Neuroprotective Efficacy of Postnatal Magnesium Sulphate in Term Infants With Birth Asphyxia

A Multicentre Double Blind Trial of the Neuroprotective Efficacy of Postnatal Magnesium Sulphate in Term/Near Term Infants With Moderate to Severe Birth Asphyxia

Birth/Perinatal asphyxia in Pakistan continues to be a leading cause of neonatal mortality and morbidity. It is estimated that around 80 to 120,000 neonates either suffer from or die from birth/perinatal asphyxia every year. In addition to the large number of deaths a larger number of babies who survive suffer from neuro-developmental disorders adding to the health burden to the society and the nation.

To date other than prevention (which requires global efforts to improve maternal education and health care) the therapies available to treat infants who have suffered from birth asphyxia have been either technically too complex or extremely expensive.

Study Overview

• Status: Completed
• Conditions: Birth Asphyxia
• Intervention / Treatment: Drug: Magnesium sulfate

Detailed Description

Birth/Perinatal asphyxia in Pakistan continues to be a leading cause of neonatal mortality and morbidity. It is estimated that around 80 to 120,000 neonates either suffer from or die from birth/perinatal asphyxia every year. In addition to the large number of deaths a larger number of babies who survive suffer from neuro-developmental disorders adding to the health burden to the society and the nation.

To date other than prevention (which requires global efforts to improve maternal education and health care) the therapies available to treat infants who have suffered from birth asphyxia have been either technically too complex or extremely expensive.

Recent evidence from animal studies and small human studies it has become clear that giving Magnesium Sulphate to term or nearterm babies with moderate to severe birth/perinatal asphyxia reduces both mortality and morbidity.

Magnesium Sulphate as a drug has been in clinical use for decades; its pharmacokinetics, safety profile and mode of action are well known. It is cheap and readily available in Pakistan thus providing an opportunity to confirm or refute the efficacy of Magnesium Sulphate in birth/perinatal asphyxia.

With this in mind the following pragmatic study has been designed using the current practices and available resources:

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Punjab Province
    • Lahore, Punjab Province, Pakistan, 54610
      • services hospital Pakistan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 1 day (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Term and near term infants (≥35 weeks gestation) with moderate to severe birth asphyxia Age at admission < 24 hours

Exclusion Criteria:

• Babies who could not be given first injection before 24 hours of age

Infants with major congenital malformations, sepsis, congenital heart defects, Intracranial hemorrhage and surgical problems

Babies received intubated in emergency

Babies receiving therapeutic hypothermia

Infants with disorders of metabolism

Infants in whom cause other than asphyxia is established as the reason for not initiating or sustaining breathing at birth.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention group; All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it up to 3.0 ml. The resulting reconstituted solution for intravenous infusion shall be 8.3% Magnesium Sulphate delivered over 30 minutes at a rate of 0.1 ml/kg/minute i.e. 8.3 mg/kg/minute. The treatment should be started as soon after birth as possible and not later than 24 hours of life. The babies who meet the exclusion criteria will not be continued into the study.	Drug: Magnesium sulfate; All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it up to 3.0 ml. The resulting reconstituted solution for intravenous infusion shall be 8.3% Magnesium Sulphate delivered over 30 minutes at a rate of 0.1 ml/kg/minute i.e. 8.3 mg/kg/minute. The treatment should be started as soon after birth as possible and not later than 24 hours of life. The babies who meet the exclusion criteria will not be continued into the study.; Other Names: neuroprotective agent
No Intervention: non intervention group; All babies with moderate or severe Hypoxic Ischemic Encephalopathy fulfilling the inclusion criteria will be randomized to receive either the standard treatment (oxygen and fluid therapy along with anticonvulsants if required) plus 3.0 ml/kg of 10% dextrose water given over 30 minutes, three dose given 24 hours apart or to receive standard treatment PLUS three doses of Magnesium Sulphate infusion given over 30 minutes at 250 mg/kg per dose given 24 hours apart. The volume of infusion shall be adjusted with 10% dextrose water to make it up to 3.0 ml. The resulting reconstituted solution for intravenous infusion shall be 8.3% Magnesium Sulphate delivered over 30 minutes at a rate of 0.1 ml/kg/minute i.e. 8.3 mg/kg/minute. The treatment should be started as soon after birth as possible and not later than 24 hours of life. The babies who meet the exclusion criteria will not be continued into the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participants died (receiving mgso4)	Mortality between the two groups (Standard management vs Magnesium Sulphate treated group). Further analyzed by the stage of asphyxia	6 hours
number of participants diednumber (difference in time of administration)	Mortality between the two groups (Standard management vs Magnesium Sulphate treated group) in those where magnesium sulphate was given within six hours of birth and those given later than six hours of birth.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of seizure episode	Frequency of seizures in the two groups and number of days to achieve seizure control.	6 hours
days in achieving full enteral feed	Number of days to achieve oral feed.	1 month
assessment of neurodevelopmental damage	Neurodevelopmental disability in survivors at 18 months of age as assessed by a developmental pediatrician blinded to the study groups using one standard developmental screening method in all babies	1 month

Collaborators and Investigators

• Sponsor: University of Health Sciences Lahore
• Investigators: Study Chair: dr sikandar hayat, MBBS, FCPS, children hospital Lahore

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2023
• Primary Completion (Actual): July 24, 2023
• Study Completion (Actual): August 10, 2023

Study Registration Dates

• First Submitted: January 22, 2023
• First Submitted That Met QC Criteria: January 22, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: magnesium sulphate; birth asphyxia; term infants
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Asphyxia Neonatorum; Physiological Effects of Drugs; Protective Agents; Sulfur Compounds; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Inorganic Chemicals; Sulfur Acids; Central Nervous System Agents; Sulfates; Sulfuric Acids; Magnesium Compounds; Magnesium Sulfate; Neuroprotective Agents
• Other Study ID Numbers: IRB/2022/1018/SIMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be collected on data record forms (DRFs) given in appendix 1. Short-term outcomes include initiation of feed in days, seizure control in days, duration of stay, cranial ultrasound findings and EEG at discharge or last reported before death and discharge or death will be recorded. Cranial ultrasound and EEG will be performed by the same sonologist and neurologist. The developmental assessment will be done at 18 months of age by the same neurodevelopmental pediatrician, blinded to the study using Griffiths scoring system.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No