Transition to extrauterine life

INTRODUCTION
In order to succeed in this transition, the respiratory system must be developed enough to assure a sufficient alveolar
exchange area, it must have a drive to offer a continuous breathing activity, and the circulatory system should start
perfusing the lungs instead of the placenta. This chapter will discuss the mechanisms preparing the fetus to be born,
the transition at birth, and the successful adaptation to the air-breathing world. This chapter will review the respiratory
system, the respiratory drive and chemoreceptor role, and the circulatory system including fetal circulation and its
changes at birth.

FETAL CIRCULATION AND ITS TRANSITION AT BIRTH

The fetal circulation is characterized by high pulmonary vascular resistance (PVR), low systemic vascular resistance
(SVR), presence of an additional low resistance vascular bed (i.e., the placental bed), and right-to-left shunting via the
foramen ovale and ductus arteriosus (DA).1 Distribution of blood flow to the lungs, systemic organs, and placenta is
determined by local vascularl resistance. The placental vascular bed receives about 40%–50% of the combined
ventricular output, whereas the lungs receive less than 10%. In response to fetal hypoxemia, distribution of cardiac
output and venous return is altered in an effort to maintain perfusion and O 2 delivery to the vital organs such as the
heart, brain, and adrenal glands.2,3 Thus, during maternofetal hypoxia, the percentage of systemic venous blood not
sent to the placenta for oxygenation is decreased, whereas the proportion of umbilical venous blood contributing to
fetal cardiac output is increased.2,3 The human placenta was widely thought of as a passive organ in which blood flow
depends only on the pressure difference between the umbilical arteries and vein connecting it to the fetus.4,5 However,
more recent evidences indicate that the regulation of vasomotor tone in the vessels of the fetoplacental circulation is
important to maintain an adequate blood supply that makes possible maternofetal gas and solute exchange.4–6 As
fetoplacental blood vessels lack autonomic innervation, control of vascular tone is mainly influenced by circulating
and/or locally released vasoactive agents as well as by physical factors, such as flow or oxygen tension.7 Accordingly,
constriction and relaxation of fetoplacental arteries and veins have been demonstrated in response to a number of
agonists and physical stimuli. Moreover, various authors have suggested that the fetoplacental vasculature shows some
form of flow matching similar to hypoxic pulmonary vasoconstriction. This mechanism, termed hypoxic fetoplacental
vasoconstriction,6,8,9 would divert blood flow to the placental areas with better maternal perfusion as hypoxic
pulmonary vasoconstriction diverts pulmonary blood flow to the better ventilated areas of the lung.9–11 Separating the
infant from the placenta by clamping the umbilical cord necessitates the rapid switch to pulmonary gas exchange
within minutes of birth. This switch not only involves aeration of the airways and gas exchange regions of the lung
but also includes a major reorganization of the fetal cardiovascular system.12 As the lung assumes the respiratory
function, the pulmonary circulation undergoes a striking transition characterized by an immediate 8- to 10-fold rise in
pulmonary blood flow and a sustained decrease in PVR.13–16 The postnatal fall in PVR and rise in SVR results in a
reversal of the relationships present in the fetus. Moreover, pulmonary blood flow must have the capacity to replace
umbilical venous return as the primary source of preload for the left ventricle when the cord is clamped.12 Increasing
blood return to the heart via the pulmonary veins raises the pressure of the left atrium above that of the right, causing
a functional closure of the foramen ovale. While the DA is still patent, the flow of blood through it will change to a
left-to-right shunt, but the DA normally achieves functional closure within 48 hours after birth. Because the foramen
ovale and DA are only functionally closed and the pulmonary circulation is very sensitive to vasoconstrictive stimuli,
the neonatal circulatory pattern can readily revert to the fetal pattern. In the following paragraphs, the different
circulatory events that take place during the transition between fetal and postnatal life will be analyzed in more detail.

Closure of the ductus venosus

The ductus venosus is a shunt between the umbilical vein and the inferior vena cava, which allows highly oxygenated
and nutrient-rich umbilical venous blood to bypass the liver and reach the central circulation rapidly. 1 A large
proportion of inferior vena caval return crosses the foramen ovale into the left atrium to the left ventricle, and is thus
distributed to the coronary and cerebral circulations. The PO2 of blood supplying the heart, brain, head, and neck is
higher by 4–5 mmHg than that of blood in the descending aorta. Although the ductus venosus has received less
attention than the DA, it is now well accepted that it plays a major role in the regulation of fetal circulation. Inlet of
the vessel is under active control and a compensatory mechanism, supported by transient dilatation, is supposed to
increase oxygenated blood flow through the ductus venosus during hypoxia or reduced umbilical flow.17 Absence of
the ductus venosus is associated with a high incidence of fetal anomalies and adverse outcomes, including associated
malformations, chromosomal aberrations, in utero heart failure, and absence of the portal vein.18 Functional closure of
the ductus venosus, which is followed by anatomic closure, is virtually complete within a few weeks of birth. However,
the ductus venosus of almost all neonates remains open for a certain period after birth with important variations in the
volume of blood flow.19 Closure of the ductus venosus is more delayed in preterm neonates, and patent ductus venosus
appears to be related to alterations in ammonia detoxification, blood coagulation, and regulation of serum total bile
acid concentration.19

Closure of the foramen ovale

Anatomically, the foramen ovale comprises overlapping portions of septum primum and septum secundum, acting
as a one-way flap valve allowing continuous right-to-left flow during fetal life.20 Immediately after birth, with the
acute increase in pulmonary blood flow, left atrium pressure rises to exceed right atrium pressure, pushing septum
primum rightward, against septum secundum, shutting the flap of the foramen ovale. Afterward, septum primum fuses
to septum secundum, completing septation of the atria. However, in 20% to 25%, incomplete fusion leads to the
persistence of the flap valve, leaving a patent foramen ovale. 20 In general, individuals with patent foramen ovale are
never identified because they have no symptoms. However, there is increasing interest in the evaluation and treatment
of patent foramen ovale, which has been associated with various pathologic conditions, such as cryptogenic stroke,
decompression sickness, platypnea–orthodeoxia syndrome, and migraine.21