Stunting, defined as height-for-age z score ≤−2 SDs below the World Health Organization (WHO) Child Growth Standards median [1], represents a chronic nutritional disorder reflecting failures in health, nutrition, and psychosocial care [2]. Globally, an estimated 149 million children younger than 5 years were stunted in 2023, with the burden disproportionately concentrated in low- and middle-income countries (LMICs) [3]. Indonesia reports one of Southeast Asia’s highest stunting prevalence rates at 21.6% according to the 2023 National Nutritional Status Survey [4], though this masks significant regional disparities ranging from 7.2% in Bali to 39.4% in Central Papua [5]. Beyond short stature, stunting leads to irreversible cognitive deficits [6], reduced educational attainment, lower adult productivity, and intergenerational poverty perpetuation [7]. This original research article aims to examine the cumulative effects of high-risk pregnancy (HRP) complications on the risk of stunting in Indonesian children younger than 5 years, applying the Developmental Origins of Health and Disease (DOHaD) framework.

The DOHaD hypothesis provides a critical framework for understanding stunting etiology. First, proposed by Barker (1990) and later expanded by Hanson and Gluckman (2015), this theory posits that environmental exposures during sensitive developmental windows have permanent effects. Recent reviews have increasingly emphasized that these effects are often the result of cumulative and synergistic exposures, rather than single insults [8], which forms the central hypothesis of our study. These exposures can alter physiological structure, metabolic programming, and disease susceptibility later in life [9,10]. Central to this concept is fetal programming, where prenatal insults such as those from HRP complications disrupt normal development [11]. In LMICs like Indonesia, where 48.9% of pregnant women experience anemia [12], the interplay between maternal nutritional status, HRP complications, and child growth outcomes represents a critical pathway [13].

HRP complications, including anemia, preeclampsia, gestational diabetes mellitus (GDM), heart disease, and asthma, expose fetuses to nutrient deprivation, hypoxia, oxidative stress, and inflammation [14]. Maternal nutrition plays a critical role in fetal development, with deficiencies in key nutrients including iron, folate, and protein contributing to both HRP complications and subsequent child stunting [15]. Recent evidence suggests these effects may be cumulative, with multiple HRP complications synergistically increasing stunting risk beyond individual conditions [16-18]. For instance, a mother with both anemia and preeclampsia may expose the fetus to combined insults that disrupt fetal programming more severely than either condition alone [19]. However, most research examines HRP complications in isolation, with limited studies assessing their combined effects on stunting in Indonesia [20].

Despite Indonesia’s National Stunting Acceleration Strategy (2023‐2024), which emphasizes integrated nutrition interventions and antenatal care (ANC) strengthening, stunting prevalence remains above the WHO’s significance threshold (>20%) [21]. Current ANC protocols primarily focus on identifying single risks such as anemia or preeclampsia [22], potentially overlooking pregnancies with overlapping complications that confer exponentially higher risk [23]. Furthermore, the role of socioeconomic confounders such as maternal education, family income, and health care access requires careful consideration to clarify the independent association between HRP and stunting [24].

This study addresses these gaps by doing the following:

The key messages for this study are as follows:

A retrospective analytical study was conducted in Sleman Regency, Yogyakarta Special Region, Indonesia, between January 2019 and December 2024. The design followed the life course epidemiology framework and employed the counterfactual framework of causation [26]. The methodology adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines [27].

Sleman Regency had 2272 documented stunting cases in 2024. The study focused on 6 subdistricts (Sleman, Brebah, Mlati, Kalasan, Godean, and Tempel), accounting for 91.6% of the regency’s stunting cases. Data were collected from the following:

The study population consisted of children aged 12 to 59 months registered in the district Integrated Nutrition Information System in 2024.

Inclusion criteria were as follows:

Exclusion criteria were as follows:

A multistage cluster sampling method was used to obtain a representative sample of children aged 12 to 59 months in Sleman Regency. The process involved three stages.

