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NORTHEASTERN UNIVERSITY
BOUVE COLLEGE OF PHARMACY AND HEALTH SCIENCES
NEONATAL RESPIRATORY CARE

NOTES
Basic Embryology
Fertilization is the union of the sperm cell and the mature ovum.  It occurs in the outer third of the fallopian tube.  Gestation is 40 weeks from that point, or about 280 days.  In the first month alone, the fetus grows in weight by nearly 3,000%.
Gestational age refers to the time since conception.  Normal human pregnancy is 10 lunar months of four weeks each (thus, 40 weeks) or 9 calendar months.  There are three trimesters of 3 calendar months each.
The “organism” is not called a fetus until around the 56th day.  It is called an ovum from the time of fertilization until implantation (about 12 to 14 days).  Then it is called an embryo until it grows to measures 3 cm from head to rump (about 54-56 days).  It is then called a fetus until birth.  All major organs have been developed once the little being is a fetus - now all they have to do is grow.

Growth originally starts as the fertilized ovum travels approximately 10-13 cm down the fallopian tube.  It reaches the uterus in about five days.  Cell division is called cleavage, and rapid division occurs in the fallopian tube.  The cells that are produced during this rapid cleavage are blastomeres and are surrounded by a transparent tissue envelope called the zona pellucida.
As cell division continues (to about 16 to 50 cells), the organism tends to shape itself into a ball called a morula.  Now it enters the uterus.  Next, fluid gathers around the morula and a cavity forms in its center.  Then fluid begins to collect in the cavity.  At this point, it is called a blastocyst.  With further development the zona pellucida is replaced by an outer layer of cells called the trophoblast.

As the blastocyst continues to expand, some of the cells gather toward one end forming the blastoderm or embryonic disc (these terms are synonymous).  This group of cells will become the fetus and the trophoblast will become the placenta and related structures.The trophoblast attaches itself to the lining of the uterus to receive nourishment.  The lining is called the endometrium.  The attachment is called implantation and this normally occurs in the upper portion of the uterus.
Eventually the blastocyst will become completely covered by the endometrium and the trophoblast will grow into the endometrium, forming what will become the placenta.
The embryonic disc includes two layers of cells (called germ layers): the ectoderm and the endoderm.  They are named according to their location: the ectoderm is the outer, thicker layer.  Another cell layer, the mesoderm, forms between the other two.  All tissues, organs, and organ systems arise from these three primary germ layers.
In the 1960’s Reid formulated some important rules related to the normal development of the human lung.  They are as follows:
1. The bronchial tree develops by the 16th week of intrauterine life.
2. After birth the alveoli develop in increasing number until the age of 8 years and increase in size until the chest wall has reached its maximum.

(The newborn infant has around 50 million alveoli; he or she has the potential to add another 250 million...the total surface area will grow from 3 square meters to about 70 as an adult...more than 80 per cent of the eventual number of 300 million alveoli will form after birth.  From newborn to adulthood, the human lung volume will increase 23-fold...alveolar number will increase six-fold...alveolar surface area will increase 21-fold...lung weight will increase by 20-fold.)
While we are on the subject of growth, think of the phenomenal rate at which an infant grows in the first year.  Body weight doubles by six months and triples by one year of age.  Interestingly, the growth of alveoli lags behind the growth of the body.  Most of the postnatal alveolar growth occurs over 1.5 years.  Then the rate of alveolar growth tends to parallel body growth.  In a compromised infant, the increased oxygen demands of growth may lag behind the actual development of the lung.
3. Blood vessels are remodeled and increase in number, certainly while new alveoli are forming and probably until the growth of the chest is complete.

Although opinions differ as to the names and milestones that make up the four phases of lung development, we will review them.  They are traditionally known as the

Now let us highlight the important events of each stage:
The Embryonic Stage (1st five weeks)
· earliest formation of the lung begins at about day 26
· outpouching  of the foregut is the first sign of the          developing lung (endoderm)
· there is further branching...structure becomes enveloped within mesoderm; eventually the right and left bronchi are differentiated
· significance of mesoderm is important here: muscle, connective tissue, cartilage, and supportive structures all are developing from the mesodermal layer
· the diaphragm develops early in this phase (is fully developed by the seventh week)
· pulmonary artery and veins in primitive form begin to appear at around days 32 - 37

The Pseudoglandular Stage (weeks 6-16)
· approximately from 4 to 25 branchings of the tracheobronchial during this phase
· the lung resembles a gland in gross appearance
· first appearance of submucosal glands in trachea(week 10); goblet cells also present by week 10; submucosal glands are in the trachea by week 16
· smooth muscle begins to appear (weeks 6 to 8) in trachea, primary and lobar bronchi
· ciliated cells in upper airways (week 7)
· fetal breathing movement begins (week 12)

The Canalicular Stage (weeks 16 - 26)
· first identifiable components of respiratory units (week 16)
· type I and II cells differentiate
· surfactant begins to be produced

The Terminal Sac Phase (weeks 27 - 40)
[Some investigators prefer to describe this phase as two subphases: a saccular phase in which interstitial tissue and saccular walls become thinner (weeks 28 to 36), and an alveolar phase in which alveoli actually develop (weeks 36 to term)].
· viability in extrauterine life (week 24 - 26)
· maturation of surfactant
· macrophages appear
· expansion of alveolar-capillary membranes; note the possibility of alveolar-capillary dysplasia)
· carotid body chemoreceptors mature (week 28)
· alveolar duct open into terminal sacs (week 32)
· alveoli develop (week 34 to 36 on to term...)
· thinning and elongation of type I alveolar cells (by week 40)

Although we are deferring the discussion of surfactant to another time, now is a good time to discuss the significance of fetal lung fluid.  As you are well aware, there is surfactant in the fetal lung fluid, just as there is in amniotic fluid.  But the role of fetal lung fluid has little to do with surface forces but a lot to do with lung maturation. The lung produces and secretes its own fluid in increasing amounts as the fetus matures.  Although exact secretion rates are not known, the human fetus is similar to the fetal lamb, which is about 100 cc/day near term.  About 30 cc of the fluid is in the lung at any one time, and this amount is said to occupy the FRC volume of the near term fetus.  The fetus expels lung fluid through the mouth into the amniotic fluid.  The production of this fluid ceases entirely at birth, but before during gestation, it is known to help the lung form and maintain its shape and to remain inflated.

From lamb studies, investigators have learned that lung growth accelerates when the lungs are fluid filled.  If a newborn lamb with hypoplastic lungs were to have one lung filled with fluid and the other ventilated with air, the fluid filled lung would grow and continue to mature rather rapidly.  The ventilated lung would remain essentially the same size.
Much is said about the risks of retained fluid in the newborn immediately after delivery.  Believe it or not, retained lung fluid was once a major cause of death or severe neurologic impairment in the otherwise healthy term neonate.  Today, it is still a common occurrence, particularly in the precipitous delivery and caesarean section, presumably because the infant’s body is not squeezed in the birth canal.  However, it is one of the more easily treated causes of respiratory distress if uncomplicated by surfactant deficiency or infection.  Be sure to read the section on page 17,  Hazards of Lung Fluid Retention.

Your book has a sketchy description of cardiovascular development.  The heart develops over the first 3 to 8 weeks of gestation.  Note that the embryo needs a blood supply pretty early because the placenta cannot provide all of the circulatory work for very long.  The first signs of a heart developing can be seen at about 21 days when the blood islands are seen.  These are little clusters that arise from the mesoderm, called angiogenic clusters, and they grow and divide rapidly until a lumen and a blood-filled network is formed. The heart, as it takes form, becomes what looks like an elongated tube.  This tube is actually two tubes with a sheath of myocardial cells around it.  Next these two tubes begin to fuse together and form a single chamber.  Not too long after this formation (at about the fourth gestational week), the primitive heart in its present form, starts to beat.  At first this beating causes a back-and-forth flow of blood.  Early in the heart’s development, it changes shape from a curved tube to a c-shaped tube and later to an S shape.  It originally was thought that the peculiar shape was because of the limited space the heart had to grow.  This theory has been disproved, and we now know that there is an inherent tendency to form this shape within the cardiac muscle.  By the fifth week, the heart has lost its S shape and is taking on the shape of the adult heart.  The too-and-fro movement of blood becomes uni-directional with the development of the four heart chambers...blood begins to flow from the sinus venosus through the chambers as it normally would, and out the truncus arteriosus.  The pulmonary arteries and the aorta as well as their valves develop from the truncus.
The fetal heart structures that are illustrated on page 18 of your book

Be sure to learn the location of the four areas of the fetal heart.  The first of these is the sinus venosus, and as its name implies, it will become the inferior and superior vena cavae and part of the right atrium.  The next two structures actually are landmarks.  They do not have names, but are dilations.  The first dilation at the superior end of the tube will later become the two atria.  The second dilation will become the  left ventricle.  The final major area is the bulbis cordis, which is most of the area to the right, consists of the structures that will become the right ventricle, the right and left ventricular outflow tracts, and the truncus arteriosus.  The truncus arteriosus is the large superior tube that will become both the pulmonary artery and the aorta.  Later in the course we will discuss many of the cardiac anomalies that result from aberrant formations of the heart.
Your book has a good discussion of the fetal circulation beginning on page 19.  In understanding the common circulatory issues affecting the infant in respiratory distress, it is absolutely vital that you memorize the fetal circulation.  The best way to do this is to follow the blood flow using the diagram on page 21 from the placenta and back again.  Be sure to find all of the landmarks and learn where they are.  The two most important are the foramen ovale and the ductus arteriosus.

It will not be necessary to discuss the placenta at this time.  I would like to move on to page 25 and the section on the amniotic fluid.  As you probably know, the amniotic fluid plays some important roles in fetal life.  Naturally it protects the fetus, but it also keeps the fetus at a stable temperature and allows the fetus to move freely.  Also it is known that the amniotic fluid plays a role in initially dilating the cervix because of the enormous pressures that it helps to generate.  It is known that the fetus drinks amniotic fluid and may play a role in nutrition and hydration in late fetal life.

Amniotic fluid measures between 500 and 1500 cc’s.  It is constantly being absorbed and replenished, and until the fetal skin develops, it permeates the skin as well.  In later fetal life, the amount of amniotic fluid depends on the fetal ability to urinate and to swallow, as these two mechanisms regulate fluid levels the most.
Maternal polyhydramnios is an excessive amount of amniotic fluid.  Usually any impairment that prevents the fetus from swallowing will allow amniotic fluid levels to rise.  The condition of polyhydramnios is said to exist when fluid levels increase to over 2 lites.  Note the more common disorders of the fetus on page 26 that can lead to polyhydramnios.
Oligohydramnios is a decreased amount of amniotic fluid.  Defects in fetal urine production usually are the cause.  Skeletal and organ deformities often result in this disorder, and hypoplastic lungs often are seen.  Compression of the umbilical cord can occur.  Most of these infants are delivered by C section.
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Fetal Milestones

Week 4
Primary lung buds appear
Heart develops; double chambers visible; heart begins to beat
Aortic arches and major veins completed
External appearance: Body flexed, C shaped; arm and leg buds
present; head at right angles to body
Crown to rump measurement: 0.4 to 0.5 cm
Weight: 0.4 gm

 Week 8
Pleural and pericardial cavities forming; branching bronchioles;
nostrils closed by epithelial plugs
Main blood vessels assume final plan; enucleated red cells
predominate in blood
External appearance: Body fairly well formed; Nose flat, eyes far
apart; digits well formed; head elevating; tail almost disappeared;
eyes, ears, nose and mouth recognizable
Crown to rump measurement: 2.5 to 3 cm
Weight: 2 gm
 

Week 12
Lungs acquire definite shape; vocal cords appear
Blood forming in marrow
External appearance: Nails appearing; resembles a human; head erect
but disproportionately large; skin pink, delicate
Crown to rump measurement: 6 to 8 cm
Weight: 19 gm
Week 16
Elastic fibers appear in lungs; terminal and respiratory
bronchioles appear
Heart muscle well developed; blood formation active in spleen
External appearance: Head still dominant; face looks human; eye,
ear, and nose approach typical appearance on gross examination;
arm-leg ratio proportionate; scalp hair appears; motor activity
present
Crown to rump measurement: 11.5 to 13.5 cm
Weight: 100 gm

Week 20
Nostrils open; increased vascularity of lungs
External appearance: Vernix caseosa appears; languno hair appears;
legs lengthen considerably; sebaceous glands appear
Crown to rump measurement: 16 to 18.5 cm
Weight: 300 gm

Week 24
Alveolar ducts and sacs present; primitive respiratory-like
movements begin; lecithin begins to appear in the amniotic fluid
Blood formation increases in bone marrow and decreases in liver
External appearance: Body lean but fairly proportioned; skin red
and wrinkled; vernix caseosa present; sweat glands forming
Crown to rump measurement:  23 cm
Weight: 600 gm

Week 28
Surfactant forming on alveolar surfaces
External appearance: Lean body, less wrinkled and red; nails are
formed
Crown to rump measurement:  27 cm
Weight: 1100 gm
Week 32
Lecithin/sphingomyelin ratio = 1.2:1
External appearance: Subcutaneous fat beginning to collect; more
rounded appearance; skin pink and smooth; has assumed delivery
position
Crown to rump measurement:  31 cm
Weight: 1800 to 2100 gm
 

Week 36
Lecithin/sphingomyelin ratio = 2:1 or greater
External appearance: Skin pink, body rounded; general languno
disappearing; body usually plump
Crown to rump measurement:  35 cm
Weight: 2200 to 2900 gm
 

Week 40
Pulmonary branching only two-thirds complete
External appearance: Skin smooth and pink; copious vernix caseosa;
moderate to profuse hair; languno on shoulders and upper body only;
nasal and alar cartilage apparent
Crown to rump measurement:  40 cm
Weight: 3200+  gm



