Normal fetal development

and growth
? Why fetal development and growth are important
⚫ FG and birthweight are important determinants of
immediate neonatal health and long-term adult
health.
⚫ Fetal, maternal and placental factors affect FG
and development.
⚫ Specific shunts in fetal circulation that ensure
that the best oxygenated blood from the placenta
is delivered to the fetal brain, and fetal circulation
transitions at birth to an adult circulation.
⚫ To be aware of normal development of fetal organs
during pregnancy, how fetal structural abnormalities
arise and what effects they have on the fetus and
neonate.
⚫ To recognize the importance of normal amniotic fluid
physiology to FG and development.
⚫ For understanding the complications that may arise
in pregnancy and for the neonate. For example, to
explain why preterm infants are at risk of RDS, and
why bowel protruding into the umbilical cord at 10
weeks’ gestation is normal and is not diagnosed as
an omphalocele (exomphalos).
Fetal growth
⚫ FG, affects long-term health of the adult, which is
associated with chronic conditions include coronary
heart disease, stroke, DM and HT, assessed by SFH
and EFW.
⚫ The fetal size is, its size for gestational age and is
presented on centile charts. Centile charts can be
designed for a population
⚫ Customized centile, depend on maternal height,
weight, parity, ethnicity and fetal sex.
⚫ SGA, is fetus less than the 10th centile.
⚫ FGR, is fetus failed to reach their full growth
potential.
A customized SFH chart illustrating the 10th, 50th
and 90th centiles and normal fetal growth
Population centile chart for EFW by US measurements. Fetus (A) has
.normal growth; fetus (B) has suboptimal growth
FGR associated with increased risk of:
⚫ Perinatal morbidity and mortality.
⚫ Intrauterine hypoxia/asphyxia.
⚫ Stillborn.
⚫ Hypoxic-ischaemic encephalopathy (HIE).
⚫ Multiorgan damage or failure
⚫ Neonatal hypothermia.
⚫ Neonatal hypoglycaemia.
⚫ Infection.
⚫ Necrotizing enterocolitis.
⚫ Cerebral palsy.
Interventions to deliver the GR fetuses early from the
intrauterine environment may improve outcome.
Determinants of FG and birth weight
⚫ FG is dependent on adequate delivery, and transfer
of nutrients and O2 across, the placenta, which relies
on:
1. Appropriate maternal nutrition
2. Placental perfusion.
3. Fetal hormones that affect the metabolic rate,
growth of tissues and organ maturation.
⚫ Insulin like growth factors (IGFs) coordinate and
increase the growth throughout late gestation.
⚫ Insulin and thyroxine (T4) are required through late
gestation to ensure appropriate growth .
⚫ Fetal hyperinsulinaemia, which occurs in
association with maternal DM when
maternal glycaemic control is suboptimal,
results in fetal macrosomia due to
excessive fat deposition.
⚫ This leads to complications such as:
1. Late stillbirth.
2. Shoulder dystocia.
3. Neonatal hypoglycaemia.
 Fetal influences:
1. Genetic: trisomies 13,18 &21. Fetal sex, with greater
birth weights in males.
2. Epigenetic: modifications of DNA, paternally expressed
promote FG, maternally expressed suppress FG.
3. Infection: Rubella, CMV, Toxoplasma and syphilis.
Maternal influences:
1. Physiological :height, weight, age , ethnic group&
parity.
2. Behavioral: Smoking, alcohol & drug abuse.
3. Chronic disease: HT, lung disease, CHD &maternal
thrombophilia.
Placental influences: Pl. insufficiency, infarction& APH.
 Fetal development
1. CVS and the fetal circulation.
2. CNS.
3. Respiratory system.
4. Alimentary system.
5. Liver, pancreas and gall bladder.
6. Kidney and urinary tract.
7. Skin and homeostasis.
8. Blood and immune system.
9. Endocrine system.
10. Behavioral states.
11. Amniotic fluid.
CVS and the fetal circulation
4 shunts, ensure that the oxygenated
blood from the placenta is delivered to
the fetal brain:
1. Umbilical circulation.
2. Ductus venosus.
3. Foramen ovale.
4. Ductus arteriosus.
.Diagrammatic representation of fetal circulation
 Abnormalities of CVS and the fetal circulation
1. Single UA: associated with reduced FG velocity and
some congenital anomalies.
2. Premature closure of the DA: due to the production of
prostaglandin E2 and prostacyclin, which act as local
vasodilators, due to the use of cyclooxygenase
inhibitors.
3. Persistent fetal circulation: as in preterm infants leading
to cyanosed , It results in congestion in the pulmonary
circulation and a reduction in blood flow to the GIT and
brain, and is implicated in the pathogenesis of
cyanosis.
