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Abstract: A bacterial strain designated as BPM3 isolated from mud of a natural hot water spring of Nambar Wild Life Sanctuary, Assam, India, strongly inhibited growth of phytopathogenic fungi (Fusarium oxysporum f. sp. ciceri, F. semitectum, Magnaporthe grisea and Rhizoctonia oryzae) and gram-positive bacterium (Staphylococcus aureus). The maximum growth and antagonistic activity was recorded at 30°C, pH 8.5 when starch and peptone were amended as carbon and nitrogen sources, respectively. In greenhouse experiment, this bacterium (BPM3) suppressed blast disease of rice by 30–67% and protected the weight loss by 35–56.5%. The maximum disease protection (67%) and weight loss protection (56.5%) were recorded when the bacterium was applied before 2 days of the pathogen inoculation. Antifungal and antibacterial compounds were isolated from the bacterium which also inhibited the growth of these targeted pathogens. The compounds were purified and on spectroscopic analysis of a purified fraction having R f 0.22 which showed strong antifungal and antibacterial activity indicated the presence of C–H, carbonyl group, dimethyl group, –CH2 and methyl group. The bacterium was characterized by morphological, biochemical and molecular approaches and confirmed that the strain BPM3 is Brevibacillus laterosporus. [Copyright &y& Elsevier]

Background: Experiences of delayed conception and infertility have been reported among women. However, the concept of intersectionality is rarely utilised in studies of infertility, and it is particularly uncommon in research from low- and middle- income countries., Research Question: What are the lived experiences of women with delayed conception in low to -middle income neighbourhoods of Delhi, India?, Methods: This was a qualitative study (n = 35) that recruited women who had failed to conceive after 18 months of regular unprotected sexual intercourse. Data were collected between February and July 2021. Data were collected through focus group discussions in low income to middle income neighbourhoods of Delhi, India. Analysis identified themes related to intersecting axes of inequality., Results: The results showed that gender intersected with economics, masculinity, patriarchal norms and class to influence the experiences of women. The intersection of gender, economics and patriarchal norms compromised women's agency to be active generators of family income, and this dynamic was exacerbated by patrilocal residence. In addition, masculinity contributed to stigmatisation and blaming of women, due to the inaccurate perception that men did not contribute to a couple's infertility. The intersection of gender and social class in medical settings created barriers to women's access to medical information., Conclusion: Findings from this study provide representative examples of the variety of axes of inequality that shape women's experiences in the study setting. Although these findings may not be generalisable to all women who are experiencing delayed conception, they highlight a need for improved awareness and education on infertility, as well as a need to ensure the availability and accessibility of fertility care for couples in need., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Adhikary et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions., Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment., Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022., Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods., Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool., Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group., Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation., Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Aim: To learn how to achieve high-quality, effective coverage of Kangaroo Mother Care (KMC), defined as 8 hours or more of skin-to-skin contact per day and exclusive breastfeeding in district Sonipat in North India, and to develop and evaluate an implementation model., Methods: We conducted implementation research using a mixed-methods approach, including formative research, followed by repeated, rapid cycles of implementation, evaluation and refinement until a model with the potential for high and effective coverage was reached. Evaluation of this model was conducted over a 12-month period., Results: Formative research findings informed the final implementation model. Programme learning was critical to achieve high coverage. The model included improving the identification of small babies, creating KMC wards, modification in hospitalisation criteria, private sector engagement and in-built programme learning to refine implementation progress. KMC was initiated in 87% of eligible babies. At discharge, 85% received skin-to-skin contact care, 60% effective KMC and 80% were exclusively breastfed. At home, 7-day post discharge, 81% received skin-to-skin care and 79% were exclusively breastfed in the previous 24 hours., Conclusion: Achieving high KMC coverage is feasible in the study setting using a model responsive to the local context and led by the Government., (© 2022 World Health Organization; licensed by Foundation Acta Paediatrica. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Introduction: The Global Health Sector Strategy on sexually transmitted infections (STIs), endorsed by the World Health Assembly in 2016 aims to end STIs as public health threat by 2030. WHO conducts global estimates of prevalence to monitor progress towards achieving the same. However, limited laboratory confirmed data exist of STIs and reproductive tract infections (RTIs) apart from few prevalence surveys among key populations and clinic-based reports, including in India. Syndromic approach is the cornerstone of RTI/STI management and to maximise the diagnostic accuracy, there is a need to determine the main aetiologies of vaginal discharge. This study aims to estimate the prevalence of common STIs and RTIs and their aetiological organisms in symptomatic and asymptomatic women living in the urban and peri-urban, mid to low socioeconomic neighbourhoods of Delhi, North India., Methods and Analysis: A cross-sectional study will be conducted among 440 married women who participated in the 'Women and Infants Integrated Interventions for Growth Study (WINGS)'. Information on sociodemographic profile, sexual and reproductive health will be collected, followed by examination and collection of vaginal swabs for nucleic acid amplification tests to diagnose Neisseria gonorrhoeae , Chlamydia trachomatis and Trichomonas vaginalis and microscopy to identify bacterial vaginosis and Candida albicans . Treatment will be as per the syndromic approach recommendations in the Indian National Guidelines. Data will be analysed to estimate prevalence, presence of symptoms and signs associated with laboratory confirmed RTIs/STIs using STATA V.16.0 (StataCorp)., Ethics and Dissemination: This study protocol has been approved by the ethics review committees of the WHO and Society for Applied Studies (SAS/ERC/RHR-RTI/STI/2020). Approval has been obtained by the WINGS investigators from SAS ethics research committee to share the contact details of the participants with the investigators. The findings will be published in peer-reviewed journals and disseminated through scientific conferences., Trial Registration Number: CTRI/2020/03/023954., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Postpartum family planning (PPFP) helps women space childbirths, increase exclusive breastfeeding and prevent unintended pregnancies, leading to reduction in maternal, infant and child morbidities and mortality. Unmet need of family planning is highest among women in the postpartum period due to lack of knowledge, cultural and religious barriers, access barriers and low antenatal care service utilization. However, in spite of low prevalence of postpartum family planning practices, birth-to-birth interval is reportedly high in Delhi, India. This study explores the postpartum contraception practices and the relationship between use of postpartum contraception and subsequent child linear growth., Methods: This is a mixed method cohort study on PPFP and is nested within an ongoing "Women and Infants Integrated Interventions for Growth Study" (WINGS). Married women aged 18-30 years who have delivered a live baby are recruited for quantitative interviews at 6 weeks, 6, 12, and 24 months postpartum. In-depth interviews are conducted with a randomly selected sub-sample of women at each of the four time points, 35 husbands and 20 local service providers to understand their perspectives on PPFP practices., Discussion: The findings from the study will provide useful insights into couples' contraception preferences and choice of contraception, modern and traditional, initiation time and the effect of birth spacing and contraception use on subsequent linear growth of the child. This knowledge will be of significant public health relevance and will help in designing appropriate interventions for appropriate postpartum contraception use and delivery strategies. The study aims to work address the Sexual and Reproductive Health and Rights goal of promoting reproductive health, voluntary and safe sexual and reproductive choices for women., Trial Registration: Trial registration number: CTRI/2020/03/023954 ., (© 2021. The Author(s).)

