Linear growth beyond 24 months and child neurodevelopment in low- and middle-income countries: a systematic review and meta-analysis.

AIM: To synthesize available evidence on the association between change in linear growth (height for age z score, HAZ) beyond the first two years of life with later child neurodevelopment outcomes in Low- and middle-income countries (LMICs). METHODS: We searched PubMed, Web of Science, and EMBASE for cohort studies on the association between change in HAZ after age two and neurodevelopment outcomes in middle or late childhood. Data extraction was done independently by two reviewers. RESULTS: A total of 21 studies, that included 64,562 children from 13 LMICs were identified. Each unit increase in change in HAZ above two years is associated with a + 0.01 increase (N = 8 studies, 27,393 children) in the cognitive scores at 3.5 to 12 years of age and a + 0.05-standard deviation (SD) increase (95% CI 0.02 to 0.08, N = 3 studies, 17,830 children) in the language score at 5 to 15 years of age. No significant association of change in HAZ with motor (standardized mean difference (SMD) 0.04; 95% CI: -0.10, 0.18, N = 1 study, 966 children) or socio-emotional scores (SMD 0.00; 95% CI: -0.02, 0.01, N = 4 studies, 14,616 participants) was observed. CONCLUSION: Changes in HAZ after the first two years of life appear to have a small or no association with child neurodevelopment outcomes in LMICs.

Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.

Child Neurodevelopment After Multidomain Interventions From Preconception Through Early Childhood: The WINGS Randomized Clinical Trial.

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.

Association of fetal ultrasound anthropometric parameters with neurodevelopmental outcomes at 24 months of age.

BACKGROUND: There is a paucity of studies which have examined associations between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants. We examined the association between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants through a secondary analysis of data collected in a large community based randomized controlled trial. METHODS: A total of 1465 mother-child dyads were included. Ultrasound based fetal anthropometric parameters which included the head circumference (HC), abdominal circumference (AC), femur length (FL), biparietal diameter (BPD) and transcerebellar diameter (TCD) were collected at 26-28 weeks of gestation and their association with neurodevelopment at 24 months of age was examined. RESULTS: Only the transcerebellar diameter z score was positively associated +0.54 units (95% CI: 0.15, 0.93) with motor composite score. When the neurodevelopment outcomes were analyzed as categorical, none of the fetal variables were associated with risk of moderate to severe neurodevelopment impairment. CONCLUSION: The findings suggest that transcerebellar diameter could be useful for early prediction of neurodevelopmental outcomes in childhood. CLINICAL TRIAL REGISTRATION: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

Burden, risk factors and outcomes associated with adequately treated hypothyroidism in a population-based cohort of pregnant women from North India.

Hypothyroidism is the commonest endocrine disorder of pregnancy, with known adverse feto-maternal outcomes. There is limited data on population-based prevalence, risk factors and outcomes associated with treatment of hypothyroidism in early pregnancy. We conducted analysis on data from an urban and peri-urban low to mid socioeconomic population-based cohort of pregnant women in North Delhi, India to ascertain the burden, risk factors and impact of treatment, on adverse pregnancy outcomes- low birth weight, prematurity, small for gestational age and stillbirth. This is an observational study embedded within the intervention group of the Women and Infants Integrated Interventions for Growth Study, an individually randomized factorial design trial. Thyroid stimulating hormone was tested in 2317 women in early (9-13 weeks) pregnancy, and thyroxin replacement started hypothyroid (TSH ≥2.5mIU/mL). Univariable and multivariable generalized linear model with binomial family and log link were performed to ascertain risk factors associated with hypothyroidism and association between hypothyroidism and adverse pregnancy outcomes. Of 2317 women, 29.2% (95% CI: 27.4 to 31.1) had hypothyroidism and were started on thyroxin replacement with close monitoring. Overweight or obesity was associated with increased risk (adjusted RR 1.29, 95% CI 1.10 to 1.51), while higher hemoglobin concentration was associated with decreased risk (adjusted RR 0.93, 95% CI 0.88 to 0.98 for each g/dL) for hypothyroidism. Hypothyroid women received appropriate treatment with no increase in adverse pregnancy outcomes. Almost a third of women from low to mid socio-economic population had hypothyroidism in early pregnancy, more so if anemic and overweight or obese. With early screening and adequate replacement, adverse pregnancy outcomes may be avoided. These findings highlight the need in early pregnancy for universal TSH screening and adequate treatment of hypothyroidism; as well as for attempts to reduce pre and peri-conception overweight, obesity and anemia. Clinical trial registration: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

Breastfeeding practices based on the gestational age and weight at birth in the first six months of life in a population-based cohort of infants from North India.

