Session 9: Fetal Growth and Development Flashcards
Define the Fetal Period
The fetal period is the stage of intra-uterine life from the end of the eighth week (beginning of ninth week) till term. During this time, systems laid down and structures created during the embryonic period grow and mature to fit the individual for birth and post-natal life. The fetal period involves preparation for the transition to independent life after birth.
- The most important body systems for determining survival outside the uterus are the nervous system, respiratory system, cardiovascular system and urinary system.
- Pre-Embryonic Period: Fertilisation => 3 weeks
- Embryonic Period: 3 => 8 weeks
- Fetal period: 8 => 38 weeks
- Pregnancy weeks calculated from date of LMP (definable event) i.e. conception weeks +2 so term is 40 pregnancy weeks. However this system is inherently inaccurate.
- The embryonic period is characterised by intense activity (morphogenesis) – organogenetic period. But absolute growth (increase in mass) is very small – except placenta! Growth and weight gain accelerate in fetal period.
Describe the pattern of growth and weight gain acceleration? What is used to measure development in early pregnancy?
Growth and weight gain accelerate during pregnancy
Crown Rump Length (CRL) increases rapidly in the pre-embryonic, embryonic and early fetal periods. Weight gain is slow at first, but increases rapidly in the mid and late fetal period. CRL is a good measure of development in early pregnancy.
[*] Embryo
- Intense morphogenesis and differentiation
- Little weight gain
- Placental growth most significant
[*] Early fetus
- Protein deposition
[*] Late fetus
- Adipose deposition (part of preparation for independent life after birth – important in thermoregulation).
Describe how body proportion changes during pregnancy
Body Proportion: body proportions change dramatically during the fetal period
[*] At week 9, the head is approximately half of the crown rump length (A)
[*] Thereafter, body length and lower limb growth accelerates. At birth the head is approximately one quarter of the crown rump length (B, C)
[*] 9 weeks: CRL is ~5cm
[*] 12 weeks: CRL is ~8.5cm
[*] 20 weeks: CRL is ~19cm
[*] 28 weeks: CRL is ~28cm
[*] 38 weeks: CRL is ~36cm.
Describe Fetal CO2 and the Lungs
Fetal CO2
[*] Maternal CO2 levels are lowered by hyperventilation stimulated by progesterone, which enable the fetus to have a relatively normal pCO2
Fetal Lungs
[*] The fetus makes breathing movements, which draw amniotic fluid into and out of the lungs 1-4 hours each day – ‘flushing lungs with amniotic fluid to keep cells nice and clear’. The lungs develop relatively late but exist by T3 although non-functioning.
[*] Surfactant is produced by type II pneumocytes from around week 20 but production is significantly increased after week 30 when the alveoli open in significant number and the surface area dramatically increases.
[*] Surfactant lowers the alveolar surface tension, such that inspiration is made with less effort post-natally.
[*] A deficiency, usually in pre-term infants, can lead to respiratory distress of the newborn.
Describe embryonic development of the lungs
there are 4 phases of maturation, which influence the viability of premature infants. The lungs develop relatively late as they are not needed until birth.
[*] Embryonic development creates only the bronchopulmonary tree (airways, no gas exchanging parts)
[*] NB: transoesophageal septum separates GI tract from respiratory tract.
[*] Functional specialisation occurs in the fetal period – creation of a membrane of which gas exchange can occur across.
[*] Major implications for pre-term survival (threshold of viability – viability is only a possibility after 24 weeks).
[*] Survival depends on:
- The presence of thin-walled air sacs for gas exchange
- Presence of surfactant to lower surface tension and allow air sacs to expand.
For the lungs and breathing, there are 4 stages of maturation. Describe the 1st Stage
Pseudoglandular (8-16 weeks): not viable, no air sacs, airways formed only as far as terminal bronchioles.
Duct systems begin to form within the bronchopulmonary segments created during the embryonic period.
