Equity in Economic Evaluations of Early Childhood Development Interventions in Low-and Middle-Income Countries: Scoping Review

Objectives This study aimed to examine how equity is integrated into economic evaluations of early childhood development interventions in low-and middle-income countries (LMICs), and to narratively synthesize the study characteristics and findings. Methods We conducted a scoping review by searching three electronic databases with terms including equity, early childhood development intervention, economic evaluation, and LMICs. Interventions that aimed to improve child cognitive, physical, language, motor, or social and emotional development through health, nutrition, security and safety, responsive caregiving, and early learning interventions between conception and age 8 years were considered. Studies published in English peer-reviewed journals in the year 2000 and later were included. Results The review included 24 cost-effectiveness studies out of 1460 identified articles based on eligibility criteria. The included studies addressed health, nutrition, social protection, and water, sanitation and hygiene interventions for child development. The common type of intervention was immunization. Mostly, equity was measured using household wealth or geographic areas, and the study findings were presented through subgroup analyses. The study settings were LMICs, but most studies were conducted by research teams from high-income countries. Overall, 63% of included studies reported that early childhood development interventions improved equity with greater intervention benefits observed in disadvantaged groups. Conclusions Consideration of equity in evaluations of early childhood interventions provides a more complete picture of cost-effectiveness, and can improve equity. Greater focus on promoting equity consideration, multi-sectoral interventions, and researchers in LMICs would support evidence-based interventions and policies to achieve equity in child development. Supplementary Information The online version contains supplementary material available at 10.1007/s10995-023-03650-3.


Introduction
The United Nations Convention on the Rights of the Child highlights that children have the right to good quality health care, clean water, nutritious food, a clean environment and an education, to meet their physical and mental needs, and develop their personality and talents to the full (United Nations, 1990). Early childhood development refers to children's cognitive, physical, language, motor, and social and emotional development, between conception and age 8 years (World Health Organization et al., 2018). Scientific evidence shows that optimal early childhood development is essential to develop intellectual skills, creativity, and wellbeing across the life course, with long-term consequences for the care of the next generation and for the wellbeing of societies (Black et al., 2017;Richter et al., 2017;Walker et al., 2011). In particular, conception to age 3 years is known as the time when adverse exposures exert the greatest harm, and effective interventions return the greatest benefit (Black et al., 2017;Richter et al., 2017). However, according to the data from 94 low-and middle-income countries (LMICs) between 2010 and 2018, 37% of children under 5 years of age were exposed to risk of poor development due to malnutrition or extreme poverty, and 39% of children (36-59 months) ever attended early care and education programs (Lu et al., 2020). Substantial gaps in early childhood development indicators across country income groups, residential areas and household wealth categories were reported. Outcomes for children in urban areas or in the richest household wealth quintiles were better than those in rural areas or the lowest wealth quintile, which demonstrates disparities in child development (Lu et al., 2020).
Health equity can be defined as the absence of systematic disparities in health between more and less advantaged social groups, and equity can also mean social justice in health with a moral dimension as a broad term (Braveman, 2014;Braveman & Gruskin, 2003;Whitehead, 1992). Health equity therefore indicates the highest possible standard of health for all people with more attention paid to the needs of disadvantaged groups (Braveman, 2014). Cookson and colleagues described two main ways of using costeffectiveness analysis to address health equity, equity impact analysis, and equity trade-off analysis (Cookson et al., 2017). However, unlike advances in diverse and complex methods to assess cost-effectiveness in health economics, relatively less effort has been made to fully incorporate equity considerations into economic evaluations. A small number of reviews have been conducted in the last decade to examine the state of integration of equity in health economic evaluations (Avanceña & Prosser, 2021;Boujaoude et al., 2018;Dukhanin et al., 2018;Johri & Norheim, 2012;Lal et al., 2018;Yang et al., 2021). The reviews concluded that feasible methods to consider equity in economic evaluations exist, yet they have not been widely used, and some challenges for application were still found including equity measurement and valuation. In addition to assessing cost-effectiveness of early childhood development interventions, equity integration will provide a clearer understanding of the broader implications of interventions. Despite the potential benefits, how equity is considered in economic evaluations of early childhood development interventions, and how specific interventions affect equity are not well understood. Therefore, this scoping review aimed to examine what methods are used for equity consideration in economic evaluations of early childhood development interventions in LMICs, and to narratively synthesize the study characteristics and findings.

