PEDIATRICS Vol. 121 No. 5 May 2008, pp. e1372-e1380 (doi:10.1542/peds.2007-2644)
ARTICLE |
Verbal Autopsy Methods to Ascertain Birth Asphyxia Deaths in a Community-based Setting in Southern Nepal
a Department of International Health, International Center for Advancing Neonatal Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
b Nepal Nutrition Intervention Project, Sarlahi, Katmandu, Nepal
c Institute of Medicine, Tribhuvan University, Katmandu, Nepal
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
OBJECTIVES. The goals of this study were to (1) develop an approach to ascertain birth asphyxia deaths by using verbal autopsy data from a community-based setting in Nepal, and (2) explore variations in birth asphyxia mortality fractions by using different birth asphyxia case definitions and hierarchical classifications.
PATIENTS AND METHODS. Data were prospectively collected during a cluster-randomized, community-based trial of health interventions on neonatal mortality in Sarlahi, Nepal from 2002 to 2006. To assign cause of death, 4 computer-assigned, symptom-based asphyxia case definitions; Nepali physician classification; and our independent review of verbal autopsy open narratives were used. Various hierarchical classification approaches to assign cause of death were also explored.
RESULTS. Birth asphyxia specific mortality ranged from 26% to 54%, depending on the computer case definition used. There was poor agreement between computer and physician classification of birth asphyxia. By comparing computer results, physician results, and our independent ascertainment of cause of death, we identified 246 cases of birth asphyxia (32% of neonatal deaths). Allowing for >1 cause of death, 30% and 42% of asphyxia cases also met criteria for prematurity and serious infection, respectively. When a hierarchy was used to assign a single cause of death, the birth asphyxia proportionate mortality was reduced to 12% when identification of deaths because of congenital anomalies, prematurity, and serious infections preceded birth asphyxia.
CONCLUSIONS. The use of various verbal autopsy definitions and hierarchical approaches to assign cause of death may substantially affect estimates of birth asphyxia-specific mortality and analyses of risk factors. Verbal autopsy methods need to be standardized and validated to generate accurate global estimates to direct policy and resource allocation in low-middle–income countries.
Key Words: asphyxia • neonatal mortality • newborn • Nepal • verbal autopsy
Abbreviations: BA—birth asphyxia • WHO—World Health Organization • CHERG—Child Health Epidemiology Research Group • NWS—Nepal Newborn Washing Study • NNIPS—Nepal Nutrition Intervention Project • LMP—last menstrual period
Birth asphyxia (BA) is estimated to account for 23% of the 4 million global neonatal deaths and an additional 1 million stillbirths annually.1,2 The burden of asphyxia-related morbidity and mortality is concentrated in low-middle–income countries, where 99% of neonatal deaths occur,1 and the majority of births occur without medical supervision.3 The lack of a standardized case definition for birth asphyxia, particularly in community-based settings, is a fundamental challenge to being able to understand its global public health impact and identify and reasses risk factors.2 The World Health Organization (WHO) defines birth asphyxia as "the failure to initiate and sustain breathing at birth"4 whereas the American Academy of Pediatrics5 classifies an asphyxiated infant with (1) an umbilical cord arterial pH of <7.0, (2) an Apgar score of 0 to 3 at >5 minutes, (3) neurologic manifestations (seizure, coma, or hypotonia), and (4) multisystem organ dysfunction (cardiovascular, gastrointestinal, hematologic, pulmonary, or renal). Apgar scores and acidosis, however, have low sensitivity and low positive predictive value for neurologic injury and morbidity.5,6 Furthermore, laboratory data and monitoring are not feasible in resource-poor regions where the majority of births occur outside of health facilities, without skilled attendants, and many deaths occur before the infant survives long enough to develop neurologic signs and organ system dysfunction. Therefore, community-level definitions of birth asphyxia must use information about an infant's clinical condition surrounding the time of death that can be described by nonmedical caretakers.1,7
Verbal autopsy is a tool used to determine causes of death in regions lacking vital registration systems and physician-assigned cause-of-death data. During a verbal autopsy, a trained interviewer asks the caretaker open and structured questions about the events and clinical symptoms surrounding their child's death. The autopsy results are either reviewed by a physician to ascertain cause of death or, alternately, to generate larger-scale epidemiologic estimates of disease distribution, computer algorithms are used to determine cause of death from specific reported symptoms.8,9 Whereas verbal autopsy has been widely used in ascertaining causes of death in children,10 determining cause of death in neonates is particularly challenging given the nonspecific and overlapping clinical symptoms of several major causes of neonatal deaths.11
The methods and accuracy of ascertaining birth asphyxia by using verbal autopsy have varied widely across studies. Kalter et al12 developed and validated 4 symptom-based case definitions of birth asphyxia by using computer algorithms; the best-performing algorithm had a sensitivity of 87% and specificity of 76%. Freeman et al13 used data from our study area in Nepal to compare these computer-based definitions with physician-assigned causes of death and found poor agreement for birth asphyxia (
= 0.17). Marsh et al11 used a different asphyxia case definition and found that the combination of computer and physician assignment performed poorly for birth asphyxia (sensitivity: 58%, specificity: 78%, positive predictive value: 57%).