Background: Short and long term benefits of early Initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) in the first six months of life are well established and recommended globally. However, reliable estimates of breastfeeding practices and impact of breastfeeding counselling interventions according to gestational age and weight at birth are not available in low and middle income countries. Objective: To assess the impact of breastfeeding counselling on EIBF and EBF during the first 6 months of life according to gestational age and weight at birth. Methods: We analysed the data collected from the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. Mothers were counselled on EIBF during third trimester of pregnancy. They were supported throughout the first 6 months to continue EBF by early problem identification, frequent home visits and assistance in expressing breastmilk when direct breastfeeding was not possible. Breastfeeding practices were ascertained through 24 h recalls at infant ages 1, 3 and 5 months for both the intervention and control groups by an independent outcome ascertainment team. The World Health Organization (WHO) definitions were used for classification of infant breastfeeding practices. Generalized linear models of the Poisson family with a log-link function were used to estimate the effect of interventions on breastfeeding practices. The relative measures of effect on breastfeeding practices were estimated in term appropriate for gestational age (T-AGA), term small for gestational age (T-SGA), preterm AGA (PT-AGA), preterm SGA (PT-SGA) infants. Results: Amongst all infants irrespective of gestational age and weight at birth, EIBF was (51.7%) higher amongst the intervention group (IRR 1.38, 95% CI 1.28-1.48) compared with the control group. The proportion of exclusively breastfed infants at ages 1 month (IRR 1.37, 95% CI 1.28-1.48), 3 months (IRR 2.13, 95% CI 1.30-1.44) and 5 months (IRR 2.78, 95% CI 2.58-3.00) were higher in intervention group than control group. We identified significant interaction (p value for interaction <0.05) between intervention and infant size and gestation at birth on exclusive breastfeeding at 3 and 5 months of age. Subgroup analysis showed that the impact of the intervention was greater on exclusive breastfeeding in PT- SGA infants at 3 months (IRR 3.30, 95% CI 2.20-4.96) and 5 months of age (IRR 5.26, 95% CI 2.98-9.28). Conclusion: This is one of the first studies wherein impact of breastfeeding counselling interventions in the first 6 months of life was assessed according to infant size and gestation at birth wherein gestational age was reliably estimated. The impact of this intervention was higher in preterm and SGA babies compared to other infants. This finding is important as preterm and SGA infants have a higher burden of mortality and morbidity during early infancy. Intensive breastfeeding counselling to these vulnerable infants is likely to improve overall breastfeeding rates and reduce the adverse outcomes.Clinical Trial Registration: [http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339%26EncHid=%26userName=societyforappliedstudies], identifier [#CTRI/2017/06/008908].

Effects of kangaroo mother care on maternal and paternal health: systematic review and meta-analysis.

Objective: To investigate the effect of kangaroo mother care for low-birth-weight and preterm infants on parents' mental and physical health. Methods: The Cochrane Central Register of Controlled Trials, Cochrane Register of Studies Online, PubMed®, Web of Science, Scopus and EMBASE® databases were searched on 16 January 2023 for randomized and quasi-randomized trials on kangaroo mother care. Records identified were screened independently by two reviewers. Pooled relative risks (RRs) are reported for categorical variables, and standardized mean differences (SMDs) or mean differences are reported for continuous variables. Evidence quality was assessed using the GRADE approach. Findings: The search identified 30 studies involving 7719 preterm or low-birth-weight infants. There was high-certainty evidence that kangaroo mother care substantially reduced the risk of moderate-to-severe postpartum maternal depressive symptoms compared with no kangaroo mother care (RR: 0.76; 95% confidence interval, CI: 0.59 to 0.96). In addition, there was low-certainty evidence that kangaroo mother care reduced scores for maternal stress (SMD: -0.82; 95% CI: -1.32 to -0.32) and anxiety (SMD: -0.62; 95% CI: -1.01 to -0.23) and increased mother-infant attachment and bonding scores (SMD: 1.19; 95% CI: 0.27 to 2.10). Limited evidence indicated father-infant interactions may be improved, though no marked effect on paternal depression or stress was observed. No trial reported parental physical health outcomes. Conclusion: Kangaroo mother care for preterm and low-birth-weight infants was associated with less postpartum maternal depression, stress and anxiety and better mother-infant attachment and bonding. More research is required to evaluate effects on paternal health.