Objective: To identify predictors of recovery in children with uncomplicated severe acute malnutrition (SAM)., Design: This is a secondary data analysis from an individual randomised controlled trial, where children with uncomplicated SAM were randomised to three feeding regimens, namely ready-to-use therapeutic food (RUTF) sourced from Compact India, locally prepared RUTF or augmented home-prepared foods, under two age strata (6-17 months and 18-59 months) for 16 weeks or until recovery. Three sets of predictors that could influence recovery, namely child, family and nutritional predictors, were analysed., Setting: Rural and urban slum areas of three states of India, namely Rajasthan, Delhi and Tamil Nadu., Participants: In total, 906 children (age: 6-59 months) were analysed to estimate the adjusted hazard ratio (AHR) using the Cox proportional hazard ratio model to identify various predictors., Results: Being a female child (AHR: 1·269 (1·016, 1·584)), better employment status of the child's father (AHR: 1·53 (1·197, 1·95)) and residence in a rental house (AHR: 1·485 (1·137, 1·94)) increased the chances of recovery. No hospitalisation (AHR: 1·778 (1·055, 2·997)), no fever, (AHR: 2·748 (2·161, 3·494)) and ≤ 2 episodes of diarrhoea (AHR: 1·579 (1·035, 2·412)) during the treatment phase; availability of community-based peer support to mothers for feeding (AHR: 1·61 (1·237, 2·097)) and a better weight-for-height Z-score (WHZ) at enrolment (AHR: 1·811 (1·297, 2·529)) predicted higher chances of recovery from SAM., Conclusion: The probability of recovery increases in children with better WHZ and with the initiation of treatment for acute illnesses to avoid hospitalisation, availability of peer support and better employment status of the father.

Objectives: Kangaroo Mother Care (KMC), prolonged skin-to-skin care of the low birth weight baby with the mother plus exclusive breastfeeding reduces neonatal mortality. Global KMC coverage is low. This study was conducted to develop and evaluate context-adapted implementation models to achieve improved coverage., Design: This study used mixed-methods applying implementation science to develop an adaptable strategy to improve implementation. Formative research informed the initial model which was refined in three iterative cycles. The models included three components: (1) maximising access to KMC-implementing facilities, (2) ensuring KMC initiation and maintenance in facilities and (3) supporting continuation at home postdischarge., Participants: 3804 infants of birth weight under 2000 g who survived the first 3 days, were available in the study area and whose mother resided in the study area., Main Outcome Measures: The primary outcomes were coverage of KMC during the 24 hours prior to discharge and at 7 days postdischarge., Results: Key barriers and solutions were identified for scaling up KMC. The resulting implementation model achieved high population-based coverage. KMC initiation reached 68%-86% of infants in Ethiopian sites and 87% in Indian sites. At discharge, KMC was provided to 68% of infants in Ethiopia and 55% in India. At 7 days postdischarge, KMC was provided to 53%-65% of infants in all sites, except Oromia (38%) and Karnataka (36%)., Conclusions: This study shows how high coverage of KMC can be achieved using context-adapted models based on implementation science. They were supported by government leadership, health workers' conviction that KMC is the standard of care, women's and families' acceptance of KMC, and changes in infrastructure, policy, skills and practice., Trial Registration Numbers: ISRCTN12286667; CTRI/2017/07/008988; NCT03098069; NCT03419416; NCT03506698., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Children born with low birth weight (LBW) tend to have lower neurodevelopmental scores compared to term normal birth weight children. It is important to determine factors that influence neurodevelopment in these low birth weight children especially in the first 2-3 years of life that represents a period of substantial brain development., Methods: This secondary data analysis was conducted using data from LBW infants enrolled soon after birth in an individually randomized controlled trial (RCT) and followed up till end of 1st year. Neurodevelopmental assessment was done at 12 months of corrected age by trained psychologists using Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-III). Factors influencing cognitive, motor and language scores were determined using multivariable linear regression model., Results: Linear growth (i.e., length for age z score, LAZ) [cognitive: Standardized ẞ-coefficient = 2.19, 95% CI; 1.29, 3.10; motor: 2.41, 95% CI; 1.59, 3.23; language: 1.37, 95% CI; 0.70, 2.04], stimulation at home [cognitive: 0.21, 95% CI; 0.15, 0.27; motor: 0.12, 95% CI; 0.07, 0.17; language: 0.21, 95% CI; 0.16, 0.25] and number of diarrhoeal episodes [cognitive: -2.87, 95% CI; -4.34, -1.39; motor: -2.62, 95% CI; -3.93, -1.29; language: -2.25, 95% CI; -3.32, -1.17] influenced the composite scores in all three domains i.e., cognitive, language and motor. While increase in LAZ score and stimulation led to increase in composite scores; an increase in number of diarrhoeal episodes was associated with decrease in scores. Weight for height z scores (WHZ) were associated with motor and language but not with cognitive scores. Additionally, a negative association of birth order with cognitive and language scores was noted., Conclusions: The findings indicate the possible importance of promoting nutrition and preventing diarrhoea as well as ensuring optimal stimulation and nurturance at home for enhancing child development in LBW infants., Competing Interests: The authors have declared that no competing interests exist.

Importance: Approximately 1 in 5 women in low- and middle-income countries experience postpartum depression, and the risk is higher among mothers of low-birth-weight (LBW) infants. Kangaroo mother care (KMC) is effective in improving survival among LBW infants, but the benefits of KMC for mothers are not well described., Objective: To estimate the effects of community-initiated KMC (ciKMC) on maternal risk of moderate-to-severe postpartum depressive symptoms and on salivary cortisol concentration, a biomarker of stress., Design, Setting, and Participants: This was an unmasked, parallel-group, individually randomized clinical trial. Participants included 1950 mothers of stable LBW infants (weighing 1500-2250 g) in rural and semiurban low-income populations in North India enrolled between April 2017 and March 2018. Data analysis was performed from January to July 2020., Interventions: Eligible participants were randomly assigned to the intervention or control group by block randomization. The mothers in the intervention group were supported to practice ciKMC until 28 days after birth or until the infant wriggled out of the KMC position (ie, was no longer staying in the KMC position). The intervention included promotion and support of skin-to-skin contact and exclusive breastfeeding through home visits., Main Outcomes and Measures: Postpartum depressive symptoms at the end of the neonatal period were measured using the Patient Health Questionnaire-9, with a score of 10 or higher used to identify moderate-to-severe depressive symptoms. Salivary cortisol concentration was measured in a subsample of 550 mothers before and after breastfeeding on day 28 after birth., Results: Of the 1950 participants (mean [SD] age, 23 [3.5] years), outcome assessment was completed for 974 of 1047 participants (93%) in the intervention group and 852 of 903 participants (94%) in the control group. Sixty-four percent of participants (1175 of 1826 participants) belonged to the lowest 3 wealth quintiles. The proportion of mothers with moderate-to-severe postpartum depressive symptoms was 10.8% (95% CI, 8.9%-12.9%; 105 of 974 mothers) in the intervention group vs 13.6% (95% CI, 11.4%-16.1%; 116 of 852 mothers) in the control group. The adjusted relative risk of moderate-to-severe maternal postpartum depressive symptoms was 0.75 (95% CI, 0.59-0.96), or an efficacy of 25%. There was no difference in day-28 salivary cortisol concentration between the ciKMC and control group mothers before or after breastfeeding. The analysis estimated that supporting 36 mothers to perform KMC at home would prevent 1 mother from experiencing moderate-to-severe postpartum depressive symptoms., Conclusions and Relevance: These findings suggest that ciKMC practice may substantially reduce the risk of moderate-to-severe maternal postpartum depressive symptoms. This evidence supports KMC as an intervention to be incorporated in essential newborn care programs in low- and middle-income settings., Trial Registration: Clinical Trials Registry-India Identifier: CTRI/2017/04/008430.

