Fetal and Neonatal Physiology pdf - Endocrinology and Reproduction

and fetal asphyxia especially cause these attempted respiratory movements.

take place beginning at the end of the first trimester of pregnancy. Tactile stimuli

to breathe in the amniotic cavity. However, attempted respiratory movements do

Respiratory System.

lymphocyte and plasma cell production in lymphoid tissue.

of the red blood cells as well as most of the white blood cells, except for continued

from the third month on, the bone marrow gradually becomes the principal source

the spleen and other lymphoid tissues of the body begin forming blood cells. Finally,

vessels. Then, at 6 weeks, the liver begins to form blood cells, and in the third month,

This is followed 1 week later (at 4 to 5 weeks) by formation of non-nucleated red

tilization, contracting at a rate of about 65 beats/min. This increases steadily to about

The human heart begins beating during the fourth week after fer-

Circulatory System.

liver, lack full development, as discussed in more detail later in the chapter.

at birth, certain structures, particularly in the nervous system, the kidneys, and the

requires the full remaining 5 months of pregnancy for complete development. Even

However, cellular development in each organ is usually far from complete and

month 4, the organs of the fetus are grossly the same as those of the neonate.

to 3 months, most of the details of the different organs are established. Beyond

different organs of the fetus have already begun to develop, and during the next 2

Within 1 month after fertilization of the ovum, the gross characteristics of all the

pounds in normal infants with normal gestational periods.

birth, the weight averages 3 pounds, 1 month before birth 4.5 pounds, and at birth

last trimester of pregnancy, the fetus gains tremendously, so that 2 months before

months) of gestation. Then, during the

and reaches 1 pound only at 23 weeks (5

Note in Figure 83–1 that the weight remains minuscule during the first 12 weeks

almost in proportion to the cube of the age of the fetus.

fetus is approximately proportional to the cube of length, the weight increases

and at term (40 weeks), 53 centimeters (about 21 inches). Because the weight of the

age. At 12 weeks, the length is about 10 centimeters; at 20 weeks, 25 centimeters;

as shown in Figure 83–1, the length of the fetus increases almost in proportion to

implantation of the blastocyst, the fetus remains almost microscopic, but thereafter,

than development of the fetus itself. In fact, during the first 2 to 3 weeks after

Growth and Functional Development

important of these.

liar to the infant itself. This chapter discusses the more

atrics. However, many physiologic principles are pecu-

ing of the child immediately after birth, and growth and

A complete discussion of fetal development, function-

Fetal and Neonatal Physiology

1042

development through the early years of life lies within
the province of formal courses in obstetrics and pedi-

of the Fetus

Initial development of the placenta and fetal membranes occurs far more rapidly

7 pounds—the final birth weight varying from as low as 4.5 pounds to as high as 11

Development of the Organ Systems

140 beats/min immediately before birth.

Formation of Blood Cells.

Nucleated red blood cells begin to be formed in the yolk sac

and mesothelial layers of the placenta at about the third week of fetal development.

blood cells by the fetal mesenchyme and also by the endothelium of the fetal blood

Respiration cannot occur during fetal life because there is no air

before implantation of the ovum; this iron is ingested

mother’s uterine progestational endometrium even

hemoglobin, which begins to be formed as early as the

and phosphate. Most of the iron is in the form of

Figure 83–2 also shows that iron

minimal drain from the mother. Much greater drain

substances in the mother’s bones. Therefore, this is a

ossification until after the fourth month of pregnancy.

matrix. Indeed x-ray films ordinarily do not show any

During the earlier part of fetal life, the bones are

the fetus.

accumulate during the last 4 weeks of gestation, which

average fetus during gestation. About one half of these

fetus, demonstrating that about 22.5 grams of calcium

Figure 83–2 shows

tion to calcium, phosphate, iron, and some vitamins.

the mother’s blood. In addition to these generalities,

protein, much if not most of the fat being synthesized

energy, and it has a high capability to store fat and

The fetus uses mainly glucose for

base balance, are almost nonexistent until late fetal life

volume and electrolyte balances, and especially acid-

Although the fetal kidneys form urine, the renal

for about 70 to 80 per cent of the amniotic fluid. Abnor-

the second trimester pregnancy, and fetal urine accounts

The fetal kidneys begin to excrete urine during

ucts from the gastrointestinal mucosa and glands.

the anus into the amniotic fluid. Meconium is composed

that time, small quantities of

function approaches that of the normal neonate. By

and during the last 2 to 3 months, gastrointestinal

By midpregnancy, the fetus begins

Tract

only after about 1 year of postnatal life.

development even at birth. Indeed, myelinization of

However, those nervous system functions that involve

present by the third to fourth months of pregnancy.

Nervous System.

thus keeping only clean fluid in the lungs.

Also, small amounts of fluid are secreted into the lungs

the fetus’s gastrointestinal tract into the amniotic fluid.

pletely deflated. The inhibition of respiration during the

for reasons unknown, and the lungs remain almost com-

During the last 3 to 4 months of pregnancy, the res-

Fetal and Neonatal Physiology

Chapter 83

1043

piratory movements of the fetus are mainly inhibited,

later months of fetal life prevents filling of the lungs
with fluid and debris from the meconium excreted by

by the alveolar epithelium up until the moment of birth,

Most of the reflexes of the fetus that

involve the spinal cord and even the brain stem are

the cerebral cortex are still only in the early stages of

some major tracts of the brain itself becomes complete

Gastrointestinal.

to ingest and absorb large quantities of amniotic fluid,

meconium are continually

formed in the gastrointestinal tract and excreted from

partly of residue from swallowed amniotic fluid and
partly of mucus and other residues of excretory prod-

Kidneys.

mal kidney development or severe impairment of
kidney function in the fetus greatly reduce the forma-
tion of amniotic fluid (oligohydramnios) and can lead to
fetal death.

control systems for regulating fetal extracellular fluid

and do not reach full development until a few months
after birth.

