Perinatal asphyxia (PA) is defined by the World Health Organization (WHO) as a failure to initiate or sustain spontaneous breathing at birth, a definition widely used in low- and middle-income countries (1). In contrast, the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) describe PA as a condition resulting from impaired gas exchange, leading to hypoxemia, hypercapnia, and metabolic acidosis. The ACOG/AAP Task Force recommends a diagnostic approach that combines biochemical criteria, such as an umbilical artery pH < 7.00 and a base deficit ≥12 mmol/L, with clinical indicators, including a 5-minute Apgar score ≤3, signs of neonatal encephalopathy, need for prolonged resuscitation, and evidence of multi-organ dysfunction (2).

Globally, PA accounts for approximately 24% of neonatal deaths, with its burden falling disproportionately in low- and middle-income countries, where it ranks as the fifth leading cause of neonatal mortality (3–5). The estimated incidence of PA in these settings ranges from 100 to 250 cases per 1,000 live births, whereas in high-income countries the rate is substantially lower, ranging from 5 to 10 cases per 1,000 live births (6). Among survivors, PA is a major cause of long-term neurodevelopmental impairment, including cerebral palsy, cognitive deficits, and epilepsy (4, 7, 8).

Several risk factors that contribute to the occurrence of PA have been identified. These include maternal sociodemographic conditions; obstetric complications such as preeclampsia, gestational diabetes, and chorioamnionitis; intrapartum factors such as prolonged labor, meconium-stained amniotic fluid (MSAF), and acute fetal distress; and neonatal factors including gestational age and birth weight (6, 9–12). On the other hand, gestational age plays a fundamental role not only in the risk of PA development but also in its pathophysiology. Ischemic and periventricular white matter lesions were more frequent in preterm neonates, whereas alterations in the basal ganglia were more frequent in term neonates than in term neonates (13).

Reliable epidemiological data on the prevalence of PA and its associated risk factors in low- and middle-income countries are essential to guide interventions aimed at reducing its occurrence. However, in Latin American countries, there is significant underreporting of PA cases in national statistics and a general scarcity of research data. These gaps are largely explained by socioeconomic disparities, geographical barriers, and limited access to healthcare services, resulting in incomplete understanding of the true burden of the condition (14). Although the overall incidence of PA in Latin America broadly aligns with global estimates, considerable variation exists between countries. For example, in Mexico, the reported prevalence in 2023 was 1.8 cases per 1,000 live births (15), whereas in Lima, Peru, a 2011–2012 study found that 14.1% of all neonatal deaths were attributable to PA (16).

A similar situation exists in Colombia, where the true burden of PA is likely to be underestimated because of underreporting. In addition, national statistics focus primarily on mortality data, overlooking the actual occurrence of the condition as only fatal cases are systematically recorded. For instance, a descriptive report from the Colombian National Institute of Health indicated that 12.4% of perinatal deaths in 2020 were attributed to PA, corresponding to a mortality rate of 0.7 per 1,000 live births (17). However, these figures lack a comprehensive analysis of underlying maternal and neonatal risk factors. Moreover, approximately one in four affected newborns may experience long-term disabilities, including cerebral palsy, neurodevelopmental impairment (motor, cognitive, or behavioral), and epilepsy (18). The scarcity of evidence-based data underscores a critical gap in the national and regional literature (19).

Given the limitations of administrative data, the scientific literature plays a crucial role in building an evidence-based understanding of PA in Colombia. This systematic review and meta-analysis aimed to estimate the prevalence of PA in newborns and to identify the most significantly associated risk factors within the Colombian context. This review focused on observational studies conducted in neonatal populations across Colombian healthcare institutions, comparing infants diagnosed with PA to those without the condition and examining both its frequency and determinants. This study sought to define the national epidemiological profile, highlight common determinants, and assess the methodological quality of available evidence. These findings are expected to inform clinical practice and public health strategies and guide the development of context-specific preventive and therapeutic interventions.

Systematic reviews and meta-analyses were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (20). The PRISMA checklist is provided in Supplementary Table S1. This systematic review was submitted to the PROSPERO registry but declined (“Rejected by PROSPERO”) because the topic did not meet the registry's eligibility criteria. All stages of protocol development, study selection, and data extraction were completed before conducting the analyses to ensure methodological transparency and minimize bias.

A total of 92 records were identified through the database searches. After removing 29 duplicates, 63 records were screened on the basis of their titles and abstracts. Of these, 51 were excluded as they did not meet the inclusion criteria. The remaining 12 full-text articles were assessed for eligibility, and 3 were further excluded due to unsuitable methodology, non-Colombian setting, or lack of relevance to PA. Ultimately, nine studies were included in the systematic review, of which six were eligible for the meta-analysis (Figure 1). The primary reasons for exclusion were unsuitable methodological design, studies conducted outside the Colombian context, and articles that did not address the research topic.

