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

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. Keywords: Child health; Early child stimulation; Growth failure; Intrauterine growth restriction; Responsive stimulation; Small for gestational age; Small vulnerable newborns; preterm. © 2024. The Author(s).The study was funded by Centre for Intervention Science in Maternal and Child Health at the University of Bergen (Bergen, Norway). The funding agency did not play any role in the design of the study and is neither involved in nor has any influence over the collection of analysis or interpretation of data.publishedVersio

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

BackgroundShort 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.ObjectiveTo 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.MethodsWe 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.ResultsAmongst 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).ConclusionThis 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]

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

Preterm birth and periodontal disease: A medical perspective

Births occurring before 37 weeks resulting in prematurity poses serious hazards to the baby from delayed growth, neurodevelopmental anomalies to death and unfortunately India is in the top four countries with maximum preterm births and leads globally in deaths by prematurity. Infection is a very important component of the etiopathogenesis of preterm labor and periodontal disease is a rather unexplored aspect of infection very often overlooked by the general gynecologist and the dental practitioner equally. Periodontal disease is a potential foci of infectious pathogens which may disseminate hematogenously and effect the fetus. In this article, an effort has been made to find an evidence-based link between periodontal disease and preterm labor to drive home the conclusion that an early screening and diagnosis in pregnancy followed up with effective treatment of periodontal disease may significantly reduce the burden of preterm births

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)

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

BackgroundThere 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.MethodsA 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.ResultsOverall, 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.ConclusionsOur 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

Child neurodevelopment after multidomain interventions from preconception through early childhood

ImportanceMultidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions.ObjectiveTo 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 ParticipantsIn 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, 2020, through February 25, 2022.InterventionsHealth, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods.Main Outcomes and MeasuresCognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool.ResultsThe 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 RelevanceMultidomain 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