A PROSPECTIVE AUTOPSY STUDY OF THE CAUSES OF PERINATAL

AND UNDER-FIVE MORTALITY AT THE UNIVERSITY OF BENIN

TEACHING HOSPITAL (U.B.T.H.), BENIN CITY, NIGERIA

BY

VHRITERHIRE CLEMENT OGHENEVWOKE

2013

A PROSPECTIVE AUTOPSY STUDY OF THE CAUSES OF PERINATAL

AND UNDER-FIVE MORTALITY AT THE UNIVERSITY OF BENIN

TEACHING HOSPITAL (U.B.T.H.), BENIN CITY, NIGERIA

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BY

VHRITERHIRE CLEMENT OGHENEVWOKE

A DISSERTATION SUBMITTED TO THE NATIONAL POSTGRADUATE

MEDICAL COLLEGE IN PART FULFILLMENT OF THE

REQUIREMENTS FOR THE AWARD OF THE FELLOWSHIP OF THE

NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA,

FACULTY OF PATHOLOGY ( FMCPath)

2013

DECLARATION

I hereby declare that this work was done by me DR C. O VHRITERHIRE of the department of Pathology, University of Benin Teaching Hospital, Benin City. It has neither been submitted to any other college or body, nor has it been sent to any journal for publication.

DR VHRITERHIRE C. O

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Signature------

Date------

CERTIFICATION

We certify that this work was carried out by DR VHRITERHIRE CLEMENT OGHENEVWOKE of the Department of Pathology, University of Benin Teaching Hospital Benin City, under our supervision.

PROF. J.U. ALIGBE

Professor/ Consultant Pathologist,

UNIBEN/UBTH

Signature------

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Date------

DR V.J. EKANEM

Senior Lecturer/ Consultant Pathologist

UNIBEN/UBTH

Signature------

Date------

DR E.E. UGIAGBE

Lecturer I/ Consultant Pathologist

UNIBEN/UBTH

Signature------

Date------

DEDICATION

To my wonderful children Charisa, Dominion, Runo, Yoma and my lovely wife Evelyn; for your love and understanding during the long absences from home.

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ACKNOWLEDGEMENT

To the Almighty God, who alone is eternally faithful, I return thanks and praise for the enablement from on high to complete this work.

My sincere gratitude goes to all my supervisors; Professor JU Aligbe, Dr VJ Ekanem and Dr

EE Ugiagbe for accepting to supervise this work. Your guidance, scrutiny and availability to review autopsies/slides even at odd hours and weekends helped to ensure the successful completion of this work. The mentorship I have received from you have undoubtedly equipped me in a most unique way for the practice of pathology

My special thanks also go to Dr (Mrs) AN Olu-Eddo and Dr DE Obaseki erstwhile and current Head of Department respectively of Department of Pathology, UBTH for your

5 administrative astuteness in taking the department to the next level. I am also grateful to Dr

GD Forae for all the useful tips and hints on this project.

Professor Omoigberale of the Department of Paediatrics and Professor ABA Ande as well as

Professor ME Aziken of the Department of Obstetrics and Gynaecology provided the template for the interdepartmental collaboration from the very inception of the work; I am grateful to you all. Mrs AH Idahosa (CNO i/c labour ward) galvanized all nurses and made the placental collection aspect of the work possible, I am grateful.

Mrs EE Adeyemi and her team of histoscientists were always available and dutifully prepared the slides from the autopsy specimen and placental samples, God will reward you all.

TABLE OF CONTENT

Title page………………………………………………………………………………….i

Declaration……………………………………………………………………………….iii

Certification………………………………………………………………………………iv

Dedication………………………………………………………………………………..v

Acknowledgement………………………………………………………………………..vi

Table of content…………………………………………………………………………..vii

Abstract………………………………………………………………………………….ix

List of tables………………………………………………………………………………x

List of figures……………………………………………………………………………..xi

1.1 Introduction…………………………………………………………………………..1

2.0 Literature review………………………………………………………………………3

2.1 Autopsy………………………………………………………………………………..3

2.2.0 Perinatal mortality………………………………………………………………….28

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2.3.0 Neonatal deaths…………………………………………………………………….40

2.4.0 Infant mortality……………………………………………………………………..41

2.5.0 Under-five mortality………………………………………………………………..42

3.0 Aim/Significance of the study………………………………………………………44

3.1. Aim and Objectives…………………………………………………………………44

3.2. Significance/ Justification of the study……………………………………………..44

4.0 Materials and Method……………………………………………………………….45

4.1 Study design…………………………………………………………………………45

4.2 Study site…………………………………………………………………………….45

4.3 Study population…………………………………………………………………….45

4.4 Exclusion criteria…………………………………………………………………….45

4.5 Duration of study……………………………………………………………………46

4.6 Sampling method……………………………………………………………………46

4.7 Categorization of the mortalities…………………………………………………….46

4.8 Study protocol……………………………………………………………………….46

4.9 Ethical considerations……………………………………………………………….47

5.0 Results………………………………………………………………………………...48

5.1 Perinatal mortality……………………………………………………………………48

5.2 Under-five mortality………………………………………………………………….50

Tables………………………………………………………………………………..53

Figures……………………………………………………………………………….63

6.0 Discussion…………………………………………………………………………….75

7.1 Conclusion…………………………………………………………………………….82

7.2 Recommendation……………………………………………………………………..82

7.3 Limitation……………………………………………………………………………..83

7.4 Further work………………………………………………………………………….83

References……………………………………………………………………………84

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Appendix……………………………………………………………………………..96

ABSTRACT

Introduction/Aim: Perinatal and childhood mortality is a global health burden with an estimated 8.1 million under-five deaths in 2009. The highest rates of child mortality is in sub-

Saharan Africa and South East Asia. The millennium development goal four (MDG-4) which targets the reduction of childhood mortality by two thirds from 1990 to 2015 can only be realizable if adequate and accurate epidemiological information is available to prioritize, plan, and implement public health interventions. Autopsy validation of cause of death information is one way of improving accuracy of our vital statistics.

Materials and Method: the study was a one year (January to December 2012) prospective autopsy study of all the perinatal and under-five mortalities for which an informed consent was duly obtained. All autopsies were performed according to a defined working protocol

Results: There were a total of 2967 deliveries recorded in UBTH for the year 2012 with a perinatal mortality rate of 119.2/1000 total births while the under-five mortality rate is

103.8/1000 live births. The perinatal autopsy rate is 50.3% while the under-five autopsy rate is 44.9%. the overall male to female ratio is 1.14:1. The most common causes of perinatal death are infection (30.3%), placental causes (20.6%), and prematurity/immaturity (16.0%).

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Congenital anomalies accounted for 10.9% of deaths. Respiratory and cardiovascular disorders specific to the perinatal period accounted for most under-five deaths (24.7%), infections were responsible for 18.4%, while prematurity was responsible for 14.4% of under-five deaths. Conclusion: This study shows that perinatal and childhood mortality is still a major problem in our environment. We would suggest that a multidisciplinary perinatal death team be put in place with a perinatal death protocol that will institutionalize perinatal autopsies.

LIST OF

TABLES………………………………………………………………………….page

Table I: Causes of perinatal death in UBTH classified using the Tulip pathophysiological classification……………………………………………………………………………………

53

Table II: Age specific causes of perinatal death in UBTH, Jan to Dec

2012…………………54

Table III: Distribution of congenital anomalies amongst the perinatal deaths………………..55

Table IV: Weight distribution of the various causes of perinatal death………………………56

Table V: Weight distribution of the various perinatal death groups…………………………….57

Table VI: Age and sex distribution of under-five deaths in

UBTH…………………………….58

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Table VII: Age and sex distribution of the various causes of under-five mortality in

UBTH…..59

Table VIII: Age distribution of the conditions originating in the perinatal period………….…..60

Table IX: Class I autopsy findings………………………………………………………..……..61

Table X: Class II autopsy findings………………………………………………………………62

LIST OF FIGURES……………..…………………………………………………..page

Figure 1: Congenital heart disease (hypoplastic left heart syndrome)…………………..63

Figure 2: Kidney in a child with ALL……………………………………………………64

Figure 3: Thanatophoric dysplasia………………………………………………………65

Figure 4: Photomicrograph of bronchopneumonia……………………………………….66

Figure 5: Gastroschisis……………………………………………………………………67

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Figure 6: Necrotizing enterocolitis………………………………………………………68

Figure 7: Intussusception…………………………………………………………..…….69

Figure 8: Menngitis with purulent exudates on the surface of the brain……………..….70

Figure 9: Retroplacental haematoma……………………………………………………..71

Figure 10: Placental infarction…………………………………………………………….72

Figure 11: Chronic villitis………………………………………………………………….73

Figure 12: Diaphragmatic hernia……………………………………………………………74

CHAPTER ONE

1.1. INTRODUCTION

Perinatal and childhood mortality is a global health burden. The United Nations Inter- agency Group for Child Mortality Estimation estimated that nearly 8.1 million children under age five died in 2009. Globally the under-five mortality rate has fallen from 89 deaths per

1,000 livebirths in 1990 to 60 in 2009.1 However the rate of decline is insufficient to meet the

Millennium Development Goal 4 (MDG 4) particularly in sub-Saharan Africa, South Asia and Oceania.1-3 The highest rates of child mortality continue to be in Sub-Saharan Africa, where 1 child in 8 dies before age five—nearly 20 times the average of 1 in 167 for developed regions.1,3 Nigeria, is one of five countries that together accounted for 50% of all global under-five deaths in 2009. In fact Nigeria accounted for about 10% of total under-five deaths worldwide in 2009.1

The persistence of high levels of childhood mortality in the developing countries led the

United Nations (U.N.) to include its significant reduction in the eight Millennium

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Development Goals (MDGs) to be reached before 2015.4 Specifically, the target of MDG-4 is to reduce the under-five mortality rates (UFMR) by two thirds, from 1990 to 2015.

Recently the World Health Organization (WHO), estimates and progress towards attainment of the Millennium Development Goals had shown poor progress on the part of many nations especially in sub-Saharan Africa including Nigeria.1,2,4

To be able to redouble efforts at actualizing the MDG-4, all countries need some epidemiological information to prioritize, plan, and implement public health interventions.

Vital event registration that includes cause-of-death data is used to establish the cause structure of mortality in high income and some middle income countries, but these are generally not available for the countries where 90% of child deaths take place.5 As in most countries of the developing world, health statistics in Nigeria are often rough estimates and most published health statistics are based on hospital records. Most published data upon which most childhood mortality statistics are derived are non-autopsy based; from patient case summaries and death certificates. Invariably mortality data derived from either clinical or autopsy materials alone, cannot be as comprehensive as those from combined clinical and autopsy materials.6 Autopsy studies have revealed that there are discrepancies between diagnoses made by clinicians and those made by pathologists through autopsy.7-13

To be able to be on track effectively towards attaining MDG-4 adequate knowledge of the cause of death structure in children under five year of age is of utmost importance. The autopsy is an invaluable tool in this regard. Tanaka et al advocated the autopsy as one of the main ways in which the perinatal mortality rate can be improved.14 Mortality statistics which are not a product of rough estimates of patient clinical records but one based on proper autopsy audit will go a long way in fast tracking the nation towards meeting MDG-4. This is in view of the fact that reliable information on the magnitude, patterns and trends of causes of death of those in the perinatal and under-five age group helps decision makers to assess areas

12 of need, prioritize interventions and monitor progress. The relevance of this prospective autopsy study is to document the pattern of perinatal and under-five mortality as well as the major causes as seen at the University of Benin Teaching Hospital (UBTH), Benin City.

CHAPTER TWO

2.0 LITERATURE REVIEW

2.1 AUTOPSY

2.1.1 DEFINITION OF AUTOPSY

Autopsy, a word which is synonymous with necropsy and post-mortem examination is derived from the Greek word “autopsia” which literally means “to see for one self”. It entails a detailed examination which includes the external examination of the corpse, and the evisceration and subsequent careful dissection of the contents of the cranial, thoracic, abdominal and pelvic cavities. Examinations restricted to a particular body cavity (either due to the relatives wishes or because of some infectious hazard), or to the sampling of the organs in the unopened body with a biopsy needle are also regarded as autopsy examination.15

2.1.2 HISTORY OF THE AUTOPSY:

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The autopsy has a long history that has been influenced by the prevailing medical models of the time as well as superstitions and religious beliefs in earlier times. Human dissections in ancient Egypt were confined to the process of mummification in which embalmers attempted to preserve the body intact. In classical Greek times though there were animal and some human dissections, there was little medical intent in the autopsy since diseases were believed to result from the imbalance of theoretical “humours” which were not considered to have a simple anatomical basis. In Anglo-Saxon England the prevailing belief was that disease was due to magical causes and that further investigation of the body was not only fruitless but might also be positively dangerous. The autopsy examination in its modern form is traceable to Giovanni Battista Morgagni (1682-1771) who emphasized the importance of and correlation of clinical and pathological findings.

Xavier Bichat at the close of the 18th century revolutionized the autopsy examination by recognizing the place of tissues and not just organs in the understanding of disease. The father of the modern day autopsy is widely regarded to be Karl Rokitansky (1804-78). He initiated the concept of a thorough and systematic autopsy examination that ensured that every part of the body would be examined in identical fashion regardless of the clinical history.15

The nineteenth century marked the golden era of the autopsy when tens of thousands of autopsies on adults provided the database that underlies modern adult medicine. The medical science of paediatrics developed in a similar way with much of that knowledge gained from paediatric autopsies. More recently, the specialties of neonatology and perinatology have benefited from autopsies on infants, neonates and foetuses.15,16

2.1.3 KINDS OF AUTOPSY:

Autopsies can be categorized as either hospital (clinical) autopsy or coroner

(forensic/medico-legal) autopsy.