Search Strategy with Eligibility Criteria
We used a combination of subject headings including MeSH and free text terms to cover the following concepts: (1) equity, (2) early childhood development intervention, (3) economic evaluation, and (4) LMICs. We developed the search strategies in consultation with an information analyst and searched MEDLINE (Ovid), EMBASE (Ovid) and EconLit on 13 July 2021. In addition, hand searching and citation checking were undertaken to supplement database searching. The search strategy for MEDLINE can be found in Supplementary Table 1. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines (Tricco et al., 2018). The protocol was not prospectively registered in PROSPERO as they do not accept scoping review protocols.
The key concepts with eligibility criteria are described in Table 1. The WHO has defined health equity as the absence of unfair, avoidable, and remediable differences in health status among groups of people (World Health Organization, 2021). Braveman and colleagues have stated that equity means social justice or fairness, and health equity is the absence of systematic disparities in health between more and less advantaged social groups (Braveman & Gruskin, 2003).
Without limiting equity to a certain concept, since equity is a broad term, we aimed to examine how existing studies conceptualized and incorporated equity into their economic evaluations. We included studies that addressed any equity aspects such as the distribution of health outcomes by income or geographical regions. Multi-country studies were not included if they only provided country-level data without equity consideration within country. We identified early childhood development interventions based on the 2016 Lancet Early Childhood Development Series (Black et al., 2017;Britto et al., 2017). We included interventions that aimed to improve domains of child development including language, cognition, motor, social and emotional development, and psychosocial wellbeing. Accordingly, we included health, nutrition, security and safety, responsive caregiving, and early learning interventions which targeted children from conception to the age of 8 years. For study type, economic evaluations such as cost-effectiveness analysis that compared both the costs and the outcomes of at least one intervention and an alternative were included. In addition, extended cost-effectiveness analysis which examined financial risk protection benefits along with health outcomes of interventions , and distributional costeffectiveness analysis which provided the information about equity impacts and the trade-offs regarding who gained the benefits and who bore the burdens (Cookson et al., 2021) were included. We excluded review papers, commentaries and conference proceedings. LMICs were identified based on the World Bank classification as per the year of publication. For 2021 fiscal year, low-income economies were defined as those with Gross National Income (GNI) per capita US$1035 or less, lower middle-income economies were those with GNI per capita between US$1036 and US$4045, and upper middle-income economies were those with GNI per capita between US$4046 and US$12,535 (World Bank, 2020). Lastly, we included original scientific literature in English peer-reviewed journals published in the year 2000 and later. The restriction on publication period was determined because research, programs, and policies on early childhood development have advanced mostly since 2000 (Black et al., 2017) and recent systematic reviews on equity in economic evaluations only identified publications after 2010 (Avanceña & Prosser, 2021;Lal et al., 2018).

Study Selection, Data Extraction, and Synthesis
One reviewer (YB) screened titles and abstracts, and assessed full text based on the eligibility criteria. Other reviewers (ZA, JF, TT, AO) addressed any uncertainties.
We used a standardized form to extract study characteristics, equity measures, and results of included studies. The data extraction form was finalized after pilot testing. The following data were extracted: author, year, country, description of intervention and comparator, study design, economic evaluation type, study perspective, equity measures and methods of analysis, and results. We present findings through a narrative synthesis due to the substantial heterogeneity in study designs, settings, interventions, characteristics of participants, and outcome measures. We used Excel, Covidence and Endnote software for data management. Since scoping reviews do not aim to produce a critically appraised and synthesized answer to a particular question, and rather aim to provide an overview or map of the evidence (Munn et al., 2018), we did not assess quality of included studies' methods or reporting practices.

Ethical Approval
Ethical approval was not required for this review as it is based on published studies and does not draw on data contributed by patients or members of the community.