The WHO International Classification of Diseases and standard epidemiologic approaches classify single, underlying causes of death to estimate the distribution of diseases as a proportion of the total number of neonatal deaths.8,9,14 Computer-based methods use a hierarchy to assign one cause of death when comorbid states are present. The Child Health Epidemiology Reference Group (CHERG) developed a standard hierarchy that sequentially attributes deaths to congenital abnormalities, neonatal tetanus, preterm birth, birth asphyxia, sepsis/pneumonia, then diarrhea.9 Once a death is assigned to a specific cause, that case may not be assigned to another cause of death that is lower in the hierarchy. When this hierarchy was applied by Baqui et al15 to assign a single cause of death in India, the estimates of asphyxia specific mortality were substantially different from when multiple causes of death were allowed to be assigned.
These issues highlight the challenges of using verbal autopsy methods to ascertain the burden of birth asphyxia at the community level. Standardizing these methods is essential to establish accurate global estimates of birth asphyxia to direct and monitor public health programs. In this article, we describe the development of an approach to identify birth asphyxia deaths by using verbal autopsy data from a low-resource, community-based setting in Nepal; explore variations in asphyxia specific mortality fractions by using different birth asphyxia case definitions and hierarchal classifications; and propose a new case definition for birth asphyxia for future evaluation at the community level.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Data Collection
Data for the Nepal Newborn Washing Study (NWS) were collected by the Nepal Nutrition Intervention Project, Sarlahi (NNIPS) during a community-based trial from 2002 to 2006 on the impact of newborn skin and umbilical cord cleansing with chlorhexidine on neonatal mortality and morbidity in southern Nepal.16,17 Study procedures have been reported in detail previously.16,17
Pregnant women were enrolled during midpregnancy and received iron-folic acid, vitamin A, tetanus immunization, albendazole, a clean birth kit, and health education on prenatal and infant care. Newborns were randomly assigned within clusters (n = 413 sectors) in a factorial design to 1 of 2 full-body skin cleansing regimens (0.25% chlorhexidine or placebo)17 and 1 of 3 cord cleaning regimens (4% chlorhexidine, soap and water, or dry cord care).16
Household interviews were conducted to gather information on socioeconomic status, maternal reproductive history, labor and delivery, and the infant's postnatal course. Study staff collected data on newborn vital status and morbidity symptoms. Verbal autopsies were conducted on all neonatal deaths (median time of verbal autopsy administration: 2.0 days after death, 75% within 1 week, and 90% within 3 weeks) by supervisory workers who were trained in verbal autopsy techniques and had 3 to 12 years of experience in conducting verbal autopsies in this setting. The interview was conducted in Nepali by using local terminology and consisted of open-ended questions to obtain a narrative of the newborn's death, followed by closed-ended questions. The verbal autopsy questionnaire was based on the WHO standard verbal autopsy form10 with minor modifications.13
Computer-based Assignment of Cause of Death
Computerized algorithms were developed for each cause of death on the basis of previously reported case definitions described below. Each definition required the union or intersection of specific symptoms extracted from the structured questions on the verbal autopsy questionnaire; the computer algorithm assigned a cause of death if the criteria for the definition were met. A literature review was conducted to identify existing case definitions of the following conditions.
Case Definitions of Birth Asphyxia
Four case definitions were used in this analysis and are shown in Table 1: the WHO standard verbal autopsy methods (definitions 3 and 4),10 the definition used by Baqui et al,15 and the definition used in the NNIPS-NWS.17 Because the computer algorithms generated separate results for each definition, for every neonatal death, we calculated a birth asphyxia score that was the sum of the number of definitions classifying the case as birth asphyxia (range: 0–4) (Fig 1). Furthermore, a consensus definition was developed that was a union of the 4 preestablished definitions (Table 1).
|
|
Validation studies have been performed using the 2 WHO definitions12 (definition 3: sensitivity 73%, specificity 72%; definition 4: sensitivity 87%, specificity 69%). Although the Baqui et al15 and NNIPS-NWS algorithms have not been formally validated, both use symptoms from the WHO definitions. Alternate definitions considered but not used in this analysis were those described by Marsh et al18 because of the poor algorithm performance; Bang et al19 because of the combined definition of asphyxia with birth injury and lack of validation of the algorithm; and Christian et al20 because of the lack of validation of specific symptoms.
