PLACENTAL PATHOLOGY IN SPONTANEOUS PRETERM BIRTHS
A Dissertation Submitted to
THE TAMILNADU DR. M.G.R MEDICALUNIVERSITY, CHENNAI
In Partial Fulfilment of the Regulations for the Award of the Degree of
M.S. (OBSTETRICS & GYNAECOLOGY) - BRANCH – II
GOVERNMENT STANLEY MEDICALCOLLEGECHENNAI
April –2016
BONAFIDE CERTIFICATE
This is to certify that this dissertation is a bonafide work of Dr. REVATHI.R.
on ‘‘PLACENTAL PATHOLOGY IN SPONTANEOUS PRETERM BIRTHS” during her M.S.,(Obstetrics and Gynaecology) course from July 2013 to July 2016 at the Government Stanley Medical College and Government Raja Sir Ramasamy Mudaliar Lying-in Hospital, Chennai.
Prof.DR. ISAAC CHRISTIAN MOSES, MD, FICP, FACP Prof. DR. P.VASANTHAMANI, MD, DGO
Dean, Professor / Head of the Department,
STANLEY MEDICAL COLLEGE & DEPT. OF OBSTETRICS &GYNAECOLOGY
GOVT.RSRMLYING IN HOSPITAL GOVT.RSRM LYING IN HOSPITAL,
Chennai–1 Stanley Medical College,
Chennai-1
Asso. Prof. DR. K.KALAIVANI MD, DGO,
DNB
Guide / Associate Professor,
Dept. of Obstetrics and Gynaecology,
GOVT.RSRM LYING IN HOSPITAL, Stanley Medical College
Chennai – 1
DECLARATION
I, Dr. REVATHI.R. Solemnly declare that the dissertation “PLACENTAL PATHOLOGY IN SPONTANEOUS PRETERM BIRTHS” is a bonafide work done by me at Government R.S.R.M Lying in Hospital, under supervision and guidance of Associate Prof. Dr. K.KALAIVANI, MD, DGO, DNB., in Department of Obstetrics and Gynaecology, Government Stanley Medical College, Chennai. This thesis is submitted to The Tamil Nadu Dr.
M.G.R. Medical University in partial fulfilment of the rules and regulations for the M.S. Degree examinations in Obstetrics and Gynaecology to be held in April 2016.
Asso. Prof. DR. K.KALAIVANI, MD, DGO, DNB Dr.REVATHI.R.
Guide / Associate Professor, M.S., P.G (Obstetrics and Gynaecology) Dept. of Obstetrics and Gynaecology, Dept. of Obstetrics and Gynaecology, GOVT.RSRM LYING IN HOSPITAL, GOVT.RSRM LYING IN HOSPITAL,
Stanley Medical College, Stanley Medical College,
Chennai – 1 Chennai – 1
ACKNOWLEDGEMENT
I gratefully acknowledge and sincerely thank Prof. DR.ISAAC CHRISTIAN MOSES, M.D, FICP, FACP DEAN, Stanley Medical College and Govt.RSRM Lying in Hospital, Chennai 600001 for permitting me to conduct the study and use the facilities of the Institution for my study.
I am extremely thankful to the Professor and Head of the Department, Prof.
DR. P.VASANTHAMANI, M.D., DGO, Govt. RSRM Lying in Hospital, Chennai, for her support in conducting this study.
I wish to express my deep sense of gratitude to my Guide and Associate Professor Dr. K.KALAIVANI, M.D, DGO, DNB., for her valuable guidance and supervision throughout my study.
My sincere thanks goes to Dr. MARY LILLY, MD (Patho)., Professor and Head of the Department of Pathology, Stanley Medical College for her personal interest and encouragement at every step of this study.
I am thankful to my Co-Guide DR. S.LAVANYA, M.D., O.G, for her valuable guidance and precise suggestions at every stage of this study.
I am thankful to the RMO and all UNIT CHIEFS for their support, advice and encouragement.
I am thankful to all Assistant Professors and Teachers for their guidance and help.
I thank my family members for their constant encouragement and moral support throughout this study.
Last, but not the least, I thank all my patients for their kind co-operation who made this study feasible.
TABLE OF CONTENTS
S.NO TITLE PAGE
NO.
I. INTRODUCTION 1
II. AIM & OBJECTIVES 3
III. REVIEW OF LITERATURE 4
IV. MATERIALS & METHODS 67
V. RESULTS & ANALYSIS 72
VI. DISCUSSION 90
VII. SUMMARY 96
VIII. CONCLUSION 98
IX. BIBLIOGRAPHY 99
X. ANNEXURES
a) PROFORMA b) ABBREVIATION c) IEC APPROVAL
d) PATIENT CONSENT FORM e) MASTER CHART
INTRODUCTION
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide and accounts for 75% of neonatal deaths and 50% of long-term morbidity, including respiratory disease and neurodevelopmental impairment1.
Preterm birth may be defined as birth between the age of viability and 37 completed weeks of gestation2.
The incidence of preterm birth range from 5% to 8% in most developed and developing countries, but it is still increasing worldwide3.
There is increasing evidence that infection may play a major role in the pathogenesis of spontaneous preterm birth.
Every year, an estimated 15 million babies are born preterm and this number is rising, of which more than 1 million died as a result of their prematurity (Blencowe et al.,2012)4.
The placenta is a very critical organ in explaining the pathogenesis of preterm birth. From this point of view, the placental pathology will be emphasized in two clinical categories of preterm birth: spontaneous preterm birth (SPB) and indicated preterm birth (IPB).
SPB can be classified into two separate clinical scenarios: 1) premature onset of labour (POL) accounting for 40-45% of cases of preterm births 2) preterm premature rupture of membranes (PPROM) seen in 25-30% of preterm births.
Clinical managements to reduce the incidence of preterm birth have not been yet very successful. They have largely been targeting treatments for individual risk factors and focused on answering clinical questions rather than pathogenic mechanisms such as placental ones.
The clinical importance of preterm birth reveals that the pathologist is and will be increasingly asked to examine placentas from preterm births in order to help explaining the pathogenesis of preterm birth.
In addition, the placental examinations from these cases may provide valuable clues for predicting which infants and why some infants may be at relatively greater risk for developing long term complications of preterm births.
AIM OF THE STUDY
To study gross and microscopic changes occurring in placenta of spontaneous preterm births in order to determine frequency of various lesions.
REVIEW OF LITERATURE
The normal placenta
According to Benirschke (2012)5, the term placenta weighs 470 g, is round to oval with a 22 cm diameter, and has a central thickness of 2.5 cm.
It is composed of a placental disc, extraplacental membranes, and three – vessel umbilical cord.
