Fetal Development and Circulation

Fetal Development Overview

This lecture covers key aspects of fetal development, including hematopoiesis, circulation, lung maturity tests, and developmental landmarks. Note that fetal biometry (abdominal circumference, crown-rump length, BPD) is discussed in the 'Orbs and Radio Integration' video.

Fetal Hematopoiesis

Fetal hematopoiesis involves changes in the site of blood cell production and the type of hemoglobin produced throughout gestation. The following table summarizes these changes:

At term, fetal hemoglobin (HbF) constitutes 75-80% of the total hemoglobin, which ranges from 16 to 18 grams per deciliter. By six months after birth, HbA becomes predominant, and HbF levels drop to less than 1%, similar to adult levels.

Hemoglobin Comparison: HbF vs. HbA

• HbF ($\alpha2\gamma2$): Higher oxygen affinity compared to HbA.
  • Oxygen dissociation curve lies to the left of the maternal curve.
  • Lower levels of 2,3-DPG and carbonic anhydrase.
  • Resistant to acid and alkali denaturation.

Clinical Significance

The resistance of HbF to acid and alkali denaturation forms the basis for:

1. Singer's Alkali Denaturation Test (Apt Test):

   • Used to differentiate vasa previa from placenta previa.
   • It is a qualitative test.
   • Reagent: 1% potassium hydroxide or sodium hydroxide (an alkali).

2. Kleihauer-Betke Test:

   • Used to calculate the dose of anti-D immunoglobulin in Rh-negative females.
   • It is a quantitative test.
   • Reagent: Citric acid phosphate buffer (acid elution test).

Cardiac Output

• Fetus: $350 \frac{ml}{kg \cdot min}$
• Newborn: $500 \frac{ml}{min}$

Fetal Circulation

Fetal circulation differs significantly from adult circulation because the placenta is the site of oxygenation.

Key Differences

1. Oxygenation Site: Placenta.
2. Umbilical Vein: Carries oxygenated blood (80% oxygen saturation) from the placenta to the fetus.

Circulation Pathway

1. Umbilical Vein: Shunts most of the oxygenated blood via the ductus venosus into the inferior vena cava (IVC). A small amount (8-10%) goes via the portal sinus into the liver.
2. Inferior Vena Cava (IVC): Receives oxygenated blood from the ductus venosus and deoxygenated blood from the liver and lower limbs. Oxygenated blood is present on the medial side and deoxygenated blood on the lateral side.
3. Right Atrium: Directs oxygenated blood through the foramen ovale into the left atrium.
4. Left Atrium: Receives oxygenated blood from the right atrium (via foramen ovale) and deoxygenated blood from the lungs.
5. Left Ventricle: Pumps blood into the aorta for systemic circulation.
6. Right Ventricle: Receives partly deoxygenated blood from the right atrium via the tricuspid valve and pumps it into the pulmonary artery.
7. Pulmonary Artery: Shunts most (90%) of the blood via the ductus arteriosus directly into the aorta. Only 10% of the blood goes to the lungs, which then returns deoxygenated to the left atrium.
8. Aorta: Distributes mixed (oxygenated and deoxygenated) blood to the systemic circulation.
9. Umbilical Arteries: Two umbilical arteries return deoxygenated blood from the fetus to the placenta.

Fetal Shunts

• Ductus Venosus: Connects the umbilical vein to the inferior vena cava.
• Foramen Ovale: Connects the right atrium to the left atrium.
• Ductus Arteriosus: Connects the pulmonary artery to the aorta.

Fetal Development: Timelines

• Fetal breathing movements: 11 weeks.
• Fetal swallowing movements: 10-12 weeks.
• Fetal urine production: 8-11 weeks (definitely by 12 weeks).
• Meconium production: 16 weeks.
• Limb movements: 7 weeks (but not perceived by the mother).
• Quickening: Perception of fetal movement by the mother.
  • Primigravida: 18 weeks.
  • Multigravida: 16 weeks.
• Fetal cardiac activity: 5 weeks gestational age (3 weeks post-fertilization, or 21 days).
• Surfactant production: Begins by 20 weeks. Seen in amniotic fluid by 28 weeks.
• Gonad formation:
  • Testes: 7 weeks.
  • Ovaries: 8 weeks.
• Internal genitalia: 10 weeks.
• External genitalia: Recognizable by 12 weeks (female earlier than male).

Hormone Production

• Insulin: 12 weeks.
• HPA axis: 12 weeks.
• Glucagon synthesis: 8 weeks.

Fetal Lung Maturity Tests

These tests are performed on amniotic fluid obtained via amniocentesis in the third trimester, particularly when preterm labor is a risk, to evaluate fetal lung maturity.

Common Tests

Lecithin/Sphingomyelin (L/S) Ratio

• Ratio ≥ 2: Mature lungs.
• Ratio < 2: Immature lungs.

Phosphatidylglycerol (PG) in Amniotic Fluid

• Best and most specific test, especially for diabetic mothers.
• Present: Mature lungs.
• Absent: Immature lungs.

Lamellar Body Count (LBC)

• Lamellar bodies are packets of surfactant.
• < 15,000 per microliter: Immature lungs.
• > 50,000 per microliter: Mature lungs.
• 15,000 - 50,000 per microliter: Indeterminate.

Shake Test (Bubble Test, Clement Test)

• Outdated bedside test.
• Amniotic fluid and alcohol are shaken in a test tube. Bubble formation indicates mature lungs (due to surfactant, a soapy material).

Nile Blue Sulfate Test

• Outdated test based on the principle that phospholipids in fetal skin cells indicate phospholipid presence (and thus maturity) in fetal lungs.
• Amniotic fluid is mixed with Nile blue sulfate dye. Skin cells with phospholipids turn orange.
• > 50% orange cells: Mature lungs.

Key Points:

• Tests for lung maturity, not skin maturity.
• Mature cells appear orange, not blue.

Phosphatidylcholine Test

• Phosphatidylcholine > 500 ng/mL in amniotic fluid indicates mature lungs.

Optical Density

• Optical density > 0.15 at 650 nm indicates mature lungs.

Accelerating Fetal Lung Maturity

• Corticosteroids: Can accelerate fetal lung maturity.