CIRCULATORY SYSTEM
Umbilical Circulation
Umbilical blood flow is dependent on the vascular resistance and the pressure gradients created
through the descending aorta, the placental circulation, and the inferior vena cava. In fetal
lambs, blood pressure in the umbilical artery slowly increases through gestation to 55 or 65 mm
Hg, although the pressure in the umbilical vein remains at about 10-12 mm Hg. The increased
volume of the vascular bed of the placenta in late gestation accounts for the increased pressure
drop across the placenta over this time. In human infants, although the transitions are similar,
the umbilical vein retains a pressure of nearly 25 mm Hg at term. The increasing arterial
pressure allows an increase in blood flow almost proportional to fetal growth, which further
allows oxygen consumption to increase in proportion to body weight.
Umbilical arteries are reactive to a variety of stimuli; vasoconstriction may be induced by high
oxygen tension, tactile stimulation, or cold, while vasodilation occurs in response to high CO2
tensions or low oxygen tensions. However, in vivo, umbilical vessels show almost no direct
local effect in response to large changes in blood gas tensions. The intra-abdominal portion of
the umbilical vein is highly innervated, however, the degree of innervation of the extraabdominal portion is much lower and may be absent.
Development of the Circulatory System
The embryo is unable to sustain growth beyond a few millimeters without a mechanism for
transporting gases, nutrients, and waste products. Therefore, the fetal cardiovascular system is
the first organ system to become functional in the developing fetus. By 3-4 weeks of age, the
heart is moving blood through the 2 mm embryo. By eight weeks of age, the partition of the
heart and its major arterial trunks is complete. At birth, the relative weight of the heart is 0.7%
of total body weight, as compared to 0.4% in the adult.
In the 15 mm embryo, heart rate is about 65 beats/minute. It peaks at 175 beats/minute at 9
weeks of age in human fetuses, slowing to 135 to 155 beats per minute at term. Variability in
the fetal heart rate will persist into adult life. Moreover, the slower the resting rate, the faster the
poststimulus rate, a trait that is also carried into postnatal life.
During fetal life, blood flow is shunted to the systemic arterial system via the ductus arteriosus
and ductus venosus. Oxygen rich umbilical venous blood (80% saturated with oxygen) enters
the right atrium of the heart via the ductus venosus and the inferior vena cava. About 50% of
venous return enters the inferior vena cava through the ductus venosus, allowing it bypass the
portal circulation and function as a low-resistance bypass to the heart. This blood then crosses
the oval foramen into the left atrium, left ventricle and systemic arterial circulation to provide
this oxygen-rich blood to the head, brain, and upper body.
Poorly oxygenated blood (< 60% saturated with oxygen) entering the superior vena cava is
directed is directed almost entirely through the tricuspid valve into the right ventricle across the
ductus arteriosus (because pulmonary resistance is so high) to the aorta from which it is reoxygenated by the placental circulation.
At birth, the ductus arteriosus and ductus venosus close, and with the rapid increase in
pulmonary blood flow, the left atrial pressure increases resulting in functional closure of the oval
foramen. This closure, however, is reversible for the fist few days of life. For example, crying
fits in infants create a right-left shunt, inducing cyanotic periods. It takes nearly a year in infants
for full fusion to occur, and in 25% of all individuals, anatomical closure is never complete.
The heart transforms from two pumps functioning partly in parallel to two pumps functioning in
series. The oxygenation and gaseous expansion of the lung mediates pulmonary arterial dilation,
decreasing pulmonary resistance, and an increase in pulmonary blood flow. Arachidonic acid
metabolites including prostaglandins I2 and E2 and inhibition of leukotriene synthesis are all
potent vasodilators at birth and may contribute to the decrease in pulmonary arterial pressure.
Systemic pressure increases, and regional blood flows shift in response to oxygen requirements.
The loss of the resistance due to the placental circulation also contributes to greatly altered
regional flows. The net result is that the lung receives a ten-fold increase in blood flow after
closure of the ductus arteriosus. Closure of the ductus venosus is triggered after the partial
pressure of oxygen exceeds ~55 mm Hg, and is thought to be mediated primarily by bradykinins
released from pulmonary tissue during initial inflation after birth.
The immediate postnatal changes in the circulation are associated with an increased cardiac
output. The mechanism for this is not fully known but fetal sheep that have been
thyroidectomized two weeks prior to delivery do not show this same increase. The prenatal
increase in thyroid hormones prior to birth may stimulate -adrenergic receptor development in
the heart making it responsive to the increased concentrations of catecholamines at birth.
Ventilation, oxygenation, decreases in the right ventricular mechanical constraints, and umbilical
cord occlusion may all contribute to the catecholamine-induced increase in ventricular output
and in heart rate at birth.
Newborns are particularly susceptible to modest increases in oxygen transport capabilities or
demands because of the high resting oxygen demands and a limited reserve for increasing
cardiac output or oxygen extraction. Oxygen uptake is relatively high in newborns compared to
the fetus. A limited preload reserve and high heart rate in the newborn that is faced with stress
do not permit adequate increases in cardiac output. Additionally, there is often a decrease in
hemoglobin concentrations postnatally (decreasing oxygen carrying capacity of the blood) and
fractional oxygen extraction is limited by the high percentage of fetal hemoglobin present.
