Introduction to Fetal Development

Key Points:
Importance of understanding normal development for recognizing
complications in pregnancy.
Example: Lung development and preterm infants' risk for
respiratory distress syndrome , Bowel protrusion into the umbilical
cord at 10 weeks is normal (not an omphalocele).
Fetal growth and the eventual weight of the fetus at birth are
important not only for the immediate health of the neonate but also
for the long-term health of the adult, and even into the next
generation. The thrifty phenotype (Barker) hypothesis says that
reduced fetal growth is strongly associated with a number of chronic
conditions later in life. This increased susceptibility results from
adaptations made by the fetus in an environment limited in its supply
of nutrients. These chronic conditions include coronary heart disease,
stroke, diabetes and hypertension.
Fetal size/growth assessment
Fetal size can be assessed antenatally in two ways:

either externally by using a tape measure to assess the uterine size

from the superior edge of the pubic symphysis to the uterine fundus
(symphysis-fundal height [SFH] measurement)
or using ultrasound to measure specific parts of the fetus and then
calculating the estimated fetal weight (EPW) using equations such as
those described by Hadlock.
The fetal size is described in terms of its size for gestational age and is
presented on centile charts.
Symphysis-fundal height measurement

Measured from the top of the pubic symphysis to the top of the uterus.
Fundal height can be used to monitor fetal growth or to roughly
estimate gestational age in an emergency.
Screen all patients > 24 weeks' gestation for fetal growth
abnormalities using symphysis fundal height.
From 20 weeks, fundal height in centimeters should roughly
approximate the week of gestation.
If comparison of fundal height and gestational age suggests growth
abnormality , perform an ultrasound: fundal height in centimeters
differs from gestational age in weeks by > 3 cm.
Assessment of fetal growth by US
Fetal biometry
- Used to calculate fetal weight, gestational age, and EDD.
- Fetal biometric parameters:
Crown rump length: first trimester
Biparietal diameter: second trimester
Fetal femoral length: second trimester
Abdominal circumference: second trimester
Head circumference: second trimester
- Up to approximately 20 weeks' gestation the range of values around the mean for
measurements of fetal length, head size and long bone length is narrow and hence
assessment of gestation based on these measures is accurate. The crown-rump
length (CRL) is used up to 13 weeks + 6 days, and the head circumference (HC)
from 14 to 20 weeks' gestation. The biparietal diameter (BPD) and femur length
(FL) can also be used to determine gestational age.
- Essentially, the earlier the measurement is made, the more accurate the prediction,
and measurements made from an early CRL (accuracy of prediction 6±5 days) will
Crown-rump length
the length of the embryo or fetus from the top of its head to bottom of
torso.
It is used as a primary measure of gestational age between 6-13 weeks.
Biparital diameter / Head circumference
The maximum diameter of a transverse section of the fetal skull at the
level of the parietal eminences.
Head circumference: more accurate than the biparital diameter
Correct BPD : correct the BPD of the head according to the length of the
head.
Shape corrected BPD = BPD x FOD/1.265. When this shape correction is
performed the BPD is equivalent to the head circumference, as a
predictor of menstrual age as is becomes shape independent.
FOD: frontal occipital diameter
Femur length
We measure the shaft only (diaphysis) only.
Abdominal
circumference
Hadlock's three-parameter (HC, AC and FL) formula:
EFW = log(10) BW = 1.335 - 0.0034(abdominal circumference [AC])
(femur length [FL]) + 0.0316(biparietal diameter) + 0.0457(AC) +
0.1623(FL)
Population centile chart for estimated fetal weight by ultrasound measurements. Fetus (A) has normal
growth; fetus (B) has suboptimal growth.
Determinants of fetal growth and
birthweight
The influence of the natural growth potential of the fetus dictated largely
by the fetal genome and epigenome, but also by the intrauterine
environment that is influenced by both maternal and placental factors.
Fetal growth is dependent on adequate delivery to, and transfer of
nutrients and oxygen across, the placenta, which relies on appropriate
maternal nutrition and placental perfusion.
The ultimate birthweight is therefore the result of the interaction
between the fetus and the maternal uterine environment.
Fetal influences
Genetic
It is recognised that fetal genome plays a significant role in determining fetal size.
Obvious and sometimes severe FGR is seen in fetuses with chromosomal defects
such as the trisomies, particularly of chromosomes 13 (Patau's syndrome) and 18
(Edward's syndrome). Less severe FGR is common in tisomy 21 (Down's syndrome).
The other genetic influence is fetal sex, with slightly greater birthweights in males.
Epigenetic
Increasingly it is recognised that epigenetic changes plays a role in determining fetal
size. Epigenetic changes are modifications of deoxyribonucleic acid (DNA), which
occur without any alteration in the underlying DNA sequence and can control whether
a gene is turned on or off and how much of a particular message is made. Genomic
imprinting is an epigenetic process that silences one parental allele, resulting in
monoallelic expression. Emerging evidence shows that genes that are paternally
expressed promote fetal growth, whereas maternally expressed genes suppress
growth.
Fetal that affect the metabolic rate, growth of tissues and
maturation of individual organs
insulin-like growth factors (IGFs) coordinate a precise and orderly
increase in growth throughout late gestation. Insulin and thyroxine (T4)
are required through late gestation to ensure appropriate growth in
normal and adverse nutritional circumstances. Fetal hyperinsulinaemia,
which occurs in association with maternal diabetes mellitus when
maternal glycaemic control is suboptimal, results in fetal macrosomia
with, in particular, excessive fat deposition. This leads to complications
such late stillbirth, shoulder dystocia and neonatal hypoglycaemia.
Infection
Congenital infection particularly rubella, cytomegalovirus, Toxoplasma
and syphilis can cause FGR
Maternal influences
Physiological factors
maternal height, prepregnancy weight, age and ethnic group.
Heavier and taller mothers tend to have bigger babies
certain ethnic groups lighter babies (e.g. South Asian and Afro-
Caribbean).
Parity is also an influence with increasing parity being associated with
increased birthweight.
Age influences relate to the association with age and parity (i.e. older
mothers are more likely to be parous).In older women, however, the
increased risk of chromosomal abnormalities and maternal disease, for
example hypertension, lead to lower birthweights. Teenage pregnancy
is also associated with FGR.
Behavioural factors

