It is about the benefit of providing MGSO4 for fetal neuroprotection in case of preterm births. Mg SO4 is proven by many textbooks and meta-analysis researches to prevent cerebral palsy resulting from extreme prematurity. This ppt discuss mechanism, timing and recommendations of MgSO4 for neuroprotection. thanks.

1. Magnesium Sulfate for Neuroprotection:
Recommendations
Dr Zelalem (R1)

2. Cerebral palsy
• Heterogeneous group of conditions involving permanent
nonprogressive central motor dysfunction that affect muscle tone,
posture, and movement.
• Cerebral palsy is the leading cause of neurologic impairment in young
children
• Prematurity and low birth weight are the most important risk factors
for developing the disease.

3. Epidemiology
GA:
•GA <28 weeks: 82 per 1000 live births
•GA 28 to 31 weeks: 43 per 1000 live births
•GA 32 to 36 weeks: 6.8 per 1000 live births
•GA >36 weeks: 1.4 per 1000 live births
BW:
•<1500 g: 59.2 per 1000 live births
•1500 to 2499 g: 10.2 per 1000 live births
•>2500 g: 1.33 per 1000 live births

4. CP associated Pathologies
●Acute intrapartum Hypoxia
●Prematurity (78 percent)
●Intrauterine growth restriction (34
percent)
●Intrauterine infection (28 percent)
●Antepartum hemorrhage (27
percent)
●Severe placental pathology (21
percent)
●Multiple pregnancy (20 percent)
Causes:
● Perinatal hypoxic-ischemic injury
● Congenital abnormalities
● Genetic susceptibility
● Stroke
● Intracranial hemorrhage
● Intrauterine infection
● Acquired postnatal causes

5. Prevention of CP
 ANTENATAL MEASURES
MgSO4
 INTRAPARTUM MEASURES
Delayed cord clamping
 POSTNATAL MEASURES
Therapeutic hypothermia
Supportive measures:

6. Mechanism
●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
N-Methyl-D- Aspartate (NMDA) receptor blocker
●Protection against oxidative injury via antioxidant effects
●Protection against inflammatory injury via anti-inflammatory effects

7. NICE GUIDELINES, 2019
Women between 24 weeks and 29 + 6 weeks of pregnancy who are:
• In established preterm labour or
• Having a planned preterm birth within 24 hours.
Intravenous magnesium sulfate should also be considered for
neuroprotection of the baby for women between 30 +0 and 33 +6
weeks of pregnancy who are:
• In established preterm labour or
• Having a planned preterm birth within 24 hours

8. ACOG GUIDELENES
• Hospitals that elect to use magnesium sulfate for fetal neuroprotection should
develop uniform and specific guidelines for their departments:
• Regarding inclusion criteria, treatment regimens, concurrent tocolysis and
monitoring in accordance with one of the larger trials

9. WHO
• Magnesium sulfate for fetal protection against neurological
complications
• The use of magnesium sulfate is recommended for
women at risk of imminent preterm birth before 32 weeks of
gestation for prevention of cerebral palsy in the infant and
child.
• Strong recommendation based on moderate-quality evidence

10. Candidates
• 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.

11. • Three dosing regimens
 IV 4 g over 20 minutes, then 1 g/hour until delivery or for
24 hours, whichever came fist;
 IV 4 g over 30 minutes or IV bolus of 4 g given as single
dose; and
 IV 6 g over 20–30 minutes, followed
by IV maintenance of 2 g/hour)
Dose

12. Dose… cont’d
• We favor administration of a 4 g loading of magnesium sulfate over
20 minutes and a maintenance dose of 1 g/hour.
• This regimen is likely to have a more favorable side effect and safety
profile than the higher-dose regimen
MoH 2020 GUIDELINE:
MgSO4 IV 20% 4 gm over 10–15 minutes, followed
by IM 5 gm every 4 hours for 24 hours.

13. Gabbe’s obstetrics recommendation
Magnesium Sulfate for Neuroprotection
• Administration of magnesium sulfate before early PTB will
improve: long-term infant outcomes and
• is recommended for anticipated deliveries before 32 weeks’
gestation after PPROM regardless of attempts at conservative
management.

14. • In a large multicenter trial that studied this issue, 92% of participants
had PROM before 32 weeks’ gestation, and treatment was effective in
preventing:
• Moderate/severe cerebral palsy (1.9% vs. 3.9%) and
• Cerebral palsy overall (4.2% vs.7.3%), by 2 years of age.
• Retreatment was attempted for those initially undelivered and those
who subsequently delivered before 34 weeks
gestation.

15. Patients treated with magnesium sulfate should be assessed
with the following examinations:
a. Deep tendon reflexes and vital signs, including respiratory
rate, should be recorded hourly.
b. Intake and output should be measured every 2 to 4 hours.
c. Magnesium levels should be monitored if any clinical
concern about side effects exists.
5. Calcium gluconate should be readily available to reverse the
respiratory depression that can be caused by magnesium.

16. • If renal function is normal, magnesium is excreted rapidly in the urine.
• In patients with evidence of renal impairment—for example, oliguria
or serum creatinine levels greater than 0.9 mg/dL—magnesium
should be administered cautiously
• Should be followed with frequent vital signs, deep tendon reflexes,
and magnesium serum levels, and
• Doses should be adjusted accordingly.

17. Our MoH 2020 guideline
Recommends MgSO4 for neuroprotection in the following
circumstances:
 PROM; If gestational age is less than 32 weeks and preterm birth is
likely within the next 24 hours, consider magnesium sulfate for
neuroprotection
 PRETERM LABOR; < 32 week

18. The two largest trials
1. Beneficial Effects of Antenatal Magnesium Sulfate-BEAM-Study
(Rouse, 2008)
• 2241 Women
• 6 g loading dose followed by 2 g/hour for maximum of 12 hours
• Death: 9.5 versus 8.5% RR 1.12
• CP: Moderate to severe cerebral palsy: 1.9 versus 3.5% RR 0.55
• Significant reduction in less than 28 week of gestation
• "Stillbirth or pediatric death" was not significantly reduced overall (RR
1.04)

19. 2. ACTOMgSO4 (Australasian Collaborative Trial of Magnesium Sulfate)
• 1062 candidates
• 4 g loading dose followed by 1 g/hour for maximum of 24 hours
• Total pediatric mortality: 13.8 versus 17.1% RR 0.83
• Cerebral palsy: 6.8 versus 8.2% RR 0.83
• Substantial gross motor dysfunction: 3.4 versus 6.6% RR 0.51
• Death or substantial gross motor dysfunction: 17.0 versus 22.7% RR
0.75

23. Controversies
Including concerns about
Potential effects of MgSO4 on fetal heart rate and increased
neonatal resuscitation ,
A lack of understanding of the neuroprotective mechanism of action
and
Inadequate studies describing long-term adverse paediatric
outcomes other than CP

24. Time for
Discussion