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The hospital autopsy is often performed on individuals in whom the disease causing death is known and manner of death is not known. In such cases the purpose of autopsy is to determine the extent of the disease and /or the effects of therapy and the presence of any undiagnosed disease of interest or that might have contributed to death. The next of kin must give permission for the autopsy and may limit the extent of the dissection.17

The forensic autopsy is ordered by the coroner or medical examiner as authorized by law with the statutory purpose of establishing the cause of death and answer other medico-legal questions. The next of kin is not required to authorize and may not limit the extent of the autopsy.17

2.1.4 BENEFITS OF THE AUTOPSY :

In both clinical and forensic autopsies, the autopsy is instrumental in accurately establishing the cause and manner of death. Autopsies also allow confirmation, classification and correction of antemortem diagnosis as well as the identification of new and re-emerging diseases, and thus they are important in both protecting the public health and improving the accuracy of vital statistics.18

The list of new diseases or the better understanding of diseases discovered and elucidated from autopsy studies are many and have advanced medical science considerably. Autopsy studies have improved and refined our understanding of such diseases as myocardial infarction and heart diseases,19 human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), Alzheimer’s disease and other dementias.19-20

From a public health perspective, autopsies have proven particularly important as an epidemiological tool for establishing risk factors and identifying potential disease outbreaks.

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A case in point is the 1999 outbreak of encephalitis that occurred in New York City, in which the aetiological agent was found to be the West Nile virus.21

Autopsy can be used for quality assessment. It actually acts as the “gold standard” for which the accuracies of current diagnostic techniques are compared with to derive test specificities and sensitivities.10 The autopsy is also able to serve as a quality assurance tool to assess standards of clinical practice. Autopsy studies have documented significant discrepancies between clinical diagnoses and autopsy diagnoses that have important implications in terms of clinical care. Moreover, major diagnostic errors detected by autopsies indicate substantial inaccuracies in death certificates and hospital discharge data that have important roles in epidemiological research and health care policy decisions.22

In terms of benefit for the family, a clearer understanding behind the cause of death can help in the grieving process. In rare situations there maybe discovery of genetic diseases which enables family counselling on the implications and subsequent management of further pregnancies.23

The autopsy also provides medical students a better opportunity to learn anatomy, gross pathology and sharpen observational skills. Students are also able to learn soft skills such as professionalism and attitude of respect. This desensitization process when observing autopsies is obviously of help in preparing students for the future when they will have to care for dying patients.24

2.1.5 CHALLENGES IN CONTEMPORARY AUTOPSY PRACTICE

The challenge in contemporary autopsy practice revolves around the issue of declining rates of autopsy practice and the threat of modern technology.

2.1.5.1 DECLINING RATES OF AUTOPSY

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Autopsy rates have been on the decline on a global basis over the past decades.25 The exact rates are difficult to delineate owing to differences in the reporting of data and to the fact that no institution is singularly responsible for collecting autopsy data systematically.

Numerous factors influence the differences in autopsy rate reporting amongst institutions; for instance whether forensic, outside bodies, stillbirths and perinatal deaths are included in the reported rates.26

It has been estimated that in the United States before 1970, autopsies were performed in 40% to 60% of all cases involving hospital deaths; in recent years this number has decreased to approximately 5%.20 In Australia the rate decreased approximately 50% between 1992 and

2003.27 Reports from Denmark also show that autopsy rate had been on the decline. The rate decreased from 45% in 1970 to 16% in 1990.28

In a Nigerian report from the University College Hospital Ibadan, the autopsy rate for the year 1996 was 39.60% with coroner’s and non-coroner cases constituting 68.17% and

31.85% respectively;12 The autopsy rate had remained consistently low.

The paediatric age group is not exempted from the general decline in autopsy rates as they have shown a downward trend also. However the paediatric autopsy rates are not declining as fast as adult autopsy rates.29 Rates as high as 26% to 40% were reported in the decade spanning the early 1980s to early 1990s in studies in the United States.9,30-31 The overall paediatric autopsy rate in year 2000 was 40% in Salt Lake City USA.4 In a study in Wales there was a decline from a rate of 66.5% in 1994 to 47.97% in 2003.32 In one of the publications from a British centre on neonatal autopsy rates, Porter and Keeling calculated the rate to be 90% in Oxford during the early 1980s.33 The fact that individual characteristics of different institutions and populations vary should be noted when comparing rates.

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In Scotland, the autopsy rate for stillbirths and neonatal deaths in 2001 was noted to have declined to 50.8% from a rate of 72.4% in 1997.34 Brodlie et al in 2002 reviewed the case records of 314 neonatal deaths in Edinburgh between 1990 and 1999. An autopsy was performed in 67% of cases but the rate declined throughout the decade by an average of 2.8% per year.11

However despite the general downward trend in autopsy rate, policy decisions at the level of individual hospitals coupled with involvement of all necessary staff and adequate staff training on the methods of and importance of the procedure can lead to rise in consent rates.

In Edinburgh there was a steady increase from 38% in 2001 to 79% in 2004 for neonatal autopsy rates through appropriate policy directions.35

In the developing countries paediatric autopsy rates are generally low compared to the developed nations. In the greater part of the 2nd half of the first decade of the 21st century, the perinatal autopsy rate in Malaysia is as low as 4.5%.36 In Nigerian studies, the paediatric autopsy rates are generally modest as in other parts of the developing world. In fact

Oluwasola et al documented that there had been a remarkable decline in hospital autopsy rate in the University College Hospital Ibadan over the last two decades. The decline affected both adult and paediatric patients37 In a review of childhood mortality at the University

College Hospital Ibadan annual paediatric autopsies fell from 60% of cases in 1961 to 18% in

1988,6 while a rate of 7.4% was found for the years 1996-2000.38 A study in Lagos (October

1993 – September 1994) revealed a paediatric autopsy rate of 24.8%,26 however by the end of the 1990s (1996—2000) the perinatal autopsy rate in Lagos University Teaching Hospital was 20.1%.39 A year 2006 to 2010 retrospective review from the University of Benin

Teaching Hospital showed a 0.8% neonatal autopsy rate.40

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Ideally, all paediatric cases should be submitted for postmortem examination. An autopsy rate of at least 75%, especially in cases of perinatal death, is necessary to achieve educational, quality control, and research goals.41

2.1.5.1.1 REASONS FOR THE DECLINE IN AUTOPSY RATE:

The reasons for the continuing decline in autopsy rate are complex and multifaceted.

Attitudes among health care professionals are certainly a factor in declining autopsy rates.

Perhaps the main reason for the decline is that clinicians are not asking for consent to have autopsy done on their patients; most times this responsibility is delegated to the most junior member of the team.42-43 Many residents, even chief residents report that they have received no instructions on the autopsy procedure, obtaining consent, and the role of religion or cultural background in attitudes towards autopsy.43-44

One study found that clinicians attributed the decline in autopsy rates in part to difficulty in obtaining permission from the family.43,45 Some clinicians may not approach grieving relatives for permission for autopsy because they have their own reservations or because they do not have confidence in their communication skills.43,46 The way a family is asked for autopsy consent goes a long way to determine if consent will be given or not. If the clinician is uncomfortable and ill-informed, it is likely that this will be communicated to the family, who, in turn, will be less likely to consent to the autopsy.

Many clinicians are not requesting autopsy because they are confident of the cause of death;47 this is as a result of over-reliance on available high technology diagnostic modalities yielding better pre-mortem diagnoses.45-47 This however is not supported by the data, which indicate that unexpected, clinically significant diseases or complications are found in 22% to 33% of autopsied patients, a figure that has not changed in 100 years.48 A discordance rate of 18.13% was seen in Ibadan for the year 1996.12

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The primary reasons families decline autopsy are fear of disfigurement, concern that the procedure will delay funeral arrangement, religious objections, lack of knowledge about the procedure and a feeling that the deceased has suffered enough.46 Cost, lack of rapport with the physician, stress around the time of death and lack of consensus with other family members regarding the procedure have also been reported as barriers to obtaining consent from the next of kin.46,49

Religious objection to the autopsy is another commonly encountered barrier to autopsy.

Different religions have placed different limitations on the autopsy. For Judaism, an autopsy may be performed when the cause of death is undetermined, when the autopsy may help to save the lives of others, or when relatives might benefit from the knowledge gained by autopsy.50 Catholicism and most protestant religions accept autopsy on almost any occasion, but specify that the body must be treated with respect and the family’s consent must be obtained.48 There are divergent opinions on the appropriateness of autopsy amongst muslims.

Most muslim leaders do not condone autopsy because of the need to bury as soon as possible after death. Consent for autopsy is usually declined unless the death is suspicious.51-52

However there have been muslim legal opinions (fatwa) stating that autopsies are acceptable because they benefit the living.53

The problem of decline in autopsy rates has been compounded in recent times by the public resistance to autopsies due to the considerable adverse media attention to the retention of organs, particularly hearts and brains.54 The recent changes in medical undergraduate curricula in some western nations are resulting in many medical students graduating from some medical schools without ever having seen an autopsy. This means that in many cases, future doctors will have even less knowledge of the role of autopsy in verifying cause of death. Neither will these new doctors have had any personal experience of autopsies to enable

20 them to give informed answers to the concerns of relatives whose agreement is being requested.54

2.1.5.2 AUTOPSY AND MODERN TECHNOLOGY

Modern diagnostic imaging techniques have been advanced as one of the formidable reasons why autopsy rates have continued to decline as they offer highly reliable antemortem diagnoses. However the usefulness of autopsy practice still stands. Advances in technology and availability of sophisticated diagnostic methods, have resulted in a reduction in class I errors detected at the autopsy in the past four decades.22 Despite this reduction, class I errors continue to be reported in up to 12% and class II errors in up to 29% of neonatal and paediatric autopsies.9 It is also established that clinicians cannot reliably predict which autopsy will yield major unexpected findings despite extensive investigations.9

Modern diagnostic methods such as computerized tomography (CT) and magnetic resonance imaging (MRI), are all still incapable of reducing diagnostic errors to an extent of rendering the autopsy irrelevant. CT scans have been reported to have very high rates of false positives, and cannot detect contusions or superficial lesions such as small haematomas or lacerations.55

Similarly MRI is limited by image resolution and can only offer less precise diagnosis. For instance where an autopsy would be able to provide a diagnosis of acute myocardial infarction secondary to coronary artery thrombosis, an MRI would only be able to determine ischaemic heart disease.24 Imaging alone is also unable to sample the body for toxins or micro-organisms or to provide tissue samples for histopathological studies or microbiological testing. Also an MRI autopsy is not cost effective and puts extra demand on resources with numerous competing interests.24

It is pertinent to note however that there is a prominent place for these other modalities in the autopsy. The X-ray has on occasion shown clearly bullets where these have been difficult to find by meticulous dissection at autopsy. CT scans are also better at detecting gas embolism

21 and small pneumothoraces than standard autopsies. Moreover, MRI and other non-invasive postmortem modalities may serve as an adequate alternative when consent for a full autopsy is declined.55

2.1.6 CLASSIFICATION OF AUTOPSY DIAGNOSES AND FINDINGS:

Autopsy studies have documented significant discrepancies between clinical diagnoses and autopsy diagnoses that have important implications in terms of clinical care.7-13,22 These discrepancies do not necessarily reflect clinician error but may reflect misinterpretation of test results, failure to respond appropriately to abnormal clinical findings, atypical clinical presentation, and the limits of current diagnostic techniques. Various studies look at different aspects and types of discrepancy and classify discrepancies in different ways. Goldman et al suggested a useful method of classification in 1983.25 Veress and Alafuzoff devised another system of classification.56 Use of a defined classification system allows comparability of different research findings.

The Goldman classification has emerged as a useful classification system in that it differentiates between major and minor discrepancies and identifies those deaths where the discrepancy had an impact on patient survival. The drawback of the Goldman classification scheme is that it relies on both objective and subjective interpretation of the findings and some assumptions must be made regarding the theoretical impact of missed or incorrect diagnosis; however there is no practical alternative approach.57

2.1.6.1 THE GOLDMAN CLASSIFICATION

The Goldman classification is into five groups (class I to V) and are composed of25

CLASS I: missed major diagnoses for which detection before death would in all probability have led to a change in management that might have resulted in cure or prolonged survival.

22

The diagnosis was missed because it was not suspected, or because test results were inconclusive.

CLASS II: missed major diagnoses for which detection before death would probably not have led to a change in management, because no therapy had been available at the time or the patient had already received appropriate therapy, even though the diagnosis was not known, or because the patient had refused further evaluation or therapy.

CLASS III: missed minor diagnoses that were related to the terminal disease process, but were not directly related to death.

CLASS IV: missed minor diagnoses that were either important unrelated diagnosis that might eventually have affected prognosis or processes that contributed to death in a terminally ill patient.

CLASS V: complete concordance between ante-mortem diagnoses and autopsy findings.

2.1.7 PROCEDURE FOR OBTAINING AN AUTOPSY CONSENT:

It is of utmost importance that the family be approached in a highly professional way, ideally by the most senior physician available. However the degree of prior clinician contact and rapport must also be considered in determining who approaches the family. The family member identified as the person who must give written permission should be the focus of discussions. The setting should be neutral and the fewer uninvolved parties who may be disruptive and raise irrelevant questions, the better.58

Misconceptions about the autopsy should be addressed. It should be clarified that autopsy studies are done by pathologists, who are specialists in the study of disease, and the body is not “experimented with” or “practiced upon” or in any way mutilated or desecrated.

Religious concerns should be addressed. The family should be told that there will be no delay in or interference with funeral arrangements and no disfigurement. In order to honour some

23 timing restrictions special adjustments may have to be made by the pathology department to expedite the autopsy.50,58

It is important that the family understands the value of the autopsy; amongst several, it helps by dispelling lingering questions about the exact cause of death and assuring that care was appropriate. There may be a question of hereditary disease that can be settled, providing reassurance to the family. 58-59

After these explanations the next of kin should receive the post mortem consent form to read and they should be encouraged to ask questions and make comments. Questions should be dealt with on an individual basis by answering them directly, truthfully, and non-forcefully in a straightforward, tactful, educational way.58

Finally the family should be informed that the result of the autopsy will be discussed with them by the clinician at the time of their choice. This conference should be undertaken without undue delay to assist with the bereavement process.58, 60

2.1.8 ROLE OF HISTOLOGY AT AUTOPSY:

The histopathological examination of lesions seen macroscopically is an integral component of the autopsy. The Royal College of Pathologists recommends that histology should be done on all major organs and any identified lesion provided sufficient consent have been obtained.