Case Definitions of Congenital Abnormality and Tetanus
Congenital abnormality and neonatal tetanus were defined by the WHO standard verbal autopsy methods10 (Fig 2).
|
Case Definition of Preterm Birth
Preterm birth was defined according to the WHO standard verbal autopsy methods (Fig 2).10 Other definitions we investigated included gestational age (<37 and < 33 weeks) by maternal report of last menstrual period (LMP) and low birth weight (<2500 g). The WHO definition was chosen in order to use a validated definition with data available from standard verbal autopsy forms, which does not include data on LMP. Furthermore, maternal report of LMP is often imprecise,21 and birth weight data were missing for many early neonatal deaths. Data on the infant being "small at birth" were not available in this study.
Case Definition of Serious Neonatal Infection
The case definition of serious neonatal infections is described in Baqui et al (Fig 2).15 Several definitions of neonatal infections were reviewed10,15,17,22,23 and this definition was selected after considering the content, information available in our data set, limitations in data from community settings, and assessment of the sepsis proportionate mortality with each definition. We chose a definition that reflects serious neonatal infections as a group, including sepsis, pneumonia and meningitis, because of overlapping clinical signs of these conditions,22,24 and frequent coexistence of these infections in newborns.25,26 Moreover, separate algorithms for these conditions have performed poorly in previous validation exercises.10,27
Assignment of Birth Asphyxia as a Final Cause of Death
In addition to the computer classification, causes of death were assigned during the study period by 2 Nepalese physicians (R.K.A., S.K.K.). They independently reviewed data from both the structured questions and verbatim history, and classified cause of death on the basis of their clinical knowledge and judgment. Specific symptom-based criteria for birth asphyxia were not preestablished before their case review. Differences in case assignment were reconciled by discussion. Whereas multiple causes of death were allowed, single causes were primarily assigned. A previous study by Freeman et al13 within our study area suggested that the Nepalese physicians were less comfortable assigning causes of death for early neonatal deaths with overlapping features and tended to underrecognize birth asphyxia.
Given these limitations and the previously reported discordance between computer and physician classifications of cause of death,13 we attempted to best determine the final cause of death with a comprehensive approach considering all the available data. We used the computerized classification of cause of death, Nepali physician assignment, and our (A.C.L., L.C.M., G.L.D.) independent review of the verbal autopsy open histories with a tiered approach (Fig 1). For all of the infants who had a high computer-assigned birth asphyxia score (3 or 4), if Nepali physicians also classified the death as asphyxia, then birth asphyxia was assigned as a final cause of death. For those with a high asphyxia score who were not assigned birth asphyxia by physician review, we further reviewed the open narratives to classify the cause of death. For those with an intermediate asphyxia score (2) both physician assignment and our independent review of the open narratives were also considered. For those with a low asphyxia score (0 or 1) but asphyxia was classified by physician assignment, we further reviewed the open narrative histories.
The goal of this case identification was to have a high sensitivity to identify all potential cases of birth asphyxia, given that these methods were used for a study of community-based risk factors of birth asphyxia.28
Use of a Hierarchy to Assign Birth Asphyxia as Single Cause of Death
We explored variations in cause-specific mortality fractions attributed to birth asphyxia by using 3 different hierarchical approaches depicted in Fig 2. Hierarchy 2 is the standard hierarchy developed by CHERG.9 Hierarchy 1 assigns cases to birth asphyxia before prematurity, which is similar to a hierarchical classification used in Winbo et al,8 and was tested to determine the broader contribution of birth asphyxia to disease burden, given the overlapping symptoms of preterm and asphyxiated infants. Hierarchy 3 removes cases of neonatal infections before asphyxia, since some hierarchical systems place antepartum infections before intrapartum asphyxia, because congenitally acquired infections may be considered the underlying cause of death.28–30
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Computer-based Classification of Birth Asphyxia as a Cause of Death
Fifty-seven percent (431 of 759) of the neonatal deaths were assigned to birth asphyxia by at least 1 definition. The nonhierarchical definition of birth asphyxia used by Baqui et al15 was the most inclusive, classifying 54% of the neonatal deaths to birth asphyxia. The WHO-4 definition was the narrowest, assigning 26% of deaths to asphyxia, given its requirement for convulsions, which may only present in cases of severe asphyxia (Table 1). The WHO-3 definition classified 247 (33%) birth asphyxia cases, NNIPS-NWS 229 (50%) cases, and the newly proposed consensus definition 249 (33%) cases. The WHO-3, WHO-4, and NNIPS-NWS definitions had excellent interalgorithm agreement (
: 0.82–0.93), whereas the Baqui et al15 algorithm had a weaker agreement with the others (: 0.35–0.42) (Table 2).
|
Of 759 neonatal deaths, 230 (30%) infants met criteria for birth asphyxia by 3 or 4 case definitions, 7 met criteria by 2 definitions, and 194 (26%) by a single definition.
