European Journal of Cardiovascular Medicine

Perinatal asphyxia is a major cause of neonatal death and disability, especially in low-resource settings.¹ It occurs when a newborn fails to breathe properly at birth, leading to oxygen deprivation and multiorgan dysfunction. WHO estimates it causes 2 million neonatal deaths annually, with the highest impact in low-income countries. Risk factors include maternal conditions (e.g., preeclampsia), fetal issues (e.g., prematurity), and complications during labor (e.g., prolonged labor).^2,3,4 Diagnosis is clinical, supported by biochemical tests and imaging. Management focuses on resuscitation and supportive care. Early detection, improved antenatal care, and better neonatal resuscitation can reduce its impact and improve survival rates.^5,6

This study evaluates the prevalence, clinical presentation, and outcomes of neonatal multiorgan dysfunction due to perinatal asphyxia in a rural tertiary care centre. It aims to highlight the burden, challenges in management, and effectiveness of current treatments. The findings will help develop targeted interventions to improve neonatal outcomes and reduce long-term complications.

Aim:

To comprehensively assess neonatal multiorgan dysfunction following perinatal asphyxia at a rural tertiary healthcare centre.

Objectives:

1. To assess neonatal multiorgan dysfunction after perinatal asphyxia.
2. To evaluate the patterns of involvement of each major organ/system and combinations of organ/systems in infants with post-asphyxia insult.

To describe associations between the dysfunction of each organ/system and long-term outcomes

This prospective observational study, conducted over 18 months in the NICU, examines term neonates with perinatal asphyxia... The sample includes 100 neonates meeting inclusion criteria viz. APGAR score <7 at 1 minute or umbilical cord blood pH <7 and exclusion criteria was preterm neonates (<37 weeks), congenital anomalies, metabolic disorders, infections, septic shock, birth trauma, or meconium aspiration syndrome.

Medical details including demographic information, perinatal history, clinical examination findings, laboratory investigations, imaging studies, and outcomes were recorded.

Variables Studied

1. Primary Outcome: Neonatal multiorgan dysfunction following perinatal asphyxia, assessed based on dysfunction in vital organ systems including the cardiovascular, respiratory, neurological, renal, hepatic, and haematological systems.
2. Secondary Outcomes: Duration of hospitalization, need for mechanical ventilation, incidence of complications such as sepsis or intraventricular haemorrhage, and mortality rates.

Data Analysis: Data analysed using appropriate statistical methods. Descriptive statistics were used to summarize demographic and clinical characteristics of the study population. Continuous variables were presented as means with standard deviations or medians with interquartile ranges, while categorical variables were presented as frequencies and percentages. Comparative analyses were performed using appropriate statistical tests, such as t-tests or chi-square tests, as applicable.

Ethical approval was obtained from the Institutional Review Board.

Patient confidentiality was strictly maintained, and informed consent was waived as there was no any intervention.

There were 55 males (55%) and 45 females (45%) in the study. Among 66 Neonates born through vaginal delivery, 53 (80.30%) had moderately depressed APGAR score & 13 (19.70%) had severely depressed APGAR score. Among 34 neonates with LSCS, 24 (70.59%) had moderately depressed APGAR score & 10 (29.41%) had severely depressed APGAR score. Most babies (50%,) were born between 38 and 40 weeks gestation, no significant association observed with APGAR score with gestational age.

It was observed that most of the neonates i.e.56 (72.72%) with birth weight 2.5-3 kg had moderately depressed APGAR score and 21(27.26%) had severely depressed score. Among the neonates with 3-3.5 kg birth weight 20(66.67%) neonates had moderately depressed APGAR score and 10(33.33%) neonates had severely depressed APGAR score. Among the neonates with birth weight birth weight 3.5-4 kg 6(75%) had moderately depressed score and 2(25%) had severely depressed score.

Table 1: Maternal Risk Factors by APGAR Score Severity

The table 1 shows the prevalence of various maternal risk factors in neonates with different levels of APGAR score severity. The results indicate that prolonged labor, leaking PV > 12 hours and PIH were significantly associated with the severity of the APGAR score (p-values < 0.05).

There was no significant difference found in the distribution of SERNAT staging between males and females (p-value = 0.99). There was no significant difference in the distribution of mild or moderate encephalopathy between the two genders.

