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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 2010ACOG , Committee Opinion 2010 SOGC Clinical Practice Guideline 2011UpToDate 19.3 , January 2012 4Slide5

Preterm Birth And CNS Injuries

A) Pathologically

:

2 CNS injuries :

Intraventricular Hemorrhage Usually diagnosed by ultrasound White Matter Injury.Usually diagnosed by MRISOGC Clinical Practice Guideline No. 258, May 2011

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MRI left lateral I.V. Hemorrhage T1 &T2

Tran cranial U/S

I.V. Hemorrhage

MRI T2 White Matter Injury

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B ) Clinically:

Adverse CNS outcomes are

1 Cerebral palsy (CP)

2 Cognitive impairment

3 Blindness,deafness & developmental delay.SOGC Clinical Practice Guideline No. 258, May 20117Slide8

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 foldAt 28-30 weeks : 46 foldAt < 28 weeks : 80 Fold

SOGC Clinical Practice Guideline No. 258, May 20118Slide9

Etiology Of CP

It is multi factorial

Prematurity :42-78 %

Intrauterine growth restriction:34%

Intrauterine infection :28%Antepartum hemorrhage : 27%Severe placental pathology : 21%Multiple pregnancy : 20%9Slide10

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 3,2011.10Slide11

Ataxic CP

Spastic CP

Spastic CP

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To date, there is no known :

Cure for CP.

Effective antenatal preventive measures

SOGC Clinical Practice Guideline No. 258, May 2011

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Use of MgSO

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in Obstetrics :

Eclampsia

:Prophylaxis & managementTocolysis :No longer recommended Fetal neuroprotection in preterm delivery : A new evidence &validation13Slide14

Evidence Of The

Neuroprotective

Effects Of MgSO

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Observational studies Randomized controlled trials Meta-analyses.Validation: Guidelines& Committee OpinionAustralian National Clinical P. Guidelines 2010ACOG , Committee Opinion 2010 SOGC Clinical Practice Guideline May 2011

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Observational Studies

Preterm 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.15Slide16

Meta-analyses 

In 2009, a milestone was reached with the

publication of 3 meta- analyses, all of which

included the same 5 RCTs and concluded that :

MgSO4 for fetal neuroprotection decreases the risk of childhood CPDoyle et al. Cochrane Database Syst Rev. 200916Slide17

Mechanism :

The mechanism is not well understood

potential neuroprotective actions include:

Antioxidant effects

Reduction in pro-inflammatory cytokines Inhibition of calcium influx into cellsStabilization of membranes Increased cerebral blood flowPrevention of large blood pressure fluctuations17Slide18

The Cochrane Review :Result 

1) MgSO

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significantly reduced the risk of :Cerebral palsy Substantial gross motor dysfunction(inability to walk without assistance ) at 2years of age2) MgSO4 had No significant effect of on pediatric (fetal, neonatal and later) mortality.Doyle et al.,

Cochrane Database Syst Rev. 200918Slide19

Cochrane review 2009 MgSO

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Vs no MgSO

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, Outcome 6 Substantial gross motor dysfunction.19Slide20

The Cochrane Systematic Review concluded that :

MgSO

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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 :

Nausea

Flushing

Hypotension Tachycardia,PalpitationThere were no differences seen in rates of :Maternal respiratory depressionPostpartum haemorrhage Caesarean deliveryDoyle et al Cochrane Database Syst Rev. 2009 21Slide22

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. 2009The 3 Meta-analyses Conclusion :  

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3- MgSO

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has not been associated with ↓ in :

CNS pathology

Intraventricular hemorrhage White matter injury(Cystic periventricular leucomalacia)Other adverse developmental outcomesDevelopmental delay& neurological impairment.BlindnessDeafnessDoyle et al Cochrane Database Syst Rev. 2009

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4 :There is no information on the effect of MgSO

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on outcomes beyond 2 years of age :

Age on learning disabilities School difficulties & disabilitiesDoyle et al Cochrane Database Syst Rev. 200924Slide25

1- The Australian National Clinical Practice Guidelines March 2010.

In women at risk of early preterm imminent

Birth(expected within 24 Hs), use MgSO

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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; 2010.25Slide26

2- The ACOG Committee Opinion on MgSO4 for March 2010.

The available evidence suggests that

MgSO

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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: 26Slide27

1)For women with

imminent preterm birth

(< 32weeks), antenatal MgSO4 administration should

b

e 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, tocolysisshould be discontinued. (III-A)SOGC Clinical Practice Guideline No. 258, May 2011SOGC Guideline Recommendations27Slide28

4) MgSO

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

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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)28Slide29

7)

No sufficient evidence is available for repeat administration of antenatal

MgSO4. (III-L

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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.29Slide30

11) MgSO

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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 Birth

Imminent preterm birth” is defined as a high

likelihood of birth due to one or both of the

following 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.SOGC Clinical Practice Guideline No. 258, May 201131Slide32

Criteria for administration :

INCLUSION

CRITERIA

EXCLUSION

CRITERIASingleton and multiple pregnanciesNulliparous and parousAnticipated vaginal or caesarean deliveryAny reason for preterm birthMagnesium sulphate already administered for preeclampsia/eclampsia<12 hours of discontinuation of previously MgSO4 infusionMagnesium sulphate contraindicatedFetus unlikely to benefit.SOGC Clinical Practice Guideline No. 258, May 201132Slide33

Close monitoring of maternal urine output is not required if MgSO

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is used for neuroprotection.

Monitoring of Serum Mg level is not required.

SOGC Clinical Practice Guideline No. 258, May 201133Slide34

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.34Slide35

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