Background: Use of uterotonics like oxytocin to induce or augment labor has been shown to reduce placental perfusion and oxygen supply to the fetus, and studies indicate that it may increase the risk of stillbirth and neonatal asphyxia. Antenatal use of uterotonics, even without the required fetal monitoring and prompt access to cesarean section, is widespread, yet no study has adequately estimated the risk of intrapartum stillbirth and early neonatal deaths ascribed to such use. We conducted a case-control study to estimate this risk., Methods: We conducted a population-based case-control study nested in a cluster-randomized trial. From 2008 to 2010, we followed pregnant women in rural Haryana, India, monthly until delivery. We visited all live-born infants on day 29 to ascertain whether they were alive. We conducted verbal autopsies for stillbirths and neonatal deaths. Cases (n = 2,076) were the intrapartum stillbirths and day-1 deaths (early deaths), and controls (n = 532) were live-born babies who died between day 8 and 28 (late deaths)., Results: Antenatal administration of uterotonics preceded 74% of early and 62% of late deaths, translating to an adjusted odds ratio (95% confidence interval [CI]) for early deaths of 1.7 (95% CI = 1.4, 2.1), and a population attributable risk of 31% (95% CI = 22%, 38%)., Conclusions: Antenatal administration of uterotonics was associated with a substantially increased risk of intrapartum stillbirth and day-1 death. See video abstract: http://links.lww.com/EDE/B707.

Background: There is a growing interest in the life course approach for the prevention, early detection and subsequent management of morbidity in women of reproductive age to ensure optimal health and nutrition when they enter pregnancy. Reliable estimates of such morbidities are lacking. We report the prevalence of health or nutrition-related morbidities, specifically, anemia, undernutrition, overweight and obesity, sexually transmitted infections (STIs) or reproductive tract infections (RTIs), diabetes or prediabetes, hypothyroidism, hypertension, and depressive symptoms, during the preconception period among women aged 18 to 30 years., Methods: A cross-sectional study was conducted among 2000 nonpregnant married women aged 18 to 30 years with no or one child who wished to have more children in two low- to middle-income urban neighborhoods in Delhi, India, in the context of a randomized controlled trial. STIs and RTIs were measured by symptoms and signs, blood pressure by a digital device, height by stadiometer and weight by a digital weighing scale. A blood specimen was taken to screen for anemia, diabetes, thyroid disorders and syphilis. Maternal depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analysis was performed to identify sociodemographic factors associated with individual morbidity., Results: Overall, 58.7% of women were anemic; 16.5%, undernourished; 26%, overweight or obese; 13.2%, hypothyroid; and 10.5% with both symptoms and signs of STIs/RTIs. There was an increased risk of RTI/STI symptoms and signs in undernourished women and an increased risk of diabetes or prediabetes in overweight or obese women. An increased risk of undernutrition was also observed in women from lower categories of wealth quintiles. A decreased risk of moderate to severe anemia was seen in overweight women and those who completed at least secondary education., Conclusions: Our findings show a high burden of undernutrition, anemia, RTIs, hypothyroidism and prediabetes among women in the study. This information will aid policymakers in planning special programs for women of reproductive age., Competing Interests: The authors have declared that no competing interests exist.

Background: In a randomized controlled trial (RCT) with 8402 stable low birthweight (LBW) infants, majority being late preterm or term small for gestational age, community-initiated KMC (ciKMC) showed a significant improvement in survival. However, the effect of ciKMC on neurodevelopment is unclear. This is important to elucidate as children born with low birth weight are at high risk of neurodevelopmental deficits. In the first 552 stable LBW infants enrolled in the above trial, we evaluated the effect of ciKMC on neurodevelopmental outcomes during infancy., Method: This RCT was conducted among 552 stable LBW infants, majorly late preterm or term small for gestational age infants without any problems at birth and weighing 1500-2250 g at birth. The intervention comprised of promotion of skin-to-skin contact and exclusive breastfeeding by trained intervention delivery team through home visits. The intervention group mother-infant-dyads were supported to practice ciKMC till day 28 after birth or until the baby wriggled-out. All infants in the intervention and control groups received Home Based Post Natal Care (HBPNC) visits by government health workers. Cognitive, language, motor and socio-emotional outcomes were assessed at infant-ages 6- and 12-months using Bayley Scale of Infant Development (BSID-III). Other outcomes measured were infant temperament, maternal depression, maternal sense of competence, mother-infant bonding and home-environment. We performed post-hoc equivalence testing using two one-sided tests of equivalence (TOST) to provide evidence that ciKMC does not do harm in terms of neurodevelopment., Results: In the intervention arm, the median (IQR) time to initiate ciKMC was 48 (48 to 72) hours after birth. The mean (SD) duration of skin-to-skin-contact was 27.9 (3.9) days with a mean (SD) of 8.7 (3.5) hours per day. We did not find significant effect of ciKMC on any of the child developmental outcomes during infancy. The TOST analysis demonstrated that composite scores for cognitive, language and motor domains at 12 months among the study arms were statistically equivalent., Conclusion: Our study was unable to capture any effect of ciKMC on neurodevelopment during infancy in this sample of stable late preterm or term small for gestational age infants. Long term follow-up may provide meaningful insights., Trial Registration: The trial is registered at clinicaltrials.gov NCT02631343 dated February 17, 2016; Retrospectively registered.

Background: The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children., Methods: An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team., Discussion: This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings., Trial Registration: Clinical Trial Registry - India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies.

