixth month onwards, an increase in fetal weight. Fetal body parts do not all grow at the same rate. Head growth, in particular, lags behind the growth of the rest of the body. For more detailed information on embryonic development (first eight weeks after fertilization), see “Embryogenesis”.

Overview of the fetal period
Weeks of development	Characteristics
Weeks 9–12	Intestinal loops return to the abdominal cavity (week 10). First breathing movements (week 11) The liver is replaced by the spleen as the primary site of hematopoiesis (week 12). Fetal sex can be identified (week 12). Start of urine production, which is excreted into the amniotic fluid Fetal waste products are delivered to the maternal circulation via the placenta. Despite a decline in head growth and doubling of the crown-rump length by the end of week 12, the head remains disproportionately large. Limbs have almost reached their final proportions.
Weeks 13–16	Start of coordinated movement of the arms and legs (week 14) As a result of active ossification, fetal bones are visible on ultrasound (week 16). Rapid growth Head and body proportions adapt to one another.
Weeks 17–20	Fetal movements become noticeable. The skin is covered with vernix caseosa. Visible hair and eyebrows Body completely covered with lanugo: short, fine, soft, nonpigmented hair, which is replaced by vellus hair during the third trimester
Weeks 21–25	Premature infants can theoretically survive from week 22. Surfactant secretion, which keeps the alveoli open, begins (week 20–22). Ductal development of the alveoli begins. Fingernails start to form. Start of fat deposition Pronounced weight gain
Weeks 26–29	Many premature infants survive at this stage with intensive medical care. Lung tissue is sufficiently mature to enable gas exchange. The CNS is mature enough to provide central respiratory drive and regulate body temperature. Hematopoiesis begins in the bone marrow (week 28). Eyelids open. Visible toenails
Weeks 30–34	The fetus responds to light. As a rule, infants survive if born at this stage of pregnancy.
Weeks 35–38	The fetus is fully mature at 37 weeks of gestation (term infant). Septation of air sacs

Fetal circulation

Fetal circulation must meet the needs of the fetus with the maternal placental supply, as it cannot rely on pulmonary respiration. It must also adapt rapidly to postnatal conditions. While the heart begins contracting in a coordinated manner at the end of week 4, resulting in directed blood flow, development of the fetal circulation extends up to week 9. In fetal circulation, delivery of oxygenated blood and clearance of deoxygenated blood follows the route described below.

Oxygenated blood

Direction: placenta (highest O₂saturation) → umbilical vein (O₂saturation ∼ 80%; PO₂∼ 30 mmHg) → liver → inferior vena cava → right atrium → foramen ovale (heart) → left atrium → left ventricle → ascending aorta → vessels of the head, neck, and arm
First bypass shunt: 50% of the oxygenated blood bypasses the liver and flows from the umbilical vein to the inferior vena cava via ductus venosus.
- Ductus venosus
  - A vein that connects the umbilical vein with the inferior vena cava
  - Loses its liver bypassing function after birth
  - Persists as ligamentum venosum of the liver
Second bypass shunt: Oxygenated blood bypasses the nonventilated lungs and enters the systemic circulation directly (right atrium → foramen ovale (heart) → left atrium).
- Foramen ovale (heart)
  - Opening in the interatrial septum of the heart
  - Usually closes during infancy as blood pressure rises in the left side of the heart after birth (see “Closure of the foramen ovale” below)
  - A foramen ovale that persists after birth is termed a patent foramen ovale (PFO).

Deoxygenated blood

Direction: vessels of the head, neck, and arm → superior vena cava → right atrium→ right ventricle → pulmonary trunk → ductus arteriosus → aortic arch and descending aorta → common iliac artery
- Return of deoxygenated blood to the placenta: internal iliac artery → umbilical artery (lowest O₂saturation) → placenta
- Supply of the lower limbs: external iliac artery → lower limbs → inferior vena cava
Third bypass shunt: The ductus arteriosus connects the pulmonary trunk with the aorta and conducts most of the blood directly from the right ventricle to the aorta, bypassing the lungs because of the increased pulmonary artery resistance.

Ductus arteriosus Directs Deoxygenated blood to the Descending aorta.

The umbilical vein transports oxygenated blood from the placenta towards the fetal heart, whereas the umbilical arteries direct deoxygenated blood from the fetus to the placenta.

Because of high resistance in the pulmonary trunk, pressure on the right side of the circulation is on average higher than that on the left side.

Postnatal adaptation of the circulatory system

Postnatal adaptation of fetal circulation
Process	Physiology	Postnatal remnant
Closure of the ductus arteriosus	↑ pO₂ in the pulmonary arteries (due to respiration) and ↓ prostaglandins (due to placental separation), which has a vasodilatory effect → ↓ pulmonary vascular resistance and ↑ pulmonary blood flow → reverse flow in the ductus arteriosus → functional closure of the duct through smooth muscle contraction within a few days → intimal proliferation and obliteration	Ligamentum arteriosum: located anterior to the left recurrent laryngeal nerve
Closure of the foramen ovale	↑ Pulmonary blood flow → ↑ pressure in the pulmonary veins and left atrium → simultaneous ↓ resistance in the pulmonary arteries → ↓ pressure in the right atrium → functional closure of the foramen ovale → adhesion of both septa → development of fossa ovalis	Fossa ovalis: remains as a remnant of the septum primum
Closure of the umbilical arteries	Contraction of the umbilical arteries to prevent blood loss Obliteration within 2–3 months	Proximal portion of the umbilical artery: remains open and forms the proximal portion of the superior vesical artery Distal portion of the umbilical artery: becomes the medial umbilical ligament in the medial umbilical fold of the anterior abdominal wall
Closure of the umbilical vein	Initially remains open after birth	Later closes to form the round ligament of the liver (included in the falciform ligament)
Closure of the ductus venosus	Obliterates after the ductus arteriosus	Ligamentum venosum: extends from the porta hepatis to the inferior vena cava

FEEtal patency of the ductus arteriosus is maintained by prostaglandins E₁ and E₂_.