What more can be done? Prioritizing the most promising antenatal interventions to improve birth weight.

BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes.

A package of care for all pregnant women within eight scheduled antenatal care contacts is recommended by WHO. Some interventions for reducing and managing the outcomes for small vulnerable newborns (SVNs) exist within the WHO package and need to be more fully implemented, but additional effective measures are needed. We summarise evidence-based antenatal and intrapartum interventions (up to and including clamping the umbilical cord) to prevent vulnerable births or improve outcomes, informed by systematic reviews. We estimate, using the Lives Saved Tool, that eight proven preventive interventions (multiple micronutrient supplementation, balanced protein and energy supplementation, low-dose aspirin, progesterone provided vaginally, education for smoking cessation, malaria prevention, treatment of asymptomatic bacteriuria, and treatment of syphilis), if fully implemented in 81 low-income and middle-income countries, could prevent 5·202 million SVN births (sensitivity bounds 2·398-7·903) and 0·566 million stillbirths (0·208-0·754) per year. These interventions, along with two that can reduce the complications of preterm (<37 weeks' gestation) births (antenatal corticosteroids and delayed cord clamping), could avert 0·476 million neonatal deaths (0·181-0·676) per year. If further research substantiates the preventive effect of three additional interventions (supplementation with omega-3 fatty acids, calcium, and zinc) on SVN births, about 8·369 million SVN births (2·398-13·857) and 0·652 million neonatal deaths (0·181-0·917) could be avoided per year. Scaling up the eight proven interventions and two intrapartum interventions would cost about US$1·1 billion in 2030 and the potential interventions would cost an additional $3·0 billion. Implementation of antenatal care recommendations is urgent and should include all interventions that have proven effects on SVN babies, within the context of access to family planning services and addressing social determinants of health. Attaining high effective coverage with these interventions will be necessary to achieve global targets for the reduction of low birthweight births and neonatal mortality, and long-term benefits on growth and human capital.

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6-7 Years: A Follow-Up of a Randomized Controlled Trial.

BACKGROUND: Deficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. OBJECTIVES: We investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6-7 y. METHODS: This is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6-30-mo-old children. The supplement contained 1.8 µg of vitamin B12, 150 µg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016-November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). RESULTS: At baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 µmol/L (95% CI: 0.09; 2.30 µmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin-adiponectin ratio in subgroups based on their nutritional status. CONCLUSIONS: Supplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations. The original trial was registered at www. CLINICALTRIALS: gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Milk-cereal mix supplementation during infancy and impact on neurodevelopmental outcomes at 12 and 24 months of age: a randomised controlled trial in India.

Inadequate protein intake and lack of micronutrients may affect neurodevelopment in infants. This randomised controlled trial was conducted to measure the effect of two milk-cereal mixes with modest and high amounts of protein and enriched with multiple micronutrients, given between 6 and 12 months, on cognitive, language, motor and behavioural scores at 12 and 24 months of age, compared with no-supplementation. The two supplements were also compared with each other. The study was conducted in urban Delhi, India, and the infants were randomised in a 1:1:1 ratio to the three study groups. At 12 and 24 months of age, 1134 and 1214 children were available, respectively. At 12 months of age, compared with no-supplement group, an increase in the motor scores (mean difference, MD 1·52, 95 % CI: 0·28, 2·75) and a decrease in the infant temperament scores (MD - 2·76, 95 % CI: -4·23, -1·29) in the modest-protein group was observed. Those in the high-protein group had lower socio-emotional scores (MD - 1·40, 95 % CI: -2·43, -0·37) and higher scores on Infant Temperament Scale (MD 2·05, 95 % CI: 0·62, 3·48) when compared with modest-protein group. At 24 months, no significant differences in any of the neurodevelopment scores between the three study groups was found. In conclusion, supplementation with modest amount of protein and multiple micronutrients may lead to short-term small improvements in motor function and infant temperament. There appears no advantage of supplementing with high protein, rather negative effects on infant behaviour were observed.

