CHAPTER – 1
INTRODUCTION
The word Placenta refers to “CAKE” in Latin and “FLAT, SLAB – LIKE” in Greek (Plakuos =
“Flat cake” in Greek)1
1.1.
CLASSIFICATION:
Placenta with umbilical cord is a bridging organ between mother and developing fetus. Placenta
is the characteristic feature of Viviparous eutherian (Placentals) mammals2. The human placenta
is termed as “Hemochorial”3,4,5, in which Hemo refers to maternal blood which directly baths the
syncytiotrophoblast, and Chorio is for Chorion – Placenta6. This Chorion in turn is separated
from the fetal blood by endothelial wall of fetal capillaries that is situated in the placental villous
tree hence the name “Hemochorioendothelial” was referred to the human placenta during older
times6. Originally this typical Hemochorial structure shall be seen only in the second and third
trimester of the pregnancy, before which the maternal – fetal relationship is best described as
“Deciduo – chorial”7. For centuries the Placenta with Umbilical cord has been attached to
cultural believes of humans all over the world. Traditionally it has been used as food in different
formats and medicine. Even though, it is the most ignored and under evaluated organ in the past
and present. The College of American Pathologist’s guidelines promote universal examination of
Placenta and Umbilical cord by delivering physician in the delivery room8 or by the pathologist6
which reflects the status of baby as well as mother. It depicts the importance of these organs.
1.2.
HISTORY: 9,10
Irrespective of the region and religion in the entire world, the Placenta holds the cultural believes
from ancient periods to the present. Ancients of Egypt considered the Placenta as Ego, Twin and
second Soul of the infant. Hence the Placenta of Royal family/ King was preserved in the First
step Pyramid till the death of the King. This mummified Placenta will be buried with the King
followed by his death, to proceed to his after life with his full soul. Later, in the process of
identifying the function of Placenta, it was assumed and believed that fetus lives by sucking
either Placenta or Umbilical cord, in the womb. By the late 1,500s the concept of “Placenta as
blood purifier” and “fact of separation of maternal and fetal blood in the Placenta” has
developed. Followed by it, respiratory function of Placenta has been understood with the
identification of Oxygen in the blood by Erasmus Darwin (Grandfather of Charles Darwin).
Placenta is being eaten by people of China, India and all over the world (“Placentophagy”). It is
also used for treating different disorders such as for skin growth factors, blood cancers, sickle
cell anemia, immune deficiency disorders, and metabolic disorders and so on.11,12,13
1.3.
DEVELOPMENT OF PLACENTA:
The earliest reliable steps of development have never been observed in vivo for ethical reasons.
Development of the human placenta is thought to be equivalent to the development in Rhesus
monkey. Many attempts have been made to study in the human by culturing human blastocysts
in vitro on mono layers of endometrial cells3. Even then, this cannot be taken in to consideration
because of the fact that different signals from endometrial stroma to developing blastocyst can’t
be established in vitro3. Placenta develops from two sources i.e. Foetal part from chorionic
frondosum and the maternal part from decidua basalis4. Development of Placenta starts from the
implantation. Blastocyst contains an outer unicellular layer called “Trophoblast” and an inner
cell mass called “Embryoblast” 4. The trophoblast in the region of embryonic pole of blastocyst
is called “Polar trophoblast” and the rest of the trophoblast is called “Mural trophoblast”.
Placenta develops mainly from the Polar trophoblast and primary mesoderm.
On the 8th day of the post conception, the trophoblast differentiates into an inner layer called
“Cytotrophoblast” and an outer layer named “syncytiotrophoblast”. Primarily the mantle of
syncytiotrophoblast develops all around the developing conceptus but gradually this
multinucleated mantle develops more on embryonic pole of conceptus than the rest 3,4,5. Vacuolar
spaces appear within the proliferating syncytiotrophoblast due to its rapid proliferation and
gradually coalesce to form larger lacunae which are the forerunners of intervillous spaces. The
lacunae communicate with each other around cords of syncytiotrophoblast which are called
“Trabeculae”. Meanwhile the endometrial stroma becomes oedematous with the congestion of
maternal blood vessels. Lacunae are filled first with the maternal venous blood with the erosion
of spiral veins first then spiral arteries hence the Utero Placental circulation establishes14.
The core of the trabeculae is now invaded by the proliferation of cytotrophoblast thus converting
the trabeculae to “Primary villi”. Eventually the lacunae are now named as “Intervillous space”.
