Efficacy of Melatonin Administration in Pregnancy in Prevention of Neonatal Respiratory Distress Syndrome in Preterm Neonates: A Randomized Controlled Trial
-
Fahimeh Ghotbizadeh Vahdani
,
Mohammad Haddadi
,
Sepideh Ahmadi
,
Zahra Panahi
,
Sedigheh Hantoushzadeh
,
Nafisseh Saedi
,
Sedigheh Borna
,
Bahar Farshidfar
Abstract
Objective: Respiratory Distress Syndrome (RDA) is a common complication in premature neonates due to immature lungs, and antenatal corticosteroid administration could reduce its incidence. We aim to investigate the role of antenatal melatonin administration in preventing RDS among women with placenta accrete spectrum who usually mandate early delivery.
Materials and methods: This is a single-blinded randomized controlled trial performed in a tertiary hospital among women with placenta accrete spectrum. The melatonin group received Melatonin 10 mg/daily for two weeks before elective cesarean section in addition to corticosteroids, and the control group just received corticosteroids. The RDS occurrence was compared between two groups.
Results: In total, 60 participants were involved in the study (30 in the melatonin group and 30 in the control group). RDS was diagnosed for five (16.7%) neonates in the melatonin group and nine (30.0%) neonates in the control group (P-value= 0.228). Among neonates with RDS, no neonate in the melatonin group required intubation, and six (66.7%) neonates intubation needed in the control group (P = 0.016).
Conclusion: Antenatal melatonin administration may reduce the need for intubation in preterm neonates with RDS, though the lower incidence of RDS observed in the melatonin group was not statistically significant. The small number of RDS cases limits the ability to draw definitive conclusions regarding intubation rates and hospitalization duration. Larger-scale, multicenter studies with long-term follow-up are needed to validate these findings and better understand melatonin's role in neonatal respiratory care.
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2. American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Obstetric care consensus No. 7: placenta accreta spectrum. Obstet Gynecol. 2018;132(6):e259-75.
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11. Urata Y, Honma S, Goto S, Todoroki S, Iida T, Cho S, et al. Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med. 1999;27(7–8):838–47.
12. Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept. 2000;9(3–4):137–59.
13. Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci. 2000;7(6):444–58.
14. Pavlyshyn Н, Sarapuk I, Kozak K. The relationship of melatonin concentration in preterm infants and adverse outcomes in the late neonatal period. Biochem Med (Zagreb). 2023;33(1):010706.
15. Gitto E, Reiter RJ, Sabatino G, Buonocore G, Romeo C, Gitto P, et al. Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment. J Pineal Res. 2005;39(3):287–93.
16. Lee JY, Song H, Dash O, Park M, Shin NE, McLane MW, et al. Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model. Am J Reprod Immunol. 2019;82(3):e13151.
17. Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, et al. Effects of melatonin treatment in septic newborns. Pediatr Res. 2001;50(6):756–60.
18. Baeeri M, Didari T, Khalid M, Mohammadi-Nejad S, Daghighi SM, Farhadi R, et al. Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats. Molecules. 2021;26(21):6603.
19. Huang SH, Cao XJ, Liu W, Shi XY, Wei W. Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. J Pineal Res. 2010;48(2):109–16.
20. Habtemariam S, Daglia M, Sureda A, Selamoglu Z, Gulhan MF, Nabavi SM. Melatonin and Respiratory Diseases: A Review. Curr Top Med Chem. 2017;17(4):467–88.
21. Lee JY, Na Q, Shin NE, Shin HE, Kang Y, Chudnovets A, et al. Melatonin for prevention of fetal lung injury associated with intrauterine inflammation and for improvement of lung maturation. J Pineal Res. 2020;69(3):e12687.
22. Shainker SA, Coleman B, Timor-Tritsch IE, Bhide A, Bromley B, Cahill AG, et al. Special Report of the Society for Maternal-Fetal Medicine Placenta Accreta Spectrum Ultrasound Marker Task Force: Consensus on definition of markers and approach to the ultrasound examination in pregnancies at risk for placenta accreta spectrum. Am J Obstet Gynecol. 2021;224(1):B2–14.
