Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
Introduction
The human lungs serve the critical purpose of
respiration, providing necessary oxygen to
functioning tissues and preventing hypoxia and
cell death.
At birth, the lungs become the source for gas
exchange between the external environment
and the blood. External respiration through the
lungs becomes essential to the survival of the
newborn.
The newborn lung continues to undergo
differentiation and growth well beyond birth
LEARNING OBJECTIVES
At the end of the discussion, you will be able
to :
1. Define what is Gestation.
2. Describe the embryology of the morula,
blastocyst, blastoderm, and trophoblast.
3. Identify the three germ layers and the body
structures that evolve from each.
4. Describe the development of the placenta
and umbilical cord and identify the major
anatomical structures of each.
5. List the five stages of fetal lung development
and the gestational age at which they occur.
6. Describe the anatomical milestones and
alveolar pulmonary development stages.
7. Describe three changes to fetal circulation
that occur during a normal delivery to assist the
newborn in transition to extrauterine life.
8. Given a marginally premature fetus, select a
method to assess fetal lung maturity.
What is Gestation?
 Gestation is the period of time between
conception and birth.
 During this time, the baby grows and
develops inside the mother’s womb.
 It is measured in Weeks, from the first
day of the woman’s last menstrual cycle
to the current date.
Arranged by Alexandra Caneda Lagahid
 A normal pregnancy can range from 38
weeks to 42 weeks.
Determining Gestational Age
 Accuracy of gestational age is important
for estimating fetal maturity, particularly
when lung development and immaturity
are concerned.
 Start of the last menstrual period to birth
typically is 280 days (40 weeks), with a
normal range of 38 weeks to 42 weeks.
 Commonly used techniques are Crown-
to-rump measurement, Biparietal
diameter, and a combination of head
circumference, abdominal
circumference, and femur length
 All measurements are taken using
abdominal or transvaginal ultrasound
1. Crown-to-rump measurement is used
in the first trimester (up to week 12), and
it is accurate starting at about 8 weeks.
- Measurement is taken from the top
of the head, or crown, to the bottom
of the buttocks, or rump.
2. Biparietal diameter, or the transverse
diameter of the head, can be used as
early at 13 weeks’ gestation to 20
weeks’ gestation, its accuracy is within
about 1 week of gestational age.
3. Combination of head circumference,
abdominal circumference, and femur
length will offer the best estimation of
fetal age at 36 weeks.
- BPD is 8.5 cm or greater, it can be
predicted that the infant will weigh
more than 2500 g (5.5 lb) or is at a
fetal age of 40 weeks.
Methods of Estimating Gestational age
1. Naegele’ s rule ( ― by Dates‖)
- estimated date of delivery is
calculated from the first day of the
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester

mother’s last period.( based on the

28 day cycle) . Then subtract 3 STAGES OF EMBRYOLOGIC
months and add 1 year and 7 days to DEVELOPMENT THROUGH IMPLANTATION
the date.

Example: For example: Your last

menstrual period began on September
9, 2020. Counting back 3 calendar
months would be June 9, 2010. Adding
1 year and 7 days would bring you to
June 16, 2021, as your estimated due
date.

Conception

 Once a month ovum is released

Ovum- A female egg
 The Egg moves through the Fallopian
Tube to the uterus
Uterus-Where the baby develops during
pregnancy
 If not fertilized it disintegrates and is
flushed away with menstruation.
BUT
If it is fertilized in the fallopian tube by a
sperm—conception occurs
- The union is called a zygote THE GERM LAYERS OF THE DEVELOPING
EMBRYO

