The perinatal autopsy and placental pathology Drucilla Roberts djroberts@partners.org
Millennium Development Goals Goal 4: Reduce child mortality rates Target 4A: Reduce by two-thirds, between 1990 and 2015, the under-five mortality rate Goal 5: Improve maternal health Target 5A: Reduce by three quarters, between 1990 and 2015, the maternal mortality ratio* *Maternal Mortality Ratio is the ratio of the number of maternal deaths per 100,000 live births
Problem To affect improvement in maternal and childhood deaths one has to know The NUMBERS Vital statistics The CAUSES Autopsy Social Verbal Anatomical
The Social Autopsy Definition: The examination of a social error to discover the cause of the error and to prevent it from occurring again. Evaluation and Program PlanningVolume 29, Issue 1, February 2006, Pages 44-54, Organizational Learning
Verbal autopsy Mechanism to determine events surrounding the death by interview
Verbal Autopsy Verbal autopsy questionnaires and algorithms need to distinguish between different possible causes of death using only information that can be recalled by caregivers.
Verbal autopsy technique assumptions Causes of death have distinct symptom complexes which can be recognized, remembered, and reported It is possible to classify deaths into useful categories based on symptom complexes
Verbal Autopsy Trained but non-medical interviewers Notification by town/village elders Home visits between 1-21 months after deaths 30-90 minute interview of respondant Family member generally head of household
Interpretation Algorithms Physicians
Pregnant < 7 months + vaginal bleeding YES abortion NO Pregnant >6 months + convulsions or Delivered < 15 days + convulsions eclampsia Pregnant > 8 months + heavy bleeding before delivery + Labor pains < 24h OR hemorrhage Delivered <4d + heavy bleeding after delivery Labor pains > 24 hours Delivered < 15 d + fever + abdominal pain obstructed labor puerperal sepsis
Validation Since verbal autopsies rely solely on information recalled by the next-of-kin for determining the cause of death, and are not based on clinical or laboratory evidence, they may be subject to relatively high misclassification errors. (Although, even diagnoses based on clinical and laboratory evidence may have substantial misclassification.) This can have a profound effect on the verbal autopsy estimate of the proportion of deaths due to a specific cause.
Confirmation studies NONE with autopsy Validation by physician review of answers Occasionally by correlation with hospital or medical records
Discrepancies between clinical diagnosis and autopsy findings 26% Medical ICU deaths - USA 17% Community hospital - USA 16% (Major) Tertiary care hospital - Brazil 15% Military hospital - Pakistan No maternal mortality data on discrepancies Internal Massachusetts death report reviews found >10%
Confirmatory studies By culture Interviewer, respondant, time By diagnosis <30% renal <50% malaria, cirrhosis, pneumonia ~90% direct maternal Lowest were combined causes, eg. AIDS and TB
If we are basing huge expenditures for public health measures on reports of causes of death - we ought to do better than that!