Fetal and postnatal circulation

Fetal organ function

Fetal circulation and organ function differ considerably from that of a child or adult. Nutrient and gas exchange takes place in the fetoplacental unit. The lungs are not ventilated and are poorly perfused. Other organ functions also develop gradually during the course of prenatal development, some even after birth. The table below provides an overview of the differences between fetal and postnatal organ function. Organ development is not discussed, but can be found in the articles on the individual organs.

System/Organ	Overview of fetal functional development ^[1]
Endocrine system	Maternal hormones: Thyroid hormones and glucocorticoids can cross the placental barrier. Fetal hormones Insulin and glucagon: formed by the fetus beginning at week 11 of development ^[2] DHEA: formed in the physiologically enlarged adrenal cortex of the fetus and used by the placenta for estrogen synthesis Cortisol: formed in the adrenal gland from week 34 of development
Lungs	Fetal breathing movement, despite not being involved in gas exchange, is important for pulmonary development. Distal pulmonary epithelial cells produce chloride-rich fluid that distends the airway. Surfactant lipoproteins produced by type II pneumocytes decrease alveolar surface tension.
Liver	Metabolic function: from week 6 of development Bilirubin excretion: remains the task of the placenta during pregnancy but is slowly overtaken by the liver after birth
Blood and immune system	Hematopoiesis In the mesenchyme of the yolk sac wall from week 3 of development Later in the liver and spleen Gas exchange O₂affinity in fetal hemoglobin (HbF) is especially high to ensure oxygen diffusion from maternal to fetal hemoglobin. This makes the release of oxygen into fetal tissue more difficult. Hemoglobin concentration High because of the nature of gas exchange via the placenta, which results in low arterial oxygen saturation (approx. 80%) in the fetus ^[3] The relative hypoxemia induces hypoxia-inducible factor 1 production, which in return stimulates the fetal kidneys to produce erythropoietin, increasing red blood cell production. Immunoglobulins The fetus does not produce immunoglobulins. Maternal IgG crosses the placenta providing passive immunity.
Gastrointestinal tract	Fully functional in the third trimester The fetus swallows amniotic fluid which is absorbed in the intestine and results in the production of meconium. Meconium is usually retained in the bowel until after birth and may sometimes be present in amniotic fluid.
Kidney	Urine production begins between weeks 9 and 12 of development. The ability to concentrate urine develops after birth.
Brain	Myelination begins in the late fetal period and continues for at least another 10–12 years of life.

Lung maturity in preterm newborns can be achieved via intramuscular injections of glucocorticoids to the mother which induce pneumocytes maturation and thus the production of surfactant. Fetal hematopoiesis

Neonatal physiology

After birth, the shunts of the fetal circulation close to accommodate pulmonary respiration and the cutting of the umbilical cord. After placental circulation is interrupted at birth, the newborn takes its first breath of air. The neonate must now regulate their own circulation (see “Postnatal adaptation of the circulatory system” above), respiration, metabolism, and temperature, which require a series of adaptations. For more information on neonatal care, see “Assessment of the newborn”.

Respiratory adaptation of the newborn infant

Initiation: start of pulmonary respiration (after cutting the umbilical cord)
Lung ventilation: first breaths → alveoli are filled with air; → lungs inflate → change in pressure conditions

Metabolism

Changes: Once the placenta can no longer ensure a continuous supply of glucose, blood sugar levels decrease in the newborn.
Adaptation: Infants born at term meet their glucose requirements through gluconeogenesis and breastfeeding (or formula).

Thermoregulation

Normal body temperature of the newborn infant: 36.5–37.5 °C (97.7–99.5°F)

Changes: Large body surface area to weight ratio and loss of intrauterine warmth contribute to heat loss.
Adaptation
- Lipolysis in brown adipose tissue produces heat.
- Peripheral vasoconstriction induced by a catecholamine surge reduces peripheral heat loss.

Newborn infants with regulation disorders especially depend on exogenous protection against cooling.

References:^[1]

References

Morton SU, Brodsky D. Fetal physiology and the transition to extrauterine life. Clin Perinatol. 2016; 43 (3): p.395-407.doi: 10.1016/j.clp.2016.04.001 . | Open in Read by QxMD
Desoye G, Nolan CJ. The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy. Diabetologia. 2016; 59 (6): p.1089-1094.doi: 10.1007/s00125-016-3931-6 . | Open in Read by QxMD
Lautt WW. Hepatic Circulation. Morgan & Claypool Publishers ; 2009

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