6
Fetal and Transitional Circulation
MICHAEL D. FREED, MD
FETAL CIRCULATION
Most of our modern understanding of the circulation
before birth comes from more than 40 years of research on
fetal lambs.1–6
The fetal circulation is arranged in parallel, rather than
in a series, the right ventricle delivering the majority of
its output to the placenta for oxygenation, and the left
ventricle delivering the majority of its output to the heart,
brain, and upper part of the body (Fig. 6-1).7 However,
there is a mixing of the streams at the atrial and great
vessel level that diverts blood from the immature lungs to
the placenta for oxygen exchange. This parallel circulation
permits fetal survival despite a wide variety of complex
cardiac lesions.
Normally, blood returning from the placenta via the
umbilical venous return splits in the liver; some of it goes
into the hepatic veins and the portal system of the liver,
whereas the remainder (slightly over half) passes through
the ductus venous into the inferior vena cava near its junc-
tion with the right atrium. In the right atrium, the blood
from the inferior vena cava is divided into two streams by
the crista dividens. About 40% of the blood returning from
the inferior vena cava (27% of the combined ventricular
output) passes across the foramen ovale into the left atrium
where it joins with the pulmonary venous return from the
lung, passing through the mitral valve into the left ventricle.
This blood is then pumped out the ascending aorta where
it supplies the coronary, carotid, and subclavian arteries, with
approximately a third of this stream (10% of combined
ventricular output) passing across the aortic arch into the
descending aorta.
Most blood returning from the inferior vena cava joins
the superior vena caval drainage and coronary sinus return
before passing through the tricuspid valve into the right
ventricle and pulmonary artery. Because the fluid-filled
lungs and constricted pulmonary arterioles offer a high
resistance to flow, most of the blood, almost 90%, passes
not to the lungs, but through the open ductus arteriosus
into the low-resistance descending aorta and placenta.
The oxygen content of the blood in the fetus is consid-
erably lower than that in the neonate or child, because of
the lower efficiency of the placenta compared with the lung
as an organ for oxygen exchange (Fig. 6-2). Blood returning
from the placenta via the umbilical veins has the highest
PO2 (32–25 mm Hg; oxygen saturation, 70%). The blood
that passed into the left ventricle has already mixed with
the less saturated vena caval and pulmonary venous return,
lowering the PO2 to 26 to 28 mm Hg (oxygen saturation
about 65%) before its distribution to the ascending aorta
and upper half of the body.
The umbilical venous return destined for the right
ventricle mixes with the superior vena caval return
(PO2 > 12–14 mm Hg; oxygen saturation, 40%), reducing
the oxygen content of blood passing into the right ventricle,
main pulmonary artery, and descending aorta to about
20 to 22 mm Hg (oxygen saturation, 50%–55%). Thus,
blood with the highest oxygen content is diverted to the
coronary arteries and brain and that with the lowest oxygen
content is diverted to the placenta, increasing the efficiency
of oxygen pickup. An additional fetal adaptation to oxygen
transport at low oxygen saturations is the presence of high
levels of fetal hemoglobin with its high affinity for oxygen
and its low p50 (partial pressure of oxygen at the point
where 50% of the hemoglobin is oxidized) of approximately
18 or 19 mm Hg. The leftward shift of the oxygen associa-
tion curve facilitates oxygen uptake at the relatively low
PO2 levels of the placental vasculature.
75
76 Normal Circulatory Physiology
FIGURE 6–1 The course of the circulation in the late gestation
fetal lamb. The numbers represent the percentage of combined
ventricular output. Some of the return from the inferior vena
cava (IVC) is diverted by the crista dividens in the right atrium
(RA) through the foramen ovale into the left atrium (LA), where
it meets the pulmonary venous return (PV) and passes into the left
ventricle (LV) and is pumped into the ascending aorta. Most of
the ascending aortic flow goes to the coronary, subclavian, and
carotid arteries, with only 10% of combined ventricular output
passing through the aortic arch (indicated by the narrowed point
in the aorta) into the descending aorta (AO). The remainder of
the inferior vena cava flow mixes with return from the superior
vena cava (SVC) and coronary veins (3%) and passes into the
right atrium and right ventricle (RV) and is pumped into the
pulmonary artery (PA). Because of the high pulmonary resistance,
only 7% passes through the lungs (PV), with the rest going into
the ductus arteriosus (DA) and then to the descending aorta
(AO), to the placenta and lower half of the body.