Characteristics of Included Studies
The search identified 1460 articles after removing duplicates. After screening titles and abstracts based on eligibility criteria, 134 studies remained for full text screening, and 24 studies were finally included in the review (Fig. 1). The general characteristics of included studies are summarized in Table 2. The review identified 20 single-country studies from 11 different countries, including Ethiopia (n = 5), India (n = 4), China (n = 2), Pakistan (n = 2), Argentina (n = 1), Brazil (n = 1), Burkina Faso (n = 1), Lao People's Democratic Republic (n = 1), Malaysia (n = 1), Nigeria (n = 1) and South Africa (n = 1). In addition, the review included four studies that used multi-country data [25 countries (n = 1), 15 countries (n = 1), four countries (n = 1), and two countries (n = 1)]. The review did not identify any studies from the Middle East, North Africa or Central Asia. Among the 24 studies, 23 studies were model-based cost-effectiveness analyses, and one study was a cost-effectiveness analysis alongside an observational study. The majority of studies solely focused on maternal, newborn, or child health (n = 18, 75%). Other studies looked at infant and child nutrition (n = 2), health and nutrition (n = 1), nutrition and social protection (n = 2), and water and sanitation (n = 1). The most common outcomes were disability-adjusted life years (DALY) averted (n = 12), followed by deaths averted or lives saved (n = 7). Some studies measured outcomes as household expenditure or financial risk protection gained (n = 6) or other health outcomes, such as stunting averted or diarrhea averted (n = 6). No study measured any domain of child development including child language, cognitive, motor, social or emotional development. Despite this review only including studies from LMICs, the majority of studies were conducted by first authors based in high-income countries (HICs) (75%) mostly from the United States. More than half of included studies were conducted by a group of authors without anyone affiliated with institutions in the study setting (54%).

Equity Incorporation
The characteristics of equity measures and description of included studies are presented in Fig. 2 and Table 3. Most studies used wealth groups (n = 16, 67%) as equity indicators, followed by geographic areas (n = 11, 46%). The wealth groups, quintiles (n = 13) or deciles (n = 2), were mostly based on the Demographic and Health Surveys Wealth Index rank derived from household's assets, materials used for housing construction and types of water access and sanitation facilities (Rutstein & Johnson, 2004). One study used the World Bank international poverty line of US$5.50 per day. Regarding equity measures, the majority of studies used one indicator (n = 15), while some studies used more than one indicator mostly using geographic areas and wealth groups together (n = 9). Subgroup analysis was the most common method used to incorporate equity into economic evaluations (n = 14, 59%), and seven studies used extended cost-effectiveness analyses.

Summary of Findings
A summary of included studies is presented in Table 3. Among eight out of 10 studies, rotavirus vaccinations were found to be more beneficial to the disadvantaged groups   Verguet et al., 2013). An extended cost-effectiveness analysis from Ethiopia reported mixed findings in terms of equity and cost-effectiveness as they varied across different measles vaccination strategies (Driessen et al., 2015). Enterotoxigenic Escherichia coli and Shigella vaccination were found to be most cost-effective when the most vulnerable and impoverished populations were vaccinated in four countries in sub-Saharan Africa (Anderson et al., 2019). Luz et al., found that maternal acellular pertussis immunization led to higher costs, but also saved infant lives and averted DALYs in Brazilian states (Luz et al., 2021). An extended cost-effectiveness analysis from Ethiopia found that both pneumococcal vaccine and pneumonia treatment would save more lives among the poorest groups, but averted more private expenditure among wealthier people . Another study looking at pneumonia treatment concluded that prioritizing regions with high mortality rates for children under the age of 5 is effective in reducing geographical inequalities in Ethiopia (Olsen et al., 2021). The equityrelated conclusions were not clear in two studies addressing skilled care initiative from Burkina Faso (Hounton & Newlands, 2012) and newborn treatment in India (Miljeteig et al., 2010) as findings varied by study outcomes and other covariates. A study from China concluded that hearing screenings for neonates were cost-effective only in more advantaged provinces but not in less advantaged provinces (Huang et al., 2012). A multi-country study reported that an equity-focused approach to child survival, health, and nutrition could save more lives, avert stunting, and reduce expenditure by families in the most deprived populations, compared to the least deprived populations (Carrera et al., 2012). A study of donor human breastmilk from South Africa reported that prioritizing infants in the lowest birthweight groups would save the most lives, whereas prioritizing infants in the highest birthweight groups would result in the highest cost savings . In China, the cost per stunting case averted through a nutritional package varied across provinces and wealth groups, but the authors concluded that the cost would be lower for children living under the poverty line in most provinces . The price subsidies on fortified packaged infant cereals which targeted poorer households were cost-effective in India, or even cost-saving for the poorest households in Pakistan (Plessow et al., 2016;Wieser et al., 2018). A study from India examining scaling up access to piped water and improved sanitation found that the poorest group gained greater child health and financial benefits (Nandi et al., 2017).

