Health equity impact of community-initiated kangaroo mother care: a randomized controlled trial.

BACKGROUND: Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival. METHODS: In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant's sex, and religion. RESULTS: Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu. CONCLUSIONS: We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02653534 . Registered January 12, 2016-Retrospectively registered.

Effect of community-initiated kangaroo mother care on survival of infants with low birthweight: a randomised controlled trial.

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.

Utilisation, equity and determinants of full antenatal care in India: analysis from the National Family Health Survey 4.

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.

S.Typhi derived OmpC peptide conjugated with Vi-polysaccharide evokes better immune response than free Vi-polysaccharide in mice.

Salmonella typhi is a causative organism for typhoid fever. Free Vi capsular polysaccharide (Vi) is licensed for use as vaccine for typhoid fever in individuals 2 years of age and older, which has limited memory response. There is dire need of protein or peptide as conjugate partner with Vi polysaccharide to improve shortcomings of Vi vaccine. Prediction of immunogenic peptide was deduced by program T sites. Carbodiimide mediated conjugation of Vi polysaccharide with OmpCp was performed utilizing ADH as linker. Immune response of Vi-conjugates along with control group was tested in mice. Ig and IgG antibodies against Vi polysaccharide was measured by ELISA. Two immunodominant regions (loop number 3a and 7) with high content of T-cell epitopes from OmpC was selected and synthesized. Vi poly/OmpCp ratios in Vi-conjugates were ~0.43-0.65. Vi polysaccharide alone elicited very low levels of Vi antibody without any booster effect. Vi-conjugate evoked 20-fold higher immune response compared to free Vi. Further, adequate levels of IgG antibodies were induced only by the Vi-conjugate suggesting that T-helper cells had been induced. Our data suggest that selected short peptide (OmpCp)as a carrier with Vi polysaccharide is assumed to be a promising molecule for candidate vaccine for typhoid fever.

Cognitive and motor outcomes in children born low birth weight: a systematic review and meta-analysis of studies from South Asia.

BACKGROUND: South Asia contributes substantially to global low birth weight population (i.e. those with birth weight < 2500 g). Synthesized evidence is lacking on magnitude of cognitive and motor deficits in low birth weight (LBW) children compared to those with normal birth weight (NBW) (i.e. birth weight ≥ 2500 g). The meta-analysis aimed to generate this essential evidence. METHODS: Literature search was performed using PubMed and Google Scholar. Original research articles from south Asia that compared cognitive and/or motor scores among LBW and NBW individuals were included. Weighted mean differences (WMD) and pooled relative risks (RR) were calculated. All analyses were done using STATA 14 software. RESULTS: Nineteen articles (n = 5999) were included in the analysis. Children < 10 years of age born LBW had lower cognitive (WMD -4.56; 95% CI: -6.38, - 2.74) and motor scores (WMD -4.16; 95% CI: -5.42, - 2.89) compared to children with NBW. Within LBW children, those with birth weight < 2000 g had much lower cognitive (WMD -7.23, 95% CI; - 9.20, - 5.26) and motor scores (WMD -6.45, 95% CI; - 9.64, - 3.27). CONCLUSIONS: In south Asia, children born LBW, especially with < 2000 g birth weight, have substantial cognitive and motor impairment compared to children with NBW. Early child development interventions should lay emphasis to children born LBW.

Severe wasting among Indian infants <6 months: Findings from the National Family Health Survey 4.

Burden and risk factors for wasting in the first 6 months of life among Indian children are not well documented. We used data from India's National Family Health Survey 4 to estimate the prevalence of severe wasting (weight for length < -3 SD) among 18,898 infants under 6 months of age. We also examined the association of severe wasting with household, maternal, and child-related factors using multivariable logistic regression analysis. Prevalence of severe wasting among infants less than 6 months of age was 14.8%, ranging from 3.5 to 21% across states. Low birth weight (<2,500 g; adjusted odds ratio [AOR] 1.40, 95% CI [1.19, 1.65]), nonutilization of supplementary nutrition by mother during lactation (AOR 1.23, 95% CI [1.05, 1.43]), and anthropometric assessment during summer (AOR 1.37, 95% CI [1.13, 1.65]) and monsoon months (AOR 1.53, 95% CI [1.20, 1.95]) were associated with higher odds of severe wasting. Infants aged 2 to 3 months (AOR 0.78, 95% CI [0.66, 0.93]) and 4 to 5 months (AOR 0.65, 95% CI [0.55, 0.73]) had lower odds of severe wasting as compared with the 0- to 1-month category. This analysis reveals a high burden of severe wasting in infants less than 6 months in India. Preventive interventions must be targeted at reducing low birth weight due to fatal growth restriction and prematurity. Appropriate care practices at facilities and postdischarge with extra attention to those born small and sick can prevent further deterioration in nutritional status.