Comprehensive Assessment to Classify Birth Asphyxia
Of the infants who met criteria for birth asphyxia by 3 or 4 definitions, 196 (85%) were assigned alternate diagnoses by the reviewing the Nepalese physicians (Fig 1). Thus, the agreement between physician-assigned and computer-assigned birth asphyxia (by 3 or 4 definitions) was weak, with 72% agreement and a score of 0.15. We reviewed the verbal autopsy open histories of a random subset of 40 of these deaths not identified as birth asphyxia by the physicians, and were unable to rule out birth asphyxia as a cause of death in any of the cases; thus, all were retained as deaths attributable to birth asphyxia. None of the cases with an intermediate asphyxia score of 2 were classified as birth asphyxia by the Nepali physicians or our independent review and, thus, were not included as cases of asphyxia. There was not sufficient evidence for including the infants who were attributed to birth asphyxia by a single computer definition. However, the physicians classified 12 of these infants as dying from asphyxia, and an additional 4 cases that were not assigned as asphyxia by any of the computer definitions. On review of the structured questions for these infants, who were drawn on by the computer algorithms, 10 of the 16 had missing data for specific signs required by the algorithms, and 5 had a "weak" as opposed to "no" cry. The narratives of death for these cases were reviewed and consistent with birth asphyxia and, thus, they were included among the final assignment of birth asphyxia cases.
After this extensive review process, a total of 246 (32%) of the 759 neonatal deaths received a final assignment of birth asphyxia as a cause of death (Fig 1).
Overlapping Causes of Death
Figure 3 shows the overlapping assignments of cause of death because of birth asphyxia, prematurity, and serious infections by using a nonhierarchical approach that allowed for assignment of >1 cause of death. Of the birth asphyxia deaths, 29% also met criteria for death because of prematurity, and 42% for serious infections. Only 98 infants (40% of cases assigned to birth asphyxia) exclusively met the criteria for birth asphyxia.
|
Classifying Single Causes of Death by Using a Hierarchy
To determine the effect of applying a hierarchy to assign a single cause of death, we applied definitions for alternate major causes of neonatal deaths in standard sequential order, as per CHERG methodology (Fig 2).31
Congenital Abnormality
Sixty-one (8%) neonatal deaths were classified as a congenital abnormality by the computer algorithm.10 We further reviewed the open narratives of these cases to determine if the malformation was a potentially lethal, rather than minor, nonlethal abnormality. Thirty (4%) cases were classified as lethal malformations (Fig 2) (ie, back lesions consistent with a neural tube defect, gross malformations of the head [missing eyes, ears, or forehead], significant genital or urinary tract malformations, midline cleft [given the potential association with cardiac defects],32,33 absent extremities, and potential clinical genetic syndromes34 [craniofacial dysmorphism and clinodactyly]). Nonlethal malformations (n = 31) included molding/caput, polydactyly, syndactyly, curved extremities, and club foot.
Tetanus
Thirty (4%) cases were attributed to tetanus by using the computer algorithm10; however, given the universal administration of tetanus toxoid by the study and that none of these cases were classified as tetanus deaths by the physicians, no cases were classified as being tetanus.
Prematurity
At total of 223 (29%) cases were classified as due to preterm birth10 when placed after congenital abnormalities and tetanus in the hierarchy (Fig 2, hierarchy 2).
Serious Neonatal Infection
A total of 225 (30%) cases were atttibuted to serious infection15 when placed after congenital abnormalities, tetanus, and preterm birth in the hierarchy (Fig 2, hierarchy 3).
Birth Asphyxia
The asphyxia-specific mortality fraction was reduced from 32% (based on nonhierarchical classification, Fig 1) to 30% with the hierarchical classification of congenital abnormalities before birth asphyxia (hierarchy 1), to 21% with the additional classification of preterm births (hierarchy 2), and to 12% with the additional classification of serious neonatal infections before birth asphyxia in the hierarchy (hierarchy 3) (Fig 2).