Discussion
This scoping review examined how equity is integrated into the economic evaluations of early childhood development interventions in LMICs, and synthesized the study characteristics and findings. The identified 24 articles covered health, nutrition, social protection, and water, sanitation and hygiene interventions from 37 LMICs, and examined their cost-effectiveness and equity. The equity issues were mostly measured by household wealth and geographic areas, and equity findings were presented by subgroup analyses. Overall, early childhood development was mostly addressed through childhood immunization alone rather than multisectoral interventions from LMICs in the regions of Asia and Africa. Most studies were conducted by research teams from HICs. More than half of studies reported that the interventions improved equity as disadvantaged groups gained more benefits than less disadvantaged groups. Wealth groups were the most common equity indicators followed by geographic areas in included studies in this review. Previous review papers also reported similar findings that socioeconomic status was the most common equity criterion in health economic evaluations (Avanceña & Prosser, 2021;Yang et al., 2021). Yang and colleagues found that socioeconomic status was categorized mostly based on wealth quintiles, and place of residence were the next common equity criterion (Yang et al., 2021). In another review, race/ethnicity and geography were also identified as common equity criteria (Avanceña & Prosser, 2021). Wealth is one of the most common social determinants of focus by policy makers, thus that could be the reason why several studies chose to use wealth groups to look at equity issues. One study adopted a deprivation index considering geographical, economic, and sociocultural factors (Carrera et al., 2012). Measuring equity based on multiple factors may provide a broader picture of distribution of health benefits and their cost-effectiveness; however, the feasibility of data collection should also be considered. Factors that imply inequity could be also context-specific, considering differences in settings and challenges.
A number of methods were applied to present equity findings. Subgroup analysis was the most common method followed by extended cost-effectiveness analysis. Presenting cost-effectiveness results by subgroups has previously been found to be the most common method, described as the straightforward way to present the different impacts of health interventions across populations in one review (Yang et al., 2021). The extended cost-effectiveness analysis or distributional cost-effectiveness analysis approach was used less commonly, and the previous review also indicated that the knowledge and application of these methods were not yet widespread in LMICs (Yang et al., 2021). Even in HICs, most research focus on effectiveness of health policies and programs without much consideration of equity. The advanced methods can provide additional information on financial risk protection benefits and tradeoffs between improving total health and reducing inequality from interventions. Addressing equity requires careful research planning and implementation, which need to be context-specific based on health systems.