Arranged by Alexandra Caneda Lagahid

Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
ORIGIN OF THE VARIOUS TISSUE
SYSTEMS FROM THE THREE EMBRYONIC
GERM LAYERS
A. ECTODERM
- Central nervous system: brain and
spinal cord
 Peripheral nervous system:
- cranial nerves and spinal nerves
- Sensory epithelia of the eyes, inner
ears, and nose
 Glandular tissues:
- posterior pituitary gland, adrenal
medulla
 Skin:
- epidermal layer
 Specializations of the skin:
- sweat and sebaceous glands, hair
follicles, nails, mammary glands
 Teeth: enamel
B. MESODERM
 Cardiovascular system:
- heart and blood vessels
- Lymphatic system vessels
 All connective tissue:
- general connective tissue, and
cartilage, bone, bone marrow, and
blood cells
 All muscle tissue:
- skeletal, cardiac, and smooth
 Skin:
- dermis and hypodermis
- Kidneys and ureters, spleen
- Reproductive tissues (not including
the germ cells)
 The three major body cavities:
- pericardium, left and right pleura,
and peritoneum
- Serous linings of organs within the
body cavities
 Teeth:
- Dentine
- cementum,
- and pulp
Arranged by Alexandra Caneda Lagahid
C. ENDODERM
• Digestive system:
- stomach, small and large intestines,
and epithelial lining of the entire
digestive system except parts of the
mouth and pharynx, and anus (which
are supplied by the ectoderm)
 Respiratory system:
- pharynx, lungs, and epithelial lining
of the trachea and lungs
 Urinary system:
- bladder, and lining of the urethra
- Liver and pancreas and epithelial
lining of all glands that open into the
digestive system
- Tonsils, thymus, thyroid, parathyroid
- Epithelial lining of auditory tube and
tympanic cavity.
DEVELOPMENT AND FUNCTION OF
INTRAUTERINE STRUCTURES
 The intrauterine structures include the
1. Placenta
2. Umbilical cord
3. Amnion
4. Amniotic fluid
Placenta
The Placenta functions as a Feto-Maternal
organ.
1. Fetal Placenta – develops from the
chorionic sac ( chorion frondosum)
2. Maternal Placenta- which develops
from the endometrium.
 Placenta acts as the organ of
respiration for the fetus.
 weighs around 1 pound, or 15% to 20%
of the fetal weight at term
 Chorionic villi are the beginning of the
placenta, where exchange of nutrients,
oxygen, CO2 , and waste takes place
between maternal and fetal blood.
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester

Amnion
- A sac that surrounds the growing
fetus and contains the amniotic fluid.
- It arises from the trophoblast around
the seventh gestational day.
- It begins as a small vesicle and
develops into a sac, which covers
the dorsal surface of the embryo.
- As gestation progresses it enlarges
and surrounds the embryo

The Umbilical Cord

Structure: It consists of mesodermal connective

tissue called the Wharton jelly, covered by
amnion.

Average length of 50cm (20 inches ) long.

It contains:
1. One umbilical vein carries oxygenated
blood from the placenta to the fetus.
2. Two umbilical arteries carry
deoxygenated blood from the fetus to
the placenta.
3. Wharton’s Jelly- prevents umbilical
cord from bending and pinch off,
stopping the flow of blood to the infant
Arranged by Alexandra Caneda Lagahid
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester

Amniotic Fluid  4 weeks – Mainstem brochi formed.

 FUNCTIONS OF AMNIOTIC FLUID  5 weeks – lobar bronchi formed
- Protection from traumatic injury  6 weeks – segmental bronchi formed 
- Thermoregulation during this stage that the diaphragm
- Facilitation of fetal movement begins its development and is fully
 Polyhydramnios- too much amniotic formed by the end of 7 weeks.
fluid or an AFI greater than 25 cm.
 Oligohydramnios- scanty or
decreased amount of amniotic fluid. AFI
below 5 cm.

Fetal Lung Development

 Lung development is divided into five
phases: Embryonic, Pseudoglandular,
Canalicular, Saccular, and Alveolar.

A. Embryonic Phase
 Begins approximately 26 days after
conception.
 21 days –primitive foregut outpouches.
 24-26 days – earliest time lung begin to
develop and lung bud identified.

