10 Physiologic Changes in the Newborn

The neonatal period is defined as the first 28 days of life. As the neonate adapts
to life after birth numerous physiologic changes occur. Thus, the anesthesiologist
must understand the anesthetic implications associated with such changes. The
following is a discussion of the pertinent aspects regarding physiologic
conditions specifically related to the first 28 days of life.

Neurologic Physiology
It is during the last trimester of pregnancy that rapid maturation of the central
nervous system occurs. Normal newborns show various primitive reflexes,
which include the moro response and grasp reflex. Such milestones of
development are useful indicators of mental development.

ANESTHETIC REQUIREMENTS: Full term neonates require lower concentrations
of volatile anesthetics than do infants. This low requirement may be related to
the immaturity of the central nervous system. The immature blood brain barrier
may contribute to the increased sensitivity of the neonate to the effects of
barbiturates and opioids. The neonatal response to neuromuscular blockers is
affected by immaturity of the neuromuscular junction and the increased
extracellular fluid associated with this sub-population. Therefore, initial dosing
of non-depolarizers is similar to that of adults. The dosage of succinylcholine,
however, is increased to as much as twice the adult dosage.

THERMOREGULATION: With regards to thermoregulation, shivering is virtually
absent in the neonate and does not appear until 3 months of age. Therefore,
nonshivering thermogenesis provided by brown fat metabolism contributes to
euthermia in the neonate. Brown fat is present in the neck, between the scapulae,
around the internal mammary arteries and around the kidneys and adrenals.
When the neonate experiences a cold environment, norepinephrine release is
increased which in turn stimulates brown fat metabolism by the breakdown of
triglycerides. This action increases cardiac output through the brown fat tissue,
thus warming the blood.

Cardiovascular Physiology
TRANSITION TO EXTRAUTERINE LIFE: Circulatory changes occur immediately
at birth when the fetus is separated from the placenta and the lungs begin to
function. This causes an acute increase in systemic vascular resistance and also a
reduction in the return of inferior vena cava blood to the heart. Concurrent with
these changes is a rapid decrease in pulmonary vascular resistance and an
increase in pulmonary blood flow. The foramen ovale, ductus arteriosus, ductus
venosus and umbilical vessels are no longer needed. The foramen ovale normally
closes functionally at birth when left atrial pressure increases and right atrial
pressure decreases. Permanent closure occurs in several months; however, in
15-20% of adults a patent foramen ovale may exist. The ductus arteriosus
becomes functionally closed within the first 10-15 hours after birth. This process
depends primarily on systemic arterial PO2 and is reversible with PGE1 and
hypoxemia. Anatomic closure of the ductus arteriosus occurs within 4-6 weeks.
The ductus venosus closes soon after birth and becomes the ligamentum
venosum; it does not seem to be sensitive to varying levels of PO2, PCO2, or pH
and its regulation postnatally is not well understood. The umbilical veins become
the ligamentum teres. The umbilical artery becomes the medial umbilical
ligaments and the superior vesical arteries, which supply the urinary bladder.

NEONATAL CARDIAC FUNCTION: During the first 10 minutes after birth, the
average range of heart rate is 120-200 beats per minute (bpm); thereafter, the
average is 120-130 bpm. Tachycardia may be found with volume depletion,
cardiorespiratory disease, drug withdrawal and hyperthyroidism. Bradycardia is
often associated with apnea and is often seen with hypoxia. The neonate is highly
dependent on heart rate for maintenance of cardiac output and blood pressure.
The vasoconstrictive response of the neonate to hemorrhage or volume
depletion is less that that of an adult; hypotension that accompanies
administration of a volatile anesthetic is most likely due to decreased
intravascular fluid volume or anesthetic overdose, or both.

Respiratory Physiology
FIRST BREATH OF LIFE: The first breath is a gasp that generates a
transpulmonary pressure of up to 80 cm of water and is the result of
diaphragmatic descent. This overcomes the surface forces that develop as the
air/fluid interface reaches the small airways, and overcomes tissue resistance.
The chest wall of a neonate is floppy because of its high cartilage content and
poorly developed musculature, rendering the ineffectiveness of accessory
muscles to breathing.

FUNCTIONAL RESIDUAL CAPACITY (FRC): The FRC is smaller than that of the
adult as a result of less compliant lungs and the more compliant chest wall. This
reduced FRC leads to more rapid inductions with inhaled anesthetics as well as
more rapid desaturation.

TYPE I MUSCLE FIBERS: The neonate is more prone to respiratory muscle
fatigue due to the low content of type I muscle fibers. Type I fibers confer fatigue
resistance. Airway compliance in neonates is twice that of adults and contributes
to their potential for collapse with exhalation and inhalation.

