A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Birth attendants as perinatal verbal autopsy respondents in low- and middle-income countries: a viable alternative?

OBJECTIVE: To assess the feasibility of using birth attendants instead of bereaved mothers as perinatal verbal autopsy respondents. METHODS: Verbal autopsy interviews for early neonatal deaths and stillbirths were conducted separately among mothers (reference standard) and birth attendants in 38 communities in four developing countries. Concordance between maternal and attendant responses was calculated for all questions, for categories of questions and for individual questions. The sensitivity and specificity of individual questions with the birth attendant as respondent were assessed. FINDINGS: For early neonatal deaths, concordance across all questions was 94%. Concordance was at least 95% for more than half the questions on maternal medical history, birth attendance and neonate characteristics. Concordance on any given question was never less than 80%. Sensitivity and specificity varied across individual questions, more than 80% of which had a sensitivity of at least 80% and a specificity of at least 90%. For stillbirths, concordance across all questions was 93%. Concordance was 95% or greater more than half the time for questions on birth attendance, site of delivery and stillborn characteristics. Sensitivity and specificity varied across individual questions. Over 60% of the questions had a sensitivity of at least 80% and over 80% of them had a specificity of at least 90%. Overall, the causes of death established through verbal autopsy were similar, regardless of respondent. CONCLUSION: Birth attendants can substitute for bereaved mothers as verbal autopsy respondents. The questions in existing harmonized verbal autopsy questionnaires need further refinement, as their sensitivity and specificity differ widely.

Causes of community stillbirths and early neonatal deaths in low-income countries using verbal autopsy: an International, Multicenter Study.

OBJECTIVE: Six million stillbirths (SB) and early neonatal deaths (END) occur annually worldwide, mostly in rural settings distant from health facilities. We used verbal autopsy (VA), to understand causes of non-hospital, community-based SB and END from four low-income countries. STUDY DESIGN: This prospective observational study utilized the train-the-trainer method. VA interviewers conducted standardized interviews; in each country data were reviewed by two local physicians who assigned an underlying causes of deaths (COD). RESULT: There were 252 perinatal deaths (118 END; 134 SB) studied from pooled data. Almost half (45%) the END occurred on postnatal day 1, 19% on the second day and 16% the third day. Major early neonatal COD were infections (49%), birth asphyxia (26%), prematurity (17%) and congenital malformations (3%). Major causes of SB were infection (37%), prolonged labor (11%), antepartum hemorrhage (10%), preterm delivery (7%), cord complications (6%) and accidents (5%). CONCLUSION: Many of these SB and END were from easily preventable causes. Over 80% of END occurred during the first 3 days of postnatal life, and >90% were due to infection, birth asphyxia and prematurity. The causes of SB were more varied, and maternal infections were the most common cause. Increased attention should be targeting at interventions that reduce maternal and neonatal infections and prevent END, particularly during the first 3 days of life.

An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders.

OBJECTIVE: To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. METHODS: The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. RESULTS: There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. CONCLUSION: This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.

Health disparities between Muslim and non-Muslim countries.

We examined differences in health indicators and associated factors across countries according to the proportion of the population who are Muslim. Of 190 UN countries, 48 were classified as Muslim-majority countries (MMC) and 142 as non-MMC. Data on 41 potential determinants of health were obtained from 10 different data sources, and 4 primary outcome measures (male and female life expectancy, maternal mortality ratio and infant mortality rate) were analysed. Annual per capita expenditure on health in MMC was one-fifth that of non-MMC. Maternal mortality and infant mortality rates were twice as high in MMC as non-MMC. Adult literacy rate was significantly higher for non-MMC. Four significant predictors explained 52%-72% of the differences in health outcomes between the 2 groups: gross national income, literacy rate, access to clean water and level of corruption.