Fetal Metabolism.

from glucose rather than being absorbed directly from

there are special problems of fetal metabolism in rela-

Metabolism of Calcium and Phosphate.

the rates of calcium and phosphate accumulation in the

and 13.5 grams of phosphorus are accumulated in the

is coincident with the period of rapid ossification of the
fetal bones and with the period of rapid weight gain of

relatively unossified and have mainly a cartilaginous

Note especially that the total amounts of calcium and

phosphate needed by the fetus during gestation repre-
sent only about 2 per cent of the quantities of these

occurs after birth during lactation.

Accumulation of Iron.

accumulates in the fetus even more rapidly than calcium

third week after fertilization of the ovum.

Small amounts of iron are concentrated in the

into the embryo by the trophoblastic cells and is used

Weight

Ovulation

Parturition

Length

Age of fetus (weeks after last menstruation)

Length (centimeters)

Weight (Kilograms)

Growth of the fetus.

Figure 83–1

12 16 20 24 28 32 36 40

Ovulation

Parturition

Iron
Calcium
Phosphorus

250

200

150

100

Age of fetus (weeks after last menstruation)

Grams of calcium or phosphorus stored

Milligrams of iron stored

Iron, calcium, and phosphorus storage in the fetus at different

Figure 83–2

stages of gestation.

minutes after birth, as shown by the third compliance

less negative and positive pressures required. Breathing

Note that the second breath is much easier, with far

fluid in the bronchioles.

40 centimeters of water, is

itive pressure, about

enters the lungs. To deflate the lungs, considerable pos-

60 centimeters of water, about 40 milliliters of air

30 mm Hg). Then, as the negative pressure increases

moving to the right. The curve shows that the volume of

beginning at the zero pressure point

breath after birth. Observe, first, the lower part of

sure-volume curve (“compliance” curve) for the first

the onset of breathing. At the top is shown the pres-

Figure 83–3 shows the tremendous negative

space.

much as 60 mm Hg negative pressure in the intrapleural

are extremely powerful, usually capable of creating as

Fortunately, the first inspirations of the normal neonate

effected with relatively weak respiratory movements.

once the alveoli do open, further respiration can be

tension and to open the alveoli for the first time. But

25 mm Hg of negative inspiratory pressure in the lungs

tension of the viscid fluid that fills them. More than

At birth, the walls of the

affecting many of the motor functions of the body.

colliculi, and in other brain stem areas, thus permanently

lesions develop mainly in the thalamus, in the inferior

delayed more than 8 to 10 minutes. Indeed, actual

failure to breathe after birth. Permanent and very

Degree of Hypoxia That an Infant Can Tolerate.

the placenta; or (4) excessive anesthesia of the mother,

the uterus, which can cut off the mother’s blood flow to

separation of the placenta; (3) excessive contraction of

(1) compression of the umbilical cord; (2) premature

serious depression of the respiratory center.

tant, prolonged fetal hypoxia during delivery can cause

tory center. Second, and probably much more impor-

result from two possible effects: First, in a few infants,

breathe or sometimes do not breathe at all. This can

importance of using as little anesthesia as feasible. Also,

delayed for several minutes, thus demonstrating the

the fetus as well, the onset of respiration is likely to be

during delivery, which at least partially anesthetizes

progressively more hypoxic and hypercapnic, which

does not breathe immediately, the body becomes

originate in the suddenly cooled skin. In an infant who

birth process, but also from (2) sensory impulses that

sudden exposure to the exterior world, probably result-

minute after birth. The promptness with which the fetus

mother who has not been depressed by anesthetics, the

infant is to begin breathing.

fore, loss of this means of metabolic support. One of the

the placental connection with the mother and, there-

The most obvious effect of birth on the baby is loss of

Onset of Breathing

the mother is helpful in preventing fetal hemorrhage,

newborn infant. Therefore, prenatal storage in the fetal

colon, the neonate has no adequate source of vitamin K

vitamin K is formed by bacterial action in the mother’s

in the fetus as well as in the mother. Because most

mother, Factor VII and prothrombin become deficient

ulation factors. When vitamin K is insufficient in the

Factor VII, prothrombin, and several other blood coag-

Vitamin K is used by the fetal liver for formation of

pregnancy.

the early embryo. In its absence in laboratory animals,

are not clear, is necessary for normal development of

Vitamin E, although the mechanisms of its functions

body fluids, large quantities of the vitamin will be stored

nal tract. If the mother has plenty of this vitamin in her

fetus, but even more important, the mother needs it for

Vitamin D is needed for normal bone growth in the

fibers of connective tissue.

intercellular substances, especially the bone matrix and

Vitamin C is necessary for appropriate formation of

nervous tissue, as well as for overall growth of the fetus.

The B vitamins, especially vitamin B

mentioned, however.

71. Special functions of several vitamins should be

same in the fetus as in the adult, as discussed in Chapter

far greater extent. In general, the vitamins function the

The fetus needs vitamins

in the liver. This iron can then be used for several

to form the very early red blood cells. About one third

1044

Unit XIV

Endocrinology and Reproduction

of the iron in a fully developed fetus is normally stored

months after birth by the neonate for formation of addi-
tional hemoglobin.

