Rguhs.ac.in



RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME : DINU SATHEESH V

ADDRESS: DEPARTMENT OF PATHOLOGY, ST. JOHN’S MEDICAL COLLEGE, BANGALORE- 560 034.

2. NAME OF THE INSTITUTION: ST. JOHN’S MEDICAL COLLEGE BANGALORE

3. COURSE OF STUDY AND SUBJECT: MD PATHOLOGY

4. DATE AND ADMISSION TO COURSE: 1st JUNE, 2013

5. TITLE OF THE TOPIC: “INFLAMMATORY PATTERNS OF THE PLACENTA AND THEIR CLINICAL CORRELATION”

6. BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY:

Inflammatory disorders of the placenta and the umbilical cord include chorioamnionitis, deciduitis, villitis, intervillositis and funisitis. Histopathological examination of the placenta is the gold standard for evaluating antenatal inflammatory conditions that may influence fetal development.

Very few studies have been done that correlate the inflammatory disorders of the placenta and umbilical cord, with pre-existing maternal conditions and neonatal outcome. Information obtained from placental histopathology is critical in early neonatal care, providing risk assessment for neurological outcome of the infant and in planning of the future pregnancies.

This study will estimate the frequency of the various inflammatory lesions in the placenta and correlate these lesions with pre existing maternal factors, pregnancy complications, intrapartum events and early neonatal complications.

6.2 REVIEW OF LITERATURE :

The placenta is an important organ that is very crucial for the growth of a healthy infant. It acts as a mediator, between the mother and the fetus and helps in fetomaternal exchange. The histopathological examination of the placenta still remains the gold standard in evaluating the various antenatal inflammatory events and its effects on adverse neonatal outcome. Detailed studies on the incidence of the various inflammatory lesions of the placenta and cord, and correlating it with maternal factors and neonatal outcome is mandatory and will add knowledge in understanding the events in the early neonatal period. The inflammatory lesions of the placenta include chorioamnionitis, deciduitis, villitis and intervillositis and the umbilical cord include umbilical vasculitis or funisitis.

CHORIOAMNIONITIS:

Acute chorioamnionitis presents as a neutrophilic infiltrate in the chorion and amnion. The initial inflammatory response is maternal in origin (Maternal Inflammatory Response-MIR.) An intra amniotic infection shows the presence of leucocytes that marginate from beneath the fibrin under the chorionic plate. Chorioamnionitis can be divided into acute, subacute and chronic depending on the type of inflammatory cells present.

The fetal inflammatory response (FIR) comprises of the fetal inflammatory cells migrating from the umbilical vessels and superficial fetal vessels in the chorionic plate. FIRs are uncommon in placentas with chorioamnionitis at before 20 weeks due to the immature fetal immune system.1 They are first seen in vessels of the chorionic plate (chorionic vasculitis) in preterm and in the umbilical vein(umbilical phlebitis) in term.

Involvement of the umbilical artery (umbilical arteritis) occurs later and the term ‘funisitis’ is used when we cannot differentiate between an umbilical arterial and venous involvement.

DECIDUITIS

Chronic deciduitis is a diffuse lymphocytic infiltration of the decidua basalis or a focal infiltrate comprising of plasma cells. Acute deciduitis is not recognised as a separate entity.2 Decidual lymphocytes and plasma cells are also seen in chronic villitis.

VILLITIS

Villitis is defined as inflammation of the placental villous tree.Villitis and chorioamnionitis are equally common, each seen in approximately 10-15% of all placentas.2 Acute villitis is uncommon and is composed entirely of neutrophils. Placentas with chronic villitis show a mixed lymphohistiocytic infiltrate with occasional neutrophils. Infectious chronic villitis by TORCH (e.g.cytomegalovirus,toxoplasmosis, and syphilis) organisms is uncommon (1-4/1000 live births)2. It usually involves the entire placenta and is usually associated with preterm delivery. Villitis of unknown aetiology (VUE) is more common (76-136/1000 live births), is associated with term placentas and generally affects only the distal villous tree. The diagnosis of chronic villitis of unknown etiology (CVUE) is a diagnosis of exclusion after ruling out infections by polymerase chain reaction.