CNS
⚫ Is one of the earliest systems to begin
and one of the last to be completed
⚫ Begins as a simple neural plate that
folds to form a groove then tube, open
initially at each end.
⚫ Failure of these opening to close
leads to (NTDs).
Respiratory system
⚫ Pulmonary surfactant, a complex mixture of
phospholipids and proteins that reduces surface
tension at the alveolus, is produced by the type II
cells starting from about 30 weeks.
⚫ Alveolar formation and maturation of the surfactant
continues between this time and delivery at term.
⚫ At birth, the production of the fluid inside the lungs
ceases and absorbed.
⚫ Production of surfactant is enhanced by cortisol, GR
and prolonged rupture of the membranes, and is
delayed in maternal DM.
⚫ In preterm fetus, RDS, tachypnoea and cyanosis
developed, within the first few hours of life, It occurs
in more than 80% of infants born between 23 and 27
weeks, falling to 10% of infants born between 34 and
36 weeks.
⚫ The incidence and severity of RDS can be reduced
by administering steroids antenatally to mothers at
risk of PTL, which stimulate the premature release
of stored fetal pulmonary surfactant in the fetal
alveoli.
⚫ Fetal breathing movements occur in utero, FBM, help
to maintain the high level of lung expansion that is
essential for it's growth and maturation.
⚫ The prolonged absence or impairment of
FBM is likely to result in a reduced lung
expansion that can lead to hypoplasia of
the lungs.
⚫ An adequate amniotic fluid volume is also
necessary for normal lung maturation.
⚫ Decreased intrathoracic space (e.g.
diaphragmatic hernia)or chest wall
deformities can result in pulmonary
hypoplasia, which leads to progressive
respiratory failure from birth.
Alimentary system
⚫ Physiological hernia occurs between 5 and
6 weeks due to the lack of space in the
abdominal cavity due to :
1. Rapidly enlarging liver .
2. Elongation of the intestine.
⚫ The gut undergoes rotation prior to
reentering the abdominal cavity by 12
weeks of gestation.
Midgut herniation
GIT anomalies
⚫ Failure of the gut to reenter lead to omphalocele.
⚫ Malrotation cause volvulus and bowel
obstruction.
⚫ Atresias , segment of bowel in which the lumen is
not patent and most commonly occur in the
upper GIT leading to polyhydramnia due to lack
of passage of amniotic fluid.
⚫ Fistulae , the most common being a
tracheo-oesophageal fistula (TOF), which may
associated with anther anomalies, VACTERL
(vertebral, anal, cardiac, tracheal, (o)
esophageal, renal and limb).
Tracheo-oesophageal fistula
⚫ Meconium aspiration syndrome, defecation
in utero, aspiration of meconium-stained
liquor , associated with post-term
pregnancies.
⚫ Preterms, a poor suck, uncoordinated
swallowing, delayed gastric emptying and
poor absorption of carbohydrates, fat and
other nutrients.
⚫ GR fetuses have reduced glycogen stores,
leading to neonatal hypoglycaemia.
Liver, pancreas and gall bladder
⚫ Haematopoiesis in the liver: begin at 6th week,
this peaks at 12–16 weeks and continues until 36
weeks.
⚫ Metabolic functions: conjugation of bilirubin
mainly done at the placenta, only a small
proportion being conjugated in the liver and
secreted in the bile .
⚫ Liver enzyme: fetal liver has a reduced ability to
conjugate bilirubin because of relative
deficiencies in glucuronyl transferase.
⚫ Preterm infant: reduced conjugation lead to
transient physiological jaundice of the newborn.
Kidney and urinary tract
⚫ Pelvic kidney: Failure of the normal
migration upward.
⚫ Duplex kidneys: Abnormal
development of the collecting duct
system.
⚫ Congenital obstruction: (pyeloureteric
junction, the vesicoureteric junction,
&posterior urethral valves), can lead
to hydronephrosis and renal interstitial
fibrosis.
Posterior urethral valves. (A) The typical ‘keyhole’ sign in the fetal
bladder (B), where the dilated upper posterior urethra is indicated
(white arrow);
.((B) dilatation of the collecting system of the fetal kidney (K
⚫ Preterm infant: maturation of concentrating
ability is gradual and continues after birth.
this lead to abnormal water, glucose,
sodium or acid–base homeostasis in
preterms.
⚫ Renal agenesis: severe reduction
(oligohydramnios) or absence of amniotic
fluid (anhydramios). bilateral agenesis
(Potter’s syndrome), widely spaced eyes,
small jaw and low set ears, usually die
either due to renal failure’ or pulmonary
hypoplasia.
Potter’s syndrome
Skin and homeostasis
⚫ In preterm infant or GR babies because of
the small amount of subcutaneous fat and
immaturity of vascular tone regulation in
the former, thermal control in cold is
limited.