Health disparities between Muslim and non-Muslim countries

We examined differences in health indicators and associated factors across countries according to the proportion of the population who are Muslim. Of 190 UN countries, 48 were classified as Muslim-majority countries [MMC] and 142 as non-MMC. Data on 41 potential determinants of health were obtained from 10 different data sources, and 4 primary outcome measures [male and female life expectancy, maternal mortality ratio and infant mortality rate] were analysed. Annual per capita expenditure on health in MMC was one-fifth that of non-MMC. Maternal mortality and infant mortality rates were twice as high in MMC as non-MMC. Adult literacy rate was significantly higher for non-MMC. Four significant predictors explained 52%-72% of the differences in health outcomes between the 2 groups: gross national income, literacy rate, access to clean water and level of corruption

Using verbal autopsy to ascertain perinatal cause of death: are trained non-physicians adequate?

OBJECTIVES: To develop a standardized verbal autopsy (VA) training program and evaluate whether its implementation resulted in comparable knowledge required to classify perinatal cause of death (COD) by physicians and non-physicians. METHODS: Training materials, case studies, and written and mock scenarios for this VA program were developed using conventional VA and ICD-10 guidelines. This program was used to instruct physicians and non-physicians in VA methodology using a train-the-trainer model. Written tests of cognitive and applied knowledge required to classify perinatal COD were administered before and after training to evaluate the effect of the VA training program. RESULTS: Fifty-three physicians and non-physicians (nurse-midwives/nurses and Community Health Workers [CHW]) from Pakistan, Zambia, the Democratic Republic of Congo, and Guatemala were trained. Cognitive and applied knowledge mean scores among all trainees improved significantly (12.8 and 28.8% respectively, P < 0.001). Cognitive and applied knowledge post-training test scores of nurse-midwives/nurses were comparable to those of physicians. CHW (high-school graduates with 15 months or less formal health/nursing training) had the largest improvements in post-training applied knowledge with scores comparable to those of physicians and nurse-midwives/nurses. However, CHW cognitive knowledge post-training scores were significantly lower than those of physicians and nurses. CONCLUSIONS: With appropriate training in VA, cognitive and applied knowledge required to determine perinatal COD is similar for physicians and nurses-midwives/nurses. This suggests that midwives and nurses may play a useful role in determining COD at the community level, which may be a practical way to improve the accuracy of COD data in rural, remote, geographic areas.

Periodontal disease and adverse birth outcomes: a study from Pakistan.

OBJECTIVE: Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan. STUDY DESIGN: This was a prospective cohort study. Enrollment occurred at 20-26 weeks of gestation. A study dentist performed the periodontal examination to assess probing depth, clinical attachment level, gingival index, and plaque index. Outcomes included stillbirth, neonatal death, perinatal death, < 32 weeks preterm birth, 32-36 weeks preterm birth, and low birthweight and are presented for increasing periodontal disease severity by quartiles. RESULTS: Dental examinations and outcome data were completed for 1152 women: 81% of the women were multiparous, with a mean age of 27 years; 33% of the women had no education. Forty-seven percent of the women had dental caries; 27% of the women had missing teeth, and 91% of the women had had no dental care in the last year. Periodontal disease was common: 76% of the women had > or = 3 teeth with a probing depth of > or = 3 mm; 87% of the women had > or = 4 teeth with a clinical attachment level of > or = 3 mm; 56% of the women had > or = 4 teeth with a plaque index of 3; and 60% of the women had > or = 4 teeth with a gingival index of 3. As the measures of periodontal disease increased from the 1st to 4th quartile, stillbirth and neonatal and perinatal death also increased, with relative risks of approximately 1.3. Early preterm birth increased, but the results were not significant. Late preterm birth and low birthweight were not related to measures of periodontal disease. CONCLUSION: Pregnant Pakistani women have high levels of moderate-to-severe dental disease. Stillbirth and neonatal and perinatal deaths increased with the severity of periodontal disease.

Chlorhexidine vaginal and neonatal wipes in home births in Pakistan: a randomized controlled trial.

