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Fetal Oxygenation
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Anna Gracia-Perez-Bonfils and Edwin Chandraharan
Handbook of CTG Interpretation: From Patterns to Physiology, ed. Edwin Chandraharan.
Fetuses, unlike adults, are not exposed to atmospheric oxygen. When confronted with hypoxia, adults can increase their rate and depth of respiration to enhance the intake of oxygen so as to maintain positive energy balance and protect their myocardium.
In contrast, a fetus when exposed to hypoxia cannot increase its oxygen supply, and therefore, it will decrease its heart rate in order to reduce the myocardial workload to maintain a positive energy balance. This reflex response to decrease the heart rate to protect the myocardium against hypoxic or mechanical stress is heard as a deceleration during fetal heart rate (FHR) monitoring.
Placentation: Impact on Fetal Oxygenation
From 12 days of life until full-term, the embryo and the fetus obtain their nutrition and oxygenation from maternal circulation to survive and grow. Therefore, it is mandatory for the well-being of an embryo and a fetus to have optimum utero-placental circulation as well as adequate placental reserve. This process of establishing an effective uteroplacental circulation is complex and requires a synergy between the trophoblasts of the embryo and the endometrium (decidua and spiral arterioles) of the mother.
Normal Placentation
Fertilization occurs in the fallopian tube, and the fertilized ovum enters the uterine cavity around the third day as a morula (12–16 blastomeres). The inner cells of the morula differentiate into an inner cell mass that will form the tissues of the embryo. In contrast, the surrounding cells differentiate into the outer cell mass that will give rise to the trophoblast, which will subsequently form the placenta.
The accumulation of fluid occurs rapidly forming a fluid-filled cavity within the morula (blastocele) and thereby creating the blastocyst. During this time, the early embryo receives its nutrition and eliminates waste products by a simple process of diffusion through the zona pellucida. About the sixth day, the cells from the trophoblast begin to penetrate between the endometrial cells of the uterus.
The process of implantation is usually completed by the tenth or eleventh postovulatory day. By that time, the original trophoblast surrounding the embryo has undergone differentiation into two layers: the inner cytotrophoblast and the outer syncytiotrophoblast, which will invade the endometrium and subsequently form the placenta.
The growth of the embryo and the disappearance of the zona pellucida induce a need for a new and more efficient method of exchange of nutrients. This need is fulfilled by the utero-placental circulation that allows a close contact to exchange gases and metabolites by diffusion between maternal and fetal blood. The formation of ‘lacunae’ within the syncytiotrophoblast aids in the development of an efficient utero-placental circulation.
The uterus at the time of implantation is in the secretory phase, and secondary to the rise in concentration of progesterone, the stroma cells of the endometrium accumulate glycogen and get enlarged. On day 12, the syncytiotrophoblast secretes enzymes that erode the endometrium and hormones that help to sustain ongoing pregnancy (B-hCG).
Enzymatic corrosion of uterine glands liberates their content for nourishment of theembryo, together with the glycogen provided by the stromal cells. Maternal vessels at the implantation site (branches of spiral arteries and endometrial veins) dilate and form
maternal sinusoids. The erosion of sinusoids by the syncytiotrophoblast results in
maternal blood bathing the lacunar network allowing the exchange of gases and nutrients
(Figure 2.1). Thus, a primitive utero-placental circulation begins by the end of the
second week with the anastomosis between trophoblastic lacunae and maternal
capillaries.
Figure 2.1 Formation of primitive utero-placental circulation by erosion of maternal blood
vessels by syncytiotrophoblast.
These cellular changes, together with an increase in endometrial vascularization,
are known as decidual reaction. It commences at the implantation site and spreads
throughout the entire endometrium within a few days, and this newly formed layer is
called the decidua. As the trophoblast continues to invade more and more sinusoids,
maternal blood begins to flow through the trophoblastic system.
