The clinical efficacy of magnesium sulfate is due to the multiple pharmacological effects of magnesium ions (Mg²⁺):

1. Central nervous system inhibition and antispasmodics: Magnesium ions are non-competitive antagonists of N-methyl-D-aspartate (NMDA) receptors in the central nervous system. By blocking the influx of calcium ions (Ca²⁺), the release of excitatory neurotransmitters is reduced, thereby raising the seizure threshold and effectively preventing and controlling eclampsia convulsions [1].

2. Vasodilation and endothelial protection: Magnesium ions can competitively inhibit the entry of calcium ions into smooth muscle cells, leading to peripheral and cerebral vasodilation, reducing vascular resistance, improving uteroplacental blood perfusion, and reducing cerebral edema and blood-brain barrier disruption [1].

3. Fetal neuroprotection: Before preterm birth, maternal infusion of magnesium sulfate can enter the fetus through the placenta, thereby blocking NMDA receptors, reducing inflammatory response and oxidative stress, and stabilizing fetal cerebral blood flow, thereby reducing the risk of hypoxic-ischemic brain injury and cerebral palsy in premature infants [2].

Magnesium sulfate is the absolute first-line drug of choice for the prevention of severe preeclampsia and the treatment of eclampsia.

1. Top publication of evidence-based medical evidence

(1) Treatment of eclampsia (Collaborative Eclampsia Trial, 1995): This international multicenter randomized controlled trial published in The Lancet (including 1687 patients) confirmed that magnesium sulfate reduced the risk of eclampsia recurrence by 52% compared with diazepam (RR 0.48, 95% CI 0.36-0.63); compared with phenytoin, the risk of recurrence was reduced by 67% (RR 0.33, 95% CI 0.21-0.53). In addition, there was a downward trend in maternal mortality in the magnesium sulfate group [3].

(2) Prevention of eclampsia (MAGPIE Trial, 2002): This landmark study, published in The Lancet, included 10,141 pregnant women with preeclampsia. The results showed that the incidence of eclampsia was only 0.8% (40/5071) in the magnesium sulfate group compared to 1.9% (96/5070) in the placebo group, and magnesium sulfate significantly reduced the relative risk of eclampsia by 58% (RR 0.42, 95% CI 0.29-0.60). At the same time, magnesium sulfate also reduced the risk of maternal mortality by 45% (RR 0.55, 95% CI 0.26-1.14) [4].

2. Chinese clinical norms and drug recommendations

According to China's "Guidelines for the Diagnosis and Treatment of Hypertensive Diseases of Pregnancy (2020)" [5]:

(1) Severe preeclampsia and eclampsia: Magnesium sulfate must be used for prevention and treatment.

(2) Non-severe preeclampsia: not absolutely contraindicated and can be considered as appropriate. Clinicians should dynamically assess the progression of the patient's condition and use preventive drugs for non-severe patients with a tendency to worsen.

(3) Standard dosing regimen: Intravenous dosing is recommended. The loading dose is 4~5g (dissolved in 20ml of 10% glucose solution), and the slow intravenous bolus (15~20 minutes); Subsequently, it is maintained by intravenous infusion at a rate of 1~2g/h. The total 24-hour dose is usually 25~30g.

(4) Postpartum treatment: After eclampsia or severe preeclampsia, magnesium sulfate is usually continued for 24~48 hours.

For fetuses at risk of preterm birth, prenatal use of magnesium sulfate significantly reduces the risk of cerebral palsy in surviving infants.

1. Top publication of evidence-based medical evidence

(1) BEAM Trial (2008): This multicenter double-blind RCT published in NEJM included 2241 pregnant women at risk of preterm birth at 24~31 weeks. Although no significant difference was found in the primary composite outcome (death before 1 year of age or moderate to severe cerebral palsy after 2 years), the incidence of moderate to severe cerebral palsy was significantly lower in the magnesium sulfate group than in the placebo group (1.9% vs. 3.5%; RR 0.55，95% CI 0.32-0.95） [6]。

(2) ACTOMgSO4 Trial (2003): The study published in JAMA included 1062 pregnant women (< 30 weeks risk of preterm birth). The results showed that the incidence of cerebral palsy in surviving infants in the magnesium sulfate group (6.8%) was significantly lower than that in the placebo group (8.2%) (RR 0.83, 95% CI 0.54-1.27), and although there was no significant difference in overall mortality, it showed a trend towards neuroprotection [7].