This will confirm the macroscopic diagnosis, refine the cause of death and assist in clinical audit.61 Diagnosis made only after histology account for up to 23% of unexpected autopsy diagnoses.13 Diseases such as neurodegenerative disease, myocarditis, abnormalities of the cardiac conduction system, and glomerulonephritis cannot be accurately diagnosed by macroscopic examination of tissue alone.24

Macroscopic diagnosis of bronchopneumonia is especially inaccurate, Roulson et al reported that the diagnosis of pneumonia could be confirmed microscopically in 23% of cases and macroscopic diagnosis was overturned by histology in 31% of cases. Pneumonia can be

24 easily confused with acute respiratory distress syndrome and some form of neoplastic associations.13

Ideally all tissue blocks and slides from all autopsies should be archived as part of a permanent medical record.61

2.1.9 THE PERINATAL AUTOPSY:

2.1.9.1 PURPOSE OF THE PERINATAL AUTOPSY AND PLACENTA

EXAMINATION.

In perinatal deaths, the purpose of the autopsy and placenta examination is to address the following issues:62

1. Independent, objective assessment of gestational age and appropriateness of development for age.

2. Quantitative evaluation of diseases in the newborn with respect to approximate time of onset and duration of influence. An estimation of the interval between intrauterine death and delivery should be included, as well as a distinction between long-standing intrauterine disease, intrapartum disease, and postnatal disease.

3. Identification of intrinsic abnormalities of the foetus incompatible with life.

4. Identification and classification of developmental disorders, including a determination of whether they are genetic, acquired, both, or unknown.

5. Identification or confirmation of abnormalities of placenta or cord that may have compromised the foetus, such as amniotic bands, cord insertion abnormalities, obstruction or rupture of vessels of the umbilical cord, premature separation, extensive infarction or atrophy caused by deficient maternal-placental perfusion, or degeneration of villi.

6. Verification of infection as contributory to premature labour and perinatal mortality.

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7.Assessment of intrauterine exposure to any maternal diseases that can adversely affect the outcome of a pregnancy, such as hypertension, diabetes mellitus, infections or disorders of coagulation, or exposure to drugs or toxins.

2.1.9.2 PERINATAL AUTOPSY PROCEDURE:

2.1.9.2.1 X-RAY EXAMINATION:

Radiology has been established to be of immense value in the practice of perinatal autopsy.

This is particularly so where there are congenital malformations, and radiology should be considered an essential part of the perinatal autopsy.63 X-ray examination, including anteroposterior and lateral views of the entire body, is necessary using a Faxitron.

Conventional X-ray studies can be performed if a Faxitron is not available. Some diagnoses cannot be made without X-ray examination. This applies particularly to bone dysplasias. The

Faxitron is not limited to bony surveys and can be used to demonstrate visceral anomalies by injection studies. By injecting a radiopaque liquid such as barium or an ionotropic contrast, fistulas can be demonstrated. This technique is particularly helpful in identifying bronchial morphology and extrahepatic and intrahepatic biliary ducts, without disrupting the anatomy.64

2.1.9.2.2 PHOTOGRAPHS:

Photographs are of the utmost importance when performing an embryonic, foetal, or infant autopsy. The external features may provide the only information necessary to make the diagnosis of a malformation syndrome. The photographs must be close enough to depict the abnormal features with adequate points of reference remaining in the field and minimum background. In situ photographs can be very helpful, preserving anatomical relationships and depicting visceral lesions before evisceration and fixation. In a paediatric autopsy, a good photograph is often more valuable than any number of microscopic sections.64

26

2.1.9.2.3 CLINICAL INFORMATION:

A complete examination cannot be performed without the important clinical information.64 A basic obstetric and neonatal history must always be specifically sought.63 Personal communication with the clinician in order to emphasize the specialist consultancy nature of the autopsy and the pathologist’s contribution as part of the perinatal care team should be sought. Hospital records should be examined in detail, and all relevant laboratory results available before or during the autopsy.

2.1.9.2.4 EXTERNAL EXAMINATION AND DISSECTION:

The objective of autopsy differs substantially between perinatal and adult autopsies, with the need to document congenital malformations in detail determining most of the differences in technique. It is essential to carry out a very detailed external examination and record in texts and photographs, all external abnormalities. Good photographs, including details of hands and feet and a record of facial and other growth parameters can be invaluable if later review by a medical geneticist is required.

Assessment of appropriateness of foetal growth in relation to clinically assessed gestational age should take place. All the internal organs should be examined in situ initially noting anatomical positions with photographs of any anomaly. Careful examination of the dural folds for significant tears and the posterior fossa for haemorrhage is important to adequately assess birth trauma.63

2.1.9.2.5 TISSUE SAMPLING AND HISTOLOGICAL EXAMINATION:

In the non-macerated stillbirth and neonate, sampling of all organs is desirable as unexpected findings such as evidence of unsuspected viral infections, iatrogenic diseases or unusual developmental malformations of potential genetic significance are common. Assessment of the time course of intrauterine events before death can be made using fat stains on the foetal

27 adrenal as well as assessing the presence of phagocytosed meconium pigment in chorionic macrophages.60

In the severely macerated foetus, histological examination can be more limited and is sometimes best achieved with connective tissue stains.63

2.1.9.3 EXAMINATION OF THE PLACENTA

Examination of the placenta as a key component of the perinatal autopsy had become a routine and regular practice in the field of paediatric pathology. Various practice guidelines had emphasized the need for placental examination in conjunction with the autopsy in determining the cause of death.61-62

In evaluating the importance of the placental examination as a component of the perinatal autopsy, relevant questions for consideration are

i. Is it possible for the cause of perinatal deaths to be revealed by placental

examination and autopsy?

ii. Is it possible for placental examination alone to explain the cause of perinatal

deaths?

iii. Is it possible for autopsy alone to explain all perinatal deaths?

In contemporary times, various perinatal autopsy studies have led credence to the relevant place of placental examination in perinatal death investigation. In a perinatal autopsy series,

2004-2008 by Tellefsen and Vogt, in Norway, the placenta had changes that could explain death in 69.2% of foetal/infant deaths, placental examination only could explain the cause of death in 48.1% of cases, autopsy alone could explain the reason for only 16.3% of perinatal deaths; Abruptio placentae (12.5%), degenerative changes (13.5%), and infection (22.1%) were some of the repeatedly observed diagnoses related to the perinatal deaths.65

28

In a study done in the United Kingdom, Heazell and Martindale demonstrated that in combination with a modern classification system, examination of the placenta reduces the proportion of “unexplained” stillbirths. Placenta examination contributed useful information to the classification of 47% of stillbirths and in 16% of cases provided the only source of information regarding the cause of death.66

2.1.9.3.1 INDICATIONS FOR PLACENTAL EXAMINATIION

The indications for carrying out placenta examination are numerous and includes:67

A. Recommended maternal indication for placental examination

i. Systemic disorders with clinical concerns for mother or infant (eg, severe

diabetes, impaired glucose metabolism, hypertensive disorders, collagen disease,

seizures, severe anaemia [less than 9 g/dL])

ii. Premature delivery 34 weeks or less gestation

iii. Peripartum fever or infection

iv. Unexplained third-trimester bleeding or excessive bleeding more than 500 mL

v. Clinical concern for infection during this pregnancy (eg, human

immunodeficiency virus, syphilis, cytomegalovirus, primary herpes, toxoplasma,

rubella)

vi. Severe oligohydramnios/ polyhydramnios

vii. Unexplained or recurrent pregnancy complication (eg, intrauterine growth

restriction, stillbirth, spontaneous abortion, premature birth)

viii. Invasive procedures with suspected placental injury

ix. Abruption

x. Thick or viscid meconium

B. Recommended foetal and neonatal indications

29

i. Admission or transfer to other than a level 1 nursery

ii. Stillbirth or perinatal death

iii. Compromised clinical condition defined as any of the following: cord blood pH

less than 7.0; Apgar score, 6 or less at 5 minutes; ventilatory assistance, more than

10 minutes; or severe anaemia, haematocrit less than 35%

iv. Hydrops foetalis

v. Birth weight less than 10th percentile

vi. Seizures

vii. Infection or sepsis

viii. Major congenital anomalies, dysmorphic phenotype, or abnormal karyotype

ix. Discordant twin growth more than 20% weight difference

x. Multiple gestation with same-sex infants and fused placentas

C. Recommended placental indications

i. Physical abnormality (eg, infarct, mass, vascular thrombosis, retroplacental

haematoma, amnion nodosum, abnormal coloration or opacification, malodour)

ii. Small or large placental size or weight for gestational age

iii. Umbilical cord lesions (eg, thrombosis, torsion, true knot, single artery, absence of

Wharton’s jelly)

iv. Total umbilical cord length less than 32 cm at term

v. Abnormalities of placental shape

vi. Long cord (more than 100 cm)

vii. Marginal or velamentous cord insertion

2.1.9.3.2 GROSS EXAMINATION OF THE PLACENTA: The placenta should be submitted to the laboratory in the fresh state so that tissue can be taken for pertinent tests, such as bacterial culture, viral culture, cytogenetics, metabolic studies and electron-

30 microscopy. Subsequently, the gross examination may be performed in the fixed or fresh state. Examining the placenta in the fresh state offers the opportunity for palpating fresh infarcts. Amniotic bands are more easily detected fresh. The membranes are less likely to be torn when they are relocated (replaced) to the in utero relationship with the cord and placental disc in the fresh state, allowing a more accurate assessment of completeness. It is also easier to ascertain whether retroplacental blood clots are adherent when examining the placenta fresh. Injection studies of the vasculature in twin placentas can only be undertaken in the fresh state.68

Examining the fixed placenta lessens the infectivity risks of fresh blood and old infarcts are better delineated following fixation. The placenta should be accorded the care and attention that other surgical specimens receive. The gross description and, if necessary, photography of abnormal areas should be meticulous. To avoid missing significant pathology, the gross examination is best performed in a systematic manner.68

The umbilical cord should be measured and its completeness ascertained. Various conditions of the cord such as short cords, long cords, absence or excessive coiling of the umbilical cord,

Umbilical cord lesions, such as true knots or clinical histories of entanglement around necks or limbs, need to be carefully assessed. The insertion pattern of the cord unto the placental disc should also be evaluated for velamentous insertion.68

The site of rupture of the amniochorial membranes should be recorded as it may provide corroboration of placenta praevia deliveries. The membranes should be inspected carefully for strands, masses, colour changes from the usual translucency, (duskiness may indicate infection or meconium staining, green membranes often signify meconium staining, and areas of haemorrhage and fibrin deposition may indicate previous retromembranous abruption).

Pale areas or plaques should be documented. The insertion pattern of the membranes into the placental disc should be documented.68

31

The weight of the placental disc trimmed of the extraplacental membranes and umbilical cord, should be recorded. The placental dimensions are then recorded; The foetal surface should be examined for excessive fibrin deposition, colour and lesions such as amnion nodosum, squamous metaplasia, cysts and subchorionic haematomas. The vessels of the chorionic plate should be examined for thrombosis. The maternal surface should then be examined for integrity or any raggedness of the basal plate and for retroplacental haematoma formation and depression. Palpation of the placenta may reveal lesional areas that will appear on slicing. The placenta should then be sliced at 10–20-mm intervals. The cut slices should be examined for focal lesions such as infarct, thrombi, and excessive fibrin; The extent of these lesions, as a percentage of the total volume of the placenta, also should be documented.

