L18: Fetal Development and Adaptation to Extra-Uterine Life

Question 1

How and when does fetal lung develop?

Answer 1

• Fetal breathing movements - just using diaphragm 1-4 h/day during REM sleep
• This distension stimulates growth
• reflex neuromuscular development

Question 2

Why is surfactant production important?

Answer 2

Reduces surface tension for inflation (phospholipid) - cortisol accelerates production of surfactant

Question 3

What stimulates production of surfactant?

Answer 3

cortisol

Question 4

How is antenatal lung treatment carried out?

Answer 4

With glucocorticoids to accelerate lung development and surfactant

Question 5

How is respiratory distress syndrome treated?

Answer 5

In premature infants treated with surfactant

Question 6

Glucocorticoids stimulate surfactant production, what else do they stimulate? how is that important?

Answer 6

Interestingly after some time of glucocorticoids administration, liver glycogen starts to rise as well, glycogen stores useful for relatively instant energy, so that the newborn has some energy to draw on, until it’s established its own supply through nutrition

Question 7

When do lungs start to develop?

Answer 7

in ~20 weeks of pregnancy

Question 8

How are foetal shunts important regarding foetal blood circulation?

Answer 8

• incorporate placenta into fetal circulation
• ensure appropriate delivery of oxygenated blood and nutrients to fetus
• largely bypass fetal lung and liver

Question 9

How does the blood circulate the foetus? Explain the key steps

Answer 9

1. oxygenated blood arrives via umbilical cord (through umbilical vein)
2. the ductus venosus shunts oxygenated blood from the placenta away from the semifunctional liver and toward the heart
3. oxygenated blood from placenta enters right atrium via inferior vena cava
4. the foramen ovale allows oxygenated blood in the right atrium to reach the left atrium
5. the ductus arteriosus connects the aorta with the pulmonary artery, further shunting blood away from the lungs and into the aorta
6. mixed blood travels to the head and body and back to the placenta via the aorta.

Question 10

What are the veins/arteries in the umbilical cord? oxygenated or deoxygenated blood travels through them?

Answer 10

• Two blue umbilical arteries, coming from the baby, going to placenta, blue because deoxygenated
• Then it gets oxygenated and comes back through umbilical vein

Question 11

What are the shunts responsible for fetal circulation?

Answer 11

1. ductus venosus
2. foramen ovale
3. ductus arteriosus

Question 12

What is the function of ductus venosus?

Answer 12

• Oxygenated blood returns via umbilical vein towards foetal liver
• Flow split into two vessels:
  i) Larger is ductus venosus – shunt that bypasses the hepatic circulation
  ii) Direct link from umbilical vein to inferior vena cava
  iii) Smaller through liver and into vena cava via hepatic veins

Question 13

What is the function of foramen ovale?

Answer 13

• ‘hole in the heart’ – between R and L atrium
• Blood returning via vena cava into right atrium (RA) split into two streams by crista dividens (projects in foramen ovale)
• Larger stream through foramen ovale into left atrium and avoids pulmonary circulation
• Smaller stream through right atrium into right ventricle

Question 14

What is the function of ductus arteriosus?

Answer 14

• Output from right ventricle split into 2 channels
• Larger flow into ductus arteriosus, which carries blood to the aorta, avoiding the pulmonary circulation
• Smaller flow into foetal lungs

Question 15

How does maturation of fetal cardiovascular system happen?

Answer 15

• prostaglandin E2 maintains patent ductus arteriosus
• increase in cardiac output (cortisol)
• increase in peripheral resistance (cortisol)
• increase in blood pressure

Question 16

What are the changes from fetal to adult circulation? describe the process

Answer 16

• Close the three shunts
• This replaces circulation incorporating the placenta with the pulmonary circulation
• Loss of umbilical circulation, and
• Fall in pulmonary vascular resistance (lung inflation with air, and increase in pulmonary oxygen) – it’s decreased when the baby gets its first breath of air – blood goes into the lung much more easily
• Drop in pressure on right side of the heart (loss of umbilical input and rise in pulmonary outflow)
• Rise in pressure on left side of heart (with pulmonary venous return)
• Transient reversal of flow through ductus arteriosus – high pO2 stimulates ductus arteriosus to contract – blood supply instantly transformed
• Ductus arteriosus constriction inhibited by low pO2 of foetal blood and high prostaglandin (PG) E2
• Note that indomethacin (inhibitor of PG synthesis) can be used to treat patent ductus arteriosus (in preterm infants, but has renal and GI side effects)
• Foramen ovale flap valve – with reversal of pressure in atria – pushed against wall separating both sides of the heart

Question 17

When cardiovascular circulation is switched from foetal to adult, does pulmonary vascular resistance rise or fall? Why?

Answer 17

Fall in pulmonary vascular resistance (lung inflation with air, and increase in pulmonary oxygen) – it’s decreased when the baby gets its first breath of air – blood goes into the lung much more easily

Question 18

When cardiovascular circulation is switched from foetal to adult, does the pressure on the right side of the heart fall or rise? Why?

Answer 18

Drop in pressure on right side of the heart (loss of umbilical input and rise in pulmonary outflow)

Question 19

When cardiovascular circulation is switched from foetal to adult, does the pressure on the left side of the heart fall or rise? Why?

Answer 19

Rise in pressure on left side of heart (with pulmonary venous return)

Question 20

What is indomethacin used for?

Answer 20

• inhibitor of PG synthesis
• can be used to treat patent ductus arteriosus (in preterm infants, but has renal and GI side effects)

Question 21

What are the chronic diseases that can be programmed by intrauterine life?

Answer 21

i) Raised stress response
ii) Cardiovascular diseases (e.g. hypertension)
iii) Obesity
iv) Diabetes

Question 22

What is Barker hypothesis?

Answer 22

• The Barker hypothesis of “fetal origins” or “fetal programming” advocates that the origins of chronic diseases of adult life lie in fetal responses to the intrauterine environment
• Smaller weight babies had an increased risk of deaths from coronary heart disease and higher prevalence of insulin resistance in men

Question 23

How were the babies that were conceived during Dutch Famine affected?

Answer 23

• During the Dutch famine if the mother conceived when she was already depleted in nutrition, then at the early stage the risks are much higher for coronary heart disease, increased obesity, altered clotting and higher proportion of people reporting poor health

Question 24

What is the importance of cortisol to foetus?

Answer 24

• Reflects maturation of nervous system – released from foetal HPA axis
• Stimulates lung growth and development, and surfactant production
• Cardiac responses (increased output, peripheral resistance and blood pressure)
• Accumulates glycogen reserves
• Stimulus for the initiation of its own labour
• Foetal programming of the stress response has effects on manifestation of chronic diseases in adulthood (e.g. coronary heart disease, diabetes)