Perinatal autopsy Definitions Death of the infant within first 2 weeks of life Death of a fetus before birth Sometimes differentiated as Previable - <20 weeks or <350g Potentially viable - >20 weeks or >350g Optimal procedure Complete and unrestricted - histopathology, microbiology Placental examination Minimalistic approach Weights and measurements Careful gross examination of body and placenta
APPROACH TO PATHOLOGIC EVALUATION Be honest, understand limitations - personal and within the field Be thorough and timely Be respectful Be available
Placental examination - WHY? The placenta explains cause of death in stillbirths in a large percentage of cases Placental pathology explains the cause of prematurity in a large percentage of cases
Gross Placental Examination
Umbilical Cord Vessels Length 50-70cm at term Diameter 1.5-3cm at term Twist/coils 3 in 10 cm Insertion Knots
Membranes Completeness Rupture Site Insertion Color
Placental Exam Set up your materials You need Formalin in jar Labels Forceps Scissors Scale Template and pen
Umbilical Cord Cut off the cord Take two samples (one from each end of the cord) place both samples in formalin jar
Membranes Cut a strip of membranes ~3cm wide and 10 cm long Hold end with forceps and roll membrane around forceps Place roll into formalin container
Disk Cut membranes off the disk Weigh disk and record Measure greatest length and record
GA SINGLETONS TWINS (COMBINED WT) percentiles percentiles 10-25 - 50-75 -90 % 10-25 - 50-75 - 90 % 12 56 14 83 16 110 18 137.8 20 145 166-190-218-245-270 22 122-138-157-176-191 191-219-251-282-310 24 145-166-189-212-233 232-267-307-346-382 26 175-200-227-255-280 284-330-380-430-475 28 210-238-270-302-331 345-401-464-527-584 30 249-281-316-352-384 409-478-554-631-700 32 290-325-364-403-438 472-554-644-734-815 34 331-369-411-453-491 531-624-727-830-923 36 372-412-457-501-542 582-684-798-912-1014 38 409-452-499-547-589 619-728-850-972-1082 40 442-487-537-587-632 638-753-879-1005-1118
Disk Sampling Lesion Use scissors and cut through placenta in 4 cm strips Measure greatest thickness and record Look for lesions Take at least two full thickness samples from the middle of the disk and place in formalin jar Take any lesions and place in formalin jar
Place the LABELED placenta in the refrigerator You should have in the LABELED formalin container: Two sections of umbilical cord One membrane roll 2-3 sections of placenta Finish
Template Placental Grossing and Sampling Template Š Singleton or separate twin placentas PATIENT ID NUM BER Date delivered PLACENTAL WORKSHEET TEMPLATE FOR DICTATION The specimen was received fresh labeled with the patient's name and unit number and consists of a singleton placenta. Singleton Twin Separate Placentas (use 2 forms) Fused Placenta (use twin placental form) Other (send placenta(s) intact) Liveborn Stillborn Neonatal death Diameter cm Weight gms Thickness cm Findings: (describe) Cord insertion c m from margin (or cm in membranes from margin) Cord length c m Number of vessels other cord findings (hypo or hyper twisted, abnormal color, nodules, masses, etc) cord color (white, yellow, green, brown, etc) Membranes inserted % (marginally, circummarginately, circumvallate) Membrane rupture site cm to margin Membrane color other membrane findings (nodu les, hemorrhage, membranous vessels, etc) The trimmed placental weight is g Disk measurement c m in greatest diameter X cm thick Fetal surface findings (nodules, masses, chorionic vascular thromboses, etc) Maternal surface (complete, disrupted, masses, calcification, fibrin, hematomas, indentations, etc) Parenchyma (normal = beefy, spongy, red ; lesions = number, size, % of mass involved, location) Summary: Cassettes:
Fetal Surface Color Vasculature Fibrin Blood
Maternal Surface Completeness Clots Color
Parenchyma Color Consistency Blood clots Infarcts
From Gross to Microscopic
Umbilical Cord 2 Arteries, 1 Vein Amnionic Epithelium Wharton s Jelly: Polysaccharides Macrophages Myofibroblasts Mast cells
Umbilical Cord- Unique Features Arterial muscular coat: crossing spiraled fibers, no internal elastic membrane, minimal elastica Venous coat: separate layers of circular fibers, possess elastic subintimal layer Endothelial cells rich in organelles; interdigitating extensions to adjacent muscle cells (enotheliomuscular system) No vasa vasorum except intra-abdominal portion after 20 wks GA No nerves within cord placenta without neural supply