Introduction: Kangaroo Mother Care (KMC) is the practice of early, continuous and prolonged skin-to-skin contact between the mother and the baby with exclusive breastfeeding. Despite clear evidence of impact in improving survival and health outcomes among low birth weight infants, KMC coverage has remained low and implementation has been limited. Consequently, only a small fraction of newborns that could benefit from KMC receive it., Methods and Analysis: This implementation research project aims to develop and evaluate district-level models for scaling up KMC in India and Ethiopia that can achieve high population coverage. The project includes formative research to identify barriers and contextual factors that affect implementation and utilisation of KMC and design scalable models to deliver KMC across the facility-community continuum. This will be followed by implementation and evaluation of these models in routine care settings, in an iterative fashion, with the aim of reaching a successful model for wider district, state and national-level scale-up. Implementation actions would happen at three levels: 'pre-KMC facility'-to maximise the number of newborns getting to a facility that provides KMC; 'KMC facility'-for initiation and maintenance of KMC; and 'post-KMC facility'-for continuation of KMC at home. Stable infants with birth weight<2000 g and born in the catchment population of the study KMC facilities would form the eligible population. The primary outcome will be coverage of KMC in the preceding 24 hours and will be measured at discharge from the KMC facility and 7 days after hospital discharge., Ethics and Dissemination: Ethics approval was obtained in all the project sites, and centrally by the Research Ethics Review Committee at the WHO. Results of the project will be submitted to a peer-reviewed journal for publication, in addition to national and global level dissemination., Study Status: WHO approved protocol: V.4-12 May 2016-Protocol ID: ERC 2716. Study implementation beginning: April 2017. Study end: expected March 2019., Trial Registration Number: Community Empowerment Laboratory, Uttar Pradesh, India (ISRCTN12286667); St John's National Academy of Health Sciences, Bangalore, India and Karnataka Health Promotion Trust, Bangalore, India (CTRI/2017/07/008988); Society for Applied Studies, Delhi (NCT03098069); Oromia, Ethiopia (NCT03419416); Amhara, SNNPR and Tigray, Ethiopia (NCT03506698)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Coverage of kangaroo mother care remains very low despite WHO recommendations for its use for babies with low birthweight in health facilities for over a decade. Initiating kangaroo mother care at the community level is a promising strategy to increase coverage. However, knowledge of the efficacy of community-initiated kangaroo mother care is still lacking. We aimed to assess the effect of community-initiated kangaroo mother care provided to babies weighing 1500-2250 g on neonatal and infant survival., Methods: In this randomised controlled, superiority trial, undertaken in Haryana, India, we enrolled babies weighing 1500-2250 g at home within 72 h of birth, if not already initiated in kangaroo mother care, irrespective of place of birth (ie, home or health facility) and who were stable and feeding. The first eligible infants in households were randomly assigned (1:1) to the intervention (community-initiated kangaroo mother care) or control group by block randomisation using permuted blocks of variable size. Twins were allocated to the same group. For second eligible infants in the same household as an enrolled infant, if the first infant was assigned to the intervention group the second infant was also assigned to this group, whereas if the first infant was assigned to the control group the second infant was randomly assigned (1:1) to the intervention or control group. Mothers and infants in the intervention group were visited at home (days 1-3, 5, 7, 10, 14, 21, and 28) to support kangaroo mother care (ie, skin-to-skin contact and exclusive breastfeeding). The control group received routine care. The two primary outcomes were mortality between enrolment and 28 days and between enrolment and 180 days. Analysis was by intention to treat and adjusted for clustering within households. The effect of the intervention on mortality was assessed with person-time in the denominator using Cox proportional hazards model. This study is registered with ClinicalTrials.gov, NCT02653534 and NCT02631343, and is now closed to new participants., Findings: Between July 30, 2015, and Oct 31, 2018, 8402 babies were enrolled, of whom 4480 were assigned to the intervention group and 3922 to the control group. Most births (6837 [81·4%]) occurred at a health facility, 36·2% (n=3045) had initiated breastfeeding within 1 h of birth, and infants were enrolled at an average of about 30 h (SD 17) of age. Vital status was known for 4470 infants in the intervention group and 3914 in the control group at age 28 days, and for 3653 in the intervention group and 3331 in the control group at age 180 days. Between enrolment and 28 days, 73 infants died in 4423 periods of 28 days in the intervention group and 90 deaths in 3859 periods of 28 days in the control group (hazard ratio [HR] 0·70, 95% CI 0·51-0·96; p=0·027). Between enrolment and 180 days, 158 infants died in 3965 periods of 180 days in the intervention group and 184 infants died in 3514 periods of 180 days in the control group (HR 0·75, 0·60-0·93; p=0·010). The risk ratios for death were almost the same as the HRs (28-day mortality 0·71, 95% CI 0·52- 0·97; p=0·032; 180-day mortality 0·76, 0·60-0·95; p=0·017)., Interpretation: Community-initiated kangaroo mother care substantially improves newborn baby and infant survival. In low-income and middle-income countries, incorporation of kangaroo mother care for all infants with low birthweight, irrespective of place of birth, could substantially reduce neonatal and infant mortality., Funding: Research Council of Norway and University of Bergen., (Copyright © 2019 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We examined the utilisation, equity and determinants of full antenatal care (ANC), defined as 4 or more antenatal visits, at least one tetanus toxoid (TT) injection and consumption of iron folic acid (IFA) for a minimum of 100 days, in India., Methods: We analysed a sample of 190,898 women from India's National Family Health Survey 4. Concentration curves and concentration index were used to assess equity in full ANC utilisation. Multivariable logistic regression model was used to examine the factors associated with full ANC utilisation., Results: In India, 21% of pregnant women utilised full ANC, ranging from 2.3-65.9% across states. Overall, 51.6% had 4 or more ANC visits, 30.8% consumed IFA for atleast 100 days, and 91.1% had one or more doses of tetanus toxoid. Full ANC utilisation was inequitable across place of residence, caste and maternal education. Registration of pregnancy, utilisation of government's Integrated Child Development Services (ICDS) and health insurance coverage were associated with higher odds of full ANC utilisation. Lower maternal education, lower wealth quintile(s), lack of father's participation during antenatal visits, higher birth order, teenage and unintended pregnancy were associated with lower odds of full ANC utilisation., Conclusions: Full ANC utilisation in India was inadequate and inequitable. Although half of the women did not receive the minimum recommended ANC visits, the utilisation of TT immunisation was almost universal. The positive association of full ANC with ICDS utilisation and child's father involvement may be leveraged for increasing the uptake of full ANC. Strategies to address the socio-demographic factors associated with low and inequitable utilisation of full ANC are imperative for strengthening India's maternal health program.

Household air pollution (HAP) secondary to the burning of solid fuels is a major risk factor for the development of COPD. Our study seeks to examine the impact of a clean cookstove, liquid petroleum gas (LPG), on respiratory outcomes. Women (n = 200) from neighboring Indian communities, one cooking with LPG and one with biomass, were enrolled. Spirometry was performed. Relationships between primary cooking fuel and spirometry measures, as raw values, Global Lung Initiative (GLI) percent predicted (pp), and GLI z-scores, were examined using linear regression. Effect modification by age was explored. Women were young (average age 33.3 years), with low education (median 5.0 years), and the majority had multiple sources of air pollution exposures. Overall, the lung function in both groups was poor [FEV1 z-score median -2.05, IQR (-2.64, -1.41). Biomass was associated with lower FEV1/FVC (raw values -7.0, p = 0.04; GLI pp -7.62, p = 0.05, and z-score -0.86, p = 0.05) and FEF25-75 (GLI pp -25.78, p = 0.05, z-score -1.24, p = 0.05), after adjusting for confounders. Increasing impairment in lung function with age was found among biomass users (p-interaction = 0.01). In conclusion, use of a clean fuel cookstove may improve lung function. These findings have broad implications for research and public policy.

Aim: To conduct implementation research in integrated community case management (ICCM) of childhood pneumonia, diarrhoea and fever by promoting accredited social health activists as treatment providers and generate lessons for upscaling this approach., Methods: In this one-sample study, 49 Accredited Social Health Activists were trained in ICCM. Community awareness and demand generation activities undertaken included announcements, pamphlets and posters. Supplies of medicines and supervision of activists were maintained throughout the 10-month implementation period. Three cross-sectional surveys were conducted in households with children aged 2-59 months for documenting two-week prevalence of illnesses and care-seeking practices. Focus group discussions and in-depth interviews were carried out with mothers/grandmothers and activists for documenting perceptions about health activists as treatment providers., Results: One third of pneumonia (113/334) and one quarter of diarrhoea (102/408) cases at end-line were treated by Accredited Social Health Activists. Proportion of households seeking care from private providers (mostly unqualified) reduced significantly from baseline to endline (81-56% for diarrhoea, p < 0.01; 78-48% for pneumonia, p < 0.01). At endline, activists were considered an acceptable and attractive source for treatment near home., Conclusion: Trained Accredited Social Health Activists can treat uncomplicated childhood illnesses and are accepted by the community in this role., (© 2018 World Health Organization; licensed by Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objectives: Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy., Design: Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices., Setting: Rural Haryana, North India., Participants: Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life., Results: We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight <2000 g (RR 3.38; 95% CI 2.71 to 4.12). The risk of hospitalisation in the neonatal period and postneonatal period was (RR 1.86; 95% CI 1.64 to 2.11) and (RR 1.13; 95% CI 1.05 to 1.21), respectively. LBWs were at increased risk of breast feeding initiation 24 hours after birth (RR 1.64; 95% CI 1.45 to 1.81), no breast feeding at 6 months (RR 1.34; 95% CI 1.23 to 1.46) and at 12 months of age (RR 1.24; 95% CI 1.18 to 1.30)., Conclusions: LBW babies, especially those with birth weight of <2000 g, were at increased risk of mortality, hospitalisation and suboptimal breast feeding practices during entire infancy and therefore require additional care beyond the first 28 days of life., Trial Registration Number: NCT01138449., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Low-birthweight (LBW) infants are at an increased risk of stunting and poor linear growth. The risk might be additionally higher in these infants when born to short mothers. However, this hypothesis has been less explored. The objective of this secondary data analysis was to determine the risk of linear growth faltering and difference in linear growth velocity in LBW infants born to short mothers (<150 cm) compared to those born to mothers with height ≥150 cm during the first year of life. This analysis uses data from a community-based randomized controlled trial of 2,052 hospital-born term infants with birthweight ≤2,500g from urban low-middle socioeconomic neighbourhoods in Delhi, India. Data on maternal height and infant birth length were available from 1,858 (90.5%) of the infants. Infant anthropometry outcomes were measured at birth, 3, 6, 9, and 12 months of age. We found that infants born to short mothers had around twofold higher odds of stunting and lower attained length-for-age Z scores compared to infants of mothers with height ≥150 cm, at all ages of assessment. Linear growth velocity was significantly lower in infants of short mothers particularly in the first 6 months of life. We conclude that LBW infants born to short mothers are at a higher risk of stunting and have slower postnatal growth velocity resulting in lower attained length-for-age Z scores in infancy. Evidence-based strategies need to be tested to optimize growth velocity in LBW infants especially those born to short mothers., (© 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.)