Babies born to mothers who smoke during pregnancy deliver babies up to

300 g lighter than non-smoking mothers. This effect may be through toxins,
for example carbon monoxide, or vascular effects on the uteroplacental
circulation. Stopping smoking, even partway through pregnancy, can lead to
increased birthweight.
Chronic disease

Chronic maternal disease may restrict fetal growth. Such diseases are largely
those that affect placental function or result in maternal hypoxia. Conditions
include hypertension (essential or secondary to renal disease) and lung or
cardiac conditions (cystic fibrosis, cyanotic heart disease). Hypertension can
lead to placental infarction that impairs its function.
Maternal thrombophilia can also result in placental thrombosis and infarction
Placental factors
Placental infarction secondary to the maternal chronic conditions
discussed above or acute premature separation as in placental
abruption can impair this transfer and hence fetal growth. Recurrent
bleeding from the placenta (antepartum haemorrhage) can, over time,
compromise placental function, leading to poor fetal growth in the
latter part of pregnanc.
Evaluation of birth weight
Appropriate-for-gestational-age infant (AGA): birth weight 10th–90th
percentile for gestational age.
Small-for-gestational-age infant (SGA): birth weight < 10th percentile for
gestational age.
Large-for-gestational-age infant (LGA): birth weight > 90th percentile for
gestational age.
SGA
A fetus that is less than the 10th centile is described as being small for
gestational age (SGA). This is a statistical concept designed to categorize on size
but not necessarily on outcome.
Severe SGA is a neonate with EFW < 3rd centile.
Historically SA has been defined by using population centile. The centiles
customised for maternal characteristics (height, weight, parity & ethnic group),
infant sex & GA at delivery, identifies small babies at higher risk of morbidity &
mortality than those identified by population centiles.
SGA may be:
Normal (constitutionally) small, 50-70% of SGA fetuses are constitutionally small,
with fetal growth appropriate for maternal size & ethnicity.
Non-placenta-mediated growth restriction (structural or chromosomal anomaly,
inborn errors of metabolism & fetal infection).
Placenta-mediated growth rest
SGA vs FGR
An SGA fetus may be constitutionally small; in other words their
growth potential was reached and they were destined to be that
small. Many fetuses that are SGA, however, have failed to reach
their full growth potential, a condition called fetal growth restriction
(FGR). FGR is associated with a significant increased risk of perinatal
morbidity and mortality.
Complications
Complications (more with FGR than SGA):
Birth hypoxia.
Stillbirth.
Impaired neurodevelopmental & neurocognitive function if SGA <10*
centile: This include impaired motor, vision, hearing & language
development in childhood.
In adult life: DM1 & HTN.
Every 3
weeks
Uterine artery interpretation

Biochemical Markers used for Down $ Screening

- Low level of the 1s▲ marker PAPP-A <0.4 MoM is a major RF serial U/S of fetal size & UmAD

from 26-28 wk.

2nd markers (aFP, β-hCG, E3, inhibin A) have limited predictive accuracy."

Uterine Artery Doppler (UtAD)

- Low-risk population: don't offer UtAD as it has limited accuracy to predict SGA.

-High-risk population: UtAD at 20-24 wk has a moderate predictive value for a severely SGA

neonate.*

- Pathophysiology:

✓ Non-pregnant & 1 artery blood flow waveforms are ass. with low EDF & an early diastolic notch.

✓ Persistent notching or abnormal flow velocity ratios after 24 wk are ass. with inadequate trophoblast invasion.

✓ However trophoblast invasion of spiral arteries is ass. with the same waveform abnormalities as early as 10-14 wk.

‫ لو المريضة هاي ريسك تعمل دوبلر للحبل السري مباشرة‬: Women with major RF -

‫طلع طبيعي هتعمل دوبلر الحبل السري برضو‬

✓ UtAD has insufficient predictive value as a screening test & therefore doesn't change care

The LR- of UtAD is insufficient to negate the risk ass. with a major RF for a SGA neonate.

✓ Arrange serial U/S of fetal size & UmAD from 26-28 wk onwards.

Women with multiple minor RFS : ‫بنعمله فقط للتأكد إنهم هاي ريسك‬

✓ Consider UtAD screening at 20-24 wk.

✓ If abnormal UtAD (PI >95th centile) &/or notching serial U/S of fetal size & UmAD from

26-28 wk.*

If abnormal UtAD, don't repeat it as subsequent normalization of UtAD is still ass, with nsk of SGA.

✔ If normal UtAD offer U/S for fetal size & UmAD during the 3rd (before that if APH or HTN).
Management