Child and adolescent health constitutes a paramount concern within global health initiatives, asserting the fundamental right of every child to survive and flourish (UNICEF, 2025). There is increasing emphasis on improving the health and wellbeing of children and adolescents, as health during these formative years shapes lifelong outcomes and contributes to a productive workforce, social stability, and sustainable national development (Call et al., Reference Call, Riedel, Hein, McLoyd, Petersen and Kipke2002). Concurrently, efforts are underway to improve neonatal and pediatric survival rates, enhance the health and development of young populations, strengthen health systems, and mitigate environmental hazards that impact child health at the community, national, and international levels (UNICEF, 2016b, 2016a). Despite these cumulative endeavors, challenges persist concerning survival and the realization of full developmental potential within this demographic. Child mortality resulting from preventable and treatable conditions such as complications related to preterm birth, birth asphyxia or trauma, pneumonia, diarrhoea, and malaria remains a significant concern (WHO, 2022b). Moreover, although extensive data are available concerning various aspects of child and adolescent health and wellbeing, notable gaps persist within the South Asian region (WHO, 2023).

The South Asian region accounts for nearly a quarter of the global population and is characterized by substantial ethnic, cultural, and socioeconomic diversity (Dasvarma, Reference Dasvarma2003). Health outcomes among children and adolescents in South Asia are influenced by a range of factors, including nutritional status, environmental exposures, infectious diseases, and rapidly changing lifestyles associated with urbanization and economic development (WHO, 2023). Despite the large population base and increasing research interest in child and adolescent health, genetically informative research designs, such as twin studies, remain relatively limited in the region compared with Europe, North America, and East Asia (Smits & Monden, Reference Smits and Monden2011). With a multiple birth rate of approximately 1% (Alsam & Rashid, Reference Alsam and Rashid2010; Chaudhary, Reference Chaudhary2016), it is important to conduct research that examines the scope and characteristics of existing twin studies in South Asia in order to identify knowledge gaps and inform future research priorities.

There are over 2.5 billion children and adolescents (aged 0−19) worldwide (United Nations Population Division, 2019), and adolescents aged 10−19 years make up more than 16% of the global population (WHO, 2022a). Moreover, children from different regions face diverse health-related challenges that require immediate attention. The Apgar score is a standardized clinical assessment used to evaluate a newborn’s condition immediately after birth, based on five components — heart rate, respiratory effort, muscle tone, reflex irritability, and skin colour, each scored from 0 to 2, with total scores ranging from 0 to 10 (Razaz et al., Reference Razaz, Cnattingius and Joseph2019). Newborns undergo several developmental stages, beginning with infancy (the first 12 months; Centres for Desease Control and Prevention [CDC], 2022), and continue to grow and develop throughout childhood. These initial two decades are crucial, as they are when a child develops complete physical, mental, and social wellbeing, laying the foundation for a healthy adult life. Consequently, a healthy childhood establishes a solid base for a healthy adulthood.

Early-life interventions are crucial for promoting healthy growth, particularly among preterm and low birth-weight infants. Kangaroo mother care (KMC) is a neonatal care practice involving prolonged skin-to-skin contact between the infant and caregiver, combined with breastfeeding support and follow-up care, and has been shown to improve survival and developmental outcomes (Chan et al., Reference Chan, Valsangkar, Kajeepeta, Boundy and Wall2016). As twins are at higher risk of preterm birth and low birth weight, KMC is especially relevant to twin neonatal care (Arora et al., Reference Arora, Kommalur, Devadas, Kariyappa and Rao2021).

Within this broader effort to understand and improve child and adolescent health, twin populations provide a uniquely powerful framework for examining developmental trajectories (Jansen et al., Reference Jansen, Mous and White2015), health risks (Kaprio et al., Reference Kaprio, Pulkkinen and Rose1993), and disease etiology (Thomsen, Reference Thomsen2015). Twins are typically classified into two types based on their zygosity. Monozygotic (MZ), or identical twins, develop from a single fertilised egg (zygote), so their genetic makeup is expected to be identical (Hall, Reference Hall2003). MZ twins share the same genomes and are always of the same sex (Cidis et al., Reference Cidis, Warshowsky, Goldrich and Meltzer1997). Dizygotic (DZ), or fraternal twins, develop from the fertilization of two separate eggs during the same pregnancy. Fraternal twins can be of the same or different sexes and share about 50% of their genes, similar to other siblings (Hall, Reference Hall2003).