The lymphocytes in VUE have been shown to be CD8-positive T lymphocytes of maternal origin.VUE maybe a maternal-fetal cellular transfer leading to a local allograft reaction against fetal cell.3

INTERVILLOSITIS

CHRONIC INTERVILLOSITIS OF UNKNOWN ETIOLOGY (CIUE):

CIUE is very rare and shows inflammatory placental lesions in the intervillous space(IVS). It is also called as massive chronic intervillositis or chronic histiocytic intervillositis. The infiltrate comprises of mononuclear cells (monocytes,lymphocytes and histiocytes) from maternal origin. This massive or moderate infiltrate is frequently associated with villous and intervillous fibrinoid deposition.4

IMPLICATIONS OF PLACENTAL PATHOLOGY ON MATERNAL CARE AND NEONATAL OUTCOME

Histologic chorioamnionitis (HCA) is associated with preterm labour and delivery and is inversely correlated with gestational age (GA) and birth weight (BW). Chorioamnionitis is a known risk factor for early-onset sepsis (EOS) ie. onset within 72 hours of age and increased neonatal morbidity including intracranial hemorrhage, periventricular leukomalacia, and cerebral palsy5. Chorioamnionitis is present in approximately 30% and 60% of placentae at 29 weeks and 23 to 24 weeks GA respectively. If perinatal inflammation is due to a low virulence organism, it is well controlled by the maternal immune system and does not cause EOS, instead it enhances the maturation of the neonatal immune system. Funisitis and chronic infectious villitis have been associated with preterm birth.

When VUE involves a larger portion of the terminal villous tree, there is an association with intrauterine growth restriction and stillbirth. Cases of extensive VUE also have a recurrence risk of approximately 10-25%.6 Associations of CVUE with maternal body mass index, multigravidity, ethnicity, unexplained prematurity, preeclampsia, and perinatal asphyxia is seen. CVUE is more frequent in pregnancies affected by autoimmune or alloimmune diseases.7 Neonatal morbidity associated with VUE can be detected early by oligohydramnios and chronic monitoring abnormalities including abnormal stress testing, abnormal pulsed flow Doppler studies, and abnormal biophysical profile.8 VUE with fetal obliterative vasculopathy is more frequent in the placentas of term infants with neurological impairment like neonatal encephalopathy and cerebral palsy.9 CIUE is associated with IUGR with oligohydramnios, intrauterine fetal death (IUFD) and spontaneous miscarriage.4

A study done by Arthur.M.Baker et al showed the relationship between parity and acute or chronic inflammation. Increasing parity was found to be protective against AFIS (Amniotic Fluid Infection Syndrome). A previous elective termination, smoking, and a low socioeconomic status were all risk factors for AFIS.10 With a history of preterm delivery there was a greater risk of having chronic villitis in a subsequent pregnancy. The chances for chronic villitis increased with parity.

6.3 AIM OF THE STUDY:

To estimate the incidence of the various inflammatory lesions (deciduitis, villitis, intervillositis, chorioamnionitis and funistis) in the placentae of preterm (37weeks) delivered either by normal vaginal delivery or LSCS in our population and to correlate the histopathological evidence of inflammation with various maternal factors and neonatal outcome.

6.4 OBJECTIVES OF THE STUDY:

1. To identify and determine the incidence of the various inflammatory lesions in the placenta (chorioamnionitis, deciduitis, villitis and intervillositis) and umbilical cord (umbilical vasculitis/ funisitis)

2. To correlate the lesions with various pre existing maternal factors and intra partum factors.

3. To correlate these inflammatory lesions with perinatal outcome (IUGR, neonatal mortality and neonatal morbidities).

4. To look for any association amongst the various inflammatory lesions.

7. MATERIAL AND METHODS

7.1a SOURCE OF DATA:

This is a descriptive comparative study of placentae received in the Department of Pathology over a period of two years (September 2013-July 2015.) The relevant clinical details will be collected from the obstetrics antenatal records, ultrasound reports (wherever applicable) and neonatal medical records.