Modified from Rudolph AM: Congenital Diseases of the Heart.
Armonk, NY: Futura Publishing, 2001, pp 3–44, with permission.
The wide communication between the atria allows for
equalization of pressures in the atria (Fig. 6-3); similarly,
the patency of the ductus arteriosus results in equalization
of pressures in the aorta and pulmonary artery. Because
atrial and great vessel pressures are equal, in the absence
of pulmonic or aortic stenosis, the ventricular pressures
FIGURE 6–2 The numbers indicate the percent of oxygen
saturation in the late gestation lamb. The oxygen saturation is
the highest in the inferior vena cava, representing flow that is
primarily from the placenta. The saturation of the blood in the
heart is slightly higher on the left side than on the right side. The
abbreviations in this diagram are the same as in Figure 6-1.
Modified from Rudolph AM: Congenital Diseases of the Heart.
Armonk, NY: Futura Publishing, 2001, pp 3–44, with permission.
are equal also, with a systolic pressure of approximately
70 mm Hg, using amniotic pressure as zero.
The fetus has a limited ability to adjust cardiac output.
The primary determinants of cardiac output are heart
rate, filling pressure (preload), resistance against which the
ventricles eject (afterload), and myocardial contractility.
Spontaneous changes in heart rate are associated with
electrocortical activity as well as with the sleep rate and
fetal activity. Using continuous measurements of left and
right ventricular output, utilizing electromagnetic flow
probes, Rudolph and Heymann8 have shown that sponta-
neous increases in heart rate are associated with increasing
ventricular output, whereas decreases in heart rate result
in a considerable fall of both right and left ventricular
output. By electrically pacing the right atrium above the
resting level of 160 to 180 beats per minute, the left
 Fetal and Transitional Circulation 77

per tissue volume, suggesting that the fetal myocardium

has much less contractile tissue than the adult. The active
tension produced in excised strips of fetal myocardium was
less than that produced by adult myocardium,11 possibly
because of the myofibrillar content, a reduced content of
sarcoplasmic reticulum and/or the T-tubule system.12
All of the above data suggest that the fetal myocardium
is structurally and functionally immature compared with
that of the older child or adult. The fetal heart appears
to work at the peak of its ventricular function curve, with
increases in preload causing little or no change in the
cardiac output, and increases in afterload resulting in a
marked depression. The limited ability of the fetal heart to
respond to stress seems to be mediated primarily through
increasing the heart rate.
The structure, hemodynamics, and myocardial function
of the fetal circulation have significant consequences in the
neonate with congenital heart disease.

1. The parallel circulation, with connections at the atrial

FIGURE 6–3 The numbers indicate the pressures observed in
late gestation lambs. Because large communications between the
atrium and great vessels are present, the pressures on both sides
of the heart are virtually identical. The abbreviations are the
same as in Figure 6-1.
Modified from Rudolph AM: Congenital Diseases of the Heart.
Armonk, NY: Futura Publishing, 2001, pp 3–44, with permission.
ventricular output eventually increases to about 15% above
resting levels. Decreasing the heart rate by 50% by vagal
stimulation caused a fall in output of approximately 30%.