Complex human traits are influenced by both nature (genetics) and nurture (environment) (Plomin & Asbury, Reference Plomin and Asbury2005). Twin studies have been used to explore the heritability of specific traits and provide means to investigate and partition the relative contributions of genes and the environment to phenotypic variability in all human traits (Polderman et al., Reference Polderman, Benyamin, De Leeuw, Sullivan, Van Bochoven, Visscher and Posthuma2015; Wright & Martin, Reference Wright and Martin2004). The traditional ‘twin design’ leverages the fact that MZ twin pairs are similar because they share 100% of their genes and, when reared together, 100% of their shared (common) environment, with differences attributed to their nonshared (unique) environment. In contrast, DZ twins are similar because they share, on average, only 50% of their genes and, when reared together, 100% of their shared (common) environment (Wright & Martin, Reference Wright and Martin2004). Both types of twins typically grow up in the same prenatal and postnatal environments, allowing researchers to compare similarities and differences between twin pairs and estimate the relative contributions of genetic and environmental influences on health and development (Posthuma et al., Reference Posthuma, Beem, Geus, Baal, Hjelmborg, Iachine and Boomsma1997). It further enables researchers to observe how shared and nonshared factors shape physical, cognitive, and psychosocial development from infancy through adolescence, critical years that determine long-term health trajectories (Hannigan et al., Reference Hannigan, Pingault, Krapohl, Mcadams, Rijsdijk and Eley2018). Although twin studies hold great potential to offer unique insights into health and wellbeing across the life course, their potential remains unevenly realised due to substantial gaps in research infrastructure and capacity. Specifically, limited investment in twin registries, insufficient training in twin research methodologies, and underrepresentation of low- and middle-income countries constrain the global applicability of twin research findings (McGregor et al., Reference McGregor, Henderson and Kaldor2014). To date, the vast majority of twin registries have been established in Western, high-income countries, with research predominantly conducted among populations of European descent. In contrast, regions such as South Asia continue to face marked shortages in both twin registries and methodological expertise required to conduct robust twin studies (Hur and Craig, Reference Hur and Craig2013). While twin research has expanded substantially in high-income settings over the past two decades (Boomsma et al., Reference Boomsma, Busjahn and Peltonen2002), no comprehensive synthesis currently exists that examines health outcomes among infant, child, and adolescent twin populations in the South Asian region. This absence of systematic evidence constrains understanding of early-life health trajectories within this highly socioculturally and environmentally diverse context and underscores a critical gap in the global twin health literature.

Therefore, this systematic review aimed to identify and synthesize health research studies that have recruited infant, child, or adolescent twin populations in South Asia, specifically within countries of the South Asian Association for Regional Cooperation (SAARC). The review sought to: (1) characterize the scope of existing twin research, including the types and volume of studies conducted; (2) critically appraise the methodological quality, contextual relevance, and key attributes of these studies across the SAARC countries; and (3) identify existing evidence gaps to inform priorities and establish a foundation for future twin research in the region.

Methodology

Protocol Development

The protocol was developed using the PICOS (Population, Intervention, Comparison, Outcomes of interest, Setting and study design) framework (Amir-Behghadami & Janati, Reference Amir-Behghadami and Janati2020). Both the protocol and search strategy were registered in the Prospero International Prospective Register of Systematic Reviews (Reg No: CRD42018105704).

Eligibility Criteria

The inclusion and exclusion criteria used to guide article selection are presented in Table 1.

Table 1.

Inclusion and exclusion criteria for selecting South Asian Twin Health Studies

Information Sources

A comprehensive literature search was conducted across multiple online bibliographic databases, including PsycINFO, CINAHL, HBE, MEDLINE, AMED, EMBASE, and BNI. To obtain relevant locally published articles within the context, Sri Lanka Journals Online (SLJOL) a database for online published journals in Sri Lanka (https://www.sljol.info/), the National Database of Indian Medical Journals (IndMED), PakMediNet a database containing research articles published in Pakistani Medical Journals, DSpace Repository (Dhaka University Institutional Repository for scholarly / published material), and IMSEAR database (via WHO’s Global Index Medicus) were searched. The references of all retrieved articles were reviewed to identify any relevant cited articles that were not identified in the review. Additionally, authors who had only published an abstract were contacted to conduct a comprehensive search for unpublished literature. The initial search between August and September 2018, and a top-up search was conducted in September 2025.

Search Strategy

A combination of specific keywords consisted of search terms and Boolean operators; for example, (twin* OR monozygot* OR dizygot* OR “multiple birth*”) AND (“Western Asia*” OR (Southeast OR Southeastern) ADJ Asia*) OR (South OR Southern) ADJ Asia*) OR (SAARC) OR Afghani* OR Bangladesh* OR Bhutan* OR India* OR “Indian Ocean Island*” OR Maldiv* OR Nepal* OR Pakistan* OR “Sri Lanka*”) were used.

Studies published between 2010 and 2025 were considered for inclusion in this review.