SHUNTING: Venous admixture is elevated in neonates, estimated as high as 20
percent compared to just 5 percent in adults. This is the result of intrapulmonary
anatomic shunting. The neonatal response to hypercapnia is not potentiated by
hypoxia. On the contrary, hypoxia may depress the hypercapnic ventilatory
response. Neonates and infants are obligate nose breathers, but up to 40 percent
of term neonates can convert to oral breathing in the face of nasal obstruction.
Dead space ventilation is similar to that of adults, however oxygen consumption
is two to three times more, which can explain the increased minute ventilation.

AIRWAY: Of note is the anatomic considerations of the infant airway that
include: narrow nares, small pharynx, large tongue, mobile, short stubby
epiglottis, high (C3) anterior tapered larynx and angled vocal cords.


Gastrointestinal Physiology
At birth, the pH of the stomach contents is mildly acidic reflecting the pH
of amniotic fluid. Normal neonates exhibit uncoordinated swallowing and
regurgitation. Immaturity of the phayrngoesophageal sphincter and absence of
lower esophageal peristaltic waves also contribute to the reflux of gastric
contents. Upwards of 6 weeks are needed to reach adult levels of lower
esophageal pressures. Persistent gastroesophageal reflux beyond 6 weeks is
pathologic and is often accompanied by reactive airway disease.

Renal Physiology
At birth, glomerular filtration rate (GFR) is up to 30% of normal adult
values but reaches 50% of normal adult values by the tenth day of life and full
adult values by the first year of life. The low GFR affects the neonatal ability to
excrete saline, water loads and drugs. Thus, adequate exogenous sodium and
water must be supplied during the preoperative period. It must be appreciated,
however, that because the neonate is likely to excrete a volume load slower than
an adult, the possibility of fluid overload is increased.

Endocrine and Metabolic Issues
Neonates undergo a metabolic adjustment after birth with regard to
glucose. It must be appreciated that they may not show symptoms in the face of
hypoglycemia. Hyperglycemia occurs in the stressed neonate, for example during
surgery. Therefore, infusion of glucose containing solutions must be judiciously
monitored. Hyperbilirubinemia is an important consideration in the neonate.
Bilirubin levels in the term neonate peak on the third day of life then gradually
decline within four weeks. In the face of hyperbilirubinemia and prematurity,
physiologic jaundice must be ruled out.

PHYSIOLOGIC JAUNDICE: Physiologic jaundice is found in 60% of term infants. In
healthy full term neonates, physiologic jaundice causes no damage; however, in
premature infants and newborns with severe systemic disease, the risk of
developing bilirubin encephalopathy is increased.

Hematologic Concerns
Immediately at birth the neonatal blood volume is between 80-95 cc/kg,
depending on time of cord clamping. Within four hours, there is volume
contraction of as much as 25 percent. Normal hemoglobin range is between 14
gm/100 ml and 20 gm/100 ml. Heel sticks performed for lab studies may confer
falsely elevated values of hemoglobin; therefore venipuncture is ideal. White
blood count may be elevated to as much as 21,000 in the first 24 hours of life and
by the first week decreased to 12,000. During the first week of life and for four
years after, the lymphocyte is the predominant cell. Neonates are more
susceptible to bacterial infection due to the immature leukocyte function.

NEONATAL POLYCYTHEMIA: 3-5% of full-term neonates are diagnosed with
neonatal polycythemia with a hematocrit > 65%. This is associated with
increased systemic and pulmonary vascular resistance as well as decreased
cardiac output. Treatment usually entails exchange transfusion to prevent
hyperviscosity syndrome.

HEMORRHAGIC DISEASE OF THE NEWBORN: Vitamin K factors are below adult
levels in the neonate due to the immature liver where syntheses of such factors
occur. All newborns should receive prophylactic vitamin K to prevent
hemorrhagic disease of the newborn (HDN). HDN is a self-limited bleeding
disorder resulting from a deficiency of the coagulation factors dependent on
vitamin K. In most instances, hemorrhagic manifestations become evident on the
second or third day of life. Melena, bleeding from the navel and hematuria are
frequent signs. Intracranial hemorrhage is also possible and can result in death
or severe central nervous system dysfunction.