Assessment of Fetal Growth and Development

Ultrasonography
Ultrasonography is an important diagnostic tools in neonatal medicine just as it is in virtually every medical discipline.  It is one of the first of the modern non-invasive technologies (since the flouroscope) that has enabled definitive examination of anatomical structures and observe them in their dynamic state.  It uses high-frequency sound waves to locate and visualize organs and tissues.  These sound waves are well below the intensity that could damage tissues.  In recent years, the technology of ultrasonography has developed to enable trained users to spot fine details that were previously missed.  Blood flow can be assessed with today’s units, and even the direction in which blood is flowing and the pressures within various vessels can be determined.
Ultrasonography is performed by placing a hand-held transducer over the mother’s abdomen.  In some cases a vaginal transducer has to be used if other points of view are necessary.  As sound waves come into contact with different density tissues, some are absorbed and others are reflected to the transducer.  The reflected waves are converted into a screen image, visually duplicating the targeted organ.  The image can then be used to identify abnormalities either in structure, size or movement.
There are two types of images produced by ultrasound: the static image, a single stationary view, and the M-mode image, or a motion mode or real-time image.  Most ultrasound examinations performed today produce both types of images.
There are two types or modes of static images.  First is the amplitude mode, or A mode, which measures distances as spikes on an oscilloscope.  This is one of the earliest forms of clinically used ultrasonic tracings.  The other mode is the brightness mode, which produces a two-dimensional picture on the screen.  In the case of a fetal ultrasound, even the untrained observer usually can make out the fetal image and appreciate the detail. M-mode imaging is used most commonly in neonatal medicine.  With this mode, the fetal movements can be seen.  The heart and its functioning valves are clearly seen as well as other organs.  Today most obstetricians perform a “sonogram” as a matter of routine on all mothers, usually by the eighteenth week of pregnancy.  By this time, most major structural defects can be picked up.  A congenital diaphragmatic hernia could be seen, for example, as well as cardiac anomalies, such as a hypoplastic left ventricle, tetralogy of fallot, and often, coarctation of the aorta.
It is important to mention here that the health of the fetus is only one aspect when performing a sonogram.  A lot can be learned about the general condition of the pregnancy as well.  The site of implantation is important to note as well as the appearance of the placenta and umbilical cord.  The volume of amniotic fluid can be determined pretty accurately also.
What abnormalities are diagnosed in utero?  Some examples are abdominal masses, diaphragmatic hernia, congenital malformations of the nervous system, omphalocele (herniation of the intra-abdominal viscera around the umbilicus), seizures, urinary tract dilation, intraventricular hemorrhage, and many congenital heart defects.
The list of ultrasound applications at the bottom of page 34 is good in that it lists the more common applications.  Keep in mind that an ultrasound can be performed throughout pregnancy and even at delivery and often is used for a quick “look-see.”  It is an easy, reliable, and relatively inexpensive tool.

Amniocentesis
Amniocentesis, which is the needle sampling of amniotic fluid, can be safely performed at about 14 WGA.  A 4-inch 20-22 gauge needle (other lengths are sometimes used) attached to a syringe is inserted into the uterine cavity.  Ultrasound is usually used to position the needle and to find an adequate pocket of fluid.  It would be rare these days to see an amniocentesis performed without ultrasound.  The fluid is aspirated for analysis.  There is analysis of the fluid itself as well as the cellular elements it contains. Complications of amniocentesis are seen in less than 1% of cases.  Complications include accidental puncturing of the fetus, umbilical cord, or placenta.  This could lead to intrauterine hemorrhage.  Infection also is a complication.  What are the specific tests that are performed on amniotic fluid today?

The most well-known is the L/S ratio to determine the presence of PG.  The following are other important tests:
Alpha-Fetoprotein (AFP) levels - AFP is the main serum protein in the developing fetus.  A significant break in the fetal skin, and especially an open spinal defect, which may occur in anencephaly or meningomyelocele (spina bifida), will cause AFP to leak from the exposed tissues into the amniotic fluid.  A high AFP level is a good indicator of a neural tube defect.  Usually acetylcholinesterase concentrations also are high in neural tube defects.  Generally it is at the 14th to the 16th week of gestation that the AFP levels will be high, and this will be the first indication of a seriously compromised fetus.
(AFP levels also can be used to identify stillbirth, low birth weight, and fetal chromosome disorders, but usually is not relied upon because of the availability of more definitive tests)
Bilirubin levels - used to determine hemolysis.  Rh incompatibility is a common hemolytic abnormality.  Bilirubin levels increase according to the degree of hemolysis.  A fetus who is destined to present with hydrops fetalis probably will have high bilirubin levels if a determination is made sometime in mid pregnancy. Bilirubin levels also are used to determine approximate gestational age.   Bilirubin levels normally taper off and may actually be absent by 36 weeks.
Creatinine levels - used to help determine fetal kidney maturity;
these levels increase as pregnancy progresses
Identification of Meconium Staining - amniotic fluid normally is clear.   Meconium staining is present if the fluid takes on a greenish appearance.  Fetal stress causes the fetus to pass meconium.  Presence of meconium suggests that there will be meconium aspiration (MAS) in the newborn.
Cytologic Examination of Cells - errors of metabolism can be identified by performing biochemical and enzymatic assays of whole cells found in the amniotic fluid.  These cells are from the skin, amnion, and tracheobronchial tree.  Also a variety of genetic and chromosomal disorders can be identified through examining these cells.  Down’s syndrome and other trisomy disorders are examples.

Postmaturity
An infant delivered after the 42nd week is said to be postmature.  Placental function tends to decrease after term, and fetal wasting may start.  These infants may be quite small for gesta- tional age.  The postmature newborn often presents with dry, cracked skin, excessive scalp hair, and loose skin because of lost subcutaneous fat.  Frequently postmature neonates have meconium staining of the skin, nails, and umbilical cord.
Postmature infants, because of the decline of placental function, are predisposed no intrauterine asphyxia and death.  The stress of labor is particularly poorly tolerated, and c-section often is performed.

Consequences of Increased Fetal Risk
Prematurity is the most common outcome in the high risk mother.
 Any delivery before 37 weeks is considered premature.  Since not all premature infants are low birth weight infants and not all low birth weight infants are premature, it is the gestational age that determines the degree of maturity.  Gestational age and neonatal mortality are inversely proportional.  The most difficult problem in prematurity is a decreased surface area for gas exchange in the lungs.  This is because lung development and appearance of surfactant occur in the final weeks of gestation.  Respiratory Distress Syndrome (RDS) or Hyaline Membrane Disease (HMD) is the most common disease associated with prematurity.  Additional problems with prematurity include the neonate’s inability to absorb nutrients from the digestive tract, poor defenses against infection, problems with heat regulation secondary to increased rate of heat loss, poor tissue perfusion secondary to immature capillary development, and increased incidence of hemorrhage, particularly into the ventricles of the brain (intraventricular hemorrhage, or IVH).

Intrauterine growth retardation (IUGR) is another common outcome of the high risk pregnancy.  This condition is also called small for gestational age (SGA) and does not imply prematurity.  If the growth retardation occurs early in the pregnancy when cells are forming (dividing), IUGR will manifest itself as hypoplasia with underweight organs.  This would be called hypoplastic IUGR.  If the IUGR occurs later in pregnancy, when the fetal cells are fully differentiated but are growing, there will be hypotrophy (underweight organs with normal number of cells).  The brain will not be acutely affected in late IUGR.
Hypotropic IUGR infants often appear to have oversized heads.  Actually the head is normal size; it is the undergrown body that is proportionally smaller than the head.  They have loose, dry skin, little subcutaneous fat, and sparse scalp hair.  They appear to be more active than one would expect for their birth weight.  Hypotropic IUGR is caused by disorders that impair placenta blood flow - conditions such as toxemia, maternal hypertension, and maternal renal disease.
Hypoplastic IUGR infants generally appear small, but uniformly so.  In fact, they are below the tenth percentile in head circum- ference, body weight and body length.  These infants were affect- ed early in fetal development perhaps by maternal malnutrition or intrauterine infection.  They are active infants, and the skin may be slightly thickened.  They are quite active.  They often have serious congenital malformations.

Both types of IUGR infants have numerous problems at birth.  They have been chronically hypoxic in utero, so they have a low tolerance for the stress of labor and can easily suffer asphyxia.  This birth asphyxia often leads to such things as meconium aspiration and cerebral edema.  Also, because of their size, they have low conservation of body heat.  They are term infants who have a higher mortality rate than normal weight term infants.  Still, they have lower mortality than low birth weight pre-term infants.  Mortality rates are affected by whether the IUGR is hypotrophic or hypoplastic, the degree of growth retardation, and the extent of congenital defects.



Asphyxia is the most problematic outcome of high risk pregnan- cies.  It is most often caused by impaired maternal blood flow to the placenta, and the result is both metabolic and respiratory acidosis and hypoxemia.  Brain injury can result, and cerebral edema, necrosis, intraventricular hemorrhage and subarachnoid hemorrhage can be the long-term problems.  Meconium aspiration is common with asphyxia, especially in term infants.

The High Risk Pregnancy
Studies of risk factors for high risk delivery of neonates have suggested that many of them are of limited use in predicting outcome.  However, there is agreement that the best way to avoid premature delivery or injury to the newborn is to monitor pregnancy through frequent cervical exams, periodic outpatient monitoring for contractions, assessing fetal heart activity, and identifying and helping to change behavior risks in the mother whenever possible.
Maternal Age and Parity
Any expectant mother who is less than 16 years of age is said to be at high risk for complications of pregnancy or childbirth.  The same is true for a  mother who is 35 or older and is in her first pregnancy.  A mother who has given birth to one or more healthy infants is not considered to be high risk until she reaches 40 years of age.  However, any mother, regardless of age, is said to be at high risk if she has delivered five times previously.
The term gravida is used to refer to pregnancy.  A first pregnancy is termed primigravida.  Multigravida is more than one pregnancy.  Para refers to completion of pregnancy resulting in a potentially viable infant.  A mother who delivers for the first time is a primipara or is primiparous.  A multiparous mother has delivered more than once.
History of Previous Birth
If a mother has had difficulty with previous pregnancies or labor, she will be considered high risk.  Among those factors which put a mother at particularly high risk are history of miscarriage, previous stillbirth or neonatal death, history of premature labor/delivery, previous cesarean delivery, infant of high birth weight, and infant who required intrauterine or neonatal exchange transfusion.

Toxemia (Pre-eclampsia) During Pregnancy and Uteroplacental
Insufficiency
Toxemia is a maternal disease of pregnancy characterized by hypertension, edema, and proteinuria.  The greatest problem in this order is hypertension, which invariable puts a strain on umbilical blood flow to the fetus.  When this happens, the result is uteroplacental insufficiency (UPI).  UPI, therefore, is common in pre-eclampsia.  Renal disease or diabetes may also cause hypertension; also essential hypertension may cause UPI.  (Anything responsible for hypertension causes UPI.
While we are talking about UPI, this condition is not only related to hypertension.  It also may occur in postmaturity, cyanotic maternal heart disease, and chronic hypoxia associated with maternal pulmonary disease.  Older primigravidas also are reported to have an increased incidence of UPI.  In any mother who has third trimester bleeding or oligohydramnios and especially in older primigravidas, UPI should be suspected.

What is Uteroplacental Insufficiency (UPI)?
To best understand, UPI, it is appropriate to take a look at placental gas exchange.  The placenta is a low resistance circulatory system six to eight inches in diameter and about one inch thick.  It weighs approximately one pound.  It serves to provide gas exchange as well as exchange of nutrients for waste products.  Maternal arterial blood enters the placenta through the uterine spiral arteries.  Blood flow then distributes itself throughout the intervillous spaces.  Within these spaces lie the chorionic villi which contain capillaries which ultimately go to the fetal circulation.  Gas exchange occurs between maternal blood and fetal blood around the chorionic villi.

Arterialized fetal blood leaves the placenta and flows to the fetus through the umbilical vein.  Two smaller umbilical arteries carry blood away from the fetus and back to the placenta.  The three blood vessels are surrounded by a gelatinous material called Wharton’s jelly, which literally prevents the cord from kinking.  It is important to be aware that the PO2 of blood in the umbilical vein is relatively low mainly because there is a 40-50 mm Hg “loss” in PO2 with virtually any membrane diffusion.  This is primarily because of diffusion limitation.  The other causes of the low PO2 and abnormally low PO2’s of fetal vein blood may be due to shunt within the maternal and fetal circulation, a high oxygen consumption within the placenta, an uneven distribution of maternal blood flow, and an uneven distribution of diffusing capacity to blood flow.  It should be noted, however, that oxygen tissue delivery is enhanced by the effect of fetal hemoglobin (HbF), which moves the oxyhemoglobin desaturation curve to the left and maintains a higher saturation of hemoglobin with oxygen for a given PO2.
UPI is associated with a decrease in intervillous blood flow secondary to with maternal vascular disease.  There is a limitation of gas and nutrient exchange across the placenta, which may limit growth to the fetus.  This is known as intrauterine growth retardation (IUGR).  While IUGR is the most common result of UPI, other problems include intrauterine fetal death, chronic intrauterine asphyxia, and meconium aspiration syndrome (MAS), which can result from neonatal asphyxia.