Introduction: Diarrhoea is a leading cause of mortality among young children in India although few receive the recommended treatment. The diarrhoea alleviation through zinc and oral rehydration salts (ORS) therapy (DAZT) team initiated a programme in Gujarat from 2011 to 2013 to increase coverage of these interventions through public and private providers at scale. This study evaluates the economic impact of diarrhoea to caregivers before and after the introduction of zinc and ORS at scale through the DAZT programme., Methods: The DAZT programme evaluation took a before-and-after study design using a two-stage clustered cross-sectional survey. Factors associated with the odds of caregivers incurring economic costs and their amounts were evaluated in a two-part modelling approach., Results: The DAZT programme lowered unadjusted economic costs to caregivers of treating a diarrhoeal episode from $4.04 to $2.49 in 2 years. Controlling for covariates, analysis showed no association between the programme and a change in odds of incurring an economic cost but did show an association with a reduction in economic cost of $2.15 (95% confidence interval (CI) $1.20-$3.11) per diarrhoea episode. A more than 4-fold increase in care-seeking from public community health workers, reduction in care-seeking from higher levels of the health system and reduced spending on drugs besides ORS and zinc may explain these results., Discussion: This study found an association between zinc introduction and a reduction in economic burden of diarrhoea treatment to caregivers in underserved rural areas of Gujarat through more efficient patterns of care-seeking and content of care., (© The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Despite the evidence for preventing childhood morbidity and mortality, financial resources are cited as a constraint for Governments to scale up the key health interventions in some countries. We evaluate the cost effectiveness of implementing IMNCI program in India from a health system and societal perspective., Methods: We parameterized a decision analytic model to assess incremental cost effectiveness of IMNCI program as against routine child health services for infant population at district level in India. Using a 15-years time horizon from 2007 to 2022, we populated the model using data on costs and effects as found from a cluster-randomized trial to assess effectiveness of IMNCI program in Haryana state. Effectiveness was estimated as reduction in infant illness episodes, deaths and disability adjusted life years (DALY). Incremental cost per DALY averted was used to estimate cost effectiveness of IMNCI. Future costs and effects were discounted at a rate of 3%. Probabilistic sensitivity analysis was undertaken to estimate the probability of IMNCI to be cost effective at varying willingness to pay thresholds., Results: Implementation of IMNCI results in a cumulative reduction of 57,384 illness episodes, 2369 deaths and 76,158 DALYs among infants at district level from 2007 to 2022. Overall, from a health system perspective, IMNCI program incurs an incremental cost of USD 34.5 (INR 1554) per DALY averted, USD 34.5 (INR 1554) per life year gained, USD 1110 (INR 49,963) per infant death averted. There is 90% probability for ICER to be cost effective at INR 2300 willingness to pay, which is 5.5% of India's GDP per capita. From a societal perspective, IMNCI program incurs an additional cost of USD 24.1 (INR 1082) per DALY averted, USD 773 (INR 34799) per infant death averted and USD 26.3 (INR 1183) per illness averted in during infancy., Conclusion: IMNCI program in Indian context is very cost effective and should be scaled-up as a major child survival strategy.

Background: To address inadequate coverage of oral rehydration salts (ORS) and zinc supplements for the treatment of diarrhea among children under-five, the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program was carried out from 2011-2013 in Gujarat and from 2011-2014 in Uttar Pradesh (UP), India. The program focused on improving the diarrhea treatment practices of public and private sector providers., Methods: We conducted cross-sectional household surveys in program districts at baseline and endline and constructed state-specific logistic regression models with generalized estimating equations to assess changes in ORS and zinc treatment during the program period., Results: Between baseline and endline, zinc coverage increased from 2.5% to 22.4% in Gujarat and from 3.1% to 7.0% in UP; ORS coverage increased from 15.3% to 39.6% in Gujarat but did not change in UP. In comparison to baseline, children with diarrhea in the two-weeks preceding the endline survey had higher odds of receiving zinc treatment in both Gujarat (odds ratio, OR = 11.2; 95% confidence interval (CI) 6.4-19.3) and UP (OR = 2.4; 95% CI 1.4-3.9), but the odds of receiving ORS only increased in Gujarat (OR = 3.6; 95% CI 2.7-4.8; UP OR = 0.9; 95% CI 0.7-1.2). Seeking care outside the home, especially from a public sector source, was associated with higher odds of receiving ORS and zinc., Conclusions: During the duration of the DAZT program, there were modest improvements in the treatment of diarrhea among young children. Future programs should build upon and accelerate this trend with continued investment in public and private sector provider training and supply chain sustainability, in addition to targeted caregiver demand generation activities.

Background: There is limited evidence on adherence to the recommended dose and duration of zinc supplementation for diarrheal episodes in children under five years of age. In selected districts of Uttar Pradesh, India, we sought to assess adherence to the nationally advised zinc treatment regimen (ie, 10 mg/day for ages 2-6 months and 20 mg/day for ages 7-59 months for 14 days) among caregivers of zinc-prescribed children., Methods: We identified and conducted follow-up visits to children advised zinc for the treatment of diarrhea. At the initial visit, we collected data on the treatment instructions received from providers. Caregivers were asked to record treatments administered on a pictorial tracking form and were asked to retain all packaging for collection at follow-up. We quantified the average dose and duration of zinc therapy and built logistic regression models to assess the factors associated with caregiver adherence to national guidelines., Results: Caregivers administered zinc for an average of 10.7 days (standard deviation (SD) = 3.9 days; median = 13 days), and 47.8% continued treatment for the complete 14 days. Among children receiving zinc syrups and tablets respectively, the age appropriate dose was received by 30.8% and 67.3%. Adherence to age appropriate dose and continuation of zinc for 14 days were highly associated with having received appropriate provider instructions., Conclusions: Our results indicate moderate-to-good adherence to national zinc treatment guidelines for diarrhea among caregivers in rural India. Our findings also highlight the importance of provider guidance in ensuring adherence to zinc dose and duration. Programs aiming to scale-up zinc treatment for childhood diarrhea should train providers to successfully communicate dosing instructions to caregivers, while also addressing the tendency of caregivers to terminate treatment once a child appears to have recovered from an acute diarrheal episode.

Increased diarrheal episode severity has been linked to better 2-week recall and improved care-seeking and treatment among caregivers of children under five. Using cross-sectional data from three Indian states, we sought to assess the relationship between episode severity and the recall, care-seeking, and treatment of childhood diarrhea. Recall error was higher for episodes with onset 8-14 days (31.2%) versus 1-7 days (4.8%) before the survey, and logistic regression analysis showed a trend toward increased severity of less recent compared with more recent episodes. This finding indicates that data collection with 2-week recall underestimates diarrhea prevalence while overestimating the proportion of severe episodes. There was a strong correlation between care-seeking and dehydration, fever, vomiting, and increased stool frequency and duration. Treatment with oral rehydration salts was associated with dehydration, vomiting, and higher stool frequency, and trends were established between therapeutic zinc supplementation and increased duration and stool frequency. However, state and care-seeking sector were stronger determinants of treatment than episode severity, illustrating the need to address disparities in treatment quality across regions and delivery channels. Our findings are of importance to researchers and diarrhea management program evaluators aiming to produce accurate estimates of diarrheal outcomes and program impact in low- and middle-income countries., (© The American Society of Tropical Medicine and Hygiene.)