A total of 990 eligible respondents were recruited from 6 subdistricts and 33 integrated health posts. However, due to incomplete data, 540 respondents were excluded. The final analytical sample comprised 450 children (300 children with stunting and 150 children without stunting).

Using the formula for estimating a proportion in a finite population (N=62,817, Z=1.96, p=0.50, e=0.046), a total sample size of 450 children was determined [28].

Data were collected through a rigorous three-step process to ensure validity and minimize bias: (1) medical record review for HRP history and maternal variables, (2) MCH handbook review for detailed pregnancy history and ANC visits, and (3) direct verification of anthropometric data at integrated health posts.

To ensure the highest data quality, a comprehensive quality assurance protocol was implemented.

Data were analyzed using Python (pandas 1.5.3, numpy 1.24.3, scipy 1.10.1; Integrated Development Environment). Descriptive statistics were presented as means with SD for continuous variables and frequencies with percentages for categorical variables. Bivariate analyses, including χ² tests for categorical variables and t tests for continuous variables, were conducted to examine the unadjusted associations between independent variables and stunting, reporting unadjusted odds ratios (OR) with 95% CI. A multivariate logistic regression model was developed to determine the independent association between HRP complications and stunting while controlling for confounders. All identified confounding variables (maternal age, education, family income, ANC visits, iron tablet consumption, maternal nutrition, and family size) were entered into the model simultaneously using a forced entry method. The model fit was assessed using the Hosmer-Lemeshow goodness-of-fit test, Nagelkerke R², and the area under the receiver operating characteristic curve. A 2-tailed P value less than .05 was considered statistically significant.

Ethical approval was obtained from the Ethics Committee Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada (Ref: KE/FK/0825/EC/2025). All data were anonymized to protect respondents’ privacy and confidentiality. Since this study was using retrospective data, informed consent was not needed. The study was conducted in accordance with the Declaration of Helsinki [34] and relevant bioethical principles [35].

The participant selection process is detailed in Figure 1. From an initial pool of 990 children recruited from the selected integrated health posts, a total of 540 children were excluded due to incomplete data. The primary reasons for exclusion were incomplete anthropometric measurements (n=400) and incomplete pregnancy history data (n=140), which were treated as mutually exclusive categories. This resulted in a final analytical sample of 450 children (300 children with stunting and 150 without stunting).

The final sample of 450 children was drawn from 6 subdistricts, with the number of participants from each stratum being proportional to the documented stunting cases (high: Sleman and Berbah; medium: Mlati and Kalasan; and low: Godean and Tempel). The distribution of children with and without stunting across these subdistricts was comparable (P=.87). The characteristics of the study participants are presented in Table 1.

Table 1 presents participant characteristics and the sampling process. The mean age was 34.6 (SD 12.8) months, with no significant difference between stunted (34.8, SD 12.9 mo) and nonstunted (34.1, SD 12.6 mo) groups (P=.43). Gender distribution was similar (158/300, 52.7% male in stunted group vs 76/150, 50.7% in nonstunted group; P=.68). Significant differences were observed in maternal education (P<.001), family income (P<.001), ANC visits (P<.001), iron supplementation (P<.001), maternal nutrition (P<.001), and family size (P<.001).

Table 2 shows the prevalence of HRP complications. Any HRP complication was significantly higher among mothers of children with stunting (206/300, 68.7% vs 48/150, 32%; P<.001). Anemia was the most common complication (145/300, 48.3% vs 34/150, 22.7%, P<.001), followed by preeclampsia (46/300, 15.3% vs 6/150, 4%; P<.001). A clear dose-response relationship was observed: children exposed to multiple HRP complications had 6.71 times higher odds of stunting (OR 6.71, 95% CI 3.54‐12.72).