Utilization and Storage of Vitamins.

equally as much as the adult and in some instances to a

and folic acid,

are necessary for formation of red blood cells and

adequate absorption of calcium from her gastrointesti-

by the fetal liver to be used by the neonate for several
months after birth.

spontaneous abortion usually occurs at an early stage of

for the first week or so of life after birth until normal
colonic bacterial flora become established in the

liver of at least small amounts of vitamin K derived from

particularly hemorrhage in the brain when the head is
traumatized by squeezing through the birth canal.

Adjustments of the Infant
to Extrauterine Life

most important immediate adjustments required of the

Cause of Breathing at Birth.

After normal delivery from a

child ordinarily begins to breathe within seconds and
has a normal respiratory rhythm within less than 1

begins to breathe indicates that breathing is initiated by

ing from (1) a slightly asphyxiated state incident to the

provides additional stimulus to the respiratory center
and usually causes breathing within an additional
minute after birth.

Delayed or Abnormal Breathing at Birth—Danger of Hypoxia.

the mother has been depressed by a general anesthetic

many infants who have had head trauma during deliv-
ery or who undergo prolonged delivery are slow to

intracranial hemorrhage or brain contusion causes a
concussion syndrome with a greatly depressed respira-

Hypoxia frequently occurs during delivery because of

which depresses oxygenation even of her blood.

In an adult,

failure to breathe for only 4 minutes often causes death,
but a neonate often survives as long as 10 minutes of

serious brain impairment often ensues if breathing is

Expansion of the Lungs at Birth.

alveoli are at first collapsed because of the surface

is usually required to oppose the effects of this surface

intrapleural pressures required to open the lungs at

the curve

and

air in the lungs remains almost exactly zero until the
negative pressure has reached

-40 centimeters water

(

required because of viscous resistance offered by the

does not become completely normal until about 40

The basic changes

the lungs.

diately after birth, virtually all the blood flows through

12 per cent of the blood flows through the lungs; imme-

tissues of the fetus. Furthermore, during fetal life, only

centa, leaving only 45 per cent to pass through all the

ferent vascular circuits of the fetus. This figure shows

Figure 83–5 gives the relative percentages of the total

umbilical arteries into the placenta, where the deoxy-

into the descending aorta, then through the two

deoxygenated blood from the head region of the fetus,

cuspid valve into the right ventricle. This blood is mainly

The blood entering the right atrium from the supe-

into the arteries of the head and forelimbs.

right side, and is pumped by the left ventricle mainly

enters mainly the left side of the heart, rather than the

Thus, the well-oxygenated blood from the placenta

foramen ovale

, mainly bypassing the liver. Then

First, as shown in Figure 83–4, blood returning from

differently from that of the newborn baby.

placenta. Therefore, special anatomical arrangements

through either the lungs or the liver. However, the fetal

because the liver is only partially functional, it is not

Specific Anatomical Structure of the Fetal Circulation.

these readjustments, we must first consider the anatom-

to this point has had very little blood flow. To describe

and more blood flow through the baby’s liver, which up

quate blood flow through the lungs. Also, circulatory

pulmonary edema. The role of surfactant in preventing

a collapse tendency of the alveoli and development of

bility to secrete sufficient surfactant, which causes both

months of gestation. Therefore, many premature babies

ing the alveoli to open easily during inspiration. The sur-

the surface tension of the alveolar fluid, therefore allow-

, a sub-

hyaline membrane.

lar epithelial cells. This condition is called

the alveoli. The fluid also contains desquamated alveo-

contain large quantities of proteinaceous fluid, almost

next day or so. The alveoli of these infants at death

the first several days after birth, and some die within the

mature infants and infants born of diabetic mothers,

A small number of infants, especially pre-

Respiratory Distress Syndrome Caused When Surfactant Secretion

for the normal adult, as shown in Chapter 38.

curve, the shape of which compares favorably with that

Fetal and Neonatal Physiology

Chapter 83

1045

Is Deficient.

develop severe respiratory distress in the early hours to

as if pure plasma had leaked out of the capillaries into

hyaline mem-

brane disease because microscopic slides of the lung
show the material filling the alveoli to look like a

One of the most characteristic findings in respiratory

distress syndrome is failure of the respiratory epithe-
lium to secrete adequate quantities of surfactant
stance normally secreted into the alveoli that decreases

factant-secreting cells (type II alveolar epithelial cells)
do not begin to secrete surfactant until the last 1 to 3

and a few full-term babies are born without the capa-

these effects is discussed in Chapter 37.

Circulatory Readjustments at Birth

Equally as essential as the onset of breathing at birth
are immediate circulatory adjustments that allow ade-

adjustments during the first few hours of life cause more

ical structure of the fetal circulation.

Because

the lungs are mainly nonfunctional during fetal life and

necessary for the fetal heart to pump much blood

heart must pump large quantities of blood through the

cause the fetal circulatory system to operate much

the placenta through the umbilical vein passes through
the ductus venosus
most of the blood entering the right atrium from the
inferior vena cava is directed in a straight pathway
across the posterior aspect of the right atrium and
through the

directly into the left atrium.

rior vena cava is directed downward through the tri-

and it is pumped by the right ventricle into the pul-
monary artery and then mainly through the ductus arte-
riosus

genated blood becomes oxygenated.

blood pumped by the heart that pass through the dif-

that 55 per cent of all the blood goes through the pla-

Changes in the Fetal Circulation at Birth.

in the fetal circulation at birth are discussed in

Pressure

Second Breath

Volume (ml)

Pressure

First Breath

Volume (ml)

Pressure

40 Minutes

Volume (ml)

reserved.)