Describe the 2nd and 3rd stages of lung maturation
Canalicular (16-26 weeks):
- Formation of respiratory bronchioles – budding from bronchioles formed during the pseudoglandular stage.
- Still no gas exchange but may be viable at the end.
- More vascular – vascularization of surrounding parenchyma
- Some terminal sacs
Terminal Sac (26 wk-term): viability improves with age.
- Terminal sacs begin to bud from the respiratory bronchioles.
- Some primitive alveoli
- Differentiation of pneumocytes
- Type 1: Gas exchange
- Type 2: Surfactant production from week 20
Describe the final stage of lung maturation
Alveolar period: late fetal to 8 years (95% of alveoli are formed post-natally)
[*] During T2 and T3 gas exchange occurs at the placenta. At birth, the lungs are filled with amniotic fluid aspirated by fetal breathing movements from wk 12-14, together with secreted fluid. Most is expelled during vaginal birth - any remaining is absorbed. Lungs must be prepared to assume full burden of gas exchange at birth.
- ‘Breathing’ movement: conditioning of the respiratory musculature
- Fluid filled: crucial for normal lung development
[*] Pulmonary resistance falls as alveoli open at the first breath. Blood flow increases in the pulmonary vessels.
Describe the development of the Nervous System
Nervous System: the first to begin development and the last to finish
[*] Whilst withdrawal from pain can be elicited at 15 weeks, thalamo-cortical projections do not reach maturity until week 29.
[*] Corticospinal (anatomical) tracts required for coordinated voluntary movements begin to form in the 4th month. Myelination of the brain only begins in the 9th month.
[*] Completion of myelination in corticospinal tracts is not complete until into the post-natal period (as evidence by increased infant mobility in the 1st year) but musculoskeletal movements are essential for fetal growth.
[*] No movement until week 8
[*] After week 6, a large repertoire of movements develops.
- ‘Practicing’ for post-natal life.
- E.g. suckling, breathing
Describe the development of the Central Nervous System
[*] The brain is the fastest developing organ in the fetus and infant. On average it accounts for 12% of the body weight at birth, falling to around 2% in adults.
[*] During the fetal period, important changes occur – structurally and functionally.
- Cerebral hemisphere becomes the largest part of the brain – gyri and sulci form after 5 months, as the brain grows faster than the head (cerebellar hemispheres grow larger than the skull)
- Histological differentiation of cortex in the cerebrum and cerebellum
- Formation and myelination of nuclei and tracts
- Relative growth of the spinal cord and vertebral column
Describe the development of the Sensory and Motor Systems
[*] Hearing and taste mature before vision.
[*] The organ of corti in the inner ear is well-developed in the fetus at 5 months but the retina is immature at birth. Little evidence exists for smell.
[*] The possibility of intra-uterine surgery on the fetus and invasive procedures in intensive care of the premature makes the development of somatic senses such as pain an important issue.
[*] Histological studies suggest that ascending tracts are present, though not myelinated, as early as 19 weeks.
Describe the clinical relevance of the development of the Sensory and Motor Systems
Fetal movements (‘quickening’)
- Fetal movements can be seen by ultrasound as early as 8 weeks, but not felt by the mother until about 17 weeks – can be up to 20 weeks in first pregnancy.
- Low cost, simply method of ante-partum fetal surveillance
- Reveals foetuses that require follow-up
Viability – is the brain sufficiently mature to control body functions e.g. breathing
Sensory awareness e.g. pain, sound
Maternal/neonatal nutrition and cortical development
Describe the fetal cardiovascular system
[*] The fetal circulation is adapted to bring oxygenated blood from the placenta to the fetus via umbilical vessels – arranged to ensure oxygenated blood collected by umbilical vein at the placenta is circulated around the fetus.
[*] The fetal lungs receive only the blood needed to sustain their own growth and development.
[*] Rapid and profound changes take place in the circulation at birth, related to the onset of air breathing.
[*] The definitive fetal heart rate is achieved around 15 weeks. Fetal bradycardia is associated with fetal demise. In identified pregnancies, additional surveillance is carried out that will measure fetal heart rate and uterine contractions.
