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800 mg of Magnesium early in 3rd trimester significantly increased brain activity in preterm infants – RCT May 2024

Prenatal Magnesium Sulfate and Functional Connectivity in Offspring at Term-Equivalent Age

JAMA Netw Open. 2024;7(5):e2413508. doi:10.1001/jamanetworkopen.2024.13508
Steven Ufkes, MSc1,2; Eleanor Kennedy, PhD3; Tanya Poppe, PhD4; et al Steven P. Miller, MDCM, MAS1,2; Benjamin Thompson, PhD3,5,6; Jessie Guo, PhD7; Jane E. Harding, DPhil, MBChB3; Caroline A. Crowther, MBChB, MD3

Key Points

  • Question Is magnesium sulfate (MgSO4) administered to women at risk of imminent preterm birth associated with increased functional connectivity on magnetic resonance imaging (MRI) in infants at term-equivalent age?
  • Findings In this cohort study of 45 infants nested within a multicenter randomized, placebo-controlled trial, 24 infants exposed to MgSO4 had greater voxelwise functional connectivity on MRI than 21 infants in the placebo group in the temporal and occipital lobes and deep gray matter structures. Exposure to MgSO4 was associated with significantly greater measures of functional segregation and integration.
  • Meaning These findings suggest that enhanced functional connectivity is a possible mechanism by which MgSO4 protects against cerebral palsy and death.

Importance Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of cerebral palsy and death.

Objective To determine whether MgSO4 administered to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks is associated with increased functional connectivity and measures of functional segregation and integration in infants at term-equivalent age, possibly reflecting a protective mechanism of MgSO4.

Design, Setting, and Participants This cohort study was nested within a randomized placebo-controlled trial performed across 24 tertiary maternity hospitals. Participants included infants born to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks who participated in the MAGENTA (Magnesium Sulphate at 30 to 34 Weeks’ Gestational Age) trial and underwent magnetic resonance imaging (MRI) at term-equivalent age. Ineligibility criteria included illness precluding MRI, congenital or genetic disorders likely to affect brain structure, and living more than 1 hour from the MRI center. One hundred and fourteen of 159 eligible infants were excluded due to incomplete or motion-corrupted MRI. Recruitment occurred between October 22, 2014, and October 25, 2017. Participants were followed up to 2 years of age. Analysis was performed from February 1, 2021, to February 27, 2024. Observers were blind to patient groupings during data collection and processing.

Exposures Women received 4 g of MgSO4 or isotonic sodium chloride solution given intravenously over 30 minutes.

Main Outcomes and Measures Prior to data collection, it was hypothesized that infants who were exposed to MgSO4 would show enhanced functional connectivity compared with infants who were not exposed.

Results A total of 45 infants were included in the analysis: 24 receiving MgSO4 treatment and 21 receiving placebo; 23 (51.1%) were female and 22 (48.9%) were male; and the median gestational age at scan was 40.0 (IQR, 39.1-41.1) weeks. Treatment with MgSO4 was associated with greater voxelwise functional connectivity in the temporal and occipital lobes and deep gray matter structures and with significantly greater clustering coefficients (Hedge g, 0.47 [95% CI, −0.13 to 1.07]), transitivity (Hedge g, 0.51 [95% CI, −0.10 to 1.11]), local efficiency (Hedge g, 0.40 [95% CI, −0.20 to 0.99]), and global efficiency (Hedge g, 0.31 [95% CI, −0.29 to 0.90]), representing enhanced functional segregation and integration.

