Effect of magnesium sulphate infusion on neonatal outcomes in babies with perinatal asphyxia

Abstract

Introduction- With a relatively scant evidence base in Indian population, this study aimed to determine the efficacy of intravenous magnesium sulphate in neonates with moderate to severe perinatal asphyxia on the severity of seizures, number of anticonvulsants used, duration of hospitalization and feeding pattern at discharge. Methodology- This was a non-blinded randomized controlled trial that was conducted among 227 neonates admitted to the SNCU of MKCG Medical College Hospital. Randomization and allocation of eligible neonates was done using software. The intervention used was magnesium sulfate given intravenously by trained pediatricians in a loading dose of 250 mg/kg/dose, given over 1 hour in 20 ml of 5% dextrose solution. This was given at the time of admission followed by two infusions of the same dosage after 24 and 48 hours of the first dose. Outcomes on neonatal feeding, survival, need for medications and seizure management were recorded and analysed using an intention to treat protocol. Results- The distribution of most clinico-social parameters were comparable between the 2 groups. The babies who received MgSO4 within 6 hours of life achieved earlier initiation of feeds (32 hours) as compared to control groups (63 hrs). They also reached full feeding significantly earlier.

Neonatal magnesium sulphate for neuroprotection: A systematic review and meta‐analysis

“…43,57 Twelve studies (41.4%) were published in the last 5 years. 29,30,33,39,42,43,47,51,52,57,59,61 There were 2099 infants randomized in the 25 RCTs, 29-47, 49-51, 53-61 and 871 infants in the non-randomized studies. 48,52,62,63 The number of infants per RCT ranged from 22 36 to 260.…”

“…Treatment with magnesium sulphate versus placebo or no treatment reduced the risk of neonatal death (RR = 0.68; 95% CI = 0.53-0.86; 13 RCTs, 31,35,36,41,42,44,46,50,51,56,58,60,61 1033 infants; low-certainty evidence [Figure 1]). No obvious asymmetry raising concern about potential publication bias was observed on visual assessment of the funnel plot (Appendix S3).…”

“…Infants treated with magnesium sulphate versus placebo or no treatment were at reduced risk of seizures (eight RCTs, 31,35,36,41,46,58,60,61 392 infants), requiring two or four anticonvulsant drugs (both two RCTs, 36,51 249 infants), having more than five seizures (one RCT, 51 227 infants), having any abnormalities on computed tomography at day 14 (four RCTs, 31,35,41,49 171 infants) and on day of discharge (one RCT, 59 66 infants), a 'composite neonatal adverse outcome' (variously defined, two RCTs, 36,46 72 infants), neurological abnormalities at discharge (variously defined, five RCTs, 31,40,46,50,59 207 infants), requiring oxygen (one RCT, 51 227 infants), experiencing 'shock' (two RCTs, 51,60 347 infants), requiring three inotropes (dobutamine, dopamine, adrenaline) (one RCT, 51 227 infants), and requiring nasogastric feeds on day 14 (Table 1).…”

“…For infants, magnesium sulphate versus placebo or no treatment was associated with an increase in 'control of fits' (one RCT, 30 260 infants), seizure control with one anticonvulsant (one RCT, 60 52 infants), requiring only one anticonvulsant (two RCTs, 36,51 249 infants), improved recovery from abnormal neurological examination within 4 days (one RCT, 60 105 infants), a 'good short-term neonatal outcome' (variously defined, four RCTs, 31,40,41,50 138 infants), normal neuromotor tone at discharge (Amiel-Tison criteria) (one RCT, 60 67 infants), normal or improved neurological status at discharge (variously defined, three RCTs, 59-61 213 infants), establishing feeding (oral or tube) at day 7 (two RCTs, 31,46 72 infants), and oral feeding at discharge (nine RCTs, 31, 40, 49-51, 56, 59-61 815 infants) (Table 1). Neonatal magnesium sulphate versus placebo or no treatment was associated with shorter duration of seizures (days) (three RCTs, 41,42,60 147 infants), recovery from neurological abnormalities (days) (not defined, one RCT, 60 120 infants), initiation of 'feeds' (days) (not further defined, one RCT, 42 62 infants), nasogastric tube feeding, paladai feeding, and direct breastfeeding (all days) (all in one RCT, 60 120 infants), hospital stay (days) (one RCT, 42 62 infants), and lower weight (kg) and length (cm) (both one RCT, 60 41 infants) at 12 months (Table 1).…”

“…Since then, a further 20 RCTs have been published. 29,30,32,33,39,40,42,43,46,47,[49][50][51][55][56][57][58][59][60][61] As expected, with the widespread implementation of therapeutic hypothermia for HIE as standard care in HICs, all 13 of the newer RCTs 30, 32, 40, 42, 46, 49-51, 56, 58-61 comparing magnesium sulphate with placebo or no treatment were conducted in LMICs (six in Pakistan 30,42,49,56,59,61 and five in India 32,46,51,58,60 ), where evidence for the efficacy of therapeutic hypothermia in neonatal encephalopathy is currently uncertain. [6][7][8] Similarly, the three RCTs comparing magnesium sulphate with an alternative agent (melatonin 33,43 or phenobarbital 57 ) in the absence of therapeutic hypothermia, were from LMICs.…”