In the absence of lesions, at least two full thickness sagittal blocks, from the foetal to maternal surfaces, should be taken.68

An important pathological consideration is the determination of the chorionicity of the placenta, as perinatal morbidity and mortality are related to chorionicity. Gross determination of the chorionicity of the fused placenta can be undertaken by visual inspection and by separating the amnion layers from the fused layer of dividing membranes. In the dichorionic placenta the dividing membranes are thicker, less translucent and separate to leave an intervening chorion layer, while in the monochorionic diamniotic placenta, the dividing membranes are thinner, almost transparent and separate without leaving an interposed chorion layer.68

2.1.9.3.3 HISTOLOGICAL EXAMINATION OF THE PLACENTA

A methodical approach to examining the placenta should assess each component of the placenta, namely the umbilical cord, amniochorial (or extraplacental) membranes and the placenta. The umbilical cord can be examined either from the outside in or from the inside out by seeking lesions of the epithelial surface, Wharton’s jelly and the vessels. The

32 extraplacental membranes can be examined from the surface down, approaching, in turn, the amniotic epithelium and subjacent mesenchyme, the chorion and the decidua parietalis. The placenta is best examined broken down into its constituent parts: chorionic plate, placental parenchyma, intervillous space and basal plate. The chorionic plate is approached from the amniotic epithelium to the subchorionic intervillous space, examining in turn the structures in between, namely, the chorionic plate itself and the chorionic vessels. The placental parenchyma is approached from the trophoblastic (or chorionic) layer inwards, assessing, in turn, the syncytiotrophoblastic layer, formation of vasculosyncytial membranes, cytotrophoblastic layer, villous stroma, cellular constituents, foetal vessels and contents of the foetal vessels. When looking at the villi, the intervillous space also is examined. The components in the basal plate, namely, cellular infiltrates, trophoblast and maternal vessels, are then examined.68

2.1.9.3.4 MAJOR PATHOLOGICAL CATEGORIES

A number of well recognized diseases readily diagnosed using the placenta includes:

Acute chorioamnionitis

Acute chorioamnionitis is defined histologically by the presence of acute inflammatory cells within the foetal membranes. It indicates infection in the amniotic cavity due to an ascending bacterial infection. There is poor correlation of histological acute chorioamnionitis with

“clinical” acute chorioamnionitis. Histological chorioamnionitis is the gold standard against which other clinical predictors of infection are measured. The mother and baby both contribute to the inflammatory response in amniotic infection. The common causative organisms include Trichomonas spp. which often elicits a heavy and dense neutrophilic infiltrate, yet has little effect on neonatal wellbeing. Conversely, Group B streptococcal infection is one of the most virulent perinatal infections, yet intraamniotic infection and neonatal sepsis may occur without identifiable histological chorioamnionitis.69

33

Necrotising chorioamnionitis is a late complication of amniotic inflammation, and is associated with an increased risk of perinatal death and preterm delivery and should be specified by the pathologist in the pathology report. Necrotising chorioamnionitis is also associated with preterm labour, premature rupture of membranes, and decreased gestational age in very low birthweight infants.70

Chronic villitis

Chronic villitis is defined histologically as an infiltrate of lymphocytes and histiocytes affecting the chorionic villi. It is a relatively common process which can be identified in up to

15% of term placentas. Chronic villitis may be infectious in which there is a specific aetiological agent, or it may be nonspecific, where no infectious cause is identified. Infectious causes of chronic villitis include the TORCH (toxoplasma, rubella, cytomegalovirus and

Herpes simplex) infections. These may recur in a minority of cases, and are associated with perinatal mortality. Infectious causes which are evident on histological examination include cytomegalovirus, syphilis, toxoplasmosis and Herpes simplex virus. The chronic inflammatory infiltrates of infectious chronic villitides include plasma cells.70 In contrast, nonspecific chronic villitis, termed villitis of unknown aetiology (VUE), is characterized histologically by an infiltrate composed of lymphocytes and histiocytes, and lacking plasma cells. Villitis of unknown aetiology is associated with intrauterine growth restriction (IUGR), and the frequency of IUGR with VUE appears to be proportional to the extent of villous involvement. High-grade VUE is also associated with an increased risk of adverse foetal neurological outcome. In addition, high-grade and diffuse VUE is commonly associated with increased perivillous fibrinoid deposition, a process that increases the risks of IUGR, prematurity and stillbirth.VUE recurs, and recurrent VUE is associated with significant perinatal mortality.70-71

34

Foetal vascular obstructive lesions and foetal thrombotic vasculopathy

Thrombotic or occlusive lesions may occur within the foetal circulation with potentially serious consequences to the foetus. Pathophysiologically, foetal vascular obstructive lesions are the result of Virchow’s triad of stasis, hypercoagulability and vascular damage within the foetal circulation of the placenta. Stasis within the foetal circulation may be the result of a compromise of blood flow through the umbilical cord resulting from prolonged umbilical cord compression, cord entanglement, abnormal insertion, or abnormal length or coiling, intrauterine foetal heart failure (hydrops foetalis), or polycythaemia. Hypercoagulability may result from poorly-controlled maternal diabetes mellitus, autoimmune conditions (e.g. antiplatelet antibodies or antiphospholipid syndrome), or maternal or foetal thrombophilias.

Foetal vascular injury may result from the foetal inflammatory response to severe chorioamnionitis, meconium toxicity or haemorrhagic endovasculitis.72 Histological manifestations include intimal fibrin cushions or fibromuscular sclerosis affecting large foetal vessels, haemorrhagic endovasculitis and avascular chorionic villi. The consequences include intrauterine foetal death, perinatal asphyxia and hydrops foetalis. Foetal systemic thromboembolism is a potential complication of thrombi in large chorionic surface veins.

Others include intrauterine growth restriction, foetal seizures, amputation necroses of foetal limbs, neonatal stroke, cerebral palsy and poor long-term neurological outcome.69

Maternal vascular malperfusion and placental infarction

Oxygenation of the placenta, and hence of the foetal circulation, depends on adequate perfusion of the maternal vascular (intervillous) space by oxygenated maternal blood via maternal uterine and decidual arteries. The maternal arteries transform to large-calibre and low-resistance vascular channels in pregnancy.69 Abnormalities of this process results in decidual vasculopathy and a spectrum of pathological features affecting the maternal

35 vasculature, including acute atherosis, mural hypertrophy of the membrane arterioles and muscularised basal plate arteries. Villous malperfusion results in accelerated villous maturation which impart to the placenta a histological appearance of development and maturation which is advanced for its actual gestational age. In addition, such placentas are often small for the gestational age and have an increased foetal-placental weight ratio.73

Complete cessation of maternal vascular perfusion to a region of the placenta results in infarction. Small infarcts at term may not have clinical significance. Large or multiple small infarcts involving a substantial proportion of the placenta, or infarcts in premature placentas are markers for significant maternal vascular disease, especially hypertension. Features of decidual vasculopathy, accelerated villous maturation and placental infarction are seen in pregnancies affected by preeclampsia and gestational hypertension, lupus erythematosus, and in women with lupus anticoagulant and antiphospholipid antibodies. The presence of antiphospholipid antibody is associated with recurrent abortions. Maternal vascular underperfusion is an important cause of foetal growth restriction, preterm rupture of membranes and preterm labour.74

Placental haematomas and thrombi

Placental haematoma or thrombi formation may occur at various anatomical localities within the placenta, and include retroplacental haematomas, marginal haematomas, intervillous thrombi, subchorionic thrombi, and subamniotic haematomas. Retroplacental haematomas are the morphological substrate for the clinical syndrome of abruptio placentae.

Morphological clues to the occurrence of a significant acute retroplacental haematoma include a fixed depression in the maternal surface, histological findings of decidual basalis haemorrhage with necrosis and inflammation, adjacent intravillous haemorrhage, and in some situations, early villous infarction. The causes of retroplacental haemorrhage are varied, but in a significant proportion, are related to abnormalities of the vascular bed

36 arteries. Retroplacental haematomas occupying more than a third of the maternal floor of the placenta are associated with significant foetal morbidity and mortality.69

Massive perivillous fibrinoid deposition and maternal floor infarction

Massive perivillous fibrinoid deposition (MPFD) and maternal floor infarction (MFI) are related entities characterized by excessive deposition of fibrinoid material in the placental parenchyma. In MPFD, the pattern of fibrinoid deposition is diffuse, while in MFI, the fibrinoid is laid down along the maternal floor of the placenta. The cause remains unknown

The clinical importance of these lesions relates to the associated poor outcome for the foetus and for the high risk of recurrence in future pregnancies. Stillbirth is reported to occur in up to 50% of affected pregnancies. There is also an increased frequency of intrauterine growth restriction, and increased incidence of preterm delivery. The disorder can occur in the first and second trimesters, when it is associated with recurrent miscarriages.69, 75

Meconium staining

The clinical significance of meconium relates to the duration of meconium discharge to delivery of the infant and placenta. The mere presence of meconium at the time of birth in a term pregnancy which is unaccompanied by staining of the placenta, correlates with acute meconium staining, and may not have clinical relevance. On the other hand, the prolonged presence of meconium in utero, characterized by progressively extensive staining of the placenta, correlates with subacute or chronic meconium staining and indicates a high risk of the foetus for meconium aspiration syndrome, perinatal asphyxia, cerebral palsy or other central nervous system deficits.69, 76 Meconium is toxic to the placenta, in particular to the membranes and umbilical cord. The amniotic epithelium, subjected to meconium exposure for several hours, undergoes degenerative changes characterized by columnarisation, formation of pseudopapillae, cytoplasmic vacuolation, and eventual necrosis and sloughing.

The membranes become oedematous with easy slippage of amnion from chorion. The

37 umbilical vein and chorionic surface vessels undergo contraction and segmental mural necrosis with degeneration of the medial myocytes. Meconium pigment may be identified in amniotic macrophages as soon as one hour after discharge, and after four to six hours, may also be identified in chorionic macrophages.69

Abnormalities of the umbilical cord

The umbilical cord consists of two umbilical arteries and the umbilical vein suspended within

Wharton’s jelly. The typical umbilical cord measures 50–60 cm at term. Abnormalities of cord length are best determined through measurement at the time of delivery. Excessively short cords (less than 30–40 cm in length) are seen in infants with syndromes associated with decreased foetal movement (e.g. trisomy 21, skeletal dysplasias).77 There is also an association with developmental anomalies such as abdominal wall defects.69 Excessively long cords (greater than 70–80 cm in length) are associated with foetal distress, cord entanglement, cord prolapse, true knots, hypercoiling, constriction and thrombosis.

Abnormalities of the coiling index often are associated with adverse perinatal outcome, including increased perinatal mortality, intrauterine growth restriction and foetal distress.

Hypercoiled cords may show stricture formation in cases of intrauterine foetal demise, and in the presence of signs of vascular obstruction, such as thrombosis, may be considered the cause of intrauterine death. Single umbilical artery (SUA) should always be looked for at birth. There is an association with growth restriction, maternal diabetes mellitus, antepartum haemorrhage, polyhydramnios and oligohydramnios. SUA may also be an isolated anomaly seen in otherwise perfectly healthy infants.78

The insertion of the umbilical cord is normally central, paracentral or eccentric. Cords inserting at the edge of the placental disc (marginal insertion) and into the membranes

(velamentous insertion) are more common in multiple pregnancies and in association with

SUA. Velamentous cord insertions result in the presence of membranous blood vessels which

38 run along the free placental membranes unprotected by Wharton’s jelly. Such vessels are vulnerable to injury, and are at risk of thrombosis or haemorrhage. Velamentous vessels located over the cervical os constitute the serious condition of vasa praevia, and pose the risk of rupture, haemorrhage and exsanguination during vaginal delivery.Thrombosis of umbilical vessels occurs most frequently near term. They may develop due to velamentous cord insertion, acute funisitis, umbilical cord knotting, hypercoiling or torsion, amniotic bands, or maternal or foetal coagulopathies. Thromboses severely compromise the foetal-placental circulation, and lead to foetal injury or death.69

2.1.9.4 ANCILLARY INVESTIGATIONS:

Ancillary investigations to the performance of the perinatal autopsy which may help in arriving at a cause of death include; cytogenetics, microbiological culture, metabolic disease evaluation, as well as post-partum laboratory evaluation of the mother for hyper-coagulable states.63

2.2.0 PERINATAL MORTALITY

2.2.1 DEFINITION

Perinatal mortality, is defined as deaths within the first seven days of life (early neonatal death) as well as stillbirths. Stillbirths (foetal deaths) is death prior to the complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of pregnancy; the death is indicated by the fact that after such separation the foetus does not breathe or show any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles. In the international statistical classification of diseases, 10th revision (ICD-10), the measurement focus is on foetal deaths in the last two trimester of pregnancy and is defined by a birth weight of 500g or more; if birthweight is unknown, by gestational age of 22 completed weeks or more or if both these criteria are unknown, by crown-heel length of 25cm or more. For international comparability

39 the World Health Organization, recommends reporting of late foetal deaths (third-trimester stillbirths at ≥1000g birth weight, ≥ 28 completed weeks of gestation or ≥ 35cm body length).79

Stillbirths are grouped into antepartum stillbirths (foetal deaths that occur before the onset of labour), and intrapartum stillbirths (foetal deaths that occur after the onset of labour and before delivery).80

Perinatal mortality is an important indicator of maternal care and of maternal health and nutrition; it also reflects the quality of obstetric and paediatric care available. Although social factors exert the main influence on the outcome of a birth, as societies advance good medical care tends to play a greater role.80

Worldwide, there were 5.9 million perinatal deaths.,in 2004, almost all of which occurred in developing countries. Stillbirths accounted for over half of all perinatal deaths. According to

2000 estimates, one third of stillbirths took place during delivery. Those intrapartum deaths are closely linked to place of, and care at, delivery and are largely avoidable with skilled care.

In developing countries, just over 40% of deliveries occurred in health facilities and little more than one in two with the assistance of a doctor, midwife or qualified nurse.81

The most common measure of perinatal mortality is the perinatal mortality rate (PMR);80 calculated as:

number of late foetal deaths( stillbirths) + number of early neonatal deaths ×1000

total births· where total births =live births +foetal deaths(stillbirths)

2.2.2 PERINATAL MORTALITY AND MILLENNIUM DEVELOPMENT GOAL- 4

The fourth goal (MDG-4) commits the international community to reducing mortality in children aged younger than 5 years by two-thirds between 1990 and 2015.4 Between 1960

40 and 1990, the risk of dying in the first 5 years of life was halved—a major achievement in child health.82

However, an increasing proportion of child deaths is now in the neonatal period; WHO global estimates for 200083 show that 38% of all deaths in children younger than age 5 years happen in the first month of life. Deaths in the first week of life have shown the least progress. In

1980, only 23% of deaths arose in the first week of life; by the year 2000 this figure had risen to an estimated 28% (3 million deaths). This translates into early neonatal deaths (a component of perinatal mortality) being responsible for some three-quarters of all neonatal deaths. To be able to meet MDG-4, a substantial reduction in deaths in the neonatal period in high-mortality countries is needed, and reducing deaths in the first week of life will be essential to progress in this direction.84

One major step to be taken in being able to tackle this issue of early perinatal deaths is to be able to explicitly define the cause of death structure. This varies from one locality to another thus local understanding of the epidemiology of perinatal mortality is needed. This can be achieved by regular perinatal mortality classifications.85

2.2.3 CLASSIFICATION OF PERINATAL MORTALITY

Classification of perinatal deaths is primarily the systematic arrangement of deaths in categories based on information known about them to aid in the process of information management.86 The basic requirements for classification systems are to record the underlying cause of death and other relevant information to aid in understanding of the true contributors to perinatal death, to be easy to apply, and to perform robustly across different settings.