after birth. (Redrawn from Smith CA: The first breath. Sci Am

opment of a nearly normal compliance curve within 40 minutes

required for breathing during the first two breaths of life and devel-

neonate immediately after birth, showing the extreme forces

Pressure-volume curves of the lungs (“compliance” curves) of a

Figure 83–3

of the ductus arteriosus. Then, during the next 1 to

to stop all blood flow. This is called

within 1 to 8 days, the constriction is usually sufficient

wall of the ductus arteriosus constricts markedly, and

in fetal life. However, after only a few hours, the muscle

ductus arteriosus, rather than in the other direction as

consequence, after birth, blood begins to flow backward

reduces the pulmonary arterial pressure.

reasons. First, the increased systemic resistance

The ductus arteriosus also closes, but for different

than the right atrial pressure, and the backpressure

throughout life normally remains 2 to 4 mm Hg greater

manent closure does not occur, the left atrial pressure

years and forms a permanent closure. But even if per-

In two thirds of all people, the valve becomes adher-

the foramen ovale.

this opening, thereby preventing further flow through

Consequently, the small valve that lies over the foramen

than in the other direction, as occurred during fetal life.

that is, from the left atrium into the right atrium, rather

low right atrial pressure

The

right atrial pressure.

through the lungs as much as fivefold, which

tion of the lungs eliminates the hypoxia. All these

blood vessels, but vasodilation takes place when aera-

severalfold. Also, in fetal life, the hypoxia of the lungs

diately on expansion, these vessels are no longer

pressed because of the small volume of the lungs. Imme-

unexpanded fetal lungs, the blood vessels are com-

as a result of expansion of the lungs. In the

Second, the

resistance at birth. This increases the aortic pressure as

The primary changes in the circulation at birth are, first,

Primary Changes in Pulmonary and Systemic Vascular

are the following.

throughout life in a few persons. Briefly, these changes

1046

Unit XIV

Endocrinology and Reproduction

Chapter 23 in relation to congenital anomalies of the
ductus arteriosus and foramen ovale that persist

Resistances at Birth

loss of the tremendous blood flow through the placenta,
which approximately doubles the systemic vascular

well as the pressures in the left ventricle and left atrium.

pulmonary vascular resistance greatly

decreases

compressed and the resistance to blood flow decreases

causes considerable tonic vasoconstriction of the lung

changes together reduce the resistance to blood flow

reduces the

pulmonary arterial pressure, right ventricular pressure,
and

Closure of the Foramen Ovale

and the high left atrial pres-

sure that occur secondarily to the changes in pulmonary

and systemic resistances at birth cause blood now to
attempt to flow backward through the foramen ovale;

ovale on the left side of the atrial septum closes over

ent over the foramen ovale within a few months to a few

keeps the valve closed.

Closure of the Ductus Arteriosus

elevates

the aortic pressure while the decreased pulmonary
resistance

As a

from the aorta into the pulmonary artery through the

functional closure

Aorta

Ductus arteriosus

Umbilical
arteries

Umbilical

vein

Foramen ovale

Lung

Gut

Liver

Superior

vena cava

Embryology. 7th ed. Philadelphia: WB Saunders Co, 1974.)

Developmental Anatomy: A Textbook and Laboratory Manual of

Organization of the fetal circulation. (Modified from Arey LB:

Figure 83–4

Forequarters

Hindquarters

Placenta

Right

atrium

Right

atrium

Right

ventricle

Right

ventricle

Ductus

arteriosus

Ductus

arteriosus

Foramen

ovale

Foramen

ovale

Left

atrium

Left

atrium

Left

ventricle

Left

ventricle

Lungs

heart flowing through each particular area.

represent the percentage of the total output from both sides of the

tion of blood flow to the different vascular areas. The numerals

Diagram of the fetal circulatory system, showing relative distribu-

Figure 83–5

that time on, increasing activity by the baby provides

per cubic millimeter by about 6 to 8 weeks of age. From

red cell production. Thus, as shown in Figure 83–6, the

first few weeks of life, presumably because the hypoxic

shown in Figure 83–6. Subsequent to this, however, few

count of about 4.75 million per cubic millimeter, as

during the first few hours of life, giving a red blood cell

If blood is stripped from the cord into the infant, the red

neonate averages about 4 million per cubic millimeter.

The red blood cell count in the

adult pressure of 115/70 is attained at adolescence.

next several months to about 90/60. Then there is a

50 mm Hg diastolic; this increases slowly during the

day after birth averages about 70 mm Hg systolic and

The arterial pressure during the first

weight as in the adult. Occasionally a child is born with

metabolism, is about twice as much in relation to body

averages 500 ml/min, which, like respiration and body

The cardiac output of the neonate

tory distress, but the extra red blood cells are often very

liliters. Some pediatricians believe that this extra blood

is lost into the neonate’s tissue spaces from this blood,

375 milliliters. Then, during the ensuing few hours, fluid

milliliters of blood enters the infant, to make a total of

blood out of its vessels into the baby, an additional 75

ately after birth averages about 300 milliliters, but if the

The blood volume of a neonate immedi-

Blood Volume.

blood gas variations.

decreases in the newborn baby’s blood gas concentra-

difference causes excessive cyclical increases and

This

tional residual capacity of the infant’s lungs is only one

volume of 640 ml/min, which is about twice as great in

ages 16 milliliters. This gives a total minute respiratory

breaths per minute, and tidal air with each breath aver-

The normal rate of respiration in a neonate is about 40

adjusted to the new way of life.

systems. This results partly from immature development

Special Functional Problems

body solids.

much as 20 per cent within the first 2 to 3 days of life.

requires several days to develop. Ordinarily, the infant’s

times that of an adult, and the mother’s milk supply

the infant’s rate of body fluid turnover averages seven

mother’s milk can be provided 2 to 3 days later.

than one half the normal value. Fortunately, however,

the first day to as low as 30 to 40 mg/dl of plasma, less

the infant’s blood glucose concentration frequently falls

which prevents significant gluconeogenesis. Therefore,

the infant’s needs for only a few hours. The liver of the

the amount of glucose stored in the infant’s body in the

glucose obtained from the mother’s blood. After birth,

Before birth, the fetus derives almost all its energy from

know almost nothing about what causes the closure.