INCLUSION CRITERIA:

All placentae received in the department whose gestational age is above 24 weeks will be included in the study. The placentae whose histopathological features are not suggestive of inflammatory lesion will be studied as control group.

EXCLUSION CRITERIA:

Placentae where clinical details are not available for correlation and improperly fixed tissue will be excluded from the study.

METHODOLOGY:

Once the placenta is received in the department, the organ will be examined and grossed. The details of the gross examination will include the following: the colour, contour, the insertion of the umbilical cord and membranes, presence of accessory lobes, intactness of the maternal cotyledons. Then the umbilical cord details like the cord length, diameter, number of vessels, nature of the Wharton’s jelly, and presence of any thrombus in the vessels, true and false knots will be recorded. If the cord insertion is eccentric the distance of the cord from the closest placental margin will be recorded. The membranes will be examined for foul smell, transparency and presence of amniotic nodules. After removing the cord and the membrane, the trimmed placental weight will be taken. The placenta will be sliced and examined for presence of infarction (extent, if present), fibrin deposition (extent of involvement), calcification, intraparenchymal hematoma and any other lesions.

The placenta will then be fixed in 10% Buffered Formalin for 24 hours following which representative bits will be taken.

A bit from the umbilical cord will be sampled. A swiss roll of membranes is made by rolling the membranes from the point of rupture as the starting point with the amnion towards the inner side, till the placental brim is reached. The membrane roll will then be sliced and sampled. One bit from the maternal and fetal surfaces and one bit full thickness will be sampled.

PROCESSING TECHNIQUE:

The tissue thus sampled will be processed by the routine automated processing method followed in the department for any other tissue sample. For every block made a slide will be cut for H&E staining. Special stains like PAS (periodic acid Schiff), Grams and Gomori’s methamine silver (GMS) {if any infective etiology is suspected} will be done as and when required.

MICROSCOPY:

A detailed microscopic examination will be done and observation will include the following:

1. Placental samples:

Decidual inflammation (type of inflammatory cells and extent of inflammation)

Villitis: Acute/chronic

Grade:

i. Very mild: 1 or 2 foci each with a few villi

ii. Mild: upto 6 foci, each upto 20 villi

iii. Moderate: multifocal, each upto half low power field

iv. Severe: large areas, involving most slides.

Intervillositis: Type of inflammatory cells and extent

Subchorionic neutrophilic infiltrate: extent of inflammation

Chorionic plate vasculitis.

Infarction and fibrin deposition.

2. Umbilical cord: Funisitis

3. Membranes: Chorioamnionitis. This will be studied as maternal inflammatory response (MIR) and fetal inflammatory response (FIR).

Maternal inflammatory response-(MIR)

Stage 1(Early)-Acute subchorionitis/acute chorionitis: PMN in sub chorionic fibrin +/or membrane trophoblast.

Stage 2(intermediate) - acute chorioamnionitis: diffuse patchy PMN in the fibrous chorion and amnion

Stage 3(late) - necrotizing chorioamnionitis.Poly karyorrhexis, amnion necrosis +/or amniotic BM thickening/ hypereosinophilia.

MIR grade:

Grade 1- mild to moderate MIR- a few scattered polymorphs

Grade 2- severe acute chorioamnionitis or with subchorionic micro abscess. (confluent polymorphs between chorion and decidua ;> or = 3 isolated foci or continuous bands

Fetal Inflammatory response: (FIR)

Stage1: chorionic vasculitis or umbilical phlebitis: intramural polymorphs in chorionic vessels or umbilical vein.

Stage 2: with umbilical vasculitis (one or both umbilical arteries+/or vein) +/or umbilical pan vasculitis: intramural polys in the umbilical artery or arteries (+ /or veins)

Stage 3: with necrotizing funisitis or with concentric umbilical perivasculitis: polymorphs+/-debris in the concentric bands or rings- halos around one or more umbilical vessels.