The maternal surface is the basal plate, which is divided by clefts into portions – termed cotyledons. Number of cotyledons varies from 10-38. These clefts mark the site of internal septa, which extend into the intervillous space.
The fetal surface is the chorionic plate, into which the umbilical cord inserts, typically in the center. Large fetal vessels that originate from the cord vessels then spread and branch across the chorionic plate before entering stem villi of the placenta parenchyma. In tracing these, fetal arteries almost invariably cross over veins. The chorionic plate and its vessels are covered by thin amnion, which can be easily peeled away from a postdelivery specimen.
Human placenta is described as hemochorio endothelial. Maternal blood bathes the syncytiotrophoblast and villi and is separated from the fetal blood by endothelium lining the fetal blood vessels.
Indications for placental examination Schindler-et al., Maternal:
Diabetes Mellitus
Pregnancy Induced Hypertension Premature rupture of membranes Preterm delivery
Postterm delivery Unexplained fever
Poor previous obstetrical history
History of drug abuse including cocaine.
Fetus/ newborn:
Stillborn Neonatal death Multiple gestation Prematurity
Intrauterine growth restriction
Congenital anomalies
Erythroblastosis fetalis Ominous fetal heart tracing Presence of meconium Apgar score <5 at 1 mt <7 at 5 mts.
Placenta and umbilical cord:
Infarcts
Abruptio placenta Vasaprevia
Placenta previa
Abnormal calcification
Abnormal appearance of placenta and cord
EVOLUTION OF KNOWLEDGE OF PLACENTA
Year Evolution
1.384-322 BC Aristotle- used the word chorion.
2.1537 Mossman- defined the placenta as fetal membrane that was in apposition and fused to the uterine wall.
3.1559 Realdus columbus used the word “The placenta”.
4.1564 Arantius – showed no direct vascular connection between the mother and the fetus.
5.17th century Placental barrier.
Embryologists
6.1750 William Hunter- Described placenta.
7.1821 John Hunter- Described decidua basalis.
8.1882 Langhan showed villi are covered with 2 layers of Cells –known as Langhan cells.
9. Dutchman Reinier de Graf (1641-73) depicted for the first time the Amnion.
10. Friedreich Schatz (1841-1920) described twin-twin transfusion and acardiac twin in monochorionic placenta.
11. Cynthia Kaplan and Geoffrey Altshuler studied about the various indications for placental examination.
12. Kurt Benirschke and Kaufmann have jointly written a complete treatise on placenta – Text book on placenta.
DEVELOPMENT OF THE PLACENTA
Human placental formation begins with the trophectoderm, which appears at the morula stage. It gives rise to a trophoblast cell layer encircling the blastocyst. From then until term, the trophoblast plays a critical part at the fetal- maternal interface.
Once the zona pellucida disappears, the cells of the trophoblasts stick to the uterine endometrium. This is known as “Implantation”. After erosion of the epithelium of the endometrial surface, the blastocyst sinks into the endometrium. It appears to have been flattened in the process of penetrating the uterine epithelium, the enlargement and multiplication of the trophoblastic cells in contact with the endometrium alone are responsible for the increase in size of the implanted blastocyst as compared with the free one. As the blastocyst contacts the endometrium, syncytiotrophoblast is differentiated from cytotrophoblast. Development of syncytiotrophoblast, undoubtedly is a major factor in the successful invasion of the endometrium.
As the invasion of the endometrium proceeds, maternal blood vessels are invaded and cytoplasmic vacuoles coalesce to form larger lacunae, that soon are filled with maternal blood. As the lacunae join, a complicated labyrinth is formed that is partitioned by solid trophoblastic columns. The trophoblast lined
labyrinthine channels form the intervillous space, and the solid cellular columns form the primary villous stalks.
The villi initially are located over the entire blastocyst surface. They later disappear exept over the most deeply implanted portion, which is destined to form the placenta.
Chorionic Villi
The functional elements of placenta are villi. Villi may be easily distinguished in the human placenta on about the 12th day after fertilisation.
Mesenchymal cords derived from extraembryonic mesoderm invade the solid trophoblast columns. These form secondary villi. Once angiogenesis begins in the mesenchymal cores, tertiary villi are formed.
Although maternal venous sinuses are tapped early in implantation, maternal arterial blood does not enter the intervillous space until around day 15.
By approximately the 17th day, however, fetal blood vessels are functional, and a placental circulation is established. The fetal-placental circulation is completed when the blood vessels of the embryo are connected with chorionic vessels.
Villi are covered by an outer layer of syncytium and an inner layer of cytotrophoblast, which are also known as Langhans cells. Cytotrophoblast proliferation at the villous tips produces the trophoblastic cell columns that form
anchoring villi. They are not invaded by fetal mesenchyme, and they are anchored to the decidua at the basal plate.
Thus, the base of the intervillous space faces the maternal side and consists of cytotrophoblasts from cell columns, the covering shell of syncytiotrophoblasts, and maternal decidua of the basal plate. The base of the chorionic plate forms the roof of the intervillous space. It consists of two layers of trophoblasts externally and fibrous mesoderm internally. The definitive chorionic plate is formed by 8 to 10 weeks as the amnionic and primary chorionic plate mesenchyme fuse together. This formation is accomplished by expansion of the amnionic sac, which also surrounds the connective stalk and
the allantois and joins these structures to form the umbilical cord (kaufmann, 1992) 6.
The blastocyst is burried in the decidua and is separated from the myometrium by the decidua basalis, and from the uterine epithelium by the decidua capsularis. The villi in contact with the decidua basalis proliferate to form the chorion frondosum-or leafy chorion- which is the fetal component of the placenta, where as those in contact with the decidua capsularis cease to grow and then degenerate
.
Until near the end of the third month, the chorion laeve is separated from the amnion by the exocoelomic cavity. Thereafter, they are in intimate contact to form an avascular amniochorion. The chorion laeve is generally more
translucent than the amnion and rarely exeeds 1 mm thickness. These two structures are important sites of molecular transfer and metabolic activity.
Moreover, they constitute an important paracrine arm of the fetal-maternal communication system.
Villus Branching:
Certain villi of the chorion frondosum extend from the chorionic plate to the decidua to serve as anchoring villi, most villi arborize and end freely within the intervillous space. As the placenta matures, the short, thick, early stem villi branch repeatedly, forming progressively finer subdivisions and greater numbers of increasingly smaller villi. Each of the main stem villi and their ramifications constitutes a placental lobule or cotyledon. Each lobule is supplied with a single truncal branch of the chorionic artery.
