Magnesium Sulfate • Perinatal Neuroprophylaxis Preeclampsia Update 2006 11/13/2018 Magnesium Sulfate • Perinatal Neuroprophylaxis Thomas R. Easterling, MD Professor Maternal-Fetal Medicine University of Washington Seattle, WA

Preeclampsia Update 2006 11/13/2018

Preeclampsia Update 2006 11/13/2018

Preeclampsia Update 2006 11/13/2018 Long Term Survival

Impaired Work Capacity Preeclampsia Update 2006 11/13/2018 Cerebral Palsy Term Rate Impaired Work Capacity Term Rate

Preeclampsia Update 2006 11/13/2018 Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial Lancet, 1995;345

Antenatal Steroids Reduce the Incidence Of Cerebral Palsy Preeclampsia Update 2006 11/13/2018 Cerebral Palsy All trials 6.4% vs. 10.2% OR 0.59 (0.35-0.97) Antenatal Steroids Reduce the Incidence Of Cerebral Palsy

• < 30 weeks’ Gestation • MgSO4 - 4 g Bolus - 1 g per Hour Preeclampsia Update 2006 11/13/2018 • < 30 weeks’ Gestation • MgSO4 - 4 g Bolus - 1 g per Hour • 2 Year Follow-up

Preeclampsia Update 2006 11/13/2018

Preeclampsia Update 2006 11/13/2018

• < 24-31 weeks’ Gestation • MgSO4 - 4 g Bolus - 2 g per Hour Preeclampsia Update 2006 11/13/2018 • < 24-31 weeks’ Gestation • MgSO4 - 4 g Bolus - 2 g per Hour • 2 Year Follow-up

Preeclampsia Update 2006 11/13/2018

Preeclampsia Update 2006 11/13/2018

• < 33 weeks’ Gestation • MgSO4 - 4 g Bolus - no maintenance Preeclampsia Update 2006 11/13/2018 • < 33 weeks’ Gestation • MgSO4 - 4 g Bolus - no maintenance • At Hospital Discharge

WMI - white matter injury Preeclampsia Update 2006 11/13/2018 WMI - white matter injury

• 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).

Cerebral Palsy

Gross Motor Dysfunction

Pediatric Mortality

Preeclampsia Update 2006 11/13/2018

Preeclampsia Update 2006 11/13/2018

Preeclampsia Update 2006 11/13/2018 1 1 2 2 3 3

Preeclampsia Update 2006 11/13/2018

Mg++ Neuroprophylaxis Mechanism NMDA - (N-methyl-D-aspartate) Preeclampsia Update 2006 11/13/2018 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

Preeclampsia Update 2006 11/13/2018

Mg++ Neuroprophylaxis Mechanism Microvascular Stabilization Preeclampsia Update 2006 11/13/2018 Mg++ Neuroprophylaxis Mechanism non-CNS Microvascular Stabilization Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial Lancet, 1995;345

Magnesium Sulfate for Neuroprotection Final Recommendations - draft Preeclampsia Update 2006 11/13/2018 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 1gm/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 MgSO4

Impaired Work Capacity Preeclampsia Update 2006 11/13/2018 Cerebral Palsy Term Rate Impaired Work Capacity Term Rate

Magnesium Sulfate for Neuroprotection Final Recommendations - draft Preeclampsia Update 2006 11/13/2018 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 1gm/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 MgSO4