Introduction: Programs aimed at reducing the burden of diarrhea among children under-five in low-resource settings typically allocate resources to training community-level health workers, but studies have suggested that provider knowledge does not necessarily translate into adequate practice. A diarrhea management program implemented in Bihar, Gujarat and Uttar Pradesh, India trained private sector rural medical practitioners (RMPs) and public sector Accredited Social Health Activists (ASHAs) and Anganwadi workers (AWWs) in adequate treatment of childhood diarrhea with oral rehydration salts (ORS) and zinc. We used cross-sectional program evaluation data to determine the association between observed diarrhea treatment practices and reported knowledge of ORS and zinc among each provider cadre., Methods: We conducted principal components analysis on providers' responses to diarrhea treatment questions in order to generate a novel scale assessing ORS/zinc knowledge. We subsequently regressed a binary indicator of whether ORS/zinc was prescribed during direct observation onto the resulting knowledge scores, controlling for other relevant knowledge predictors., Results: There was a positive association between ORS/zinc knowledge score and prescribing ORS and zinc to young children with diarrhea among private sector RMPs (aOR: 2.32; 95% CI: 1.29-4.17) and public sector ASHAs and AWWs (aOR 2.48; 95% CI: 1.90-3.24). Controlling for knowledge score, receipt of training in the preceding 6 months was a good predictor of adequate prescribing in the public but not the private sector. In the public sector, direct access to ORS and zinc supplies was also highly associated with prescribing., Conclusions: To enhance the management of childhood diarrhea in India, programmatic activities should center on increasing knowledge of ORS and zinc among public and private sector providers through biannual trainings but should also focus on ensuring sustained access to an adequate supply chain.

Diarrhea remains a leading cause of morbidity and mortality among children under 5 years of age in low- and middle-income countries. In 2006, the Indian government formally endorsed the World Health Organization guidelines that introduced zinc supplementation and low-osmolarity oral rehydration salts (ORS) for the treatment of diarrhea. Despite this, zinc is rarely prescribed and has not been available in the public sector in India until very recently. The Diarrhea Alleviation Through Zinc and ORS Treatment (DAZT) project was implemented in Gujarat between 2011 and 2013 to accelerate the uptake of zinc and ORS among public and private providers in 6 rural districts. As part of an external evaluation of DAZT, we interviewed 619 randomly selected facility- and community-based public and private providers 2-3 months after a 1-day training event had been completed (or, in the case of private providers, after at least 1 drug-detailing visit by a pharmaceutical representative had occurred) and supplies were in place. The purpose of the interviews was to assess providers' knowledge of appropriate treatment for diarrhea in children, reported treatment practices, and availability of drugs in stock. More than 80% of all providers interviewed reported they had received training or a drug-detailing visit on diarrheal treatment in the past 6 months. Most providers in all cadres (range, 68% to 100%) correctly described how to prepare ORS and nearly all (range, 90% to 100%) reported routinely prescribing it to treat diarrhea in children. Reported routine prescription of zinc was lower, ranging from 62% among private providers to 96% among auxiliary nurse-midwives. Among providers who reported ever not recommending zinc (n = 242), the 2 most frequently reported reasons for not doing so were not completely understanding zinc for diarrhea treatment and not having zinc in stock at the time of contact with the patient. In a multiple logistic regression analysis, recent training or drug-detailing visits and having zinc in stock were associated with reported zinc prescribing (P<.05). Recent training among public providers was significantly associated with having correct knowledge of zinc treatment duration and dosage, but the same was not true of drug-detailing visits among private providers. Treating diarrhea with zinc and low-osmolarity ORS is new for public and private providers in India and other low- and middle-income countries. Sufficient training and logistics support to ensure consistent supplies are critical if providers are to begin routinely treating all diarrhea episodes with zinc and ORS., (© Fischer Walker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly cited. To view a copy of the license, visit http://creativecommons.org/licenses/by/3.0/)

Background: Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age., Methods: We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220., Findings: Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32])., Interpretation: The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy., Funding: Bill & Melinda Gates Foundation to WHO., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd. All rights reserved.)

Background: Child diarrhea persists as a leading public health problem in India despite evidence supporting zinc and low osmolarity oral rehydration salts as effective treatments. Across 2 years in 2010-2013, the Diarrhea Alleviation using Zinc and Oral Rehydration Salts Therapy (DAZT) program was implemented to operationalize delivery of these interventions at scale through private and public sector providers in rural Gujarat and Uttar Pradesh, India., Methods/design: This study evaluates the cost-effectiveness of DAZT program activities relative to status quo conditions existing before the study, comparing a Monte Carlo simulation method with net-benefit regression, discussing the strengths and weaknesses of each approach. A control group was not included in the 'before and after' study design as zinc has proven effectiveness for diarrhea treatment. Costs will be calculated using a societal perspective including program implementation and household out-of-pocket payments for care seeking, as well as estimates of wages lost. Outcomes will be measured in terms of episodes averted in net-benefit regression and in terms of the years of life lost component of disability-adjusted life years in the method based on Monte Carlo simulation. The Lives Saved Tool will be used to model anticipated changes in mortality over time and deaths averted based on incremental changes in coverage of oral rehydration salts and zinc. Data will derive from cross-sectional surveys at the start, midpoint, and endpoint of the program. In addition, Lives Saved Tool (LiST) projections will be used to define the reference case value for the ceiling ratio in terms of natural units., Discussion: This study will be useful both in its application to an economic evaluation of a public health program in its implementation phase but also in its comparison of two methodological approaches to cost-effectiveness analysis. Both policy recommendations and methodological lessons learned will be discussed, recognizing the limitations in drawing strong policy conclusions due to the uncontrolled study design. It is expected that this protocol will be useful to researchers planning what method to use for the evaluation of similar before and after studies.

Objective: To investigate the clinical characteristics of children who died from diarrhoea in low- and middle-income countries, such as the duration of diarrhoea, comorbid conditions, care-seeking behaviour and oral rehydration therapy use., Methods: The study included verbal autopsy data on children who died from diarrhoea between 2000 and 2012 at seven sites in Bangladesh, Ethiopia, Ghana, India, Pakistan, Uganda and the United Republic of Tanzania, respectively. Data came from demographic surveillance sites, randomized trials and an extended Demographic and Health Survey. The type of diarrhoea was classified as acute watery, acute bloody or persistent and risk factors were identified. Deaths in children aged 1 to 11 months and 1 to 4 years were analysed separately., Findings: The proportion of childhood deaths due to diarrhoea varied considerably across the seven sites from less than 3% to 30%. Among children aged 1-4 years, acute watery diarrhoea accounted for 31-69% of diarrhoeal deaths, acute bloody diarrhoea for 12-28%, and persistent diarrhoea for 12-56%. Among infants aged 1-11 months, persistent diarrhoea accounted for over 30% of diarrhoeal deaths in Ethiopia, India, Pakistan, Uganda and the United Republic of Tanzania. At most sites, more than 40% of children who died from persistent diarrhoea were malnourished., Conclusion: Persistent diarrhoea remains an important cause of diarrhoeal death in young children in low- and middle-income countries. Research is needed on the public health burden of persistent diarrhoea and current treatment practices to understand why children are still dying from the condition.