Maternal Diabetes Mellitus
Maternal diabetes mellitus (DM) is one of the most serious risk factors for a number of neonatal problems.  Infants of diabetic mothers (IDM) frequently are delivered prematurely.  Many others are postmature or are very large for their gestational age (macrosomic).  The macrosomic neonate quite often has suffered traumatic birth injury because of cervical disproportion.  IDM’s also can be affected by a wide range of congenital anomalies, the most common being congenital heart disease.  Some IDM’s are stillborn.
The diabetic also is predisposed to the development of toxemia, which may lead to UPI and IUGR.  But the classic IDM is a fat, plethoric infant.  The difference in how the fetus of the diabetic mother develops most likely has to do with the class or type of diabetes.  For example, Class A diabetes is a mild form which can be controlled by diet.  Class A IDM’s generally are very large but have no other problems.  Classes through F diabetics are insulin dependent.  Class B’s have had a recent onset of diabetes, have had a short duration of the disease, and have had no vascular involvement.  Class F’s had a juvenile onset, have had a long history of diabetes, and have vascular and kidney involvement.  Classes C through F usually have normal size or small for gestational age (SGA) infants.
The important factor to remember with regard to IDM’s is that DM influences the maturation of fetal lungs.  More serious diabetes actually accelerates fetal lung maturity while milder forms slow lung maturity.  This means that a neonate delivered by a mother with a mild form of diabetes may be very large but have premature lung development.  In fact, the infant may be premature but large with lungs even more premature than his gestational age would predict.  On the other hand, an IDM of a Class B through F mother could be SGA but have surprisingly mature lungs.
IDM’s are more likely to have infections, partly because of immature lungs and partly because diabetic mothers have a high incidence of urinary tract infections.  IDM’s also are more likely to have hypoglycemia, hypocalcemia, and hyperbilirubinemia.

Alcohol, Drugs and Tobacco
Teratogenesis is the development of abnormal structures in an embryo, resulting in a deformed, or dysmorphic fetus.  Alcohol, drugs, and tobacco are the most common teratogens taken by the mother.
Studies show that cigarette smoking of more than one pack a day is associated with an increased risk of low birth weight and associated problems, including intrauterine growth retardation.  Smoking also is responsible for decreasing nutrients delivered to the fetus as well as intermittent fetal hypoxia.  Acute alcohol consumption prior to delivery causes no fetal abnormalities other than tremors and seizures from withdrawal.  Chronic alcohol consumption in the pregnant mother creates a much more serious problem known as fetal alcohol syndrome.  This syndrome involves fetal wasting, low birth weight, failure to thrive, various developmental disorders, abnormal brain development, facial dysmorphia, and increased likelihood of more serious anomalies such as microcephaly and cardiac anomalies.
Drugs taken by the mother on a chronic basis result in prematurity, IUGR, SGA, and neonatal withdrawal.  Convulsions and death are sometimes seen.  The most common drugs affecting the fetus are cocaine and marijuana.  Withdrawal is not seen in marijuana use.

Maternal Infections
The most common infections which result in neonatal distress or poor fetal development include rubella, toxoplasmosis, herpes, cytomegalovirus (CMV), and syphilis.
Rubella is known to cause cardiac defects, cataracts, and deafness.  IUGR also is seen.  Infection with the virus early in the pregnancy is most likely to cause these problems.  Interestingly, many infants born to mothers infected with rubella show no signs of infection initially, but later may become septic or develop a pneumonia.
Toxoplasmosis causes serious inflammation of the eye in the neonate and can lead to blindness.  Splenomegaly, hepatomegaly, jaundice, anemia, convulsions, hydrocephalus, and pneumonia also are seen with this infection.  Impaired psychomotor development is another long-term result.  Toxoplasmosis is caused by a protozoa which can be acquired in the mother by eating contaminated raw or uncooked meat or from oral contact with contaminated cat feces or soil.  It is hard to diagnose in the mother because there are few symptoms.
Cytomegalovirus (CMV) also frequently goes undiagnosed in the mother, but it has a wide range of devastating effects in the neonate.  The most common of these is pneumonia, bleeding disorders, CNS disorders that may lead to apnea syndromes or seizure disorders, and IUGR.
Herpes occurs in two strains, types 1 and type 2.  Type 2 is sexually transmitted and infects the genitalia.  The infant acquires the infection by coming into contact with vaginal secretions after passing through the birth canal.  Also there is evidence that the virus can be passes to the fetus vertically after rupture of the membranes.  A cesarean section is recommended in the mother with a known genital infection to avoid fetal contact.  The newborn may develop either a disseminated infection or one that is localized.  The disseminated infection can affect virtually ever organ system and often is fatal.  The localized form may affect only the skin and the eyes.  But the CNS may be affected.
Maternal syphilis is easy to diagnose, but the newborn who is infected with the causative organism (Treponema pallidum) often is born to a mother who had no prenatal care.  Maternal syphilis can cause intrauterine death or premature birth.  Congenital syphilis in the newborn is associated with hepatitis, hyperbilirubinemia, hepatosplenomegaly, CNS abnormalities,skin lesions, bone disorders, and sometimes pneumonia.
Anatomic Abnormalities
Small pelvic opening, uterine malformations, and an incompetent cervix may increase fetal risk due to the problems they present.  Usually a c-section is indicated if the pelvic opening is small to avoid trauma to the infant’s head.  Uterine malformations and incompetent cervix may increase the risk of premature delivery.
 



Fetal Heart Rate (FHR) Monitoring
The fetal heart rate (FHR) correlates with fetal well-being.  Thus, FHR monitors are widely used.  Fetal heart rate can be heard with a stethoscope.  FHR monitoring can identify fetal distress that otherwise might be hard to detect.  Actually there are four well-known signs of fetal distress.  These are as follows:
1) Presence of meconium in the amniotic fluid
2) loss of beat-to-beat variability in the FHR
3) FHR >160 or <100
4) a drop in FHR between contractions (late decelerations)

There are three ways to monitor the fetal heart rate.  Doppler sensors can be placed on the mother’s abdomen.  These sense fetal heart movement.  A more sensitive method is to place EKG electrodes on the abdomen which pick up both the maternal and fetal heart rates.  Electronically, the fetal heart rate can be sorted out.  The most accurate way to monitor fetal heart rate is to place a small spiral electrode into the fetal scalp.  The amniotic membranes have to be manually ruptured for this, which presents a small risk for infection.  A new type of scalp pulse oximeter recently has been introduced also.
Monitoring uterine contractions also is important during labor, and there are two devices for this in common use today.  One is the tocodynamometer, which is strapped to the mother’s abdomen at the level of the uterine fundus.  A gauge is depressed according to the degree of uterine contraction, and the intensity, timing, and duration of contractions is plotted on graph paper.  This is not a very accurate monitor and is subject to artifact.
Another device for monitoring intrauterine contractions is the intrauterine pressure catheter.  This catheter is inserted into the uterus through the cervix following rupture of the amniotic membranes.  It measures actual pressures generated by uterine contractions and is very accurate.  Prolonged, difficult labors require this type of monitoring.
There are some basic fetal heart patterns that are found on the FHR monitor.  These are correlated with intrauterine contractions to help identify possible problems during labor.
Baseline heart rate is determined by watching the heart rate for at least 10 minutes.  The normal heart rate is 120-160.  Low gestational age fetuses will generate a heart rate on the high end, but term fetuses can be at either the high or low end.  An increase or decrease of 20 - 30 bpm, even if still within the normal rate, is problematic and may suggest distress.
Variability is an important characteristic of the fetal heartbeat.  A healthy, awake fetus has a constantly changing heart rate, usually between 5 - 10 bpm.  This variability is lost in the CNS depressed fetus, whether it is due to hypoxia, immaturity, sleep, or the effects of narcotics or sedatives.  Bradycardia is a FHR <120 or 20 bpm less than baseline.  THE MOST DANGEROUS CAUSE OF FETAL BRADYCARDIA IS ASPHYXIA.  Usually the first action taken when fetal bradycardia is recognized is to give the mother supplemental oxygen.  Other causes of fetal bradycardia are congenital heart block (which usually accompanies other congenital cardiac malformations), maternal lupus erythematosus, administration of paracervical blocks and beta blockers (mothers sometimes are placed on propranolol, for example), and fetal hypothermia.
So, when bradycardia appears, it is important first to rule out asphyxia as the cause.  A scalp blood pH is used for this.
Bradycardia that is seen in the second stage of labor is divided into end-stage and terminal bradycardia.  End-stage bradycardia, while worrisome, is accompanied by standard variability and a prior normal FHR tracing.  Normal vaginal delivery is usually permitted.  However, terminal bradycardia indicates serious fetal distress.  It is recognized by the absence of variability.  Delivery is performed in the fastest possible manner.  Often a c-section is performed.
Tachycardia is present when the baseline FHR is above 160.  The most common cause is maternal fever.  Other causes include maternal or fetal infection, fetal dysrhythmia, maternal dehydration, maternal anxiety, stimulation of the fetus, and asphyxia.  Sympathomimetic drugs administered to the mother to stop contractions also can cause tachycardia.  Terbutaline is the most commonly used drug these days, but others include ritodrine and salbutamol.  Obviously, those drugs administered to the mother which have the effect of increasing the heart rate in the mother will have the same effect on the fetus.  For example, some mothers receive atropine.
An acceleration is said to occur when FHR exceeds 160 for less than 2 minutes.  Accelerations during labor are good signs and indicate good response to intrauterine contractions.
A deceleration is said to occur when FHR drops below 120 for less than 2 minutes.  Decelerations can be harmless or threatening depending on their characteristics and timing.  There are three types:
Early or Type I decelerations - closely follow uterine contractions.  It is possible for the FHR to drop to 60 to 80 during the contraction and rapidly return to baseline once the contraction ends.  This type of deceleration is caused by compression of the fetal head against the cervix.  Hypoxia is not present here; this is a parasympathetic response.  Late or Type II decelerations do not follow uterine contractions.  They usually start 10-30 seconds before the contraction starts and they continue until the contraction is over.  Even a small decrease of 10-20 from baseline FHR is problematic.  This type of deceleration occurs when there is uretoplacental insufficiency during contractions leading to fetal asphyxia.  The vessels of the placenta and uterus are compressed during contractions, which decreases maternal to fetus blood transfer.  More frequent and intense contractions cause the hypoxia to worsen, so the decelerations begin to last longer and beat-to-beat variability is lost.  The heart rate dips lower and lower with each contraction and worsening hypoxia.
Variable or Type III decelerations are independent of uterine contractions and occur randomly without any pattern to duration or severity.  This type of deceleration occurs as a result of compression of the umbilical cord and the resulting hypoxia.  The cord could be around the fetus’ neck or pinched between the fetus and the mother’s pelvis.  It is not a dangerous type of deceleration unless it occurs frequently or becomes severe.  To relieve the umbilical compression, the mother may be turned from side-to-side or placed in a knee to chest position.  Manipulating the position of the fetus may also be tried.

Fetal Scalp pH
Fetal scalp pH is measured to assess fetal well-being in situations where there is absence of baseline variability, late decelerations with decreasing variability, or abnormal FHR/intrauterine contraction tracings.
A significant decrease in maternal to fetus transfer of blood via the placenta will produce a markedly low fetal pH.  There are two potential reasons for this.  First is the rise in PCO2 simply because there would be impairment of CO2 removal at the placenta.  Second, with severe hypoxia, the fetal tissues begin to metabolize glycogen (anaerobic metabolism) and produce lactic acid.
Fetal blood pH is normally above 7.25.  A pH of 7.2 to 7.24 indicates slight asphyxia.  A pH less than 7.2 is severe asphyxia.  Sometimes the maternal pH is determined also, since maternal pH can affect fetal pH.
In the future there may be non-invasive scalp pH transcutaneous monitors for the fetus similar to those already available which will provide scalp SpO2.

Estimating the Delivery Date
The delivery date is called the estimated day of confinement (EDC).  It can be estimated according to the following methods:
Nagele’s Rule - most common method.  EDC is calculated by subtracting 3 months from the date of the last menstrual period and adding 7 days.
Fundal Height - the fundus of the uterus is the end opposite the cervix. It can be measured on the abdominal wall as it grows with the fetus.  This method is reliable over the first two trimesters but unreliable in the third trimester.  The distance from the symphysis pubis to the top of the fundus is measured.  Each centimeter represents one week of growth.
Quickening - the first sensation of fetal movement.  Usually this occurs during week 20.  A rough estimate of EDC can be made by this method.
Determination of Fetal Heartbeat - can be heard by doppler at week 8.  A rough estimate of EDC can be made by this method.
Ultrasonography  - can be used to estimate EDC in four ways: 1) measurement of gestational sac dimensions which is accurate at week 8; 2) measurement of the crown-rump length of the fetus is accurate between weeks 7 and 14; 3) measurement of femur length is accurate after week 12; measurement of biparietal diameter (BPD) (the fetal skull) , which should be 8.7 cm at 36 WGA.

Biophysical Tests of Fetal Well-Being
Stress Tests
There are two main types of stress tests used to assess FHR during intrauterine contractions.  The first of these is the Contraction Stress Test CST), which is simply evaluation of the FHR during spontaneous contractions.  Repetitious late decelerations during contraction indicate a positive CST, which is a good predictor of fetal asphyxia.
With this stress test, the mother may manually stimulate her nipples if there are few spontaneous contractions.  If there are still insufficient contractions, the oxytocin contraction test (OST) may be tried, which involves using a small I.V. dose of the drug oxytocin to stimulate contractions.
The nonstress test (NST) is an evaluation of fetal heart rate during fetal movements.  Normally the FHR increases with fetal movements.  A nonreactive or negative stress test occurs when the FHR does not accelerate or accelerates only slightly.  This is a frequently performed test because it takes little time and is easy to perform.
A negative (nonreactive) NST usually is followed by a CST to try to identify the cause of inactivity.  A fetus being affected by hypoxia will have a negative NST and a positive CST.  If the NST is negative and the CST is negative, the problem is most likely fetal sleep or maternal narcotic or sedative ingestion.

Acoustic Stimulation
Acoustic stimulation involves setting off a loud buzzer or other noisemaker against the mother’s abdomen and monitoring the FHR for accelerations.  Normally there will be accelerations, and if there are none, further evaluation is indicated.