Operationalising integrated community case management of childhood illnesses by community health workers in rural Haryana.

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.

Low-birthweight infants born to short-stature mothers are at additional risk of stunting and poor growth velocity: Evidence from secondary data analyses.

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.

Vitamin-D status and neurodevelopment and growth in young north Indian children: a secondary data analysis.

BACKGROUND: Vitamin-D deficiency has been linked with impaired development in animal studies; however, the evidence from human studies is scanty. Evidence as to whether vitamin-D deficiency during early childhood affects growth is also limited and conflicting. We examined the extent to which vitamin-D deficiency (<10 ng/ml) is associated with neurodevelopment and physical growth in young children. METHODS: We used data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in children aged 6 to 30 months conducted in Delhi, India. We measured vitamin-D status and  neurodevelopment by the Ages and Stages Questionnaire-3 (ASQ-3) at 12 to 36 months of age. Multiple logistic and linear regressions were used to examine the association between vitamin-D deficiency at baseline and neurodevelopment and growth 6 months follow-up. RESULTS: 25-hydroxy-vitamin-D (25OHD) concentration was measured at baseline for 960 (96%) children. Of these, 331 (34.5%) children were vitamin-D deficient. The total and subscale (except for the Personal social scale) ASQ-3 scores, were not different between the vitamin-D deficient and non-deficient children. Vitamin-D deficiency was also not associated with physical growth at baseline and at follow -up. CONCLUSION: Our data do not support the hypothesis that vitamin-D deficiency is associated with poor growth and neurodevelopment. TRIAL REGISTRATION: NCT00717730 and CTRI/2010/091/001090 . Date of registration: 08 October, 2010.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. METHODS: We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). FINDINGS: 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. INTERPRETATION: Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. FUNDING: Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.

Immune response of S. Typhi-derived Vi polysaccharide and outer membrane protein a conjugate in mice.

Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more effective vaccine for typhoid fever. Here, we cloned and expressed S. Typhi outer membrane protein A (OmpA). The conjugation of Vi-polysaccharide with OmpA was carried out by the carbodiimide (EDAC) method employing ADH as a linker. Total Ig and IgG generated against OmpA, and Vi polysaccharide was quantified by ELISA. Vi polysaccharide alone induced very low levels of Vi polysaccharide antibody. Vi-OmpA conjugate (Vi-conjugate) elicited a robust immune response compared to Vi polysaccharide alone and showed booster response. Further, IgG was only evoked by Vi-OmpA conjugate, not with Vi polysaccharide alone. OmpA antibody induction in both the Vi-OmpA conjugate and OmpA were similar level. Taken together, we show that OmpA as a carrier protein conjugated to Vi polysaccharide is immunogenic. We predict OmpA antibodies will contribute protection along with antibodies generated by Vi-polysaccharide. Past and current literature supports that OmpA is highly conserved protein not only among Salmonellae but entire Enterobacteriacea family with 96-100% identity.

Effect of kangaroo mother care initiated in community settings on financial risk protection of low-income households: a randomised controlled trial in Haryana, India.

INTRODUCTION: Many families in low-income and middle-income countries have high out-of-pocket expenditures (OOPE) for healthcare, and some face impoverishment. We aimed to assess the effect of Kangaroo Mother Care initiated in community setting (ciKMC) on financial risk protection estimated by healthcare OOPE, catastrophic healthcare expenditure (CHE) and impoverishment due to healthcare seeking for low birthweight infants, using a randomised controlled trial design. METHODS: We included 4475 low birthweight infants randomised to a ciKMC (2491 infants) and a control (1984 infants) arm, in a large trial conducted between 2017 and 2018 in Haryana, India. We used generalised linear models of the Gaussian family with an identity link to estimate the mean difference in healthcare OOPE, and Cox regression to estimate the HRs for CHE and impoverishment, between the trial arms. RESULTS: Overall, in the 8-week observation period, the mean healthcare OOPE per infant was lower (US$20.0) in the ciKMC arm compared with the control arm (US$25.6) that is, difference of -US$5.5, 95% CI -US$11.4 to US$0.3, p=0.06). Among infants who sought care it was US$8.5 (95% CI -US$17.0 to -US$0.03, p=0.03) lower in the ciKMC arm compared with the control arm. The HR for impoverishment due to healthcare seeking was 0.56 (95% CI 0.36 to 0.89, p=0.01) and it was 0.91 (95% CI 0.74 to 1.12, p=0.37) for CHE. CONCLUSION: ciKMC can substantially reduce the cost of care seeking and the risk of impoverishment for households. Our findings show that supporting mothers to provide KMC to low birthweight infants at home, in addition to reducing early infant mortality, may provide financial risk protection. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010114.

