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Neuroprotective effects of in utero exposure to

magnesium sulfate
Authors: Hyagriv N Simhan, MD, MS, Katherine P Himes, MD, MSCR
Section Editor: Vincenzo Berghella, MD
Deputy Editor: Vanessa A Barss, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2020. | This topic last updated: Jun 24, 2020.

INTRODUCTION

Cerebral palsy is the leading cause of neurologic impairment in young children, and
prematurity and low birth weight are the most important risk factors for developing the
disease. (See "Cerebral palsy: Epidemiology, etiology, and prevention".)

In utero exposure to magnesium sulfate before early preterm birth appears to decrease the
incidence and severity of cerebral palsy. The use of magnesium sulfate for neuroprotection
will be reviewed here. Use of magnesium sulfate for tocolysis or for seizure prevention in
women with preeclampsia/eclampsia is discussed separately. (See "Inhibition of acute
preterm labor", section on 'Magnesium sulfate' and "Preeclampsia: Management and
prognosis", section on 'Regimen'.)

MECHANISM

The mechanism for the neuroprotective effects of magnesium sulfate in preterm infants is
not well understood. The following mechanisms have been proposed [1,2]:

● Stabilization of cerebral circulation by stabilizing blood pressure and normalizing

cerebral blood flow.

● Prevention of excitatory injury by stabilization of neuronal membranes and blockade of

excitatory neurotransmitters, such as glutamate.

● Protection against oxidative injury via antioxidant effects.

● Protection against inflammatory injury via anti-inflammatory effects.

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Antenatal magnesium sulfate has not been associated with a decreased risk of brain injuries
that are believed to cause cerebral palsy, such as severe intraventricular hemorrhage or
cystic white matter injury [3-6], but it has been associated with a reduction in cerebellar
hemorrhage in preterm infants [7].

EVIDENCE OF EFFICACY FROM RANDOMIZED TRIALS AND META-ANALYSES

Evidence of the neuroprotective effects of magnesium sulfate is based on data from

randomized trials and meta-analyses of these trials. There is significant heterogeneity among
the three major trials designed solely to assess the neuroprotective benefits of magnesium
sulfate: the Australasian Collaborative Trial of Magnesium Sulfate (ACTOMgSO4) [3], the
Beneficial Effects of Antenatal Magnesium Sulfate (BEAM) trial [4], and the PREMAG trial [5,8].
These trials are summarized in the table ( table 1). It is important to emphasize that the
combined outcome of "cerebral palsy or death" is important methodologically, as cerebral
palsy and death are competing outcomes.

Death and/or cerebral palsy — Multiple meta-analyses have evaluated the neuroprotective

effects of magnesium sulfate administered to women at risk of preterm birth and have
consistently found a reduction in cerebral palsy in offspring [9-13]. The 2009 Cochrane meta-
analysis of magnesium sulphate for women at risk of preterm birth for neuroprotection of
the fetus is a representative example of this evidence [11]. Five randomized trials were
included: The three trials described above were specifically designed to evaluate the
neuroprotective effect of magnesium sulfate [3-5,8], a fourth trial had both a tocolytic arm
and a neuroprotective arm [6], and a fifth trial, Magpie, was designed to assess the efficacy
of magnesium sulfate for prevention of seizures in women with preeclampsia [14]. These
trials included 6145 infants, of whom 1493 were delivered preterm.

For subgroup analysis, studies were classified by their primary study intent: neuroprotection
[3,4,6,8] or "other," which included seizure prophylaxis (Magpie trial [14]) in preeclamptic
women or tocolysis of preterm labor [6]. For the purpose of the review, the trial with tocolytic
and neuroprotective arms was treated as two separate trials, with the subgroup of women in
the neuroprotection arm considered along with the other trials designed specifically to
assess the neuroprotective role of magnesium sulfate.

Major findings were:

● In the trials overall, "any" cerebral palsy was significantly reduced (relative risk [RR] 0.68,
95% CI 0.54-0.87). The absolute risk of cerebral palsy was 3.4 percent for fetuses exposed
to antenatal magnesium sulphate therapy versus 5 percent for unexposed fetuses,
giving an absolute risk reduction of 1.6 percent. The number of women that would need
to be treated to prevent one child from developing cerebral palsy was 63 (95% CI 43-87).