23. Gharehbaghi MM, Yeganedoust S, Shaseb E, Fekri M. Evaluation of melatonin efficacy in prevention of bronchopulmonary dysplasia in preterm newborn infants. Turk J Pediatr. 2022;64(1):79–84.
24. Nouraeyan N, Lambrinakos-Raymond A, Leone M, Sant'Anna G. Surfactant administration in neonates: A review of delivery methods. Can J Respir Ther. 2014;50(3):91-5.
25. Ng EH, Shah V. Guidelines for surfactant replacement therapy in neonates. Paediatr Child Health. 2021;26(1):35-49. doi: 10.1093/pch/pxaa116. PMID: 33552321; PMCID: PMC7850281.
26. Goodyear MD, Krleza-Jeric K, Lemmens T. The Declaration of Helsinki. BMJ. 2007;335(7621):624-5.
27. González-Candia A, Veliz M, Araya C, Quezada S, Ebensperger G, Serón-Ferré M, et al. Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep. Am J Obstet Gynecol. 2016;215(2):245.e1-7.
28. Gitto E, Reiter RJ, Cordaro SP, La Rosa M, Chiurazzi P, Trimarchi G, et al. Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin. Am
J Perinatol. 2004;21(4):209–16.
29. Shawky Elfarargy M, Adam Ali D, Al-Ashmawy GM. Melatonin Supplementation as Adjuvant Therapy for the Prevention of Bronchopulmonary Dysplasia in Neonates. IJN. 2020;11(2):85–90.
30. Nakamura Y, Tamura H, Kashida S, Takayama H, Yamagata Y, Karube A, et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res. 2001;30(1):29–33.
31. Aly H, Elmahdy H, El-Dib M, Rowisha M, Awny M, El-Gohary T, et al. Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. J Perinatol. 2015;35(3):186–91.
2. American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Obstetric care consensus No. 7: placenta accreta spectrum. Obstet Gynecol. 2018;132(6):e259-75.
3. Vahdani FG, Shabani A, Haddadi M, Ghalandarpoor-Attar SM, Panahi Z, Hantoushzadeh S, et al. Novel markers of Doppler ultrasonography in the placenta accreta spectrum to predict complications. J Turk Ger
Gynecol Assoc. 2023 6;24(4):228-234.
4. Yadav S, Lee B. Neonatal respiratory distress syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
5. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;3(3):CD004454.
6. Mosayebi Z, Doroudian Motlagh M, Haddadi M, Shariat M. Magnesium as a Prognostic Factor in Neonates with Respiratory Distress Syndrome. Iranian journal of neonatology. 2023;14(4):28-34.
7. National Center for Complementary and Integrative Health. Melatonin: what you need to know. Bethesda (MD): NCCIH; [updated 2024 Mar 21; cited 2024 Mar 21]. Available from: https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know
8. Vine T, Brown GM, Frey BN. Melatonin use during pregnancy and lactation: A scoping review of human studies. Braz J Psychiatry. 2022;44(3):342–8.
9. Reiter RJ, Tan DX, Sainz RM, Mayo JC, Lopez-Burillo S. Melatonin: reducing the toxicity and increasing the efficacy of drugs. J Pharm Pharmacol. 2002;54(10):1299–321.
10. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann N Y Acad Sci. 2000;917:376–86.
11. Urata Y, Honma S, Goto S, Todoroki S, Iida T, Cho S, et al. Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med. 1999;27(7–8):838–47.
12. Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept. 2000;9(3–4):137–59.
13. Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci. 2000;7(6):444–58.
14. Pavlyshyn Н, Sarapuk I, Kozak K. The relationship of melatonin concentration in preterm infants and adverse outcomes in the late neonatal period. Biochem Med (Zagreb). 2023;33(1):010706.
15. Gitto E, Reiter RJ, Sabatino G, Buonocore G, Romeo C, Gitto P, et al. Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment. J Pineal Res. 2005;39(3):287–93.