According to Whitfield, the purpose of classification is ‘to identify deficiencies in the provision of care, to focus attention where improvements are already possible and to indicate where new developments or knowledge may be expected to lead to further advance’.87 The

41 causes of perinatal death seldom operate in isolation and in many cases, there is no single cause which can adequately explain the sequence of events leading to death.

Different classification systems have been designed for different reasons with different approaches, definitions, levels of complexity and availability of guidelines. No single system is universally accepted and each has strengths and weaknesses.88 Some of the commonly used systems are:

2.2.3.1 ABERDEEN CLASSIFICATION: The modified Aberdeen is a clinicopathological classification, the first version was proposed by Baird et al.89 and aim is to classify each death in accordance with the factor which probably initiated “the train of events ending in death”. It is almost entirely based on clinical information as in the experience of the designers of the system, post-mortem examinations fail to explain cause of death in many cases. It has eight defined categories. There have been two attempts to update and rationalize the classification.87,90

2.2.3.2 WIGGLESWORTH CLASSIFICATION: Wigglesworth advocated a pathophysiological approach and the goal of the classification is to subdivide cases into groups with clear implications for priorities for prevention and alterations in clinical management. There are five categories.91 Areas of ambiguity have been addressed by various works92-93 The classification has been found to be particularly useful in developing countries94 There has been a variety of classifications based on the Wigglesworth classification but using an “extended” categorization; these classifications have proved less reliable than the original. Thorton and O’Hara found that autopsy findings resulted in changes in classifications in 21% of deaths95 whereas the original grouping was changed in only 9% of perinatal deaths when classified before or after considerations of postmortem findings93

2.2.3.3 PERINATAL SOCIETY OF AUSTRALIA AND NEW ZEALAND –

PERINATAL DEATH CLASSIFICATION: is similar to Aberdeen classification in that it

42 is based on antecedent obstetric factors and seeks to identify the factor that initiated the sequence of events leading to the death. It is based on clinical and autopsy findings, including placental pathology. It is mainly hierarchical in descending order with some qualifications that are delineated in the guidelines.96

2.2.3.4 TULIP CLASSIFICATION: is a system that aims to define the underlying cause and mechanisms of perinatal mortality based on clinical and pathological findings for the purpose of counselling and prevention. Cause of death was defined as the initial demonstrable pathophysiological entity initiating the chain of events that irreversibly led to death. It consist of six main classes with subclasses. The mechanism of death is defined as organ failure that is not compatible with life, initiated by the cause of death that has directly led to death.88

2.2.3.5 ReCoDe CLASSIFICATION SYSTEM: the ReCoDe classification system (relevant condition at death) was developed to define relevant clinical categories for stillbirths. It seeks to identify the relevant condition at the time of death in utero. The system aims to establish what went wrong and not necessarily why.97 It is not designed for allocation of cause of death.

2.2.3.6 CLASSIFICATION BY HEY et al: This classification has a pathological approach based on foetal and neonatal entities and aim is to define the clinicopathological process within the baby and the way they contribute to, and help to explain the baby’s death.98

2.2.3.7 CLASSIFICATION BY HOVATTA et al: a system especially designed for the group of stillbirths. Aim is to classify underlying cause of death considering both clinical and autopsy findings. The classification groups are based on maternal, fetal, placental or a combination of these entities. Definitions for the placental causes, however, do not exist.99

2.2.3.8 CLASSIFICATION BY GALAN-ROOSEN et al: is one of the few systems based on maternal, foetal and placental entities. Aim is to serve prevention and classify underlying

43 cause of death with a clinicopathological approach based on the entities that initiated the chain of events leading to death.100

2.2.4 COMPARISON OF CLASSIFICATION SYSTEMS

Not all of the systems address maternal, foetal and placental factors together, and the information required to assign a cause of death varies between systems. Vergani et al compared ReCoDe, Wigglesworth, Tulip, and Galen-Roosen using 154 stillbirths diagnosed at the San Gerardo Hospital Italy from 1995 to 2007. Autopsy and placental examinations was performed in 98.7% of the stillbirths. The proportion of cases classified as unexplained were 45% for Wigglesworth, 14% for ReCoDe, and 16% for Tulip. The proportion of congenital anomalies in Wigglesworth and Tulip were similar at 35.7% and 33.8% respectively. The reduction of rates of ‘unexplained’ in the recent systems has been due to the inclusion of fetal growth restriction and pathology of the placenta.101 The authors also indicated that the autopsy and placental pathology are of utmost importance for evaluating the stillbirth.

Flenady et al evaluated Amended Aberdeen, Extended Wigglesworth, PSANZ-PDC,

ReCoDe, Tulip and CODAC classification systems for stillbirth. The Wigglesworth and

Aberdeen classifications were shown to have the highest proportion of unexplained stillbirths

(50.2% and 44.3% respectively) and CODAC the least with 10.2% of cases unexplained.

They concluded that the extended Wigglesworth and Amended Aberdeen systems cannot be recommended for classification of stillbirths.102

2.2.5 RISK FACTORS ASSOCIATED WITH PERINATAL MORTALITY:

A number of consistent and striking associations have been found for perinatal mortality.

These risk factors are defined as maternal characteristics as well as foetal factors associated

44 with perinatal deaths but without a known causal pathways leading to the death. These include;103

MATERNAL AGE: there is generally a U-shaped variation with the risk of perinatal death, very young and older mothers having the highest rates. However there are differences in pattern according to time of death, with the stillbirth rate increasing with maternal age and a shallow U-shape for neonatal deaths. In Jamaica it was found that the relationship between advanced maternal age and stillbirths was mainly associated with antepartum fetal deaths and was explained by the increased rates of hypertension, bleeding, and syphilis in older mothers.

PARITY: parity is measured as the number of previous pregnancies resulting in live or stillbirths. The parities with least risk of perinatal death are parities one and two. Thereafter in general, the risk rises with increasing parity. There is some evidence that the difference in risk between parities 0 and 1 has decreased over time but is still apparent in most countries.

PAST OBSTETRIC HISTORY: outcome of previous pregnancy is one of the most important factors in predicting the risk to the current pregnancy. In Britain a history of previous miscarriages resulted in a 68% increase in perinatal death but the increase was 200% if there had been a previous perinatal death. A similar increased pattern of risk as a result of past bad obstetric history also reported from Jamaica.

INTERPREGNANCY INTERVAL: there is reliable evidence from Britain and Norway that a prolonged interval between pregnancies carries an increased risk of stillbirths, but that a short interval (less than six months from preceding pregnancy to current one) carries an increased of neonatal death.

ETHNIC GROUP: in the United States perinatal mortality rate among the black population are greater than among whites; in Australia, the Aborigines have a higher mortality rate than the white settlers. In Sweden and the United Kingdom immigrants have a higher mortality rate than the population of parents born in the country. Reasons for the differences vary from

45 country to country and are multiple. In the United Kingdom, immigrants from India,

Bangladesh, and Pakistan have the highest rates.

SOCIAL CLASS: the classification of the father’s occupation into different classes reflects differing risks in perinatal mortality with the perinatal mortality rate in social class 5 being almost twice that in social class 1. Rural dwellers had a higher risk of perinatal deaths when compared to urban residents. This is due to better access to perinatal care facilities in the urban areas reflecting social inequalities between the two groups.

PARENTAL EDUCATION: there is a strong trend between parental education and perinatal mortality rate with the highest rates in parents who had the lowest level of education. In

Greece a U-shaped variation was found where women with lowest and highest education levels had the highest mortality rates, but in Jamaica there is no independent effect of maternal education level.

SINGLE PARENTS: In general, foetal mortality rates were lower for married women than for unmarried women and this was true regardless of maternal age. Marital status may be a marker for the presence or absence of social, emotional, and financial resources.

OTHERS: other factors implicated as risk factors for perinatal mortality include maternal smoking, sex of the foetus, and birth weight.

2.2.6 PERINATAL MORTALITY RATE:

The perinatal mortality rate decreased dramatically in the 1970s in the developed countries with the neonatal mortality rate falling almost twice as fast as stillbirths. A significant decrease in the neonatal mortality rate is due to changes in the birthweight and gestational age distribution of the newborns towards heavier infants and longer gestations.92 This was largely attributed to the improvement in the socioeconomic factors such as comprehensive

46 antenatal care, better maternal nutrition, easier availability of family planning services with more optimal child spacing. Also low birthweight deliveries were better managed with neonatal intensive care. In this same period, Dawodu and Effiong reported a similar pattern of reduction in mortality of infants of normal birthweight in developing countries. However

Survival of low-birth-weight infants which requires additional high technical, financial, and manpower resources, which most centers in developing countries cannot afford remained unchanged.104

Perinatal mortality rate in developed nations have generally been low. In the United States in

1991, the perinatal mortality rate was as low as 8.7 perinatal deaths per 1000 live births and fetal deaths. This is 19% lower than the rate in 1985.105 In the Netherlands, at the early part of the new millennium (2000—2006) perinatal mortality rate among singletons declined from

10.5 to 9.1per 1000 total births.106 For the United Kingdom(UK), at about the same time period (2000—2007), the perinatal mortality rate decreased from 8.3 to 7.7 per 1000 total births.107

Perinatal mortality rate is generally high in most developing countries due to the low socio- economic conditions and poor standard of obstetric and neonatal services. This was seen in the study by Kidanto et al in Tanzania with a perinatal mortality rate of 124 per 1000 total births for the period 1999-2003.108 In an earlier study in another African country, Naeye et al in a multi-centre hospital based study of perinatal mortality in Addis Ababa, Ethiopia in

1974-75, reported a perinatal mortality rate of 65.3 per 1000 livebirths.109

In illustrating the importance of perinatal mortality studies, Wilkinson reported a perinatal mortality rate of 60/1000 total births in a pilot study in South Africa in 1988; areas where appropriate interventions could have saved lives were identified. In a subsequent interventional study at the same locale, strategies were devised using the information from

47 the pilot study and the perinatal mortality rate dropped by almost one-third (41/1000 total births).110

Various studies in Nigeria have consistently shown the high perinatal mortality rate in the country. In Lagos, in one of the very early reports on perinatal mortality in Nigeria, Abudu and Akinkugbe retrospectively studied all the perinatal deaths at the Lagos University

Teaching Hospital between January 1973 and December 1977. A perinatal mortality rate of

45.9/1000 total births was reported for the period. There was a rise in the rate from 39.8/1000 in 1973 to 59.2/1000 in 1977.111 A more recent study (1996-2000) at the same institution showed a perinatal mortality rate of 84.8/1000.39 At the Wesley Guild Hospital Ilesa in

South-West Nigeria, Kuti et al reported a rate of 77.03 per 1000 total births for the period

January 1996 to December 2000.112

More recent studies in Nigeria in the new millennium113-114 are all still in keeping with a high perinatal mortality rate of over 70/1000 total births. This high rate have great implications for the possibility of Nigeria to attain the Millennium Development Goal -4.

2.2.7 CAUSES OF PERINATAL MORTALITY

Most perinatal deaths are caused by congenital malformations, infections, pregnancy-related complications, such as placenta praevia and abruptio placentae; and delivery-related complications, including premature birth, intrapartum asphyxia and birth trauma.

Additionally, there are many indirect causes of early infant death, including poor maternal health, untreated maternal infections, including sexually-transmitted diseases, urinary tract infections, and chorioamnionitis.109 In many developing countries including Nigeria, a significant proportion of perinatal deaths are without diagnosis. This stems from lack of diagnostic facilities, non-performance of perinatal autopsies and also because many of these deaths occur at home and never get registered.

48

Stillbirths and early neonatal deaths differ substantially with respect to their principal causes, although conditions such as birth asphyxia and abruptio placentae play a major role for both stillbirths and early neonatal deaths. (Appendix I)115

Stillbirths are traditionally divided into three categories: early preterm, typically using 28 weeks or 1000 g as an upper cut-off; late preterm from 28 to 36 weeks; and those occurring at term, 37 weeks and more. Stillbirths are also classified according to their timing in relationship to labour, i.e. antenatal or intrapartum. The older concept of macerated versus fresh stillbirth roughly corresponds to these concepts.116

Important causes of stillbirth include congenital anomalies, infection and asphyxia related to pre-eclampsia, placental abruption and umbilical cord accidents. Rhesus disease and maternal and foetal trauma have also been implicated as causal for stillbirth. In most series, even with careful investigation, the aetiology of nearly 50% of stillbirths remains unclear.116

However international comparisons of the estimates of causes of stillbirths is impeded by multiple classification systems.115

The most important causes of early neonatal deaths are prematurity, asphyxia and congenital anomalies.117

2.2.7.1 CONGENITAL MALFORMATIONS:

Congenital malformations which were almost equally frequent causes of death in stillbirth and early neonatal deaths decades ago are now about twice as common in early neonatal deaths as in stillbirths. Studies on perinatal mortality from hospital-based registries in Europe, the United States, and Canada showed a 65 to 80 per cent decline in total perinatal mortality during the past 50 years, whereas the proportion of perinatal deaths attributable to congenital anomalies increased by up to 30 per cent.118 The reduction of perinatal mortality was in great part associated with progress in the medical and surgical management of some of the major

49 causes of perinatal deaths, including haemolytic disease of the newborn, labour complications and birth injury, asphyxia, infections, and premature birth.

De Galan-Roosen et al in Netherlands in a 10 year (1983–1992) descriptive study of the contribution of congenital malformations to perinatal mortality reported the overall incidence of congenital malformations in the perinatal death-group as 33%. Lethal congenital malformations were found in 51% of the cases in the stillbirth-group and 70% of the cases in the neonatal death-group. Congenital malformations of the central nervous system are mostly lethal in the stillbirth-group (45%). Cardiovascular- and pulmonary-defects were more prominent in the neonatal period (27% and 33% respectively of the neonatal deaths). Uro– genital and minor malformations (miscellaneous) are more often seen in perinatal deaths without being a contributor to the cause of death.119 Abudu et al reported similar findings in

Nigeria.120

2.2.7.2 ASPHYXIA:

Perinatal asphyxia results from compromised placental or pulmonary gas exchange. Asphyxia can occur before, during, or after birth. Antepartum events, such as maternal hypotension or trauma, account for 4 to 20 percent of cases. Intrapartum events, such as placental abruption or umbilical cord prolapse, are seen in 56 to 80 percent.