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In the neuroprotection trials subgroup, both "any" cerebral palsy and moderate/severe
cerebral palsy were significantly reduced (RR 0.71, 95% CI 0.55-0.91 and RR 0.64, 95% CI
0.44-0.92, respectively).

● Substantial gross motor dysfunction was significantly reduced overall (RR 0.61, 95% CI
0.44-0.85) and in the neuroprotection trials subgroup (RR 0.60, 95% CI 0.43-0.83).

● "Death or cerebral palsy" was not significantly reduced overall (RR 0.94, 95% CI 0.78-1.12)
but was reduced in the neuroprotection trials subgroup (RR 0.85, 95% CI 0.74-0.98).

● "Stillbirth or pediatric death" was not significantly reduced overall (RR 1.04, 95% CI 0.92-
1.17) or in the neuroprotection trials subgroup (RR 0.95, 95% CI 0.80-1.12).

Given the concern about competing outcomes, the finding that antenatal magnesium
sulfate had no significant effect on the combined outcome of "death or cerebral palsy" in
the overall group of trials merits discussion. It is possible that the nonsignificant
difference of the combined outcome is due to an increased risk of fetal or infant death in
a subgroup of magnesium exposed fetuses, as suggested by two trials [4,6]. For this
reason, some clinicians do not administer magnesium sulfate for neuroprotection,
despite the protective effect against cerebral palsy. On the other hand, the combined
outcome of "death or cerebral palsy" was reduced significantly when only trials designed
specifically to assess the neuroprotective effect of magnesium sulfate were analyzed; we
believe this provides significant reassurance that the decrease in occurrence and severity
of cerebral palsy is not achieved as a result of an increased risk of death.

Other short-term outcomes — Short-term pediatric outcomes other than death and

cerebral palsy have also been evaluated by meta-analysis, and no benefit was found in terms
of a reduction in risk of blindness, deafness, or developmental delay [10]. Importantly,
magnesium exposure did not decrease the frequency of adverse effects, such as Apgar score
less than seven at five minutes, intraventricular hemorrhage, periventricular leukomalacia,
neonatal seizures, or need for ongoing respiratory support. The effect of gestational age at
randomization (<30 weeks versus <32 to 34 weeks) did not make a significant difference. (See
'Gestational age' below.)

Outcomes at school-age — Only one of the randomized trials discussed above,

ACTOMgSO4, reported on long-term outcomes after magnesium sulfate prophylaxis [15].
The follow-up study included data on 669 children (77 percent of the original study) at a
mean age of 8.4 years, corrected for prematurity. The magnesium sulfate and placebo
groups had similar rates of cerebral palsy, abnormal motor function, and other neurologic,
cognitive, and behavioral outcomes at school age, but magnesium exposure was associated
with a trend towards improved survival (RR 0.80, 95% CI 0.62-1.03). The lack of benefit at
school age in this trial does not negate the benefit of magnesium sulfate therapy in

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decreasing cerebral palsy risk given results of meta-analyses of randomized trials. There are
significant differences in patient population and study protocols among three large
randomized trials, and thus long-term outcome data from other trials are needed before
making definitive conclusions about long-term outcomes.

CLINICAL APPROACH

The following discussion reflects the authors' approach to use of magnesium sulfate for
neuroprotection before preterm birth. This approach is based on the evidence cited above
and below and is generally consistent with American College of Obstetricians and
Gynecologists guidance [16]. (See 'Evidence of efficacy from randomized trials and meta-
analyses' above and 'Guidelines from selected organizations' below.)

Candidates for treatment — Women at high risk of imminent (ie, within 24 hours) preterm
birth are appropriate candidates of magnesium sulfate neuroprotection. This includes
women with recent preterm premature rupture of membranes, preterm labor with intact
membranes, or planned medically or obstetrically indicated preterm delivery.

Women enrolled in the various trials of magnesium sulfate for neuroprotection represented
the full range of obstetric indications for preterm birth, but differed significantly in the
proportion of subjects comprising each indication. For example, in the Australasian
Collaborative Trial of Magnesium Sulfate (ACTOMgSO4) [3] and PREMAG [8] trials, 63 to 88
percent of women were in preterm labor. In contrast, in the Beneficial Effects of Antenatal
Magnesium Sulfate (BEAM) trial [4], the majority (85 percent) of women had preterm
premature rupture of membranes. The significant heterogeneity among subjects makes it
impossible to determine whether fetuses born prematurely due to a specific subtype of
preterm birth are more likely to benefit from antenatal magnesium sulfate administration
compared with other subtypes.