16. Lee JY, Song H, Dash O, Park M, Shin NE, McLane MW, et al. Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model. Am J Reprod Immunol. 2019;82(3):e13151.
17. Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, et al. Effects of melatonin treatment in septic newborns. Pediatr Res. 2001;50(6):756–60.
18. Baeeri M, Didari T, Khalid M, Mohammadi-Nejad S, Daghighi SM, Farhadi R, et al. Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats. Molecules. 2021;26(21):6603.
19. Huang SH, Cao XJ, Liu W, Shi XY, Wei W. Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. J Pineal Res. 2010;48(2):109–16.
20. Habtemariam S, Daglia M, Sureda A, Selamoglu Z, Gulhan MF, Nabavi SM. Melatonin and Respiratory Diseases: A Review. Curr Top Med Chem. 2017;17(4):467–88.
21. Lee JY, Na Q, Shin NE, Shin HE, Kang Y, Chudnovets A, et al. Melatonin for prevention of fetal lung injury associated with intrauterine inflammation and for improvement of lung maturation. J Pineal Res. 2020;69(3):e12687.
22. Shainker SA, Coleman B, Timor-Tritsch IE, Bhide A, Bromley B, Cahill AG, et al. Special Report of the Society for Maternal-Fetal Medicine Placenta Accreta Spectrum Ultrasound Marker Task Force: Consensus on definition of markers and approach to the ultrasound examination in pregnancies at risk for placenta accreta spectrum. Am J Obstet Gynecol. 2021;224(1):B2–14.
23. Gharehbaghi MM, Yeganedoust S, Shaseb E, Fekri M. Evaluation of melatonin efficacy in prevention of bronchopulmonary dysplasia in preterm newborn infants. Turk J Pediatr. 2022;64(1):79–84.
24. Nouraeyan N, Lambrinakos-Raymond A, Leone M, Sant'Anna G. Surfactant administration in neonates: A review of delivery methods. Can J Respir Ther. 2014;50(3):91-5.
25. Ng EH, Shah V. Guidelines for surfactant replacement therapy in neonates. Paediatr Child Health. 2021;26(1):35-49. doi: 10.1093/pch/pxaa116. PMID: 33552321; PMCID: PMC7850281.
26. Goodyear MD, Krleza-Jeric K, Lemmens T. The Declaration of Helsinki. BMJ. 2007;335(7621):624-5.
27. González-Candia A, Veliz M, Araya C, Quezada S, Ebensperger G, Serón-Ferré M, et al. Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep. Am J Obstet Gynecol. 2016;215(2):245.e1-7.
28. Gitto E, Reiter RJ, Cordaro SP, La Rosa M, Chiurazzi P, Trimarchi G, et al. Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin. Am
J Perinatol. 2004;21(4):209–16.
29. Shawky Elfarargy M, Adam Ali D, Al-Ashmawy GM. Melatonin Supplementation as Adjuvant Therapy for the Prevention of Bronchopulmonary Dysplasia in Neonates. IJN. 2020;11(2):85–90.
30. Nakamura Y, Tamura H, Kashida S, Takayama H, Yamagata Y, Karube A, et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res. 2001;30(1):29–33.
31. Aly H, Elmahdy H, El-Dib M, Rowisha M, Awny M, El-Gohary T, et al. Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. J Perinatol. 2015;35(3):186–91.
| Files | ||
| Issue | Vol 19, No 3 (September 2025) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v19i3.20063 | |
| Keywords | ||
| Melatonin Respiratory Distress Syndrome Placenta Accreta | ||
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How to Cite
1.
Ghotbizadeh Vahdani F, Haddadi M, Ahmadi S, Panahi Z, Hantoushzadeh S, Saedi N, Borna S, Farshidfar B. Efficacy of Melatonin Administration in Pregnancy in Prevention of Neonatal Respiratory Distress Syndrome in Preterm Neonates: A Randomized Controlled Trial. J Family Reprod Health. 2025;19(3):240-246.