Contrary to the significant effects of increasing or
decreasing heart rate on fetal cardiac output, increasing
preload (even to levels as high as a right atrial pressure
of 20 mm Hg) produces only very small increases in the
ventricular output,9 suggesting that the fetal ventricle
normally functions near the top of its function curve and
has little reserve to increase cardiac output. Increasing the
work of the heart by increasing afterload (by inflating a
balloon in the fetal descending aorta or by methoxamine)10
produces a dramatic fall in right ventricular output,
suggesting that the fetal heart is very sensitive to increases
in afterload.
Morphometric studies on the fetal myocardium have
demonstrated a significant decrease in myofibrillar content
and great vessel level, allows a wide variety of cardiac
malformations to provide adequate transport of blood
to the placenta to pick up oxygen and deliver it to the
tissues.
2. The right ventricle performs approximately two thirds
of the cardiac work before birth. This is reflected in the
size and thickness of the right ventricle before and
after birth and may explain why left-sided defects are
poorly tolerated after birth, compared with right-sided
lesions.
3. Because the normal flow across the aortic isthmus is
small (10% of ventricular output), the aortic isthmus
is especially vulnerable to small changes in intracar-
diac flow from various congenital defects. This may
account for the relatively high incidence of narrowing
(coarctation of the aorta) or atresia (interrupted aortic
arch) in this region.
4. Because the pulmonary flow in utero is very small
compared with that immediately after birth, anomalies
preventing normal pulmonary return (total anomalous
pulmonary return, mitral stenosis, etc.) may be masked
in utero when pulmonary venous return is so low
anyway.
5. The low levels of circulating oxygen before birth
(PO2, 26–28 mm Hg in the ascending aorta and
20–22 mm Hg in the descending aorta) may account
for the relative level of comfort of infants with cyan-
otic heart disease who may be quite active and
comfortable, and may feed well with an arterial PO2
of 20 to 25 mm Hg, a level that would lead to cere-
bral and cardiac anoxia, acidosis, and death within a
few minutes for the older child or adult.
78 Normal Circulatory Physiology
6. The limited ability of the fetal myocardium to
respond to stress makes the hemodynamic conse-
quences of congenital heart disease after birth that
much more difficult to tolerate.
7. Birth is a time of stress for the left ventricle. Because
of the switch from parallel to serial circulation, there
is an increased amount of blood to pump. The
ductus arteriosus may, at least briefly, shunt left to
right. The work of respiration must be assumed. Of
greater importance is the loss of the incubator effect
of the uterus; the body metabolism and the circula-
tion must adapt to maintaining body temperature.
The possible role of the thyroid in these events has
been noted.13
TRANSITIONAL CIRCULATION
Within a few moments of birth, profound changes must
occur as the newborn rapidly switches from the placenta to
the lung as the organ of respiration.2,14 Failure of any one
of a complex series of pulmonary or cardiac events that
take place within minutes of birth leads to generalized
hypoxemia and brain damage or death.
Soon after the onset of spontaneous respiration, the
placenta is removed from the circulation, either by clamp-
ing the umbilical cord or, more naturally, by constriction of
the umbilical arteries. This suddenly increases the systemic
resistance as the lower-resistance placenta is excluded from
the circulation. At approximately the same time the onset
of spontaneous respiration expands the lungs and brings
oxygen to the pulmonary alveoli. Reduction in the pulmonary
vascular resistance results from simple physical expansion
of the vessels and from the chemo-reflex vasodilation of
the pulmonary arteries caused by the high level of oxygen
in the alveolar gas.
This sudden increase in systemic vascular resistance and
drop in pulmonary vascular resistance causes a reversal of
the flow through the ductus arteriosus and an increase in
pulmonary flow. Before birth the relative pulmonary and
systemic resistances cause 90% of the blood to go through
the ductus arteriosus into the descending aorta; by a few
minutes after birth 90% goes to the pulmonary arteries,
with the pulmonary blood flow increasing from 35 mL/kg/min
to 160 to 200 mL/kg/min.
