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Dr. Azadeh Pravin PatelSecond Year P. G Student V. S.

HospitalGuided By :

Dr. Sushma Shah | Dr. Megha Patel | Dr. Shashwat Jani

Is MgSO4 a Neuroprotector in Preterm delivery?

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Defination of Preterm Labor Labor is preterm when it occurs in a

patient whose gestation is less than 37 completed weeks (less than 259 days) from the first day of last menstrual period.

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Sources of Evidence PubMed (RCT , Meta analysis & Reviews) 3-

2012 Cochrane Library till 3-2012. Australian National Clinical P. Guidelines

2010 ACOG , Committee Opinion 2010 SOGC Clinical Practice Guideline 2011 UpToDate 19.3 , January 2012

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Preterm Birth And CNS Injuries

A) Pathologically :2 CNS injuries :

(1) Intraventricular Hemorrhage

Usually diagnosed by ultrasound

(2) White Matter Injury.

Usually diagnosed by MRI

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MRI left lateral I.V. Hemorrhage T1 &T2

Tran cranial U/SI.V. Hemorrhage

MRI T2 White Matter Injury

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B ) Clinically:

Adverse CNS outcomes are

1 Cerebral palsy (CP)

2 Cognitive impairment3 Blindness,deafness & developmental delay.

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CEREBRAL PALSY

CP is the most common cause of severe motor

disability in childhood.

PREVELENCE : 2 TO 2.5 per 1000 live births.

For ALL Live birth ,Compared with infants at term the

CP risk is: At 34-36 weeks : 3 fold

At 30-33 weeks : 8- 14 fold

At 28-30 weeks : 46 fold

At < 28 weeks : 80 FoldSOGC Clinical Practice Guideline No. 258, May 2011

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Etiology Of CP

It is multi factorialPrematurity :42-78 %

Intrauterine growth restriction:34%

Intrauterine infection :28%

Antepartum hemorrhage : 27%

Severe placental pathology : 21%

Multiple pregnancy : 20%

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Clinical Types of CP

There are 4 main types of CP:1. Spastic (increased muscle tone)2. Dyskinetic (slow, uncontrolled movements)3. Ataxic (problems with balance and depth

perception)4. MixedThe most common pattern is spasticity plusdyskinetic movements.CP can be reliably diagnosed by the age of 2

years.Center for Disease Control and Prevention (CDC).. Accessed March 3,2011.

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Ataxic CPSpastic CP

Spastic CP

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To date, there is no known :

Cure for CP.

Effective antenatal preventive

measures

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Use of MgSO4 in Obstetrics : Eclampsia:Prophylaxis & management

Tocolysis :No longer recommended

Fetal neuroprotection in preterm delivery :

A new evidence &validation

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Evidence Of The Neuroprotective Effects Of MgSO4

Observational studies Randomized controlled trials Meta-analyses.Validation: Guidelines& Committee Opinion

Australian National Clinical P. Guidelines 2010

ACOG , Committee Opinion 2010

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Observational StudiesPreterm infants born to women with preeclampsia

had a lower incidence of adverse CNS outcomes

than those without preeclampsia.

There was an association between antenatal

MgSO4 administration and reduction of of CP

among infants born < 1500 g.

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Meta-analyses 

In 2009, a milestone was reached with thepublication of 3 meta- analyses, all of which included the same 5 RCTs and concluded

that :MgSO4 for fetal neuroprotection decreases the risk of childhood CP

Doyle et al. Cochrane Database Syst Rev. 2009

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Mechanism :

The mechanism is not well understood potential neuroprotective actions include:

Antioxidant effects Reduction in pro-inflammatory cytokines Inhibition of calcium influx into cells Stabilization of membranes Increased cerebral blood flow Prevention of large blood pressure fluctuations

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The Cochrane Review :Result 1) MgSO4 significantly reduced the risk of :

Cerebral palsy

Substantial gross motor dysfunction

(inability to walk without assistance ) at 2

years of age

2) MgSO4 had No significant effect of on

pediatric (fetal, neonatal and later) mortality.Doyle et al., Cochrane Database Syst Rev. 2009

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Cochrane review 2009 MgSO4 Vs no MgSO4 , Outcome 6 Substantial gross motor dysfunction.

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The Cochrane Systematic Review concluded that : MgSO4 reduced the risk of cerebral palsy by 32 % (from 5.4% to 3.7% with absolute risk reduction of 1.7 %.)* The Number needed to treat(NNT) to benefit one baby was 63 women. These compare favorably with the 70 women with preeclampsia to preventone eclamptic fit.