Conclusions and Relevance In this cohort study, infants exposed to MgSO4 had greater voxelwise functional connectivity and functional segregation, consistent with increased brain maturation. Enhanced functional connectivity is a possible mechanism by which MgSO4 protects against cerebral palsy and death.
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References that have Magnesium in the title
  • Crowther CA, Middleton PF, Voysey M, et al; AMICABLE Group. Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: an individual participant data meta-analysis. PLoSMed. 2017;14(10): e1002398. doi:10.1371/journal.pmed.1002398
  • 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. JObstet Gynaecol Can. 2011;33(5):516-529. doi:10.1016/S1701-2163(16)34886-1
  • Committee Opinion No. 455: magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2010;115(3):669-671. doi:10.1097/A0G.0b013e3181d4ffa5
  • National Institute for Care and Excellence. Quality statement 6: magnesium sulfate for women between 24+0 and 29+6 weeks of pregnancy. Updated August 2,2019. Accessed April 17,2024. https://www.nice.org.uk/guidance/ qs135/chapter/Quality-statement-6-magnesium-sulfate-for-women-between-240-and-296-weeks-of-pregnancy
  • The Antenatal magnesium Sulphate For Neuroprotection Guideline Development Panel. Antenatal magnesium sulphate prior to preterm birth for neuroprotection of the fetus, infant and child: national clinical practice guidelines. 2010. Accessed April 17,2024. https://ontrack.perinatalsociety.org.nz/wp-content/uploads/ 2020/04/Antenatal-magnesium-sulphate-prior-to-preterm-birth-for-neuroprotection-of-the-fetus- infant-child-National-clinical-practice-guidelines.pdf
  • Mildvan AS. Role of magnesium and other divalent cations in ATP-utilizing enzymes. magnesium. 1987;6(1): 28-33.
  • Nakagawa M, Oono H, Nishio A. Enhanced production of IL-1P and IL-6 following endotoxin challenge in rats with dietary magnesium deficiency. J Vet MedSci. 2001;63(4):467-469. doi:10.1292/jvms.63.467
  • Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A. magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984;307(5950):462-465. doi:10.1038/307462a0
  • HirtzDG, Weiner SJ, Bulas D, etal; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Antenatal magnesium and cerebral palsy in preterm infants. JPediatr. 2015;167(4):834-839.e3. doi:10.1016/j.jpeds.2015.06.067
  • Gano D, Ho ML, Partridge JC, et al. Antenatal exposure to magnesium sulfate is associated with reduced cerebellar hemorrhage in preterm newborns. JPediatr. 2016;178:68-74. doi:10.1016/j.jpeds.2016.06.053
  • PoppeT, Thompson B, Boardman JP, etal; MagNUM Study Group. Effect of antenatal magnesium sulphate on MRI biomarkers of white matter development at term equivalent age: the MagNUM Study. EBioMedicine. 2022; 78:103923. doi:10.1016/j.ebiom.2022.103923
  • Crowther CA, Middleton PF, Wilkinson D, Ashwood P, Haslam R; MAGENTA Study Group. magnesium sulphate at 30 to 34 weeks' gestational age: neuroprotection trial (MAGENTA)-study protocol. BMC Pregnancy Childbirth. 2013;13(1):91. doi:10.1186/1471-2393-13-91
  • Crowther CA, Ashwood P, Middleton PF, McPheeA, TranT, Harding JE; MAGENTA Study Group. Prenatal intravenous magnesium at 30-34 weeks' gestation and neurodevelopmental outcomes in offspring: the MAGENTA randomized clinical trial. JAMA. 2023;330(7):603-614. doi:10.1001/jama.2023.12357
  • Macdonald RL, Curry DJ, Aihara Y, Zhang ZD, Jahromi BS, Yassari R. magnesium and experimental vasospasm. J Neurosurg. 2004;100(1):106-110. doi:10.3171/jns.2004.100.1.0106
  • RantoneTH, Gronlund JU, Jalonen JO, et al. Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure on circulatory adaptation in preterm infants. Clin Physiol Funct Imaging. 2002;22(1):13-17. doi: 10.1046/j.1475-097X.2002.00387.x

Brain development completed before the Magnesium was given in this study

Details at Ensure a healthy pregnancy and baby - take Vitamin D before conception

VitaminDWiki - 7 studies in both categories Magnesium and Cognitive

This list is automatically updated

VitaminDWiki - Pregnancy helped by Magnesium - many studies

Clearly adding Magnesium during all trimesters would help in many ways

Table of Contents as of May 2024
The Role of Magnesium in Pregnancy and in Fetal Programming of Adult Diseases - 2020
Effect of Magnesium Supplement on Pregnancy Outcomes: RCT - 2017
Preterm labor 1.8X more likely if low Magnesium - 2014
Importance of Magnesium in Pregnancy – Sept 2016
Pre-eclampsia inversely proportional to serum Magnesium – Oct 2014
Cochrane review of a variety of Magnesium compounds during pregnancy found some benefit - 2014
10 studies in both of the VitaminDWiki categories Pregnancy and Magnesium
Google Sites has the following
  Low magnesium associated with miscarriage
  Low magnesium, phosphorus found in threatened miscarriage
  100% of previously infertile women gave birth after normalizing magnesium levels
  Magnesium deficiency linked to miscarriage and birth defects
  Magnesium prevents preterm labor
  Magnesium deficiency during pregnancy associated with fetal death in animals
  Low calcium, iron, zinc and magnesium associated with higher rate of miscarriage
  Magnesium deficiency leads to insulin resistance
  Low magnesium associated with premenstrual tension
See also PubMed
  Preterm birth and the role of neuroprotection.- Jan 2015
  The use of intravenous magnesium in non-preeclamptic pregnant women: fetal/neonatal neuroprotection. - May 2015
  Magnesium and pregnancy. Article in Japanese - Aug 2012
  Magnesium sulphate for preventing preterm birth in threatened preterm labour
See also web
  Benefits of Magnesium during pregnancy - May 2015
  Magnesium Sulfate slows or stops preterm labor - 2014
  Magnesium Sulfate reduced cerebral palsy in premies - Dec 2013
  More Magneiusm, half as many pregnancy leg cramps - RCT Aug 2012
  Magnesium appears to decrease morning sickness
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VitaminDWiki – Magnesium and Vitamin D contains

354 items in category, see also

Mg and Vitamin D

Dr. Dean

Number of studies in both of the categories of Magnesium and:

Bone 16,  Cardiovascular 17,   Diabetes 28. Depression 14,  Obesity 11,   Omega-3 36,  Zinc 24,  Pregnancy 11,  Headache 11,   Virus 26,   Calcium 27   Virus 26   Mortality 9   Hypertension 12   Inflammation 3   Pain 7 etc.

Attached files

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21260 Prenatal Magnesium_CompressPdf.pdf admin 03 Jun, 2024 237.92 Kb 23