A Randomized Controlled Trial of Intramuscular Magnesium Sulphate in Neonates with Severe Perinatal Asphyxia

Kamalarathnam, C N (2013) A Randomized Controlled Trial of Intramuscular Magnesium Sulphate in Neonates with Severe Perinatal Asphyxia. Masters thesis, Madras Medical College, Chennai.


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INTRODUCTION: Neonatal encephalopathy following perinatal hypoxia and ischemia is a major cause of neonatal morbidity and mortality globally. In resource rich countries, the incidence of severe perinatal asphyxia (causing death or severe neurological impairment) is about 1/1000 live births. In developing countries, rates of birth asphyxia are several folds higher, ranging from 4.6 per1000 in Cape Town to 26 per 1000 in Nigeria and fatality rates may be 40% or higher. Data from hospital-based studies suggest an incidence of 5–10/1000 live births. In India, the National Neonatal Perinatal Database reported an incidence of 5% of intramural live births among studies conducted in 16 medical institutes. As per World Health Organization (WHO) statistics, between four and nine million newborns develop birth asphyxia each year. Of those, an estimated 1.2 million die and at least the same number develop severe consequences, such as epilepsy, cerebral palsy, and developmental delay. Encephalopathy occurs in 50% to 60% patients with severe perinatal asphyxia. Moderate/severe hypoxic ischemic encephalopathy (HIE) causes significant morbidity and death in the neonatal period and permanent neurodevelopmental handicaps among survivors. Among neonates with moderate HIE, 20% to 37% die and 30% to 40% develop neurodeficits, whereas 50% of patients with severe HIE die and almost all survivors develop neurological deficits. Neurological abnormality at discharge is a strong predictor of long term neurodevelopment delay. AIM OF THE STUDY: To determine whether intramuscular magnesium sulphate given within six hours after birth improves the short-term outcome in neonates with severe Perinatal Asphyxia. OBJECTIVES: Primary Objective: Death or survival with neurological impairment. Secondary Objectives: 1) Serum. Magnesium levels, 2) Progression of severity of encephalopathy, 3) Need for assisted ventilation, 4) Incidence of seizures, 5) Hypotension requiring inotropic support, 6) Time taken for achieving full oral feeds, 7) Abnormal findings in neurosonogram done before discharge. MATERIALS AND METHODS: Setting: Tertiary care Maternity hospital with around 15,000 deliveries per year (Inborn unit) and Tertiary care 500 bedded Paediatric hospital (Out born unit) in Chennai, Tamilnadu. Subjects: Population consisting of all neonates �36 weeks, born either vaginally or through caesarean section. Sample size: Based on previous Indian studies with an alpha error of 5% and power of 80%, 116 neonates (58 in each group) with moderate to severe asphyxia were studied to allow a detection of 25% reduction in the primary outcome. Inclusion Criteria: Babies (≥ 36 wks), less than six hrs of age at the time of admission and born with severe perinatal asphyxia were eligible for the study. Definition of perinatal asphyxia - babies with any 2 of following 3 criteria: i) H/O fetal distress (late deceleration, fetal bradycardia, meconium stained amniotic fluid). ii) Need for assisted ventilation initiated at birth & continued for more than two minutes after delivery. iii) Apgar score of 0 to 3 at 1minute of age. Exclusion criteria: No features of HIE by six hours of age. Major congenital anomalies requiring surgery, Suspected inborn error of metabolism, Chromosomal anomalies / syndromes associated with cerebral dysgenesis. Design: Doubled blind randomized controlled trial. Study period: May 2012 to February 2013. RESULTS: A total of 1615 neonates admitted to both outborn and inborn unit of our hospital over a period of ten months were screened for perinatal asphyxia. Three hundred and ninety neonates were diagnosed to have perinatal asphyxia. One hundred and fifty two babies had moderate to severe asphyxia and of these 32 were excluded (23 did not develop features of encephalopathy within six hours of age, seven had major congenital malformation or suspicion of inborn error of metabolism and parents refused consent for enrollment for two neonates). One hundred and twenty neonates who fulfilled the inclusion criteria were enrolled in the study. Sixty neonates were assigned randomly to saline (placebo group) and 60 to the magnesium group (treatment group). After randomization two parents chose to withdraw from the study even before commencing treatment. Fifty eight neonates in each group continued treatment and were analysed. The baseline maternal and neonatal characteristics are shown in Table 1 & 2. CONCLUSION: • Intramuscular magnesium sulphate probably has a neuroprotective role in neonates with asphyxial injury. • Magnesium does not alter the mortality rate but reduces neurological impairment among survivors. • Intramuscular magnesium once a day for three days can achieve neuroprotective levels of serum magnesium, which can be maintained for 72 hours. • Adverse side effects like hypotension or respiratory depression were not a concern with this route and dose. • Neonates who had normal neurological examination at discharge or on day 14 may need a long-term neurodevelopmental follow up to be definitive about their outcome. • Though the present study could not convincingly demonstrate the neuroprotective role of magnesium, a larger study with a longer follow up period, with additional support of MRI and EEG technique may give better outcomes.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Intramuscular Magnesium Sulphate, Neonates, Severe Perinatal Asphyxia, Randomized Controlled Trial.
Subjects: MEDICAL > Neonatology
Depositing User: Kambaraman B
Date Deposited: 13 Jan 2020 04:05
Last Modified: 13 Jan 2020 04:05
URI: http://repository-tnmgrmu.ac.in/id/eprint/11812

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