Selection Process

After removing duplicates, the lead reviewer (JO) and four other reviewers (OS, LD, AH, ICE) used the Rayyan Systematic Review tool to independently screen the ‘title and abstract’ of the records. Following the screening stage, the reviewers resolved the decision conflicts. If consensus could not be reached, the record was added for full-text review. The full-text publications were uploaded to the Rayyan Systematic Review tool and independently reviewed by three reviewers (JO, BH, and KJ). The conflicts in decisions were resolved by the lead reviewer (JO) and two subject experts (KJ and AS). The screening process is illustrated in Figure 1, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria for record selection.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram illustrating the study selection process. The diagram depicts the number of records identified through database searching, records after duplicates were removed, records screened, full-text articles assessed for eligibility, and the final number of studies included in the review. Reasons for exclusion at the full-text stage are also shown.

Study Risk of Bias Assessment

The Joanna Briggs Institute (JBI) critical appraisal tools (https://joannabriggs.org/research/critical-appraisal-tools.html) were used for the quality assessment of the studies. JBI critical appraisal tools are a set of checklists (13) or standardized assessment tools for variety of study designs. Each checklist includes 7–11 questions, depending on the types of study designs. The JBI critical appraisal tools were chosen as they cover the full range of study designs included in the current review (e.g., qualitative studies, case reports, case studies, cohort studies, diagnose test accuracy, mixed-method studies, validation studies, text and opinion papers). Quality assessments were performed independently by SJ and BS.

Each article included was rated based on the study purpose, study design, sample size, response rate, method of data analysis, the validity of the results and reporting of the findings.

Results

A total of 18 studies were included in this systematic review, focusing on research involving twins in health studies conducted in South Asia. Using the search strategy, 1245 records were identified across various databases. After removing duplicates, 1089 records remained for screening. Seventy-four articles were selected for full-text review, of which 18 studies met the inclusion criteria (see Figure 1 for the PRISMA flow diagram). The included studies differed by study area, objectives, study design, geographic area, participant demographics and sample size.

Of all the studies included in the systematic review, the majority focused on twin pregnancy, constituting 61% of the total. Seventeen per cent of the studies concerned dentistry, while 11% addressed both ocular health and gut microbiota. Figure 2 shows how the included studies differed by study area.

Figure 2.

Distribution of included studies by study area. The figure illustrates how the studies included in the systematic review were categorized according to their research focus. The majority of studies examined twin pregnancy (61%), followed by dentistry (17%), while ocular health and gut microbiota each accounted for 11% of the total.

Twin Pregnancy

According to two studies conducted at Sir Ganga Ram Hospital in Lahore and B. P. Koirala Institute of Health Sciences in Nepal, the incidence of twin pregnancies ranges from 0.92% to 0.97% (Alsam & Rashid, Reference Alsam and Rashid2010; Chaudhary, Reference Chaudhary2016). It was also found that 44.29% of twins were monochorionic and 55.71% were dichorionic (Alsam & Rashid, Reference Alsam and Rashid2010). The combined birth weight of twin pairs was reported to be significantly higher in dichorionic twins (median 4250 g, interquartile range 3530–4810) compared with monochorionic twins (Singh et al., Reference Singh, Singh and Nirmalan2014).

Among monochorionic twins, most had an Apgar (Appearance, Pulse, Grimace, Activity, and Respiration) score of 7 or higher. A higher Apgar score at 5 minutes after birth was observed in twins with an interdelivery interval of less than 30 minutes. The Apgar score of the first twin was higher than that of the second twin in both preterm and overall gestation (Baral et al., Reference Baral, Dangal, Baral and Subedi2021). It was also found that the difference in Apgar scores between 1 minute and 5 minutes after birth increased significantly in the second twin. According to a study conducted at B. P. Koirala Institute of Health Sciences in Nepal, 98.9% of twins had low birth weight (Chaudhary, Reference Chaudhary2016).

A study was carried out in India on the management of twin low birth-weight neonates using kangaroo mother care. It was observed that the mean weight gain in the kangaroo mother care group (13.48 ± 1.76 g/kg/day) was significantly higher than the mean weight gain in the conventional method of care group (11.99 ± 1.20 g/kg/day). It was discovered in this study that early initiation of breastfeeding and high self-confidence of mothers to manage the low birth-weight neonates were prevalent in neonates under kangaroo mother care (Gonuguntla et al., Reference Gonuguntla, Metgud and Mahantshetti2018).

In a study conducted at Fatima Memorial Hospital, Pakistan, to compare the outcomes of twin pregnancies, 40.9% of the study population had planned cesarean sections, and 59.01% had planned vaginal deliveries. In comparison, nearly 33.33% of births were delivered via cesarean section (Ahmed et al., Reference Ahmed, Naeem and Yasir2013).