Monitoring Fetal Movement
Monitoring fetal movement is one of the easiest means of fetal assessment.  It involves having the mother keep a record of the number of fetal movements that she detects within a certain period, usually one hour.  Jerky movements of the fetus have been detected as early as 7 weeks and reaches its greatest activity between weeks 28 and 34.  Movements decrease in the last few weeks simply because of a greater fetal size and less amniotic fluid volume.  A healthy fetus is active, and if there are few or no periods of inactivity, further examination is indicated.
The Biophysical Profile
The biophysical profile is considered an important and useful overall fetal evaluation test.  Its importance rivals the Apgar score.  The profile uses five tests : the NST, fetal movement, fetal breathing movements, fetal limb tone, and amniotic fluid volume.  Ultrasound is used to evaluate the latter four areas.  Each area is scored, and any action on the part of the physician is decided by the total score.
Meconium Presence in Amniotic Fluid
Meconium is the thick, dark greenish stool found in the fetal intestine.  There is about 200-600 gm in the term infant intestine.  Meconium passes into the amniotic fluid in about 40% of postterm infants older than 42 WGA.  10% of term infants pass meconium in utero as do 3-5% of premature infants.
Amniocentesis or amnioscopy reveals the presence of meconium, which is believed to be released when fetal asphyxia causes relaxation of the anal sphincter.  Also there may be increased peristalsis in the intestine.
Chorionic Villus Sampling
Chorionic villus sampling is a new procedure that has not caught on well in the U.S.  This procedure involves sampling tissue from the fetal chorion by suctioning through a catheter inserted into the dilated cervix and guided by ultrasound to the placenta.  This procedure is performed at 9 to 12 weeks from the last menstrual period.
 

Since the cardiorespiratory status of the newborn will be our focus, we will frequently discuss what can go wrong.  Understand, however, that complicated pregnancies and births are really rare and that it is far more typical to see a normal progression of development and birth events.

High Risk Pregnancy Factors

Socioeconomic Factors
1. Low income and poor housing
2. Severe social problems
3. Unwed status, especially adolescent
4. Minority status
5. Poor nutritional status

Demographic Factors
1. Maternal age under 16 and over 35 years
2. Obese or underweight prior to pregnancy
3. Height less than 5 feet
4. Familial history of inherited disorders

Medical Factors
1. Obstetric History
a. History of infertility
b. History of ectopic pregnancy
c. History of miscarriage
d. Previous multiple gestations
e. Previous stillbirth or neonatal death
f. Uterine/cervical abnormality
g. High parity (many children)
h. History of premature labor/delivery
i. History of prolonged labor
j. Previous cesarean delivery
k. History of low birth weight infant
l. Previous delivery with forceps
m. History of infant with malformation, birth injury, or neurologic deficit
n. History of hydatiform mole or carcinoma

2. Maternal Medical History

a. Maternal cardiac disease
b. Maternal pulmonary disease
c. Maternal diabetes or thyroid disease
d. History of chronic renal disease
e. Maternal gastrointestinal disease
f. Maternal endocrine disorders
g. History of hypertension
h. History of seizure disorder
i. History of venereal and other infectious diseases
j. Weight loss greater than 5 pounds
k. Surgery during pregnancy
l. Major anomalies of the reproductive tract
m. History of mental retardation and emotional disorders

3. Current Obstetric Status

a. Absence of prenatal care
b. Rh sensitization
c. Excessively large or small fetus
d. Premature labor
e. Preeclampsia
f. Multiple gestations
g. Poly- and oligohydramnios
h. Premature rupture of the membranes
i. Vaginal bleeding
j. Placenta previa
k. Abruptio placentae
l. Abnormal presentation
m. Postmaturity
n. Abnormalities in prenatal tests (stress, nonstress)
o. Maternal anemia

4. Habits

a. Smoking
b. Regular alcohol intake
c. Drug use and abuse
 
 
 

Review Suggestions and Questions at Mid-Term
Review the terms primipara, multipara, primigravida, multigravida.
What mothers are high risk?
What happens in preeclampsia?  What are the problems both to the mother and to the fetus?
Review the anatomy of the umbilical cord.
What is different about fetal hemoglobin in terms of its function?  How does it benefit the fetus/newborn?
What are the potential outcomes when there is uteroplacental insufficiency?
Transplacental pneumonia and the other pneumonias encountered in the neonate:
what are the common organisms?
Can you define/explain the term teratogenesis?
Of all the bacteria and viruses we talked about, which one of them is most likely to cause a pneumonia shortly after birth.  Some of them are responsible for other infections and sequelae, but one of them seems to be the cause of pneumonia more than the others.
What are some possible abnormalities encountered in multiple gestational births?
Basically what happens in twin transfusion syndrome?
Describe what occurs in placenta previa (the different types).
What is the problem in PROM?  How can it be harmful to the fetus/newborn?
Can you differentiate between hypoplastic and hypotrophic IUGR?
What can go wrong in the high risk pregnancy?  What are the potential outcomes?
What are some ways of determining the extent of pulmonary maturity of the newborn?  If a quick way were needed in the delivery room, what could be done?
What does a biophysical profile tell you?  What is a non-stress test?
What is surfactant composed of?  What is the major major component? When dophosphalipids first begin to appear in fetal lungs?  Certain factors and “stresses” accelerate lung maturation.  Can you name a few of them?
What is apposition?
Of course you know what the major function of surfactant is...but do you know some of the lesser known but important functions.  Review these!  Review very briefly the development of the heart.  The basic picture of RDS...what is the pathophysiology?  What is seen on x-ray?
What is the progression of the disease?
What is tocolysis?  Can you explain how it is accomplished?
What is dystocia?
Do you recall the types of normal and abnormal presentation?
The types of decelleration: are any of them life-threatening?
Details of the fetal circulation: know where the fetal shunts are...
Normal values for FRC, Vt, other data...
How does the V/Q ratio differ in the neonate?
How does postmaturity affect the neonate?
Do you know all of the causes of TTN?
What is the treatment for TTN?
What are the problems in meconium aspiration?  What complicates the picture...why does the patient sometimes require NO and ECMO?
 

DELIVERY NOTES
Over the second half of the third trimester, the mother and fetus take on some changes that get them ready for the birth process.  Sometimes the mother goes into a false labor with mild contractions.  These contractions are referred to as Braxton-Hicks contractions and are milder than real contractions.  They are rhythmic, however, which makes them seem like real contractions.
Delivery is a continuous process which consists of four stages.  The first stage, (Stage I) begins with the onset of the first contraction.  Contraction come in waves, and in the beginning are 10 minutes apart and last 30-90 seconds.  They generally start as short contractions and get progressively longer with time.
The cervix begins to stretch and widen when contractions begin.  When the cervix stretches, it also thins.  This is called effacement and is expressed as a percentage.  At 100% effacement, the cervix is completely against the uterine wall.  The widening of the cervix is called dilatation, and the degree of dilatation is expressed in centimeters.  The cervix is said to be fully dilated at 10 cm.  Effacement and dilatation occur because uterine contractions push the amniotic fluid and the fetus against the cervix.  The cervix primarily effaces during the early part of stage I.  Dilatation is very slight over the first part of stage I and then progresses rapidly over the latter part of stage I.  Effacement is almost 100% when rapid dilatation begins.  Stage I lasts until the cervix is fully effaced and dilated.  Average time for this stage is 7 to 12 hours in the multigravida and 16 to 18 hours in the primigravida.  Understand, however, that in complex or premature labors or in high risk pregnancies, these average times would be an exception.
Stage II of labor is the actual delivery of the fetus.  Movement of the fetus through the birth canal is aided by the contraction of the abdominal muscles and diaphragm by the mother.  This increases abdominal pressure so that with uterine contractions, the fetus is pushed out.
95% of all births occur with the fetus in the head down position.  This is called the vertex position.  However, there are a number of variations of the vertex position, depending on the way the fetus is facing.
The term engagement is used to describe the presence of the fetus in the birth canal.  When the top of the fetal head reaches the level of the ischial spines, the head is engaged in the birth canal.
The birth canal is divided into stations.  Each station represents 1 centimeter above or below the level of the ischial spines.  Stations above the ischial spines are numbered consecutively from-1 to -5.  Below the level of the ischial spines they are numbered 1 to 5.  The level at the ischial spines is a station of 0.  When the head of the fetus is engaged, it is at a station of 0.
Once the fetus is going down the birth canal, he turns his head face down so that there is easier passage through the pelvis.  Once the head is through, the body rotates internally so that the shoulders will pass easily.  The upper shoulder emerges first and then the lower shoulder.  This part of the delivery has been the most time-consuming.  Once the shoulder is present, the remainder of the body emerges quickly.  The umbilical cord is then clamped.
Although it seems unbelievable, Stage II can last two hours without any major danger to the fetus.  It usually lasts 20 to 45 minutes.
Stage III of labor is expulsion of the placenta.  This takes 5 to 45 minutes.  Contractions continue until the placenta tears away from the uterine wall and is expelled.  If the neonate is placed at the mother’s breast, he can stimulate secretion of oxytocin to increase these contractions.  Manual pressure to the abdominal wall also helps.
After the placenta passes, the uterus starts to shrink and eventually returns to its original size.  The immediate period after delivery of the placenta is called stage IV.  It is during this stage also that homeostasis is reestablished in the mother.

Abnormal Labor and Delivery
Premature labor is one of the most difficult of perinatal problems.  One strategy that is used to deal with a premature birth is to try to stop premature labor.  The process for doing so is called tocolysis.  Many premature labors are stopped or slowed by using drugs.  This is called pharmacologic tocolysis and is usually accomplished by using sympathomimetic (adrenergic) drugs, which relax smooth muscle.  The only drug that is FDA approved is ritrodine, but terbutaline is being used extensively.  Albuterol also is being used.
If the mother has an underlying cardiomyopathy or an infection, ritrodine can cause pulmonary edema.
There are side effects to using beta adrenergic drugs to both the mother and the fetus.  Both the mother and fetus can become tachycardic and hyperglycemic.  In fact, the neonate may overproduce insulin in response to his initial hyperglycemia, which will cause him to have a rebound hyperglycemia.  Maternal hypokalemia is another side effect as well as nausea and vomiting.
Another drug in widespread use for stopping uterine contractions is magnesium sulfate, which is an anticonvulsant drug.  It works by decreasing muscle contractility, and its side effects include decreased muscle tone, drowsiness and decreased serum calcium levels in the neonate.
Indomethacin (Indocin) is a drug that inhibits prostaglandin synthetase.  Since prostaglandins induce labor, Indocin seems to be a useful drug for tocolysis.  However, this drug also causes closure of the ductus arteriosus of the fetus in utero, which can be a devastating problem.
Nifedipine, a calcium channel blocker, has been used with some success for tocolysis with few side effects.
There is no form of tocolysis other than pharmacologic.  Counseling and educating the high risk mother where applicable is the only alternative.
In order for tocolysis to be tried the mother/fetus must meet 6 criteria:
1) true labor must be present
2) the cervix must not be dilated more than 4 cm and effaced more than 50%
3) the fetus must be 20 - 36 WGA
4) there must be no signs of fetal distress or disease
5) there must be no medical or obstetric disorder that would contraindicate the continuation of labor
6) the mother must give informed consent

Dystocia is a prolonged labor because of uterine, pelvic, or fetal problems.  It is present when stage I and II exceed 20 hours.  It also is present when stage II exceeds 2 hours in primigravidas and 1 hour in multigravidas.
There are three major dangers to a prolonged labor.  First, there is increased chance that the placenta will separate from the fetus.  This would cause serious asphyxia.  Second, there is more of a chance that the umbilical cord will be compressed.  Third, premature rupture of the amniotic sac is more likely.  The danger of fetal infection rises significantly with rupture of the amniotic membranes, especially if delivery has not occurred within 24 hours.
A common cause of dystocia is dysfunction of the uterus.  There are cases where the uterus contracts excessively strong (hypertonic) or, more frequently, too mildly (hypotonic).  When there are hypertonic contractions, the cervix may not dilate and efface properly.  As a result, the placenta and/or the umbilical cord maybe compressed, causing asphyxia.  Hypotonic contractions may occur because of anesthetic overdose or failure of the fetus to descend normally.  Contractions are not strong enough to dilate and efface the cervix and expel the fetus.

Cephalopelvic disproportion (CPD) is another common cause of dystocia.  The disproportion can be either a fetal head too large or a maternal pelvic opening too small.  In either of these cases the fetus is unable to enter and pass through the birth canal and labor is prolonged.  One well-known situation is in the accelerated growth of the fetus which occurs in diabetic mothers.  Sometimes the fetus reaches 5-6 kg.  Another situation is hydrocephaly.  The pelvic opening can be small as a result of contracture, which may be a congenital problem in the mother or be due to poor nutrition or pelvic fractures or disorders.  Small pelvic openings also are seen in Asian populations and in many women less than 20 years old.

Abnormal presentation is any position of the fetus before birth other than vertex.  The breech position is the most common abnormal presentation and comprises 3.5% of all births.  There are three types of breech presentations: the complete breech, where the feet, legs, and buttocks all present together; the frank breech, where the legs are flexed against the body and the feet are near the face so that the buttocks are presenting; and the footling, or incomplete breech, where one or both feet descend into the birth canal first.
The problem with breech presentations is greatest when there is diminished pelvic size or enlarged fetal head.  In these cases, the fetal body can be easily delivered but the disproportional head will not engage the birth canal.  By this time it is too late to perform a C-section, so the head must be passed by means of manipulation.  Spinal cord damage and hemorrhage in the brain can occur from pulling on the fetal body.