Table 3 presents bivariate and multivariate analysis results. After adjustment for all confounders, anemia (adjusted OR [aOR] 3.21, 95% CI 2.12‐4.86), preeclampsia (aOR 4.37, 95% CI 2.18‐8.76), and gestational diabetes (aOR 2.85, 95% CI 1.42‐5.72) remained significantly associated with stunting. Children exposed to multiple HRP complications showed a 5.8-fold increased risk (aOR 5.80, 95% CI 3.26‐10.32). Among confounders, maternal education (aOR 0.72, 95% CI 0.58‐0.89), family income (aOR 0.68, 95% CI 0.52‐0.89), and ANC visits (aOR 0.85, 95% CI 0.76‐0.95) were independently protective (Figure 2).

The multivariate model showed good fit (Hosmer-Lemeshow test: χ²=6.84, P=.55; Nagelkerke R²=0.412; area under receiver operating characteristic curve=0.812) with no multicollinearity (all variance inflation factor <2.5).

This study provides compelling evidence that the cumulative burden of HRP complications, rather than isolated conditions, is the most powerful prenatal factor associated with stunting in Indonesian children. Our finding of a dose-response relationship, where exposure to two or more HRP complications increased stunting risk nearly 6-fold (aOR 5.80), offers strong empirical support for the DOHaD hypothesis [16]. Critically, our findings extend the DOHaD framework by demonstrating that it is not merely the presence of a single prenatal insult but the synergistic interaction of multiple simultaneous exposures that most profoundly disrupts fetal programming and elevates disease risk later in life [10,11,16]. This challenges the current ANC paradigm in Indonesia, which predominantly focuses on identifying and managing single risks like anemia or preeclampsia, potentially overlooking pregnancies with overlapping complications that confer substantially higher risk.

While anemia and preeclampsia remained significant independent predictors, their impact must be contextualized within the broader landscape of cumulative risk. Anemia (aOR 3.21) was the most prevalent single complication in our study (48.3% in the stunted group), consistent with Indonesia’s high national maternal anemia burden of 48.9% [12]. However, its effect size was substantially lower than that of multiple HRP exposures. Similarly, preeclampsia (aOR 4.37), while strongly associated, was also outpaced by the combined risk. These findings indicate that isolated management of single risks during ANC may miss HRPs with overlapping complications, underscoring the need to understand the synergistic biological pathways that make the cumulative effect so profound.

Our finding that multiple HRP complications exponentially increase stunting risk suggests synergistic biological effects rather than a simple additive model. According to the DOHaD framework, the fetus adapts to the intrauterine environment. However, multiple simultaneous stressors can overwhelm these adaptive mechanisms, leading to permanent alterations in developmental programming. Several interconnected pathways likely explain this phenomenon. First, placental dysfunction serves as a central hub. Conditions like preeclampsia directly impair placental blood flow, a process increasingly understood through specific placental biomarkers that predict adverse outcomes [36], leading to fetal hypoxia and nutrient restriction. When combined with maternal anemia, which reduces the oxygen-carrying capacity of the blood, the placenta’s ability to deliver oxygen and nutrients is severely compromised, amplifying fetal growth restriction [19]. Second, oxidative stress and inflammation are common final pathways for many HRP complications. Preeclampsia, GDM (through hyperglycemia), and anemia (through hypoxia-reperfusion injury) all independently increase the production of reactive oxygen species. The concurrent presence of these conditions creates a pro-inflammatory and prooxidant intrauterine environment that can damage developing fetal tissues and disrupt metabolic programming [37]. Finally, the combined metabolic disruption is critical. For instance, a fetus exposed to both maternal anemia (nutrient deprivation) and GDM (excess glucose) receives conflicting and damaging signals, forcing it to adapt to both scarcity and toxicity simultaneously. This metabolic dissonance can have a more profound impact on endocrine and cardiovascular system development than either condition alone, setting the stage for postnatal growth faltering and stunting [38].