The cytotrophoblast meanwhile proliferates and forms protrusions penetrating into
the syncytiotrophoblast all around the blastocyst. These extensions are known as
primary villi. On day 16, after being invaded by the chorionic mesoderm, secondary
villi are formed. This is followed by the development of blood vessels within the
chorionic mesoderm leading to the formation of tertiary villi on day 21. Secondary andtertiary villi are often termed as chorionic villi, and hypoxia or lower tissue oxygen
content in the decidua is critical for normal trophoblast invasion and formation of these
villi.
The embryonic circulation is anatomically separated from the maternal circulation
by the endothelium of the villus capillaries, the connective tissue in the core of the
villus, a layer of cytotrophoblast and a layer of syncytiotrophoblast.
By the end of fourth week, tertiary stem villi surround the entire chorion and
establish contact with the extraembryonic circulatory system, connecting the placenta
and the embryo (Figure 2.2). This ensures that nutrients and oxygen are supplied to the
fetus and metabolic waste products are removed when the fetal heart begins to start
beating.
Figure 2.2 Maternal spiral arteries and their branches as well as the intervillous space
formed by the intercommunicating lacunae within the trophoblast. The terminal branches of
spiral arterioles feed oxygenated blood while the tributaries of the endometrial veins drain
deoxygenated blood and metabolic waste products.Figure 2.3 Impaired placental circulation in a diabetic pregnancy secondary to
hyperplacentosis and resultant reduction in the utero-placental pool.
Impact of Placental Reserve on Fetal Growth and Well-being
If the placental reserve is low (utero-placental sinuses are smaller) during the antenatal
period, the fetus might have restricted his/her growth to supply oxygenated blood to the
vital organs. During labour, the onset of uterine contractions might lead to a rapid
development of hypoxia and acidosis due to the compression of branches of the uterine
artery by the contracting myometrial fibres. Similarly, an injudicious use of oxytocin
may increase the frequency, duration and strength of uterine contractions and thereby
reduce the perfusion of utero-placental sinuses leading to the development of hypoxia
and metabolic acidosis. Similarly in diabetic pregnancies, hyper-placentosis may
reduce the amount of placental pools available for gaseous exchange (Figure 3.3)
leading to a rapid development of hypoxia and acidosis.
Fetal Adaptation to Hypoxic IntrauterineEnvironment
The fetus lives in a relatively hypoxic intrauterine environment with an arterial oxygen
saturation of 70 per cent prior to the onset of labour. During labour, intermittent uterine
contractions may further reduce fetal oxygen saturation down to 30 per cent. Unlike
adults, a fetus has 18–22 g of fetal haemoglobin, which helps to increase the oxygencarrying capacity of fetal blood. In addition, unlike adult haemoglobin (HbA), fetal
haemoglobin (HbF) has increased affinity for oxygen. This results in the binding of
oxygen molecules at higher partial pressures of oxygen and the releasing of oxygen
rapidly at very low oxygen tensions. This enables the fetus to maintain adequate
oxygenation of the central organs even when it is not exposed to external environment.
Moreover, an increased level of fetal haemoglobin acts as an effective buffering system
in the presence of metabolic acidosis to help avoid fetal neurological damage (Figure
2.4).
Figure 2.4 Fetal adaptation to hypoxia.
The fetal circulatory system consists of ductus venosus and foramen ovale, both of
which preferentially shunt oxygenated blood from the umbilical vein to the heart and the
brain (vital organs). In addition, ductus arteriosus diverts the blood from the pulmonary
artery to the descending aorta by passing nonfunctional lungs. This vascular arrangement
enables the fetus to supply the central organs with relatively well-oxygenated blood as
compared to the peripheral tissues. In order to rapidly distribute the blood to vital
organs, unlike in adults, fetal myocardium beats at a higher rate (110–160 bpm).Abnormal Placentation
A failure of trophoblast invasion into the uterine endometrium would result in
inadequate formation of placental lacunae. This would lead to a reduction in the size of
pools of oxygenated blood within the uterine venous sinuses. Therefore, there may be
intrauterine growth restriction (IUGR) during the antenatal period to divert available
oxygen and nutrients to the vital organs. During labour, with the onset of uterine
contractions, due to the compression of the branches of spiral arteries, there may be a
rapid development of hypoxia and acidosis. In addition, placental disorders such as
infarction, villitis, vasculopathies and failure of trophoblastic invasion (e.g.
preeclampsia) may lead to a reduction of placental pools resulting in utero-placental
insufficiency (Table 2.1).