Contraindications — Use of magnesium sulfate is contraindicated in women with

myasthenia gravis since it can precipitate a severe myasthenic crisis [17,18]. It should also be
avoided in women with known myocardial compromise or cardiac conduction defects
because of its anti-inotropic effects. Since magnesium is eliminated by the kidneys, women
with impaired renal function will have an exaggerated rise in serum magnesium
concentration and may develop magnesium toxicity at the usual maintenance infusion
doses. Maintenance infusion dosing must be adjusted or eliminated in women with renal
insufficiency (defined as a serum creatinine greater than 1.0 mg/dL [88.4 micromol/L]), but a
standard loading dose is given since their volume of distribution is not altered.

Gestational age

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Lower limit — For women at risk for imminent delivery at the limit of viability (see
"Periviable birth (Limit of viability)"), we confer with the neonatology team and jointly counsel
families about possible management strategies. If the family opts for neonatal interventions
at this gestational age, we administer magnesium sulfate for neuroprotection. None of the
randomized trials of magnesium sulfate for neuroprotection included pregnancies at <24
weeks of gestation, although a prospective observational study included pregnancies as
early as 22+0 weeks [19].

Upper limit — We limit use of magnesium sulfate for neuroprotection to pregnancies <32
weeks of gestation because the majority of data from randomized trials was derived from
pregnancies <32 weeks.

The upper limit of gestational age for the neuroprotective effect of antenatally administered
magnesium has not been well-studied. In a meta-analysis that stratified by the gestational
age at randomization: <32 to 34 weeks (5235 fetuses) versus <30 weeks (3107 fetuses),
benefits were similar for both gestational age ranges [9]. The numbers needed to prevent
one case of cerebral palsy in the <32 to 34 weeks group and the <30 weeks group were 56
and 46 women, respectively. The potential value of magnesium sulfate for neuroprotection of
the term fetus is unknown [20].

Dose — We favor administration of a 4 g loading of magnesium sulfate over 20 minutes and

a maintenance dose of 1 g/hour. We believe this regimen is likely to have a more favorable
side effect and safety profile than the higher-dose regimen used in one of the seminal trials (
table 1). In addition, it seems biologically plausible that the neuroprotective effects of
magnesium sulfate are secondary to residual concentrations of the drug in the neonate's
circulation, despite findings from one of the other seminal trials that omitted the
maintenance dose.

Data are limited regarding optimal maternal loading and maintenance doses to confer
neonatal benefit and avoid potential harm. One group has proposed that it is theoretically
possible that magnesium sulfate may have both neuroprotective and toxic fetal effects
depending on dose/exposure [21]. Thus, this is a crucial area for future investigation.

Timing — We administer magnesium sulfate to women whom we believe will deliver within
24 hours, with the following caveats:

● Every effort should be made to reserve therapy for women who are at high risk of
imminent delivery rather than women who are simply diagnosed with threatened
preterm labor or preterm premature rupture of membranes without preterm labor;
however, these assessments are somewhat subjective.

● For women who will undergo scheduled cesarean delivery, we administer the loading
dose and then initiate maintenance therapy. Available data are insufficient to inform the
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optimal duration of maintenance therapy before delivery. In our practice, we aim for 6 to
12 hours of maintenance therapy prior to a scheduled cesarean delivery.

● If emergency or expeditious delivery is indicated because of maternal or fetal status, it

should not be delayed to administer magnesium sulfate.

● If induction of labor is likely to take longer than 24 hours, it is reasonable to delay

administration until cervical ripening is achieved and delivery is more proximate since we
do not administer magnesium sulfate for more than 24 hours. (See 'Duration' below.)

Duration — Magnesium sulfate is discontinued when the infant is delivered.

We limit the magnesium sulfate infusion to a maximum of 24 hours, even if delivery has not
occurred, as this was the maximum duration of therapy in seminal trials ( table 1).

The minimum duration of in utero exposure to achieve a benefit is unknown; the upper limit
of safe and effective exposure in this setting (ie, neuroprotection) is also not well defined. A
secondary analysis of the BEAM trial noted no difference in cerebral palsy or neonatal death
rates among newborns with less than 12 hours, 12 to 18 hours, or greater than 18 hours of
in utero exposure [22].

