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Revista Brasileira de Ginecologia e Obstetrícia

Print version ISSN 0100-7203

Rev. Bras. Ginecol. Obstet. vol.35 no.8 Rio de Janeiro Aug. 2013

https://doi.org/10.1590/S0100-72032013000800001 

EDITORIAL

 

Procedures for fetal neuroprotection: use of magnesium sulfate

 

Procedimentos para neuroproteção fetal: uso do sulfato de magnésio

 

 

Antonio Fernandes Moron; Edward Araujo Júnior; Luciano Marcondes Machado Nardozza

Obstetrics Department of Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP - São Paulo (SP), Brazil

Correspondence

 

 

Perinatal factors resulting from prematurity are the main agents responsible for high child morbidity and mortality worldwide1. Therefore, the impact of premature birth is currently one of the biggest obstetric challenges. Prematurity is classified as spontaneous or elective2. The spontaneous one is the result from spontaneous delivery labor in the strict sense of this term or from rupture of the membranes, and it occurs more frequently in multiple pregnancies. On the other hand, elective prematurity is a consequence of a medical indication due to maternal intercurrent events (hypertensive emergencies, diabetic decompensation or placental displacement, among others).

Extreme prematurity is the most feared condition, which results from deliveries at gestational ages of less than 32 weeks. Because prematurity may perform an irreversible neurological damage to the child, it has the capacity to cause a wide spectrum of diseases and permanent conditions, with varying degrees of impairment with regard to both neurological and psychomotor development3.

Although use of magnesium sulfate to provide prophylaxis against eclampsia and inhibit preterm delivery labor is a well-established therapeutic approach, its use with the aim of fetal neuroprotection has been addressed only in more recent studies. Magnesium promotes cerebral vasodilatation, thereby it reduces the production of cytokines and free radicals and the entry of calcium into the intracellular medium, which minimizes cell injury and consequent death and optimizes the cerebral blood flow4. In 1995, a case-control study reported that sulfation in cases of extreme prematurity was probably associated with fetal neuroprotection effects5. Following this, other analyses were conducted on its applicability within obstetrics as a prevention for neurological lesions in extremely premature infants.

Since only some of the subsequent studies showed that magnesium sulfate had a neuroprotective effect6,7, while others reported that this effect might not be sustainable8-10, new randomized studies were developed.

A systematic review from the Cochrane Collaboration produced a meta-analysis of five randomized clinical trials that assessed the effect of neuroprotection provided through using magnesium sulfate in cases of prematurity11. This review showed that its use significantly reduced the risk of cerebral palsy, but did not increase fetal, neonatal, infant (up to two years of age) or maternal mortality. The dose used in the different studies ranged on average from 4 to 6 g, administered intravenously, 20 to 30 minutes after the mother's eclamptic seizure. This included a maintenance dose of 1 to 2 g per hour, for around 12 to 24 hours11. From the systematic review, management protocols were determined, however they did not have any consensus regarding the dose and inclusion criteria for use of medication.

In 2010, the American College of Obstetricians and Gynecologists (ACOG)12 formally stated its opinion, through a committee, that sulfation presented encouraging evidence with regard to neuroprotection. However, it was only in 2012 that ACOG determined the inclusion and exclusion criteria regarding sulfation for fetal neuroprotection13. This procedure is indicated for pregnant women with a gestational age of less than or equal to 31 weeks and 6 days, presenting a risk of delivery within the next 30 minutes to 24 hours, with either a single or a multiple pregnancy, and also in cases of delivery labor with dilatation of 4.0 to 8.0 cm or spontaneous membrane rupture, if this occurs after the gestational age of 22 weeks has been reached. Another inclusion criterion is that sulfate should be used in cases of elective prematurity, in which delivery is indicated within the next 24 hours (severe preeclampsia). The exclusion criteria include maternal contraindications and uncertainty regarding whether the intervention would bring real benefits to the fetus, although the latter criterion is not very clearly defined. This probably correlates with situations in which the fetus presents minimal chances of survival or the length of time for drug action would be insufficient, like deliveries that take place during the expulsive period.

Other guidelines have also been established, such as the one of the Society of Obstetricians and Gynaecologists of Canada (SOCG) in 2011, in which sulfation is indicated only for pregnant women of gestational age of more than 31 weeks and 6 days, when preterm delivery is imminent (i.e. the active phase of delivery labor, with dilatation greater than or equal to 4.0 cm, with or without membrane rupture, or in situations of elective prematurity)14.