Table 2.1 Causes of abnormal placentation
Fetal Response to Hypoxic Stress
In response to hypoxic stress, the fetus attempts to safeguard the positive energy balance
of the myocardium to avoid myocardial hypoxia and acidosis. As the fetus, unlike adults,
cannot rapidly increase oxygen levels by increasing the rate and depth of respiration, it
decreases the myocardial workload by a reflex slowing of the FHR. This is termed
deceleration.
If this reflex response to hypoxic stress is insufficient to maintain oxygenation of
the central organs (brain, heart and adrenal glands), the fetus would conserve
nonessential activity by stopping movements leading to a loss of accelerations in the
cardiotocograph (CTG) trace. If intrapartum hypoxia progresses further, a fetus would
Infarction
Villitis
Vasculopathies
Failure to trophoblastic invasion (preeclampsia)release catecholamines (adrenaline and noradrenaline) to increase the heart rate, thereby
increasing oxygenation from the placental bed and also causing peripheral
vasoconstriction to divert blood from nonessential peripheral organs to central organs
(Figure 2.5). In addition, catecholamines increase breakdown of glycogen to glucose to
increase energy substrate to continue maintaining a positive energy balance within the
myocardium.
Figure 2.5 Fetal response to hypoxic stress.
This leads to a compensated response, and the fetus would continue to demonstrate
a stable baseline FHR and a reassuring baseline variability (5–25 bpm), albeit with
continuing decelerations and a rise in baseline FHR.
This is followed by the onset of decompensation in the central nervous system
leading to a loss of baseline FHR variability followed by the onset of myocardialhypoxia and acidosis characterized by unstable baseline and a progressive reduction of
the heart rate (‘stepwise pattern to death’).
Summary
Fetus is not exposed to atmospheric oxygen during intrauterine life and, therefore,
develops cardiovascular, metabolic and haematological adaptation to ensure adequate
oxygenation to central organs. In response to hypoxic stress, the only organ the fetus
attempts to safeguard is the myocardium (‘the pump’) so as to maintain continued
perfusion to other vital organs. A reflex decrease in FHR (deceleration), conservation of
energy (loss of fetal movements) and release of catecholamines to increase placental
circulation redistribute blood from peripheral organs to central organs and increase the
availability of energy substrate (glucose). Failure in any of these mechanisms may lead
to the onset of hypoxia and metabolic acidosis, leading to neurological damage or death.
Further Reading
1. Sadler T W. Langman’s Medical Embryology. 12th edition. Baltimore: Wolters
Kluwer/Lippincott Williams & Wilkins; 2012.
2. Sadler T W. Third Week of Development: Trilaminar Germ Disc. In: Langman’s Medical
Embryology. 12th edition. Baltimore: Wolters Kluwer/Lippincott Williams & Wilkins; 2012. p.
59–61.
3. Schoenwolf G C, Bleyl S B, Brauer P R, Francis-West P H. Second Week: Becoming
Bilaminar and Fully Implanting. In: Larsen’s Human Embryology. 4th edition. Philadelphia:
Churchill Livingstone Elsevier; 2009. p. 51–68.
4. Carlson B M. Placenta and Extraembryonic Membranes. In: Human Embryology and
Developmental Biology. 5th edition. Philadelphia: Mosby Elsevier; 2014. p. 120–129.
5. FitzGerald M J T, FitzGerald M. Implantation. In: Human Embryology. 1st edition.
London: Baillière Tindall; 1994. p. 15–20.6. Hardy K. Embryology. Chapter In: Bennett P, Williamson C. (eds). Basic Science in
Obstetrics and Gynaecology. 4th edition. Churchill Livingston; 2010.
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