Retreatment — The authors do not administer more than one course of magnesium sulfate
for neuroprotection as there are limited data regarding any benefit for women who do not
deliver after the initial course. Of the trials designed to assess the neuroprotective benefits of
magnesium sulfate, only the BEAM trial [4] allowed retreatment. These investigators
readministered the full dose of magnesium sulfate if delivery was again considered
imminent, the woman was <34 weeks of gestation, and the initial magnesium infusion had
been discontinued for more than six hours. Based on this trial, some clinicians, including the
section editor of this topic, offer retreatment using the BEAM criteria. Although magnesium
sulfate is not costly and there is no known risk of harm from retreatment, a prudent
approach to decision making may be to individualize retreatment based on factors such as
the gestational age at the time for initial treatment, time since initial administration, and
indication(s) for/urgency of delivery.

The importance of appropriate patient selection and timing of the single course of therapy
was suggested by a study that reported exposure to magnesium <12 hours before delivery
was associated with a reduced odds of cerebral palsy compared with exposure >12 hours
before delivery [23].

Side effects — Given the widespread use of magnesium sulfate for prevention of eclampsia,
most providers are familiar with magnesium toxicity and the common maternal, fetal, and
neonatal side effects. (See "Preeclampsia: Management and prognosis", section on 'Signs of
magnesium toxicity'.)

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The 2009 Cochrane systematic review and meta-analysis of magnesium sulphate for women
at risk of preterm birth for neuroprotection of the fetus discussed above found [11]:

● No significant differences between magnesium and placebo control groups in severe

maternal outcomes, including death, cardiac arrest, or respiratory arrest.

● Women assigned to the magnesium group often experienced side effects that led to
cessation of therapy.

Monitoring — Urine output and deep tendon reflexes should be closely monitored in all
patients. The maintenance phase of treatment should be continued only if a patellar reflex is
present (loss of reflexes being the first manifestation of symptomatic hypermagnesemia),
respirations exceed 12 per minute, and the urine output exceeds 100 mL per four hours. (See
"Preeclampsia: Management and prognosis", section on 'Regimen'.)

Antenatal corticosteroids — A course of antenatal corticosteroids is routinely administered

to pregnancies <34 weeks of gestation at risk for delivery within the next seven days because
this therapy reduces the rate of respiratory distress syndrome, intraventricular hemorrhage,
necrotizing enterocolitis, and neonatal death. (See "Antenatal corticosteroid therapy for
reduction of neonatal respiratory morbidity and mortality from preterm delivery".)

Data regarding the combination of antenatal corticosteroids and magnesium sulfate in

extremely preterm pregnancies are limited but are reassuring that improved survival is not
associated with increased neurodevelopmental impairment. In pregnancies at 22+0 to 26+6
weeks of gestation, a prospective study reported that the combination of antenatal
corticosteroids and magnesium sulfate was associated with a 30 to 50 percent reduction in
the composite outcome of death or severe neurodevelopmental impairment at 18 to 26
months corrected age compared with use of either therapy alone or neither therapy [19].
These findings in children born extremely preterm, who are at high risk for death and
neurodevelopmental impairment, underscore the importance of administering both
therapies to minimize both mortality and morbidity.

Choice of tocolytic for women in preterm labor — If tocolysis is indicated, the most
effective agent with the most favorable side effect profile should be given. In most cases, this
will be indomethacin or a calcium channel blocker, or atosiban (where available). (See
"Inhibition of acute preterm labor".)

Maternal side effects are increased when magnesium sulfate is administered concomitantly
with beta agonists or calcium channel blockers. We acknowledge that the data on the
combined use of calcium channel blockers and magnesium sulfate are sparse; however, case
reports suggest an increased risk of symptomatic hypocalcemia, hypotension, and cardiac
suppression [9,10,14]. Thus, in women <32 weeks of gestation who are candidates for

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tocolysis, we use indomethacin for labor inhibition in women also receiving magnesium
sulfate for fetal neuroprotection.

Magnesium sulfate should not be chosen for tocolysis based solely upon fetal
neuroprotective effects.

GUIDELINES FROM SELECTED ORGANIZATIONS

No standard approach has been established for use of magnesium sulfate for
neuroprotection. We have described our approach and the rationale for our choices. Others
have taken a slightly different approach, including administering magnesium sulfate as early
as 23 weeks of gestation, using a 6 g loading dose with a 2 g maintenance dose, stopping
treatment after 12 hours, and retreating patients who meet criteria for treatment and have
been off therapy for more than six hours [24,25].