Placenta previa is reported to be a common cause of breech presentation.
Other abnormal presentations are the face, brow, and transverse lie (shoulder).
It is important to note here that the fetal skull is not solid like in the adult.  It is made up of several bony plates separated by what are known as sutures.  In the birth canal, these sutures overlap, making the diameter of the skull smaller.  In the face or brow presentations, the head enters the birth canal in such a way that the sutures cannot override.  If the fetal head/ maternal pelvic opening proportion is tight, the head will have trouble passing through the birth canal.  The neonate will be likely to suffer from facial trauma and edema, but also may have experienced asphyxia from the prolonged labor and time in the birth canal.
Delivery of a fetus in the transverse lie position is very difficult.  The only possibility for a vaginal delivery lies in manipulating and repositioning.  Usually a c-section is performed.
The umbilical cord consists of an umbilical vein and two umbilical arteries.  These vessels are surrounded and protected by Wharton’s jelly. The thickness of this jelly material keeps the cord from bending and cutting off circulation.  But it does not prevent the cord from being compressed between body parts.  This is a common cause of asphyxia in the fetus.
Sometimes the umbilical cord passes through the birth canal before the fetus.  This is called prolapse of the umbilical cord.  This problem is common in breech presentations (especially footling breech) and the transverse lie presentation.  It also is seen in multiple gestations (twins).  In prolapse the fetus can easily compress the cord when passing through the birth canal.  Or, there can be compression of the cord within the uterus, which is called occult prolapse.
There are a few placental abnormalities which make labor and delivery difficult.  One of the most common is placenta previa.  In most pregnancies, the blastocyst attaches itself somewhere in the upper portion of the uterus.  Placenta previa occurs when implantation occurs in the lower portion of the uterus.  There are three varieties.  A low implantation is a for m of placenta previa which occupies the lower portion of the uterus but does not cover the cervical opening.  A partial placenta previa is so low in the uterus that it covers part of the cervical opening.  Total placenta previa is a situation in which the placenta covers all of the cervix.
Placenta previa can be diagnosed by ultrasound, and in most cases a c-section is planned.  Vaginal delivery is possible, but manipulating fetus and placenta through the birth canal is very difficult.
A more serious problem with the placenta is abruptio placentae, which is the premature separation of a normally attached placenta.  (This condition also is called abruption)  Often this separation causes labor to begin, so premature labor and delivery is the result.  This is a life-threatening event for the mother, and maternal mortality is 2 - 10%.  Fetal mortality is close to 50%.
Maternal hypertension of any origin is the most common cause of abruptio placentae.  One form of hypertension in the mother is the condition known as preeclampsia, in which proteinuria, edema, and hypertension occur after 20 WGA.
There are mothers with a history of abruption, which makes them at greater risk for the disorder.  Other mothers who are at risk are those who have had a high number of previous pregnancies.  trauma, short umbilical cord, uterine abnormalities, and compression of the inferior vena cava.
Separation of the placenta can be either partial or complete.  Bleeding is an immediate complication.  Bleeding from the vagina
 is called apparent hemorrhage.  If no bleeding is evident, there is said to be concealed hemorrhage.  There are four classifications or grades in describing the severity of the disorder.  The mildest, grade 0, is not identified until after delivery when a small clot is discovered behind the placenta.  Grade 1 involves some vaginal bleeding with some tetany and tenderness of the uterus.  Grade 2 is similar to grade 1, except that there may or may not be vaginal bleeding and there is fetal distress.  Grade 3 is the most serious because maternal shock and persistent abdominal pain are present.  Again, there may or may not be vaginal bleeding.  Fetal demise is present, and the uterine tetany is so severe that it takes on a very stiff, firm consistency.  In about 30% of grade 3’s, there are signs of coagulapathy in the mother.
So, in abruptio placentae the mother may show vaginal bleeding, tetany and tenderness of the uterus and hypovolemic shock.  The fetus loses placental surface area which can result in severe hypoxia and asphyxia along with blood loss and hypovolemic shock.
Treatment of abruptio placentae involves intensive management of maternal blood/fluid volume with packed red blood cells, whole blood, or crystalloid administration.  The hematocrit is maintained at 30%.  The mother often must lie in a lateral position to enhance fetal circulation.  Intensive monitoring of both the mother and the fetus are important as well as capability for emergency delivery or c-section in the event of maternal shock or fetal distress.
Premature Rupture of Membranes (PROM)
The likelihood of fetal infection (most commonly pneumonia) is increased with PROM.  Premature rupture is said to occur when the rupture occurred more than 24 hours before delivery.  If there is PROM with prolonged labor, this increases the risk of infection.  PROM occurs more often with premature labor, and sometimes a prolonged labor is tolerated while steroids are administered to increase fetal lung maturity.

Cesarean section (c-section) is a delivery via a surgical incision through the abdomen and uterus.  They are performed under anesthesia and there are 7 indications.  These are the following:
1) large fetus in relation to maternal pelvis
2) severe maternal preeclampsia
3) hemorrhage
4) partial or total placenta previa
5) failure of the cervix to dilate
6) fetal depression from maternal anesthesia
7) fetal distress

Complications of cesarean section include traumatic injury to the fetus, placenta or umbilical cord which can lead to hemorrhage and anemia.  Another complication is transient tachypnea of the newborn (TTN), which arise from the retention of lung fluid because the fetus was not squeezed in the birth canal.
Multiple gestation is the presence of twins, triplets or more fetuses during the same pregnancy.  the incidence of fatality is greater in multiple gestations because there is a higher incidence of premature labor.  There is also increased incidence of congenital abnormalities, growth retardation, bacterial infection, and hypoglycemia.
Multiple gestations are more common in the black population and very uncommon in Asian populations.  Familial inheritance is a factor in fraternal twins.  Older mothers, ages 35 to 39, also tend to have multiple gestations.  Mothers who receive the fertility drug clomiphene citrate (Clomid), which is used to induce ovulation, and gonadotropins also have multiple gestations.  There is some evidence that multiple gestations appear in mothers who discontinue the use of oral contraceptives.
The most common form of multiple gestations is twinning.  This occurs in about 1 out of 99 pregnancies.  Two thirds of all twins are fraternal, which means that they are dizygotic and arise from the fertilization of two separate ova.
Fraternal twinning is an autosomal recessive trait that is carried by daughters of mothers of fraternal twins.  The other one third of twins are identical and are of the same sex.  They arise from the fertilization of one ovum.  They are identical in appearance.  Identical twinning occurs at random, and there is greater mortality in this twin group.  Studies have shown that the second twin is usually more compromised than the first and female twins are more healthy than male twins.
Congenital abnormalities, bacterial infection, and hypoglycemia are more common in multiple gestational births.  Prematurity is highly associated with multiple gestation pregnancies, especially identical twins. Problems with the umbilical cord, the placenta, and IUGR also occur with multiple gestation as well as abnormal presentation (such as breech).  In many of these pregnancies, the placenta is smaller in one twin which makes him develop smaller.  Twins in this situation are called discordant twins.
The twin transfusion syndrome, or the intrauterine parabiotic syndrome, is a situation in which the circulatory systems of the two twins are connected.  Transfer of blood from one twin to the other occurs, and one becomes polycythemic and the other becomes anemic.  The polycythemic twin will be likely to develop conges- tive heart failure.  Because of the increased number of red blood cells, hemolysis may occur, which will increase bilirubin.  The other twin will be more likely to be in shock.
 

The Birth Process
Lung Inflation at Birth
It is thought that the respiratory movements of the fetus in utero prepare it for extrauterine breathing.  Breathing movements are noted to increase in activity over the last ten weeks of gestation.  When the neonate is delivered, there must be stimuli present for it to take its first breath and to begin rhythmic breathing.  There are three factors believed to be responsible for initially stimulating breathing.
1. Asphyxia  (increased PaCO2, decreased PaO2 and pH stimulate chemoreceptors found in the aortic arch and carotid bodies)
2. Recoil of the thorax  (as the thorax passes through the birth canal, it is compressed; as the fetus exits the birth canal, the natural recoil of the thorax creates a negative pressure in the thoracic cavity, which pulls air into the lungs)
3. Environmental changes stimulate crying (changes from dark to light, warm to cold, silence to noise; tactile stimuli)

To establish the functional residual capacity (FRC) of the lung, there has to be an extreme negative pressure generated by the first breath.  This negative pressure has been found to be as high as -100 cm H2O, which is necessary to overcome surface forces.  Surfactant in the term infant aids in this process, and if surfactant levels are low, there is a great tendency for the lung to collapse despite high negative inspiratory pressures.  The FRC continues to increase in size over the first few hours of life as more fluid is cleared from the lungs, collapsed alveoli are expanded, and as more air remains.

Change from Fetal to Adult Circulation
In addition to having to initiate breathing rather quickly, the neonate must make a transition from the fetal to an adult circulation.
At birth, the umbilical cord is clamped.  This causes some major changes in the fetal circulation.  Before clamping, the umbilicus and placenta provided a low resistance to blood flow.  When the umbilical cord is clamped, blood that normally would have gone to the placenta is forced to perfuse the lower extremities.  This causes the systemic arterial pressure to increase back to the left ventricle and left atrium.
At the same time, the neonate starts breathing, which greatly reduces the pulmonary artery pressure.  This pressure is reduced because the establishment of an FRC decreases the pressure around the pulmonary vasculature from fluid.  But more importantly, this pressure is reduced because arterial PO2 increases which relaxes smooth muscle within the pulmonary circulation.  So with a decrease in pulmonary artery pressure, there is a decrease in right ventricular and right atrial pressures.
One important result of the changes in systemic and pulmonary vascular pressure is the closing of fetal shunts.  Obviously with the pressure in the left atrium higher than in the left, the “mechanical” tissue flap on the foramen ovale closes.  Blood in the right atrium now flows to the right ventricle.
The ductus arteriosus also closes.  Actually, over the last few weeks of gestation, smooth muscle around the ductus starts to develop.  This smooth muscle remains relaxed so that the ductus will stay open before birth.  The mechanism that keeps the ductus open is the presence of prostaglandins.  The production of these prostaglandins are stimulated by a low PO2, so when the PO2 rises at birth, prostaglandin levels decrease quickly and allow the ductus smooth muscle to constrict.  The ductus arteriosus conn ects the aorta with the pulmonary artery.  If the ductus did not close, there would be right-to-left shunting, left-to-right shunting, and congestive failure.
The clamped umbilical arteries eventually become ligaments as does the ductus venosus.
 

Postmaturity
An infant delivered after the 42nd week is said to be postmature.  Placental function tends to decrease after term, and fetal wasting may start.  These infants may be quite small for gesta- tional age.  The postmature newborn often presents with dry, cracked skin, excessive scalp hair, and loose skin because of lost subcutaneous fat.  Frequently postmature neonates have meconium staining of the skin, nails, and umbilical cord.
Postmature infants, because of the decline of placental function, are predisposed no intrauterine asphyxia and death.  The stress of labor is particularly poorly tolerated, and c-section often is performed.
Consequences of Increased Fetal Risk
Prematurity is the most common outcome in the high risk mother.  Any delivery before 37 weeks is considered premature.  Since not all premature infants are low birth weight infants and not all low birth weight infants are premature, it is the gestational age that determines the degree of maturity.  Gestational age and neonatal mortality are inversely proportional.  The most difficult problem in prematurity is a decreased surface area for gas exchange in the lungs.  This is because lung development and appearance of surfactant occur in the final weeks of gestation.  Respiratory Distress Syndrome (RDS) or Hyaline Membrane Disease (HMD) is the most common disease associated with prematurity.  Additional problems with prematurity include the neonate’s inability to absorb nutrients from the digestive tract, poor defenses against infection, problems with heat regulation secondary to increased rate of heat loss, poor tissue perfusion secondary to immature capillary development, and increased incidence of hemorrhage, particularly into the ventricles of the brain (intraventricular hemorrhage, or IVH).
Intrauterine growth retardation (IUGR) is another common outcome of the high risk pregnancy.  This condition is also called small for gestational age (SGA) and does not imply prematurity.  If the growth retardation occurs early in the pregnancy when cells are forming (dividing), IUGR will manifest itself as hypoplasia with underweight organs.  This would be called hypoplastic IUGR.  If the IUGR occurs later in pregnancy, when the fetal cells are fully differentiated but are growing, there will be hypotrophy (underweight organs with normal number of cells).  The brain will not be acutely affected in late IUGR.
Hypotropic IUGR infants often appear to have oversized heads.  Actually the head is normal size; it is the undergrown body that is proportionally smaller than the head.  They have loose, dry skin, little subcutaneous fat, and sparse scalp hair.  They appear to be more active than one would expect for their birth weight.  Hypotropic IUGR is caused by disorders that impair placenta blood flow - conditions such as toxemia, maternal hypertension, and maternal renal disease.
Hypoplastic IUGR infants generally appear small, but uniformly so.  In fact, they are below the tenth percentile in head circum- ference, body weight and body length.  These infants were affect- ed early in fetal development perhaps by maternal malnutrition or intrauterine infection.  They are active infants, and the skin may be slightly thickened.  They are quite active.  They often have serious congenital malformations.
Both types of IUGR infants have numerous problems at birth.  They have been chronically hypoxic in utero, so they have a low tolerance for the stress of labor and can easily suffer asphyxia.  This birth asphyxia often leads to such things as meconium aspiration and cerebral edema.  Also, because of their size, they have low conservation of body heat.  They are term infants who have a higher mortality rate than normal weight term infants.  Still, they have lower mortality than low birth weight pre-term infants.  Mortality rates are affected by whether the IUGR is hypotrophic or hypoplastic, the degree of growth retardation, and the extent of congenital defects.
Asphyxia is the most problematic outcome of high risk pregnan- cies.  It is most often caused by impaired maternal blood flow to the placenta, and the result is both metabolic and respiratory acidosis and hypoxemia.  Brain injury can result, and cerebral edema, necrosis, intraventricular hemorrhage and subarachnoid hemorrhage can be the long-term problems.  Meconium aspiration is common with asphyxia, especially in term infants.