The rapid drop in systemic venous return to the inferior
vena cava as the umbilical venous flow is cut off, as well as
the increase in pulmonary venous return as the pulmonary
blood flow increases, causes the left atrial pressure to rise
and the right atrial pressure to fall. When left atrial pres-
sure exceeds right atrial pressure, the flap valve of the fora-
men ovale closes against the edge of the crista dividens,
eliminating left-to-right or right-to-left shunting (Fig. 6-3).
There have been questions in the past regarding how
much these marked circulatory changes are influenced by
the mechanical changes in the lung parenchyma due to the
onset of ventilation, how much by the vasodilatory effects
of oxygen, and how much by the increase in systemic
vascular resistance, with constriction of the umbilical vessels
removing low-resistance placenta from the circulation.
Tietel,15 using monitored fetal sheep near term, found
that ventilation alone caused dramatic changes in the
central flow patterns, attributable to a large decrease in
pulmonary vascular resistance and an associated increase
in pulmonary blood flow. Ventilation alone increased the
pulmonary venous return from 8% of combined ventricu-
lar output to 31%, whereas right ventricular output (which
had formerly ejected 90% to the ductus arteriosus) was
reduced to less than 50%. Oxygenation further changed
the flow patterns so that more than 90% of the flow from
the main pulmonary artery went to the lungs rather than
through the ductus arteriosus. Umbilical cord occlusion
had few additional effects.
Usually, the ductus arteriosus remains patent for several
hours or days after birth. Initially, the pulmonary vascular
resistance exceeds systemic vascular resistance so that there
is a small right-to-left (pulmonary artery-to-aorta) shunt
with some systemic desaturation to the lower half of the
body. Anything that increases the pulmonary vascular resist-
ance, such as acidosis, hypoxemia, polycythemia, or lung
disease, may exacerbate or prolong the normal transient
left-to-right shunt. Within a few hours of birth, however,
in the normal child, the pulmonary vascular resistance has
fallen lower than systemic vascular resistance, resulting
in a small “physiologic’’ left-to-right (aorta-to-pulmonary
artery) shunt. Normally, within 10 to 15 hours of birth, the
ductus arteriosus has closed, although permanent struc-
tural closure may not take place for another 2 to 3 weeks.
The mechanism of closure of the ductus arteriosus is not
completely understood. It has been clear for some time
that oxygen plays a role.
Coceani and Olley16 have shown that prostaglandins of
the E series are responsible for maintaining patency of the
ductus arteriosus during fetal life. It has been possible to
keep the ductus open for days, weeks, or months, or even
longer in infants with congenital heart disease, by infusion
of exogenous prostaglandin E,17 and it has been possible to
close the ductus arteriosus in about 80% of preterm infants
weighing less than 1750 g with indomethacin, a nonselective
prostaglandin synthetase inhibitor.18
Clyman and coworkers19 observed a decrease in the
ability of the ductus arteriosus to dilate and contract within
a few hours of postnatal ductal constriction, before the loss
of an anatomically patent lumen, in both human newborns
and full-term lambs. They postulated that this change
reflects early ischemic damage to the inner muscle wall.
 Fetal and Transitional Circulation
Fay and Cooke20 proposed that irreversibility reflects a
mechanical restraint imposed by cellular necrosis, with a
loss of intact endothelium leading to constriction from
opposing walls until an anatomic lumen is eliminated.
The etiology of the necrosis is unknown but it has been
postulated that it is caused by interruption of luminal
blood flow.
Although some hypoxemia is present soon after birth,
because of right-to-left shunting through the ductus arte-
riosus over the first few hours of life, with continued
vasodilation and improved ventilation/perfusion ratios, the
normal arterial PO2 gradually increases from 50 mm Hg at
10 minutes to 62 at 1 hour and 75-83 between 3 hours and
2 days of age. With continued vasodilation the pulmonary
pressure gradually falls to about 30 torr within approxi-
mately 48 hours. Although further falls in the pulmonary
vascular resistance continue for several weeks, the transition
to adult circulation is virtually completed within the first
few days of life.
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