OBJECTIVE: To assess tolerance and safety of 0.6% chlorhexidine vaginal and neonatal wipes to improve perinatal outcomes in home deliveries in Pakistan and the ability of traditional birth attendants and project staff to perform a randomized trial of this intervention. METHODS: Focus groups of pregnant and nonpregnant women and in-depth interviews of traditional birth attendants explored barriers to the use of chlorhexidine wipes. Then, a study was performed of women delivering at home attended by traditional birth attendants. Consenting women were randomly assigned to receive either 0.6% chlorhexidine or saline vaginal and neonatal wipes. Women and their infants were followed up on postpartum days 7, 14, and 28. Acceptability and tolerance of vaginal and neonatal wipes, as well as maternal and neonatal outcomes, were assessed. RESULTS: The focus groups and interviews indicated that the chlorhexidine intervention would be acceptable to women and their providers. Of the 213 eligible pregnant women approached, 203 (95%) gave informed consent and were enrolled and allocated to groups. Traditional birth attendants had no difficulty administering chlorhexidine vaginal and neonatal wipes in a home setting. Of the 203 births, 103 (51%) of whom received 0.6% chlorhexidine, there were no allergic reactions, vaginal itching, burning, or requests for study termination. Follow-up at 28 days postpartum was more than 95%. Although this study was not powered to show significant differences in neonatal outcomes between treatment groups, the lower rates of some neonatal adverse clinical outcomes in the chlorhexidine group were encouraging. CONCLUSION: Use of 0.6% chlorhexidine vaginal and neonatal wipes for the prevention of neonatal infection is well-tolerated and seems safe. A trial of this intervention by traditional birth attendants in a home-delivery setting is feasible. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00121394 LEVEL OF EVIDENCE: I.

Status of rheumatic heart disease in rural Pakistan.

OBJECTIVES: To determine the community based prevalence of rheumatic heart disease (RHD) in the rural population of the district of Rahim Yaar Khan in Pakistan. SUBJECTS AND METHODS: A representative sample of the rural population of Rahim Yaar Khan district was selected. RHD was screened for by physical examination and the diagnosis was confirmed with echocardiographic Doppler studies. Sociodemographic data on each screened person were collected. RESULTS: 54 cases of RHD were found among the 9430 people screened (prevalence of 5.7 in 1000, 95% confidence interval 4.2 to 7.2). Females were significantly more likely to be affected. There was no significant relation with other factors studied (education, crowding, and socioeconomic status). Less than 20% of those found to have RHD were aware of their diagnosis before participation in this study and only three affected people (8%) were taking rheumatic prophylaxis. CONCLUSIONS: There is a high prevalence of RHD among the rural population of Pakistan. The prevalence has not declined over the past three decades. Nearly all people with RHD, including most of those who know their diagnosis, do not receive the benefit of potentially life saving secondary prevention measures.

Community and facility surveys illuminate the pathway to child survival in Liben Woreda, Ethiopia.

OBJECTIVES: To apply "Pathway to Survival" analysis to baseline assessments to inform integrated management of childhood illness programmes. DESIGN: A cross-sectional survey evaluating community-based knowledge, practices and coverage and health facility quality. SETTING: Liben Woreda (population 122, 410), a district in Borana Zone, of Ethiopia's Oromia region, from August 1997-Febuary 1998. SUBJECTS: Three hundred and sixty eight mother-child pairs (age < 24 months) seen in the community and 28 children (age < 5 years) in health facilities. RESULTS: Of the 368 mothers interviewed 50% reported that their child was ill in the previous two weeks (184/368). Amongst the 101 mothers of children under the age of six months only 24% reported exclusive breast-feeding (24/101). There were 194 children who should have completed their immunisation schedule; only 17% of them had done so (33/194). Amongst the 111 children who had diarrhoea, only 17% had received home treatment with ORS (19/111). Thirty per cent of mothers of children with possible pneumonia (25/83) and 28% who reported malaria (14/50) sought appropriate care. Amongst those caregivers seen at the health facility only 26% had an understanding of treatment recommendations. CONCLUSIONS: Based on the pathway to survival analysis, mother's knowledge of illness recognition is limited and they practice both home care and care seeking poorly. Thus few children are likely to receive and comply with standard case management.

Household members of hepatitis C virus-infected people in Hafizabad, Pakistan: infection by injections from health care providers.

