Maternal mortality in six low and lower-middle income countries from 2010 to 2018: risk factors and trends.

BACKGROUND: Maternal mortality is a public health problem that disproportionately affects low and lower-middle income countries (LMICs). Appropriate data sources are lacking to effectively track maternal mortality and monitor changes in this health indicator over time. METHODS: We analyzed data from women enrolled in the NICHD Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR) from 2010 through 2018. Women delivering within research sites in the Democratic Republic of Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia are included. We evaluated maternal and delivery characteristics using log-binomial models and multivariable models to obtain relative risk estimates for mortality. We used running averages to track maternal mortality ratio (MMR, maternal deaths per 100,000 live births) over time. RESULTS: We evaluated 571,321 pregnancies and 842 maternal deaths. We observed an MMR of 157 / 100,000 live births (95% CI 147, 167) across all sites, with a range of MMRs from 97 (76, 118) in the Guatemala site to 327 (293, 361) in the Pakistan site. When adjusted for maternal risk factors, risks of maternal mortality were higher with maternal age > 35 (RR 1.43 (1.06, 1.92)), no maternal education (RR 3.40 (2.08, 5.55)), lower education (RR 2.46 (1.54, 3.94)), nulliparity (RR 1.24 (1.01, 1.52)) and parity > 2 (RR 1.48 (1.15, 1.89)). Increased risk of maternal mortality was also associated with occurrence of obstructed labor (RR 1.58 (1.14, 2.19)), severe antepartum hemorrhage (RR 2.59 (1.83, 3.66)) and hypertensive disorders (RR 6.87 (5.05, 9.34)). Before and after adjusting for other characteristics, physician attendance at delivery, delivery in hospital and Caesarean delivery were associated with increased risk. We observed variable changes over time in the MMR within sites. CONCLUSIONS: The MNHR is a useful tool for tracking MMRs in these LMICs. We identified maternal and delivery characteristics associated with increased risk of death, some might be confounded by indication. Despite declines in MMR in some sites, all sites had an MMR higher than the Sustainable Development Goals target of below 70 per 100,000 live births by 2030. TRIAL REGISTRATION: The MNHR is registered at NCT01073475 .

Development of the Global Network for Women's and Children's Health Research's socioeconomic status index for use in the network's sites in low and lower middle-income countries.

BACKGROUND: Socioeconomic status (SES) is an important determinant of health globally and an important explanatory variable to assess causality in epidemiological research. The 10th Sustainable Development Goal is to reduce disparities in SES that impact health outcomes globally. It is easier to study SES in high-income countries because household income is representative of the SES. However, it is well recognized that income is poorly reported in low- and middle- income countries (LMIC) and is an unreliable indicator of SES. Therefore, there is a need for a robust index that will help to discriminate the SES of rural households in a pooled dataset from LMIC. METHODS: The study was nested in the population-based Maternal and Neonatal Health Registry of the Global Network for Women's and Children's Health Research which has 7 rural sites in 6 Asian, sub-Saharan African and Central American countries. Pregnant women enrolling in the Registry were asked questions about items such as housing conditions and household assets. The characteristics of the candidate items were evaluated using confirmatory factor analyses and item response theory analyses. Based on the results of these analyses, a final set of items were selected for the SES index. RESULTS: Using data from 49,536 households of pregnant women, we reduced the data collected to a 10-item index. The 10 items were feasible to administer, covered the SES continuum and had good internal reliability and validity. We developed a sum score-based Item Response Theory scoring algorithm which is easy to compute and is highly correlated with scores based on response patterns (r = 0.97), suggesting minimal loss of information with the simplified approach. Scores varied significantly by site (p < 0.001). African sites had lower mean SES scores than the Asian and Central American sites. The SES index demonstrated good internal consistency reliability (Cronbach's alpha = 0.81). Higher SES scores were significantly associated with formal education, more education, having received antenatal care, and facility delivery (p < 0.001). CONCLUSIONS: While measuring SES in LMIC is challenging, we have developed a Global Network Socioeconomic Status Index which may be useful for comparisons of SES within and between locations. Next steps include understanding how the index is associated with maternal, perinatal and neonatal mortality. Trial Registration NCT01073475 Socioeconomic status (SES) is an important determinant of health globally, and improving SES is important to reduce disparities in health outcomes. It is easier to study SES in high-income countries because it can be measured by income and what income is spent on, but this concept does not translate easily to low and middle income countries. We developed a questionnaire that includes 10 items to determine SES in low-resource settings that was added to an ongoing Maternal and Neonatal Health Registry that is funded by the National Institutes of Child Health and Human Development's Global Network. The Registry includes sites that collect outcomes of pregnancies in women and their babies in rural areas in 6 countries in South Asia, sub-Saharan Africa and Central America. The Registry is population based and tracks women from early in pregnancy to day 42 post-partum. The questionnaire is easy to administer and has good reliability and validity. Next steps include understanding how the index is associated with maternal, fetal and neonatal mortality.