FIR grade:

Grade1: mild to moderate

Grade2: severe-near confluent intramural polymorphs in the chorionic and or umbilical vessels with attenuation / degeneration of vascular smooth muscle.

The following maternal conditions and intrapartum conditions will be noted from the mother’s case files.

1) Maternal age (>35years),

2) Parity

3) Pre-existing maternal diseases like gestational diabetes mellitus (GDM), pre-pregnancy diabetes, pregnancy induced hypertension (PIH), chronic hypertension, pre-eclampsia, anaemia, and chronic endometritis.

4) Intrapartum events like premature rupture of membranes (PROM), preterm premature rupture of membranes (PPROM), intrauterine growth restriction (IUGR)

5) Past obstetric history including previous elective termination, previous preterm and bad obstetric history (BOH)

The neonatal parameters assessed will include:

6) Birth weight.

7) APGAR score.

8) Preterm and still birth

9) Neonatal mortality

10) Neonatal sepsis

Other neonatal morbidities such as: Respiratory Distress Syndrome(RDS), pneumonia, chronic lung disease (CLD), Necrotising Enterocolitis (NEC), Patent Ductus Arteriosus(PDA), perinatal asphyxia, intraventricular hemorrhage, Periventricular leukomalacia(PVL), Retinopathy of Prematurity(ROP), anemia and hypoglycaemia.

The placental histopathological findings will be correlated with the above mentioned maternal and neonatal factors.

7.1b SAMPLE SIZE:

The established incidence of these various inflammatory lesions of the placenta varies from 5% to 15% for villitis, intervillositis and chorioamnionitis in literature. With a power of 80% and alpha error of 5%, approximately 150 placentas will be studied to establish the incidence of the various inflammatory disorders in our population. This data will also be sufficient to run appropriate statistical tests.

7.1c STATISTICAL ANALYSIS:

This is descriptive comparative study. The placentas which do not show inflammatory lesions will be studied as “controls” against the placentas showing inflammatory pathology i.e. “cases.” Descriptive statistics will be used to study the incidence of the various inflammatory lesions. Wherever correlation can be done chi-square or Fischer’s exact correlation test will be used.

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMAN OR ANIMALS?

NO

7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?

CONSENT FORM: Not applicable

8. LIST OF REFERENCES:

1. Baergen RN. Infectious diseases. In: Manual of Pathology of the Human Placenta, Second edition. New York: Springer Dordrecht Heidelberg, 2011. p. 281-319.

2. Redline RW. Inflammatory responses in the placenta and cord. Semin Fetal Neonat Med 2006;11: 296-301.

3. Redline RW, Patterson P. Villitis of Unknown Etiology is associated with major infiltration of fetal tissue by maternal inflammatory cells. Am J Pathol 1993;143: 473-9.

4. Parant Olivier, Capdet Jerome, Kessler Sylvie, Aziza Jacqueline, Berrebi Alain. Chronic intervillositis of unknown etiology (CIUE): Relation between placental lesions and perinatal outcome. Eur J Obstet Gynecol Reprod Bio 2009;143: 9-13.

5. M Veleminsky Jr, J Pradna, M Veleminsky Sr, J Tosner. Relationship of amniotic-type placental inflammation to PPROM, PROM and risk of early onset neonatal sepsis. Neuro. Endocrinol Lett 2008;29(4):447-50.

6. Redline RW, Abramowsky CR. Clinical and pathologic aspects of recurrent placental villitis. Human Pathol 1985;16:727-31.

7. Redline.RW. Villitis of unknown etiology: noninfectious chronic villitis in the placenta. Human Pathol 2007;38:1439-46.

8. Redline RW, Patterson P. Patterns of placental injury: correlations with gestational age, placental weight and clinical diagnosis. Arch Pathol Lab Med 1994;118:698-701.

9. Redline RW. Severe fetal placental vascular lesions in term infants with neurological impairment. Am J Obstet Gynecol 2005;192:452-7.

10. Baker AM, Braun JM, Salafia CM, Herring AH, Daniels, Rankins N, et al. Risk Factors for Uteroplacental Vascular Compromise and Inflammation. Am J Obstet Gynecol 2008;199(3):256e1-256e9.