Table 2: Cardiovascular System Conditions by APGAR Score Severity Percentage

Hypotension was significantly associated with the severity of the APGAR score (p-values < 0.05) as shown in table 2.

Table 3: Renal System Conditions by APGAR Score Severity

Urine output ≤0.5ml/kg/hr was significantly associated with the severity of the APGAR score (p-values < 0.05) as shown in table 3.

Table 4: Distribution of study participants with Multi Organ Dysfunction Syndrome (MODS) as per involvement of Respiratory system

Significant association was found between APGAR severity and respiratory failure requiring mechanical ventilation as depicted in table 4.

Table 5: Gastrointestinal System Conditions by APGAR Score Severity

The result in table 5 indicates that feeding disturbances and NNE were significantly associated with the severity of the APGAR score (p-values < 0.05).

There was no significant association with hematologic conditions like thrombocytopenia or coagulation abnormality and low APGAR score.

Table 6: Outcomes of Neonates with Multiorgan Dysfunction by APGAR Score Severity

The table 6 shows the significant association between outcomes like survival and death and APGAR score.

Outcome of the neonates with MODS was assessed at 3 month by Trivandrum Development Screening Chart (TDSC). It was observed that out of 32 moderately depressed survived babies 3 had neurological impairment and 29 had normal development, however all (i.e.4) severely depressed babies developed neurological impairment.

The sample consisted of 55 males and 45 females, representing 55% and 45% of the population, respectively. In simpler terms, the study included a balanced sample of male and female neonates, and this gender distribution is unlikely due to chance. This strengthens the generalizability of the study's findings, as they are likely to represent the broader population of neonates experiencing similar conditions. When comparing our findings to the studies by Pattar Ramesh, Singh K S, and Iribarren et al., it's evident that the gender distribution falls within the range reported by these previous investigations. Pattar Ramesh et al. reported a higher proportion of males (71.9%). Singh K S et al. reported , the proportion of males in Singh K S's study was even higher at 76%, suggesting a potential bias towards male neonates in their sample. Iribarren et al. reported, while the proportion of males in Iribarren et al.'s study was lower than in the other two, it still exceeded the gender balance observed in our study. ^7,8,9

Mode of delivery and gestational age :( Table no. 2 & 3)

This finding suggests a potential preference for vaginal delivery in this specific study population. However, the chi-square test only indicates a statistical difference, not necessarily a cause-and-effect relationship. Further investigation would be needed to understand the reasons behind the observed delivery mode distribution. Pattar Ramesh et al. reported, there were no home deliveries. 36.8% of the babies were delivered by LSCS and 63.2% were delivered vaginally.⁷ While Singh K S et al. reported , 22 % of the babies were delivered by LSCS and78 % were delivered vaginally⁸ Iribarren et al. reported , 26 % of the babies were delivered by LSCS and74 % were delivered vaginally. ⁹

Maternal Risk Factors for Multiorgan Dysfunction

These findings underscore the crucial role of maternal health and well-being during pregnancy in determining neonatal outcomes. Kuppusamy P, et al. reported, the prevalence of high-risk pregnancies among Indian women was 49.4%, with 33% of women having a single high-risk, and 16.4% having multiple high-risk pregnancies.¹⁰ Watson RS et al. reported, pediatric MODS is common among PICU patients, occurring in up to 57% depending on the population studied.¹¹

SERNAT Staging Distribution by Gender and SERNAT Staging in participants with MODs

Specifically, males were more likely to have severe encephalopathy compared to females. However, there was no significant difference in the distribution of mild or moderate encephalopathy between the two genders. These findings suggest that gender may be a factor in the severity of neonatal encephalopathy. Similar findings were reported by Pattar Ramesh et al. while other authors Richmond-Virginia Njie AE, et al. not included this parameter in their research work. ^7,12