Although the ductus venosus rarely fails to close, we

force portal venous blood flow through the liver sinuses.

rises from near 0 to 6 to 10 mm Hg, which is enough to

of flow. As a consequence, the portal venous pressure

However, within 1 to 3 hours the muscle wall of the

amount passing through the channels of the liver.

still flows through the ductus venosus, with only a small

umbilical vein ceases, but most of the portal blood

Immediately after birth, blood flow through the

liver.

below the heart but above the liver, thus bypassing the

umbilical vein, and these together pass by way of the

from the fetus’s abdomen joins the blood from the

In fetal life, the portal blood

Closure of the Ductus Venosus

prostaglandins, often leads to closure.

, which blocks synthesis of

prostaglandins in the ductus wall. In fact, administration

quences of which are discussed in Chapter 23. The

, the conse-

close, resulting in a

In one of several thousand infants, the ductus fails to

within a few hours after birth. Furthermore, many

15 to 20 mm Hg, but it increases to about 100 mm Hg

ductus. In fetal life the P

The cause of ductus arteriosus closure relates to the

4 months, the ductus arteriosus ordinarily becomes

Fetal and Neonatal Physiology

Chapter 83

1047

anatomically occluded by growth of fibrous tissue into
its lumen.

increased oxygenation of the blood flowing through the

of the ductus blood is only

experiments have shown that the degree of contraction
of the smooth muscle in the ductus wall is highly related
to this availability of oxygen.

patent ductus arteriosus

failure of closure has been postulated to result from
excessive ductus dilation caused by vasodilating

of the drug indomethacin

ductus venosus directly into the vena cava immediately

ductus venosus contracts strongly and closes this avenue

Nutrition of the Neonate

form of liver and muscle glycogen is sufficient to supply

neonate is still far from functionally adequate at birth,

appropriate mechanisms are available for the infant to
use its stored fats and proteins for metabolism until

Special problems are also frequently associated with

getting an adequate fluid supply to the neonate because

weight decreases 5 to 10 per cent and sometimes as

Most of this weight loss is loss of fluid rather than of

in the Neonate

An important characteristic of the neonate is instability
of the various hormonal and neurogenic control

of the different organs of the body and partly from the
fact that the control systems simply have not become

Respiratory System

relation to the body weight as that of an adult. The func-

half that of an adult in relation to body weight.

tions if the respiratory rate becomes slowed because it
is the residual air in the lungs that smooths out the

Circulation

infant is left attached to the placenta for a few minutes
after birth or if the umbilical cord is stripped to force

which increases the hematocrit but returns the blood
volume once again to the normal value of about 300 mil-

volume caused by stripping the umbilical cord can lead
to mild pulmonary edema with some degree of respira-

valuable to the infant.

Cardiac Output.

an especially low cardiac output caused by hemorrhage
of much of its blood volume from the placenta at birth.

Arterial Pressure.

much slower rise during the subsequent years until the

Blood Characteristics.

blood cell count rises an additional 0.5 to 0.75 million

new red blood cells are formed in the infant during the

stimulus of fetal life is no longer present to stimulate

average red blood cell count falls to less than 4 million

the appropriate stimulus for returning the red blood cell

storing proteins. Indeed, with an adequate diet, as much

The neonate is especially capable of synthesizing and

in the blood is unstable and low.

at least the first week of life, the glucose concentration

Third, because the liver functions imperfectly during

milk, is frequently inadequately absorbed.

sequently, milk with a high fat content, such as cow’s

tract is somewhat less than that in the older child. Con-

Second, absorption of fats from the gastrointestinal

is deficient, so that the neonate uses starches less ade-

First, secretion of pancreatic amylase in the neonate

older child, with the following three exceptions.

In general, the ability of the neonate to digest, absorb,

Metabolism of Energy Foods;

Digestion, Absorption, and

4. The liver of the neonate usually also forms too

until sufficient feeding can occur.

mg/dl (about 40 per cent of normal), and the infant

particularly deficient. As a result, the blood glucose

3. The gluconeogenesis function of the liver is

plasma proteins, so that the plasma protein

2. The liver of the neonate is deficient in forming

life.