Causes of bleeding in Dengue

Dengue virus, the main cause of dengue fever induces bone marrow
suppression. Since bone marrow is the manufacturing centre of blood
cells its suppression causes deficiency of blood cells leading to low
platelet count. Anaemia and spontaneous severe bleeding are the other
resultant factors of bone marrow suppression.
Results of a study done by Wang et al. shows that dengue virus can even bind
to platelets of human blood in the presence of virus-specific antibody.
When vascular endothelial cell that are infected with dengue virus gets
combined with platelets they tend to destroy platelets. This is one of the
major causes of low platelet count in dengue fever.
Even the antiplatelet antibodies that are produced after infection of dengue
virus can contribute in destruction of platelets, thus lowering the platelet
count

Low platelet count in dengue fever leads to life threatening condition i.e.
hemorrhagic dengue fever that is categorised by spontaneous bleeding tendency
and shock.

Anatomical Variants in the Newborn

Cardiovascular System
At birth the cardiovascular system undergoes extensive remodelling
under the changed haemodynamics of the now activated pulmonary system. In
addition, umbilical vessels and vascular shunts are initially functionally closed
and then eventually structurally (anatomically) closed. The remnants of some
vessels remain in the adult as ligaments. This page gives a brief overview of
some of these human neonatal vascular changes.
The heart at birth is anatomically higher and lies more transverse than seen in
the adult, tilting of the heart occurs between 2 to 6 years of age.

Umbilical Vasculature
The umbilical blood vessel cavity is lost postnatally over the course of
weeks to months after birth.
The adult anatomical remnant of the umbilical vein between the
umbilicus and liver is the ligamentum teres.

Foramen Ovale
There are two separate forms of foramen ovale closure; functional and
structural. Functional closure begins at the first breath and is rapid. Structural
(anatomical) closure is much slower and generally occurs before the end of the
first year.

Ductus Arteriosus
The ductus arteriosus is a direct connection between the pulmonary
trunk and the dorsal aorta. Postnatal closure occurs initially by by smooth
muscle contraction and begins at the first breath and is rapid, completed within
the first day (about 15 hr after birth). Anatomical closure is much slower
occuring by 23 weeks after birth (33% of infants), by 2 months (90% of infants)
and by 1 year (99% of infants).
The adult anatomical remnant of the ductus arteriosus is the ligamentum
arteriosum.

Ductus Venosus
The ductus venosus connects portal and umbilical blood to the inferior
vena cava. Functional closure occurs postnatally within hours. Structural closure
commences days after birth and completes by 18 to 20 days.
The adult anatomical remnant of the ductus venosus is the ligamentum
venosum (a dorsal fissure on the liver).

Integumentary System

A healthy newborn at birth typically has:
Deep red or purple skin and bluish hands and feet. The skin darkens before the
infant takes his or her first breath (when they make that first vigorous
cry).
A thick, waxy substance called vernix covering the skin. This substance
protects the fetus's skin from the amniotic fluid in the womb. Vernix
should wash off during the baby's first bath.
Fine, soft hair (lanugo) that may cover the scalp, forehead, cheeks, shoulders,
and back. This is more common when an infant is born before the due
date. The hair should disappear within the first few weeks of the baby's
life.
Newborn skin will vary, depending on the length of the pregnancy.
Premature infants have thin, transparent skin. The skin of a full-term infant is
thicker.
By the baby's 2nd or 3rd day, the skin lightens somewhat and may
become dry and flaky. The skin still tends to turn red when the infant cries. The
lips, hands, and feet may turn bluish or spotted (mottled) when the baby is cold.
Other changes may include:
Milia are tiny, pearly-white, firm raised bumps on the face. They disappear on
their own.
Mild acne that usually clears in a few weeks. This is caused by some of the
mother's hormones that remain in the baby's blood.
Erythema toxicum is a common, harmless rash that looks like little pustules on
a red base. It tends to appear on the face, trunk, legs, and arms about 1 - 3
days after delivery and disappears by 1 week.

Colored birthmarks or skin markings may include:
Congenital nevi are moles (darkly pigmented skin markings) that may be
present at birth. They range in size from as small as a pea to large enough
to cover an entire arm or leg, or a large portion of the back or trunk.
Larger nevi carry a greater risk of becoming skin cancer. The health care
provider should follow all nevi.
Mongolian spots are blue-gray or brown spots. They can emerge on the skin of
the buttocks or back, mainly in dark-skinned babies. They should fade
within a year.
Caf-au-lait spots are light tan, the color of coffee with milk. They often appear
at birth, or may develop within the first few years. Children who have
many of these spots, or large spots, may be more likely to have a
condition called neurofibromatosis.

Red birthmarks may include:
Port-wine stains are growths that contain blood vessels (vascular growths).
They are red to purplish in color. They are frequently seen on the face, but
may occur on any area of the body.
Hemangiomas are a collection of capillaries (small blood vessels) that may
appear at birth or a few months later.

Stork bites are small red patches on the baby's forehead, eyelids, back of
the neck, or upper lip. They are caused by stretching of the blood vessels. They
usually go away within 18 months.