Distribution of Cardiovascular Involvement

This analysis compares our study's findings on the association between APGAR scores and CVS complications with those reported by Pattar Ramesh et al. and Singh P et al. In our study, we examined two main CVS conditions: cardiac dysfunction (defined as heart rate outside the normal range) and hypotension (low blood pressure). The results indicate that hypotension was significantly associated with the severity of the APGAR score (p-values < 0.05). Pattar Ramesh et al. focused on signs of poor perfusion in neonates, emphasizing clinical signs indicative of compromised circulation and tissue perfusion(101),  While our study assessed specific CVS conditions in relation to APGAR scores. Singh P et al.'s meticulous approach to detecting cardiac abnormalities complements our study's focus on the association between APGAR scores and CVS conditions. All these three studies recognize that neonates exhibiting signs of distress or low APGAR scores are more susceptible to cardiovascular complications. Pattar Ramesh et al. and Singh P et al., there is a consistent recognition of the vulnerability of distressed neonates to cardiovascular dysfunctions such as hypotension and cardiac abnormalities.^7,8

Distribution of Renal Involvement

This analysis compares our study's findings on the association between APGAR scores and renal system complications with those reported by Pattar Ramesh et al. and Singh K et al. (101) Both studies identified elevated serum creatinine as a significant indicator of renal dysfunction in neonates with low APGAR scores. Singh K et al. reported a higher overall prevalence (52.1%) of renal involvement compared to our study. This could be due to differences in study populations or diagnostic criteria. A notable percentage (5.7%) of neonates in Singh K et al.'s study developed AKI requiring renal replacement therapy, indicating severe renal impairment. Our study did not report on the necessity for such interventions. Our study, along with those of Pattar Ramesh et al. and Singh K et al., underscores the significant impact of asphyxia and low APGAR scores on renal function in neonates. The consistent finding across all studies is that renal complications are more prevalent and severe in neonates with lower APGAR scores.^7,8

Distribution of Respiratory system involvement:

Study conducted by Pattar Ramesh et al. revealed that respiratory system was most frequently involved system other than Central Nervous system in neonates with MODS after perinatal asphyxia. Overall involvement of respiratory system was seen in 63.1% neonates with asphyxia. Singh K et al. revealed that respiratory system was involved in 44% of neonates with birth asphyxia. This was more compared to our study._7,8

Distribution of Gastrointestinal Involvement

Using the chi-square test, we found a significant association between lower APGAR scores and the presence of GI complications (p-values < 0.05). Specifically among participants with GI involvement 43.3% had feeding disturbances, 29.54% had developed NNE, and 27.2% had transaminase disturbances. Singh K et al. reported that GI involvement was the least common organ system affected, observed in 4.7% of cases among asphyxiated neonates. (102) Both our study and that of Pattar RS identified NEC as a critical GI condition in neonates. However, our study also included feeding disturbances and transaminase disturbances, providing a broader assessment of GI involvement. In comparison, Singh K et al. reported low prevalence of GI involvement, occurring exclusively in the context of multiorgan dysfunction. (102) Pattar RS highlighted NEC as a significant GI complication but did not provide prevalence data or correlations with APGAR scores.^7,8

Distribution of Hematologic Involvement

Our study reported a higher prevalence (46.0%) compared to 27.8% in Singh K et al.'s study. This difference may stem from variations in study populations or the severity of asphyxia among the neonates. We found prolonged PT/INR values in 15% of cases, whereas Singh K et al. reported elevated prothrombin time in 13.6% of neonates. While Singh K et al. reported anemia and hyperbilirubinemia, our study did not specifically assess these conditions, focusing instead on thrombocytopenia, prolonged clotting times, and DIC. (102) Both our study and Singh K et al.'s research highlights a significant association between low APGAR scores and hematologic complications in neonates. ⁸

Clinical outcome:

It was observed that out of 32 moderately depressed survived babies 3 had neurological impairment and 29 are normally developed, however All (i.e.4) severely depressed babies developed neurological impairment. Study conducted by Gedefaw GD et al. revealed that overall incidence of mortality among the neonates with birth asphyxia was 38.86/1000 (95% CI: 33.85– 44.60).¹³

Significance of the Study

Understanding the prevalence and severity of MOD in neonates after perinatal asphyxia is essential for several reasons. First, it helps quantify the burden of disease in a specific population, providing a basis for healthcare planning and resource allocation. Our study provides a detailed assessment of which organ systems are most commonly affected by MOD. This information is critical for clinicians to prioritize diagnostic evaluations and interventions. For example, knowing that CNS involvement is prevalent can lead to early implementation of neuroprotective strategies such as therapeutic hypothermia. Our study found that low birth weight, prematurity, prolonged labor, and maternal hypertension were significant risk factors for the development of MODS. This aligns with findings from other studies, such as those by Bekele GG et al. and Mamo SA et al. ^13,14

 Additionally, understanding the effectiveness of different management strategies can help refine treatment protocols to improve survival rates and reduce long-term complications.