Later the cells of the cytotrophoblast from the tips of Primary villi penetrate the syncitium on the
outer aspect (decidual aspect) of Intervillous space to establish contacts with the similar
extensions to form the outer cytotrophoblastic shell. This cytotrophoblastic shell divides the
syncitium at outer wall of the intervillous space into an “outer” and “inner layers”, both of which
undergo some fibrinoid degeneration. Trophoblast invades more deeply in to the basal plate at
the tips of the stem villi. As a result, portions of basal plate between the villi projects into the
intervillous space as Placental septa4,5,14
The formation of lacunae, trabeculae, Utero Placental circulation, primary villi and Intervillous
space takes place between 9 and 13th day after fertilization. Whereas the outer cytotrophoblastic
shell layer develops in the early part of the 3rd week14.
In the later part of the 2nd week a loose network of primary extra embryonic mesoderm appears
between amnion and primary yolk sac internally (embryonic aspect) and trophoblast externally.
The extra embryonic coelom appears in the extra embryonic mesoderm and divides the extra
embryonic mesoderm into Somatopleuric (lines the cytotrophoblast and amnion) and
splanchnopleuric layers (covers the yolk sac). The trophoblast together with the Somatopleuric
layer is known as “Chorion” 4,5, 14,15.
Cells from the primary mesoderm of chorion invade the core of primary villi to covnert the later
into Secondary chorionic villi. These mesodermal cells will not reach the outer cytotrophoblastic
shell hence it does not form the outer wall of intervillous space. The mesodermal core of
Secondary chorionic villi contains angioblasts, from which blood vessels develop within
mesodermal core, converting the Secondary chorionic villi into Tertiary villi. At the end of the
4th week all the placental villi are tertiary villi. These villi have 60 – 200mm diameter and rich in
mesnchyme with few blood vessels. After the 9th to 16th week the tertiary villi transforms to
Intermediate immature villi with the rapid proliferation of tertiary villi mesenchyme, trophoblast
and endothelial cells. After 26thweek of gestational age, longer and thinner villi (60 – 200mm in
diameter) with richer capillary network develop. These are called Mature intermediate villi.
These Mature intermediate villi forms the terminal or free villi (40 – 80mm diameter) and new
trophoblast buds of mature Placenta.3, 14,16
1.4.
DEVELOPMENT OF UMBILICAL CORD:
The Umbilical cord develops from the Connecting stalk in the 5th week of the development. The
embryoblast arranges into bilaminar germ disc in the 2nd week. Amniotic and yolk sac cavities
are formed followed by it. The extra embryonic mesoderm and coelom develops in the same
week of the development. Gradual increase in the size of extra embryonic coelom separates the
amniotic cavity, yolk sac and bilaminar germ disc from the chorion except at the caudal region of
the bilaminar germ disc. In this region the germ disc is connected to the chorion by a cord of
cells derived from the extra embryonic mesoderm called connecting stalk or body stalk. In the 3rd
week of development, the bilaminar germ disc converts into trilaminar germ disc with the
formation of intra embryonic mesoderm between ecto and endoderms. A tubular endodermal
outgrowth called allanto – enteric diverticulum or allantoic diverticulam develops from the dorsi
- caudal part of the yolk sac (at the caudal end of the germ disc) and extends into the mesoderm
of the connecting stalk. The allantoic helps in vascularization of placenta3,17 hence the placenta
can be termed as Chorio allantic placenta17. At this stage the body stalk contains allontois and
umbilical vessels embedded in the mesenchyme of connecting stalk.
With the folding of trilaminar germ disc and expansion of amniotic cavity the connecting stalk
with its structures brought to the ventral surface of the folded embryo to the junction of lateral,
caudal and cephalic folds where amnion envelops the connecting stalk hence forth is called
umbilical cord18. Wharton’s jelly develops from the extra embryonic mesoblasts. 17,19
1.5.
MORPHOLOGY AND MORPHOMETRY OF PLACENTA:
At term, the Placenta is usually round (discoid) or/to Oval3,4,5,20 in shape with 15 to 22 cm21
diameter, approximately 2.521 – 33,5 cm thick at the center and 1 cm thick at the periphery. The
placenta weighs around 47021 - 500gms3,5. It comprises one peripheral margin and two surfaces
or plates i.e. 1. Fetal surface or Chorionic or Amnionic surface or Chorionic plate and 2.
Maternal surface or Uterine surface or Basal plate3,4,20,21. These two plates fuse with each other at
the periphery to form peripheral margin.
The gross features of individual surfaces or plates are as follows.
