Magnesium Sulfate Perinatal Neuroprophylaxis Thomas R Easterling MD

Magnesium Sulfate • Perinatal Neuroprophylaxis Thomas R. Easterling, MD Professor Maternal-Fetal Medicine University of Washington Seattle, WA 1

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Long Term Survival 4

Cerebral Palsy Term Rate Impaired Work Capacity Term Rate 5

Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial Lancet, 1995; 345 6

Cerebral Palsy Antenatal Steroids Reduce the Incidence Of Cerebral Palsy All trials 6. 4% vs. 10. 2% OR 0. 59 (0. 35 -0. 97) 7

• < 30 weeks’ Gestation • Mg. SO 4 - 4 g Bolus - 1 g per Hour • 2 Year Follow-up 8

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• < 24 -31 weeks’ Gestation • Mg. SO 4 - 4 g Bolus - 2 g per Hour • 2 Year Follow-up 11

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• < 33 weeks’ Gestation • Mg. SO 4 - 4 g Bolus - no maintenance • At Hospital Discharge 18

WMI - white matter injury 19

• 5 Clinical Trial with 6145 Babies • Cerebral Palsy (RR) 0. 68 CI (0. 54 to 0. 87) • Gross Motor Dysfunction (RR) 0. 61 CI (0. 44 to 0. 85) “The neuroprotective role for antenatal magnesium sulfate … is now established. ” The number of women to treat to benefit one baby is 63; 95% CI (43 to 155). 20

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Cerebral Palsy 22

Gross Motor Dysfunction 23

Pediatric Mortality 24

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Mg++ Neuroprophylaxis Mechanism CNS NMDA - (N-methyl-D-aspartate) Hypoxia • activation of NMDA and non-NMDA receptors by the excitatory neurotransmitter, glutamine • increased intracellular Ca++ • intracellular Ca++ - free radical generation and cell death 29

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Mg++ Neuroprophylaxis Mechanism non-CNS Microvascular Stabilization Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial Lancet, 1995; 345 31

Magnesium Sulfate for Neuroprotection Final Recommendations - draft • Indication Imminent preterm delivery Not limited by cause of risk (eg. PROM, PTL, preeclampsia, bleeding…) • Gestational Age < 28 weeks gestation – recommended 28 -34 weeks gestation - offered with counseling • Dose 4 gm bolus, followed by 1 gm/hour infusion. Mg levels not indicated without renal complications. • Discontinuation undelivered in 12 hours • Restart recurrent risk for preterm delivery >3 hours from d/c - rebolus • Urgent delivery should not be delayed to wait for Mg. SO 4 32

Cerebral Palsy Term Rate Impaired Work Capacity Term Rate 33

Magnesium Sulfate for Neuroprotection Final Recommendations - draft • Indication Imminent preterm delivery Not limited by cause of risk (eg. PROM, PTL, preeclampsia, bleeding…) • Gestational Age < 28 weeks gestation – recommended 28 -34 weeks gestation - offered with counseling • Dose 4 gm bolus, followed by 1 gm/hour infusion. Mg levels not indicated without renal complications. • Discontinuation undelivered in 12 hours • Restart recurrent risk for preterm delivery >3 hours from d/c - rebolus • Urgent delivery should not be delayed to wait for Mg. SO 4 34