A randomized controlled trial of hospital versus home based therapy with oral amoxicillin for severe pneumonia in children aged 3 - 59 months: The IndiaCLEN Severe Pneumonia Oral Therapy (ISPOT) Study.

BACKGROUND: Pneumonia is the leading cause of child mortality under five years of age worldwide. For pneumonia with chest indrawing in children aged 3-59 months, injectable penicillin and hospitalization was the recommended treatment. This increased the health care cost and exposure to nosocomial infections. We compared the clinical and cost outcomes of a seven day treatment with oral amoxicillin with the first 48 h of treatment given in the hospital (hospital group) or at home (home group). METHODS: We conducted an open-label, multi-center, two-arm randomized clinical trial at six tertiary hospitals in India. Children aged 3 to 59 months with chest indrawing pneumonia were randomized to home or hospital group. Clinical outcomes, treatment adherence, and patient safety were monitored through home visits on day 3, 5, 8, and 14 with an additional visit for the home group at 24 h. Clinical outcomes included treatment failure rates up to 7 days (primary outcome) and between 8-14 days (secondary outcome) using the intention to treat and per protocol analyses. Cost outcomes included direct medical, direct non-medical and indirect costs for a random 17% subsample using the micro-costing technique. RESULTS: 1118 children were enrolled and randomized to home (n = 554) or hospital group (n = 564). Both groups had similar baseline characteristics. Overall treatment failure rate was 11.5% (per protocol analysis). The hospital group was significantly more likely to fail treatment than the home group in the intention to treat analysis. Predictors with increased risk of treatment failure at any time were age 3-11 months, receiving antibiotics within 48 h prior to enrolment and use of high polluting fuel. Death rates at 7 or 14 days did not differ significantly. (Difference -0.0%; 95% CI -0.5 to 0.5). The median total treatment cost was Rs. 399 for the home group versus Rs. 602 for the hospital group (p < 0.001), for the same effect of 5% failure rate at the end of 7 days of treatment in the random subsample. CONCLUSIONS: Home based oral amoxicillin treatment was equivalent to hospital treatment for first 48 h in selected children of chest indrawing pneumonia and was cheaper. Consistent with the recent WHO simplified guidelines, management with home based oral amoxicillin for select children with only fast breathing and chest-indrawing can be a cost effective intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01386840, registered 25th June 2011 and the Indian Council of Medical Research REFCTRI/2010/000629.

Consequences of household air pollution on child survival: evidence from demographic and health surveys in 47 countries.

BACKGROUND: Over one-third of the world's population is exposed to household air pollution (HAP) but the separate effects of cooking with solid fuel and kerosene on childhood mortality are unclear. OBJECTIVES: To evaluate the effects of both solid fuels and kerosene on neonatal (0-28 days) and child (29 days-59 months) mortality. METHODS: We used Demographic and Health Surveys from 47 countries and calculated adjusted relative risks (aRR) using Poisson regression models. RESULTS: The aRR of neonatal and child mortality in households exposed to solid fuels were 1.24 (95% CI: 1.14, 1.34) and 1.21 (95% CI: 1.12, 1.30), respectively, and the aRR for neonatal and child mortality in households exposed to kerosene were 1.34 (95% CI: 1.18, 1.52) and 1.12 (95% CI: 0.99, 1.27), controlling for individual, household, and country-level predictors of mortality. CONCLUSIONS: Kerosene should not be classified as a clean fuel. Neonates are at risk for mortality from exposure to solid fuels and kerosene.

Childhood illness in households using biomass fuels in India: secondary data analysis of nationally representative national family health surveys.