1.5.1. Fetal surface or Chorionic plate:4,5,6,21
This surface faces the amniotic cavity and developing fetus and covered by transparent, glossy
and avascular membrane called Amnion under which chorionic vessels radiates from umbilical
cord. Umbilical cord attaches to this surface at or nearer to the center. Chorionic vessels pierce
the chorionic plate to supply the cotyledon.
Chorionic plate composed of Primary mesoderm with branches of Umbilical vessels,
Cytotrophoblast and Syncytiotrophoblast (Amnion to Intervillous space) 4
The periphery of this surface contains subchorial closing ring which connects the placenta with
chorio-amniotic membranes. Few of the placentas contains broad subchorial ring, such placentas
are termed as “Placenta marginata” 21
1.5.2. Maternal surface or Uterine surface or Basal plate4,5,6,21,22:
This surface abuts to the uterine endometrium. It is rough, spongy and pale red in colour5,23.
A thin grayish shaggy layer which is the remnant of decidua basalis (compact and spongy layer)
can be seen on this placenta followed by the delivery. This maternal surface presents slightly
elevated, polygonal, convex areas incompletely separated from each other with grooves of
variable depth are called cotyledons or lobes. 10 – 40 cotyledons can be seen on this surface.
These grooves correspond to placental septa, which projects into intervillous space incompletely.
4,24
.
The basal plate consists of4 Stratum spongiosum, Outer layer of syncytiotrophoblast (Nitabuch’s
layer), Outer shell of cytotrophoblast and Inner layer of syncytiotrophoblast (mother to fetus).
1.5.3. STEM VILLI:4,5,6,21,24,25
Stem villi make the parenchyma of the placenta. Villi arises from chorionic plate towards basal
plate and connect both chorionic and basal plates24. Each cotyledon contains 3 – 4 major stem
villi. About 800 – 1000 stem villi present in the placenta in the early stage of pregnancy4,5.
Villous volume decreases with high altitude26.
1.5.4. INTERVILLOUS SPACE:3,4,5,6
Is the labyrinth type of space between the stem villi of placenta filled with maternal blood comes
from the spiral arteries of uterus. These spaces are not water tight and communicated with
surrounding intervillous spaces. Internally it is lined on all the sides by syncitiotrophoblast.
Projecting branching villi congests the space. The volume of the space is about 140ml, which
increases with high altitudes.26
1.6. MORPHOLOGY AND MORPHOMETRY OF UMBILICAL CORD:
The umbilical cord or Funis is a cord like structure, which connects the fetus with the foetal
surface of placenta. Normally umbilical cord contains two arteries and one vein surrounded by
Wharton's jelly, all enclosed in a layer of amnion5,27,28. It is dull white and moist6. Aristotle
(384–322 BC) originally identified the umbilical cord as the connection between the mother and
unborn child29. The average length of umbilical cord at term is 50 – 60cm 30, with around 0.8 2cm breadth4,6 Most of the cords twists spirally31 with more left side twits/spirals than right
side.32 Remnant of the Umbilical vesicle/Yolk sac, its Vitelline duct (at placental end) and
Allantois (at fetal end) may be found in the umbilical cord5
Placenta and Umbilical cord plays an efficient role alongside maternal health condition and
genetics of the parents in controlling the growth and health of the developing fetus by holding
nutritive, respiratory, endocrine, immunological and excretory functions.
Any abnormality in the Placenta and Umbilical cord may lead to the impairment of the fetal
growth and health by disturbing the fore said functions. Because of the differential development,
Placenta and Umbilical cord are more prone to present different types of abnormalities such as
Placental shape aberrations, Placenta Extrachorialis, Placenta succenturiata, Marginal,
Velamentous, Furcate cords, cord vascular and Wharton’s jelly abnormalities33.
Etiology behind the development of these abnormalities is very unclear even though impaired
maternal health thought to be one of the causatives besides the hypothesis such as
“TROPOTROPHISM”34 and “CHORIONIC VASCULAR BRANCHING PATTERN”35.
TROPOTROPHISM refers to the phenomenon where placenta develops towards the richly
vascularized area of decidua/uterus while atrophying at poorly vascularized areas.34
Placental and cord abnormalities are found to be more prevalent among twin gestations and
pregnancies of In vitro fertilization (IVF).