Objective: To determine the effect of implementation of the Integrated Management of Neonatal and Childhood Illness strategy on treatment seeking practices and on neonatal and infant morbidity., Design: Cluster randomised trial., Setting: Haryana, India., Participants: 29,667 births in nine intervention clusters and 30,813 births in nine control clusters., Main Outcome Measures: The pre-specified outcome was the effect on treatment seeking practices. Post hoc exploratory analyses assessed morbidity, hospital admission, post-neonatal infant care, and nutritional status outcomes., Interventions: The Integrated Management of Neonatal and Childhood Illness intervention included home visits by community health workers, improved case management of sick children, and strengthening of health systems. Outcomes were ascertained through interviews with randomly selected caregivers: 6204, 3073, and 2045 in intervention clusters and 6163, 3048, and 2017 in control clusters at ages 29 days, 6 months, and 12 months, respectively., Results: In the intervention cluster, treatment was sought more often from an appropriate provider for severe neonatal illness (risk ratio 1.76, 95% confidence interval 1.38 to 2.24), for local neonatal infection (4.86, 3.80 to 6.21), and for diarrhoea at 6 months (1.96, 1.38 to 2.79) and 12 months (1.22, 1.06 to 1.42) and pneumonia at 6 months (2.09, 1.31 to 3.33) and 12 months (1.44, 1.00 to 2.08). Intervention mothers reported fewer episodes of severe neonatal illness (risk ratio 0.82, 0.67 to 0.99) and lower prevalence of diarrhoea (0.71, 0.60 to 0.83) and pneumonia (0.73, 0.52 to 1.04) in the two weeks preceding the 6 month interview and of diarrhoea (0.63, 0.49 to 0.80) and pneumonia (0.60, 0.46 to 0.78) in the two weeks preceding the 12 month interview. Infants in the intervention clusters were more likely to still be exclusively breast fed in the sixth month of life (risk ratio 3.19, 2.67 to 3.81)., Conclusion: Implementation of the Integrated Management of Neonatal and Childhood Illness programme was associated with timely treatment seeking from appropriate providers and reduced morbidity, a likely explanation for the reduction in mortality observed following implementation of the programme in this study.Trial registration Clinical trials NCT00474981; ICMR Clinical Trial Registry CTRI/2009/091/000715., (© Mazumder et al 2014.)

The antioxidant property of the 70% aqueous ethanol extract of Phyllanthus amarus roots and its ether-soluble, ethyl acetate-soluble, and aqueous fractions were investigated by various in vitro assays. The root extracts showed higher DPPH, hydroxyl, superoxide, and nitric oxide radical scavenging and reducing power activity. Among all the samples, the ethyl acetate-soluble fraction demonstrated highest radical scavenging activity and total phenolics content. Twenty-eight different phenolic compounds were identified by LCMS/MS analysis of the ethyl acetate-soluble fraction. The majority of the compounds were found to exist as their glycosides, and many of these were gallic acid derivatives. Free epicatechin and gallic acid were also identified in the ethyl acetate-soluble fraction. The present investigation suggested that P. amarus root is a potent antioxidant and can be used for the prevention of diseases related to oxidative stress.

Objective: To evaluate the Indian Integrated Management of Neonatal and Childhood Illness (IMNCI) programme, which integrates improved treatment of illness for children with home visits for newborn care, to inform its scale-up., Design: Cluster randomised trial., Setting: 18 clusters (population 1.1 million) in Haryana, India., Participants: 29,667 births in intervention clusters and 30,813 in control clusters., Intervention: Community health workers were trained to conduct postnatal home visits and women's group meetings; physicians, nurses, and community health workers were trained to treat or refer sick newborns and children; supply of drugs and supervision were strengthened., Main Outcome Measures: Neonatal and infant mortality; newborn care practices., Results: The infant mortality rate (adjusted hazard ratio 0.85, 95% confidence interval 0.77 to 0.94) and the neonatal mortality rate beyond the first 24 hours (adjusted hazard ratio 0.86, 0.79 to 0.95) were significantly lower in the intervention clusters than in control clusters. The adjusted hazard ratio for neonatal mortality rate was 0.91 (0.80 to 1.03). A significant interaction was found between the place of birth and the effect of the intervention for all mortality outcomes except post-neonatal mortality rate. The neonatal mortality rate was significantly lower in the intervention clusters in the subgroup born at home (adjusted hazard ratio 0.80, 0.68 to 0.93) but not in the subgroup born in a health facility (1.06, 0.91 to 1.23) (P value for interaction = 0.001). Optimal newborn care practices were significantly more common in the intervention clusters., Conclusions: Implementation of the IMNCI resulted in substantial improvement in infant survival and in neonatal survival in those born at home. The IMNCI should be a part of India's strategy to achieve the millennium development goal on child survival., Trial Registration: Clinical trials NCT00474981; ICMR Clinical Trial Registry CTRI/2009/091/000715.

Background: Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo., Methods/design: The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation., Discussion: The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.

Objective: To determine if educating caregivers in providing zinc supplements to infants < 6 months old with acute diarrhoea is effective in treating diarrhoea and preventing acute lower respiratory infections (ALRIs), and whether it leads to a decrease in the use of oral rehydration salts (ORS)., Methods: In this retrospective subgroup analysis of infants aged < 6 months, six clusters were randomly assigned to intervention or control sites. Care providers were trained to give zinc and ORS to children with acute diarrhoea at intervention sites, and only ORS at control sites. Surveys were conducted at 3 and 6 months to assess outcomes. Differences between intervention and control sites in episodes of diarrhoea and ALRI in the preceding 24 hours or 14 days and of hospitalizations in the preceding 3 months were analysed by logistic regression., Findings: Compared with control sites, intervention sites had lower rates of acute diarrhoea in the preceding 14 days at 3 months (odds ratio, OR: 0.60; 95% confidence interval, CI: 0.43-0.84) and 6 months (OR: 0.72; 95% CI: 0.54-0.94); lower rates of acute diarrhoea in the preceding 24 hours at 3 months (0.66; 95% CI: 0.50-0.87) and of ALRI in the preceding 24 hours at 6 months (OR: 0.59; 95% CI: 0.37-0.93); and lower rates of hospitalization at 6 months for all causes (OR: 0.40; 95% CI: 0.34-0.49), diarrhoea (OR: 0.34; 0.18-0.63) and pasli chalna or pneumonia (OR: 0.36; 95% CI: 0.24-0.55)., Conclusion: Educating caregivers in zinc supplementation and providing zinc to infants < 6 months old can reduce diarrhoea and ALRI. More studies are needed to confirm these findings as these data are from a subgroup analysis.

Objective: To compare the acceptability and energy intake of Ready-to-Use Therapeutic Food (RUTF) with cereal legume based khichri among malnourished children., Design: An acceptability trial with cross-over design., Setting: Urban low to middle socioeconomic neighbor-hoods in Delhi., Subjects: 31 children aged > or =6 to < or =36 months with malnutrition, defined as Weight for height (WHZ) < -2 to > or = -3 SD, with no clinical signs of infection or edema., Intervention: Children were offered weighed amounts of RUTF and khichri in unlimited amounts for 2 days, one meal of each on both days. Water was fed on demand. Caregivers interviews and observations were conducted on the second day., Outcome Measures: Acceptability of RUTF compared to khichri based on direct observation and energy intake for test and control meals., Results: The proportion of children who accepted RUTF eagerly was 58% as against 77% for khichri. 42% children on RUTF and 23% on khichri accepted the meal but not eagerly. The median (IQR) energy intake over the two day period in children aged 6 to 36 months from RUTF was 305 (153, 534) kcal, and from khichri was 242 (150, 320) kcal (P=0.02)., Conclusion: RUTF and khichri were both well accepted by study children. The energy intake from RUTF was higher due to its extra energy density.