Four articles were selected for the meta-analysis of PA prevalence (23–26). For the meta-analysis of risk factors, four studies were included for acute fetal distress (24, 27–29), four for preeclampsia (24, 27–29), three for maternal morbidity (9, 26, 29, 30), four for MSAF (27–30), and three for the prolonged expulsive phase (27, 28, 30). Regarding the study design, two studies included in the prevalence analysis were cross-sectional, whereas the other two were cohort studies. Five studies used a case-control design to analyze risk factors.

The characteristics of the included studies are summarized in Table 1. All the included studies were conducted in major cities and departmental capital in Colombia. Three studies were conducted in Bogotá, three in Cali, one in Barranquilla, one in Cúcuta, and one in Popayan. These cities were the most populous in terms of their departments. Regarding hospital type, six studies were conducted in public hospitals, whereas three were performed in private institutions. All the studies were conducted in high-complexity university hospitals. With respect to population characteristics, four studies reported gestational age (23, 24, 28, 29).

This systematic review and meta-analysis provide the first comprehensive synthesis of the prevalence and risk factors of PA in Colombia, based on institutional-level data. The pooled prevalence was 5.92% (95% CI: 0.00%–25.3%), with risk factors including MSAF, prolonged second stage of labor, and intrapartum fetal distress. While the pooled prevalence provides a general overview of the available evidence, the small number of included studies (k = 4), the very wide 95% CI, and the high heterogeneity (I² = 99.2%), which is expected in low- and middle-income settings where diagnostic and reporting practices vary widely, indicate substantial statistical uncertainty. To further characterize this variability, a 95% prediction interval was calculated (0.0%–92.5%), revealing that the true prevalence could vary widely among future studies owing to the lack of standardized diagnostic and methodological approaches. Consequently, the pooled estimate should be interpreted as exploratory and descriptive rather than conclusive, primarily to highlight the evidence gap and the need for more methodologically consistent national research and multicenter studies to generate reliable national data on PA epidemiology in Colombia.

Furthermore, the variability in methodological quality among the included studies may have contributed to the observed heterogeneity. While most studies demonstrated moderate to good quality according to NOS and JBI assessments, some cross-sectional and cohort studies exhibited weaknesses in the outcome measurement and comparability domains. These limitations likely introduced variability in the prevalence estimates and reduced the precision of the pooled results, emphasizing the need for future high-quality, prospectively designed studies to improve the reliability of national estimates.

A notable limitation of the included studies was the marked heterogeneity in the diagnostic criteria for PA. Some studies used comprehensive definitions, including biochemical markers (e.g., umbilical artery pH < 7.0) and neurological assessment tools, such as the Sarnat staging system, whereas others relied primarily on clinical parameters, such as Apgar scores or the need for advanced resuscitation. This inconsistency likely contributed to the substantial between-study heterogeneity in prevalence estimates and may have affected the comparability of risk factor associations. These variations underscore the urgent need for standardized diagnostic frameworks to ensure accurate case identification and improve cross-study comparability.

The lack of standardization across Colombian epidemiological studies contrasts sharply with international recommendations, which emphasize four essential criteria: biochemical evidence of metabolic acidosis at birth, determined by umbilical cord or early neonatal blood gas analysis (pH < 7.0 or base deficit ≥12 mmol/L), clinical evidence of moderate or severe neonatal encephalopathy, neuroimaging findings, particularly magnetic resonance imaging (MRI) consistent with hypoxic-ischemic injury, and exclusion of alternative identifiable causes (2, 31). The absence of standardized protocols in Colombia limits the generalizability of our findings and complicates the formulation of evidence-based public health strategies. Therefore, future epidemiological studies aiming to establish the burden and causes of PA in Colombia should adopt standardized diagnostic criteria to improve disease characterization and generate reliable evidence to inform policies and targeted interventions. The adoption of these standardized criteria across Colombian institutions is essential for the accurate surveillance, early intervention, and policy-driven reduction of preventable neonatal deaths.

Furthermore, the limited number of epidemiological studies on PA in Colombia contrasts with the substantial clinical burden of this condition. Although global reductions in PA-related mortality have been achieved, the incidence remains high and continues to fall short of the Sustainable Development Goals for 2030 (32). In Colombia, based on national registry data, PA is the third leading cause of neonatal death, accounting for 24% of all neonatal deaths, with a mortality rate of 2.2 per 1,000 live births (33). Beyond mortality, PA imposes a significant long-term burden on the affected infants, their families, and the healthcare system.