Additional guidelines are available from the following sources:

● American College of Obstetricians and Gynecologists [16]

● Society of Obstetricians and Gynaecologists of Canada [26]

SUMMARY AND RECOMMENDATIONS

● For women at imminent risk of preterm birth, we suggest antenatal administration of

magnesium sulfate for neuroprotection (Grade 2B). Randomized placebo-controlled
trials of maternal administration of magnesium sulfate in women expected to have a
preterm delivery within 24 hours have consistently demonstrated a decreased risk of
cerebral palsy and severe motor dysfunction in offspring; however, the possibility of an
increased risk of death in a subgroup of fetuses or infants has not conclusively been
excluded. (See 'Evidence of efficacy from randomized trials and meta-analyses' above.)

● A course of antenatal corticosteroids should also be administered according to standard

guidelines. (See 'Antenatal corticosteroids' above.)

● We limit magnesium sulfate therapy for neuroprotection to pregnancies that have

reached a gestational age at which the family opts for neonatal interventions but are
less than 32 weeks of gestation. (See 'Gestational age' above.)

● We administer a 4 g intravenous loading dose followed by a 1 g/hour infusion. Treatment

is discontinued at delivery or by 24 hours after initiation if delivery has not occurred. (See
'Dose' above and 'Duration' above.)

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● If emergency delivery is necessary given maternal or fetal status, it should not be

delayed to administer magnesium sulfate. (See 'Timing' above.)

● If tocolysis is indicated, the most effective agent with the most favorable side effect
profile should be chosen. In general, we use indomethacin. (See 'Choice of tocolytic for
women in preterm labor' above.)

● For women who do not deliver after an initial course of magnesium sulfate therapy, we
suggest not retreating (Grade 2C). (See 'Retreatment' above.)

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REFERENCES
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neuroprotection in the preterm infant. Semin Fetal Neonatal Med 2007; 12:311.

2. Costantine MM, Drever N. Antenatal exposure to magnesium sulfate and

neuroprotection in preterm infants. Obstet Gynecol Clin North Am 2011; 38:351.

3. Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for
neuroprotection before preterm birth: a randomized controlled trial. JAMA 2003;
290:2669.

4. Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate
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5. Marret S, Marpeau L, Zupan-Simunek V, et al. Magnesium sulphate given before very-

preterm birth to protect infant brain: The randomised controlled PREMAG trial*. BJOG
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6. Mittendorf R, Dambrosia J, Pryde PG, 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.

7. Gano D, Ho ML, Partridge JC, et al. Antenatal exposure to magnesium sulfate is

associated with reduced cerebellar hemorrhage in preterm newborns. J Pediatr 2016;
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8. Marret S, Marpeau L, Follet-Bouhamed C, et al. [Effect of magnesium sulphate on

mortality and neurologic morbidity of the very-preterm newborn (of less than 33 weeks)
with two-year neurological outcome: results of the prospective PREMAG trial]. Gynecol
Obstet Fertil 2008; 36:278.
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9. Costantine MM, Weiner SJ, Eunice Kennedy Shriver National Institute of Child Health
and Human Development Maternal-Fetal Medicine Units Network. Effects of antenatal
exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a
meta-analysis. Obstet Gynecol 2009; 114:354.

10. Doyle LW, Crowther CA, Middleton P, Marret S. Antenatal magnesium sulfate and
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11. Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulphate for women at risk of
preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009;
:CD004661.

12. Zeng X, Xue Y, Tian Q, et al. Effects and Safety of Magnesium Sulfate on
Neuroprotection: A Meta-analysis Based on PRISMA Guidelines. Medicine (Baltimore)
2016; 95:e2451.

13. Wolf HT, Huusom LD, Henriksen TB, et al. Magnesium sulphate for fetal neuroprotection
at imminent risk for preterm delivery: a systematic review with meta-analysis and trial
sequential analysis. BJOG 2020; 127:1180.

14. Altman D, Carroli G, Duley L, et al. Do women with pre-eclampsia, and their babies,
benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled
trial. Lancet 2002; 359:1877.

15. Doyle LW, Anderson PJ, Haslam R, et al. School-age outcomes of very preterm infants
after antenatal treatment with magnesium sulfate vs placebo. JAMA 2014; 312:1105.