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Establishing accurate estimates of birth asphyxia in low-middle–income countries is a key priority to guide public health programming. To generate epidemiologic estimates of disease burden, computer-based methods are commonly used to interpret verbal autopsy data.10,15 Comparing 4 established asphyxia case definitions, the birth asphyxia mortality fraction ranged from 26% to 54%. Although they each incorporate the basic WHO definition of "failing to sustain breathing at birth," the definitions differ with respect to timing of death and coexisting infant clinical symptoms. Alternate definitions published in the literature have included asphyxia risk factors such as prolonged labor,11 breech presentation,11,19 presence of meconium,19 IUGR,19 or twin pregnancy19; however, verbal autopsy definitions that incorporate these risk factors have not been validated. Furthermore, incorporation of risk factors may be inappropriate in a clinical case definition for birth asphyxia, because they do not directly define the condition. Future research requires the validation and use of a standard community-level case definition of birth asphyxia to generate consistent global estimates. We propose a definition (Table 1) for future evaluation that is a consensus of the 4 tested definitions.
We found poor agreement between computer and Nepali physician-assigned cause of death, which has been reported in a previous verbal autopsy study.13 To most accurately ascertain cause of death, in addition to using computer algorithms, we incorporated data from physician-assigned cause of death and conducted an additional independent review of open narratives. The majority (85%) of infants assigned birth asphyxia as the cause of death by 3 or 4 algorithms were not identified as asphyxia deaths by physician review. The nonspecific and vague symptoms of birth asphyxia may contribute to this discord. Physicians assigned a single cause of death to all but 1 infant, with their top 2 cause-of-death assignments being "uncertain" (40%) and preterm birth (22%). Hence, the physicians may have been more likely to assign alternate causes of death with more distinct signs that were easier to distinguish on verbal autopsy review, or not assign a cause at all in cases of ambiguity. This finding highlights the potential for the underrecognition of birth asphyxia by physician review of verbal autopsy data alone. In cases of birth asphyxia identified by physician review alone, the computer algorithms failed to classify birth asphyxia either attributable to missing data or the report of "weak" as opposed to "no" cry.
Current standards for classification of causes of death support the assignment of single as opposed to multiple causes of death to calculate cause-specific mortality fractions.8,14 However, multiple disease processes may contribute to the complex pathophysiology leading to a newborn's death. We have previously reported a significant synergistic relationship between prematurity and maternal infections in the risk for birth asphyxia mortality.28 By classifying only a single cause of death, this interaction would not have been recognized. Furthermore, the overlapping clinical presentation of neonatal conditions presents challenges in discriminating cause of death with verbal autopsy methods, which often use nonspecific symptoms and rely on subtle differences that may not be discernable by caregivers. For example, a preterm or septic infant may be neurologically depressed at birth and also meet criteria for birth asphyxia by "failing to cry at birth," "failing to breathe," or being "unable to suck." In these data, over half of the infants who were classified as having birth asphyxia also met criteria for an alternate diagnosis. In many cases, a newborn may experience several comorbidities that are, furthermore, challenging to differentiate by verbal autopsy; and thus, classifying only a single cause of death fails to acknowledge complex disease processes and inaccurately influences estimates of true disease burden.
To identify a single underlying cause of death, various hierarchical classification schemes have been devised. The fixed disease categories and hierarchy tested in this study were developed by CHERG9 to standardize approaches in classifying causes of neonatal death and produce disease estimates for programmatic relevance. Some hierarchical systems assign deaths on the basis of categories that indicate the timing of the events leading to death (eg, antenatal, intrapartum, postnatal).30 The Office of National Statistics in England uses such a hierarchal classification system in the International Classification of Diseases, which assigns neonatal deaths to congenital anomalies, antepartum infections, and immaturity-related conditions before assigning deaths to asphyxia.35 However, in another classification system used in Sweden by Winbo et al,8 asphyxia is instead placed ahead of preterm birth (defined as < 33 weeks' gestation or < 2500 g). We found that the asphyxia-specific proportionate mortality was reduced from 30% to 21% when the order of asphyxia was changed from before to after preterm birth in the hierarchy (hierarchy 1 vs 2). The Neonatal and Intrauterine Cause of Death by Etiology classification system is used to identify underlying etiology of death, and places specific conditions, including fetal infections, above most causes of birth asphyxia.29 In our analysis, placing infections above asphyxia reduced the asphyxia proportionate mortality to 12%.