Placental septa:
The origin and exact composition of the placental septa continue to stimulate controversy. These appear to consist of decidual tissue in which trophoblastic elements are encased, and thus the septa very likely are of dual origin, that is, fetal and maternal
.
Placental growth:
In the first trimester, placental growth is more rapid than that of the fetus.
But by approximately 17 postmenstrual weeks, placental and fetal weights are approximately equal. By term, placental weight is approximately one sixth of fetal weight. The total number of placental lobes remains the same throughtout gestation, and individual lobes continue to grow- although less actively in the final weeks (Crawford, 1959)7. Although grossly visible lobes are commonly referred to as cotyledons, this is not accurate. Correctly used, lobules or cotyledons are the functional units supplied by each main stem villus.
Placental maturation:
As villi continue to branch and the terminal ramifications become more numerous and smaller, the volume and prominence of cytotrophoblasts decrease. As the syncytium thins, the fetal vessels become more prominent and lie closer to the surface. The villous stroma also exhibits changes as gestation progresses. In early pregnancy, the branching connective tissue cells are separated by an abundant loose intercellular matrix. Later, the villous stroma becomes denser, and the cells more spindly and more closely packed.
Another change in the stroma involves the infiltration of Hofbauer cells, which are fetal macrophages. These are nearly round with vesicular, often eccentric nuclei and very granular or vacuolated cytoplasm. Hofbauer cells are characterized histochemically by intracytoplasmic lipid and by phenotypic
markers specific for macrophages. They increase in numbers and maturational state throughout pregnancy and appear to be important mediators of protection at the maternal-fetal interface (Johnson, 2012)8. These macrophages are phagocytic, have an immunosuppressive phenotype, can produce various cytokines, and are capable of paracrine regulation of trophoblast functions (Cervar,1999; Vince,1996)9.
Some of the histological changes that accompany placental growth and maturation provide an increased efficiency of transport and exchange to meet increasing fetal metabolic requirements. Among these changes are decreased syncytiotrophoblast thickness, significantly reduced cytotrophoblast number, decreased stroma, and increased number of capillaries with close approximation to the syncytial surface.
By 16 weeks, the apparent continuity of the cytotrophoblast is lost. At term, villi may be focally reduced to a thin layer of syncytium covering minimal villous connective tissue in which thin-walled fetal capillaries abut the trophoblast and dominate the villi.
Histology of placenta:
Histological studies of the placenta reveal that it consists mostly of villous tissue and intervillous space plus fibrin. The villi consists of trophoblast, the stroma and the fetal vessels. In early pregnancy, the villous is plump, about 160 micron in diameter with its stroma and centrally placed fetal vessel. It has two
continuous layers of trophoblast, the inner cytotrophoblast and the outer syncytial layer.
But in the second half of pregnancy, after continued branching, the mean diameter of the villous gets reduced to 40 micron, the fetal vessels are larger and the trophoblastic layer, especially cytotrophoblastic layer markedly thinned out. Internal to the basement membrane which most likely plays an important role in the barrier function of the placenta.
The syncytium shows much regional variation the thickness varying from 2-10 micron. There is evidence of sub-specialisation in the syncytiotrophoblast. The relatively thin areas which overlie the fetal capillaries are probably the site of transfer and the thicker areas containing excessive endoplasmic reticulum are presumably the main site of placental synthesis.
Although there is formidable literature on the structure of the placenta and its correlation with its functions, these are mostly quantitative studies.
Planimetry has been the most popular method for such a study, however it has limitations. Aherne and Dunhill (1966) employed a morphometric Technique based on the point counting technique. Mathur and Das Gupta (1974) have further simplified the method wherein by the analysis of the placenta the volume proportions of the various components can be established.
Placental examination:
All placentas should be considered potentially infectious and should be handled accordingly. Gross examination can be performed when the specimen is received fresh, or it may be performed 1 to 2 days after immersion of the placenta in formalin. We prefer gross examination of fresh placentas with tissue samples fixed in formalin overnight before trimming.
Placentas from stillborn fetuses should not be fixed in formalin because placental fibroblasts may be needed for cytogenetic or other metabolic analyses.
Microbial cultures should be performed in the labor and delivery suite, and not in the pathology laboratory hours after birth.
Placentas must be weighed and measured. Different approaches to placental weighing (removing cord, removing extraplacental membranes, or draining maternal intervillous blood) may be taken, but one method must be used consistently and documented in the pathology report.
The fetoplacental weight ratio increases throughout gestation, and abnormally high or low ratios are likely indicators of fetoplacental pathology.
The placental parenchyma is grossly examined by slicing perpendicular to the maternal surface and chorionic plate at approximately 1 cm intervals, leaving the chorionic plate intact. Each surface of each slice is examined for
obvious lesions (e.g., infarct or intervillous thrombi) or subtle lesions, such as increased villous granularity (e.g., villous swelling or chronic villitis).
Villous tissue should be uniform in color; dark and pale areas may mark microscopic pathology. Examination of decidual vasculature is important and often overlooked in placental evaluation. Especially in the fixed placenta, decidual spiral vessels can be seen as small irregularities or an S shape on the maternal surface.
Several thin slices of the basal plate may be placed in one cassette and generally yield at least one decidual vessel for examination. A minimum of two samples of villous parenchyma from grossly normal villi, plus sections from any lesions, will permit identification of most lesions.
ABNORMALITIES OF THE PLACENTA
Abnormal Feto-Placental Weight Ratio:
Ratio should be 4 at 24 wks and increases to 7 at term (Driscoll and Langston)
Ratio is reduced in hydrops, diabetes.
Ratio is increased in placental insufficiency.
Shape and Size
Bilobate placenta
Placentas may infrequently form as separate, nearly equally sized discs.
This is a bilobate placenta, but is also known as bipartite placenta or placenta duplex. In these, the cord inserts between the two placental lobes- either into a connecting chorionic bridge or into intervening membranes.
Multilobate placenta
A placenta containing three or more equally sized lobes is rare and termed multilobate.
Succenturiate lobe
More frequently, one or more small accessory lobes - succenturiate lobes - may develop in the membranes at a distance from the main placenta.
These lobes have vessels that course through the membranes. If these vessels overlie the cervix to create a vasa previa, they can cause dangerous fetal hemorrhage if torn. An accessory lobe may also be retained in the uterus after delivery and cause postpartum uterine atony and hemorrhage.
Placenta membranacea
All or nearly all of the membranes are covered with villi. This placentation may occasionally give rise to serious hemorrhage because of associated placenta previa or accreta (Greenberg, 1991)10.
A ring - shaped placenta may be a variant of placenta membranacea. The placenta is annular, and a partial or complete ring of placental tissue is present.
