Fetal Gut Development

Question 1

How does the function of the newborn/adult gut differ from the fetal gut?

Answer 1

• In the newborn/adult gut GI system must be able to digest (breakdown mechanically or chemically) ingested food and absorb nutrients and water into the blood stream
• Therefore in the small intestine where most absorption of nutrients take place there must be mature villi to increase SA and facilitate absorption
• In the fetus nutrients are delivered directly to circulation via the placenta
• The function of the gut in the fetus is to develop sufficiently to a point where it can take on the role of nutrient absorption after birth
• This includes swallowing amniotic fluid

Question 2

Describe the development of the fetal GI system:

Answer 2

1. The GIT first appears at approximately 22 days of gestation as a constriction of the dorsal end of the yolk sac
2. Within 3 days, the primitive GIT develops into tubule that spans from what will be the mouth to the anus- this tubule is divided into a foregut, midgut and hind gut:

Foregut gives rise to: pharynx, oesophagus, respiratory tract, thyroid, thymus, stomach, upper duodenum, liver and pancreas

Midgut gives rise to: lower duodenum, small intestine and upper 1/2 of large intestine

Hindgut gives rise to: the lower half of the large intestine

3. Once the primitive structures arise, the small and large intestine continue to grow in size and complexity
4. By 7 weeks of gestation, the rapid growth of the liver forces the intestines to herniate into the umbilical cord
5. Between weeks 7 and 12 of gestation the intestines continue to develop within the umbilical cord
6. In week 12 of gestation, the abdomen is sufficiently large to allow the intestines to be retracted into the abdomen, whilst undergoing a series of controlled rotations to organise them into a more mature structure and morphology
7. For the remainder of gestation the GI system continues to develop within the abdominal cavity aided by fetal swallowing and the ingestion of amniotic fluid

Question 3

Explain the features of exomphalos:

Answer 3

• Exomphalos is a gut development defect in which the intestines fail to fully retract into the abdominal cavity
• This occurs in 1:600 live births
• It can vary in severity, with minor cases having a good outcome but severe (giant) or ruptured cases resulting in in utero/post natal deaths, respiratory insufficiency and oral feeding difficulties
• 80% of cases have no known cause and there has been no change in incidence of the condition

Question 4

Explain the features of gastroschisis:

Answer 4

• This is a hernia of the abdominal contents external to the umbilical cord caused by a defect in the abdominal wall
• It occurs in 1:3500 live births
• The rate of the condition is increasing (5 fold in 20 years)
• The risk is much higher in babies of women <20 (9 fold increase in 20 years), it is hypothesised this may be due to maternal drug intake

Question 5

Describe the characteristics of fetal swallowing:

Answer 5

• Fetal swallowing begins to occur around half way through the gestational period
• It has been shown experimentally that fetal swallowing involves the contraction of muscles in the neck, causes an increase in pharyngeal pressure and an increase in the flow of fluid in the oesophagus
• Fetal swallowing occurs in a pattern of single swallowing (<1/s) which mimics the swallowing of saliva or repetitive swallowing (0.5-3/s for >30 seconds) which mimics suckling
• It is unknown what drives fetal swallowing but it allows the ingestion of amniotic fluid which is very important for fetal gut development

Question 6

How does the ingestion of amniotic fluid aid gut development?

Answer 6

• The swallowing of amniotic fluid has been shown in vitro to induce the growth of intestinal explants and also in vivo increase intestinal weight and promote differentiation and development via increase in mucosal layer thickness and enterocyte migration
• It is hypothesised that this is due to factors in the amniotic fluid such as low levels of protein, growth factors and regulatory peptides promoting development, in addition to the stretch of the GI tract due to swallowed amniotic fluid promoting the production of local growth factors

Question 7

What other factors affect gut development (other than fetal swallowing)?

Answer 7

1. Cortisol: stimulates enterocyte proliferation and migration
2. Hypoxia/asphyxia: leads to IUGR which results in redirected blood flow away from the GI system so there is less oxygen and nutrients avaliable to the GI tract for growth in addition to the cessation of fetal swallowing so the GI tract no longer is able to ingest amniotic fluid

Question 8

What is an apical endocytic complex and its role in the fetus/newborn?

Answer 8

1. AECs are the vacuoles within enterocytes that form as a result of the enterocyte membrane engulfing fluid and endocytosing it into the cells
   - These vacuoles mostly converge on a large lysosome for digestion or may be delivered into the blood or lymphatic circulation
   - These AECs are present prior to and after birth

Role in the Fetus:
- In the fetus stomach acid secretion is suppressed so whole proteins are delivered to the intestines and there must be a means of absorbing them (they are too large to diffuse across the villi)

Role in Newborn:

• Stomach acid begins to be produced after birth, however milk is an excellent buffer so ingested proteins are not degraded in the stomach
• Therefore intact proteins including maternal antibodies are delivered directly to the small intestine epithelium where AECs allow them to be absorbed into the enterocytes
• These maternal antibodies provide passive immunity to the newborn
• The AECs eventually are no longer present soon after birth

Question 9

What is necrotising enterocolitis and a potential treatment?

Answer 9

• NEC is the inflammation and death of GI tissue
• It is primarily a disease of prematurity (90% of NEC is in preterm babies)
• It has a 20-30% morality rate (70% if surgery is required)
• Very difficult to diagnose early
• Treatments include:
  1. Antibiotics
  2. Cessation of oral feeds
  3. Fluid therapy
• Potential treatment: probiotics- have been shown to increase microbial diversity and stimulate enterocyte proliferation and is linked to reduced NEC