The nonspecificity of computer algorithms for certain conditions may lead to misclassification,36 and the placement of these conditions early in the hierarchy may result in the erroneous removal of cases from the pool of infants whose cause of death would have been classified as birth asphyxia. For example, of the cases assigned by computer algorithm as being congenital abnormalities, our independent review of narratives reclassified half of the cases as nonlethal malformations. Similarly for tetanus, on physician review, all of the computer-assigned cases were eliminated because of the universal administration of tetanus toxoid and the lack of a clear description of classic signs of tetanus such as opisthotonus or trismus. In general, if hierarchical methods are to be used, specificity is of paramount importance for those algorithms near the top of the hierarchy; thus, congenital anomalies and tetanus, both of which have shown high specificity in previous neonatal verbal autopsy validation studies (specificity 95% and 89%, respectively),10 typically appear at the top of hierarchical approaches (Fig 3). Because the definition of preterm birth used here ("being born early") had a low specificity of 78% in a previous validation study,10 positioning this above birth asphyxia in the hierarchy may have resulted in undue overclassification of preterm births and an apparent underestimate of birth asphyxia-proportionate mortality.36
Given the frequent comorbidity of neonatal diseases, current limitations in the accuracy of case definitions,36 and the substantial variations in estimates generated from different hierarchical approaches, we recommend allowing the classification of multiple causes of death, to generate more accurate and consistent estimates of disease distribution. Marsh et al37 also reported considerable changes in estimates of cause of death with single versus multiple cause attribution in Karachi, Pakistan, and recommended allowing multiple causes of death to better guide health program planning. Bang et al40 observed in Gadichivoli that 83% of neonatal deaths had greater than one morbidity infants with >1 morbidity had higher case fatality rates, and suggested the assigning of a single cause of death, which can be misleading and miss intervention opportunities. New verbal autopsy methods are being developed to analyze multiple causes of death that may simplify methods, reduce the assumptions required to make assignments, and improve the accuracy and reproducibility of estimates of cause-specific mortality rates.38
Limitations to these methods include the lack of validation of cause of death by using direct physiologic criteria or physician monitoring/measurements, given that the majority of births and deaths occurred at home.39 The WHO definitions of birth asphyxia were previously validated on a small sample of 105 infants, of which 19 were birth asphyxia cases.12 Verbal autopsy methods also rely on retrospective recall and self-report of maternal and infant symptoms. Approximately half of the verbal autopsies were conducted within 2 days of death. Verbal autopsies conducted closer to the time of death are more accurate and less subject to recall bias; however, a short time for bereavement may also potentially distress the family and result in higher refusal rates.39 The time between death and verbal autopsy here (75% within 1 week) may be shorter than in other settings, where a lag time of several weeks to a few months is more common. The long-standing relationship between the NNIPS project and the community (>20 years) and the extensive training and experience in conducting sensitive verbal autopsy interviews, however, likely facilitated the low refusal rate of 1%.
|
CONCLUSIONS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
In interpreting burden of disease data on the basis of verbal autopsy, it is critical to understand the underlying methodology that may substantially influence the estimates. We demonstrate that the distribution of neonatal deaths attributed to birth asphyxia may vary considerably on the basis of (1) the choice of verbal autopsy case definition, (2) whether single or multiple causes of death are allowed, and (3) the order of hierarchical assignment of cause of death, particularly for diseases lower in the hierarchy and neonatal conditions with overlapping symptoms, which are challenging to distinguish by verbal autopsy. Unfortunately, this applies to the 3 major causes of neonatal mortality: neonatal infections, preterm birth, and birth asphyxia. In the case of birth asphyxia, the placement of preterm birth above asphyxia in standard hierarchies may substantially underestimate asphyxia-specific mortality by as much as 30%. Such misclassification might also undermine analyses to elucidate asphyxia risk factors at the community level and lead to underestimation of the potential overall impact of interventions aiming to reduce mortality from birth asphyxia. Verbal autopsy methods for birth asphyxia need to be further standardized and validated to generate accurate global estimates to direct policy and resource allocation in communities that face the highest rates of neonatal mortality.
|
ACKNOWLEDGMENTS |
|---|
This study was conducted by the Department of International Health, Johns Hopkins Bloomberg School of Public Health, and National Institutes of Health grants HD 44004, HD 38753, and R03 HD 49406, the Bill and Melinda Gates Foundation, (grant 810–2054), and Cooperative Agreements between Johns Hopkins University and the Office of Health and Nutrition, US Agency for International Development, Washington DC (grants HRN-A-00-97-00015-00 and GHS-A-00-03-000019-00). Commodity support was provided by Procter and Gamble Company, Cincinnati, Ohio.
We would also like to thank Dr Rebecca Rosenberg for her helpful feedback on the manuscript.
|
FOOTNOTES |
|---|
Accepted Jan 18, 2008.