SKELETAL SYSTEM
Skull in the newborn. At birth the skull is large in proportion to other
skeletal parts; the facial region is relatively small and constitutes only about one-
eighth of the neonatal cranium, compared with half in adult life
Smallness of the face at birth is largely due to the rudimentary stage of
development of the mandible and maxillae - the teeth are unerupted. The nose
lies almost entirely between the orbits, and the lower border of the nasal
aperture is only slightly lower in position than the orbital floors

The large size of the calvaria, especially the neurocranium, reflects early


Frontal and parietal tuberosities are prominent; in the frontal view, the
greatest width occurs between the parietal tuberosities. The glabella,
superciliary arches and mastoid processes are not developed. Cranial base is
relatively short and narrow

Ossification is incomplete, and many bones are still in several elements
united by fibrous tissue or cartilage. Two halves of the frontal bone and
mandible, and the squamous, lateral and basilar parts of the occipital bone are all
separate

Parts of the temporal bones are separate except that fusion of the
tympanic with the petrous and squamous parts has started. The fibrous
membrane that forms the cranial vault before ossification is unossified at the
angles of the parietal bones, producing six fontanelles: two median (anterior and
posterior) and two lateral pairs (sphenoidal/anterolateral and
mastoid/posterolateral).

The anterior fontanelle is the largest and measures approximately 4 cm in
between the sagittal, coronal and frontal sutures and is therefore rhomboid in
shape .The posterior fontanelle lies at the junction between the sagittal and
lambdoid sutures and is therefore triangular.

The sphenoidal (anterolateral) and mastoid (posterolateral) fontanelles
are small, irregular and occur at the sphenoidal and mastoid angles of the
parietal bones respectively.

At birth the orbits appear relatively large. The developing tooth germs are
generally contained within the alveolar crypts, although eruption of the upper
central incisor teeth can occur prior to, or shortly after, birth


tympanic cavity, auditory ossicles and mastoid antrum are all almost adult in
size. The tympanic plate is an incomplete ring which has usually started to fuse
with the squamous part, and the mastoid process is absent.

The external aspect of the tympanic membrane faces more inferiorly than
laterally. The stylomastoid foramen is exposed on the lateral surface of the skull,
the styloid process has not fused with the temporal bone, the mandibular fossa is
flat and more lateral, and its articular tubercle is undeveloped.

The mandibular fossa is flat and more lateral, and its articular tubercle is
undeveloped. The paranasal sinuses are rudimentary or absent and only the
maxillary sinuses are usually identifiable


scalp which is more central in the birth canal is often temporarily oedematous as
a result of interference with venous return, and is called the caput succedaneum

Fontanelles and the openness and width of the sutures allow bones of the
cranial vault some overlap. The skull is compressed in one plane with
compensatory orthogonal elongation. These effects disappear within the first
week after birth.


RESPIRATORY SYSTEM
Lung and chest wall development (2-8 yrs). The process of alveolization
continues beyond the infant age 20-50 million alveoli at birth in a term infant,
300 million by the age of 8 years. The increase in alveoli parallels the increase in
alveolar surface area 2.8 m2 at birth 32 m2 at 8 years of age 75 m2 by adulthood

Key Function
- Collateral ventilation through the pores of Kohn and Lamberts canal are not
well developed in the early years
- Collateral pathways may help prevent atelectasis, which is more common in
children than in adults

Interbronchiolar
Bronchiolealveolar 6 yrs
Interalveolar 12 yrs

Developmental Mechanics of Breathing
The lung matrix of a neonate contains only small amounts of collagen; the
elastin-to collagen ratio changes during the first months and years of life and
affects lung stiffness and potential for overdistension and recoil. Lung recoil
increase with age in children over 6 years of age (more elastin).

Lung Elastic Recoil
The presence of an airliquid interface increases the elastic recoil of the
lung because of surface tension forces
Surfactant, a phospholipid protein complex, has been shown to profoundly
lower surface tension

Classic model of the distal lung in which individual alveoli are controlled by
Laplaces law (P=2T/r). Small alveoli would empty into large alveoli
Compliance of the Lung and Chest Wall
During the first year of life, the compliance of the respiratory system
increases by as much as 150% (mainly lung).
The infant chest wall is remarkably compliant and compliance decreases
with increasing age. The elastic recoil of an infants chest wall is close to zero and
with age increases because of the progressive ossification of the rib cage and
increased intercostal muscle tone

Children vs Adult
Considerable structural changes in the chest wall may change infant and
childhood predisposition to respiratory failure, lung injury, and ventilation-
associated lung injury. The orientation of the ribs is horizontal in the infant; by
10 years of age, the orientation is downward.