The High Risk Pregnancy
Studies of risk factors for high risk delivery of neonates have suggested that many of them are of limited use in predicting outcome.  However, there is agreement that the best way to avoid premature delivery or injury to the newborn is to monitor pregnancy through frequent cervical exams, periodic outpatient monitoring for contractions, assessing fetal heart activity, and identifying and helping to change behavior risks in the mother whenever possible.
Maternal Age and Parity
Any expectant mother who is less than 16 years of age is said to be at high risk for complications of pregnancy or childbirth.  The same is true for a  mother who is 35 or older and is in her first pregnancy.  A mother who has given birth to one or more healthy infants is not considered to be high risk until she reaches 40 years of age.  However, any mother, regardless of age, is said to be at high risk if she has delivered five times previously.
The term gravida is used to refer to pregnancy.  A first pregnancy is termed primigravida.  Multigravida is more than one pregnancy.  Para refers to completion of pregnancy resulting in a potentially viable infant.  A mother who delivers for the first time is a primipara or is primiparous.  A multiparous mother has delivered more than once.
History of Previous Birth
If a mother has had difficulty with previous pregnancies or labor, she will be considered high risk.  Among those factors which put a mother at particularly high risk are history of miscarriage, previous stillbirth or neonatal death, history of premature labor/delivery, previous cesarean delivery, infant of high birth weight, and infant who required intrauterine or neonatal exchange transfusion.

Toxemia (Pre-eclampsia) During Pregnancy and Uteroplacental
Insufficiency
Toxemia is a maternal disease of pregnancy characterized by hypertension, edema, and proteinuria.  The greatest problem in this order is hypertension, which invariable puts a strain on umbilical blood flow to the fetus.  When this happens, the result is uteroplacental insufficiency (UPI).  UPI, therefore, is common in pre-eclampsia.  Renal disease or diabetes may also cause hypertension; also essential hypertension may cause UPI.  (Anything responsible for hypertension causes UPI.
While we are talking about UPI, this condition is not only related to hypertension.  It also may occur in postmaturity, cyanotic maternal heart disease, and chronic hypoxia associated with maternal pulmonary disease.  Older primigravidas also are reported to have an increased incidence of UPI.  In any mother who has third trimester bleeding or oligohydramnios and especially in older primigravidas, UPI should be suspected.
What is Uteroplacental Insufficiency (UPI)?
To best understand, UPI, it is appropriate to take a look at placental gas exchange.  The placenta is a low resistance circulatory system six to eight inches in diameter and about one inch thick.  It weighs approximately one pound.  It serves to provide gas exchange as well as exchange of nutrients for waste products.  Maternal arterial blood enters the placenta through the uterine spiral arteries.  Blood flow then distributes itself throughout the intervillous spaces.  Within these spaces lie the chorionic villi which contain capillaries which ultimately go to the fetal circulation.  Gas exchange occurs between maternal blood and fetal blood around the chorionic villi.

Arterialized fetal blood leaves the placenta and flows to the fetus through the umbilical vein.  Two smaller umbilical arteries carry blood away from the fetus and back to the placenta.  The three blood vessels are surrounded by a gelatinous material called Wharton’s jelly, which literally prevents the cord from kinking.  It is important to be aware that the PO2 of blood in the umbilical vein is relatively low mainly because there is a 40-50 mm Hg “loss” in PO2 with virtually any membrane diffusion.  This is primarily because of diffusion limitation.  The other causes of the low PO2 and abnormally low PO2’s of fetal vein blood may be due to shunt within the maternal and fetal circulation, a high oxygen consumption within the placenta, an uneven distribution of maternal blood flow, and an uneven distribution of diffusing capacity to blood flow.  It should be noted, however, that oxygen tissue delivery is enhanced by the effect of fetal hemoglobin (HbF), which moves the oxyhemoglobin desaturation curve to the left and maintains a higher saturation of hemoglobin with oxygen for a given PO2.
UPI is associated with a decrease in intervillous blood flow secondary to with maternal vascular disease.  There is a limitation of gas and nutrient exchange across the placenta, which may limit growth to the fetus.  This is known as intrauterine growth retardation (IUGR).  While IUGR is the most common result of UPI, other problems include intrauterine fetal death, chronic intrauterine asphyxia, and meconium aspiration syndrome (MAS), which can result from neonatal asphyxia.
 
 

Assessment of Fetal Growth and Development

Ultrasonography
Ultrasonography is an important diagnostic tools in neonatal medicine just as it is in virtually every medical discipline.  It is one of the first of the modern non-invasive technologies (since the flouroscope) that has enabled definitive examination of anatomical structures and observe them in their dynamic state.  It uses high-frequency sound waves to locate and visualize organs and tissues.  These sound waves are well below the intensity that could damage tissues.  In recent years, the technology of ultrasonography has developed to enable trained users to spot fine details that were previously missed.  Blood flow can be assessed with today’s units, and even the direction in which blood is flowing and the pressures within various vessels can be determined.
Ultrasonography is performed by placing a hand-held transducer over the mother’s abdomen.  In some cases a vaginal transducer has to be used if other points of view are necessary.  As sound waves come into contact with different density tissues, some are absorbed and others are reflected to the transducer.  The reflected waves are converted into a screen image, visually duplicating the targeted organ.  The image can then be used to identify abnormalities either in structure, size or movement.
There are two types of images produced by ultrasound: the static image, a single stationary view, and the M-mode image, or a motion mode or real-time image.  Most ultrasound examinations performed today produce both types of images.
There are two types or modes of static images.  First is the amplitude mode, or A mode, which measures distances as spikes on an oscilloscope.  This is one of the earliest forms of clinically used ultrasonic tracings.  The other mode is the brightness mode, which produces a two-dimensional picture on the screen.  In the case of a fetal ultrasound, even the untrained observer usually can make out the fetal image and appreciate the detail.
M-mode imaging is used most commonly in neonatal medicine.  With this mode, the fetal movements can be seen.  The heart and its functioning valves are clearly seen as well as other organs.  Today most obstetricians perform a “sonogram” as a matter of routine on all mothers, usually by the eighteenth week of pregnancy.  By this time, most major structural defects can be picked up.  A congenital diaphragmatic hernia could be seen, for example, as well as cardiac anomalies, such as a hypoplastic left ventricle, tetralogy of fallot, and often, coarctation of the aorta.
It is important to mention here that the health of the fetus is only one aspect when performing a sonogram.  A lot can be learned about the general condition of the pregnancy as well.  The site of implantation is important to note as well as the appearance of the placenta and umbilical cord.  The volume of amniotic fluid can be determined pretty accurately also.
What abnormalities are diagnosed in utero?  Some examples are abdominal masses, diaphragmatic hernia, congenital malformations of the nervous system, omphalocele (herniation of the intra-abdominal viscera around the umbilicus), seizures, urinary tract dilation, intraventricular hemorrhage, and many congenital heart defects.
The list of ultrasound applications at the bottom of page 34 is good in that it lists the more common applications.  Keep in mind that an ultrasound can be performed throughout pregnancy and even at delivery and often is used for a quick “look-see.”  It is an easy, reliable, and relatively inexpensive tool.
Amniocentesis
Amniocentesis, which is the needle sampling of amniotic fluid, can be safely performed at about 14 WGA.  A 4-inch 20-22 gauge needle (other lengths are sometimes used) attached to a syringe is inserted into the uterine cavity.  Ultrasound is usually used to position the needle and to find an adequate pocket of fluid.  It would be rare these days to see an amniocentesis performed without ultrasound.  The fluid is aspirated for analysis.  There is analysis of the fluid itself as well as the cellular elements it contains. Complications of amniocentesis are seen in less than 1% of cases.  Complications include accidental puncturing of the fetus, umbilical cord, or placenta.  This could lead to intrauterine hemorrhage.  Infection also is a complication.  What are the specific tests that are performed on amniotic fluid today?
The most well-known is the L/S ratio to determine the presence of PG.  The following are other important tests:
Alpha-Fetoprotein (AFP) levels - AFP is the main serum protein in the developing fetus.  A significant break in the fetal skin, and especially an open spinal defect, which may occur in anencephaly or meningomyelocele (spina bifida), will cause AFP to leak from the exposed tissues into the amniotic fluid.  A high AFP level is a good indicator of a neural tube defect.  Usually acetylcholinesterase concentrations also are high in neural tube defects.  Generally it is at the 14th to the 16th week of gestation that the AFP levels will be high, and this will be the first indication of a seriously compromised fetus.
(AFP levels also can be used to identify stillbirth, low birth weight, and fetal chromosome disorders, but usually is not relied upon because of the availability of more definitive tests)
Bilirubin levels - used to determine hemolysis.  Rh incompatibility is a common hemolytic abnormality.  Bilirubin levels increase according to the degree of hemolysis.  A fetus who is destined to present with hydrops fetalis probably will have high bilirubin levels if a determination is made sometime in mid pregnancy. Bilirubin levels also are used to determine approximate gestational age.   Bilirubin levels normally taper off and may actually be absent by 36 weeks.
Creatinine levels - used to help determine fetal kidney maturity;
these levels increase as pregnancy progresses
Identification of Meconium Staining - amniotic fluid normally is clear.   Meconium staining is present if the fluid takes on a greenish appearance.  Fetal stress causes the fetus to pass meconium.  Presence of meconium suggests that there will be meconium aspiration (MAS) in the newborn.
Cytologic Examination of Cells - errors of metabolism can be identified by performing biochemical and enzymatic assays of whole cells found in the amniotic fluid.  These cells are from the skin, amnion, and tracheobronchial tree.  Also a variety of genetic and chromosomal disorders can be identified through examining these cells.  Down’s syndrome and other trisomy disorders are examples.

Meconium Presence in Amniotic Fluid
Meconium is the thick, dark greenish stool found in the fetal intestine.  There is about 200-600 gm in the term infant intestine.  Meconium passes into the amniotic fluid in about 40% of postterm infants older than 42 WGA.  10% of term infants pass meconium in utero as do 3-5% of premature infants.
Amniocentesis or amnioscopy reveals the presence of meconium, which is believed to be released when fetal asphyxia causes relaxation of the anal sphincter.  Also there may be increased peristalsis in the intestine.
Chorionic Villus Sampling
Chorionic villus sampling is a new procedure that has not caught on well in the U.S.  This procedure involves sampling tissue from the fetal chorion by suctioning through a catheter inserted into the dilated cervix and guided by ultrasound to the placenta.  This procedure is performed at 9 to 12 weeks from the last menstrual period.

Over the second half of the third trimester, the mother and fetus
take on some changes that get them ready for the birth process.  Sometimes the mother goes into a false labor with mild contractions.  These contractions are referred to as Braxton-Hicks contractions and are milder than real contractions.  They are rhythmic, however, which makes them seem like real contractions.
Delivery is a continuous process which consists of four stages.  The first stage, (Stage I) begins with the onset of the first contraction.  Contraction come in waves, and in the beginning are 10 minutes apart and last 30-90 seconds.  They generally start as short contractions and get progressively longer with time.
The cervix begins to stretch and widen when contractions begin.  When the cervix stretches, it also thins.  This is called effacement and is expressed as a percentage.  At 100% effacement, the cervix is completely against the uterine wall.  The widening of the cervix is called dilatation, and the degree of dilatation is expressed in centimeters.  The cervix is said to be fully dilated at 10 cm.  Effacement and dilatation occur because uterine contractions push the amniotic fluid and the fetus against the cervix.

The cervix primarily effaces during the early part of stage I.  Dilatation is very slight over the first part of stage I and then progresses rapidly over the latter part of stage I.  Effacement is almost 100% when rapid dilatation begins.

Stage I  lasts until the cervix is fully effaced and dilated.  Average time for this stage is 7 to 12 hours in the multigravida and 16 to 18 hours in the primigravida.  Understand, however, that in complex or premature labors or in high risk pregnancies, these average times would be an exception.

Stage II of labor is the actual delivery of the fetus.  Movement of the fetus through the birth canal is aided by the contraction of the abdominal muscles and diaphragm by the mother.  This increases abdominal pressure so that with uterine contractions, the fetus is pushed out.
95% of all births occur with the fetus in the head down position.  This is called the vertex position.  However, there are a number of variations of the vertex position, depending on the way the fetus is facing.
The term engagement is used to describe the presence of the fetus in the birth canal.  When the top of the fetal head reaches the level of the ischial spines, the head is engaged in the birth canal.
The birth canal is divided into stations.  Each station represents 1 centimeter above or below the level of the ischial spines.  Stations above the ischial spines are numbered consecutively from-1 to -5.  Below the level of the ischial spines they are numbered 1 to 5.  The level at the ischial spines is a station of 0.  When the head of the fetus is engaged, it is at a station of 0.
Once the fetus is going down the birth canal, he turns his head face down so that there is easier passage through the pelvis.  Once the head is through, the body rotates internally so that the shoulders will pass easily.  The upper shoulder emerges first and then the lower shoulder.  This part of the delivery has been the most time-consuming.  Once the shoulder is present, the remainder of the body emerges quickly.  The umbilical cord is then clamped.
Although it seems unbelievable, Stage II can last two hours without any major danger to the fetus.  It usually lasts 20 to 45 minutes.

Stage III of labor is expulsion of the placenta.  This takes 5 to 45 minutes.  Contractions continue until the placenta tears away from the uterine wall and is expelled.  If the neonate is placed at the mother’s breast, he can stimulate secretion of oxytocin to increase these contractions.  Manual pressure to the abdominal wall also helps.
After the placenta passes, the uterus starts to shrink and eventually returns to its original size.  The immediate period after delivery of the placenta is called stage IV.  It is during this stage also that homeostasis is reestablished in the mother.