Government-led initiative increased the effective use of Kangaroo Mother Care in a region of North India.

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.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

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.

Impact of a package of health, nutrition, psychosocial support, and WaSH interventions delivered during preconception, pregnancy, and early childhood periods on birth outcomes and on linear growth at 24 months of age: factorial, individually randomised controlled trial.

OBJECTIVE: To determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care. DESIGN: Individually randomised factorial trial. SETTING: Low and middle income neighbourhoods of Delhi, India. PARTICIPANTS: 13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D). INTERVENTIONS: Health, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods. MAIN OUTCOME MEASURES: The primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D). RESULTS: The proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction -3.80%, 98.3% confidence interval -6.99% to -0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; -1.71%, -4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; -5.59%, -10.32% to -0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; -8.32%, -12.31% to -4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; -7.98%, -14.24% to -1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564). CONCLUSIONS: An intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008908.

Early child stimulation, linear growth and neurodevelopment in low birth weight infants.

BACKGROUND: Children with low birth weight (LBW) are at risk of linear growth faltering and developmental deficits. Evidence suggests that early child stimulation and care reflected as responsive caregiving and opportunities for learning can promote development. The current analysis aimed to measure the extent to which linear growth and early child stimulation modify each other's association with neurodevelopmental outcomes among LBW infants. METHODS: This is a secondary data analyses from a randomized controlled trial on the effect of community-initiated kangaroo mother care in LBW infants on their neurodevelopment at 12 months of corrected age. Bayley Scales of Infant and Toddler Development was used to assess cognitive, motor and language scores. Stimulation at home was assessed by the Pediatric Review of Children's Environmental Support and Stimulation (PROCESS) tool. PROCESS scores were categorized into three groups: < Mean-1SD (low stimulation); Mean ± 1 SD (moderate stimulation) and > mean + 1SD (high stimulation). RESULTS: A total of 516 infants were available for neurodevelopment assessments. Interactions were observed between length for age z-score (LAZ) and PROCESS score categories. In the low stimulation group, the adjusted regression coefficients for the association between LAZ and cognitive, motor and language scores were substantially higher than in the moderate and high stimulation group. Stimulation was positively associated with neurodevelopmental outcomes in both stunted and non-stunted infants; however, the association was twice as strong in stunted than in non-stunted. CONCLUSION: Moderate to high quality stimulation may alleviate the risk of sub-optimal development in LBW infants with linear growth deficits. CLINICAL TRIAL REGISTRATION: The primary trial whose data are analysed is registered at clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02631343 ).

Effect of community-initiated kangaroo mother care on breastfeeding performance in low birthweight infants: A randomized clinical trial.

This individually randomized trial was conducted to estimate the effect of promoting community-initiated kangaroo mother care (ciKMC) in low birthweight (LBW) infants on infant breastfeeding performance. It was designed as a substudy within a larger primary trial on ciKMC and infant survival. Five hundred fifty stable LBW mother-infant dyads (1500-2250 g) who provided consent, were consecutively enroled for breastfeeding performance assessment. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding (EBF) through home visits during the neonatal period. The primary outcome was effective breastfeeding performance indicated by an infant breastfeeding assessment tool score of ≥10 after the end of the neonatal period. As secondary outcomes, we reported maternal satisfaction related to infant breastfeeding, and EBF after the end of the neonatal period. We completed outcome assessments in 96% of participants. In the ciKMC arm, 92% of the infants showed effective breastfeeding performance against 81% in the control arm [adjusted prevalence ratio (aPR): 1.24, 95% confidence interval (CI): 1.16-1.32]. In the ciKMC arm, 65% of the mothers reported to be very satisfied with their infants' breastfeeding against 51% in the control arm (aPR: 1.22, 95% CI: 1.05-1.41). The proportion of infants practicing EBF was 89% in the ciKMC arm against 45% in the control arm (aPR: 1.62, 95% CI: 1.45-1.81). Our study findings suggest that promotion of ciKMC can improve effective breastfeeding, EBF and maternal satisfaction related to breastfeeding in LBW infants.