These abnormalities appear to be associated with a greater likelihood of antepartum and postpartum bleeding and fetal-growth restriction (Faye- Petersen, 2006)11.
Placenta fenestrata
The central portion of a placental disc is missing. In some instances there is an actual hole in the placenta, but more often, the defect involves only villous
tissue, and the chorionic plate remains intact. Clinically, it may erroneously prompt a search for a retained placental cotyledon.
Placentomegaly
The normal placenta increases its thickness at a rate of approximately 1 mm per week. Although not measured as a component of routine sonographic evaluation, this thickness typically does not exceed 40mm (Hoddick,1985)12. Placentomegaly defines those thicker than 40 mm and commonly results from striking villous enlargement. It occur in
1) Maternal diabetes 2) Severe maternal anemia 3) Fetal hydrops
4) Infection (Syphilis, Toxoplasmosis,or Cytomegalovirus) Placentomegaly may result from collections of blood or fibrin.
1) Massive perivillous fibrin deposition 2) Intervillous or subchorionic thrombosis 3) Large retroplacental hematomas.
Extrachorial Placentation
The chorionic plate normally extends to the periphery of the placenta and has a diameter similar to that of the basal plate. With extrachorial placentation,
however, the chorionic plate fails to extend to this periphery and leads to a chorionic plate that is smaller than the basal plate.
1) Circummarginate placenta: fibrin and old hemorrhage lie between the placenta and the overlying amniochorion.
2) Circumvallate placenta: the peripheral chorion is a thickened, opaque, grey-white circular ridge composed of a double fold of amnion and chorion. Sonographically, the double fold can be seen as a thick, linear band of echoes extending from one placental edge to the other. On cross section, it appears as a “shelf”.
Clinically, most pregnancies with an extrachorial placenta have normal outcomes. In observational studies in which the diagnosis was made by placental examination, circumvallate placenta was associated with increased risk for antepartum bleeding and preterm birth (Lademacher, 1981; Suzuki, 2008a)13.
Placenta Accreta, Increta And Percreta
In these types villous tissue is seen adjacent to or within the myometrium without intervening decidua, causing poor placental separation and bleeding.
They are often identified in hysterectomy specimens (Benirschke and Kaufmann 1990), (Mac pherson & Szulman 1990).
Maternal Uteroplacental Vasculature
Infarction
Chorionic villi themselves receive oxygen solely from maternal circulation supplied to the intervillous space. Any uteroplacental disease that diminishes or obstructs this supply can result in infarction of individual villous.
These are common lesion in mature placentas and are benign in limited numbers. If they are numerous, however, placental insufficiency can develop.
When they are thick, centrally located, and randomly distributed, they may be associated with preeclampsia or lupus anticoagulant.
Gross lesions progress from dark red firm, granular areas to hard white areas. Central lesions are more significant as small marginal infarcts occur incidentally (Macpherson & Szulman et al.,).
Intervillous Thrombus
These is a collection of coagulated maternal blood normally found in the intervillous space mixed with fetal blood from a break in a villous. Grossly, these round or oval collections vary in size upto several centimeters. They appear red if recent or white-yellow if older, and they develop at any placental depth.
Intervillous thrombi are common and typically not associated with adverse fetal sequelae. Because there is potential for a communication between
maternal and fetal circulations, they can cause elevated maternal serum alpha- fetoprotein levels (Salafia, 1988)14.
Subchorionic Fibrin Deposition
These are caused by slowing of maternal blood flow within the intervillous space with subsequent fibrin deposition. Blood stasis specifically occurs in the subchorionic area, and lesions that develop are commonly seen as white or yellow firm plaques on the fetal surface.
Perivillous Fibrin Deposition
Maternal blood flow stasis around an individual villous results in fibrin deposition and can lead to diminished villous oxygenation and syncytiotrophoblastic necrosis. Within limits, these grossly visible small yellow-white placental nodules are considered to be normal placental aging.
Maternal Floor Infarction
This extreme variant of perivillous fibrinoid deposition is a dense fibrinoid layer within the placental basal plate and is erroneously termed an infarction. The lesion has a thick, white, firm, corrugated surface that impedes normal maternal blood flow into the intervillous space. These lesions are
associated with miscarriage, fetal-growth restriction, preterm delivery, and stillbirths (Andres, 1990; Mandsager, 1994)15.
These adverse outcomes occasionally recur in subsequent pregnancies.
Their etiopathogenesis is not well defined, but some cases are associated with lupus anticoagulant (Sebire, 2002, 2003)16. Although unsettled, other cases may be associated with maternal thrombophilias (Gogia, 2008; Katz, 2002)17.
Hematoma
The maternal-placental-fetal unit can develop a number of hematoma types as
1) Retroplacental hematoma - between the placenta and its adjacent decidua
2) Marginal hematoma - between the chorion and decidua at the placental periphery - known clinically as subchorionic hemorrhage
3) Subchorial thrombosis - also known as Breus mole - along the roof of the intervillous space and beneath the chorionic plate
4) Subamnionic hematoma - these are of fetal vessel origin and found beneath the amnion but above the chorionic plate.
Extensive retroplacental, marginal, and subchorial collections have been associated with higher rates of miscarriage, placental abruption, fetal-growth
restriction, preterm delivery, and adherent placenta (Ball, 1996; Madu, 2006;
Nagy, 2003)18.
Fetal Placental Vasculature
Fetal thrombotic vasculopathy
Distal to the obstruction, affected portions of the villous become infarcted and nonfunctional. Thrombi in limited numbers are mormally found in mature placentas, but these may be clinically significant if many villi become infarcted.
Subamnionic Hematoma
They most often are acute events during third-stage labor when cord traction ruptures a vessel near the cord insertion. Chronic lesions may cause fetomaternal hemorrhage or fetal-growth restriction (Deans, 1998)19.
Doppler interrogation will show absence of internal blood flow that permits differentiation of hematomas from other placental masses.
Placental Calcification
Calcium salts may be deposited throughout the placenta, but are most common on the basal plate. Calcification accrues with advancing gestation and is associated with nulliparity, smoking, higher socioeconomic status, and increasing maternal serum calcium levels (Fox, 2007)20.
Calcium can easily be seen sonographically, and Grannum and co- workers (1979)21 created a grading scale from 0 to 3 that reflected increasing calcification with increasing numerical grade. However such grading criteria have not been found useful to predict neonatal outcome (Hill, 1983; McKenna, 2005; Montan, 1986; Sau, 2004)22.
Abnormalities Of The Cord
Length
Most umbilical cords are 40 to 70 cm long, and very few measure < 32 cm or >100 cm. Cord length is influenced positively by both amniotic fluid volume and fetal mobility. Short cords may be associated with fetal-growth restriction, congenital malformations, intrapartum distress, and a twofold risk of death (Berg, 1995; Krakowiak, 2004)23. Excessively long cords are more likely to be linked with cord entanglement or prolapse and with fetal anomalies, acidemia, and demise.
