Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Perinatal Medicine

Official Journal of the World Association of Perinatal Medicine

Editor-in-Chief: Dudenhausen, MD, FRCOG, Joachim W.

Ed. by Bancalari, Eduardo / Chappelle, Joseph / Chervenak, Frank A. / D'Addario , Vincenzo / Genc, Mehmet R. / Greenough, Anne / Grunebaum, Amos / Konje, Justin C. / Kurjak M.D., Asim / Romero, Roberto / Zalud, MD PhD, Ivica

9 Issues per year

IMPACT FACTOR 2017: 1.558
5-year IMPACT FACTOR: 1.653

CiteScore 2017: 1.26

SCImago Journal Rank (SJR) 2017: 0.594
Source Normalized Impact per Paper (SNIP) 2017: 0.684

See all formats and pricing
More options …
Volume 42, Issue 1


Influence of antenatal magnesium sulfate application on cord blood levels of brain-derived neurotrophic factor in premature infants

Muhammad Adrianes Bachnas
  • Corresponding author
  • Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Sebelas Maret University, Moewardi Hospital, Solo, Surakarta, Indonesia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Johanes Cornelius Mose
  • Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Padjadjaran University, Hasan Sadikin Hospital, Bandung, Indonesia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jusuf Sulaeman Effendi
  • Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Padjadjaran University, Hasan Sadikin Hospital, Bandung, Indonesia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Wiku Andonotopo
  • Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Indonesia University, Tangerang General District Hospital, Banten, Indonesia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-09-24 | DOI: https://doi.org/10.1515/jpm-2013-0137


Aim: To investigate the influence of antenatal magnesium sulfate (MgSO4) application on cord blood brain-derived neurotrophic factor (BDNF) levels – the first-line neuroprotection for preventing cerebral palsy in prematurely born infants.

Subjects and methods: A randomized controlled trial was conducted by observing 72 pregnant women who were divided into three groups: group I (preterm pregnancy with MgSO4), group II (preterm pregnancy without MgSO4), and group III (full-term pregnancy as control group). Groups I and II were selected by block permutation randomization on subjects. Inclusion criteria consisted of preterm pregnancy at 34 weeks of gestation or less who were in labor or having planned terminations and receiving antenatal corticosteroids. Exclusion criteria consisted of previous complications caused by MgSO4, previous history of antenatal MgSO4 application in the current pregnancy infant was born before 4 h administration of MgSO4 or unborn more than 72 h after maximum course of antenatal MgSO4 of 24 h, prolonged antenatal MgSO4 treatment (>24 h), refusal to participate, and emergent adverse events during the study. Group I was given intravenous MgSO4; initial dose was 4 g, which was maintained at 1 g/h up to maximum of 24 h. Meanwhile, groups II and III were not given any special treatment. BDNF was examined by ELISA by taking 5 mL cord blood sample shortly after birth. The result was statistically measured by ANOVA.

Results: The cord blood BDNF levels in premature infants with antenatal MgSO4 was significantly higher than in premature infants without antenatal MgSO4 (11,568 vs. 5027 pg/mL, P=0.000). Moreover, the result was statistically comparable to full-term infants (11,568 vs. 13,300 pg/mL, P=0.085).

Conclusion: The application of antenatal MgSO4 in preterm delivery increased cord blood BDNF levels, which could have a potential role on fetal neuroprotection. Further investigation is needed.

Keywords: Atenatal magnesium sulfate; brain-derived neurotrophic factor; neuroprotection; prematurity


  • [1]

    Afify MF, Mohamed GB, El-Maboud MA, Alrayhany MA. Brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels in newborn cord sera. J Pediatr. 2005;19:159–64.Google Scholar

  • [2]

    American College of Obstetricians and Gynecologists. Committee Opinion: Magnesium sulfate before anticipated preterm birth for neuroprotection; 2010:1–2. Available at: http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Magnesium_Sulfate_Before_Anticipated_Preterm_Birth_for_Neuroprotection.

  • [3]

    Anderson P, Doyle LW. Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. J Am Med Assoc. 2003;289:3264–72.Google Scholar

  • [4]

    Bain E, Middleton P, Crowther CA. Different magnesium sulphate regimens given to women at risk of preterm birth to help protect the baby’s brain and improve long term outcomes. Cochrane Database Syst Rev. 2012;1:1–3.Google Scholar

  • [5]

    Chouthai NS, Sampers J, Desai N, Smith GM. Changes in neurotrophin levels in umbilical cord blood from infants with different gestational ages and clinical conditions. Pediatr Res. 2003;53:965–9.Google Scholar

  • [6]

    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;200:595–609.Web of ScienceGoogle Scholar

  • [7]

    Costantine MM, Weiner SJ. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a metaanalysis. Am J Obstet Gynecol. 2009;114:354–64.Web of ScienceGoogle Scholar

  • [8]

    Crowther CA, Hiller JE, Doyle LW, Haslam RR. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. J Am Med Assoc. 2003;290:2669–76.Google Scholar

  • [9]

    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;(1):CD004661.Google Scholar