Address correspondence to Gary L. Darmstadt, MD, MS, Director, International Center for Advancing Neonatal Health, Department of International Health E-8153, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St, Baltimore, MD 21205. E-mail: gdarmsta{at}jhsph.edu
The authors have no financial relationships or competing interests relevant to this article to disclose.
| What's Known on This Subject Birth asphyxia accounts for 2 million global neonatal deaths and stillbirths annually and occurs largely in developing countries without adequate vital registration systems. Verbal autopsy is a promising tool to determine cause of death in such settings.
|
| What This Study Adds Estimates of birth asphyxia proportionate mortality vary substantially when using different verbal autopsy definitions and hierarchal approaches to assign cause of death. Neonatal deaths frequently have multi/overlapping causes. Verbal autopsy methods for asphyxia need to be standardized and validated.
|
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
1. Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: When? where? why? Lancet. 2005;365 (9462):891 –900[CrossRef][Web of Science][Medline]
2. Lawn JE, Manandar A, Haws R, Darmstadt GL. Reducing one million child deaths from birth asphyxia: policy and programme gaps and priorities based on an international survey. Health Res Policy Syst. 2007;5 :4[CrossRef][Medline]
3. Knippenberg R, Lawn JE, Darmstadt GL, et al. Systematic scaling up of neonatal care in countries. Lancet. 2005;365 (9464):1087 –1098[Web of Science][Medline]
4. World Health Organization, eds. Basic Newborn Resuscitation: A Practical Guide. Geneva, Switzerland: World Health Organization; 1997
5. Committee on Fetus and Newborn, American Academy of Pediatrics, and Committee on Obstetric Practice, American College of Obstetricians and Gynecologists. Use and Abuse of the Apgar Score.
Pediatrics. 1996;98
(1):141
–142
6. Ruth VJ, Raivio KO. Perinatal brain damage: predictive value of metabolic acidosis and the apgar score.
BMJ. 1988;297
(6640):24
–27
7. Bang AT, Bang RA, Baitule SB, Reddy HM, Deshmukh MD. Management of birth asphyxia in home deliveries in rural gadchiroli: the effect of two types of birth attendants and of resuscitating with mouth-to-mouth, tube-mask or bag-mask. J Perinatol. 2005;25 (suppl 1):S82 –S91[CrossRef][Medline]
8. Winbo IG, Serenius FH, Dahlquist GG, Kallen BA. A computer-based method for cause of death classification in stillbirths and neonatal deaths.
Int J Epidemiol. 1997;26
(6):1298
–1306
9. Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000.
Int J Epidemiol. 2006;35
(3):706
–718
10. Anker M, Black RE, Coldham C, et al. A Standard Verbal Autopsy Method for Investigating Causes of Death in Infants and Children. WHO/CDS/CSR/ISR/99.4. World Health Organization, Geneva. 1999:1 –78
11. Marsh DR, Sadruddin S, Fikree FF, Krishnan C, Darmstadt GL. Validation of verbal autopsy to determine the cause of 137 neonatal deaths in Karachi, Pakistan. Paediatr Perinat Epidemiol. 2003;17 (2):132 –142[CrossRef][Web of Science][Medline]
12. Kalter HD, Hossain M, Burnham G, et al. Validation of caregiver interviews to diagnose common causes of severe neonatal illness. Paediatr Perinat Epidemiol. 1999;13 (1):99 –113[CrossRef][Web of Science][Medline]
13. Freeman JV, Christian P, Khatry SK, et al. Evaluation of neonatal verbal autopsy using physician review versus algorithm-based cause-of-death assignment in rural Nepal. Paediatr Perinat Epidemiol. 2005;19 (4):323 –331[CrossRef][Web of Science][Medline]
14. Morris SS, Black RE, Tomaskovic L. Predicting the distribution of under-five deaths by cause in countries without adequate vital registration systems.
Int J Epidemiol. 2003;32
(6):1041
–1051
15. Baqui AH, Darmstadt GL, Williams EK, et al. Rates, timing and causes of neonatal deaths in rural India: implications for neonatal health programmes. Bull World Health Organ. 2006;84 (9):706 –713[CrossRef][Web of Science][Medline]
16. Mullany LC, Darmstadt GL, Khatry SK, et al. Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial. Lancet. 2006;367 (9514):910 –918[CrossRef][Web of Science][Medline]
17. Tielsch JM, Darmstadt GL, Mullany LC, et al. Impact of newborn skin-cleansing with chlorhexidine on neonatal mortality in southern Nepal: a community-based, cluster-randomized trial. Pediatrics. 2007;119 (2). Available at: www.pediatrics.org/cgi/content/full/119/2/e330
18. Marsh DR, Darmstadt GL, Moore J, Daly P, Oot D, Tinker A. Advancing newborn health and survival in developing countries: a conceptual framework. J Perinatol. 2002;22 (7):572 –576[CrossRef][Medline]
19. Bang AT, Bang RA; the SEARCH Team. Diagnosis of causes of childhood deaths in developing countries by verbal autopsy: suggested criteria. Bull World Health Organ. 1992;70 (4):499 –507[Web of Science][Medline]