Often delivering obstetrician is intrigued to know the outcome of various abnormalities of
Placenta and Umbilical cord which are routinely encountered in the labor room. If not all, many
of these abnormalities are found to be associated with various kinds of fetal impairments such as
Intra Uterine Growth Retardation (IUGR), Low Birth Weight (LBW), Low APGAR score and
congenital anomalies of Newborn like obstructive uropathies, Esophageal atresia, congenital hip
dislocations, asymmetrical head shape, spina bifida, Ventricular Septal Defect (VSD), Atrial
Septal Defect (ASD), limb anomalies, trisomy 21 so on. 33
Detection and management of congenital anomalies of newborn is a challenging and one of the
main goals of prenatal and newborn care. Congenital anomalies are also known as birth defects,
congenital disorders or congenital malformations. Congenital anomalies can be defined as
structural or functional anomalies, including metabolic disorders, which are present at the time of
birth and principle recognizable in early life. These anomalies can be classified in to Major
anomalies – which impair viability and require intervention, and Minor anomalies – which do
not impair viability and doesn’t require any intervention. However, these congenital anomalies
are causing 3.2 million Birth Defect related disabilities every year36 worldwide, accounts for 8 –
15% of perinatal deaths and 13 – 16% of neonatal deaths in India37. Different studies from India
shows the prevalence of congenital anomalies on average at 2.5% and this value rises to 4% if
the children are followed up to 5 years of their age and ranked third most frequent cause of
perenatal mortality in India.38 Neural tube defects, specifically Spina bifida are the most common
birth defect in north India. 38 The same is occurring 1 in 330 births in Tamil Nadu. Whereas
Kolkata holding the lowest prevalence. Musculo-skeletal and Cardio vascular system anomalies
are most common in the rest of the India i.e. in South India. 38 The reasons for this geographic
distribution are unknown.
Many Birth Defects can be prevented by controlling maternal infections, proper diet
supplements, vaccines and with efficient antenatal care. Even after all the above, Birth Defects
are accounting for a considerable number. Etiology of these congenital anomalies is very unclear
even after finding Low Socio Economic status, Genetics, Infections, Maternal Malnutrition,
Environmental factors, Maternal Health related problems and certain Drugs as causatives.8,36
However, these congenital anomalies have the great impact on better living of individuals,
families, health-care systems and also emotional disturbances in the society.
In 2010 the World Health Assembly adopted a resolution calling all Member States to promote
primary prevention and the health of children with congenital anomalies by: 36
1. Developing and strengthening registration and surveillance systems
2. Developing expertise and building capacity
3. Strengthening research and studies on etiology, diagnosis and prevention
4. Promoting international cooperation.
Hence this present hospital based study aimed to evaluate the relationship of Placental &
Umbilical cord abnormalities with anomalies of Newborn in uncomplicated singleton
pregnancies which will provide sufficient knowledge on whether we need to be attentive on fetal
anomalies when we find Placental and/or Umbilical cord abnormalities either by USG or at the
time of delivery and for further diagnosis & better intervention.
In the existing studies Placenta Previa, Abruptio placentae, Cord prolapse, Malignancies, Tumors
and pathology of Placenta & Umbilical cord also included under the heading of abnormalities39.
Lagging of confounders exclusion in most of the studies couldn’t establish the true relationship
between Placenta & Umbilical cord abnormalities and anomalies of Newborn. Hence we have
omitted the pathology of Placentas & Umbilical cord and excluded all the possible confounders
in the current study by adding only developmentally malformed conditions under the heading –
Abnormalities in order to achieve true relationship between Placenta & Umbilical cord
abnormalities and anomalies of Newborn.
1.7. AIM AND OBJECTIVES:
1.7.1. AIM:
To find out the association of Placental & Umbilical cord abnormalities with anomalies of
Newborn
1.7.2. Main Objective:
To determine the association of Placental and Umbilical cord abnormalities with
anomalies of newborn
1.7.3. Sub Objectives:
1. To find out the prevalence and pattern of Placental and Umbilical cord abnormalities
2. To evaluate the prevalence and pattern of Congenital anomalies among newborns within
the study
3. To evaluate the prevalence of Placental and Umbilical cord abnormalities in relation to
increasing Gravidity
4. To evaluate the prevalence of Congenital anomalies of baby in relation to increasing
Gravidity
5. To observe the distribution of Placental and Umbilical cord abnormalities with increasing
maternal age
6. To observe the distribution congenital anomalies of newborn with increasing maternal
age
7. To compare the mean of Patient (Mother), Placenta & Umbilical cord and Newborn
parameters between normal and abnormal sample(Placenta and Umbilical cord)
8. To compare the mean of Patient (Mother), Placenta & Umbilical cord and Newborn
parameters between normal and anomalous newborns
9. To observe the birth weight patterns in placental and umbilical cord abnormalities
10. To observe the gestational age patterns in placental and umbilical cord abnormalities