1. Woday A, Muluneh A, St Denis C. Birth asphyxia and its associated factors among newborns in public hospital, northeast Amhara, Ethiopia. PLoS One. 2019 Dec 20;14(12):e0226891.
2. Wosenu L, Worku AG, Teshome DF, Gelagay AA. Determinants of birth asphyxia among live birth newborns in University of Gondar referral hospital, northwest Ethiopia: A case-control study. PloS one. 2018;13(9):e0203763.
3. Lee AC, Mullany LC, Tielsch JM, Katz J, Khatry SK, LeClerq SC, Adhikari RK, Shrestha SR, Darmstadt GL. Risk factors for neonatal mortality due to birth asphyxia in southern Nepal: a prospective, community-based cohort study. Pediatrics. 2008 May;121(5):e1381-90
4. Golubnitschaja O, Yeghiazaryan K, Cebioglu M, Morelli M, Herrera-Marschitz M. Birth asphyxia as the major complication in newborns: moving towards improved individual outcomes by prediction, targeted prevention and tailored medical care. EPMA J. 2011 Jun;2(2):197-210
5. Biban, P., Silvagni, D. (2016). Early Detection of Neonatal Depression and Asphyxia. In: Buonocore, G., Bracci, R., Weindling, M. (eds) Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-319-18159-2_178-1
6. Boskabadi H, Zakerihamidi M, Moradi A. Predictive value of biochemical and hematological markers in prognosis of asphyxic infants. Caspian J Intern Med. 2020 Fall;11(4):377-383
7. Pattar RS, Raj A, Yelamali BC. Incidence of multiorgan dysfunction in perinatal asphyxia. Int J Contemp Pediatr 2015;2:428-32.
8. Singh KS. A study of multiorgan dysfunction in asphyxiated neonates. Indian J Pediatr. 2016;3(2):123-45.
9. Iribarren I, Hilario E, Álvarez A, Alonso-Alconada D. Neonatal multiple organ failure after perinatal asphyxia. An Pediatr (Engl Ed). 2022 Oct;97(4):280.e1-280.e8. doi: 10.1016/j.anpede.2022.08.010.
10. Kuppusamy P, Prusty RK, Kale DP. High-risk pregnancy in India: Prevalence and contributing risk factors - a national survey-based analysis. J Glob Health. 2023 Sep 15;13:04116
11. Watson RS, Crow SS, Hartman ME, Lacroix J, Odetola FO. Epidemiology and Outcomes of Pediatric Multiple Organ Dysfunction Syndrome. Pediatr Crit Care Med. 2017 Mar;18(3_suppl Suppl 1):S4-S16.
12. Njie AE, Nyandiko WM, Ahoya PA, Moutchia JS. A comparative analysis of APGAR score and the gold standard in the diagnosis of birth asphyxia at a tertiary health facility in Kenya. PLoS One. 2023 May 24;18(5):e0285828.
13. Gedefaw GD, Abate AT, Worku DT, Ayenew ME, Daka DT. Length of hospital stay and its factor associated among neonates with perinatal asphyxia in the Northwest Amhara Region, Northwest Ethiopia 2023: a multicentre retrospective cross-sectional study. BMJ Open. 2025 Feb 5;15(2):e087995. doi: 10.1136/bmjopen-2024-087995. PMID: 39909526; PMCID: PMC11800223.
14. Bekele GG, Roga EY, Gonfa DN, et al. Incidence and predictors of mortality among neonates admitted with birth asphyxia to neonatal intensive care unit of West Shewa Zone Public Hospitals, Central Ethiopia. BMJ Paediatrics Open 2024;8:e002403. doi:10.1136/ bmjpo-2023-002403
15. Mamo SA, Teshome GS, Tesfaye T, Goshu AT (2022) Perinatal asphyxia and associated factors among neonates admitted to a specialized public hospital in South Central Ethiopia: A retrospective cross-sectional study. PLOS ONE 17(1): e0262619. https://doi.org/10.1371/journal.pone.0262619