Household members of people with hepatitis C are at increased risk of HCV infection. The prevalence and routes of transmission of HCV to household members in Hafizabad, Pakistan were investigated. Household members of 24 index cases were given a risk factor questionnaire, tested for HCV infection, and the risk factors between the infected and uninfected were compared. Twelve of 74 household members (16.2%) were seropositive for HCV antibody. This was 2(1/2) times the rate of infection in the general population (OR = 2.8; P = 0.01). None of the routes of transmission studied within the household was associated with an increased risk. Household members who received more than 4 injections per year were 11.9 times more likely to be infected than those who had not (P = 0.016). In Hafizabad, the greatest risk for HCV infection to household members of infected people is injections given by health-care workers rather than household contact with infected persons.

HIV antibody seroprevalence and associated risk factors in sex workers, drug users, and prisoners in Sindh, Pakistan.

OBJECTIVE: To determine prevalence of HIV infection and risk behaviors in commercial sex workers (CSWs), drug users, and prisoners in Sindh, Pakistan. METHODS: A medical clinic was established in a "red-light" district of Karachi. Eighty-one CSWs who registered at the clinic between November 1993 and June 1994 were provided HIV counseling and testing and administered a risk factor questionnaire. Next, 316 male drug users were tested for HIV-1 antibody from April to July 1994. Finally, a voluntary serosurvey of HIV-1 and HIV-2 and risk behaviors of 3525 prisoners in Sindh was conducted between July 1994 and December 1994. Abbott Recombinant HIV third-generation enzyme-linked immunosorbent assay (ELISA) and confirmatory testing with Western blot analysis were used in all three groups. RESULTS: None of 81 CSWs tested for HIV-1 antibody were positive. None of 316 drug users tested positive for HIV-1 antibody. Of 3441 male prisoners, 1 was HIV-1 infected, and of 84 female prisoners, 1 was HIV-1 infected. No prisoner was positive for HIV-2 antibody. DISCUSSION: The prevalence of HIV in CSWs, drug users, and prisoners in Sindh is low at present. Intervention programs implemented at this stage can make an impact in HIV prevention.

PIP: A three-stage study conducted in Pakistan's Sindh province in 1993-94 investigated HIV seroprevalence in commercial sex workers, drug users, and prisoners. First, the 81 sex workers who registered at a medical clinic established in a "red light" district in Karachi in a 7-month period were provided HIV counseling and testing and administered a risk factor questionnaire. Second, 316 male drug users who presented to a charitable drug rehabilitation center over a 3-month period (n = 202) or were arrested in a drug raid and sent to the center (n = 114) were tested. The third stage entailed voluntary HIV-1 and -2 testing and a risk factor questionnaire for 3525 prisoners. Recombinant HIV third-generation enzyme-linked immunosorbent assay with confirmatory testing by Western blot were used in all three groups. There were no cases of HIV-1 infection among either sex workers or drug users. HIV-1 antibody was present in 1 of the 3441 male prisoners and 1 of the 84 female prisoners. The infected male prisoner reported multiple encounters with sex workers in Bombay in 1990; the only identifiable risk factor in the HIV-positive female prisoner was several injections at the prison dispensary with reused syringes. No prisoner was positive for HIV-2 antibody. 65% of the sex workers used no contraception and condom use was negligible. 52% of injecting drug users shared needles. 22% of the male prisoners reported sexual relations with men prior to incarceration. Of concern was the finding that 26% of drug users and 23% of prisoners were paid blood donors. The low prevalence of HIV in high-risk groups in Pakistan, despite an alarming incidence of high-risk behaviors, provides a window of opportunity for implementation of AIDS prevention programs.

Macrosomia: maternal and fetal outcome.

This retrospective case--control study analyses the prevalence and outcome of macrosomia in a part of the underdeveloped world. Out of 6,093 deliveries at a large tertiary care centre, 234 (3.8%) were macrosomic. Maternal risk factors associated with the condition included age over 35, obesity, grand multiparity, postmaturity and impaired glucose tolerance. Operative deliveries were more common as was shoulder dystocia, birth trauma, fetal distress, the need for neonatal intensive care and perinatal loss.