BACKGROUND: Half of the world's population uses solid fuels for energy and cooking, resulting in 1.5 million deaths annually, approximately one-third of which occur in India. Most deaths are linked to childhood pneumonia or acute lower respiratory tract infection (ALRI), conditions that are difficult to diagnose. The overall effect of biomass combustion on childhood illness is unclear. OBJECTIVES: To evaluate whether type of household fuel is associated with symptoms of ALRI (cough and difficulty breathing), diarrhea or fever in children aged 0-36 months. METHODS: We analyzed nationally representative samples of households with children aged 0-36 months from three national family health surveys conducted between 1992 and 2006 in India. Households were categorized as using low (liquid petroleum gas/electricity), medium (coal/kerosene) or high polluting fuel (predominantly wood/agricultural waste). Odds ratios adjusted for confounders for exposure to high and medium polluting fuel were compared with low polluting fuel (LPF). RESULTS: Use of high polluting fuel (HPF) in India changed minimally (82 to 78 %), although LPF use increased from 8% to 18%. HPF was consistently associated with ALRI [adjusted odds ratio (95% confidence interval) 1.48 (1.08-2.03) in 1992-3; 1.54 (1.33-1.77) in 1998-9; and 1.53 (1.21-1.93) in 2005-6). Fever was associated with HPF in the first two surveys but not in the third survey. Diarrhea was not consistently associated with HPF. CONCLUSIONS: There is an urgent need to increase the use of LPF or equivalent clean household fuel to reduce the burden of childhood illness associated with IAP in India.

Zinc and copper supplementation are not cost-effective interventions in the treatment of acute diarrhea.

BACKGROUND: Diarrhea is one of the principal causes of morbidity and mortality among children in the developing world. Cumulative costs of treating diarrhea would be high and would further increase if zinc was used as an adjunct to treatment of acute diarrhea. OBJECTIVE: To determine the impact of zinc supplementation on the mean predicted costs of treating acute diarrhea and the incremental cost-effectiveness (CE) as compared with placebo, from the provider's (government) and patient's perspective. STUDY DESIGN AND SETTING: In a randomized, double-blind, placebo-controlled clinical trial, 808 children aged 6-59 months with acute diarrhea were individually randomized to placebo (Pl), zinc (Zn) only, and zinc and copper (Zn + Cu) together with standard treatment of acute diarrhea. The actual resource utilization and cost data were collected for all participants. The incremental CE ratio and its 95% confidence interval (95% CI) were assessed. RESULTS: The relative CE for treating acute diarrhea was 1.5 (95% CI: 1.50, 1.52) times more when supplemented with zinc and 1.7 (95% CI: 1.69, 1.71) times more when supplemented with Zn + Cu with no additional beneficial effect. CONCLUSION: This study showed that zinc or zinc with copper supplementation were not cost-effective in the treatment of acute diarrhea in this study population.

A novel cost-effective medium for the production of Bacillus thuringiensis subsp. israelensis for mosquito control.

Bacillus thuringiensis subsp. israelensis (Bti) has been used for mosquito-control programmes the world-wide. Indeed, the large-scale production of Bti for mosquito control is very expensive due to the high cost of its culture. In the present study, we attempted to widen the scope in developing cost-effective culture medium for Bti production, based on the raw materials available on the biosphere, including coconut cake powder, CCP (Cocos nucifera), neem cake powder, NCP (Azadirachta indica) and groundnut cake powder, GCP (Arachis hypogea). Among these raw materials, the biomass production of Bti, sporulation and toxin synthesizing from 'CCP' in combination with mineral salt (MnCl(2)) was comfortably satisfactory. Bioassays with mosquito species (Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti) and field trials were also satisfactory. The present investigation suggests that coconut cake-based culture medium can be used as an alternative for industrial production of Bti in mosquito-control programme. Therefore, the study is very important from the point of effective production of Bti from cost-effective culture medium for the control of mosquito vectors.

A tool for rapid socioeconomic assessment.