It needs to be borne in mind that use of magnesium sulfate is not risk-free for the mother, especially in the presence of toxicity signs from this drug. Facial rubor and flushes are acceptable sensations from its use, but continuous monitoring of maternal clinical parameters is needed in order to ensure safe use. The parameters to be monitored include the pulse (heart rate - HR), respiratory rate (RR), arterial blood pressure (BP), patellar reflex (PR), and urinary output (UO). This last parameter especially should be measured while use of this drug continues. The infusion should always be halted in the following situations: HR<12 respiratory movements per minute, absence of RR, hypotension and UO<100 mL over a four-hour period. In situations of intoxication due to magnesium sulfate, the antidote used is calcium gluconate, which should be always easily accessible, with a dose already prepared as soon as the seizure dose of sulfate has been administered in the same way as done in preeclampsia treatment15.

The possibility of neuroprotection for full-term fetuses using sulfation has also been addressed, as seen in the Cochrane systematic review. However, this showed that there was insufficient evidence to state that its use was effective and safe16.

Therefore, despite the divergences in the criteria related to the gestational age for indication, dosage and effects of magnesium sulfate on preterm gestation, it is clear that magnesium sulfate has an effect with regard to neurological protection, especially at early gestational ages (less than 32 weeks). For better definition of the eligibility of sulfation use for neuroprotection, further randomized studies should be encouraged.

 

References

1. Barda G, Ben-Haroush A, Barkat J, Malinger G, Luria O, Golan A, et al. Effect of vaginal progesterone, administered to prevent preterm birth, on impedance to blood flow in fetal and uterine circulation. Ultrasound Obstet Gynecol. 2010;36(6):743-8.         [ Links ]

2. Bittar RE, Zugaib M. [Risk predictors for preterm birth]. Rev Bras Ginecol Obstet. 2009;31(4):203-9. Portuguese.         [ Links ]

3. 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;13:91.         [ Links ]

4. Gathwala G, Khera A, Singh J, Balhara B. Magnesium for neuroprotection in birth asphyxia. J Pediatr Neurosci. 2010;5(2):102-4.         [ Links ]

5. Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birth weight infants? Pediatrics. 1995;95(2):263-9.         [ Links ]

6. Finesmith RB, Roche K, Yellin PB, Walsh KK, Shen C, Zeglis M, et al. Effect of magnesium sulfate on the development of cystic periventricular leukomalacia in preterm infants. Am J Perinatol. 1997;14(5):303-7.         [ Links ]

7. Schendel DE, Berg CJ, Yeargin-Allsopp M, Boyle CA, Decoufle P. Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA. 1996;276(22):1805-10.         [ Links ]

8. Canterino JC, Verma UL, Visintainer PF, Figueroa R, Klein SA, Tejani NA. Maternal magnesium sulfate and the development of neonatal periventricular leucomalacia and intraventricular hemorrhage. Obstet Gynecol. 1999;93(3):396-402.         [ Links ]

9. Grether JK, Hoogstrate K, 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(3):717-25.         [ Links ]

10. Kimberlin DF, Hauth JC, Goldenberg RL, Bottoms SF, Iams JD, Mercer B, et al. The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or = 1000- gram infants. Am J Perinatol. 1998;15(11):635-41.         [ Links ]

11. 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.         [ Links ]

12. American College of Obstetricians and Gynecologists Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee Opinion No. 455: magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2010;115(3):669-71.         [ Links ]

13. Patient safety checklist no. 7: magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2012;120(2 Pt 1):432-3.         [ Links ]

14. Magee L, Sawchuck D, Synnes A, von Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for neuroprotection. J Obstet Gynaecol Can. 2011;33(5):516-29.         [ Links ]

15. Smith JM, Lowe RF, Fullerton J, Currie SM, Harris L, Felker-Kantor E. An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management. BMC Pregnancy Childbirth. 2013;13:34.         [ Links ]

16. Nguyen TM, Crowther CA, Wilkinson D, Bain E. Magnesium sulphate for women at term for neuroprotection of the fetus. Cochrane Database Syst Rev. 2013;(2):CD009395.         [ Links ]

 

 

Correspondence:
Edward Araujo Júnior
Fetal Medicine Program in the Obstetrics Department of EPM-Unifesp
Rua Napoleão de Barros, 875
Zip code: 04024-002 São Paulo (SP), Brazil

Received 10/07/2013
Accepted with modifications 08/08/2013
Conflict of interest: none.

 

 

Study carried out at the Fetal Medicine Program in the Obstetrics Department of Escola Paulista de Medicina, Universidade Federal de São Paulo - UNIFESP - São Paulo (SP), Brazil.

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