Coiling
Usually the umbilical vesssels spiral through the cord in a sinistral, that is, left-twisting direction (Lacro, 1987)24. The number of complete coils per centimeter of cord length has been termed the umbilical coiling index (Strong,
1994)25. A normal antepartum index derived sonographically is 0.4, and this contrasts with a normal value of 0.2 derived postpartum by actual measurement (Sebire, 2007)26.
Clinically, hypocoiling has been linked with fetal demise. Whereas hypercoiling has been associated with fetal-growth restriction and intrapartum fetal acidosis. Both have been reported in the setting of trisomic fetuses and with single umbilical artery (de Laat, 2006, 2007; Predanic, 2005b)27.
Vessel Number
The most common aberration is that of a single umbilical artery, with a cited incidence of 0.63 percent in liveborn neonates, 1.92 percent with perinatal deaths, and 3 percent in twins (Heifetz, 1984) 28.
Fetuses with major malformations frequently have a single umbilical atery, and when seen in an anomalous fetus, the aneuploidy risk is greatly increased, amniocentesis is recommended (Dagklis, 2010; Lubusky, 2007)29. The most frequent anomalies described are cardiovascular and genitourinary.
Insertion
The cord normally inserts centrally into the placental disc, but eccentric, marginal, or velamentous insertions are variants.
Marginal insertion is a common variant - referred to as a battledore placenta - in which the cord anchors at the placental margin.
Velamentous insertion is a variant of considerable clinical importance.
The umbilical vessels characteristically spread within the membranes at a distance from the placental margin, which they reach surrounded only by a fold of amnion, vessels are vulnerable to compression which may lead to fetal hypoperfusion and acidemia, incidence is approximately 1 percent.
Furcate insertion the topographic site of cord connection onto the placental disc is central, but umbilical vessels lose their protective Wharton jelly shortly before they insert. As a result, they are covered only by an amnion sheath and prone to compression, twisting, and thrombosis.
Knots
True knots are caused by fetal movements and are seen in approximately 1 percent of births. They are especially common and dangerous in monoamnionic twins. When true knots are associated with singleton fetuses, the stillbirth risk is increased four to tenfold (Airas, 2002;Sornes, 2000)30.
False knots are of no clinical significance and appear as knobs protruding from the cord surface. These are focal redundancies of a vessel or Wharton jelly.
Cord Stricture
Focal narrowing of its diameter that usually develops near the fetal cord insertion (Peng, 2006)31. Characteristic pathological features of strictures are absence of Wharton jelly and stenosis or obliteration of cord vessels at the narrow segment (Sun, 1995)32. In most instances, the fetus is stillborn (French, 2005)33.
PRETERM
Definition
Preterm labour is defined by the WHO as the onset of labour prior to the completion of 37 weeks of gestation in a pregnancy beyond 20 weeks of gestation.
Preterm labour is defined as the onset of regular, painful, frequent, uterine contractions causing progressive effacement and dilatation of cervix occurring before 37 completed weeks from the first day of last menstrual period (Anderson 1977)34.
Threshold Of Viability
Defined as gestational age at which 50% of infants survive.
Births before 26 weeks, especially those weighing less than 750 g are at the current threshold of viability and these preterm infants pose a variety of complex medical, social and ethical considerations (ACOG, 2002, 2008).
According to current guidelines of American Academy of Pediatrics (Braner, coworkers 2008) it is considered appropriate not to initiate resuscitation for infants younger than 23 weeks or birth weight less than 400 g these infants are described as fragile and vulnerable because of their immature organ systems (Vohr and Allen, 2005).
Problems Of Preterm Birth
Apart from survival, appreciable physical and intellectual compromise afflicts preterm infants. Eichenwald and Stark (2008)35 studied extensively on short term and long term complications of preterm infants.
Short Term Problems
Apnea of prematurity
Respiratory Distress Syndrome Bronchopulmonary dysplasia Hyperbilirubinemia
Immune deficiency Necrotising enterocolitis Retinopathy of prematurity Intraventricular haemorrhage Periventricular leukomalacia Hypotension
Anemia of prematurity Patent Ductus Arteriosus
Long Term Problems
Failure to thrive
Reactive Airway Disease Asthma
Cholestasis
Short bowel syndrome Bronchiolitis
Respiratory syncytial virus infections Cerebral palsy
Hearing loss
Neuro developmental delay Blindness
Myopia
Retinal detachment Pulmonary Hypertension Impaired glucose regulation Hypertension in adulthood
Preterm birth classified as
1) Extremely preterm < 28 wks (5%) 2) Very preterm 28 - <32 wks (15%) 3) Moderate preterm 32 - <34 wks (20%)
4) Late preterm 34 -< 37 completed wks (60-70%).
Epidemiology
1)Race
Goldenberg and colleagues 2008 reported higher risk of preterm birth in Black, African-American and Afrocaribbean.
Black women have increased risk of recurrent preterm birth (Kistka and Colleagues, 2007). African American women have an increased rate of preterm deliveries when compared to other races as stated by the Center for Health statistics.
2)Age
Preterm labour is more common in extremes of age, Lumley JM et al 199336 reported high incidence of preterm delivery in women under 17 years and over 35 years.
3)Weight
Poor ion, pre pregnancy weight and weight gain during pregnancy play a important role in causing preterm labour. Hickly and colleagues 2005 have low maternal prenatal gain is specifically associated with preterm birth.
4)Stature
Short statured women have more tendencies to produce small babies.
5)Socioeconomic Status
Women from lower socio economic status tends to be less educated and would not have satisfactory general, prenatal and antenatal care (Goffinet F 2005).
6)Addictions
Women who smoke cigarettes or who abuse cocaine are at increased risk of preterm labour (Bens 2004). Cigarette smoking has resulted in the increased incidence of preterm birth under 34 weeks gestation especially those who smoke more than 20 cigarettes per day.
Shah & Bracken reported that smoking was an important etiological factor in the causation of preterm delivery. Boer et al 1993, Volpe studied the increased incidence of preterm birth in women addicted to opioids.
However there are not enough studies relating the risk of preterm labour with the consumption of alcohol.
7)Occupational hazards
Those involved in manual work are more prone for preterm labour.
Predisposing Factors
Stress
Psychological factors such as depression, anxiety and chronic stress have been reported in association with preterm birth (Copper; 1996, Li 2008, Littleton 2007). Careers which involve considerable physical work and psychological stress are associated with increased preterm births (Papiernik and Kaninski 1994)37. Prolonged standing decreases the uteroplacental flow and increases the frequency of large placental infarcts causing growth retardation.