1. The liver of the neonate conjugates bilirubin with

neonate may be quite deficient, as evidenced by the

During the first few days of life, liver function in the

tion, and, more rarely, overhydration.

important problems of infancy are acidosis, dehydra-

of acid, one can readily understand that among the most

sidering the immaturity of the kidneys, together with the

instead of the adult three to four times. Therefore, con-

instance, the kidneys of the neonate can concentrate

until the end of about the first month of life. For

which gives a tendency toward acidosis in the infant.

great in relation to body mass as in the adult, which

The rate of metabolism in the infant is also twice as

cause rapidly developing abnormalities.

weight as in the adult, which means that even a slight

The rate of fluid intake and fluid excretion in the

and Renal Function

Fluid Balance, Acid-Base Balance,

seriously in 1 of every 50 to 100 neonates.

cal therapeutics, this condition occurred either mildly or

quate red cells. Before the advent of modern obstetri-

releasing extreme quantities of bilirubin into the fetus’s

blood cells, and her antibodies destroy fetal red cells,

against the Rh-positive factor (a protein) in the fetus’s

Rh negative. The mother then becomes immunized

positive red cells from the father, while the mother is

erythroblastotic baby

mother. Briefly, the

erythroblastosis fetalis,

However, by far the most important abnormal cause

a week or two.

infant’s skin and especially of the sclerae of its eyes for

is shown in Figure 83–6, and it

liver becomes functional. This effect, called

1 mg/dl to an average of 5 mg/dl during the first 3 days

excretion into the bile. Consequently, the plasma biliru-

neonate’s own liver, which for the first week or so of life

mother, but immediately after birth, the only means

neonate is about 45,000 per cubic millimeter, which is

ately after birth, the white blood cell count of the

count to normal within another 2 to 3 months. Immedi-

1048

Unit XIV

Endocrinology and Reproduction

about five times as great as that of the normal adult.

Neonatal Jaundice and Erythroblastosis Fetalis.

Biliru-

bin formed in the fetus can cross the placenta into
the mother and be excreted through the liver of the

for ridding the neonate of bilirubin is through the

functions poorly and is incapable of conjugating signi-
ficant quantities of bilirubin with glucuronic acid for

bin concentration rises from a normal value of less than

of life and then gradually falls back to normal as the

physiologic

hyperbilirubinemia,
is associated with mild jaundice (yellowness) of the

of serious neonatal jaundice is
which is discussed in detail in Chapter 32 in relation
to Rh factor incompatibility between the fetus and

inherits Rh-

plasma and often causing fetal death for lack of ade-

newborn infant is seven times as great in relation to

percentage alteration of fluid intake or fluid output can

means that twice as much acid is normally formed,

Functional development of the kidneys is not complete

urine to only 1.5 times the osmolality of the plasma

marked fluid turnover in the infant and rapid formation

Liver Function

following effects:

glucuronic acid poorly and therefore excretes
bilirubin only slightly during the first few days of

concentration falls during the first weeks of life to
15 to 20 per cent less than that for older children.
Occasionally the protein concentration falls so low
that the infant develops hypoproteinemic edema.

level of the unfed neonate falls to about 30 to 40

must depend mainly on its stored fats for energy

little of the blood factors needed for normal blood
coagulation.

and Nutrition

and metabolize foods is no different from that of the

quately than do older children.

Age in weeks

Bilirubin

Red blood count

Serum bilirubin (mg/dl)

Red blood cell count (millions/mm

)

Changes in the red blood cell count and in serum bilirubin con-

Figure 83–6

centration during the first 16 weeks of life, showing physiologic
anemia at 6 to 12 weeks of life and physiologic hyperbilirubine-
mia during the first 2 weeks of life.

1. If a pregnant mother bearing a female child is

special instances in which the endocrinology of infancy

immediate endocrine abnormalities. However, there are

developed at birth, and the infant seldom exhibits any

Ordinarily, the endocrine system of the infant is highly

appear. This relation of immunity to allergy is discussed

nity develop, these allergic manifestations usually dis-

trointestinal abnormalities, and even anaphylaxis. As

can develop, often resulting in serious eczema, gas-

antibodies first begin to form, extreme allergic states

Several months later, however, when the infant’s own

The newborn infant is seldom subject to allergy.

Allergy.

life.

therefore, for full safety, the infant requires immuniza-

Conversely, the inherited antibodies against whooping

diseases before 6 months is usually unnecessary.

and polio. Therefore, immunization against these

hood infectious diseases, including diphtheria, measles,

birth, the antibodies inherited from the mother protect

months.

antibodies, and the gamma globulin concentration

after, the baby’s own immunity system begins to form

level, with a corresponding decrease in immunity.There-

bodies, have decreased to less than one half the original

the baby’s gamma globulins, which contain the anti-

own to a significant extent. By the end of the first month,

However, the neonate does not form antibodies of its

mother’s blood through the placenta into the fetus.

The neonate inherits much immunity from the mother

acid are often prescribed by the third week of life.

this reason, orange juice or other sources of ascorbic

which has only one fourth as much as human milk. For

poor supplies of ascorbic acid, especially cow’s milk,

lular structures of the infant. Furthermore, milk has

proper formation of cartilage, bone, and other intercel-

quantities in the fetal tissues; yet it is required for

third month of life.

sonably large quantities of iron, or the administration of

feeding of the infant with egg yolk, which contains rea-

about 3 months of life. To prevent this possibility, early

diet, severe anemia is likely to occur in the infant after

birth. But if the mother has had insufficient iron in her

diet, the liver of the infant usually has stored enough

even less effectively than those of normal infants.

weeks. This is particularly true in premature babies

absence of vitamin D. Therefore, the vitamin D–

adequately by the usual diet of milk. Yet absorption of

throughout infancy is needed. This is ordinarily supplied

bones at birth, so that a ready supply of calcium

The neonate is in a stage of rapid ossification of its

are provided in the diet. However, three specific prob-

more, function of the gastrointestinal system is usually

vided the mother has had an adequate diet. Further-

neonate is usually in complete nutritional balance, pro-

At birth, a

Nutritional Needs During the Early Weeks of Life.

temperature, which are also shown in Figure 83–7.

the early days of life, allowing marked deviations in

returns to normal in 7 to 10 hours. Still, the body tem-

premature infants, falls easily. Figure 83–7 shows that

the body temperature of the neonate, particularly of

body mass, heat is readily lost from the body. As a result,

about twice that of the adult, which accounts also for

The normal meta-

Metabolic Rate and Body Temperature.

centage than in adults.

formation of body proteins. This is a much higher per-

Fetal and Neonatal Physiology

Chapter 83

1049

as 90 per cent of the ingested amino acids are used for

bolic rate of the neonate in relation to body weight is

the twice as great cardiac output and twice as great
minute respiratory volume in relation to body weight in
the infant.