The results of this study contrast with those of meta-analyses from other regions. For example, in Ethiopia, the pooled prevalence of PA ranges from 19.3% to 24.06% across different reviews (34–36). Similarly, a meta-analysis from Central and East Africa reported a prevalence of 15.9% (95% CI: 10.8%–21.0% (37). These figures highlight the comparatively lower prevalence reported in Colombia, which may reflect differences in healthcare access, diagnostic definitions, data collection methodologies, the denominator of live births, inclusion of NICU-only populations, and geographic coverage across studies.

However, research on PA in Latin America is limited. In Brazil, the mortality rate due to PA has been reported at 0.65 per 1,000 live births in various neonatal units (38). Similarly, the Iberoamerican Neonatology Network (SIBEN) reported that hypoxic-ischemic encephalopathy (HIE), a consequence of PA, affected 5.1% of neonates admitted to neonatal intensive care units (NICUs) with a mortality rate of 42% (14). This prevalence among Latin American NICUs belonging to the SIBEN closely aligns with the findings of the present study. Therefore, there is an urgent need for more robust and regionally representative data from Colombia and Latin America to better characterize the true burden of PA.

In contrast, the risk factors identified in this meta-analysis, MSAF, intrapartum fetal distress, and prolonged labor, are consistent with robust evidence from international meta-analyses reporting strong associations between these variables and PA (34–36). Similarly, other factors described in studies from South America and global reviews, such as emergency cesarean section, inadequate prenatal care, maternal anemia, low birth weight, labor induction, and non-cephalic presentation (14, 34–36), were confirmed as significant predictors in the qualitative synthesis. However, they could not be included in the meta-analysis because of the inconsistent reporting across the included studies.

It is noteworthy that some pooled OR, particularly for intrapartum fetal distress and prolonged second stage of labor, presented wide 95% CI, despite reaching statistical significance. This imprecision likely reflects the substantial heterogeneity observed among studies, differences in diagnostic definitions, and small sample sizes. These factors limit the strength of the observed associations and highlight the importance of conducting future studies with standardized diagnostic approaches, larger populations, and improved control of confounding variables to confirm these findings.

From a policy perspective, the identification of these risk factors suggests potential intervention points to strengthen maternal and perinatal health strategies in Colombia. Although the findings should be interpreted cautiously, they highlight the importance of reinforcing prenatal surveillance systems, ensuring timely access to obstetric and neonatal care, and promoting the use of standardized diagnostic criteria across healthcare facilities.

Strengthening targeted strategies for the management of high-risk pregnancies could facilitate the earlier recognition and prevention of complications associated with PA. Collaboration between healthcare providers and policymakers is essential to translate these preliminary findings into actionable improvements in perinatal care.

In other regions of Latin America and the Caribbean, the implementation of comprehensive maternal–neonatal health packages has been associated with up to a 23% reduction in deaths attributable to PA (39). In this context, the data from our review provides a useful starting point for guiding local research priorities and informing the design of future interventions aimed at reducing the burden of PA in Colombia.

The geographical distribution of the available studies represents another limitation. All studies were conducted in tertiary-level university-affiliated hospitals located in large Colombian cities, with no representation from rural or low-resource areas. This urban bias limits the generalizability of our findings to the broader national population. Recent national data have shown persistent and widening inequalities in infant outcomes across socioeconomic and geographic strata, with infants born in dispersed rural areas exhibiting an 8% higher risk of first-year mortality compared with those in urban centers (40). Such disparities highlight that the burden of PA may be underestimated in underserved regions where access to timely obstetric and neonatal care is limited. Future multicenter research including diverse geographic settings and health system levels is crucial to provide a more representative picture of PA in Colombia.

The initial study design intended to explore gestational age as a key factor influencing both the risk and pathophysiological profile of PA, recognizing that its causes and outcomes differ between preterm and term infants. However, only four of the included studies reported sufficient data to characterize the population by gestational age; therefore, this subgroup analysis could not be performed.

This study highlights the limited number of studies that have comprehensively addressed PA in Colombia and underscores the need for further research to better understand its prevalence, determinants, and clinical consequences. Unlike national mortality data, which provide only a partial picture, this analysis offers an initial synthesis of both the prevalence and associated risk factors.

Nevertheless, the findings must be interpreted with caution because of the small number of available studies, substantial heterogeneity, and variability in the diagnostic definitions, which should be interpreted as exploratory.

Rather than providing a definitive estimate or serving as a basis for clinical or policy decision-making, the results should be regarded as exploratory evidence that outlines current knowledge gaps and guides priorities for future research.

These findings emphasize the urgent need for standardized diagnostic criteria, multicenter data collection, and methodologically rigorous studies to generate reliable national estimates and to support evidence-based neonatal care and prevention strategies.