OBJECTIVE: To validate a simple wealth index scale (WIS) based assessment of socioeconomic status and compare it with existing kuppuswamy(KUP) scale. METHODS: Families of 300 children aged 6 to 59 months of acute diarrhoea enrolled in a cross-sectional study were interviewed for socio economic status using both 8 item ownership scale (WIS) and Kuppuswamy (KUP) scale, validated against a reference standard Income Scale (IS). RESULTS: Out of 111 people classified as low based on Income scale (IS), 17% were identified by WIS, and 21% by KUP. In the upper low, 69.4% were identified by WIS and 84.3 % by KUP. Amongst the low middle group the WIS identified 27.6% while KUP identified 10.6% and amongst upper middle patients 30% were identified by WIS and 15 % by KUP. There were none in the upper income of WIS or KUP category. The WIS performed well in all income categories whereas the KUP was better for upper low and low income categories. The agreement between WI and KUP was 55.56%. CONCLUSION: KUP scale is lengthy and difficult to administer by pediatric students and biased towards professional qualifications and education, rather than actual standard of living. It can be replaced by a simple 8 item ownership scale (WI) which is robust for all income groups and also shows good agreement with KUP.

Quality of life in children with sickle cell hemoglobinopathy.

OBJECTIVE: To identify specific domains and traits that are most affected in patients with sickle cell anemia and traits with respect to normal children. METHODS: Children attending the regional hemoglobinopathy center at IGMC, Nagpur in age group of 8-14 years were assessed. Of 52 children studied, 25 had sickle cell anemia (SCA), 12 had sickle cell trait (SCT) and 15 wre normal control. The (quality of life (QOL) was assessed using multidimensional interview based questionnaire. RESULTS: All domains, physical, psychosocial, cognitive and morbidity were affected. In SCA playing and mobility were most affected. There was feeling of sadness or disinterest and lack of support from teachers. The school attendance, vocational achievement perception, entertainment and participation in cultural activities were also affected. The intensity of weakness and pain was greater in SCA children who left that they were affected by a major illness. The unusual finding was that the SCT children also showed affection of all domains as compared to normal children, which was perhaps due to the stigma of the disease. CONCLUSION: QOL is affected in children with sickle cell disease (SCD) and to a lesser extent in SCT. Interventions to improve QOL should target the affected items. Improving awareness of the disease and its manifestation will help to alleviate the psychosocial affliction of children with SCT.

Economic evaluation of zinc and copper use in treating acute diarrhea in children: A randomized controlled trial.

BACKGROUND: The therapeutic effects of zinc and copper in reducing diarrheal morbidity have important cost implications. This health services research study evaluated the cost of treating a child with acute diarrhea in the hospital, the impact of micronutrient supplementation on the mean predicted costs and its cost-effectiveness as compared to using only standard oral rehydration solution (ORS), from the patient's and government's (providers) perspective. METHODS: Children aged 6 months to 59 months with acute diarrhea were randomly assigned to receive either the intervention or control. The intervention was a daily dose of 40 mg of zinc sulfate and 5 mg of copper sulfate powder dissolved in a liter of standard ORS (n = 102). The control was 50 mg of standard ORS powder dissolved in a liter of standard ORS (n = 98). The cost measures were the total mean cost of treating acute diarrhea, which included the direct medical, the direct non-medical and the indirect costs. The effectiveness measures were the probability of diarrhea lasting leq; 4 days, the disability adjusted life years (DALYs) and mortality. RESULTS: The mean total cost of treating a child with acute diarrhea was US $14 of which the government incurred an expenditure of 66%. The factors that increased the total were the number of stools before admission (p = 0.01), fever (p = 0.01), increasing grade of dehydration (p = 0.00), use of antibiotics (p = 0.00), use of intra-venous fluids (p = 0.00), hours taken to rehydrate a child (p = 0.00), the amount of oral rehydration fluid used (p = 0.00), presence of any complications (p = 0.00) and the hospital stay (p = 0.00). The supplemented group had a 8% lower cost of treating acute diarrhea, their cost per unit health (diarrhea lasting leq; 4 days) was 24% less and the incremental cost-effectiveness ratio indicated cost savings (in Rupees) with the intervention [-452; 95%CI (-11306, 3410)]. However these differences failed to reach conventional levels of significance. CONCLUSION: An emphasis on the costs and economic benefits of an alternative therapy is an important aspect of health services research. The cost savings and the attractive cost-effectiveness indicates the need to further assess the role of micronutrients such as zinc and copper in the treatment of acute diarrhea in a larger and more varied population.