⚫ Hair follicles begin to develop (12 and 16
weeks). By 24 weeks the hair follicles
produce delicate fetal hair called lanugo,
this lanugo is usually shed before birth.
Blood and immune system
⚫ RBCs are derived from pluripotent haematopoietic
cells of the yolk sac. By 8 weeks is replaced by the
liver and by 20 weeks are produced by the bone
marrow.
⚫ IgG originates from the maternal circulation and
crosses the placenta to provide passive immunity .
⚫ The fetus normally produces only small amounts of
IgM and IgA, which do not cross the placenta.
⚫ Detection of IgM/IgA in the newborn, without IgG, is
indicative of fetal infection.
⚫ Most haemoglobin in the fetus is (HbF), which has
(alpha-2, gamma-2).
⚫ 90% of fetal Hb is HbF ( 10 and 28) weeks
gestation.
⚫ (28 to 34 )weeks, a switch to HbA occurs.
⚫ At term the ratio of HbF to HbA is 80:20.
⚫ By 6 months of age, only 1% of Hb is HbF.
⚫ HbF is a higher affinity for O2, enhances transfer
of O2 across the placenta.
⚫ Abnormal Hb production results in thalassaemia.
B.thalassaemia reduced or absent production of
the B-globin chains. As the switch from HbF to
HbA occurs, destruction of these cells within the
BM and spleen.
B-thalassaemia major : inheritance of two
abnormal beta genes, this leads to severe
anaemia, FGR, poor musculoskeletal
development and skin pigmentation due to
increased iron absorption.
Alpha-thalassaemia, in which no
alpha-globin chains , severe fetal anaemia
occurs with cardiac failure,
hepatosplenomegaly and generalized
oedema. The infants are stillborn or die
shortly after birth.
Endocrine system
⚫ The hypothalamic–pituitary axis is in place by 12
weeks gestation.
⚫ (TRH) and (GnRH) have been identified in the fetal
hypothalamus by the end of the first trimester.
⚫ Testosterone produced by the interstitial cells of the
testis is synthesized in the first trimester , leading to
the differentiation of the male urogenital tract.
⚫ GH and T4 detectable in the circulation from 12
weeks.
⚫ GR fetuses exist in a state of relative hypothyroidism,
as a compensatory measure to decrease metabolic
rate and O2 consumption.
Behavioral states
The first activity is the
⚫ Beating of the FH at 6 weeks .
⚫ FM at 7–8 weeks.
⚫ Breathing , yawning, sucking and
swallowing by 12 weeks .
An understanding of fetal behavior can
assist in assessing fetal condition and
wellbeing.
Fetal behavioral states
⚫ 1F is quiescence, similar to quiet or non-REM
sleep in the neonate
⚫ 2F is characterized by frequent and periodic
gross body movements with eye movements,
similar to REM sleep
⚫ 3F no gross body movements but eye
movements, similar to quiet wakefulness
⚫ 4F vigorous continual activity again with eye
movements, similar to active wakefulness .
Amniotic fluid
⚫ Phospholipid hydrolysis: by 12 weeks’ gestation,
the amnion comes into contact with the inner
surface of the chorion, but never fuse. Neither
the amnion nor the chorion contains vessels or
nerves, but both do contain a significant quantity
of phospholipids as well as enzymes .
⚫ Choriodecidual function: play a role in the
initiation of labour through the production of
PGE2 and PGF2a.
⚫ The amniotic fluid is initially secreted by the
amnion, but by the 10th week it is mainly a
transudate of the fetal serum via the skin and
umbilical cord.
⚫ From 16 weeks’ gestation, the fetal skin becomes
impermeable to water, production of fluid through
the kidneys and lung, and removal by fetal
swallowing.
⚫ The amniotic fluid contains growth factors as well
as multipotent stem cells, the function of which at
present is unknown.
⚫ Amniotic fluid volume increases progressively:
•10 weeks: 30 ml.
•20 weeks: 300 ml.
•30 weeks: 600 ml.
•38 weeks:1,000 ml.
⚫ But from term there is a rapid fall in volume:
•40 weeks: 800 ml.
•42 weeks: 350 ml.
⚫ The reason for the late reduction has not been
explained.
⚫ The function of the amniotic fluid is to:
Protect the fetus from mechanical injury.
Permit fetal movement.
Preventing limb contracture.
Prevent adhesions between fetus and
amnion.
Permit fetal lung development in which
there is two-way movement of fluid into the
fetal bronchioles; absence of amniotic fluid
in the second trimester is associated with
pulmonary hypoplasia.
⚫ Oligohydramnios
Renal agenesis
Cystic kidneys
FGR
⚫ Polyhydramnios
Congenital neuromuscular disorders
Anencephaly
Oesophageal/duodenal atresia
The (AFI) is the total measurement of the deepest pool
.in the 4 quadrants of the uterus