Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

Journal of Perinatology volume 31, pages 21–24 (2011)Cite this article

Subjects

Abstract

Objective:

The aim of this study is to evaluate the influence of antenatal magnesium sulfate (MgSO4) treatment on the clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis and on that of symptomatic patent ductus arteriosus (sPDA) to indomethacin treatment in premature neonates.

Study Design:

This is a retrospective study of 160 consecutively admitted neonates with a gestational age of <28 weeks (41 MgSO4 exposed and 119 controls) who received indomethacin prophylaxis.

Result:

Incidence of early closure of the ductus arteriosus was lower in the MgSO4-exposed neonates than in the control group (59 vs 84%, respectively; P=0.002), whereas incidence of an sPDA was higher (46 vs 24%, respectively; P=0.006). Response to indomethacin treatment was similar between the two groups. Logistic regression analysis indicated increased risk of failure of early ductus arteriosus closure following antenatal MgSO4 treatment (odds ratio, 4.03; P=0.002).

Conclusion:

In extremely preterm neonates, antenatal MgSO4 treatment reduces clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis but not that of sPDA to indomethacin treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Norwitz ER, Robinson JN, Challis JR . The control of labor. N Engl J Med 1999; 341: 660–666.

    Article  CAS  Google Scholar 

  2. Lewis DF . Magnesium sulfate: the first-line tocolytic. Obstet Gynecol Clin North Am 2005; 32: 485–500.

    Article  Google Scholar 

  3. Greene MF . Magnesium sulfate for preeclampsia. N Engl J Med 2003; 348: 275–276.

    Article  Google Scholar 

  4. Duley L, Gulmezoglu AM, Henderson-Smart DJ . Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Systemic Reviews 2003, Issue 2. Art. no.: CD000025.

  5. Mittendorf R, Dammann O, Lee KS . Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor. J Perinatol 2006; 26: 57–63.

    Article  CAS  Google Scholar 

  6. Grimes DA, Nanda K . Magnesium sulfate tocolysis: time to quit. Obstet Gynecol 2006; 108: 986–989.

    Article  CAS  Google Scholar 

  7. Elliott JP, Lewis DF, Morrison JC, Garite TJ . In defense of magnesium sulfate. Obstet Gynecol 2009; 113: 1341–1348.

    Article  CAS  Google Scholar 

  8. Hermes-DeSantis ER, Clyman RI . Patent ductus arteriosus: pathophysiology and management. J Perinatol 2006; 26 (Suppl 1): S14–S18; discussion S22–S23.

    Article  Google Scholar 

  9. Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344: 1966–1972.

    Article  CAS  Google Scholar 

  10. Fowlie PW, Davis PG . Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Systemic Reviews 2002, Issue 3. Art. no.: CD000174.

  11. 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: 154–157.

    Article  CAS  Google Scholar 

  12. Kovalcik V . The response of the isolated ductus arteriosus to oxygen and anoxia. J Physiol 1963; 169: 185–197.

    Article  CAS  Google Scholar 

  13. Nakanishi T, Gu H, Hagiwara N, Momma K . Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit. Circ Res 1993; 72: 1218–1228.

    Article  CAS  Google Scholar 

  14. Zhang A, Cheng TP, Altura BM . Magnesium regulates intracellular free ionized calcium concentration and cell geometry in vascular smooth muscle cells. Biochim Biophys Acta 1992; 1134: 25–29.

    Article  CAS  Google Scholar 

  15. Yoshimura M, Oshima T, Matsuura H, Ishida T, Kambe M, Kajiyama G . Extracellular Mg2+ inhibits capacitative Ca2+ entry in vascular smooth muscle cells. Circulation 1997; 95: 2567–2572.

    Article  CAS  Google Scholar 

  16. Satake K, Lee JD, Shimizu H, Uzui H, Mitsuke Y, Yue H et al. Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells. Magnes Res 2004; 17: 20–27.

    CAS  PubMed  Google Scholar 

  17. Toyoshima K, Momma K, Nakanishi T . Fetal reversed constrictive effect of indomethacin and postnatal delayed closure of the ductus arteriosus following administration of transplacental magnesium sulfate in rats. Neonatology 2009; 96: 125–131.

    Article  CAS  Google Scholar 

  18. Donovan EF, Tsang RC, Steichen JJ, Strub RJ, Chen IW, Chen M . Neonatal hypermagnesemia: effect on parathyroid hormone and calcium homeostasis. J Pediatr 1980; 96: 305–310.

    Article  CAS  Google Scholar 

  19. Rantonen T, Kaapa P, Jalonen J, Ekblad U, Peltola O, Valimaki I et al. Antenatal magnesium sulphate exposure is associated with prolonged parathyroid hormone suppression in preterm neonates. Acta Paediatr 2001; 90: 278–281.

    Article  CAS  Google Scholar 

  20. Stigson L, Kjellmer I . Serum levels of magnesium at birth related to complications of immaturity. Acta Paediatr 1997; 86: 991–994.

    Article  CAS  Google Scholar 

  21. Cotton DB, Strassner HT, Hill LM, Schifrin BS, Paul RH . Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study. J Reprod Med 1984; 29: 92–97.

    CAS  PubMed  Google Scholar 

  22. Tolsa JF, Gao Y, Raj JU . Developmental change in magnesium sulfate-induced relaxation of rabbit pulmonary arteries. J Appl Physiol 1999; 87: 1589–1594.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Satoshi Nakago for his thoughtful review of the paper.

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Takatsuki General Hospital, Osaka, Japan

    Y Katayama, H Minami, M Enomoto, T Takano, S Hayashi & Y K Lee

Authors
  1. Y Katayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Minami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Enomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Takano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y K Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y Katayama.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katayama, Y., Minami, H., Enomoto, M. et al. Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates. J Perinatol 31, 21–24 (2011). https://doi.org/10.1038/jp.2010.62

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2010.62

Keywords

This article is cited by

Search

Advanced search

Quick links