Preterm birth is increased in women living alone, and those who are subjected to physical abuse. Henrikson et al 1995 reported that heavy vigorous exercise in the third trimester increased the risk of preterm delivery while regular and moderate exercise were actually showing a reduced risk.
Coitus
Yost NP et al in 200738 reported that coitus was not found to be associated but increasing numbers of sexual partners increased the risk of recurrent preterm delivery.
Reproductive History
a)Previous preterm birth
Spong, 2007 concluded prior preterm delivery to be a major risk factor for preterm labour.
History of one previous preterm birth is associated with a recurrence risk of 16-41% (Williams 22nd edition)39. Risk increases with the number of preterm birth and decreases with the number of term deliveries. There is an increase in the risk of preterm delivery whenever there is a history of previous preterm delivery. This risk is on a increasing trend whenever the number of prior preterm births increases (Hoffman 1981). When compared to women who have got a previous term delivery, women having a prior preterm delivery have threefold times the risk of recurrence. This risk becomes eight fold whenever there is a history of two preterm deliveries. Some of the integral factors that may contribute to the recurrence are the cervical length and inherent biological property of the cervix.
b)Previous abortion
There is increase in the preterm deliveries in women who experienced one or more second trimester abortions.
c)Cervical incompetence
d)Uterine anomalies
Interval between pregnancies
Intervals shorter than 18 months and longer than 59 months associated with increased risk for preterm & small for gestational age infants (Conde – Agudelo 2006).
A significant increase in preterm births was observed when the interval between birth and LMP of next pregnancy was less than 3 months.
A previous occurrence of preterm birth before 34 weeks may increase the risk of recurrence (Krymko et al 2004).
Fetal Gender
Fetal gender influencing the rate of preterm delivery is fetal sex, with preponderance of males delivering preterm.
Multiple Pregnancies
Preterm delivery occurs in 43.6 percent of all twin deliveries compared to 5.6 percent in singleton pregnancies (Patel et al 1983).
Monochorionicity has a greater association with preterm labour.
REASONS FOR PRETERM DELIVERY
THE FOUR MAIN DIRECT REASONS FOR PRETERM BIRTHS
1. Spontaneous unexplained preterm labour with intact membranes 2. Idiopathic preterm premature rupture of membranes (PPROM) 3. Delivery for maternal or fetal indications and
4. Twins and higher-order multifetal births.
Of all preterm births, 30 to 35 percent are indicated, 40 to 45 percent are due to spontaneous preterm labour, and 30 to 35 percent follow preterm membrane rupture (Goldenberg, 2008)1.
Preterm births that follow spontaneous labour and PPROM are together designated spontaneous preterm births.
Reasons for preterm birth have multiple, often interacting, antecedents and contributing factors. This complexity has greatly confounded efforts to prevent and manage this complication. This is particularly true for preterm ruptured membranes and spontaneous preterm labor, which together lead to 70 to 80 percent of preterm births.
Analogous to other complex disease processes, multiple coexistent genetic alterations and environment may lead to preterm births (Esplin,2005;
Ward, 2008)40.
They are polymorphisms in genes associated with inflammation and infection and in those associated with collagen turnover (Velez, 2008)41. Inherited mutations in genes regulating collagen assembly may predispose individuals to cervical insufficiency or prematurely ruptured membranes (Anum, 2009; Wang, 2006; Warren.2007)42.
The understanding of preterm birth as a syndrome with multiple etiologies and diverse mechanisms resulting in premature activation of the common pathway of parturition.
Common Pathway of Parturition
The common pathway of parturition has three components:
1. Cervical ripening,
2. Activation of the myometrium, and 3. Activation of the fetal membranes.
In normal term birth these components are activated simultaneously. In preterm birth it is not unusual to have predominant activation of one or two of the components, resulting in variations in symptoms and signs.
Premature ripening of the cervix is the predominant feature in women with incompetent cervix, premature activation of the membranes is the key event in women with preterm rupture of membranes, and premature activation
of the myometrium is the cardinal feature in women with preterm labor with intact membranes.
Cervical Ripening
Cervical ripening consists of the transformation of the cervix from a structure that is long, hard, and rigid to a tissue that is soft and easily distendable.
The cervix is made up of smooth muscle fibers and fibrous connective tissue. The connective tissue is the predominant element and is formed by fibroblasts and an extracellular matrix or ground substance. The muscle fibers represent less than 10% of the organ. The extracellular matrix is made up of substances produced by the fibroblast, mainly collagen, glycosaminoglycans, and glycoproteins.
Before pregnancy all the elements comprising the cervix, particularly the collagen fibers, are tightly aggregated giving to the organ its peculiar hard consistency. At the end of the pregnancy, before and during the early stages of labor, collagenase activity in the extracellular matrix increases and there is increased fibroblastic production of hyaluronic acid, a hydrophilic molecule. As a consequence of these changes the collagen content decreases and the water content of the cervix increases.
The role of sex steroid hormones is evidenced by the administration of progesterone antagonists, such as RU486, a powerful inducer of cervical ripening in humans and in other animal species. Also, there is laboratory evidence demonstrating the ability of estradiol to stimulate collagen degradation.
Prostaglandins are powerful pharmacologic inductors of cervical ripening and may play a central role in the physiology of the process. Prostaglandins exert their effects on the cervix by modulating fibroblast activity and inducing the production of hyaluronic acid with mobilization of water into the extracellular matrix and by promoting changes in the glycoprotein composition of the cervix.
Prostaglandins also have the ability to mobilize leukocytes and macrophages into the extracellular matrix that will be responsible for the production of enzymes that will cause changes in the cervical ground substance.
Activation Of The Fetal Membranes
In term and preterm births, there are a series of biochemical reactions that cause the separation of the chorioamnion from the decidua in the lower uterine segment and culminate with rupture of the membranes.
Most of the tensile strength of the fetal membranes depends on the concentration and cross-linkage of collagen and the presence of elastin, laminin, and fetal fibronectin in the amnion. Fibronectin is the cement for the fusion of the chorioamniotic membranes with the decidua, a process that is completed after 22 weeks of gestation.
One of the most important features during membrane activation is the loss of tensile strength of the amnion due to alterations in collagen concentration and function. The degradation of collagen is the result of the sequential and concerted activity of several matrix metalloproteinases. The increased activity of matrix metalloproteinases occurs simultaneously with a decrease in the activity of specific tissue inhibitors of those metalloproteinases.
The trigger of membrane activation is not known. There are several substances that may be responsible for this process but cytokines and prostaglandins are thought to be the best candidates.