20. Christian P, West KP, Khatry SK, et al. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in nepal.
Am J Clin Nutr. 2003;78
(6):1194
–1202
21. Berg AT, Bracken MB. Measuring gestational age: an uncertain proposition. Br J Obstet Gynaecol. 1992;99 (4):280 –282[Web of Science][Medline]
22. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet. 1999;354 (9194):1955 –1961[CrossRef][Web of Science][Medline]
23. Bang AT, Bang RA, Stoll BJ, Baitule SB, Reddy HM, Deshmukh MD. Is home-based diagnosis and treatment of neonatal sepsis feasible and effective? Seven years of intervention in the Gadchiroli field trial (1996 to 2003). J Perinatol. 2005;25 (suppl 1):S62 –S71[CrossRef][Medline]
24. Darmstadt GL, Black RE, Santosham M. Research priorities and postpartum care strategies for the prevention and optimal management of neonatal infections in less developed countries. Pediatr Infect Dis J. 2000;19 (8):739 –750[Web of Science][Medline]
25. The WHO Young Infants Study Group. Bacterial etiology of serious infections in young infants in developing countries: results of a multicenter study. Pediatr Infect Dis J. 1999;18 (suppl 10):S17 –S22[CrossRef][Web of Science][Medline]
26. Muhe L, Tilahun M, Lulseged S, et al. Etiology of pneumonia, sepsis and meningitis in infants younger than three months of age in Ethiopia. Pediatr Infect Dis J. 1999;18 (suppl 10):S56 –S61[CrossRef][Web of Science][Medline]
27. Weber MW, Carlin JB, Gatchalian S, et al. Predictors of neonatal sepsis in developing countries. Pediatr Infect Dis J. 2003;22 (8):711 –717[Web of Science][Medline]
28. Lee A, Mullany L, Tielsch J, et al. Risk factors for birth asphyxia mortality in southern Nepal: a prospective, community-based cohort study. Pediatrics. 2008(5):e1381 –e1390
29. Winbo IG, Serenius FH, Dahlquist GG, Kallen BA. NICE, a new cause of death classification for stillbirths and neonatal deaths: neonatal and intrauterine death classification according to etiology.
Int J Epidemiol. 1998;27
(3):499
–504
30. Alberman E, Botting B, Blatchley N, Twidell A. A new hierarchical classification of causes of infant deaths in England and Wales.
Arch Dis Child. 1994;70
(5):403
–409
31. Lawn J, Shibuya K, Stein C. No cry at birth: global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths. Bull World Health Organ. 2005;83 (6):409 –417[Web of Science][Medline]
32. Milerad J, Larson O, Hagberg C, Ideberg M. Associated malformations in infants with cleft lip and palate: a prospective, population-based study.
Pediatrics. 1997;100
(2 pt 1):180
–186
33. Shafi T, Khan MR, Atiq M. Congenital heart disease and associated malformations in children with cleft lip and palate in pakistan. Br J Plast Surg. 2003;56 (2):106 –109[CrossRef][Web of Science][Medline]
34. Suri M. Craniofacial syndromes. Semin Fetal Neonatal Med. 2005;10 (3):243 –257[CrossRef][Web of Science][Medline]
35. Dattani N, Rowan S. Causes of neonatal deaths and stillbirths: a new hierarhical classification in ICD-10. Health Stat Q. 2002;15 :16 –22
36. Anker M. The effect of misclassification error on reported cause-specific mortality fractions from verbal autopsy.
Int J Epidemiol. 1997;26
(5):1090
–1096
37. Marsh D, Husein K, Lobo M, Shah MA, Luby, S. Verbal autopsy in Karachi slums: comparing single and multiple cause of child deaths.
Health Policy Plan. 1995;10
(4):395
–403
38. King, G, Lu Y. Verbal autopsy methods with multiple causes of death. Stat Sci. In press
39. Soleman N, Chandramohan D, Shibuya K. Verbal autopsy: current practices and challenges. Bull World Health Organ. 2006;84 (3):239 –245[CrossRef][Web of Science][Medline]
40. Bang AT, Reddy HM, Bang RA, et al. Why do neonates die in rural Gadichivoli, India (Part II)? Estimating Population Attributable Risks and Contribution of Multiple Morbidities for Identifying a Strategy to Prevent Deaths. Journal of Perinatology. 2005;25 :S35 –S43[CrossRef]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. C. Lee, G. L. Darmstadt, S. K. Khatry, S. C. LeClerq, S. R. Shrestha, and P. Christian Maternal-Fetal Disproportion and Birth Asphyxia in Rural Sarlahi, Nepal Arch Pediatr Adolesc Med, July 1, 2009; 163(7): 616 - 623. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