Because the body surface area is large in relation to

the body temperature of even a normal infant often falls
several degrees during the first few hours after birth but

perature regulatory mechanisms remain poor during

more than adequate to digest and assimilate all the
nutritional needs of the infant if appropriate nutrients

lems do occur in the early nutrition of the infant.

Need for Calcium and Vitamin D

calcium by the gastrointestinal tract is poor in the

deficient infant can develop severe rickets in only a few

because their gastrointestinal tracts absorb calcium

Necessity for Iron in the Diet

If the mother has had adequate amounts of iron in her

iron to keep forming blood cells for 4 to 6 months after

iron in some other form is desirable by the second or

Vitamin C Deficiency in Infants

Ascorbic acid (vitamin C) is not stored in significant

Immunity

because many protein antibodies diffuse from the

returns essentially to normal by the age of 12 to 20

Despite the decrease in gamma globulins soon after

the infant for about 6 months against most major child-

cough are normally insufficient to protect the neonate;

tion against this disease within the first month or so of

the child grows older and still higher degrees of immu-

in Chapter 34.

Endocrine Problems

is important:

treated with an androgenic hormone or if an

Hours after birth

Days after birth

0 2 4 6 8 10 12

4 6 8 10 12 14 16 18

Body temperature (

Birth

and instability of body temperature during the first few days of life.

Fall in body temperature of the neonate immediately after birth,

Figure 83–7

limits of 20 to more than 100 mg/dl, depending princi-

brings on hypocalcemic tetany. Also, the blood glucose

because of immature liver development, often leading

Likewise, the blood protein concentration is usually low

when the rate of food intake varies from time to time.

acid-base balance can vary tremendously, particularly

homeostatic mechanisms of the body. For instance, the

Control Systems in the

Instability of the Homeostatic

phoid system, which often leads to serious infection.

which allows rapid development of anemia; and (4)

of the blood-forming mechanism of the bone marrow,

as to serious fluid balance abnormalities; (3) immaturity

body of acids, thereby predisposing to acidosis as well

of coagulation factors; (2) immaturity of the kidneys,

often a bleeding tendency as a result of poor formation

premature infant includes (1) immaturity of the liver,

vitamin D intake.

before the difficulty is recognized. For this reason,

calcium and, therefore, can develop severe rickets

mature infant must have a low-fat diet. Furthermore,

inadequate. The absorption of fat is so poor that the pre-

If the infant is more than 2 months premature, the

with periodic breathing of the Cheyne-Stokes type.

common cause of death. Also, the low functional resid-

As a consequence,

infant. Also, surfactant secretion is depressed or absent.

be underdeveloped in the premature infant. The vital

The respiratory system is especially likely to

in the premature infant, but some require particular

Immature Development of the

homeostatic control systems. Because of these effects, a

under the following two headings: (1) immaturity of

exacerbated in prematurity. They can be categorized

of Prematurity

Special Problems

This causes the condition called

6. In a fetus lacking thyroid hormone secretion, the

thyrotropin during gestation, and the child might be

woman had had her thyroid gland removed, her

thyroid gland. Conversely, if before pregnancy a

treated with excess thyroid hormone, the infant is

5. If a pregnant woman has hyperthyroidism or is

, which can

adrenal cortices, often resulting from

4. Occasionally a child is born with hypofunctional

earlier in the chapter.

, described

mortality rate. Two thirds of the infants who die

fetuses that do come to term, there is still a high

rate of intrauterine mortality, and among those

neonate are often impaired. Also, there is a high

mother, and growth and tissue maturation of the

(caused by lack of insulin secretion), fetal growth

increased fetal growth. However, most of the

weight. Increased supply of glucose and other

increases in plasma insulin concentration. The high

cause of large babies. Type II diabetes in the

only rarely develops.

neonate, unlike in the adult, insulin shock or coma

shortly after birth. Fortunately, however, in the

concentration may fall to lower than 20 mg/dl

As a consequence, the infant’s blood glucose

of the islets of Langerhans in the pancreas.

3. An infant born of an untreated diabetic mother will

develops.

then become inflamed, or infectious mastitis

during the first days of life. Sometimes the breasts

cause the neonate’s breasts to form milk

the mother’s glands during pregnancy occasionally

2. The sex hormones secreted by the placenta and by

masculinization of her sexual organs, thus resulting

androgenic tumor develops during pregnancy,

1050

Unit XIV

Endocrinology and Reproduction

the child will be born with a high degree of

in a type of hermaphroditism.

have considerable hypertrophy and hyperfunction

from this low level of blood glucose concentration

Maternal type II diabetes is the most common

mother is associated with resistance to the
metabolic effects of insulin and compensatory

levels of insulin are believed to stimulate fetal
growth factor and contribute to increased birth

nutrients to the fetus may also contribute to

increased fetal weight is due to increased body fat;
there is usually little increase in body length
although the size of some organs may be increased
(organomegaly).

In the mother with uncontrolled type I diabetes

may be stunted because of metabolic deficits in the

succumb to respiratory distress syndrome

agenesis of

the adrenal glands or exhaustion atrophy
occur when the adrenal glands have been vastly
overstimulated.

likely to be born with a temporarily hyposecreting

pituitary gland may secrete great quantities of

born with temporary hyperthyroidism.

bones grow poorly and there is mental retardation.

cretin dwarfism,

discussed in Chapter 76.