  • [10]

    Drummond PM, Colver AF. Analysis by gestational age of cerebral palsy in singleton births in north-east England 1970–94. Paediatr Perinat Epidemiol. 2002;16:172–80.Google Scholar

  • [11]

    Ferrer I. Neuronal death mechanisms in cerebral ischemia. Rev Neurol. 1999;29:515–21.PubMedGoogle Scholar

  • [12]

    Geremia NM, Pettersson LME, Hasmatali JC, Hryciw T, Danielsen N, Schreyer DJ, et al. Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons. Exp Neurol. 2010;223:128–42.Web of ScienceGoogle Scholar

  • [13]

    Golan H, Kashtuzki I, Hallak M, Sorokin Y, Huleihel M. Maternal hyopoxia during pregnancy induces fetal neurodevelopmental brain damage – a partial protection by magnesium sulfate. J Neurosci Res. 2004;78:430–41.CrossrefGoogle Scholar

  • [14]

    Grether JK, Cummins SK, Nelson KB. The California Cerebral Palsy Project. Paediatr Perinat Epidemiol. 1992;6:339–51.CrossrefPubMedGoogle Scholar

  • [15]

    Grether JK, Hoogstrate J, Walsh-Greene E, Nelson KB. Magnesium sulfate for tocolysis and risk of spastic cerebral palsy in premature children born to women without preeclampsia. Am J Obstet Gynecol. 2000;183:717–25.Google Scholar

  • [16]

    Hack M, Costello DW. Trends in the rates of cerebral palsy associated with neonatal intensive care of preterm children. Clin Obstet Gynecol. 2008;51:763–74.Web of ScienceGoogle Scholar

  • [17]

    Hallak M, Hotra JW, Kupsky WJ. Magnesium sulfate protection of fetal rat brain from severe maternal hypoxia. J Obstet Gynecol. 2000;96:124–8.Google Scholar

  • [18]

    Han BH, D’Costa A, Back SA, Parsadanian M, Patel S, Shah AR, et al. BDNF blocks caspase-3 activation in neonatal hypoxia-ischemia. Neurobiol Dis. 2000;7:38–53.PubMedCrossrefGoogle Scholar

  • [19]

    Hiroshi S, Tsuyomu I. Long term magnesium sulfate treatment as protection gainst hypoxic ischemic brain injury in seven day old rats. Am J Obstet Gynaecol. 2001;184:185–90.Google Scholar

  • [20]

    Huleihel M, Golan H, Hallak M. Intrauterine infection/inflammation during pregnancy and offspring brain damages: possible mechanism involved. Reprod Biol Endocrinol. 2004;2:1–8.Google Scholar

  • [21]

    Husson I, Rangon CM, Lelièvre V, Bemelmans AP, Sachs P, Mallet J, et al. BDNF-induced white matter neuroprotection and stage dependent neuronal survival following a neonatal excitotoxic challenge. Cereb Cortex Res. 2005;15:250–61.Google Scholar

  • [22]

    Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WEF, et al. Activated human T cells, B cells, and monocytes produce brain derived neurotrophic factor in vitro and in inflammatory brain lession: a neuroprotective role of inflammation. J Exp Med. 1999;189:865–70.Google Scholar

  • [23]

    King Edward Memorial Hospital Australia. Clinical Guidelines. Antenatal magnesium sulphate prior to preterm birth for neuro protection of the fetus post birth; 2010.Google Scholar

  • [24]

    Kuban KC, Leviton A. Cerebral palsy. N Engl J Med. 1994;330:188–95.Google Scholar

  • [25]

    Kuban KC, Leviton A, Pagano M, Fenton T, Strassfeld R, Wolff M. Maternal toxemia is associated with reduced incidence of germinal matrix hemorrhage in premature babies. J Child Neurol. 1992;7:70–6.PubMedCrossrefGoogle Scholar

  • [26]

    Lang UE, Günther L, Scheuch K, Klein J, Eckhart S, Hellweg R, et al. Higher BDNF concentrations in the hippocampus and cortex of an aggressive mouse strain. Behav Brain Res. 2009;197:246–9.Web of ScienceGoogle Scholar

  • [27]

    Lin W, Meng H, Lu Y, Wang Z, Li N, Cui L, et al. Neuronal injury and brain derived neurotrophic factor expression in a rat model of amygdala. Neural Regeneration Res. 2010;5:585–90.Google Scholar

  • [28]

    Marret S, Marpeau L, Benichou J. Benefit of magnesium sulfate given before very preterm birth to protect infant brain. J Am Acad Pediatrics. 2008;121:225–6.Google Scholar

  • [29]

    Marret S, Marpeau L, Zupan-Simunek V, Eurin D, Leveque C, Hellot MF, et al. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial. Br Med J Obstet Gynaecol. 2007;114:310–8.Google Scholar

  • [30]

    McDonald JW, Silverstein FS, Johnston MV. Magnesium reduces N-methyl-D-aspartate (NMDA)-mediated brain injury in perinatal rats. Neurosci Lett. 1990;109:234–8.Google Scholar