Growth faltering in early infancy: highlights from a two-day scientific consultation.

Faltering of growth in early life has been recognized as a public health challenge among Indian babies. A two-day consultation on growth faltering in early infancy was organized to examine the data and evidence on identification and management of early growth failure and to identify knowledge gaps and future areas of research. The consultation was supported by the Biotechnology Industry Research Assistance Council (BIRAC), the Indian Academy of Pediatrics (Nutrition Chapter), Vardhman Mahavir Medical College and Safdarjung Hospital, and the Society for Applied Studies. It brought together researchers, clinicians, policy makers and program managers.

Management of possible serious bacterial infection in young infants closer to home when referral is not feasible: Lessons from implementation research in Himachal Pradesh, India.

BACKGROUND: Government of India and the World Health Organization have guidelines for outpatient management of young infants 0-59 days with signs of Possible Serious Bacterial Infection (PSBI), when referral is not feasible. Implementation research was conducted to identify facilitators and barriers to operationalizing these guidelines. METHODS: Himachal Pradesh government implemented the guidelines in program settings supported by Centre for Health Research and Development, Society for Applied Studies. The strategy included community sensitization, skill enhancement of Accredited Social Health Activists (ASHA), Auxiliary Nurse Midwives (ANMs) and Medical Officers (MOs) to identify PSBI and treat when referral was not feasible. The research team collected information on facilitators and barriers. A technical support unit provided training and oversight. FINDINGS: Among 1997 live births from June 2017 to January 2019, we identified 160 cases of PSBI in young infants resulting in a coverage of 80%, assuming an incidence of 10%. Of these,29(18.1%) had signs of critical illness (CI), 92 (57.5%) had clinical severe infection (CSI), 5 (3.1%)had severe pneumonia (only fast breathing in young infants 0-6 days), while 34 (21%) had pneumonia (only fast breathing in young infants 7-59 days). Hospital referral was accepted by 48/160 (30%), whereas 112/160 (70%) were treated with the simplified treatment regimens at primary level facilities. Of the 29 infants with CI, 18 (62%) accepted referral; 26 (90%) recovered while 3 (10%) who had accepted referral, died. Of the 92 infants who had CSI, 86 (93%) recovered, 65 (71%) received simplified treatment and one infant who had accepted referral, died. All the five infants who had severe pneumonia, recovered; 3 (60%) had received simplified treatment. Of the 34 pneumonia cases, 33 received simplified treatment of which 5 (15%) failed treatment; two out of these 5 died. Overall, 6/160 infants died (case-fatality-rate 3.4%); 2 in the simplified treatment (case-fatality-rate 1.8%) and 4 in the hospital group (case-fatality-rate 8.3%). Delayed identification and care-seeking by families and health system weaknesses like manpower gaps and interrupted supplies were challenges in implementation. CONCLUSIONS: Implementation of the guidelines in program settings is possible and acceptable. Scaling up would require creating community awareness, early identification and appropriate care-seeking, strengthening ASHA home-visitation program, building skills and confidence of MOs and ANMs, uninterrupted supplies and a dependable referral system.

Burden of preconception morbidity in women of reproductive age from an urban setting in North India.

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.

Impact of an integrated nutrition, health, water sanitation and hygiene, psychosocial care and support intervention package delivered during the pre- and peri-conception period and/or during pregnancy and early childhood on linear growth of infants in the first two years of life, birth outcomes and nutritional status of mothers: study protocol of a factorial, individually randomized controlled trial in India.

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.

Vitamin D deficiency and mild to moderate anemia in young North Indian children: A secondary data analysis.