9. SIGNATURE OF CANDIDATE:

10. REMARKS OF THE GUIDE:

11. NAME AND DESIGNATION OF

11.1 GUIDE: DR.JULIAN CRASTA, MD., DNB.

Additional Professor of Pathology, SJMC

11.2 SIGNATURE

11.3 CO-GUIDE 1: DR.R.GAYATRI, MD.

Lecturer in Pathology, SJMC

11.4 SIGNATURE

11.5 CO-GUIDE 2: DR.SUMAN RAO, MD,DM(NEONATOLOGY)

Associate Professor, SJMCH

11.6 SIGNATURE

11.7 HEAD OF DEPARTMENT: Dr. MARJORIE CORREA, MD,

Professor and Head of Pathology, SJMC

11.8 SIGNATURE

12. 12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL: 12.2

PROFORMA

|MATERNAL DETAILS |MRD NO |SP NO |

|NAME |AGE |MATERNAL BMI |

|OBSTETRIC SCORE |G P L A | |

|PRE EXISTING DISEASES |CHRONIC HYPERTENSION |OLIGOHYDRAMNIOS |

|GDM |PRE ECLAMPSIA |OTHERS |

|PRE-PREGNANCY DIABETES |ANAEMIA | |

|PIH |CHRONIC ENDOMETRITIS | |

|INTRAPARTUM EVENTS |PAST OBSTETRIC HISTORY | |

|PROM |PREVIOUS LSCS | |

|PPROM |PREVIOUS PRETERM | |

|IUGR |BOH | |

|NEONATAL PARAMETERS |BIRTH WEIGHT_______kg |APGAR SCORE _________ |

|PRETERM/STILL BIRTH |NEONATAL DEATH |NEONATAL SEPSIS |

|RDS |PNEUMONIA |CHRONIC LUNG DISEASE |

|NEC |PDA |PERINATAL ASPHYXIA |

|IVH |PVL |ROP |

|ANAEMIA |HYPOGLYCEMIA |TORCH |

PLACENTAL GROSS EXAMINATION

1.MEMBRANES: MEMBRANE RUPTURE SITE: _________________ cms to margin

MEMBRANE COLOUR: Transparent Cloudy

MECONIUM STAINED Yes No

OTHER MEMBRANE FINDINGS: Nodules Foul odour

UMBILICAL CORD: CORD LENGTH:_________cms CORD DIAMETER: ________cms

CORD COLOUR: White Green Yellow Brown

CORD ATTACHMENT Central Eccentric Marginal Velamentous

NO OF VESSELS: _____________ THROMBI + / _

NATURE OF WHARTON’S JELLY: __________________

OTHER CORD FINDINGS: Nodules True knots False knots

PLACENTAL DISC: TRIMMED WEIGHT: ____________gms

DISC MEASUREMENT: ______ x ______ x _______ cms

FETAL SURFACE FINDINGS: Nodules Colour

MATERNAL SURFACE FINDINGS: Cotyledons intact Nodules Colour

PARENCHYMA: Beefy Spongy Red

LESIONS Fibrin deposition, infarction, calcification ,intraparenchymal hematoma

Lesions Number___________ Size_________% Involvement

Location Central Peripheral ACCESSORY LOBES: + / -

PLACENTAL HISTOPATHOLOGY

1. DECIDUITIS : Acute Chronic Diffuse Focal

2. VILLITIS: Acute Chronic Cell type

Grade Very mild Mild Moderate Severe

3. INTERVILLOSITIS: Acute Chronic Cell type

SUBCHORIONIC INFLAMMATION

CHORIONIC PLATE VASCULITIS

INFARCTION AND FIBRIN DEPOSITION Maternal vessels Fetal vessels

4. UMBILICAL CORD FUNISITIS PHLEBITIS VASCULITIS

5. CHORIOAMNIONITIS

MIR Stage 1 2 3 Grade 1 2

FIR Stage 1 2 3 Grade 1 2

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download