Activation Of The Myometrium
During normal pregnancy the uterus is under the effect of a series of inhibitors of uterine contractions, among them progesterone, relaxin, nitric oxide, and prostacyclin. At the end of the pregnancy the quiescent effect of these substances begins to disappear and the uterus becomes responsive to
estrogen and increases the synthesis of gap junctions, oxytocin and prostaglandins receptors, and calcium channels, becoming prepared to respond to the effect of uterotonic substances such as oxytocin and prostaglandins
(Arias et al.,1999)43.
CONDITIONS CAUSING PREMATURE ACTIVATION OF THE COMMON PATHWAY OF PARTURITION
The common pathway of parturition can be activated by multiple agents.
The most clearly identified is chorioamniotic infection. Other causes are maternal or fetal stress, placental insufficiency, and bleeding in the choriodecidual interface.
Etiology Of Preterm Labour
Infection
Infection is the most clearly recognized and more widely studied cause of preterm birth. Infection is responsible for between 20 and 40% of all cases of preterm birth.
Ledger and Bobitt44 first suggested that unrecognized chorio amnionitis may be causally related to preterm labour. They documented positive cultures via transcervical needle aspiration or intrauterine catheters. As many as 50% of spontaneous preterm births may be associated with infection (Klein LL, Gibbs
RS 2005)45, the common pathway of intrauterine infection is the ascending route.
Changes in the antibacterial properties of the cervical mucous (Hein et al.,2001)46 may also play an important role in facilitating ascending infection.
Colonization of genital tract with Group B Streptococcus infection is associated with preterm labour (Bobitt and Lamont et al). Very often Group B Streptococcus has been related to the causation of preterm labour and preterm rupture of membranes. The current recommendation is to screen high risk women and to treat with antibiotics.
Colonization with Chlamydia trachomatis (Martin et al, Harrison et al)47 Mycoplasma hominis and ureaplasma urealyticum (Klein et al 2008) is associated with preterm labour.
Asymptomatic bacterial vaginosis and trichomonas vaginalis infection confers modest risk of preterm labour.
Edward et al, reported higher incidence of positive gonorrhea culture in preterm labour48.
Presence of infection in the genital tract either as a result of overgrowth of normal bacterial flora or abnormal vaginal flora at 26-32 weeks gestation has been shown to be associated with preterm labour (Kiss et al 2004).
23 percent of neonates born between 23 and 32 weeks have positive umbilical blood cultures for genital mycoplasmas (Goldenberg and collegues 2008 a).
Hillier 1995; Kurki 1992, Leitich 2003 proved association of bacterial vaginosis with spontaneous abortion, preterm labour, preterm rupture of membranes and chorioamnionitis.
The ability to mount a severe inflammatory reaction and develop preterm labor is genetically determined and it has been shown that women with bacterial vaginosis and polymorphisms in the promoter region of the tumor necrosis factor (TNF) gene are at higher risk of developing preterm labor than women with bacterial vaginosis and intact TNF gene (Macones et al., 2004)49. It is apparent that the host response is as important as the properties of the infecting organism in the production of preterm labor of infectious/inflammatory origin.
Infection may be overt or subclinical.
Acute Chorioamnionitis
Acute chorioamnionitis occurs in 0.5-1.0% of all pregnancies.
Diagnosis of chorioamnionitis (Gibbs et al., 1982)50 Fever (>37.8₀ C or 100.4 F) and two or more of :
1. Maternal pulse > 100 bpm
2. Uterine tenderness
3. Fetal heart rate > 160 bpm 4. Foul smelling vaginal discharge 5. Leukocytosis > 15,000
6. C-reactive protein > 2.7 mg/dl No other site of infection.
Women with sings and symptoms of overt acute chorioamnionitis have reached a final stage in the progression of their uterine infection.
The bacteria most frequently found in the amniotic fluid and the placenta of women with chorioamnionitis are Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, Fusobacterium spp., Bacteroides bivius, group B streptococcus, peptostreptococci, Escherichia coli, and enterococci (Gibbs et al., 1988)51.
In majority of cases the infection is polymicrobial and the cultures identify more than one type of bacteria. The mycoplasmas (U. Urealyticum and M. Hominis) are the bacteria most frequently isolated.
Some of them are more virulent than others and group B streptococcus, E.
Coli, and Enterobacteriaceae which are present in only 20% of cases of chorioamnionitis are responsible for 67% of the cases of maternal and fetal bacteremia and clinical sepsis.
Chorioamniotic infection by anaerobic bacteria usually does not cause systemic maternal signs or symptoms of sepsis and the neonates, although foul smelling, rarely develop significant septic complications.
Acute chorioamniotic infection may be recognized in practically 100% of the cases by histologic examination of the placenta. The opposite is not true and histologic evidence of infection is frequently found in women without sings or symptoms of infection.
Safarti et al (1968)52 found histologic evidence of infection in 27% of placentas and membranes obtained after preterm delivery.
Arias et al., (1993)53 histologic chorioamnionitis in approximately 40%
of women who had preterm delivery as a result of preterm labor.
Hillier et al., (1988)54 isolated microorganisms from the area between the chorion and the amnion in 61% of women who delivered before 37 weeks.
Zhang et al., (1985)55 were able to culture pathogenic organisms in 44%
of placentas with varied degrees of histologic chorioamnionitis.
Romero et al., (1992)56 studied the correlation between histologic chorioamnionitis and amniotic fluid cultures and found a prevalence of positive cultures of 38%.
Acute inflammation of the chorionic plate and the umbilical cord were the most sensitive indicators of the presence of bacteria in the amniotic fluid.
Extrauterine Infection:
Robertson et al (2008) reported high prematurity rate with asymptomatic bacteruria.
Systemic illness like pneumonia, pyelonephritis, and periodontal disease is associated with preterm labour (Xiong X 2006)57.
Vergnes and Sixoci (2007) reported a strong association between periodontal disease and preterm birth. Golpfert (2005) in his study found an increased incidence of preterm labour in patients having periodontal infection.
Placental
Abnormal placentation Anatomical abnormalities Placenta praevia
Abruptio placenta Uterine
1. Congenital abnormalities 1- 3% especially septate and bicornuate uterus 2. Incompetent cervix and cervical anatomical abnormalities
3. Overdistension of uterus
Michalas 1991; Raga 1997 reported any structural anomaly that alters the uterine cavity is likely to cause miscarriage, preterm labour or malpresentation of fetus.
Genetic
Genetic factors have a pivotal role in the occurence of preterm delivery.
Gibson, 2007; Hampton, 2006; Li 2004; Macones, 2004 reported literature on genetic variants causing preterm labour.