Objective: The purpose of this work was to evaluate whether education about zinc supplements and provision of zinc supplements to caregivers is effective in the treatment of acute diarrhea and whether this strategy adversely affects the use of oral rehydration salts., Patients and Methods: Six clusters of 30,000 people each in Haryana, India, were randomly assigned to intervention and control sites. Government and private providers and village health workers were trained to prescribe zinc and oral rehydration salts for use in diarrheal episodes in 1-month-old to 5-year-old children in intervention communities; in the control sites, oral rehydration salts alone was promoted. In 2 cross-sectional surveys commencing 3 months (survey 2) and 6 months (survey 3) after the start of the intervention, care-seeking behavior, drug therapy, and oral rehydration salts use during diarrhea, diarrheal and respiratory morbidity, and hospitalization rates were measured., Results: In the 2 surveys, zinc was used in 36.5% (n = 1571) and 59.8% (n = 1649) and oral rehydration salts in 34.8% (n = 1571) and 59.2% (n = 1649) of diarrheal episodes occurring in the 4 weeks preceding interviews in the intervention areas. In control areas, oral rehydration salts were used in 7.8% (n = 2209) and 9.8% (n = 2609) of episodes. In the intervention communities, care seeking for diarrhea reduced by 34% (survey 3), as did the prescription of drugs of unknown identity (survey 3) and antibiotics (survey 3) for diarrhea. The 24-hour prevalences of diarrhea and acute lower respiratory infections were lower in the intervention communities (survey 3). All-cause, diarrhea, and pneumonia hospitalizations in the preceding 3 months were reduced in the intervention compared with control areas (survey 3)., Conclusions: Diarrhea is more effectively treated when caregivers receive education on zinc supplementation and have ready access to supplies of oral rehydration salts and zinc, and this approach does not adversely affect the use of oral rehydration salts; in fact, it greatly increases use of the same.

Zinc is recommended for the treatment of acute diarrhea in children but the effect of its introduction on drug and oral rehydration solution use is unclear. Government care providers, private practitioners and community workers were trained to distribute zinc and oral rehydration solution to children seeking care for diarrhea. Periodic surveys showed that village-based workers became a common source of diarrhea treatment and private practitioners were used less. Zinc was used in approximately half of the episodes; the prescription and use rates of oral rehydration solution packets increased from 7% at baseline to 44.9% 6 months later. Reduction in use of drugs during diarrhea ranged from 34% for tablets to 64% for injections 6 months later. The cost of treatment to families declined significantly. These findings need confirmation in a randomized controlled trial.

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities., Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization., Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p<0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation., Conclusions: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvement.

A lectin with molecular mass around 200 kDa was isolated from the serum of the Indian catfish Clarias batrachus. The bioactivity of this serum lectin was Ca2+ and pH dependent. The lectin appeared to be specific for alpha-methyl galactose and sialoglycoproteins like porcine and bovine submaxillary mucin and could agglutinate human, rabbit, mice, rat and chicken erythrocytes. This fish lectin was able to specifically agglutinate different gram negative bacteria. When it was checked against different strains of the fish pathogen Aeromonas sp., it significantly altered the viability and pathogenicity of the bacteria. Binding of the lectin to Aeromonas sp., resulted in a dose dependent increase in the bactericidal activity of fish macrophages. However, when the lectin was checked against different gram positive bacteria it could not agglutinate or affect the viability of those strains and also failed to bring about any significant change in the bactericidal potential of fish macrophages. The lectin was able to induce the proliferation of head kidney lymphocytes of Clarias and helped in the release of 'IL-1' like cytokines from head kidney macrophages.

This paper assessed gender bias within hospitalisation rates to ascertain whether differential care-seeking practices significantly contribute to excess female mortality. It then examined the impact of socio-economic factors, particularly maternal education and economic status, on gender bias. The results find both the clear and significant impact of gender on hospitalisation rates, as well as the simultaneous inability of rising education and economic status to alleviate this bias. A secondary analysis was conducted within a uniquely large and ongoing randomised control trial that sought to measure the impact of Zinc supplementation on hospitalisations and deaths in low-income communities in New Delhi, India. During the course of the study, 85,633 children were enrolled and monitored over one year of follow-up. Of the 430 deaths that occurred, 230 were female (0.57% of total females), while 200 were male (0.43% of all males). Despite this higher mortality amongst females (p<0.02), girls were hospitalised far less frequently than boys. Of the 4418 children who were hospitalised at least once, 2854 (64.6%) were males and only 1564 (35.4%) were females, indicating a significantly lower rate of care-seeking for females (p<0.00). Curiously, our results show that gender bias is highest amongst highly educated mothers, and decreases steadily for children of mothers with a middle school education, a primary school education, and is lowest amongst mothers with no formal education. Put differently, female children of mothers with no formal education were significantly more likely to be hospitalised than children of mothers with several years of formal education, even after adjusting for all other factors. Economic status was not found to affect the association of gender and hospitalisation, though overall odds of hospitalisation rose with increasing economic status. Paternal education was found not to be significantly related to hospitalisation.

Complementary feeding practices are often inadequate in developing countries, resulting in a significant nutritional decline between 6 and 18 mo of age. We assessed the effectiveness of an educational intervention to promote adequate complementary feeding practices that would be feasible to sustain with existing resources. The study was a cluster randomized controlled trial in communities in the state of Haryana in India. We developed the intervention through formative research. Eight communities were pair matched on their baseline characteristics; one of each pair was randomly assigned to receive the intervention and the other to no specific feeding intervention. Health and nutrition workers in the intervention communities were trained to counsel on locally developed feeding recommendations. Newborns were enrolled in all of the communities (552 in the intervention and 473 in the control) and followed up every 3 mo to the age of 18 mo. The main outcome measures were weights and lengths at 6, 9, 12, and 18 mo and complementary feeding practices at 9 and 18 mo. All analyses were by intent to treat. In the overall analyses, there was a small but significant effect on length gain in the intervention group (difference in means 0.32 cm, 95% CI, 0.03, 0.61). The effect was greater in the subgroup of male infants (difference in mean length gain 0.51 cm, 95% CI 0.03, 0.98). Weight gain was not affected. Energy intakes from complementary foods overall were significantly higher in the intervention group children at 9 mo (mean +/- SD: 1556 +/- 1109 vs. 1025 +/- 866 kJ; P < 0.001) and 18 mo (3807 +/- 1527 vs. 2577 +/- 1058 kJ; P < 0.001). Improving complementary feeding practices through existing services is feasible but the effect on physical growth is limited. Factors that limit physical growth in such settings must be better understood to plan more effective nutrition programs.

Dyslipidaemia when diagnosed in childhood predicts the development of clinical atherosclerotic disease in adulthood. Ever since we became aware of the abnormally high incidence of coronary artery disease amongst Indians, there always has been an ever-growing need for study of lipid values amongst Indian children and adolescents. Five hundred and eighty-six children (352 boys and 234 girls) from a public school aged between 8 and 18 years (mean age: 12.86 for boys and 12.15 for girls) were included in the study for assessment of lipid profile during the period from April, 1999 to March, 2000. Fasting venous blood was drawn from each child and total cholesterol and triglyceride levels were measured by enzymatic method, high-density lipoportein (HDL)-cholesterol was measured using specific precipitation method and lipoprotein (a) [Lp (a)] was measured by immunoturbidimetric method. After biochemical estimation was completed reference values and percentiles were calculated for each lipid component. Mean cholesterol and triglyceride values were higher amongst girls compared to boys. HDL-cholesterol values were lower amongst Indian boys compared to girls. Mean Lp (a) values were higher amongst both Indian boys and girls and more so amongst girls compared to boys. Since Lp(a) values remain unchanged through ages, these values should represent corresponding values in adult Indian males and females. It is being expected that data presented in this study should form guidelines with regard to dietary and pharmacological intervention for dyslipidaemia amongst children and adolescents.