TO STUDY THE EFFECT OF ANTENATAL MAGNESIUM SULPHATE FOR NEUROPROTECTION IN PRETERM BABIES

Strong from five randomized controlled trials and five meta-analyses has demonstrated that magnesium sulfate, when administered significantly reduces the risk of neurological disabilities. In our study, we aimed at assessing the effectiveness and safety of antenatal magnesium sulphate for neuroprotection in the

629 disability associated with preterm birth is one of the major persistent challenge. The risk of morbidity & mortality is inveresly related to gestational age at birth.
In observational studies, antenatal administration of magnesium sulphate has been considered as neuroprotective . The dose of 4g given intravenously over 15 min continued by 1g/h until maximum 24 hr& minimum 4 hr is standard regimen proposed in most guidelines. Owing to its biological properties , including its action on N-methyl-Daspartate receptor blocker &its antiinflammatory effects, magnesium is a good candidate for neuroprotection. Aim of this study is to determine the effectiveness of magnesium sulphate given for neuroprotection to women at risk of preterm birth before 32 week gestation in preventing neurological deficit.

Methods:-
This was prospective randomized controlled trial conducted during the period of January 2019 to 2020 in the department of obstetrics & gynecology at patna medical college and hospital, Patna. The study recruited 586 patients admitted in labour ward .They were randomised into 2 groups.
Group A : 294 Patients in preterm labour receiving magnesium sulphate as neuroprotective agent Group B: 292 Patients in preterm labour receiving sodium chloride solution.
These patient had regular antenatal checkup & routine blood investigations & satisfied the inclusion and exclusion criteria.

Inclusion Criteria
1. All pregnant women with single, twin fetus younger than 32 week gestational age withpretermlabour . 2. Who consent to be part of the study Exclusion Criteria 1. Women with gestational age more than 32 weeks 2. Women in second stage of labour 3. History of receiving magnesium sulphate therapy in this pregnancy(e.g magnesium sulphate used for eclampsia, hypertensive disease of pregnancy). 4. Contraindications to magnesium sulphate-respiratory rate <16/min Absent patellar reflex Urine output<100ml in previous 4 hrs Renal failure Hypocalcemia Eligible women who gave written informed consent were enrolled . patients in both groups underwent through history taking, clinical examination, ultrasonography to confirm gestational age.

Intervention
In group A patients were given a loading infusion of 8ml (4g) [16mmol] of magnesium sulphate for 20 mins followed by a maintainence infusion of 2ml/h until birth (if occurred within 24 hr) or upto 24 hrs.
In groupB patients were given infusion of 8 ml of sodium chloride solution for 20 min followed by maintainence infusion of 2ml/h until birth (if occurred within 24 hr) or upto 24 hrs.
Pulse rate, blood pressure , respiratory rate, knee jerk, urine output were monitored throughout infusion and any adverse effects were recorded. The loading and maintainence dose were stopped if respiratory rate decrease more than 4 min, bp fall more than 15 mm hg below baseline.
All surviving infants had a cranial ultrasound performed within first7 days of life to detect intraventricular hemorrhage & a later ultrasound (beyond 4 week at age or at time of discharge) to identify periventicularleukomalacia .

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Statistical Analysis Data analysis used χ2 or Fisher's exact test, as appropriate, for categorical variables and the ANOVA test for continuous variables. P value <0.05 is applied as statistically significant.     Table 3. shows complications due to intervention in both groups like nausea& vomiting, headache, flushing &sweating, hypotension, palpitation, it was found that complications noted in both the groups were statistically insignificant. There was no hyporeflexia in any group . There was 1 case of respiratory depression ingroupA that lead to termination of intervention. In 9 cases, postpartum hemorrhage occurred in group A & 4 cases in group B which was successfully managed conservatively.

Discussion:-
In the late 1990s studies of infants born to mother given magnesium sulphate to prevent eclamptic seizures or as tocolysis showed reduction in rate of cerebral palsy. Although exact mechanism of action of magnesium sulphate as neuroprotective agent is unknown but it is seen that it acts as NMDA (N-methyl-D-aspartic acid) receptor antagonist present on oligodendrocyte which is important in glial injury process. Magnesium sulphate may reverse the harmful effects of hypoxic/ischemic brain injury by blocking NMDA recptors, acting as calcium antagonist and reducing calcium influx in cells. It also protect from free radical injury & act as vasodilator, prevet hypoxic injury,attenuates cytokine or excitatory amino acid induced cell damage and has anti apoptotic activity. Magnesium form complex with adenosine triphosphate which is required for activity of ion pumps, enzymes, proteins and various transporters.
Five randomized controlled trials, three meta -analyses, and a Cochrane review was conducted. On the basis of these studies , the university of Adelaide issued, in march 2010, a guideline on best practice for clinical care in the use of antenatal magnesium sulphate prior to preterm birth for the neuroprotection of fetus, infant and child. 633 In a systematic review study conducted by Doyle et al. in 2009 with the aim of studying the effect of antenatal MgSO 4 on neurologic outcomes in preterm infants, the results showed that use of MgSO 4 dramatically reduced the risk of cerebral palsy in the children of women at risk of preterm birth also, a significant decrease was observed in the rate of substantial gross motor dysfunction butno statistically significant effect on pediatric mortality, or on other neurologic impairments or disabilities, in the early years of life of children . In general, there are many reports that show that MgSO 4 increases the antioxidant properties of the brain, protects the brain cells against hypoxia and apoptosis, and normalizes platelet aggregation .
Since 2010, an increasing number of obstetrical societies have recommended its use to improve the neurological outcomes of preterm infants, especially the International Federation of Gynecology and Obstetrics and World Health Organization in 2015, and France in 2017 A study by Petrova and Mehta in 2012 revealed that there was no significant association between the use of magnesium sulfate, IVH, and parenchyma injury.
The Cochrane review of trials concluded that antenatal magnesium sulphate therapy given to mother at risk of preterm birth substantially reduced the risk of cerebral palsy in their children , there was also significant reduction in rate of gross motor dysfunction.

Conclusion:-
Although various studies have suggested that magnesium sulphate is cost effective and efficient neuroprotective agent in preterm babies but in our study we could not find significant difference between magnesium and placebo group , but it is proved to be efficient in preventing intraventricular hemorrhageand overall mortality.
More study is needed to clarify the impact of magnesium on the cognitive outcome.