Using Observational Data to Estimate the Effect of Hand Washing and Clean Delivery Kit Use by Birth Attendants on Maternal Deaths after Home Deliveries in Rural Bangladesh, India and Nepal.

BACKGROUND: Globally, puerperal sepsis accounts for an estimated 8-12% of maternal deaths, but evidence is lacking on the extent to which clean delivery practices could improve maternal survival. We used data from the control arms of four cluster-randomised controlled trials conducted in rural India, Bangladesh and Nepal, to examine associations between clean delivery kit use and hand washing by the birth attendant with maternal mortality among home deliveries. METHODS: We tested associations between clean delivery practices and maternal deaths, using a pooled dataset for 40,602 home births across sites in the three countries. Cross-sectional data were analysed by fitting logistic regression models with and without multiple imputation, and confounders were selected a priori using causal directed acyclic graphs. The robustness of estimates was investigated through sensitivity analyses. RESULTS: Hand washing was associated with a 49% reduction in the odds of maternal mortality after adjusting for confounding factors (adjusted odds ratio (AOR) 0.51, 95% CI 0.28-0.93). The sensitivity analysis testing the missing at random assumption for the multiple imputation, as well as the sensitivity analysis accounting for possible misclassification bias in the use of clean delivery practices, indicated that the association between hand washing and maternal death had been over estimated. Clean delivery kit use was not associated with a maternal death (AOR 1.26, 95% CI 0.62-2.56). CONCLUSIONS: Our evidence suggests that hand washing in delivery is critical for maternal survival among home deliveries in rural South Asia, although the exact magnitude of this effect is uncertain due to inherent biases associated with observational data from low resource settings. Our findings indicating kit use does not improve maternal survival, suggests that the soap is not being used in all instances that kit use is being reported.

Is essential newborn care provided by institutions and after home births? Analysis of prospective data from community trials in rural South Asia.

BACKGROUND: Provision of essential newborn care (ENC) can save many newborn lives in poor resource settings but coverage is far from universal and varies by country and place of delivery. Understanding gaps in current coverage and where coverage is good, in different contexts and places of delivery, could make a valuable contribution to the future design of interventions to reduce neonatal mortality. We sought to describe the coverage of essential newborn care practices for births in institutions, at home with a skilled birth attendant, and at home without a skilled birth attendant (SBA) in rural areas of Bangladesh, Nepal, and India. METHODS: We used data from the control arms of four cluster randomised controlled trials in Bangladesh, Eastern India and from Makwanpur and Dhanusha districts in Nepal, covering periods from 2001 to 2011. We used these data to identify essential newborn care practices as defined by the World Health Organization. Each birth was allocated to one of three delivery types: home birth without an SBA, home birth with an SBA, or institutional delivery. For each study, we calculated the observed proportion of births that received each care practice by delivery type with 95% confidence intervals, adjusted for clustering and, where appropriate, stratification. RESULTS: After exclusions, we analysed data for 8939 births from Eastern India, 27 553 births from Bangladesh, 6765 births from Makwanpur and 15 344 births from Dhanusha. Across all study areas, coverage of essential newborn care practices was highest in institutional deliveries, and lowest in home non-SBA deliveries. However, institutional deliveries did not provide universal coverage of the recommended practices, with relatively low coverage (20%-70%) across all study areas for immediate breastfeeding and thermal care. Institutions in Bangladesh had the highest coverage for almost all care practices except thermal care. Across all areas, fewer than 20% of home non-SBA deliveries used a clean delivery kit, the use of plastic gloves was very low and coverage of recommended thermal care was relatively poor. There were large differences between study areas in handwashing, immediate breastfeeding and delayed bathing. CONCLUSIONS: There remains substantial scope for health facilities to improve thermal care for the newborn and to encourage immediate and exclusive breastfeeding. For unattended home deliveries, increased handwashing, use of clean delivery kits and basic thermal care offer great scope for improvement.

Association between clean delivery kit use, clean delivery practices, and neonatal survival: pooled analysis of data from three sites in South Asia.

BACKGROUND: Sepsis accounts for up to 15% of an estimated 3.3 million annual neonatal deaths globally. We used data collected from the control arms of three previously conducted cluster-randomised controlled trials in rural Bangladesh, India, and Nepal to examine the association between clean delivery kit use or clean delivery practices and neonatal mortality among home births. METHODS AND FINDINGS: Hierarchical, logistic regression models were used to explore the association between neonatal mortality and clean delivery kit use or clean delivery practices in 19,754 home births, controlling for confounders common to all study sites. We tested the association between kit use and neonatal mortality using a pooled dataset from all three sites and separately for each site. We then examined the association between individual clean delivery practices addressed in the contents of the kit (boiled blade and thread, plastic sheet, gloves, hand washing, and appropriate cord care) and neonatal mortality. Finally, we examined the combined association between mortality and four specific clean delivery practices (boiled blade and thread, hand washing, and plastic sheet). Using the pooled dataset, we found that kit use was associated with a relative reduction in neonatal mortality (adjusted odds ratio 0.52, 95% CI 0.39-0.68). While use of a clean delivery kit was not always accompanied by clean delivery practices, using a plastic sheet during delivery, a boiled blade to cut the cord, a boiled thread to tie the cord, and antiseptic to clean the umbilicus were each significantly associated with relative reductions in mortality, independently of kit use. Each additional clean delivery practice used was associated with a 16% relative reduction in neonatal mortality (odds ratio 0.84, 95% CI 0.77-0.92). CONCLUSIONS: The appropriate use of a clean delivery kit or clean delivery practices is associated with relative reductions in neonatal mortality among home births in underserved, rural populations.

A non-innovator version of etanercept for treatment of arthritis.

Etanercept is a soluble tumor necrosis factor (TNF) receptor originally approved for treatment of moderate-to-severe rheumatoid arthritis, juvenile rheumatoid arthritis, and psoriatic arthritis. We have developed a non-innovator version of the recombinant protein etanercept, with the investigational name AVG01 (trade name AVENT™), using a novel expression vector-based technology. Here we show, by extensive analytical characterization, that AVG01 is highly similar to the reference product Enbrel® and demonstrates similar efficacy in pre-clinical studies.