OBJECTIVES: The aim of this study was to examine the association between vitamin D deficiency and anemia status among young children in the resource-poor setting of northern urban India. METHODS: We used data from a randomized controlled trial of daily supplementation with folic acid, vitamin B12, or both for 6 mo in children 6 to 30 mo of age conducted in Delhi, India. We measured serum vitamin D status, hemoglobin, plasma vitamin B12, folate, soluble transferrin receptor, and homocysteine levels at baseline. Children with severe anemia (hemoglobin [Hgb] <7 g/dL) were excluded from enrollment. Multivariable logistic and multinomial logistic regressions were used to examine the association between vitamin D and anemia status at baseline. RESULTS: 25-Hydroxyvitamin-D (25 OHD) concentration was measured for 960 (96%) children. Of the children, 331 (34.5%) were vitamin-D deficient (<10 ng/mL). Approximately 70% of the enrolled children were anemic, with ∼46% having moderate (Hgb 7-9.9 g/dL) and 24% mild (Hgb 10-10.9 g/dL) anemia. There was no association between vitamin D and anemia status after adjusting for confounders; however, the risk for moderate anemia was significantly higher among vitamin D-deficient children than those who were vitamin-D replete (relative risk, 1.58; 95% confidence interval, 1.09-2.31). CONCLUSIONS: Vitamin D deficiency was associated with moderate anemia among young children and the effect was independent of iron deficiency. The causal association of vitamin D deficiency with anemia risk remains debatable. The role of vitamin D in risk for anemia needs to be examined in further studies.

Factors associated with the decline in under-five diarrhea mortality in India: a LiST analysis.

BACKGROUND: India has achieved 86% reduction in the number of under-five diarrheal deaths from 1980 to 2015. Nonetheless diarrhea is still among the leading causes of under-five deaths. The aim of this analysis was to study the contribution of factors that led to decline in diarrheal deaths in the country and the effect of scaling up of intervention packages to address the remaining diarrheal deaths. METHODS: We assessed the attribution of different factors and intervention packages such as direct diarrhea case management interventions, nutritional factors and WASH interventions which contributed to diarrhea specific under-five mortality reduction (DSMR) during 1980 to 2015 using the Lives Saved Tool (LiST). The potential impact of scaling up different packages of interventions to achieve universal coverage levels by year 2030 on reducing the number of remaining diarrheal deaths were estimated. RESULTS: The major factors associated with DSMR reduction in under-fives during 1980 to 2015, were increase in ORS use, reduction in stunting prevalence, improved sanitation, changes in age appropriate breastfeeding practices, increase in the vitamin-A supplementation and persistent diarrhea treatment. ORS use and reduction in stunting were the two key interventions, each accounting for around 32% of the lives saved during this period. Scaling up the direct diarrhea case management interventions from the current coverage levels in 2015 to achieve universal coverage levels by 2030 can save around 82 000 additional lives. If the universal targets for nutritional factors and WASH interventions can be achieved, an additional 23 675 lives can potentially be saved. CONCLUSIONS: While it is crucial to improve the coverage and equity in ORS use, an integrated approach to promote nutrition, WASH and direct diarrhea interventions is likely to yield the highest impact on reducing the remaining diarrheal deaths in under-five children.

A Phase 4, multicentre, randomized, single-blind clinical trial to evaluate the immunogenicity of the live, attenuated, oral rotavirus vaccine (116E), ROTAVAC®, administered simultaneously with or without the buffering agent in healthy infants in India.

BACKGROUND: The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration. Because ROTAVAC®, a WHO prequalified vaccine, was derived from the 116E neonatal strain, we evaluated the immunogenicity and safety of ROTAVAC® without buffer and ROTAVAC® with buffer in a phase 4, multicentre, single-blind, randomized clinical trial in healthy infants in India. METHODS: 900 infants, approximately 6, 10 and 14 weeks of age, were assigned to 3 groups to receive ROTAVAC® (0.5 mL dose) orally: (i) 2.5 mL of citrate-bicarbonate buffer 5 minutes prior to administration of ROTAVAC® (Group I), (ii) ROTAVAC®, alone, without any buffer (Group II), or (iii) ROTAVAC®, mixed with buffer immediately before administration (Group III). Non-inferiority was compared among the groups for differences in serological responses (detected by serum anti-rotavirus IgA) and safety. RESULTS: Geometric mean titers post vaccination at day 84 (28 days after dose 3) were 19.6 (95%CI: 17.0, 22.7), 20.7 (95%CI: 17.9, 24) and 19.2 (95%CI: 16.8, 22.1) for groups I, II and III respectively. Further, seroconversion rates and distribution of adverse events were similar among groups. CONCLUSIONS: Administration of ROTAVAC® at a 0.5 mL dose volume without buffering agent was shown to be well tolerated and immunogenic. Given the homologous nature of the strain, it is plausible that ROTAVAC® replicates well and confers immunity even without buffer administration.