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Neuroscience

A Boost for Infant Brain Development

Magnesium sulfate lessens possible neural consequences of pre-term birth.

Key points

  • Infants born to individuals who received magnesium sulfate had greater neural connectivity.
  • Increased connectivity suggests faster brain maturation.
Suhyeon Choi/Unsplash
Source: Suhyeon Choi/Unsplash

The incidence of pre-term birth is on the rise globally due to a slew of unknown reasons, although some suggest that psychological stressors, such as chronic stress, unstable housing, and poor nutrition, as well as obesity and having children later in life, could contribute to it.1 This increasing trend poses a higher likelihood of developmental delay and cerebral palsy in affected infants.2

The use of magnesium sulfate has emerged as a method to treat women at risk of imminent early pre-term birth to prevent these neurodevelopmental outcomes.3 While magnesium sulfate is known to reduce the effects of brain injuries and enhance white matter development in very pre-term infants, its effects on other aspects of brain development remain unclear.4,5

Specifically, its role in brain connectivity is not understood, leaving scientists and physicians uncertain about its precise mechanism and neurological effects. If doctors had this additional information, they could better prescribe magnesium sulfate tailored to an individual patient’s needs.

To address this gap, bioinformatician Steven Ufkes and his team led a multi-institutional study to understand how magnesium sulfate affects neonatal brain connectivity.6

The study involved infants born to mothers at a gestational age between 30 and 34 weeks in Australia or New Zealand from the Magenta trial and who had had an MRI scan as part of a related study.7 In the intervention, pregnant mothers received either 4 grams of magnesium sulfate or a placebo intravenously for 30 minutes. Then, after birth, the researchers used MRI and fMRI data to determine functional connectivity in the brains of pre-term infants by examining correlations in activity between different brain regions.

Scans from 45 infants (23 female, 22 male) were used for analysis. The research team found that treatment with magnesium sulfate was associated with greater voxelwise functional connectivity in the temporal lobe, occipital lobe, and deep gray matter structures. Additionally, in those whose mothers had received the magnesium sulfate treatment, researchers found increased functional segregation in the brain, improving local connectivity and clustering of brain regions.

The infants born to mothers who underwent treatment with magnesium sulfate had improved connectivity in regions crucial for motor function, vision, hearing, and smell, all of which are functions that play important roles in human development and are used throughout life. The increased connectivity also suggests that these infant brains underwent faster maturation, which aligns well with previous evidence demonstrating that magnesium sulfate can reduce the risk of brain abnormalities and serve as a protective factor against brain injuries in infants after birth.

The researchers note that the sample size was relatively small, which could have reduced the power of the study to detect subtle differences. Furthermore, MRI scans were collected across different sites and scanners, potentially introducing variability into the data.

Functional connectivity is important at every age but plays a foundational role in early childhood development, facilitating the acquisition of new skills and the formation of relationships.8,9 From a broader perspective, magnesium sulfate treatment delivered intravenously for pregnant individuals not expected to carry a child to term has the potential to improve the infant’s development starting in utero and continuing after birth. Early intervention could lead to positive developmental outcomes as the child grows.

Luis Arias / Unsplash
Source: Luis Arias / Unsplash

References

1. Christensen, J. (2024, February 2). Preterm birth rate in the US is rising, study finds, but the reasons are a mystery. CNN. https://www.cnn.com/2024/02/02/health/preterm-birth-study-wellness/inde…

2. Blencowe, H., Lee, A. C., Cousens, S., Bahalim, A., Narwal, R., Zhong, N., Chou, D., Say, L., Modi, N., Katz, J., Vos, T., Marlow, N., & Lawn, J. E. (2013). Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatric research, 74 Suppl 1(Suppl 1), 17–34. https://doi.org/10.1038/pr.2013.204

3. Crowther, C. A., Middleton, P. F., Voysey, M., Askie, L., Duley, L., Pryde, P. G., Marret, S., Doyle, L. W., & AMICABLE Group (2017). Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis. PLoS medicine, 14(10), e1002398. https://doi.org/10.1371/journal.pmed.1002398

4. Nakagawa, M., Oono, H., & Nishio, A. (2001). Enhanced production of IL-1beta and IL-6 following endotoxin challenge in rats with dietary magnesium deficiency. The Journal of veterinary medical science, 63(4), 467–469. https://doi.org/10.1292/jvms.63.467

5. Anblagan, D., Bastin, M. E., Sparrow, S., Piyasena, C., Pataky, R., Moore, E. J., Serag, A., Wilkinson, A. G., Clayden, J. D., Semple, S. I., & Boardman, J. P. (2015). Tract shape modeling detects changes associated with preterm birth and neuroprotective treatment effects. NeuroImage. Clinical, 8, 51–58. https://doi.org/10.1016/j.nicl.2015.03.021

6. Ufkes, S., Kennedy, E., Poppe, T., Miller, S. P., Thompson, B., Guo, J., Harding, J. E., & Crowther, C. A. (2024). Prenatal Magnesium Sulfate and Functional Connectivity in Offspring at Term-Equivalent Age. JAMA network open, 7(5), e2413508. https://doi.org/10.1001/jamanetworkopen.2024.13508

7. Crowther, C. A., Ashwood, P., Middleton, P. F., McPhee, A., Tran, T., Harding, J. E., & MAGENTA Study Group (2023). Prenatal Intravenous Magnesium at 30-34 Weeks' Gestation and Neurodevelopmental Outcomes in Offspring: The MAGENTA Randomized Clinical Trial. JAMA, 330(7), 603–614. https://doi.org/10.1001/jama.2023.12357

8. Bruchhage, M. M. K., Ngo, G. C., Schneider, N., D'Sa, V., & Deoni, S. C. L. (2020). Functional connectivity correlates of infant and early childhood cognitive development. Brain structure & function, 225(2), 669–681. https://doi.org/10.1007/s00429-020-02027-4

9. Bray, K., Pozzi, E., Vijayakumar, N., Richmond, S., Seal, M., Pantelis, C., Anderson, V., & Whittle, S. (2022). Empathy and resting-state functional connectivity in children. Neuroimage: Reports, 2(4), 100142. https://doi.org/10.1016/j.ynirp.2022.100142

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