Birth asphyxia is the fifth largest cause of under-five child deaths (8.5%), after pneumonia, diarrhoea, neonatal infections and complications of preterm birth. Birth asphyxia accounts for an estimated 0.92 million neonatal deaths annually and is associated with another 1.1 million intrapartum stillbirths.121

2.2.7.3 PRETERM BIRTH COMPLICATIONS. Preterm birth acts as a risk factor for mortality as well as a direct cause of death.

According to the International Classification of Disease, the direct cause of death is only attributed to preterm birth if the death results from complications specific to preterm birth or

50 is in a severely preterm baby. For example, if a moderately preterm baby has an infection and dies, the death is most appropriately attributed to infection and preterm birth is acting as a risk factor. Thus, many infants recorded as dying from infection are also preterm. The mortality rate is high in developing countries, especially those of Sub-Saharan Africa. The perinatal mortality rate is 70 deaths per 1000 births; the neonatal mortality rate is 45 deaths per 1000 live births. Preterm birth is the strongest independent predictor of mortality in the

United States. Preterm delivery accounts for 75-80% of all neonatal morbidity and mortality.121

2.3.0 NEONATAL DEATHS:

The neonatal period begins with birth and ends 28 complete days after birth. In the year 2000, an estimated 4 million neonatal deaths occurred globally. 98% of these deaths occurred in developing countries with the risk highest in Africa, mainly in Sub-Saharan Africa.80 The most recent UN estimates suggest that 3.6 million neonatal deaths occurred in the year 2008, with neonatal deaths comprising not less than 40% of total under-five deaths.3 One in three deaths in children under five occur during the neonatal period. Reducing neonatal death is therefore an essential step towards reducing under five mortality and achieving MDG-4.80

The most common measure of neonatal mortality is the neonatal mortality rate (NMR) which is the number of neonatal deaths (deaths in the first 28 days of life) per 1,000 live births. The neonatal mortality rate vary between different regions3 and more than two-thirds of the world’s neonatal deaths occur in sub-Saharan Africa and South Asia.80 The NMR in

Japan, a high income country is 1 per 1000 live-births while it is as high as 61/1000 live- births in Somalia122 and is 49/1000 live-births in Nigeria. In fact Nigeria is one of five countries that together account for more than 2 million newborn deaths of the annual global total.3

2.3.1 MAIN CAUSES OF NEONATAL DEATH

51

The three major causes of neonatal deaths in high-mortality countries are, infections, complications of preterm birth, and intrapartum-related neonatal deaths or “birth asphyxia’’.

These account for more than 80% of all neonatal deaths globally.3 Rapid reductions have been made in reducing neonatal tetanus and there has been apparent progress towards reducing neonatal infections. Limited, if any, reduction has been made in reducing global deaths from preterm birth and for intrapartum-related neonatal deaths. 3

The relative proportions of the three main causes of death vary between countries as well as within countries. For settings with very high NMR (greater than 45 neonatal deaths per 1000 live births), approximately one-half of neonatal deaths are caused by infections, including tetanus. 84 In low-mortality settings (NMR<15), approximately

15% of deaths are caused by infections and are more likely to take place in hygienic settings with access to antibiotics, so preventing these deaths requires more complex inputs.

2.3.1.1 NEONATAL INFECTIONS

Neonatal infections are estimated to cause globally about 36% of deaths in children under five years of age in 2000. In high mortality countries, neonatal infections account for almost

50% of deaths unlike about 20% for low NMR countries.

2.4.0 INFANT MORTALITY

This is the death of new borns within the first 365 days of life. It is measured as the infant mortality rate (IMR). This is statistically defined as the probability that a child born in a specific year will die before reaching the age of one, if subject to current age-specific mortality rates. Expressed as the number of deaths within the first year of life per 1,000 livebirths. It is a potentially important indicator. As the rate of under-five mortality decreases, infant deaths; especially neonatal deaths—make up an increasing proportion of all under-five deaths

2.5.0 UNDER-FIVE MORTALITY:

52

This is death in children younger than five years of age. The most common measure is the under-five mortality rate which is expressed as the number of deaths per 1000 livebirths. It is recognized as the most appropriate indicator of the cumulative exposure to the risk of death during the first five years of life. Marked reductions in childhood deaths occurred during the

2nd half of the 20th century, with a decline in under-five mortality from over 13 million in

1980 to 10.5 million in 1999.82

The global under-five mortality rate has declined by a third, from 89 deaths per 1,000 live births in 1990 to 60 in 2009 with nearly 8.1 million deaths for the year 2009. Sub-Saharan

Africa accounted for nearly half, and Southern Asia a third of the total. About half occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan and China.

India(21 percent) and Nigeria (10 percent) together account for nearly a third of all under-five deaths worldwide. The under-five mortality rate estimate for Nigeria for 1990 and 2009 is

212 per 1000 and 138 per 1000 respectively, and with the millennium development goal target for 2015 of 71 per 10001 means Nigeria is not on track towards achieving the MDG-4 goal.

2.5.1 CAUSES OF UNDER-FIVE MORTALITY:

The most recent estimates of causes of childhood mortality (under-fives) show that most childhood deaths globally (64%) are due to infectious causes. Of all the infectious disorders, pneumonia, diarrhea, and malaria are the leading causes of death worldwide. (Appendix.2)123

40% of deaths in children younger than five years occurred in the neonatal period, most often because of preterm birth complications, intrapartum-related complications and neonatal sepsis or meningitis.123

After the first month of life, two-thirds of child deaths globally are due to pneumonia, diarrhoea and malaria.123 Undernutrition contributes to child mortality in more than one-third of cases by increasing children’s risk of dying from infections.3

53

While the major causes of newborn and child deaths are similar across countries, the proportions vary, especially for those countries more affected by HIV/AIDS. For example even though HIV/AIDS accounts for only 4% of child deaths in the African region overall, in

South Africa, more than half of child deaths are due to HIV/AIDS.124

Distribution of deaths and their causes vary widely across various regions of the world.

(Appendix 3).123 For example, estimates for Africa indicate that 30% of all child deaths occur in the neonatal period unlike 52% for South East Asia. Also a higher proportion of deaths in

Africa were due to malaria (15%) and AIDS (4%) while in South East Asia, malaria was just due to 1% of childhood deaths. 123

CHAPTER THREE

3.0 AIM / SIGNIFICANCE OF THE STUDY

3.1 AIM AND OBJECTIVES

54

3.1.1 AIM: To help in better understanding of the causes of perinatal and under-five mortality.

3.1.2 OBJECTIVES:

1. To determine the causes of perinatal and under-five mortality in the University of Benin

Teaching Hospital, Benin City.

2. To evaluate the age specific mortality rates.

3. To analyze age and sex distribution of the causes of death.

4. To determine the frequency of the various causes of death.

5. To determine the perinatal and under-five autopsy rate

6. To assess clinico-pathological discordance in cause of death.

3.2 SIGNIFICANCE/JUSTIFICATION OF THE STUDY

In view of the absence of any detailed autopsy study at the University of Benin Teaching

Hospital of perinatal and underfive mortality, this study therefore is timely to document the pattern as well as the major causes of perinatal and underfive mortality as seen in this hospital.

Documentation of these factors will provide the much needed information upon which areas of need can be well assessed and interventional strategies well prioritized.

CHAPTER FOUR

4.0 MATERIALS AND METHODS

4.1 STUDY DESIGN

55

This was a one year prospective autopsy study designed to establish the cause of death and other relevant pathological processes that might have contributed to deaths in stillbirths and underfive mortalities at the University of Benin Teaching Hospital (UBTH), Benin City.

4.2 STUDY SITE

The mortuary and histopathology laboratory of the department of Pathology, University of

Benin Teaching Hospital, Benin City was the location of the study.

4.3 STUDY POPULATION

The study population included all stillbirths delivered in the labour rooms of the Department of Obstetrics and Gynaecology, all deaths in children under five years of age in all the units of the Department of Paediatrics (Special Care Baby Unit, Children Emergency Room,

Paediatric Wards) as well as accidental cases under five years of age dying in the Accident and Emergency unit for which an informed consent was duly obtained.

4.4 EXCLUSION CRITERIA

The exclusion criteria for this study were;

1. Abortuses

2. Autolyzed bodies for which a reasonable autopsy diagnosis is precluded

3. Bodies brought into the mortuary from outside

4.5 DURATION OF STUDY

This study was carried out for a period of twelve (12) months (January 2012 to December

2012).

56

4.6 SAMPLING METHOD

Total population sampling was used for this study. Thus all perinatal and under-five mortalities in the hospital for which an appropriate consent was obtained during the duration of the study were autopsied and constituted the sample size.

4.7 CATEGORIZATION OF THE MORTALITIES

The deaths were categorized into the following age groupings:

1. Stillbirths ---- all stillborn foetuses weighing 1000g and above.

2. Early Neonatal Deaths ---- between birth and 7 days of life.

3. Late Neonatal Deaths ---- eight to 28th day of life.

4. Infants mortality ---- one month to 12 months

5. Preschool age group mortality ---- thirteen months to 59 months.

4.8 STUDY PROTOCOL

Relevant clinical information such as sex, date of birth, case summary, laboratory results/reports of other ancillary investigations, provisional clinical diagnosis/differentials were extracted from patient records.

All autopsies were performed according to a defined working protocol. Full autopsies including external and internal examinations were performed on all bodies meeting the inclusion criteria for the one year duration of the study. Photographs were taken of the whole body and significant features. Body weight and the individual weights of the internal organs

(brain, thymus, heart, lungs, liver, spleen, adrenal glands, and kidney) were measured.

Anthropometric measurements (crown-to-heel, crown-to-rump, cranial perimeter, toe-to-heel, hand, middle finger of the hand, inner canthal distance, outer canthal distance) were taken.

Where applicable, blood culture from the superior sagittal sinus and microbiological cultures

57 from percutaneous aspiration of the lung were obtained and processed. The placenta was examined as a surgical specimen after the autopsy in the appropriate cases.

The causes of deaths in the perinatal group were classified using the Tulip classification.88

The causes of death for the under-five mortalities were classified into broad groups using the tenth revision of the International statistical Classification of Diseases and related health problems (ICD-10) as our guide.79

The results obtained were analyzed using the statistical package for social sciences (SPSS) version 16.0. Comparisons of discrete data was done using the chi square test, while the student t-test was used for continuous variables, with level of significance being set at

P≤0.05.

4.9 ETHICAL CONSIDERATIONS

The confidentiality of the patients/parents was ensured by making use of numbers rather than names, addresses or phone numbers and data generated was stored in a pass-worded computer accessible only to the researcher and the supervisors.

The approval of the hospital ethics committee was obtained for the study to be carried out.

CHAPTER FIVE

5.0 RESULTS

58

During the period of the study spanning January to December 2012, a total of 3967 deliveries were recorded at the University of Benin Teaching Hospital (UBTH). Out of this number there were two hundred and forty (240) stillbirths, giving 3727 as the total number of live deliveries.

There were a total of four hundred and seventy three (473) perinatal deaths giving a perinatal mortality rate of 119.2/ 1000 total births and a total of three hundred and eighty seven (387) under-five deaths giving an under-five mortality rate of 103.8/ 1000 live births.

A total of two hundred and thirty-eight (238) perinatal deaths (115 early neonatal deaths, 75 macerated stillbirths and 48 fresh stillbirths) and one hundred and seventy-four (174) under- five deaths (115 early neonatal deaths, 20 late neonatal deaths,20 infant deaths and 19 pre- school deaths) had autopsies carried out on them during the one year period of the study. This gives a perinatal autopsy rate of 50.3% and an under-five autopsy rate of 45%.

The overall male:female ratio in this autopsy study is 1.14:1. The age ranged between day 0 and 1470 days with a median age of 69.47 days and stillborn neonates being the modal population.

5.1 PERINATAL MORTALITY

There were a total of two hundred and thirty-eight (238) perinatal deaths in this study composed of 115(48.3%) early neonatal deaths, 75(31.5%) macerated stillbirths and

48(20.2%) fresh stillbirths. The male:female sex ratio of perinatal deaths was 1.2:1.The perinatal mortality rate was 119.2/1000 total births. The stillbirth rate was 60.5/1000 total births, while the early neonatal death rate was 62.5/1000 live births.

59

Most of the perinatal deaths were due to infections (30.3%). This was followed by placental causes (20.6%) and prematurity/immaturity (16.0%). Congenital anomalies accounted for

10.9% of deaths.(Table I). The category of others (7.1%) included cases of ruptured uterus, birth trauma and hydrops of unknown cause.

Placental causes (56.25%) were the most common cause of fresh stillbirth, followed by other obstetric causes like ruptured uterus (18.79%) with congenital anomaly (10.4%) as a distant third. The cause of death in antepartum (macerated stillbirths) is unknown in most (40%) of the cases, this is followed by infections (28%) and placental causes (22.6%) (Table II)

The most common cause of death amongst the early neonatal deaths is infections (44.3%) , closely followed by prematurity (32.2%) and congenital anomaly (13.9%) as the third most common cause of death.

Among the perinatal deaths with congenital anomaly, the organ systems that had the highest frequency of involvement were the central nervous system and the respiratory system each with a frequency of 19.2% of total congenital anomalies, followed by the cardiovascular and digestive systems each with 15.3% of total congenital anomalies.(Table III)

The single most common CNS congenital anomaly was anencephaly (3 cases were seen during the study out of five congenital CNS lesions). On an individual basis, the single most common congenital anomalies are anencephaly, gastroschisis and diaphragmatic hernia.

Apart from the congenital anomalies specific to particular organ systems, there was one case of VACTERL association and two cases of Potter sequence with involvement of multiple organ systems.