Low birth-weight and preterm neonates were significantly higher in twins compared to singletons. Preterm and low birth-weight neonates were more prone to perinatal mortality than term and typically weighed babies. Another complication discovered in twin neonates was that they were hypothermic and hypoxic compared to singletons. (Meshram & James, Reference Meshram and James2022). Also, birth asphyxia was more common among the second twin than first twin (Konar et al., Reference Konar, Sarkar and Paul2016). Respiratory distress syndrome and jaundice were more commonly diagnosed among twin neonates than among singleton neonates. Respiratory distress syndrome was the most common cause of death in twin neonates. It was also observed that the neonatal mortality and the length of hospital stay were significantly higher in twin neonates (Meshram & James, Reference Meshram and James2022). Perinatal morbidity was found to be significantly higher in second twins than in first twins, although neonatal mortality was not statistically significant. It was also reported that admission to the hospital nursery was also considerably higher for the second twin compared to the first twin (Jamala et al., Reference Jamala, Akhtar, Karim and Yasmin2014).

Another study indicated that hospital mortality rate was 10.87%, and 37.5% of the twin infants had complications (Chaudhary, Reference Chaudhary2016). A study conducted at a tertiary care hospital in Kolkata, India, revealed that the second twin in vertex–vertex presentation is more susceptible to perinatal mortality than twins in vertex–nonvertex and nonvertex–other presentations. Perinatal outcome was adverse when both twins were delivered vaginally, compared to both cesarean deliveries and cesarean deliveries after first vaginal delivery (Konar et al., Reference Konar, Sarkar and Paul2016). In another study carried out on twin pregnancy maternal complications, anemia complications were presented in twin pregnancies as the most common maternal complication, followed by gestational hypertension. It has also been recorded that prematurity is the most common neonatal complication (Gupta et al., Reference Gupta, Faridi, Goel and Zaidi2014; Shahi et al., Reference Shahi, Agrawal and Sinha2022).

Dentistry

A study conducted in Kerala, India, found that lower birth-weight twins are more susceptible to dental caries than higher birth-weight twins. The second twin also showed an increased risk of dental caries compared to the first. It was additionally reported that male twins have a higher susceptibility to dental caries than female twins. Specifically, 90% of male twins exhibited dental caries, whereas only 45% of female twins did. Twins who were exclusively breastfed were noted to have an increased risk of dental caries. Twin children with bad oral habits demonstrated higher susceptibility to dental caries, with the strongest correlation found between an excessive liking for sweets and the prevalence of dental caries (Zarina et al., Reference Zarina, Kuriakose, Lalithamma, D’souza, Padmakumari and Jeeva2019). Heritability estimates for the number of teeth that erupted were highest in the age group from 5 to 7 years, when the first molars and incisors emerged (Sharma, Reference Sharma2014). The prevalence of early childhood caries was estimated at 18.7%, and there was a significant correlation for early childhood caries among twins. A relatively low genetic influence was suggested for early childhood caries in twins (Kuppan et al., Reference Kuppan, Rodrigues, Samuel, Ramakrishnan, Halawany, Abraham, Jacob and Anil2017).

Gut Microbiota

Twins with more severe stunting had a less diverse microbiota and a denser covariance network. Acidaminococcus has been found in higher proportions in children at risk of future growth deficits (Gough et al., Reference Gough, Stephens, Moodie, Prendergast, Stoltzfus, Humphrey and Manges2015).

Ocular Health

In a study conducted in Kodinhi village, India, the prevalence of refractive errors among twins was 10.5%. It was found that 7.9% had myopia and 2.6% were reported to have hyperopia. The prevalence of myopia, hyperopia, and emmetropia among DZ twins was 12.5%, 4.2%, and 83.3% respectively, and all the MZ twins were emmetropic in this population. Most of the MZ twins showed statistically significant differences in convergence and contrast sensitivity. At the same time, there was also statistical significance in the accommodation of the right eye, the anterior chamber depth (ACD) of the left eye, contrast sensitivity, and the axial length (AL) of both eyes between MZ and DZ twins (Kalikivayi & Kalikivayi, Reference Kalikivayi and Kalikivayi2022). According to a prospective study conducted in a tertiary care hospital in North India, the incidence of retinopathy of prematurity was approximately 45.57%. Low gestational age, low birth weight, and multiple gestation were identified as independent risk factors for Retinopathy of Prematurity (Sood et al., Reference Sood, Chellani, Arya and Guliani2012). Table 2 illustrates variations in the country of study, study design, participant age range, aims and objectives, and sample size across studies on twin pregnancy, dentistry, gut microbiota and ocular health.

Table 2.

Studies related to twin pregnancies, dentistry, gut microbiota and ocular health, carried out in South Asia

Note: KMC, kangaroo mother care; LBW, low birth weight; MZ, monozygotic; DZ, dizygotic; ECC; early childhood caries; ROP, retinopathy of prematurity.