Am J Perinatol
DOI: 10.1055/s-0044-1779620
Original Article

Effect of Antenatal Magnesium Sulfate Exposure on Patent Ductus Arteriosus in Premature Infants

1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
2   Division of Perinatology, Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, Ankara, Turkey
,
Mehmet Seckin Ozisik
2   Division of Perinatology, Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, Ankara, Turkey
,
Doğacan Sarısoy
3   Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
Batuhan Aslan
4   Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, Ankara, Turkey
,
Maide Selin Çakır
4   Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, Ankara, Turkey
,
Ferhan Demirtaş
1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
Mehmet Gökhan Ramoğlu
5   Division of Pediatric Cardiology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
Tayfun Uçar
5   Division of Pediatric Cardiology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
Omer Erdeve
1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
Begum Atasay
1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
,
Acar Koc
2   Division of Perinatology, Department of Obstetrics and Gynecology, Ankara University Faculty of Medicine, Ankara, Turkey
,
Saadet Arsan
1   Division of Neonatology, Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
› Author Affiliations
Funding None.

Abstract

Objective Magnesium sulfate (MgSO4) provides effective fetal neuroprotection. However, there is conflicting evidence regarding the association between antenatal MgSO4 exposure and patent ductus arteriosus (PDA). Thus, herein, we aimed to evaluate the association between antenatal MgSO4 exposure and PDA.

Study Design Preterm infants born between 240/7 and 316/7 weeks of gestation were included in this retrospective study. Infants who died within the first 72 hours of life and those with significant congenital anomalies were excluded from the study. Echocardiographic and clinical assessment parameters were used to define PDA and hemodynamically significant PDA (hsPDA). Treatments were planned according to the standard protocols of the unit. The following data were collected from hospital medical records: perinatal characteristics, neonatal outcomes, detailed PDA follow-up findings, and maternal characteristics including MgSO4 exposure and doses.

Results Of the 300 included infants, 98 (32.6%) were exposed to antenatal MgSO4. hsPDA rates were similar in the infants exposed and not exposed to antenatal MgSO4, when adjusted for antenatal steroid administration, gestational age, and birth weight (OR: 1.6, 95% CI: 0.849–3.118, p = 0.146). The rates of PDA ligation and open PDA at discharge were similar between the groups. A cumulative MgSO4 dose of >20 g was associated with an increased risk of hsPDA (crude OR: 2.476, 95% CI: 0.893–6.864, p = 0.076; adjusted OR: 3.829, 95% CI: 1.068–13.728, p = 0.039). However, the cumulative dose had no effect on the rates of PDA ligation or open PDA at discharge. Rates of prematurity-related morbidities and mortality were similar between the groups.

Conclusion Although antenatal MgSO4 exposure may increase the incidence of hsPDA, it may not affect the rates of PDA ligation or open PDA at discharge. Further studies are required to better evaluate the dose-dependent outcomes and identify the MgSO4 dose that not only provides neuroprotection but also has the lowest risk of adverse effects.

Key Points

  • Antenatal exposure of MgSO4 may cause PDA.

  • Antenatal MgSO4 exposure may not increase the rates of PDA ligation or open PDA at discharge.

  • Further studies are required to better evaluate the dose-dependent outcomes and optimal MgSO4 dose.

Ethical Approval

Approval was obtained from the Ethics Committee of Ankara University Faculty of Medicine. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.




Publication History

Received: 22 August 2023

Accepted: 12 January 2024

Article published online:
06 February 2024

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  • References

  • 1 The American College of Obstetricians and Gynecologists. Committee Opinion No 652: Magnesium Sulfate Use in Obstetrics. Obstet Gynecol 2016; 127 (01) e52-e53
  • 2 Magee L, Sawchuck D, Synnes A, von Dadelszen P. Magnesium Sulphate For Fetal Neuroprotection Consensus Committee, Maternal Fetal Medicine Committee. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet Gynaecol Can 2011; 33 (05) 516-529
  • 3 Crowther CA, Brown J, McKinlay CJ, Middleton P. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2014; (08) CD001060
  • 4 Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am J Obstet Gynecol 2009; 200 (06) 595-609
  • 5 Costantine MM, Weiner SJ. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal–Fetal Medicine Units Network (MFMU). Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol 2009; 114 (2 Pt 1): 354-364
  • 6 Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009; (01) CD004661
  • 7 Jacquemyn Y, Zecic A, Van Laere D, Roelens K. The use of intravenous magnesium in non-preeclamptic pregnant women: fetal/neonatal neuroprotection. Arch Gynecol Obstet 2015; 291 (05) 969-975
  • 8 Satake K, Lee JD, Shimizu H. et al. Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells. Magnes Res 2004; 17 (01) 20-27
  • 9 Dice JE, Bhatia J. Patent ductus arteriosus: an overview. J Pediatr Pharmacol Ther 2007; 12 (03) 138-146
  • 10 Özkan H, Erdeve Ö, Kutman HGK. Turkish Neonatal Society guideline on the management of respiratory distress syndrome and surfactant treatment. Turk Pediatri Ars 2018; 53 (Suppl. 01) S45-S54
  • 11 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
  • 12 Bell MJ, Ternberg JL, Feigin RD. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (01) 1-7
  • 13 International Committee for the Classification of Retinopathy of Prematurity. The International Classification of retinopathy of prematurity revisited. Arch Ophthalmol 2005; 123 (07) 991-999
  • 14 Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (07) 1723-1729
  • 15 Mertens L, Seri I, Marek J. et al; Writing Group of the American Society of Echocardiography (ASE), European Association of Echocardiography (EAE), Association for European Pediatric Cardiologists (AEPC). Targeted neonatal echocardiography in the neonatal intensive care unit: practice guidelines and recommendations for training. Eur J Echocardiogr 2011; 12 (10) 715-736
  • 16 Magee LA, De Silva DA, Sawchuck D, Synnes A, von Dadelszen P. No. 376-Magnesium sulphate for fetal neuroprotection. J Obstet Gynaecol Can 2019; 41 (04) 505-522
  • 17 Fawcett WJ, Haxby EJ, Male DA. Magnesium: physiology and pharmacology. Br J Anaesth 1999; 83 (02) 302-320
  • 18 Takizawa T, Oda T, Arishima K. et al. A calcium channel blocker verapamil inhibits the spontaneous closure of the ductus arteriosus in newborn rats. J Toxicol Sci 1994; 19 (03) 171-174
  • 19 del moral T, Gonzalez-Quintero VH, Claure N, Vanbuskirk S, Bancalari E. Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants. J Perinatol 2007; 27 (03) 154-157
  • 20 Qasim A, Jain SK, Aly AM. Antenatal magnesium sulfate exposure and hemodynamically significant patent ductus arteriosus in premature infants. AJP Rep 2019; 9 (04) e353-e356
  • 21 Mittendorf R, Dambrosia J, Dammann O. et al. Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage. J Pediatr 2002; 140 (05) 540-546
  • 22 Scudiero R, Khoshnood B, Pryde PG, Lee KS, Wall S, Mittendorf R. Perinatal death and tocolytic magnesium sulfate. Obstet Gynecol 2000; 96 (02) 178-182
  • 23 Mikhael M, Bronson C, Zhang L, Curran M, Rodriguez H, Bhakta KY. Lack of evidence for time or dose relationship between antenatal magnesium sulfate and intestinal injury in extremely preterm neonates. Neonatology 2019; 115 (04) 371-378