Doyle et al Cochrane Database Syst Rev. 2009 *

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The Cochrane Systematic Review Maternal side effects :NauseaFlushing Hypotension Tachycardia,Palpitation

There were no differences seen in rates of : Maternal respiratory depression Postpartum haemorrhage Caesarean delivery Doyle et al Cochrane Database Syst

Rev. 2009

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Despite these favourable results, strong

Evidence is lacking with respect to 4 clinical issues:.

1-The gestational age below which this therapy should be offered.

2. The optimal loading and maintenance doses.

Doyle et al Cochrane Database Syst Rev. 2009

The 3 Meta-analyses Conclusion :  

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3- MgSO4 has not been associated with ↓ in :

CNS pathology

Intraventricular hemorrhage

White matter injury(Cystic periventricular

leucomalacia)

Other adverse developmental outcomes

Developmental delay& neurological impairment.

Blindness

Deafness Doyle et al Cochrane Database Syst Rev. 2009

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 4 :There is no information on the

effect of MgSO4 on outcomes

beyond 2 years of age : Age on learning disabilities

School difficulties & disabilities

Doyle et al Cochrane Database Syst Rev. 2009

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1- The Australian National Clinical Practice Guidelines March 2010.

In women at risk of early preterm imminentBirth(expected within 24 Hs), use MgSO4 for neuroprotection of the fetus, infant and child:

The gestational age : < 30 weeksDosage: 4g IV loading dose, over 30 minutes.

followed by a 1g/hr , maintenance infusion until birth.

The Antenatal Magnesium Sulphate for Neuroprotection Guideline Development Panel. : National Clinical Practice Guidelines. The Australian Research Centre for Health of Women and Babies, The University of Adelaide; 2010.

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2- The ACOG Committee Opinion on MgSO4 for March 2010.The available evidence suggests that MgSO4 givenbefore anticipated early preterm birth reduces therisk of cerebral palsy in surviving infants.No official opinion was given on a gestational age cut-off.It was recommended that physicians developguidelines around the issues of inclusion criteria, dosage, concurrent tocolysis, and monitoring .larger trials.American College of Obstetricians and Gynecologists ACOG Committee on Obstetric Practice; Society for Maternal-Fetal Medicine. Committee Opinion 19. No. 455:

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1)For women with imminent preterm birth (< 32weeks), antenatal MgSO4 administration should

be considered for fetal neuroprotection. (I-A)2) Antenatal MgSO4 should be considered from

viability to < 32 weeks. (II-1B) (still controversial)

3) If antenatal MgSO4 has been started, tocolysis

should be discontinued. (III-A)SOGC Clinical Practice Guideline No. 258, May 2011

SOGC Guideline Recommendations

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4) MgSO4 should be discontinued if delivery is no longer imminent or maximum of 24 hours therapy has been administered (II-2B)

5) RECOMMENDED DOSE :4g MgSO4 IV loading dose, over 30 minutes, followed by a maintenance infusion of 1g/ hours until birth or for 24hours, whichever comes first. .(II-2B)

6) Mg SO4 should be started, ideally within 4 hours before birth .(II-2B)

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7) No sufficient evidence is available for repeat administration of antenatal MgSO4. (III-L)

8) Delivery should not be delayed if there are maternal and/or fetal indications for emergency delivery. (III-E)

9)When MgSO4 is given for fetal neuroprotection, maternal care providers should use existing protocols to monitor women who are receiving MgSO4 for preeclampsia/eclampsia. (III –A)

10) Fetal Heart Rate should be monitored.

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11) MgSO4 has potential to alter neonate’s neurological evaluation, causing hypotonia or apnea, so health care providers caring for neonate should have increased awareness of this effect. (III-C)

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What is the Imminent Preterm BirthImminent preterm birth” is defined as a highlikelihood of birth due to one or both of thefollowing conditions (II-2):1-Active labour with ≥ 4 cm of cervical dilation,with or without PPROM.2-Planned preterm birth for fetal or maternal indications.

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Criteria for administration :INCLUSION CRITERIA EXCLUSION CRITERIASingleton and multiple pregnancies

Nulliparous and parous

Anticipated vaginal or caesarean delivery

Any reason for preterm birth

Magnesium sulphate already administered for preeclampsia/eclampsia

<12 hours of discontinuation of previously MgSO4 infusion

Magnesium sulphate contraindicated

Fetus unlikely to benefit.

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Close monitoring of maternal urine output is not required if MgSO4 is used for neuroprotection.

Monitoring of Serum Mg level is not required.

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Conclusion Magnesium sulphate has proven role to

reduce the rate of cerebral palsy in case of imminent preterm delivered babies.

Dose being : 4gm MgSO4 i.v. slowly over 30mins, and 1gm/hour infusion until birth or 24 hours which ever is earliest.

There is no increase risk to the mother as compared to its use in pre eclampsia/ eclampsia.

Maternal urine output and serum magnesium level need not to be monitored.

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