All the problems in neonatal life just noted are severely

certain organ systems and (2) instability of the different

premature baby seldom lives if it is born more than 3
months before term.

Premature Infant

Almost all the organ systems of the body are immature

attention if the life of the premature baby is to be saved.

Respiration.

capacity and the functional residual capacity of the
lungs are especially small in relation to the size of the

respiratory distress syndrome is a

ual capacity in the premature infant is often associated

Gastrointestinal Function.

Another major problem of the

premature infant is to ingest and absorb adequate food.

digestive and absorptive systems are almost always

the premature infant has unusual difficulty in absorbing

special attention must be paid to adequate calcium and

Function of Other Organs.

Immaturity of other organ

systems that frequently causes serious difficulties in the

which results in poor intermediary metabolism and

which are particularly deficient in their ability to rid the

depressed formation of gamma globulin by the lym-

Premature Infant

Immaturity of the different organ systems in the pre-
mature infant creates a high degree of instability in the

to hypoproteinemic edema. And inability of the infant
to regulate its calcium ion concentration frequently

concentration can vary between the extremely wide

the female.

because of much delayed uniting of the epiphyses, so

however, undergoes much more prolonged growth

age—mainly between ages 13 and 17 years. The male,

the male, which causes extra growth at a slightly later

ceases. This contrasts with the effect of testosterone in

14th to 16th year of life, so that growth in height then

the ages of 11 and 13 years, the female estrogens begin

exactly until the end of the first decade of life. Between

girls from the time of birth until the age of 20 years.

Figure 83–8 shows the changes in heights of boys and

tions of this book on metabolism and endocrinology.

for growth, which have been fully covered in the sec-

The major physiologic problems of the child beyond the

Growth and Development

breathed, but some child physiologists believe that com-

causes permanent blindness. For this reason, it is par-

This condition, known as

eye’s clear vitreous humor should be.

from the pupil to the retina. And still later, the vessels

growing all through the vitreous humor, blocking light

therapy is stopped, the blood vessels try to make up for

new blood vessels in the retina. Then when oxygen

The reason is that too much oxygen stops the growth of

especially in early prematurity, can lead to blindness.

that use of excess oxygen in treating premature infants,

treating prematurity. However, it has been discovered

tory distress, oxygen therapy has often been used in

in the Premature Infant

the incubator in treatment of prematurity.

of death, which explains the almost mandatory use of

the low 90°s or even in the 80°s F. Statistical studies

temperature, the infant’s temperature may stabilize in

approach that of its surroundings. At normal room

normal body temperature. Its temperature tends to

Instability of Body Temperature.

ment of the premature infant, that mortality is high.

pally on the regularity of feeding. It is no wonder, then,

Fetal and Neonatal Physiology

Chapter 83

1051

with these extreme variations in the internal environ-

One of the particular prob-

lems of the premature infant is inability to maintain

show that a body temperature maintained below 96°F
(35.5°C) is associated with a particularly high incidence

Danger of Blindness Caused
by Excess Oxygen Therapy

Because premature infants frequently develop respira-

lost time and burst forth with a great mass of vessels

are replaced with a mass of fibrous tissue where the

retrolental fibroplasia,

ticularly important to avoid treatment of premature
infants with high concentrations of respiratory oxygen.
Physiologic studies indicate that the premature infant is
usually safe with up to 40 per cent oxygen in the air

plete safety can be achieved only at normal oxygen con-
centration in the air that is breathed.

of the Child

neonatal period are related to special metabolic needs

Note especially that these parallel each other almost

to be formed and cause rapid growth in height but early
uniting of the epiphyses of the long bones at about the

that his final height is considerably greater than that of

Age in months

Age in years

20 24

4 8 12 16

Boys

Height (inches)

Girls

Average height of boys and girls from infancy to 20 years of age.

Figure 83–8

Vocalizes

Walks with support

Walks alone

Age in months

Birth

Stands alone

Pulls up

Grasps

Crawls

Sits briefly

Rolls over

Hand control

Head control

Smiles

Suckles

Figure 83–9

Behavioral development of the infant during the first year of life.

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MacLellan WR, Schneider MD: Genetic dissection of

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Johnson MH: Functional brain development in humans. Nat

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Holemans K, Aerts L, Van Assche FA: Lifetime conse-

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Bissonnette JM: Mechanisms regulating hypoxic respiratory

parison of this chart with the baby’s actual development

chart for the infant during the first year of life. Com-

2 years of life. Figure 83–9 shows a normal progress

fontanels and sutures of the skull, which allows only 20

second year. This is also associated with closure of the

the adult brain mass and 55 per cent at 1 year, but it

At birth, the infant brain mass is only 26 per cent of

occur.

ated functions, such as vision, seem to require several

fully functional at birth. The brain cortex and its associ-

until the end of the first year of life. For this reason,

nervous system from maturity caused by training.

of the nervous system. It is extremely difficult to

1052

Unit XIV

Endocrinology and Reproduction

Behavioral Growth

Behavioral growth is principally a problem of maturity

dissociate maturity of the anatomical structures of the

Anatomical studies show that certain major tracts in the
central nervous system are not completely myelinated

it is frequently stated that the nervous system is not

months after birth for final functional development to

reaches almost adult proportions by the end of the

per cent additional growth of the brain beyond the first

is used for clinical assessment of mental and behavioral
growth.

References

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2004.