Arranged by Alexandra Caneda Lagahid

Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
B. Pseudoglandular Phase
 gland-like appearance of the lung
during this stage.
 7 Weeks - the airway has branched to
about four generations. Develop
cartilage, smooth muscle cells, and
mucus glands.
- Larynx is also developing during this
phase. The tissue that will form the
epiglottis is present.
 8 Weeks - the vocal cords appear as
small folds of connective tissue in the
larynx.
- Also lymphatics appear first in the
hilar region of the lung.
 10 Weeks - cilia appear on the surface
of the epithelium of the trachea and the
mainstem bronchi.
- Lymphatics appears on the lung
itself.
 12 Weeks-major lobes of the lung
(three on the right side and two on the
left) are identifiable.
- Form the posterior wall of the large
bronchi.
 13 Weeks – Starting to have mucus in
the fetal lungs.
- Bronchial glands begin to develop,
which contain mucus-producing cells
and serous cells.
 14 Weeks - T lymphocytes can be found
in the respiratory system
Arranged by Alexandra Caneda Lagahid
C. Canalicular Phase
 Canalicular phase follows the
pseudoglandular phase and lasts from
approximately week 17 to about Week
26.
 Appearance of vascular channels, or
capillaries, which begin to grow by
forming a capillary network around the
air passages.
 Terminal non-respiratory bronchioles
undergo 2-4 more generations into
respiratory bronchioles.
 Formation of the acinus.
 Early differentiation into 2 distinct types
of pneumocytes is evident.
 Type I will form the alveolar capillary
membrane Type II cells will produce
pulmonary surfactant.
 Gas exchange units develops from
respiratory bronchioles.
 Breathing movement can be detected
between 18and 20 weeks.
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester

D. Saccular Phase
 True alveoli begin to appear at about 30
- 17 weeks - respiratory bronchioles weeks in the airways distal to the
develop. terminal bronchioles, forming short,
- 20-22 weeks – types 1 and type II shallow sacs known as saccules.
cells are identified.  Each saccule is made up of type I and
- Immature surfactants (sphigomylin type II cells and functions as an
and lecithin) seen. alveolar-capillary membrane.
- 24- 26 weeks – pulmonary  Saccules are closely grouped, making
capillaries develop. Cartilage may be the space between them, called the
present in about 10 to 14 airway septa, twice as thick as an alveolar wall.
generations.  Week 35, mature surfactant begins to
- Airway changes from grandular to appear. A neonate born at this point is at
tubular and increase in length and minimal risk for pulmonary complications
diameter. at birth caused by lung immaturity.
- Acinar units are formed, consisting
of a respiratory bronchiole, alveolar
ducts, and alveolar sacs.
- Fetal lung fluid is secreted by
epithelial cells of the lung to help
maintain the patency of the airways
and acinar units during their growth
until delivery.
- Fetal lungs secrete 250 to 300 mL
of fluid per day. It has very low pH,
bicarbonate, and protein levels, but
higher sodium and chloride
concentrations.

Arranged by Alexandra Caneda Lagahid

Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester

E. Alveolar Phase
 Alveolar phase begins at about week
36, approximately 1 month before a full-
term delivery.
 Mature Alveoli formation are quickly
proliferating during this phase, growing
in number to the millions by the time of
delivery.
 36-40 weeks –Lecithin production rises
rapidly . • Phosphatidylglycerol present.
 Alveolar mature and increase rapidly.
 Birth – 2 years- alveoli development
parallels alveolar growth.
 There is published evidence to show
that the number of alveoli present in the
lungs at term range from zero to 50
million.

Arranged by Alexandra Caneda Lagahid

Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester

When does the unborn baby’s heart begin

to beat?
PHASES OF FETAL LUNG DEVELOPMENT
 The heart beats begin between the 18th
and 25th day.
 ( Usually in Day 22, , cardiac
contractions are detectable and
bidirectional tidal blood flow begins)
 At 3.5 weeks the fetus:
- Will have formed the heart
- Begins development of the brain
and spinal cord.
- Starts forming the gastrointestinal
tract.