Abnormal Labor and Delivery
Premature labor is one of the most difficult of perinatal problems.  One strategy that is used to deal with a premature birth is to try to stop premature labor.  The process for doing so is called tocolysis.  Many premature labors are stopped or slowed by using drugs.  This is called pharmacologic tocolysis and is usually accomplished by using sympathomimetic (adrenergic) drugs, which relax smooth muscle.  The only drug that is FDA approved is ritrodine, but terbutaline is being used extensively.  Albuterol also is being used.
If the mother has an underlying cardiomyopathy or an infection, ritrodine can cause pulmonary edema.
There are side effects to using beta adrenergic drugs to both the mother and the fetus.  Both the mother and fetus can become tachycardic and hyperglycemic.  In fact, the neonate may overproduce insulin in response to his initial hyperglycemia, which will cause him to have a rebound hyperglycemia.  Maternal hypokalemia is another side effect as well as nausea and vomiting.
Another drug in widespread use for stopping uterine contractions is magnesium sulfate, which is an anticonvulsant drug.  It works by decreasing muscle contractility, and its side effects include decreased muscle tone, drowsiness and decreased serum calcium levels in the neonate.
Indomethacin (Indocin) is a drug that inhibits prostaglandin synthetase.  Since prostaglandins induce labor, Indocin seems to be a useful drug for tocolysis.  However, this drug also causes closure of the ductus arteriosus of the fetus in utero, which can be a devastating problem.
Nifedipine, a calcium channel blocker, has been used with some success for tocolysis with few side effects.
There is no form of tocolysis other than pharmacologic.  Counseling and educating the high risk mother where applicable is the only alternative.
In order for tocolysis to be tried the mother/fetus must meet 6 criteria:
1) true labor must be present
2) the cervix must not be dilated more than 4 cm and effaced more than 50%
3) the fetus must be 20 - 36 WGA
4) there must be no signs of fetal distress or disease
5) there must be no medical or obstetric disorder that would contraindicate the continuation of labor
6) the mother must give informed consent

Dystocia is a prolonged labor because of uterine, pelvic, or fetal problems.  It is present when stage I and II exceed 20 hours.  It also is present when stage II exceeds 2 hours in primigravidas and 1 hour in multigravidas.
There are three major dangers to a prolonged labor.  First, there is increased chance that the placenta will separate from the fetus.  This would cause serious asphyxia.  Second, there is more of a chance that the umbilical cord will be compressed.  Third, premature rupture of the amniotic sac is more likely.  The danger of fetal infection rises significantly with rupture of the amniotic membranes, especially if delivery has not occurred within 24 hours.
A common cause of dystocia is dysfunction of the uterus.  There are cases where the uterus contracts excessively strong (hypertonic) or, more frequently, too mildly (hypotonic).  When there are hypertonic contractions, the cervix may not dilate and efface properly.  As a result, the placenta and/or the umbilical cord maybe compressed, causing asphyxia.  Hypotonic contractions may occur because of anesthetic overdose or failure of the fetus to descend normally.  Contractions are not strong enough to dilate and efface the cervix and expel the fetus.

Cephalopelvic disproportion (CPD) is another common cause of dystocia.  The disproportion can be either a fetal head too large or a maternal pelvic opening too small.  In either of these cases the fetus is unable to enter and pass through the birth canal and labor is prolonged.  One well-known situation is in the accelerated growth of the fetus which occurs in diabetic mothers.  Sometimes the fetus reaches 5-6 kg.  Another situation is hydrocephaly.  The pelvic opening can be small as a result of contracture, which may be a congenital problem in the mother or be due to poor nutrition or pelvic fractures or disorders.  Small pelvic openings also are seen in Asian populations and in many women less than 20 years old.
Abnormal presentation is any position of the fetus before birth other than vertex.  The breech position is the most common abnormal presentation and comprises 3.5% of all births.  There are three types of breech presentations: the complete breech, where the feet, legs, and buttocks all present together; the frank breech, where the legs are flexed against the body and the feet are near the face so that the buttocks are presenting; and the footling, or incomplete breech, where one or both feet descend into the birth canal first.
The problem with breech presentations is greatest when there is diminished pelvic size or enlarged fetal head.  In these cases, the fetal body can be easily delivered but the disproportional head will not engage the birth canal.  By this time it is too late to perform a C-section, so the head must be passed by means of manipulation.  Spinal cord damage and hemorrhage in the brain can occur from pulling on the fetal body.
Placenta previa is reported to be a common cause of breech presentation.
Other abnormal presentations are the face, brow, and transverse lie (shoulder).
It is important to note here that the fetal skull is not solid like in the adult.  It is made up of several bony plates separated by what are known as sutures.  In the birth canal, these sutures overlap, making the diameter of the skull smaller.  In the face or brow presentations, the head enters the birth canal in such a way that the sutures cannot override.  If the fetal head/ maternal pelvic opening proportion is tight, the head will have trouble passing through the birth canal.  The neonate will be likely to suffer from facial trauma and edema, but also may have experienced asphyxia from the prolonged labor and time in the birth canal.
Delivery of a fetus in the transverse lie position is very difficult.  The only possibility for a vaginal delivery lies in manipulating and repositioning.  Usually a c-section is performed.
 The umbilical cord consists of an umbilical vein and two umbilical arteries.  These vessels are surrounded and protected by Wharton’s jelly. The thickness of this jelly material keeps the cord from bending and cutting off circulation.  But it does not prevent the cord from being compressed between body parts.  This is a common cause of asphyxia in the fetus.
Sometimes the umbilical cord passes through the birth canal before the fetus.  This is called prolapse of the umbilical cord.  This problem is common in breech presentations (especially footling breech) and the transverse lie presentation.  It also is seen in multiple gestations (twins).  In prolapse the fetus can easily compress the cord when passing through the birth canal.  Or, there can be compression of the cord within the uterus, which is called occult prolapse.
There are a few placental abnormalities which make labor and delivery difficult.  One of the most common is placenta previa.  In most pregnancies, the blastocyst attaches itself somewhere in the upper portion of the uterus.  Placenta previa occurs when implantation occurs in the lower portion of the uterus.  There are three varieties.  A low implantation is a for m of placenta previa which occupies the lower portion of the uterus but does not cover the cervical opening.  A partial placenta previa is so low in the uterus that it covers part of the cervical opening.  Total placenta previa is a situation in which the placenta covers all of the cervix.
Placenta previa can be diagnosed by ultrasound, and in most cases a c-section is planned.  Vaginal delivery is possible, but manipulating fetus and placenta through the birth canal is very difficult.
A more serious problem with the placenta is abruptio placentae, which is the premature separation of a normally attached placenta.  (This condition also is called abruption)  Often this separation causes labor to begin, so premature labor and delivery is the result.  This is a life-threatening event for the mother, and maternal mortality is 2 - 10%.  Fetal mortality is close to 50%.
Maternal hypertension of any origin is the most common cause of abruptio placentae.  One form of hypertension in the mother is the condition known as preeclampsia, in which proteinuria, edema, and hypertension occur after 20 WGA.
There are mothers with a history of abruption, which makes them at greater risk for the disorder.  Other mothers who are at risk are those who have had a high number of previous pregnancies.  trauma, short umbilical cord, uterine abnormalities, and compression of the inferior vena cava.
Separation of the placenta can be either partial or complete.  Bleeding is an immediate complication.  Bleeding from the vagina is called apparent hemorrhage.  If no bleeding is evident, there is said to be concealed hemorrhage.  There are four classifications or grades in describing the severity of the disorder.  The mildest, grade 0, is not identified until after delivery when a small clot is discovered behind the placenta.  Grade 1 involves some vaginal bleeding with some tetany and tenderness of the uterus.  Grade 2 is similar to grade 1, except that there may or may not be vaginal bleeding and there is fetal distress.  Grade 3 is the most serious because maternal shock and persistent abdominal pain are present.  Again, there may or may not be vaginal bleeding.  Fetal demise is present, and the uterine tetany is so severe that it takes on a very stiff, firm consistency.  In about 30% of grade 3’s, there are signs of coagulapathy in the mother.
So, in abruptio placentae the mother may show vaginal bleeding, tetany and tenderness of the uterus and hypovolemic shock.  The fetus loses placental surface area which can result in severe hypoxia and asphyxia along with blood loss and hypovolemic shock.
Treatment of abruptio placentae involves intensive management of maternal blood/fluid volume with packed red blood cells, whole blood, or crystalloid administration.  The hematocrit is maintained at 30%.  The mother often must lie in a lateral position to enhance fetal circulation.  Intensive monitoring of both the mother and the fetus are important as well as capability for emergency delivery or c-section in the event of maternal shock or fetal distress.
Premature Rupture of Membranes (PROM)
The likelihood of fetal infection (most commonly pneumonia) is increased with PROM.  Premature rupture is said to occur when the rupture occurred more than 24 hours before delivery.  If there is PROM with prolonged labor, this increases the risk of infection.  PROM occurs more often with premature labor, and sometimes a prolonged labor is tolerated while steroids are administered to increase fetal lung maturity.

Cesarean section (c-section) is a delivery via a surgical incision through the abdomen and uterus.  They are performed under anesthesia and there are 7 indications.  These are the following:
1) large fetus in relation to maternal pelvis
2) severe maternal preeclampsia
3) hemorrhage
4) partial or total placenta previa
5) failure of the cervix to dilate
6) fetal depression from maternal anesthesia
7) fetal distress

Complications of cesarean section include traumatic injury to the fetus, placenta or umbilical cord which can lead to hemorrhage and anemia.  Another complication is transient tachypnea of the newborn (TTN), which arise from the retention of lung fluid because the fetus was not squeezed in the birth canal.
Multiple gestation is the presence of twins, triplets or more fetuses during the same pregnancy.  the incidence of fatality is greater in multiple gestations because there is a higher incidence of premature labor.  There is also increased incidence of congenital abnormalities, growth retardation, bacterial infection, and hypoglycemia.
Multiple gestations are more common in the black population and very uncommon in Asian populations.  Familial inheritance is a factor in fraternal twins.  Older mothers, ages 35 to 39, also tend to have multiple gestations.  Mothers who receive the fertility drug clomiphene citrate (Clomid), which is used to induce ovulation, and gonadotropins also have multiple gestations.  There is some evidence that multiple gestations appear in mothers who discontinue the use of oral contraceptives.
The most common form of multiple gestations is twinning.  This occurs in about 1 out of 99 pregnancies.  Two thirds of all twins are fraternal, which means that they are dizygotic and arise from the fertilization of two separate ova.
Fraternal twinning is an autosomal recessive trait that is carried by daughters of mothers of fraternal twins.  The other one third of twins are identical and are of the same sex.  They arise from the fertilization of one ovum.  They are identical in appearance.  Identical twinning occurs at random, and there is greater mortality in this twin group.  Studies have shown that the second twin is usually more compromised than the first and female twins are more healthy than male twins.
Congenital abnormalities, bacterial infection, and hypoglycemia are more common in multiple gestational births.  Prematurity is highly associated with multiple gestation pregnancies, especially identical twins. Problems with the umbilical cord, the placenta, and IUGR also occur with multiple gestation as well as abnormal presentation (such as breech).  In many of these pregnancies, the placenta is smaller in one twin which makes him develop smaller.  Twins in this situation are called discordant twins.
The twin transfusion syndrome, or the intrauterine parabiotic syndrome, is a situation in which the circulatory systems of the two twins are connected.  Transfer of blood from one twin to the other occurs, and one becomes polycythemic and the other becomes anemic.  The polycythemic twin will be likely to develop conges- tive heart failure.  Because of the increased number of red blood cells, hemolysis may occur, which will increase bilirubin.  The other twin will be more likely to be in shock.

The Birth Process
Lung Inflation at Birth
It is thought that the respiratory movements of the fetus in utero prepare it for extrauterine breathing.  Breathing movements are noted to increase in activity over the last ten weeks of gestation.  When the neonate is delivered, there must be stimuli present for it to take its first breath and to begin rhythmic breathing.  There are three factors believed to be responsible for initially stimulating breathing.
1. Asphyxia  (increased PaCO2, decreased PaO2 and pH stimulate chemoreceptors found in the aortic arch and carotid bodies)
2. Recoil of the thorax  (as the thorax passes through the birth canal, it is compressed; as the fetus exits the birth canal, the natural recoil of the thorax creates a negative pressure in the thoracic cavity, which pulls air into the lungs)
3. Environmental changes stimulate crying (changes from dark to light, warm to cold, silence to noise; tactile stimuli)

To establish the functional residual capacity (FRC) of the lung, there has to be an extreme negative pressure generated by the first breath.  This negative pressure has been found to be as high as -100 cm H2O, which is necessary to overcome surface forces.  Surfactant in the term infant aids in this process, and if surfactant levels are low, there is a great tendency for the lung to collapse despite high negative inspiratory pressures.  The FRC continues to increase in size over the first few hours of life as more fluid is cleared from the lungs, collapsed alveoli are expanded, and as more air remains.

Change from Fetal to Adult Circulation
In addition to having to initiate breathing rather quickly, the neonate must make a transition from the fetal to an adult circulation.
At birth, the umbilical cord is clamped.  This causes some major changes in the fetal circulation.  Before clamping, the umbilicus and placenta provided a low resistance to blood flow.  When the umbilical cord is clamped, blood that normally would have gone to the placenta is forced to perfuse the lower extremities.  This causes the systemic arterial pressure to increase back to the left ventricle and left atrium.
At the same time, the neonate starts breathing, which greatly reduces the pulmonary artery pressure.  This pressure is reduced because the establishment of an FRC decreases the pressure around the pulmonary vasculature from fluid.  But more importantly, this pressure is reduced because arterial PO2 increases which relaxes smooth muscle within the pulmonary circulation.  So with a decrease in pulmonary artery pressure, there is a decrease in right ventricular and right atrial pressures.
One important result of the changes in systemic and pulmonary vascular pressure is the closing of fetal shunts.  Obviously with the pressure in the left atrium higher than in the left, the “mechanical” tissue flap on the foramen ovale closes.  Blood in the right atrium now flows to the right ventricle.
The ductus arteriosus also closes.  Actually, over the last few weeks of gestation, smooth muscle around the ductus starts to develop.  This smooth muscle remains relaxed so that the ductus will stay open before birth.  The mechanism that keeps the ductus open is the presence of prostaglandins.  The production of these prostaglandins are stimulated by a low PO2, so when the PO2 rises at birth, prostaglandin levels decrease quickly and allow the ductus smooth muscle to constrict.  The ductus arteriosus conn ects the aorta with the pulmonary artery.  If the ductus did not close, there would be right-to-left shunting, left-to-right shunting, and congestive failure.
The clamped umbilical arteries eventually become ligaments as does the ductus venosus.