Describe the fetal kidneys
[*] Fetal waste is ultimately excreted by the placenta.
[*] The functional fetal kidney is the metanephros
- Ascent is completed and function begins around 10 weeks.
- Kidneys have a lobulated form, until 4-5 years of age.
- Glomeruli and some tubules are present at 10 weeks, pelvis, calyces etc by 23 weeks.
- Histological differentiation of cortex and medulla is almost complete by 8 months.
- Fetal urine is a major contributor to amniotic fluid volume.
- Fetal kidney function is not necessary for survival during pregnancy, but without it there is oligohydramnios.
Describe the bladder in the fetus
- In the fetus and infant it lies in the abdominal cavity. Urine enters the bladder and is emptied into the amniotic fluid, to be swallowed by the fetus.
- The bladder fills and empties every 40-60 minutes in fetus – can be seen on ultrasound scans.
- This is used clinically to assess fetal urinary function.
Describe the Fetal Glucose
[*] The fetus relies upon relatively high maternal blood glucose to drive glucose across the placenta and support fetal growth and development.
[*] Fetal insulin secretion commences at week 10.
What is classified as growth restriction? Differentiate between asymmetrical and symmetrical growth restriction
[*] A fetus is regarded as having ‘growth restriction’ if weight is below the 10th percentile for gestational age. Depending on the cause a fetus with growth restriction may be compromised in the uterine environment and require closer monitoring in order to allow the continuation of the pregnancy to term
[*] Symmetrical Growth Restriction
- Growth restriction is generalised and proportional
[*] Asymmetrical Growth Restriction
- Abnormal growth lags
- Relative sparing of head growth
- Tends to occur with deprivation of nutritional and oxygen supply to fetus
Why is it important to estimate fetal age?
Estimation of fetal age: it is important to be able to distinguish between a fetus born prematurely, i.e. pre-term and one showing intra-uterine growth retardation (i.e. full term but small).
Age may be estimated by a range of methods of varying accuracy.
What development criteria can you use to estimate foetal age?
Accurate measurements and predictions can be made in utero by ultrasound
- Crown-rump (CR) length (used in T1)
Measured between 7 and 13 weeks to date the pregnancy and estimate the Estimated Due Date (EDD).
Scan in T1 also used to check location, number and viability
Becomes less accurate in later pregnancy.
- Foot length
- Biparietal diameter of head (used in T2/T3): the distance between the parietal bones of the fetal skull. Used in combination with other measurements to date pregnancies.
- Abdominal Circumference and femur length used in combination with biparietal diameter for dating and growth monitoring, and is also useful for anomaly detection e.g. foetal growth retardation which may or may not be head-sparing.
- 3- or 4-D ultrasound: new wave of obstetric ultrasonography but not likely to replace standard ultrasound scan – can be a complimentary tool.
- Weight after delivery
- Appearance after delivery
How can Symphysis-Fundal Height be used to estimate foetal age?
Ante-natal assessment of fetal well-being involves regular measurements of uterine expansion, which is a crude measure of growth of fetus.
- Distance between symphysis pubis to top of uterus (i.e. fundus). It can be measured with a tape measure (e.g. about 20cm at 20 weeks, 36 cm at 36 weeks then, plateaus).
- Alternatively, the height of the fundus is assessed in relation to other structures such as the umbilicus or xiphisternum.
- But can only be done when the uterus has moved into the abdomen - uterus is palpable above the pelvis after gestational week 12.
- A lag of 4 cm or more of the fundal height is suggestive of intrauterine growth restriction/fetal growth restriction.
- Sources of variability:
- Number of fetuses
- Volume of amniotic fluid
- Extent of engagement of head
- The lie of the fetus
What is meant by Daily Rhythms`/
A fetus has daily rhythms of heart rate, breathing and activity which are good indicators of maturity and development of physiological functions.