The weight distribution of the perinatal deaths show a high proportion (34.9%) of deaths to be above 2500g in weight. This will be explained by the high proportion of perinatal deaths

60 due to placental causes. However most of the perinatal deaths due to prematurity were in the weight categories of 1500g and below.(Table IV)

Most of the FSB are over 2.5kg, while the MSB and Early Neonatal Deaths are more diffusely distributed amongst the different weight categories (Table V).

5.2 UNDER-FIVE MORTALITY

Table VI show that early neonatal deaths constitute 66.1% of the total under-five deaths studied during the one year duration of the study. This is followed by late neonatal and infant mortality each of which accounted 11.5% of cases. Thus there is a decline in death rate from the early neonatal age group down to the pre-school age group. There were 92 males and 82 females giving a male to female ratio of 1.1:1.

Table VII show that death in under-fives is most commonly due to conditions originating in the perinatal period (60.3%). A further characterization of the conditions originating in the perinatal period show that the sub-classification of respiratory and cardiovascular disorders specific to the perinatal period under which birth asphyxia, respiratory distress syndrome, congenital pneumonia, neonatal aspiration syndromes and pulmonary haemorrhage are listed accounted for most (24.7%) under-five deaths in this study (Table VIII). Infections specific to the perinatal period accounted for 11.5% of total deaths, this combined with specific infections (6.9%) make infectious causes (18.4%) the second most common cause of under- five deaths. Other common causes of death are prematurity(14.4%), congenital malformations (12.6%), and nervous system diseases(8.0%) in decreasing frequency of occurrence. There were five cases of neoplasms seen in this study accounting for 2.9% of deaths.

5.2.1 EARLY NEONATAL DEATH

61

The leading causes of Early Neonatal Death in the present study using the ICD-10 classification are respiratory and cardiovascular disorders specific to the perinatal period

(birth asphyxia, respiratory distress syndrome, congenital pneumonia, neonatal aspiration syndromes, perinatal pulmonary haemorrhage) accounting for 35.6% of all early neonatal deaths. Others in decreasing order of frequency are, prematurity (21.7%), congenital malformation (13.0%), infections (8.7%), haemorrhagic/haematologic disorders (7%), {Table

VII}

5.2.2 LATE NEONATAL DEATHS

Infection was the leading cause of death in this group. Infections specific to the perinatal period (neonatal sepsis) was responsible for 50% of late neonatal deaths in this study. An additional 10% of cases was due to specific infections (neonatal tetanus), making infectious causes to be responsible for 60% of late neonatal deaths. Congenital malformations involving the gastrointestinal tract dominantly were also prominent (20%).

5.2.3 INFANT MORTALITY

The leading cause of infant mortality in the study were of infectious causes. Specific infections accounted for 25% of total infant deaths. These include tetanus, cerebral malaria and paediatric AIDS. Meanwhile another 20% each of the total infant deaths were as a result of infections involving the respiratory system (bronchopneumonia) and nervous system

(meningitis). The second most common cause of Infant deaths is congenital malformations

(15%) involving the respiratory and cardiovascular systems mainly.

5.2.4 PRE-SCHOOL MORTALITY

Infections remained an important leading cause of death in this mortality group with specific infections accounting for 26.3% of the deaths. Infections involving particular organ systems;

62

respiratory system (bronchopneumonia and lung abscess) are responsible for 21% of the

deaths, while nervous system and digestive system infections together accounted for 26.3%.

Thus infectious causes of death were responsible for a majority of pre-school deaths. Also

significant in this age group is the emergence of malignant causes of death (21-1%). The

tumour types encountered in this study are retinoblastoma, and acute lymphoblastic

leukaemia.

The 174 under-five deaths were evaluated for clinico-pathological discordance and as shown

in Tables IX and X, there were nineteen cases of clinico-pathological discordance. This gives

a discordance rate of 10.9%. There were ten (10) class I autopsy findings all of which related

to the cause of death (Table IX) while class II major findings were seen in nine (9) cases

(Table X).

TABLE I: CAUSES OF PERINATAL DEATHS IN UBTH, CLASSIFIED USING

THE TULIP PATHOPHYSIOLOGICAL CLASSIFICATION

CAUSE OF DEATH MALE FEMALE FREQUENCY (%)

CONGENITAL ANOMALY 12 14 26(10.9%)

PLACENTAL 26 23 49(20.6%)

PREMATURITY/IMMATURITY 22 16 38(16.0%)

63

INFECTION 42 30 72(30.3%)

OTHER 7 10 17(7.1%)

UNKNOWN 22 14 36(15.1%)

TOTAL 131 107 238(100%)

TABLE II: AGE-SPECIFIC CAUSES OF PERINATAL DEATH IN UBTH

Age Group Cause of Death Total

CongenitalAnomaly Placental Prematurity Infection Other Unknown

FSB 5 27 1 0 9 6 48

MSB 5 17 0 21 2 30 75

ENND 16 5 37 51 6 0 115

64

TOTAL 26 49 38 72 17 36 238

KEY: FSB: fresh stillbirth MSB: macerated stillbirth ENND: early neonatal death

ORGAN SYSTEM FREQUENCY PERCENTAGE(%)

Central nervous system 5 19.23

Respiratory system 5 19.23

Heart and circulatory system 4 15.38

65

Digestive system 4 15.38 TABLE III:

Syndrome 3 11.54 DISTRIBUTION

OF Urogenital System 2 7.69 CONGENITAL

Musculoskeletal 1 3.85 ANOMALIES

Neoplasm 1 3.85 AMONGST THE

Other 1 3.85 PERINATAL

TOTAL 26 100 DEATHS

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TABLE IV: WEIGHT DISTRIBUTION OF THE VARIOUS CAUSES OF PERINATAL DEATH

IN UBTH

CAUSE OF DEATH WEIGHT CATEGORIES TOTAL

<1000g 1001-1500g 1501-2000g 2001-2500g >2500g

Congenital Anomaly 0 2 5 6 13 26

Placental 1 7 10 4 27 49

Prematurity 13 14 6 5 0 38

Infection 7 18 22 13 12 72

Other 0 0 0 4 13 17

Unknown 1 6 8 3 18 36

TOTAL 22 47 51 35 83 238

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TABLE V: WEIGHT DISTRIBUTION OF THE VARIOUS PERINATAL DEATH GROUPS

GROUP WEIGHT CATEGORIES TOTAL

<1000g 1001-1500g 1501-2000g 2001-2500g >2500g

FSB 2 3 9 4 30 48

MSB 4 17 14 12 28 75

ENND 16 27 28 19 25 115

TOTAL 22 47 51 35 83 238

KEY:

FSB: fresh stillbirth

MSB: macerated stillbirth

ENND: early neonatal death

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TABLE VI: AGE AND SEX DISTRIBUTION OF UNDER-FIVE DEATHS AT THE UNIVERSITY

OF BENIN TEACHING HOSPITAL.

SEX TOTAL

MALE FEMALE (%) AGE GROUPING

Early Neonatal Death 65 50 115(66.1%)

Late Neonatal Death 12 8 20(11.5%)

Infant Mortality 4 16 20(11.5%)

Pre-School Mortality 11 8 19(10.9%)

TOTAL 92 82 174(100%)

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TABLE VII: AGE AND SEX DISTRIBUTION OF THE VARIOUS CAUSES OF UNDER-FIVE

MORTALITY AS SEEN AT THE UNIVERSITY OF BENIN TEACHING HOSPITAL

TOTAL

(%) DISEASE CLASS MORTALITY GROUP

ENND Late NND Infant Pre-school

M F M F M F M F

Infections(Specific) 0 0 2 0 1 4 3 2 12(6.9%)

Conditions originating in the 57 35 8 4 0 1 0 0 105(60.3%)

Perinatal Period

Congenital Malformations 4 11 2 2 1 2 0 0 22(12.6%)

Accidental Injury 0 0 0 0 0 1 0 0 1(0.6%)

Neoplasms 0 1 0 0 0 0 1 3 5(2.9%)

Diseases of Blood/ Blood 0 0 0 0 0 0 1 0 1(0.6%)

Forming Organs

Nervous system diseases 2 4 1 0 0 4 1 2 14(8.0%)

Circulatory system diseases 0 0 0 0 0 1 0 0 1(0.6%)

Respiratory system diseases 0 1 0 1 2 2 4 0 10(5.7%)

Digestive system diseases 0 0 0 0 1 0 1 1 3(1.7%)

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TOTAL 63 52 13 7 5 15 11 8 100

TABLE VIII: AGE DISTRIBUTION OF THE CONDITIONS ORIGINATING IN THE

PERINATAL PERIOD

Mortality Group

ENND Late ND Infant Pre- TOTAL/(%) SUB- CLASS Mortality school

Complications of placenta cord and 1 0 0 0 1(0.6%)

membranes

Disorders of length of 25 0 0 0 25(14.6%)

gestation(prematurity)

Birth trauma 2 0 0 0 2(1.1%)

Respiratory/cardiovascular disorders 41 1 1 0 43(24.9%)

specific to the perinatal period

Infections specific to the perinatal 10 10 0 0 20(11.5%)

period

Haemorrhagic/haematologic disorders 8 0 0 0 8(4.6%)

Digestive system Disorders 4 1 0 0 5(2.9%)

Others 1 0 0 0 1(0.65)

TOTAL 92 12 1 0 105(60.3%)

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TABLE IX: CLASS I AUTOPSY FINDINGS

CLINICAL DIAGNOSIS AGE AUTOPSY DIAGNOSIS

Preterm,LBW, RDS 2days Bronchopneumonia

Severe birth asphyxia, HIE III 1 day Hypoplastic left heart syndrome

Neonatal sepsis 2 days Hyaline membrane disease

Meningitis 2 1/2yrs Ileo-ileal intussusception

Syndromic child with multiple congenital 1 day Hepatoblastoma Hydrops fetalis anomalies ?congenital neurosarcoma

Severe malaria, Uraemia 28months Bronchopneumonia

Disseminated TB. ?tuberculous meningitis 14months Acute bronchopneumonia

RDS 1day Congenital pneumonia

Preterm. VLBW. SBA. RDS. 1day Complex congenital heart disease

Preterm. Fetal Ascites 1day Meconium Peritonitis. Intrauterine ileo-ileal intussusception. Intestinal Atresia.

KEY LBW: Low birth weight RDS: Respiratory distress syndrome HIE III: Hypoxic ischaemic encephalopathy grade III TB: Tuberculosis VLBW: Very low birth weight SBA: Severe birth asphyxia

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TABLE X: CLASS II AUTOPSY FINDINGS

CLINICAL DIAGNOSIS AGE AUTOPSY DIAGNOSIS

Cerebral malaria; Septicaemia 9months Meningitis

Preterm VLBW at risk of sepsis 1day Intraventricular haemorrhage

Severe birth asphyxia, HIE III 4days Pulmonary haemorrhage

Preterm, LBW, Hydrocephalus 2° stenosis 1day Hydranencephaly; Intra-uterine infection

Cyanotic congenital heart disease 1day Intraventricular haemorrhage

Preterm; LBW; neonatal sepsis; meningitis 1day Congenital pneumonia; No meningitis

Preterm, VLBW, Progressive sepsis 5days Meningitis.

Univentricular heart, Pulmonary stenosis 35days Hypoplastic left heart syndrome

Omphalocele major 2days Gastroschisis.

KEY: VLBW: Very low birth weight HIE III: Hpoxic ischaemic encephalopathy grade III LBW: Low birth weight

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FIGURE 1: congenital heart disease(hypoplastic left heart syndrome) in a term neonate dying within one day of life.

Atretic ascending aorta.

Enlarged pulmonary trunk draining a common ventricular cavity.

74

Single dominant ventricular cavity.

FIGURE 2: Cut surface of the kidneys in a child with acute lymphoblastic leukaemia(ALL) showing numerous areas of haemorrhage. Histology of same kidney show marked infiltration of the parenchyma by leukaemic cells.

75

FIGURE 3:THANATOPHORIC DYSPLASIA in female neonate who died within hours of birth showing extremely short extremities, narrow chest, depressed nasal bridge and oedema.

76

FIGURE 4: photomicrograph of a lung specimen showing marked neutrophilic infiltration of the alveolar spaces with accompanying oedema in acute bronchopneumonia.

77

FIGURE 5: A case of Gastroschisis in a female neonate who died on the second day of life. The hernia sac contained oedematous small intestines which were matted together, part of the liver, spleen pancreas and caecum.

Line arrow shows the umbilical cord stump attachment

Block arrow shows the paraumbilical hernia sac

78

FIGURE 6: Neonatal necrotizing enterocolitis showing distension of the intestines and feacal contamination of the peritoneal cavity due to gut perforation.

79

FIGURE 7: Intussusception of the ileo-ileal variety showing oedema and vascular compromise of the intussusceptum in a 30 month old male.

Intussuscipiens.

Intusscusceptum.

80

Location of intusscusception

FIGURE 8: Meningitis with purulent exudates on the surface of the brain.

81

FIGURE 9: retroplacental haematoma with marked compression of the placental parenchyma from a 24years old female with severe pre-eclampsia who delivered a fresh stillbirth weighing 2.1kg

82

FIGURE 10: Gross and histology of placental infarction. Histology show areas of infarction which reveals ghost outlines of villi enmeshed in fibrin. Some viable small villi are present adjacent to the infarct on the right.

83

FIGURE 11: Histology of the term placenta of a stillborn showing chronic villitis with the intervillous space filled with dominantly mononuclear cell infiltrates. The mother presented with a one day history of not feeling foetal movements.

84

FIGURE 12 showing left diaphragmatic hernia with herniation of left lobe of the liver, stomach as well as intestines into the left hemithorax and dextroposition of the heart. There was bilateral lung hypoplasia. The neonate died within the first 24 hours of life.

Line arrow showing hypoplastic lung in right hemithorax.