Fetal
Dolan and colleagues (2007) reported that birth defects were associated with preterm birth and low birth weight.
Preterm Labour of Unknown Origin
About 20-30% of preterm deliveries occur without any demonstrable etiology.
Clinicopathological Scenarios
The placenta is a very critical organ in explaining the pathogenesis of preterm birth. From this point of view, the placental pathology will be emphasized in two clinical categories of preterm birth: spontaneous preterm birth (SPB) and indicated preterm birth (IPB).
SPB can be classified into two separate clinical scenarios: (i) premature onset of labor (POL) defined as regular contractions with accompanying cervical change and with intact membranes, and accounting for 40-45% of cases of preterm births or (ii) preterm premature rupture of membranes (PPROM) defined as spontaneous rupture of membranes at less than 37 weeks of gestation and at least one hour before the onset of contractions, and seen in 25-30% of preterm births.
IPB is defined when the labor is induced or caesarean section is performed for maternal or fetal reasons. It has a high frequency of associated maternal vascular changes in the placenta, similar to those described for hypertension or diabetes, as well as placental abruptions.
Placental pathology in spontaneous preterm birth
POL and PPROM are likely to be the pathological results of abnormal microbial and non-microbial activation of imbalances among these normally orchestrated components and mediators.
POL may result from (i) acute chorioamnionitis, (ii) uteroplacental underperfusion, (iii) uterine fundal and cervical abnormalities or fetal anomalies. However, non-microbial etiologies appear more prevalent. Acute uteroplacental underperfusion may be due to a retroplacental hemorrhage (placental abruption). Chronic uteroplacental underperfusion is seen in maternal chronic hypertension or diabetes.
The placenta in PPROM often shows evidence of ascending infection (amniotic fluid infection sequence) or vasculopathic problems (hemorrhage or thrombi). Amniotic fluid infection has clinical significance for the neonate beyond just causing preterm birth. The fetus may reveal an inflammatory response associated with cytokine release that can cause damage to the developing brain and lungs. This inflammatory response is evident microscopically by neutrophils migrating from the fetal vasculature of the umbilical cord or chorionic plate towards the infected amniotic fluid.
Placental pathology of intrauterine infections and inflammatory processes in SPB
Intrauterine infection is clinically a common etiology of SPB following POL and PPROM. It is most prevalent and severe in early preterm infant.
Bacterial infection is very common and predisposes to preterm delivery.
Microbiological studies of amniotic fluid have shown that overall rates of infection in SPB are 25-40%. Approximately 32.5% of women with POL and over 75% with PPROM have positive amniotic fluid cultures.
Acute chorioamnionitis
Gross examination of the placenta reveals membranous edema, clouding, or yellowish-green discoloration and congestive placentomegaly. The cord may show punctate yellowish lesions characteristic of candidiasis, although minute whitish lesions may rarely be seen in severe bacterial infections.
The inflammatory response to ascending infection consists of an acute inflammatory neutrophilic infiltrate composed of maternal neutrophils from the intervillous circulation and small venules in the membranous decidua. In many cases this maternal response is supplemented by a fetal response composed of neutrophils emanating from large vessels of the umbilical cord and chorionic plate. Therefore, acute chorioamnionitis should be separated into two
components, the maternal and fetal inflammatory responses. Each of these in turn should be characterized in terms of its spatiotemporal progression (stage) and severity (grade) 58.
Maternal inflammatory response begins in the decidua of the external membranes as patchy deciduitis and progresses to margination of neutrophils along the deciduochorionic junction, and additionally infiltration of the subchorionic maternal space. Therefore, the stages of maternal response are:
Stage 1 (early chorioamnionitis or acute subchorionitis): Neutrophils are restricted to subchorionic fibrin and the membranous decidual-chorionic interface.
Stage 2 (acute chorioamnionitis): Neutrophils are located at in chorion and amnion.
Stage 3 (necrotizing chorioamnionitis): There are signs of amnion necrosis including karyorhexis of neutrophils, desquamation of amnionic epithelial cells, and bandlike eosinophilia of the amnionic basement membrane.
Severe maternal inflammatory responses are characterized by large accumulations of neutrophils (microabcesses) under the chorion. Stage 1 response is generally clinically silent. Stages 2 and 3 are associated with increased risk of neonatal morbidity and mortality. Stage 2 is most common in preterm births, but especially in the earliest periods of gestation 59.
The fetal inflammatory response to infection is manifested by migration of neutrophils from chorionic plate vessels and from the umbilical cord vessels.
The staging of fetal response is;
Stage 1: Neutrophils are located at in chorionic vessels (chorionic vasculitis) and/or umbilical vein (umbilical phlebitis).
Stage 2: There is umbilical arterial infiltration of neutrophils (umbilical arteritis) or trivasculitis.
Stage 3: There are neutrophils and neutrophilic debris forming arcs around umbilical vessels in the Wharton’s jelly (necrotizing funisitis).
Fetal grade 2, in particular, is strongly correlated with the presence of high fetal levels of circulating proinflammatory cytokines and inflammatory mediators, such as interleukin-6. This condition is referred to as the fetal inflammatory response syndrome (FIRS).
Certain organisms have been more strongly associated with both intense chorionic plate inflammation and fetal vasculitis including Actinomyces species, Corynebacterium species, Mycoplasma species, Escherichia coli, Ureaplasma Urealyticum and group B, group D, alpha hemolytic, and anaerobic streptococci. However, it should be remembered that group B streptococcal infection is not consistently accompanied by significant inflammation.
Subacute necrotizing funisitis is a subset of acute chorioamnionitis characterized by peripheral microabscesses of the umbilical cord. The classic gross finding is the presence of pinpoint yellow-white nodules on the umbilical cord that track the coils of the underlying vessels. These foci correspond to histological subamniotic microabscesses and include mineralization of the arcs of inflammatory detritus. The vast majority of these cases are due to Candida albicans but C parasilopsis and other species have been identified.
Intrauterine infection by Candida, although a less common cause of acute chorioamnionitis is more prevalent in preterm deliveries and is associated with significant mortality rates in the extreme and severely preterm infant 60.
Subacute chorioamnionitis is another acute inflammatory placental pathology of infectious etiology in SPB. This is a histopathological diagnosis characterized by a chorionic mononuclear (histiocytic) infiltrate admixed with degenerating neutrophils and karyorrhectic debris that is most prominent in the upper zone of the chorionic plate and indicates a more prolonged duration of intrauterine infection. It may represent infection by organisms of low pathogenicity or recurrent mild infection. Clinically it is seen in gestations complicated by repeated second and/or third trimester episodes of bleeding 61.