Heart rate variability is a good index of developing control systems. This development process continues after birth for 3 or 4 months
Describe the foetal circulation in detail
[*] The fetus must cope with low pO2 blood arriving in the wrong place (blood would have lost much of its oxygen before reaching the brain) but this is not a major problem, as in the foetus the lower body is relatively small and not that active metabolically.
[*] Umbilical venous blood (~70% oxygen saturated) is shunted around the liver by the ductus venosus. It mixes with a small amount of desaturated venous blood from the lower body in the ascending inferior vena cava (the venous side of fetal circulation) so saturation drops to 65%.
[*] Mixing with venous blood from the brain, which arrives at the right atrium via the descending superior vena cava, is largely prevented by the crista dividens, which directs the oxygenated blood towards the foramen ovale, a hole between the right and left atrium, which allows blood to by-pass the right ventricle and the lungs and enter the left heart directly. Right atrial pressure > left.
[*] Dexoygenated blood from the brain passes through the right heart towards the lungs. The collapsed (fluid-filled, oxygen-deficient) lungs of the fetus offer a high resistance to blood flow (via hypoxic pulmonary vasoconstriciton) and most of the output of the right heart flows instead through the ductus arteriosus, which links the pulmonary artery with the aorta, joining the latter at a level below the arterial outflow to the brain.
[*] The oxygenated blood directed to the left heart via the foramen ovale is therefore mixed with very little blood from the lungs in the left atrium, and remains well oxygenated (~60%), so that the left ventricle can pump it out to the aorta and up to the brain. Oxygen content is ~ 7 mmol.l-1 which is enough to support brain growth and development.
[*] The remaining arterial flow joins the flow from the ductus arteriosus to supply the rest of the body (whose needs are less critical) and to return to the placenta (which has very low resistance) via the 2 umbilical arteries (branches of internal iliac arteries) for reoxygenation.
[*] In summary, flow goes left heart – right heart rather than vice versa. This pattern of circulation requires that the pressure in the left atrium should be lower than that in the right, so blood will flow the right way through the foramen ovale, and the pressure in the pulmonary artery is higher than that in the aorta, so flow in the ductus arteriosus will be in the right way. Both requirements are met in the fetus because of the high flow resistance of lungs (hypoxic pulmonary vasoconstriction)
Describe Adaptations of the Foetal Circulation at birth
[*] At birth, a combination of physical trauma and cold temperatures induces the neonate to take its first breath. This leads to a dramatic reduction in pulmonary vascular resistance (removal of hypoxic pulmonary vasoconstriction) and a dramatic rise in arterial pO2.
[*] The fall in pulmonary vascular resistance causes left atrial pressure to rise in response to the right atrial pressure (greater venous return to LA), so closing the foramen ovale (pressure in LA>RA). This occurs within minutes.
[*] Smooth muscle sensitive to high pO2 in the wall of the ductus arteriosus contracts to close the ductus, so both fetal shunts are rapidly closed just by taking the first breath. Both shunts close off completely within a few weeks.
[*] Increased O2 saturation of blood and decreased [prostaglandins] (placenta has been removed) lead to constriction of both ductus arteriosus and the umbilical arteries.
[*] The ductus venosus variably remains open for several days after birth, but closes within two-three months. A sphincter in the vessel constricts shortly after birth, re-directing all blood through the liver sinusoids; this is again regulated by pO2 levels.
- Stasis of blood in umbilical vein and ductus venosus
- Clotting of blood
- Closure due to subsequent fibrosis
What is meant by the Double Bohr Effect?
Double Bohr Effect: an increase in pCO2 or [H+] concentrations results in Haemoglobin losing affinity for and releasing more oxygen. This is called the Bohr effect. This happens both in the maternal and fetal blood (partially because of acid-base changes), so is termed the Double Bohr Effect
The umbilical artery has a higher amount of pCO2 and lower pH compared to the umbilical vein. The uterine artery has a higher amount of pCO2 and lower pH compared to the uterine vein.
Fetus has a higher haematocrit than mum - more Hb and different (HbF).