While the biological mechanisms explain the heightened vulnerability from cumulative HRP exposures, our analysis also identified key protective factors. Maternal education (aOR 0.72), family income (aOR 0.68), and ANC visits (aOR 0.85) were significantly associated with reduced stunting risk. However, their modest effect sizes reveal a complex reality and highlight the limitations of current interventions. This complexity is further illustrated by the shifting significance of iron tablet consumption and maternal nutrition. Both showed strong associations in bivariate analysis but lost significance after adjustment for socioeconomic confounders, suggesting their effects are largely mediated by upstream factors like education and income [26]. It appears that mothers with higher education and greater resources are better equipped to maintain adequate nutrition and adhere to supplementation, positioning these socioeconomic conditions as more fundamental determinants of child growth [3,14]. This finding underscores that interventions focusing solely on nutrient provision or increasing ANC visit frequency, without addressing the underlying socioeconomic context, are likely to have limited long-term impact on stunting prevention.

This study has several methodological strengths. First, the large, representative sample with rigorous multistage cluster sampling enhances external validity. Second, comprehensive adjustment for socioeconomic and health care confounders strengthens our analytical approach. Third, the use of contemporary international guidelines [22,25] for HRP diagnosis ensures methodological rigor and comparability. Fourth, triangulation of multiple data sources minimizes misclassification bias. Fifth, the application of advanced statistical methods with appropriate model fit assessment ensures the robustness of our findings.

Despite these strengths, several limitations must be acknowledged. Our interpretation of the findings is constrained by the study’s retrospective observational design and data sources, which also impact the generalizability of our results.

Our findings align with studies from other LMICs showing strong associations between maternal HRP and child stunting. A recent systematic review by Beal et al [20] reported similar effect sizes for anemia and preeclampsia in Indonesian children. However, our study adds significant value by being the first to examine multiple HRP complications simultaneously, demonstrating their synergistic cumulative effect while controlling for a comprehensive set of confounders using contemporary international guidelines [22,25].

The Indonesian context presents unique challenges and variations. In our study area of Sleman, anemia prevalence was high (48.3%), yet the national stunting burden shows stark disparities, from 7.2% in Bali to 39.4% in Central Papua [4,5], a pattern where the latest analyses confirm that socioeconomic factors remain a primary driver of stunting nationally [13,40]. This complex landscape, characterized by a dual burden of malnutrition and epidemiological transition, underscores why a single-risk approach is insufficient. Our analysis demonstrates that cumulative risk assessment better predicts stunting in this diverse environment.

Given this robust evidence, our findings have direct and critical implications for MCH policy in Indonesia. The current single-risk-focused ANC paradigm is insufficient to address the complex, cumulative risks we have identified. We recommend the following actionable shifts:

Strengthen health system Capacity: Addressing cumulative risk requires a well-trained and empowered workforce. Investment in training for ANC providers to identify, manage, and counsel patients with multiple complications is essential. This includes training on the DOHaD framework to enhance their understanding of the long-term implications of prenatal care quality.

By adopting a cumulative risk framework aligned with the DOHaD hypothesis, Indonesia can accelerate progress toward reducing stunting and breaking the cycle of intergenerational malnutrition.

Prospective cohort studies are needed to establish temporality and explore mediating pathways in the HRP-stunting relationship. Implementation research on integrated HRP-stunting prevention programs could identify effective delivery strategies. Finally, exploration of biological mechanisms could advance our understanding of developmental programming and identify novel intervention targets.

In conclusion, this study provides compelling evidence that the cumulative burden of HRP complications is the most powerful factor associated with stunting in Indonesian children. While individual complications remain significant, their impact is substantially lower than that of cumulative exposures. This challenges the current single-risk-focused ANC paradigm and highlights the urgent need for a shift toward integrated, cumulative risk management strategies. Such a paradigm shift, aligned with the DOHaD framework, is essential for effectively breaking the intergenerational cycle of malnutrition in Indonesia.