Surfactant: Endogenous and Exogenous
It is important to relate surfactant physiology to respiratory
distress syndrome, so we have waited until now to focus on surfactant.  There is much investigation underway in the area of surfactant replacement as well as ways in which endogenous surfactant production can be stimulated in the fetus at an earlier gestational age.  Interestingly, however, if one takes a look at perinatal research over recent months, much is being reported on how to delay or postpone labor.  Only in the past decade have we seen such emphasis placed on prevention, especial-ly when alternatives are either hopeless with regard to the outcome or economically costly.
What is surface tension?  As its name implies, it is the attrac-
tion that like molecules have for each other.  An example would be, say, two small streams of water running parallel and very close to each other.  If they were to become so close as to touch each other, they would join together into a single large stream.  This is due to the attraction of like molecules.  In the lung, the alveolar wall produces a pressure which tends to collapse the alveoli.  The reason for this is related to the Law of LaPlace, which states that the pressure within a sphere is directly related to its surface tension and inversely related to its radius.  The law is expressed mathematically as P = 2ST/r.  The important concept here is how radius is inverse to pressure.  One can illustrate this by drawing a small sphere connected by a tube to a sphere that is twice as large (in other words, the radius is twice as large).  The surface tension of both spheres would be the same (they are made out of the same material), so it is their radii that are different, the larger one having a radius twice as large as the other.  If one applies LaPlace’s Law to this, it means that the pressure in the smaller sphere is twice that in the larger sphere.  Because it would be difficult for these two spheres to communicate with each other and be of different pressures, the smaller is going to empty into the larger.
Using the above illustration as an example, one can see that the general condition of the lung without surfactant would be for smaller alveoli that are in communication with larger ones to empty into those larger ones.  This would create a non-homogenous character to the millions of alveoli and would perhaps create a situation of both atelectasis and hyperinflation all at the same
 time.  If you can place this into your imagination, you can visualize exactly what takes place in diseases in which there is surfactant deficiency.
The role of surfactant is to stabilize alveolar surfaces.  It
does this primarily by lowering the surface tension, although it has other effects as well.  This enables large and small alveoli to co-exist without significant differences in their pressure because of their differing radii.  The end effect is that infla-tion pressure to open airways is reduced as is pulmonary compli-ance.  The work of breathing is less because little (or less) pressure has to be generated to move gas through the airways to the alveoli.
Eighty-five per cent (85%) of surfactant consists of
phospholipids.  Another five per cent are the neutral lipids, and their role is essentially unknown.  Ten per cent are the three proteins, sometimes called appoproteins (some say that there are more than three, but the others, if they exist, have not been identified).  The proteins, while having unique functions, can generally be said to be responsible for the spreading and distri-bution of the entire surfactant material.
Remember that the most prominent phospholipid is dipalmitoyl phosphatidylcholine, or DPPC.  Most of the time we shorten this name to phosphatidylcholine, or PC.  This is the surfactant that begins to appear at 24 weeks gestation.  There is evidence that this surfactant starts to decline in late gestation as phosphatidylglycerol, or PG, begins to appear at 35 to 36 weeks.  PG is sometimes called the “mature surfactant.”
Along with their ability to distribute surfactant over the alveolar surfaces, the surfactant proteins help to bind the surfactant to the alveolar epithelium.  They also help in regu-lating surfactant synthesis and metabolism.  SP-A is the most abundant surfactant protein, and it is thought to have a role in surfactant recycling, or the re-uptake of surfactant by the lamellar bodies.  It is hydrophilic.  And, it is said to have immunologic properties.

The other two surfactant proteins, SP-B and SP-C, are hydropho-bic, so they would have much to do with helping surfactant molecules “line up” in order along the alveolar epithelium.  They also help sustain the surface active-functions of the phospholipids.
By the end of the cannicular stage of lung development, the type II cell is able to take up the components of surfactant, package these components in it lamellar bodies, empty the lamellar bodies into the alveoli, and recycle the previously secreted surfactant.
Respiratory distress syndrome (RDS), also called hyaline membrane disease (HMD), is a syndrome associated with prematurity or stressed, high-risk infants.  RDS is caused by insufficient amounts of pulmonary surfactant or depressed surfactant activity, leading to massive atelectasis and hypoxemia.  The severity of the disease is inversely related to gestational age.
Although RDS is a classic surfactant deficiency disease, it is
important to note that surfactant deficiency can affect every age.  Adult respiratory distress syndrome (ARDS) is a surfactant deficient disease, for example.
Pulmonary (alveolar) perfusion and alveolar expansion must be adequate at birth to sustain life.  If one were to look at a histological sample or cross-section of the lung, as we did in Dr. Rosenfeld’s video Fetal Lung Development, it would be possi-ble to see alveolar ducts and respiratory bronchioles but not alveoli.  It would also be possible to see pulmonary capillaries, but they would not be in close contact with the bronchioles or alveolar ducts.

At about the 28th week, alveoli start to develop rapidly, and mature type I squamous epithelial cells which form the alveolar lining are present at weeks 34-35.  Pulmonary capillaries develop along with the alveoli.  Along with alveolar perfusion and expansion, there must be mature pathways for the formation and secretion of surfactant.  As we discussed earlier, the three phospholipids begin being produced at different points in time over the gestational period, and all peak in their production at different points as well.  But surfactant production depends on the presence of type II cells, which also line the alveoli.
So, keep in mind that two major factors are necessary for ade-
quate lung function: alveolar-capillary development and surfac-tant production pathways.  Infants born before 35 weeks of gestation are at risk for developing RDS because of pulmonary immaturity.  Also some infants who have been stressed at an advanced gestational age or have suffered asphyxia during the fetus-to-neonate transition will have suppressed surfactant production because of hypoxia and acidosis.  And, as we discussed earlier, those infants born of some diabetic mothers and those with Rh incompatibility also are at high risk for RDS.
There is some evidence that the surfactant that is present in the very premature infant is too immature to be fully effective.  This we assume to be true because of the relatively small amounts of the most important phospholipid phosphatidylcholine.  But in addition to this, relatively recent research has suggested that the premature newborn cannot reuse surfactant through the recy-cling process that Dr. Rosenfeld mentioned.  There is extensive evidence to back up the point that SP-A is more deficient in premature neonates, and this could well be the reason for the poor recycling.
The fundamental problem in RDS is atelectasis, which causes a ventilation perfusion inequality.  With the neonate’s limited ability to overcome the atelectasis, hypoventilation andhypercarbia result.
Surfactant has a secondary effect on the lung to keep it dry.  It
does this by helping to limit the continuous fluid filtration out of the capillary into the interstitial space (adjacent to the alveoli).  Normally, this fluid filtration helps to hydrate the alveoli, and the fluid is cleared by the lymphatics.  Without surfactant, there is a tendency for more fluid filtration to enter the interstitium and the alveoli themselves.  At the same time, progressive hypoxemia and actually causes damage to capil-lary endothelial cells.  This allows even more fluid as well as blood components to cross over into the alveoli.  As protein from the blood enters the alveoli, fibrin-clot formation occurs when dying epithelial cells are encountered. Thus, hyaline membranes are formed.

If one were to examine a histologic sample of a lung affected by RDS, the most obvious abnormalities would be bronchial basement edema and sloughing of respiratory epithelial cells.  There would be patchy areas of atelectasis.  And there would be the classic hyaline membranes which form as proteinaceous fluid enters air spaces.  After about 72 hours, alveolar macrophages appear and begin to phagocytize the hyaline membranes.  If no further damage to the lungs occurs, resolution of the disease will occur in about five to seven days.

It is important to note that secondary hemodynamic effects cause additional problems.  Acidosis and hypoxemia causes pulmonary arteriole constriction, which produces pulmonary hypertension.  Typically, the infant with RDS presents with signs of respiratory distress at birth or soon after birth.  Even if the infant is premature, however, it is easy to confuse the diagnosis of RDS with sepsis. Respiratory distress is manifested by nasal flaring, intercostal and substernal retractions, expiratory grunting, central or acrocyanosis, and paradoxical chest/abdominal move-ment.  The clinical signs progressively worsen.  The infant usually is intubated and ventilated long before the peak of the disease, which is 48 to 72 hours.  Breath sounds are very dimin-ished and dry crackles usually are heard.  In conditions of severe hypoxia, there can be peripheral vasoconstriction with poor capillary refill, and the baby can become pale or gray.  Pitting edema accompanies this situation along with a poor urine output. There are increasing oxygen requirements as respiratory distress increases, just to keep PaO2 50 to 60.  PaCO2 gradually increases, and acid-base status becomes mixed respiratory and metabolic acidosis.The chest x-ray of the premature neonate with RDS shows a diffuse reticulogranular or ground glass appearance, and air bronchograms are frequently seen in both lung fields.  A complete whiteout occurs in severely affected infants because
 their alveoli become fluid-filled and atelectatic.  Lung volumes are typically reduced.

The goals for treating RDS are to prevent or reverse(1) furtheralveolar atelectasis; (2) the side effects of asphyxia and poor perfusion; and (3) infection, pulmonary air leaks, pulmonary edema and hemorrhage, bronchopulmonary dysplasia, congestive heart failure from a patent ductus arteriosus, intracranial hemorrhage, anemia, retinopathy of prematurity, and all the potential complications resulting from therapeutic interventions.  The use of nasal cannula CPAP and continuous flow IMV is the most accepted way in which neonates with RDS are managed.  However, keep in mind that many neonatologists now advocate the assist control mode of ventilation, weaning only the PIP, and extubating from high rates.  This new trend has been shown to have some advantages in that sedation requirements are less, ventilator course is shorter, incidence of barotrauma is less, and apnea during weaning is less of a problem.  This mode of ventilation only seems to work over the long term if the infant can flow trigger inspiration and can control inspiratory time through some kind of termination-of-inspiratory-flow sensitivity mechanism.
Many of the above treatment goals for RDS can be met by theappropriate use of an exogenous surfactant preparation.  The essential features of an effective exogenous surfactant would be the ability to lower surface tension at the air-liquid interface, the ability to be rapidly absorbed to a liquid surface and rapidly spread along that surface at body temperature, and a physical/chemical form that can be delivered into the terminal airways and alveolar spaces.  There are four types of exogenous surfactant.  They are natural surfactants, modified natural surfactants, synthetic surfactants, and naturalized synthetic surfactants.  Only two brands of exogenous surfactant are FDA approved for use in the U.S.  These are Survanta, which is a modified natural surfactant, and Exosurf Neonatal, which is synthetic.  Surfactant replacement therapy can be classified as either prophylactic or rescue.  Those patients who are being considered for prophylactic therapy are usually less than 30 WGA or are less than 1250 gm.  Rescue therapy is given to those infants who already are showing signs of surfactant deficiency: they require ventilatory support, they are a young gestational age, and their chest x-ray suggests RDS.
Reduction in the severity of RDS is the most consistently report-ed benefit of surfactant replacement.  There has been a reported reduction in pulmonary air leak, reduction in overall infant mortality (the single most important factor in dramatically reducing infant mortality since the mechanical ventilator), and reduction in BPD and other complications of prematurity.  Prob-lems associated with surfactant replacement include pulmonary hemorrhage, PIE (once “nicknamed” Exosurf lung), and obstruction of the endotracheal tube.
 

Mechanics of Ventilation
If a pressure/volume curve could be plotted for the newborn lung, we would see that there would be separate inspiration/expiration limbs.  The difference between inspiration and expiration is called hysteresis.  Surface forces within the lung are said to be the greatest cause of hysteresis.
.  Whitaker illustrates
the changes in the hysteresis curve at birth on page 76. It should be noted that the lower percentage inflation volume per unit pressure on the inspiratory limb is due to the surface forces that must be overcome even with the help of surfactant.  Also note that at a pressure of 0 there is an FRC of 25% of the lung volume.
The normal FRC of the term newborn is 17 ml/kg.  Normal
compliance is .055 L/cm H2O.  Airway resistance is, as expected, quite high at around 50 cm H2O/L/sec.  Airway resistance increases with lower lung volumes.
Time constants are used to express inspiratory and expiratory
time.  The normal newborn will inspire a normal tidal volume is .25 sec.  Normal expiratory time is .75 sec.  It is important to visualize the effects of prolonged expiratory times and the creation of autoPEEP in respiratory diseases which increase airway resistance.

The work of breathing in a newborn can appear high if one is not accustomed to the normal.  Respiratory rate is around 40/min.  Reduced compliance tends to cause an increase in respiratory rate and a decreased tidal volume.  Increased airway resistance tends to cause a slower respiratory rate.  In either of these situations, fatigue can result.
Tidal volume in the term newborn is 16.5 ml., VD is 4.1 ml., minute ventilation is 660 ml., and alveolar ventilation is 496 ml.  Respiratory rate decreases with size.  Volumes increase with height.
In the adult lung, the ventilation/perfusion ratio changes greatly from the apices to the bases of the lung with it being as high as 3 to 1.  The gradient is much smaller in the infant.  Shunting is more of a pronounced problem in the newborn, and the anatomical shunts present serious problems for oxygenation.
Oxygen and carbon dioxide diffusion occurs according to the same gradients in the newborn lung as compared to the adult.  However, the diffusing capacity is much smaller.
As for blood transport, it is important to recognize the effect of fetal hemoglobin (HbF).  HbF causes the oxyhemoglobin dissociation curve to shift to the right, which increases the hemoglobin’s affinity for oxygen for a given PO2.