Serum lactate dehydrogenase as an early diagnostic biomarker to differentiate respiratory distress syndrome from transient tachypnea of the newborn

Authors

  • Raid M. R. Umran Department of Pediatrics, College of Medicine, University of Kufa, Najaf, Iraq https://orcid.org/0000-0002-5921-4770
  • Karar A. Abd Department of Pediatrics, Al Zahra Teaching Hospital, Najaf Health Directorate, Najaf, Iraq

DOI:

https://doi.org/10.18203/2349-3291.ijcp20260733

Keywords:

RDS, TTN, Transient tachypnea of the newborn, LDH, Neonatal biomarkers

Abstract

Background: Early differentiation between respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN) remains clinically challenging, particularly in settings where imaging and advanced diagnostics may be delayed. Lactate dehydrogenase (LDH) is a marker of cellular injury and hypoxic stress and may assist in early etiologic discrimination. Objectives of the study were to evaluate the diagnostic performance of serum LDH measured within the first 12 hours of life in differentiating RDS from TTN, and to examine whether LDH provides independent diagnostic value beyond gestational age and birthweight.

Methods: In this prospective diagnostic study, 151 neonates were enrolled: 50 normal controls, 63 with TTN, and 38 with RDS. Serum LDH levels were measured within 12 hours of birth. Group comparisons were performed using appropriate parametric or non-parametric tests. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Univariable and multivariable logistic regression models were constructed to evaluate the independent association of LDH with RDS.

Results: LDH levels differed significantly across groups, demonstrating a stepwise increase from normal neonates to TTN and RDS (p<0.001). In symptomatic infants (TTN versus RDS), LDH showed good discriminatory accuracy (AUC=0.84; 95% CI: 0.75–0.92). A cutoff of 657 U/l yielded 97.4% sensitivity and 69.8% specificity. In univariable analysis, LDH predicted RDS (OR per 100 U/l=1.25; 95% CI: 1.08–1.45; p=0.003). However, after adjustment for gestational age and birthweight, LDH was no longer independently associated with RDS.

Conclusions: Serum LDH demonstrates good early discriminatory performance for differentiating RDS from TTN and shows a biologically plausible gradient across disease severity. However, its association is largely mediated by prematurity and illness severity. LDH may serve as a useful adjunctive biomarker but should be interpreted in conjunction with perinatal and clinical parameters.

Metrics

Metrics Loading ...

References

Orloff KE, Turner DA, Rehder KJ. The Current State of Pediatric Acute Respiratory Distress Syndrome. Pediatr Allergy Immunol Pulmonol. 2019;32(2):35-44. DOI: https://doi.org/10.1089/ped.2019.0999

Qari SA, Alsufyani AA, Muathin SH, Margoushy NE. Prevalence of Respiratory Distress Syndrome in Neonates. Egyptian J Hospital Med. 2018;70(2):257-64. DOI: https://doi.org/10.12816/0043086

Edwards MO, Kotecha SJ, Kotecha S. Respiratory distress of the term newborn infant. Paediatr Respir Rev. 2013;14(1):29-37. DOI: https://doi.org/10.1016/j.prrv.2012.02.002

Negi R, Pande D, Karki K, Kumar A, Khanna RS, Khanna HD. A novel approach to study oxidative stress in neonatal respiratory distress syndrome. BBA Clin. 2014;3:65-9. DOI: https://doi.org/10.1016/j.bbacli.2014.12.001

Yoon SJ, Han JH, Cho KH, Park J, Lee SM, Park MS. Tools for assessing lung fluid in neonates with respiratory distress. BMC Pediatr. 2022;22(1):354. DOI: https://doi.org/10.1186/s12887-022-03361-8

Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet. 2022;400(10358):1145-56. DOI: https://doi.org/10.1016/S0140-6736(22)01485-4

Silveira Neves G, Silveira Nogueira Reis Z, Maia de Castro Romanelli R, Dos Santos Nascimento J, Dias Sanglard A, Batchelor J. The role of chest X-ray in the diagnosis of neonatal respiratory distress syndrome: a systematic review concerning low-resource birth scenarios. Glob Health Action. 2024;17(1):2338633. DOI: https://doi.org/10.1080/16549716.2024.2338633

Halvorsen CP, Olson L, Araújo AC, Karlsson M, Nguyễn TT, Khu DTK, et al. A rapid smartphone-based lactate dehydrogenase test for neonatal diagnostics at the point of care. Sci Rep. 2019;9(1):9301. DOI: https://doi.org/10.1038/s41598-019-45606-0