16. American College of Obstetricians and Gynecologists Committee on Obstetric Practice,

Society for Maternal-Fetal Medicine. ACOG Committee Opinion No. 455: Magnesium
sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol 2010;
115:669. Reaffirmed 2018.

17. Benshushan A, Rojansky N, Weinstein D. Myasthenia gravis and preeclampsia. Isr J Med
Sci 1994; 30:229.

18. Piura B. The association of preeclampsia and myasthenia gravis: Double trouble. Isr J
Med Sci 1994; 30:243.

19. Gentle SJ, Carlo WA, Tan S, et al. Association of Antenatal Corticosteroids and
Magnesium Sulfate Therapy With Neurodevelopmental Outcome in Extremely Preterm
Children. Obstet Gynecol 2020; 135:1377.

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20. Nguyen TM, Crowther CA, Wilkinson D, Bain E. Magnesium sulphate for women at term
for neuroprotection of the fetus. Cochrane Database Syst Rev 2013; :CD009395.

21. Pryde PG, Mittendorf R. Contemporary usage of obstetric magnesium sulfate:

Indication, contraindication, and relevance of dose. Obstet Gynecol 2009; 114:669.

22. McPherson JA, Rouse DJ, Grobman WA, et al. Association of duration of neuroprotective
magnesium sulfate infusion with neonatal and maternal outcomes. Obstet Gynecol
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23. Turitz AL, Too GT, Gyamfi-Bannerman C. Proximity of magnesium exposure to delivery
and neonatal outcomes. Am J Obstet Gynecol 2016; 215:508.e1.

24. Reeves SA, Gibbs RS, Clark SL. Magnesium for fetal neuroprotection. Am J Obstet
Gynecol 2011; 204:202.e1.

25. Raju TN, Mercer BM, Burchfield DJ, Joseph GF Jr. Periviable birth: executive summary of
a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and
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GRAPHICS

Major placebo-controlled randomized trials of treatment of pregnant women with

magnesium sulfate for neuroprotection of offspring

Gestational
Number Magnesium
age at Cerebral Composite Other
Trial of sulfate Death
randomization palsy outcome outcomes
subjects dose
(weeks)

ACTOMgSO4 1062 <30 4 g loading Total Cerebral Death or Substantial

dose followed pediatric palsy: cerebral gross motor
by 1 g/hour for mortality: 6.8 palsy: dysfunction:
maximum of 13.8 versus 19.8 3.4
24 hours versus 8.2% versus versus
17.1% RR 24.0% 6.6%
RR 0.83 RR 0.83 RR
0.83 95% 95% CI 0.51
95% CI 0.66- 95% CI
CI 0.54- 1.03 0.29-
0.64- 1.27 0.91
1.09 Death or
substantial
gross motor
dysfunction:
17.0
versus
22.7%
RR
0.75
95% CI
0.59-
0.96

BEAM 2241 24 to 31 6 g loading Death: Moderate to Stillbirth or  

dose followed 9.5 severe infant death
by 2 g/hour for versus cerebral by one year of
maximum of 8.5% palsy: corrected age
12 hours RR 1.9 or moderate
1.12 versus or severe
3.5% cerebral palsy
95%
RR at or beyond
CI
0.55 two years of
0.85-
corrected
1.47 95%
age:
CI
0.32- 11.3
0.95* versus
11.7%
RR 0.97
95% CI
0.77-
1.23

PREMAG 573 <33 4 g loading     Cerebral palsy  

dose, no or death:
maintenance OR 0.65
dose 95% CI
0.42-
1.03
Severe motor
dysfunction
or death:

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OR 0.62
95% CI
0.41-
0.93

ACTOMgSO4: Australasian Collaborative Trial of Magnesium Sulphate; RR: relative risk; BEAM: Beneficial Effects of Antenatal
Magnesium Sulfate; OR: odds ratio.
* When evaluated in terms of gestational age at randomization (<28 weeks versus ≥28 weeks), only infants of pregnancies
randomized at <28 weeks had a significant reduction in moderate or severe cerebral palsy.

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3/11/2020 Neuroprotective effects of in utero exposure to magnesium sulfate - UpToDate

Contributor Disclosures
Hyagriv N Simhan, MD, MS Nothing to disclose Katherine P Himes, MD, MSCR Nothing to
disclose Vincenzo Berghella, MD Consultant/Advisory Boards: ProtocolNow [Clinical
guidelines]. Vanessa A Barss, MD, FACOG Nothing to disclose

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