Membranes Amnion Chorion Extravillous Trophoblast Decidua Capsularis
from Baergen, R.N. Manual of Benirschke and Kaufmann s Pathology of the Human Placenta Chorionic Plate
Basal Plate
Parenchyma Villous Tree Materna l Blood Fetal Vessels
Villous Histology
Malarial Sequestration
FETAL RESPONSE Fetal response to acute chorioamnionitis includes: Inflammatory cells migrating from fetal vessels Umbilical cord Chorionic plate Vasculitis is a risk factor for neurodevelopmental delay/cerebral palsy
Placental insufficiency Small placenta (<10th, often <3rd %ile) Decidual vasculopathy Atherosis Ischemic changes/pressure related injury Infarcts Hypermaturity Small villi (1 capillary, smaller than free knots) Many knots (usually 1/3-5 villi, here 1/1 villous and >10 nuclie per knot!) Lots of space between villi Abruption
Severe decidual vasculopathy with atherosis
Normal vessels in decidua capsularis Decidual vasculopathy with atherosis
Hypermature villi - distal villous hypoplasia
Regular type of infarct - maternal perfusion defect
Usual type infarct histology
Small, central, round infarct Small sclerotic villi Usually multiple Large syncytial knots watershed zone Lots of intervillous space Indication of global/chronic ischemia HYPERMATURE VILLI
Chronic abruption
Chronic abruption histology
Acute abruption
Intravillous hemorrhage - acute abruption/cord accident
Fetal deaths Deaths in utero Prematurity related deaths Delivery related deaths
SECOND TRIMESTER LOSSES Infections Anomalies Placental Maternal
THIRD TRIMESTER LOSSES PLACENTA PLACENTA PLACENTA Abruption Insufficiency Uterine rupture Other: Consider micro and virology studies Blood spot for metabolic studies Lethal anomalies
STILLBIRTH/IUFD PATHOLOGY Difficult emotionally and professionally 50-80% failure rate to determine etiology of death Placental examination essential
APPROACH TO AUTOPSY Pictures are critical no matter how disturbing. Always XRAY Eviscerate and fix organs in LARGE volume formalin for 24 hours before dissection. Save placental and skin tissue for special studies Blood spot saved for metabolic screen
FETAL HISTOLOGY IN STILLBIRTH/IUFD Ghosts possible in most autolyzed tissue CMV HSV Rhabdomyomata Hematological disturbances Tumors
PLACENTAL FINDINGS Often best preserved of all tissues Metabolic, hematological, infectious etiologies easily identified. Fetal vascular events Anatomic findings Cord insertions
FETAL VASCULAR EVENTS Thromboemboli in fetal vasculature - in placental or viscera Loose or occlusive Differential diagnosis: Anatomic vascular damage Endothelial damage Sepsis Primary thrombophilia Maternal diabetes
COMPLETE EXAM INCLUDES Complete autopsy Placental examination Fetal X-Ray Fetal labs- Hct,blood type, bacterial cultures Maternal-blood type, KB, TORCH titers
Chorion Nodosum Rupture of the amnion early in gestation (before the middle of the second trimester) Fetus develops between the amnion and chorion Differential diagnosis: Iatrogenic Maternal/fetal collagen defects Limb-body wall syndrome
Limb-body wall syndrome: short umbilical cord chorion nodosum
Normal Progression of Autolysis during retention of IUFD 6 hours: desquamation >/= 1cm Brown-red discoloration of cord 12 hours: desquamation of face, abdomen or back 18 hours: desquamation >5% of body surface 24 hours: brown skin discoloration Moderate to severe desquamation 2 weeks: mummification
Reporting Liveborn/Stillborn Male/female Infant/fetus Weight, crown-rump length, etc and EGA based on these measurements Placenta - weight, cord length, color Findings with a focus on biology
Example Liveborn female fetus (1320g, CRL = cm; EGA based on autopsy measurements of wks), age at death, 2 hours. No congenital/structural anomalies Placenta - 120g Immature placenta Severe acute chorioamnionitis [maternal stage 2 grade 2; fetal stage 2 grade 2] Massive acute villous edema Cause of death: Extreme prematurity, pulmonary immaturity, aspiration pneumonia Cause of premature delivery: acute chorioamnionitis (cultures of lung and placenta grew GBS).