DEVELOPMENT OF THE RESPIRATORY

SYSTEM

Arranged by Alexandra Caneda Lagahid

Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
FETAL CARDIAC DEVELOPMENT
 Early Development
- Day 16 Angiogenic clusters (blood
islands) appear
- Day 18 Heart tubes form
- Day 21 Heart tubes fuse. They have
formed two tubes surrounded by a
sheath of myocardial cells(cardiac
muscle cells), fuse at the midline and
form a single, continuous chamber.
 Chamber Development
- Day 22 Fusion of heart tubes
complete. Heart begins to beat,
Bidirectional blood flow begins
- Day 23 Folding, looping, ballooning
begin
- Day 25 Atrial septation begins with
growth of septum primum
- Day 28 Ventricular septation starts
Endocardial cushions form
Unidirectional blood flow begins
- Day 32 Septum secundum starts
- Day 37 Foramen ovale complete
 Maturation
- Day 46 Ventricle formation complete
- Day 49 Four chambers complete
Valve formation matures
- Day 52 Aorta/pulmonary artery
complete separation
- Day 56 Valve formation complete
Arranged by Alexandra Caneda Lagahid
FETAL NEUROLOGICAL DEVELOPMENT
Neural system development is one of the
earliest to begin and is the last to be completed
after birth.
 Week 7- Neural plates develop.
 Week 9- Fetus makes spontaneous
movement. Germinal matrix appears
exponentially.
 Week 10- Fetus take his first breath
 Week 20- 27- Fetus responds with
arousal and body movement when
sound are delivered to maternal
abdomen.
 Week 22- Brain appears smooth.
 Week 25- Fetus will display stimulus
induced heart rate acceleration.
 Week 34- Germinal Matrix will begin to
disappear
 Week 36- Fetus reacts with FHR
acceleration, head turning and eye
movement.
Maternal–Fetal Gas Exchange
 As the umbilical cord matures, finger-
like projections extend into the outer
lining of the chorion, or chorionic
villi.
 Within the chorionic villi a capillary
network forms and connects to the
umbilical stalk.
 The villi intertwine into the blood-filled
lacunar cavities of the endometrium of
the maternal uterus.
 Oxygen, carbon dioxide, and nutrients
diffuse through the vast capillary surface
area of this indirect connection between
mother and fetus.
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
 As fetal development continues, the
region of this interface becomes limited
to the discus shaped placenta,
because the amniotic sac completely
fills the chorionic cavity.
 The umbilical cord connects the
placenta to the fetus with one large
vein and two smaller arteries.
 As the cord grows, the vessels tend to
spiral. Wharton’s jelly, a gelatinous
substance inside the umbilical cord,
helps protect the vessels and may
prevent the cord from kinking
The Fetal Circulation Shunts:
1. Ductus Venosus
2. Foramen Ovale
3. Ductus Arteriosus
Ductus Venosus
 In the fetus, the ductus venosus shunts
a portion of the left umbilical vein blood
flow directly to the inferior vena cava.
 Thus, it allows oxygenated blood from
the placenta to bypass the liver.
Arranged by Alexandra Caneda Lagahid
 The majority of the blood enters the
ductus venosus, a shunt which
bypasses the liver and puts blood to the
hepatic veins.
Foramen Ovale
 The foramen ovale is an anatomic
adaptation in the fetus to allow
oxygenated blood coming from the
umbilical vein via the inferior vena cava
to bypass the pulmonary circulation.
 Blood is shunted from the right atrium to
the left atrium, skipping the lungs.
 More than one third of the blood takes
this route.
 Hole in the inter atrial septum to shunt
oxygenated blood from the right to left
atria.
Ductus Arteriosus
 In the developing fetus, the ductus
arteriosus, also called Ductus Botalli, is
a blood vessel connecting the
pulmonary artery to the proximal
descending aorta.
 It allows most of the blood from the right
ventricle to bypass the fetus’s fluid-filled
non-functioning lungs.
 Most of this blood is shunted into the
aortic arch through the ductus
arteriosus.