  • [31]

    Mittendorf R, Dambrosia J, Pryde PG, Lee KS, Gianopoulos JG, Besinger RE, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol. 2002;186:1111–8.Google Scholar

  • [32]

    Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008;359:262–73.Web of ScienceGoogle Scholar

  • [33]

    O’Shea TM, Klinepeter KL, Dillard RG. Prenatal events and the risk of cerebral palsy in very low birth weight infants. Am J Epidemiol. 1998;147:362–9.Google Scholar

  • [34]

    Petrini JR, Dias T, McCormick MC, Massolo ML, Green NS, Escobar GJ. Increased risk of adverse neurological development for late preterm infants. J Pediatr. 2009;154:169–76.Web of ScienceGoogle Scholar

  • [35]

    Petterson B, Nelson KB, Watson L, Stanley F. Twins, triplets, and cerebral palsy in births in Western Australia in the 1980s. Br Med J. 1993;307:1239–43.Google Scholar

  • [36]

    Pharoah PO, Cooke T, Johnson MA, King R, Mutch L. Epidemiology of cerebral palsy in England and Scotland, 1984–9. Arch Dis Child Fetal Neonatal Ed. 1998;79:F21–5.Google Scholar

  • [37]

    Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008;359:895–905.Web of ScienceGoogle Scholar

  • [38]

    Silbereis JC, Huang EJ, Back SA, Rowitch DH. Towards improved animal models of neonatal white matter injury associated with cerebral palsy. Dis Model Mech. 2010;3:678–88.PubMedGoogle Scholar

  • [39]

    SOGC Clinical Practice Guide lines, Magnesium sulphate for fetal neuroprotection; 2011.Google Scholar

  • [40]

    Stanley FJ. Survival and cerebral palsy in low birthweight infants: implications for perinatal care. Paediatr Perinat Epidemiol. 1992;6:298–310.PubMedCrossrefGoogle Scholar

  • [41]

    Turner RJ, Dasilva KW, O’Connor C, van den Heuvel C, Vink R. Magnesium gluconate offers no more protection than magnesium sulphate following diffuse traumatic brain injury in rats. J Am College Nutrition. 2004;23:541S–4S.CrossrefGoogle Scholar

  • [42]

    Vincer MJ, Allen AC, Joseph KS, Stinson DA, Scott H, Wood E. Increasing prevalence of cerebral palsy among very preterm infants: a population-based study. Pediatrics. 2006;118:e1621–6.Google Scholar

  • [43]

    Wittenberg GF. Neural plasticity and treatment across the lifespan for motor deficits in cerebral palsy. Dev Med Child Neurol. 2009;51:130–3.Web of ScienceGoogle Scholar

  • [44]

    Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med. 2006;355:685–94.Google Scholar

  • [45]

    Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage and counteract learning disability after traumatic brain injury in rats. J Am Med Assoc. 2004;21:1457–67.Google Scholar

  • [46]

    Xiaojie L, Zhihai L, Zhongren S. Effects of enriched environmental stimulation on brain development in cerebral palsy rats. Chinese J Rehabil Med. 2006;12:1–8.Google Scholar

About the article

Corresponding author: Muhammad Adrianes Bachnas, MD, Fetomaternal Division, Department of Obstetrics and Gynecology, Medical Faculty of Sebelas Maret University, Moewardi Hospital, Solo, Surakarta, Indonesia, Tel.: +628122692928, E-mail:

Received: 2013-06-13

Accepted: 2013-08-14

Published Online: 2013-09-24

Published in Print: 2014-01-01

Citation Information: Journal of Perinatal Medicine, Volume 42, Issue 1, Pages 129–134, ISSN (Online) 1619-3997, ISSN (Print) 0300-5577, DOI: https://doi.org/10.1515/jpm-2013-0137.

Export Citation

©2014 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Clément Chollat, Loic Sentilhes, and Stéphane Marret
Developmental Medicine & Child Neurology, 2018
María Martínez, Berta Soldevila, Anna Lucas, Inés Velasco, Lluis Vila, and Manel Puig-Domingo
Endocrinología, Diabetes y Nutrición (English ed.), 2018, Volume 65, Number 2, Page 107
María Martínez, Berta Soldevila, Anna Lucas, Inés Velasco, Lluis Vila, and Manel Puig-Domingo
Endocrinología, Diabetes y Nutrición, 2018, Volume 65, Number 2, Page 107
Sana Usman, Lin Foo, Jasmine Tay, Phillip R Bennett, and Christoph Lees
The Obstetrician & Gynaecologist, 2017, Volume 19, Number 1, Page 21
Xinli Xiang, Depeng Zhao, Chonglan Gao, Kai Wang, Qian Zhou, Jiuhong Kang, and Tao Duan
International Journal of Developmental Neuroscience, 2017, Volume 56, Page 52
S. Marret and P.-Y. Ancel
Journal de Gynécologie Obstétrique et Biologie de la Reproduction, 2016, Volume 45, Number 10, Page 1418

Comments (0)

Please log in or register to comment.
Log in