Mehta R, Scheffler M, Tapia L, Aideyan L, Patel KD, Jewell AM, et al. Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity. Influenza Other Respir Viruses. 2014;8(6):617-25. DOI: https://doi.org/10.1111/irv.12276

Besiri K, Begou O, Lallas K, Kontou A, Agakidou E, Deda O, et al. Gastric Fluid Metabolomics Predicting the Need for Surfactant Replacement Therapy in Very Preterm Infants Results of a Case-Control Study. Metabolites. 2024;14(4):196. DOI: https://doi.org/10.3390/metabo14040196

Ider M, Naseri A, Ok M, Uney K, Erturk A, Durgut MK. Biomarkers in premature calves with and without respiratory distress syndrome. J Vet Intern Med. 2021;35(5):2524-33. DOI: https://doi.org/10.1111/jvim.16217

Majors CE, Smith CA, Natoli ME, Kundrod KA, Richards-Kortum R. Point-of-care diagnostics to improve maternal and neonatal health in low-resource settings. Lab. Chip. 2017;17:3351-87. DOI: https://doi.org/10.1039/C7LC00374A

Sun H, Xu F, Xiong H, Kang W, Bai Q, Zhang Y, et al. Characteristics of respiratory distress syndrome in infants of different gestational ages. Lung. 2013;191(4):425-33. DOI: https://doi.org/10.1007/s00408-013-9475-3

Hermansen CL, Mahajan A. Newborn Respiratory Distress. Am Fam Physician. 2015;92(11):994-1002.

Moustafa A, Mohamed Ahmed M, El-Mazary A. Can Serum Lactate Dehydrogenase Differentiate between Respiratory Distress Syndrome (RDS) and Transient Tachypnea of Newborn (TTN) in Preterm Neonates? Ann Neonatol. 2024;6(2):92-101.

Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2023 Update. Neonatology. 2023;120(1):3-23. DOI: https://doi.org/10.1159/000528914

An YS, Kim IU, Yang MY, Jeong H, Kim H. Serum enzymes in predicting transient tachypnea of newborn and respiratory distress syndrome. Korean J Perinatol. 2014;25(4):284-91. DOI: https://doi.org/10.14734/kjp.2014.25.4.284

Lee M, Lee N, Bae MH, Han YM, Park KH, Byun SY, et al. Using lactate dehydrogenase to predict the severity of respiratory distress in term newborn infants with no perinatal asphyxia. Turk J Pediatr. 2021;63(3):393-403. DOI: https://doi.org/10.24953/turkjped.2021.03.006

Elfarargy MS, Al-Ashmawy GM, Abu-Risha S. Novel predictor markers for early differentiation between transient tachypnea of newborn and respiratory distress syndrome in neonates. Int J Immunopathol Pharmacol. 2021;35:20587384211000554. DOI: https://doi.org/10.1177/20587384211000554

Srinivasan S, Aggarwal N, Makhaik S, Jhobta A, Kapila S, Bhoil R. Role of lung ultrasound in diagnosing and differentiating transient tachypnea of the newborn and respiratory distress syndrome in preterm neonates. J Ultrason. 2022;22(88):e1-e5. DOI: https://doi.org/10.15557/JoU.2022.0001

Atay FY, Kutman GK, Bidev D, Oguz SS. The Role of Cardiovascular and Inflammatory Markers in Elucidating the Etiology of Respiratory Distress in the Newborn. Haydarpaşa Numune Med J. 2019;59(4):370-4.

Ismail AQ, Gandhi A. Using CRP in neonatal practice. J Matern Fetal Neonatal Med. 2015;28(1):3-6. DOI: https://doi.org/10.3109/14767058.2014.885499

De Bernardo G, De Santis R, Giordano M, Sordino D, Buonocore G, Perrone S. Predict respiratory distress syndrome by umbilical cord blood gas analysis in newborns with reassuring Apgar score. Ital J Pediatr. 2020;46(1):20. DOI: https://doi.org/10.1186/s13052-020-0786-8

Najafian B, Aminsaburi A, Fakhraei SH, Afjeh A, Eghbal F, Noroozian R. Predicting Factors of INSURE Failure in Low Birth Weight Neonates with RDS; A Logistic Regression Model. Iran J Neonatol. 2015;5(4):30-4.

Downloads

Published

2026-03-06

How to Cite

Umran, R. M. R., & Abd, K. A. (2026). Serum lactate dehydrogenase as an early diagnostic biomarker to differentiate respiratory distress syndrome from transient tachypnea of the newborn. International Journal of Contemporary Pediatrics, 13(4), 547–552. https://doi.org/10.18203/2349-3291.ijcp20260733

Issue

Section

Original Research Articles