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
Changes to Fetal Circulation at Delivery
 The change from intrauterine to
extrauterine circulation occurs within
minutes to hours after birth, and the first
breaths a newborn takes help to make
this transition possible.
 The first breath has to overcome the
surface forces of the lung, and it helps
create a gaseous functional residual
capacity (FRC) to replace the fetal lung
fluid initially held there.
Several factors during delivery that
stimulate a newborn to breathe.
1. Chemoreceptors in the aorta and
carotid artery regulate ventilation in
humans
- As the fetus descends into the birth
canal, he or she is cut off from the
placenta. This causes a drop in the
partial pressure of oxygen in the
blood which is detected by the
chemoreceptors and causes a
chemical message to be sent to the
brainstem to increase ventilation.
2. Thorax is compressed during
delivery.
- The thorax is compressed through
the birth canal during delivery, then
expands to normal size at delivery
creating a negative intrathoracic
pressure and causing air to enter the
lung.
3. Change of environment.
- Environmental changes from a dark
and warm uterus to a bright, cold,
and noisy delivery room.
4. Physical stimulation - the physical
stimulation of the infant by handling will
trigger his or her crying reflex by rubbing
the feet or the back of the infant.
TRANSITION TO EXTRAUTERINE LIFE
1. Clamping the umbilical vessels
removes the low-pressure system of
the placenta from fetal circulation.
2. Clearance of fetal lung fluid
Arranged by Alexandra Caneda Lagahid
- At delivery, the alveoli have no air in
them. Fetal lung fluid is secreted by
type II alveolar cells to stabilize the
structure of the lung in utero. In late
gestation and shortly before birth,
fetal lungs convert from fluid
secretion to fluid reabsorption.
- Epinephrine released during labor
inhibits the chloride channel within
type II cells, which causes the
secretion of lung fluid. It
simultaneously stimulates sodium
channels, which absorb lung fluid.
- Through this mechanism, the lungs
of a healthy term neonate after labor
contain only a minimal amount of
lung fluid.
- The majority of the fluid left is
mechanically expelled during
delivery, and any remaining fluid is
reabsorbed by the lymphatic system
during the first hours to days of
extrauterine life.
3. Filling of the lungs with air
- Fetuses begin ―practice breathing‖
during the second trimester (weeks
12 to 24) but refine the technique in
the last 10 weeks of gestation.
Inflation of the lungs initiates gas
exchange, which in turn dilates the
pulmonary arterioles.
4. Secretion of surfactant
-Surfactant will reduce the pressure and
also prevent the alveoli from collapsing
again during exhalation.
5. Establishment of functional residual
capacity
- The first breath has to overcome the
surface forces of the lung, and it
helps create a gaseous functional
residual capacity (FRC) to replace
the fetal lung fluid.
- Over the first few hours of life, FRC
will gradually increase and stabilize
the alveoli more permanently.
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
6. Vasodilatation of the pulmonary
vasculature and decrease in
pulmonary vascular resistance
- Rising systemic arterial oxygen
pressure (PaO2) stimulates the
release of endogenous pulmonary
vasodilating cytokines that act locally
to increase the diameter of the
pulmonary arterial vasculature and
stretching of the pulmonary
parenchyma also physically expands
the vasculature
7. Functional closure of two fetal
channels (foramen ovale and ductus
arteriosus)
- Once the cord is clamped and the
PVR decreases, pressures in the
right side of the heart decrease and
pressures in the left side increase.
- Because the foramen ovale flap
allows blood to flow only from right to
left, it closes when the pressures in
the left atrium become greater than
those in the right atrium. Closing the