(3) Cochrane Review (updated 2024): The latest meta-analysis of six RCTs (involving 6107 children) confirmed that antenatal magnesium sulfate significantly reduced the risk of cerebral palsy in preterm infants within 2 years of age (RR 0.71, 95% CI 0.57-0.89; NNTB=60), while reducing the composite risk of death or cerebral palsy (RR 0.87, 95% CI 0.77-0.98) without increasing the risk of death [2].

2. Chinese clinical norms and drug recommendations

According to the Chinese Medical Association's "FIGO2021 Practical Recommendations on the Use of Magnesium Sulfate for Neuroprotection in Premature Infants" [8]:

(1) Applicable gestational age: recommended for patients with a gestational week to 30 weeks of gestation and at risk of preterm birth; For patients at risk of preterm birth at < 32~34 weeks, it can be considered.

(2) Timing of administration: It should be used when preterm labor is planned or expected to be delivered within 24 hours. It should also be used if less than 4 hours before the expected delivery time (and may still benefit).

(3) Dosing regimen: recommended loading dose 4g intravenous infusion (20~30 minutes), followed by maintenance infusion at 1g/h until delivery or up to 24 hours. If there is no delivery after 24 hours, the drug should be stopped; If you are at risk of preterm birth again, consider repeating the dose.

In Chinese primary clinical practice, magnesium sulfate is often used off-label for totosis inhibition (fetal preservation) in preterm birth. However, this practice lacks evidence-based medical support.

(1) A Cochrane Review (2014) clearly pointed out that magnesium sulfate, as a tocolytic agent, is ineffective in delaying labor or preventing preterm birth, and does not improve neonatal outcomes, but may increase the risk of maternal adverse effects [9].

✿ Clinical advice: Magnesium sulfate is not recommended as a conventional tocolytic. In patients with threatened preterm birth, the only clear purpose of magnesium sulfate use should be fetal neuroprotection, not inhibition of contractions themselves.

1. Blood magnesium concentration and clinical monitoring (characteristics of Chinese population)

The internationally recognized effective therapeutic concentration of magnesium sulfate is 1.8~3.0mmol/L, and there is a risk of poisoning if it exceeds 3.5mmol/L (manifested as loss of knee tendon reflex, respiratory depression, cardiac arrest, etc.).

However, studies have shown that a significant proportion of Chinese patients may have serum magnesium ion concentrations below 1.8 mmol/L when treated with standard doses of magnesium sulfate, but still achieve clinical effects in preventing convulsions without adverse events [10].

✿ Clinical advice: Do not blindly pursue specific blood magnesium values, but use clinical symptoms as the core monitoring indicator. Before and during each medication, it must be confirmed:

(1) Knee tendon reflex exists

(2) Respiratory rate≥ 16 beats/minute

(3) Urine output≥ 17ml/h or ≥400ml/24h

(4) Antidote (10% calcium gluconate 10ml)

2. Dose adjustment in patients with renal insufficiency

Magnesium sulfate is almost entirely excreted through the kidneys. In pregnant women with impaired kidney function, magnesium ions are highly susceptible to accumulation and poisoning.

✿ Clinical recommendation: For patients with mild to moderate renal insufficiency (e.g., serum creatinine > 1.2 mg/dL or 106 μmol/L), the maintenance dose must be reduced (e.g., halved to 0.5 g/h), the maximum total dose (no more than 20 g) within 48 hours must be strictly limited, and the frequency of monitoring of serum magnesium concentration must be increased [11]. Patients with severe renal insufficiency or oliguria/anuria should be contraindicated.

3. Medication expiration warning

ACOG recommends that magnesium sulfate should generally not be used for more than 48 hours when used for obstetric indications. Continuous use of magnesium sulfate for a long period of time (> 5~7 days) may lead to decreased blood calcium and bone demineralization in fetal/neonates (FDA warning) [12].