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Effective early childhood development interventions require collective work across sectors to ensure that every child reaches their full potential in physical, cognitive, and psychosocial development, yet this review only identified a few studies with multi-sectoral interventions. Additionally, no study in our review measured any domain of child development including language, cognitive, motor, social or emotional development as outcomes. Overall, we discovered that current research trends heavily focused on childhood immunization interventions in Asia and Africa regions. A large proportion of immunization studies reflect global efforts to reduce preventable deaths and increase child survival over the past few decades. Beyond survival, the global agenda is now also focused on enabling children to thrive. The WHO's Nurturing Care Framework highlights that children need nurturing care which is the conditions that promote health, nutrition, security, safety, responsive caregiving and early learning to develop to their full potential (World Health Organization et al., 2018). A multi-sectoral framework to promote child development has been also proposed, highlighting the need for interventions through services and programs of several sectors in the context of a supportive environment of policies, coordination, and financing (Richter et al., 2017). Furthermore, combining key interventions as packages of care for child development has been suggested including complementary feeding education and provision, micronutrient supplementation, and integrated responsive caregiving and early learning interventions (Vaivada et al., 2022).
Research in early childhood development has advanced since 2000, and over 4000 publications were identified between 2000 and 2014 (Black et al., 2017). However, our review identified only 24 publications considering equity in economic evaluations of early childhood development in LMICs since 2000, which highlights the need for more investment in this field. Overall, 63% of included studies reported that early childhood development interventions improved equity, with more benefits to disadvantaged groups. Focusing solely on cost-effectiveness of interventions may not provide a full picture of interventions' impacts, thus considering equity would be more desirable for informed decision-making. Equity consideration requires more emphasis on the most disadvantaged children to ensure their full development, and to achieve social justice and realize the United Nations Sustainable Development Goals globally (United Nations, 2015).
Even though included studies focused on early childhood development in LMICs, most studies were conducted by researchers based in HICs. Researchers from LMICs have greater knowledge and lived experience about contexts and cultural factors in specific LMICs, and can provide deeper insights into potential solutions (Nafade et al., 2019), thus their involvement in research is paramount. However, the underrepresentation of LMICs in global health has been identified in terms of authorships, conference participations, and editorial boards in previous studies (Iyer, 2018;Nafade et al., 2019;Velin et al., 2021). The data showed that 35% of the authors of research articles were affiliated with LMICs (Iyer, 2018), 11% of journal editors were women based in LMICs (Nafade et al., 2019), 4% of global health conferences were hosted in LMICs and 39% of attendees were from LMICs (Velin et al., 2021). Research resources, infrastructure, and funding are dominated by HICs, which leads to less involvement from LMICs in shaping the global health agenda, priority setting, and policies. Considering that challenges in LMICs take a huge part in global health, more efforts to promote equity, diversity, and inclusion are required to achieve health for all.
The few relevant studies conclude that there is a need for more economic evidence to promote child development with equity considerations. First, technical guidance to support design, implementation, and evaluation of equity-informed economic evaluations in LMICs would be helpful. Second, the few identified multi-sectoral interventions indicate that strengthening a multi-sectoral approach is required to ensure holistic child development. Collective work across multiple sectors including health, nutrition, security and safety, responsive caregiving, and education can maximize the impact of interventions to meet diverse needs of children. Third, providing more technical and financial support to researchers in LMICs will support context-based evidence generation. Lastly, policy makers will also need clear and informed guidance on translating evidence to refine child development strategies and programs. This review has some limitations. As a scoping review, we did not conduct quality assessment and quantitative synthesis of results. Given breadth of early childhood development interventions covered, rather than a quantitative synthesis, this review aimed to provide an overview of existing evidence on how equity is integrated into economic evaluations in research in LMICs, and equity findings. Additionally, the search was restricted to English literature in scientific journals, which may have missed some studies. Lastly, we acknowledge the limitation of having one author conducting study selection and data extraction, but note that other authors were involved in discussions and decisions to address any uncertainties.

Conclusions
Every child has the right to reach their full potential, and equity is key to ensure that. Considering equity in economic evaluation could provide a broader picture to make more informed-decisions in priority setting. The small number of relevant studies in the review highlights that more emphasis on equity integration into economic evaluation, coordinated work across multiple sectors, and strong involvement of researchers based in LMICs, are necessary to improve child development.

Acknowledgements
The authors would like to thank Lorena Romero, a research librarian at Alfred Hospital in Australia, for substantial support in development of the search strategy. At the time of submission, YB is supported by the Australian Government Research Training Program (RTP) Scholarship. JF is supported by the Finkel Professorial Fellowship which is funded by the Finkel Family Foundation. TT is supported by a Monash Strategic Bridging Fellowship. The sponsors had no role in study design and publication of the study.
Author Contributions YB, ZA, JF, TT, AO conceptualized the study. YB developed the search strategy with support from a research librarian, searched the literature, and conducted study selection and data extraction. YB drafted the first manuscript and the others contributed to the revision of the manuscript. All authors have read and approved the final manuscript.
Funding Open Access funding enabled and organized by CAUL and its Member Institutions. The authors received no financial support for this research.
Data Availability All data generated or analyzed during this study are included in this article.
Code Availability Not applicable.

Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval Not required as the manuscript is not based upon clinical study or patient data.

Consent for Publication Not applicable.
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