foramen ovale further facilitates the
increase of blood flow to the lungs
necessary to maintain normal
extrauterine circulation.
- The functional closure of the ductus
arteriosus occurs as a result of being
exposed to an increase in PaO2, a
decrease in PVR leading to the
reduction in blood pressure within
the ductal lumen, a decrease in the
local production of prostaglandins,
and a reduction in the number of
prostaglandin receptors within.
Arranged by Alexandra Caneda Lagahid
ASSESSING FETAL LUNG MATURITY
A healthy neonatal period relies on proper fetal
growth and a normal labor and delivery
process.
Several tests for FLM are currently available •
 Lung profile test, consisting of:
a. Lecithin-sphingomyelin (L/S)
ratio
b. Presence of PG
 Shake test (also known as the foam
test)
 Surfactant-albumin (S/A) ratio (also
known as the TDx Fetal Lung Maturity
test)
 Lamellar body concentration
I. Lung Profile Test
A. Lecithin-sphingomyelin (L/S) ratio
- Developed in 1971
- It tests the ratio of lecithin, a principal
active component of surfactant, also
known as phosphatidylcholine (PC),
to the level of sphingomyelin, a
phospholipid found mostly in body
tissues other than the lungs.
- Lecithin levels in the amniotic fluid
increase in late gestation but
sphingomyelin remains constant
throughout pregnancy.
- An L/S ratio at 31 to 32 weeks’
gestation is usually around 1:1, and it
increases to 2:1 by 35 weeks’
gestation
- L/S ratio of 2:1 means that the lungs
are mature, and there is only a 2%
chance the fetus will develop RDS if
delivered
Topic 2: FETAL DEVELOPMENT AND TRANSITION TO EXTRAUTERINE LIFE
Neonatal Respiratory Care
Premid Outline, 1st Semester
B. PG Presence
- Phosphatidylglycerol ( PG) is a
minor constituent of surfactant that
generally appears several weeks
after the increase in lecithin
concentration.
- PG enhances the spread of
phospholipids on the alveolar
surface. - its presence indicates
advanced state of fetal pulmonary
maturity.
- PG appears first in amniotic fluid at
around 35 weeks’ gestation, when
mature surfactant is produced, and
levels increase at 37 to 40 weeks.
- The laboratory will report PG as
either “present” or “absent,”
making it a useful marker late in
pregnancy.
- This test is a good predictor of
mature lungs of the fetus.
II. Shake test
- also known as the foam test, is a
simple test that can be used to
indicate the need for further testing.
- A small sample of amniotic fluid is
mixed with ethanol and shaken for
15 seconds.
- It is left to sit for 15 minutes, and
then a reading is taken.
- The presence of a ring of bubbles in
the ethanol shows that there is
enough lecithin present to create
stable foam.
- A negative result (no foam present)
indicates that an L/S ratio should be
performed.
III. S/A ratio (Surfactant/Albumin
Ration)
- more widely known by its brand
name, TDx Fetal Lung Maturity test.
Arranged by Alexandra Caneda Lagahid
- measures the relative concentrations
of surfactant and albumin (milligrams
of surfactant per gram of albumin)
- A result showing more than 55 mg of
surfactant per 1 g of albumin is
considered mature
- values of less than 40 mg
surfactant per 1 g albumin are
considered immature - values of 40
mg to 54 mg surfactant per 1 g
albumin are considered
indeterminate.
IV. Lamellar Body Count
- Surfactant is stored within type II
cells in the form of lamellar bodies.
- These bodies are actively secreted
into the alveolar space and end up in
the amniotic fluid.
- smear of amniotic fluid is used to
count the number of lamellar bodies
in a given specimen.
- There is no clear consensus on
cutoff values that would predict
absence of RDS, however some
studies found success with lamellar
body count (LBC) of greater than
50,000.
- Testing must be conducted quickly to
avoid negatively low results.
- The lack of consensus on maturity
cutoffs and guidelines for test
validation make this a less frequently
ordered test.