Timing of Umbilical Cord Rupture
Blood flow continues through the placenta for approximately 1.5 min after the first breath;
constriction of umbilical vessels and stoppage of placental flow (as well as initiation of placental
separation) is initiated primarily by the change in oxygen tension associated with the shift from
placental to pulmonary respiration. Transfer of placental blood into the fetal system is not
complete until this umbilical constriction occurs. Placental transfusion is accomplished by a
combination of vessel constriction within the placental vascular bed (effectively reducing
vascular capacity), uterine contractions, and gravity. The umbilical arteries close prior to the
umbilical veins, allowing placental blood to continue to flow into the fetus after fetal blood has
stopped flowing to the placenta. Gravity is an important consideration in humans; if the infant is
held above the level of the placenta, reverse flow can occur. A smaller residual volume of blood
will remain in the placenta if the cord is clamped after respiration has been initiated. Expansion
of the pulmonary vascular bed will require about 10-20% of the neonatal blood volume, which in
itself will serve to draw in more placental blood as systemic pressure is reduced accordingly.
Either placental transfusion or fetal blood loss can occur at delivery; both can have dramatic
effects on blood volume and clinical outcomes in the neonate.
The benefits or risks associated with delaying clamping of the umbilical cord have been debated
for nearly fifty years. The definitions applied to early- and late-clamping of the cord has created
much variation in the literature, and data interpretation is complicated. Early clamping has been
applied at any time from delivery of the buttocks to 1 minute after birth, while late clamping has
been applied to anything from the first breath to 5 or more minutes. Obviously, what is
considered late-clamping by some researchers has been considered early by others. However,
for our purposes, we will consider delayed clamping to be anything beyond a minute and early as
anything earlier than a minute after birth; keep in mind there is considerable variation within the
parameters applied to the data presented and it may seem to be inconsistent.
Delayed umbilical cord clamping in premature infants results in increased packed cell volume
and arterial-alveolar oxygen tension differences and decreased reliance on supplemental oxygen.
Placental transfusion in infants can increase blood volume by ~ 100 ml and the available iron
pool by ~32 mg at a time when anemia is a common problem. The transfusion allows an
increase from 20-60% of original blood volume. Respiration is initiated earlier if the umbilical
cord is clamped early, although respiration rates are similar during the first 30 minutes after
birth. However, by three hours of age, late-clamped infants have a faster rate of respiration
which persists at least for the next several days. Transfused infants also have lower lung
compliance and a smaller functional residual capacity. Transudation of plasma into the highly
vascular pulmonary epithelium does occur, however, no causal relationship has been established
between the degree of transudation and incidence of respiratory distress syndrome.
Concerns have been raised as to the ability of the neonate to cope with this added volume of
blood; this is of special concern in premature infants. Heart load may increase beyond the
capacity of the newborn to adapt and left-right shunts may be re-established. Within 30 minutes,
fluid shifts occur from intravascular to extravascular pools; these shifts take about 12 hours to
complete in infants. The transudation of plasma may account for up to 50% of initial blood
volume in late-clamped infants but is not seen to occur at all in early-clamped infants. Central
and portal venous pressures average 5.7 mm Hg in late-clamped and 1.7 mm Hg in earlyclamped infants. Systolic pressures are higher for the first 6 hours of life in late-clamped infants.
Pulmonary pressures are 90% of aortic pressures in late-clamped infants during the first day of
life and less than 70% in early-clamped infants. These increased pressures create a large
workload for the neonatal heart. In infants where the cord is clamped early (within seconds of
delivery), changes in the electrocardiogram after birth are different than in late-clamped (3
minutes after birth) infants. Early clamped infants have a slower and narrower range of heart
rate during the first hours of life and a greater increase in rate after a cry than late-clamped
infants. They also have shorter intervals (P duration, P-R segment, P-R interval, QRS duration,
Q-Tc), lower deflections (PII, QV6, RV6, SV6, TV1). Earlier inversion of the T wave in V1, and
a higher T wave in V6 on the first day of life. The P wave differences are still apparent at the
end of the first week of life. In extremely premature infants, aggressive cord-stripping has been
reported to cause cardiac failure, presumably from volume overload. In addition, respiratory
distress has been reported to occur in infants with high blood hematocrits or increased blood
viscosity. Renal response to this high volume load is important. Urine flow is significantly
higher in late-clamped infants through the first 12 hours of life; in this same period, the
glomerular filtration rate is also higher. .
In cattle, the relatively short umbilical cord often ruptures as the hind legs are expelled from the
birth canal. Assistance to these calves often ruptures the umbilical cord earlier than would occur
in an unassisted delivery. Stressed calves demonstrate delayed behavioral adaptations, irregular
respiration rates, and failure to thermoregulate; these same clinical problems were reported by
Mahaffey (1961) as responses to premature rupture of the umbilical vessels in both foals and
lambs. Premature rupture resulted in a loss of ~1500 ml of placental blood in foals, roughly
30% of the total blood volume at birth. The decreased blood volume was theorized to result in
decreased ability to perfuse vital organs, especially the pulmonary system and the central
nervous system, inducing many of the clinical outcomes observed in these neonates. The same
loss in blood volume has been reported in infants with placenta previa or abruptio placenta, and
has been theorized as a major cause of death in infants born from these types of pregnancies.
Deficits in oxygen delivery in these infants leads to a much higher incidence of permanent
neurological deficit.
Cesarian-derived infants are typically pulled from a non-contracting uterus and placed on their
mother’s abdomen prior to clamping the cord. This can result in significant blood loss; plasma
volume is ~35 ml/kg, red cell volume is ~31 ml/kg, and blood volume is ~66 ml/kg. Delaying
clamping for 3 minutes while holding the infant below the level of the placenta increases blood
volume and red cell volume by 20%. Distressed infants subjected to emergency cesarian section
have blood volumes more closely resembling infants from a normal vaginal delivery.