Block arrow showing part of the liver in the left hemithorax

Block arrow showing dextroposition of the heart

85

CHAPTER SIX

6.0 DISCUSSION

In this study there were a total of four hundred and seventy-three (473) perinatal deaths and 387 Under-

Five deaths with a total of 3967 deliveries for the year 2012. The Perinatal mortality rate is 119.2/̸1000 total births while the Under-Five mortality rate is 103.8/1000 live births.

Perinatal mortality is regarded as a sensitive index of the quality of obstetric and neonatal care available in any setting. The Perinatal Mortality Rate of 119.2/1000 total births in this study is on the high side. Whereas the incidence of Perinatal Mortality in developed countries is low107 a rising trend has been reported in recent hospital based studies39,112,125-126 in Nigeria. The national average for perinatal mortality rate as released by the 2003 Nigeria Demographic and Health Survey, NDHS 2003 is put at 90/1000 total births127. The result of our study is higher.

The high Perinatal Mortality Rate (PMR) is particularly worrisome in view of the Millennium

Development Goals. Reducing the 1990 childhood mortality levels by two-thirds by the year 2015

(MDG-4) looks unrealizable. This is in view of the fact that a component of perinatal mortality (early neonatal deaths) constitute a very significant percentage of Under-five mortality80. The high PMR is a pointer that perinatal health in our environment is still inundated with many problems despite advances in neonatal and obstetric care services in this institution.

One very significant factor in the high PMR is the fact that UBTH receives a very high proportion of high risk pregnancies. The underlying factors are the perceived high cost of services at the UBTH, poor health seeking behaviour in our local population with many never attending ANC, resorting to spiritual homes and traditional settings for delivery. The cumulative effect is that referral to this hospital is a last resort following failure of other intervention measures.

The perinatal autopsy rate in this study is 50.3%. This is higher than the rate of 20.1% reported from

Lagos39 but is in keeping with the 46% reported from Ibadan by Akang et al6. Previously in our centre

86

Ugiagbe et al40 reported a neonatal autopsy rate of 0.8%. However in this study we have been able to establish that with adequate enlightenment of parents and enthusiasm on the part of health workers, particularly clinicians the autopsy rate can be higher. The absence of bonding and the desire to have a better outcome in subsequent pregnancies is a factor in parents consenting to perinatal autopsy.

However consent was more difficult to obtain for the under-fives (especially outside of the early neonatal period).

The causes of perinatal death were classified using the Tulip classification88. The advantage of the

Tulip classification is that it aims at identifying the unique initial demonstrable entity on the causal pathway to death for the purpose of counselling and prevention. The strength is that it is based on the combination of clinical findings and diagnostic test results including pathological findings while keeping in view the mother, the fetus and the placenta which are all involved in the complex process of perinatal mortality.

The distribution of perinatal deaths according to the Tulip classification {Infections (30.3%), Placental

Causes (20.6%), Prematurity/Immaturity(16%), Congenital Anomalies(10.9%)} clearly revealed areas where interventions are required. Due to differences in definition, it is difficult to compare percentages with other studies where other classification systems have been used128 as unknown in Tulip is not the same as unknown or unclassifiable in other systems. In the perinatal mortality studies from Ibadan,

Lagos and Ife6,39,111-112 the causes of death were classified using systems such as Wigglesworth and

Modified Aberdeen. In these systems, Asphyxial cause of death group is always prominent. However asphyxia is a clinical condition of an underlying cause of death which can be defined. For instance most cases in the placental cause of death group will manifest features of asphyxia.

The distribution of the causes of death in the various cause of death categories shows that effective interventions to improve the quality of obstetric and neonatal care, in addition to the utilization of prenatal care and the quality of intrapartum supervision would reduce perinatal mortality significantly.

87

Under-Five mortality is a useful index of the quality of health care available in a community. In this study the under-five mortality rate is 103.8/1000 live births. The distribution of under-five mortality showed that early neonatal deaths accounted for 60.2% of total under-five deaths. In fact most early neonatal deaths occurred within the first twenty four hours of life. This is similar to the finding in

Ibadan where Ayoola et al reported neonatal deaths constituting more than half of paediatric mortality38. However our figures are not directly comparable with those of a number of other previous hospital based studies due to differences in definitions of mortality (hospital death rate as a percentage of those admitted vis-à-vis mortality as a factor of total livebirths).

The under-five mortality rate is lower than the national average of 138/1000 live births estimated for the year 20091. Also the Nigeria Demographic and Health Survey 2003 estimated under-five mortality rate at 201/1000 Live Births127. The estimate for the South-South zone of the country where University of Benin Teaching Hospital is located is 176/1000 live births. Also the proportion of early neonatal deaths amongst the total under-five mortality in this study is higher than the global estimate of 28%84.

The disparity in the figures obtained in this study and the national estimates as published is due to the fact that this study suffers from the limitation of being hospital-based. Hospital based data as this study is may potentially underestimate the true rate of Under-Five mortality because neonates who form a very significant portion of this group are not followed up after discharge from hospital and moreover a very good percentage of births in Nigeria are home based127,129 . These figures however are a reflection of the under-five mortality profile of the community that serves as the catchment for this hospital.

The Under-Five Autopsy rate in this study is 44.9%. this is comparable to the paediatric autopsy studies reported from Ibadan6 by Akang et al. However the study by Ayoola et al also from Ibadan reported an autopsy rate of 7.4% in a more recent study. Meanwhile Abdulkareem et al from Lagos reported an autopsy rate of 24.8%26. The two studies from Ibadan reflect the reduction in autopsy rates over time. In our study, early neonatal deaths constituted 60.09% of our study population and the desire

88 to know what went wrong and steps to take to avoid a reoccurrence were significant driving forces in parents consenting to autopsy. Consent for autopsy was more difficult in the higher age groups with most parents declining on the basis that the autopsy will never restore life to the dead child.

Low autopsy rates have always been lamented by relevant stakeholders, however policy decisions at the level of individual hospitals/clinical departments coupled with involvement of all necessary staff and adequate staff training on the methods of and importance of the procedure can lead to rise in consent rates35. This was our experience in this study.

The under-five mortality Male: Female Ratio in this study is 1.1: 1. This is different from the 1.6:1 recorded in Lagos and the 1.3:1 reported from Ibadan. This difference may be due to different study populations, however they are all in keeping with the predominance of male mortality over female mortality.

The distribution of the causes of death according to the ICD-10 categories clearly unveils areas where interventions are critically needed in the march towards actualizing MDG-4. The distribution of the cause of death categories showed that Conditions Originating in the Perinatal period constitute the single largest cause of death category in this study (60.3%). The sub-category, Respiratory and

Cardiovascular Disorders Specific to the Perinatal Period which encompass Birth Asphyxia,

Respiratory Distress Syndrome, Congenital Pneumonia, Neonatal Aspiration Syndromes and

Pulmonary Haemorrhage accounted for most Under-Five deaths (24.7%). This is in tandem with numerous other studies where the category of Birth Asphyxia was listed as one of the commonest causes of death. It was reported as the second commonest cause of childhood mortality in the autopsy study of childhood mortality from Ibadan6 after Infections while it was occupying the third position after Neonatal Tetanus and Prematurity in the study by Ayoola et al also from Ibadan38.

The prominence of the Respiratory and Cardiovascular Conditions Specific to the Perinatal period as the most common cause of death group brings to the fore the prominent place that improvement in

89 neonatal care services hold in the march towards actualization of MDG-4. This prominence is a factor of the percentage contribution of Early Neonatal Deaths in total Under-Five mortality.

Infections specific to the perinatal period accounts for 11.5% while specific infections as a broad group accounts for 6.9% of total Under-Five deaths, making “Infectious” causes responsible for some

18.4% of total Under-Five deaths. This constitutes the second highest cause of death group. Most of these deaths are in the Early neonatal period. Most of the infectious causes of death are due to neonatal sepsis which account for 62.5% of Infectious Causes of death. Neonatal sepsis was reported as the third commonest cause of death in childhood in Ibadan38. Other specific infections which are important causes of childhood deaths are severe malaria/cerebral malaria, Neonatal tetanus and Paediatric AIDS.

This is not surprising as it is estimated that a high proportion of childhood deaths in Africa were due to malaria (16%) and AIDS (4%)3.

Neonatal tetanus is not a very dominant cause of death in this study. Only three cases were recorded in this study unlike in the study from Ibadan by Ayoola et al where Neonatal Tetanus alone accounted for

13.8% of total childhood deaths38. This may be a reflection of the aggressive immunization programmes of government. Globally it is acknowledged that successful vaccination programmes have reduced the worldwide total for deaths caused by measles and tetanus3. Also note worthy is the fact that there was no death in this study traceable to measles.

It is noteworthy that Prematurity constituted the third leading cause of death(14.4%) in this study. This is comparable to the study from Ibadan where prematurity was the third leading cause of childhood deaths (11.5%)38. Significant predisposing factors are pre-eclampsia/Eclampsia, Ante-partum haemorrhage, and multiple pregnancy as well as unbooked status. Globally in all children younger than 5 years, prematurity is also the third leading cause of death3.

Congenital malformations were the fourth leading cause of Under-Five deaths (12.6%) in this study. It is slightly higher than the 10% by Akang et al6 and 9.3% by Abdulkareem et al26 in different paediatric

90 autopsy studies in Ibadan and Lagos respectively. The slightly higher figure may be due to the fact that this study examined only Under-Five mortality while the other two examined all paediatric deaths up to the age of fifteen years. However in another report from Ibadan, Ayoola et al reported Congenital

Malformations as being responsible for 1% of the overall causes of childhood death38. This low figure is most likely due to the fact that the study was a clinical one unlike the autopsy studies that yielded higher figures. Sixty-eight percent (68%) of the congenital anomalies were seen amongst the Early

Neonatal Deaths with Late Neonatal Deaths accounting for eighteen percent (18%) and the remaining were infant deaths. This is comparable to other studies were most deaths due to congenital anomalies occurred in the neonatal age group6,26.

Most of the cases seen in this study were congenital malformations of the gastrointestinal tract (36.4%) made up of three cases of Gastroschisis, two cases of Omphalocele Major, one case each of

Imperforate Anus, Duodenal Atresia, and Oesophageal Atresia. This is closely followed by the

Cardiovascular System (22.7%) made up of two cases of Hypoplastic Left Heart Syndrome, and one case each of Atrioventricular Septal Defect, Aortic stenosis and Ventricular Septal Defect. This is closely comparable to findings by Akang et al in Ibadan where the Gastrointestinal tract was the most common site (30%), closely followed by the cardiovascular system (26%)6. Another common anatomical site for congenital malformation is the Respiratory System (18.1%) with two cases of

Diaphragmatic hernia, and one case each of tracheo-oesophageal fistula and pulmonary hypoplasia.

Other causes of death of note in this study are Nervous System diseases(8%) mainly made up of pyogenic meningitis, Respiratory system disorders (5.7%), and Neoplastic lesions (2.9%). The

Neoplastic lesions are composed of two cases of retinoblastoma and acute lymphoblastic lymphoma in pre-school age children and one case of congenital hepatoblastoma in a day old child. The low number of neoplastic lesions causing Under-Five deaths is in contrast to western nations where the percentage is higher. Also accidental deaths were relatively infrequent in this study. There was only one case of a six month old baby who was a victim of a road traffic accident in the company of the parents.

91

Epidemiological and social conditions in our environment explain why some of the disease patterns are the way they are.

Collectively, the most important single causes of death are Sepsis (13.8%), Prematurity (12.1%),

Meningitis (8.0%), and Congenital Pneumonia (7.5%).

Correlation of clinical diagnoses with autopsy diagnoses show that errors in clinical diagnoses have persisted despite advances in diagnostic technology. There was a 10.9% discordance rate in this study.

This is in keeping with numerous studies on new major diagnoses9-10,25 which is in the region of 10%.

The slightly higher discordance rate in this study is most likely due to the absence of numerous high technological imaging facilities in our environment compared to western nations.

92

CHAPTER SEVEN

7.1 CONCLUSION

In conclusion this study shows that perinatal and childhood mortality is still a major problem in our environment. The causes of most of the perinatal deaths are infections, placental causes and prematurity in descending order of frequency using the Tulip classification of perinatal death while conditions originating in the perinatal period constituted the bulk of the causes of under-five mortality classified using ICD-10. This is readily explainable by virtue of the fact that early neonatal deaths constituted over 60% of the total under-five mortalities seen in UBTH.

Thus the march towards actualization of the MDG-4 target of 71/1000 live births for Nigeria remains a very tall order and very urgent interventions in the area of neonatology are needed to get us back on track towards achieving MDG-4.

7.2 RECOMMENDATION

It is recommended that a standing perinatal mortality team should be put in place by the hospital. This team should be multidisciplinary comprising the obstetricians, paediatricians, paediatric pathologists as well as nursing staff. The team should put in place a defined perinatal death assessment protocol for the hospital. The protocol should institutionalize perinatal autopsy for all perinatal deaths to be able to explicitly explain away every perinatal death and keeping in view strategies to prevent reoccurrence.

The purpose should not be about statistics, rather emphasis should be about improving quality of care, saving more lives and learning from mistake and success.

.

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7.3 LIMITATION

The limitations of this study are

1. The fact that this study is a hospital based study and as such may not necessarily be truly

representative of the epidemiological profile as in the community

2. The inability to do cytogenetic analysis.

7.4 FURTHER WORK

This study has established a preliminary data on the causes of perinatal death as well as under-five mortalities as seen at the University of Benin Teaching Hospital. From this further study could be done to evaluate cytogenetics of babies with congenital anomalies as well as maternal screening in perinatal deaths to reduce the proportion of unknown cause of death.

94

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APPENDIX I115

CAUSES OF PERINATAL MORTALITY

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APPENDIX 2123

GLOBAL CAUSES OF CHILD DEATHS

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APPENDIX 3123

REGIONAL CAUSES OF CHILDHOOD DEATHS IN 2010

109

110