Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial) (BEAM)

Randomized Clinical Trial of the Beneficial Effects of Antenatal Magnesium Sulfate (BEAM)

As many more premature infants survive, the numbers of these infants with health problems increases. The rate of cerebral palsy (CP) in extremely premature infants is approximately 20%. Magnesium sulfate, the most commonly used drug in the US to stop premature labor, may prevent CP. This trial tests whether magnesium sulfate given to a woman in labor with a premature fetus (24 to 31 weeks out of 40) will reduce the rate of death or moderate to severe CP in the children at 2 years. The children receive ultrasounds of their brains as infants and attend three follow-up visits over two years to assess their health and development.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy; Intraventricular Hemorrhage; Pulmonary Edema; Periventricular Leukomalacia; Abruptio Placentae
• Intervention / Treatment: Drug: magnesium sulfate

Detailed Description

The prevalence of cerebral palsy is increasing as the survival rate of extremely premature infants is improving. Studies have suggested an apparent association between maternal magnesium sulfate administration and a reduced risk of cerebral palsy. Other studies have suggested a possible association between magnesium sulfate and a reduction in neonatal cranial ultrasound abnormalities which may be markers for subsequent development of cerebral palsy.

This multicenter trial tests whether prophylactic magnesium sulfate given to women, for whom preterm delivery is imminent, reduces the risk of death or moderate to severe cerebral palsy in their children. Women presenting from 24.0 to 31.6 weeks gestation with advanced preterm labor or premature rupture of the membranes (pPROM) and no recent exposure to magnesium sulfate are randomized to receive either intravenous magnesium sulfate or masked study drug placebo. The study drug is administered as a 6 gram loading dose followed by a 2 gram/hour infusion (or equivalent rate for placebo). If after 12 hours, delivery has not occurred and is not anticipated, the infusion is stopped. No other parenteral tocolytics other than the IV medication may be used. Retreatment with study medication is given any time labor recurs or delivery is anticipated until gestational age is > 34.0 wks. Standard clinical management and therapy is to be maintained for all study patients. Patients are assessed for signs of intolerance to the study medications and maternal data are collected up to hospital discharge. A sample of venous blood is collected and neonatal cranial ultrasounds are performed. Up to three follow-up visits are scheduled over two years where certified examiners, masked to study group assignment, collect physical and neurological data, including a modified Gross Motor Function Classification Scale. The Bayley Scales of Infant Development is also administered. Cranial ultrasounds are reviewed centrally.

The primary outcome is a composite outcome of death or moderate to severe cerebral palsy. Secondary outcomes include maternal infectious morbidity, pulmonary edema and placental abruption, neonatal stillbirth and death, intraventricular hemorrhage, periventricular leukomalacia, neonatal infectious and noninfectious morbidity.

• Study Type: Interventional
• Enrollment (Actual): 2136
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Florida
    • Miami, Florida, United States, 33136
      • Dept of OB/GYN, University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Dept of OB/GYN, Hutzel Hospital
  • New York
    • New York, New York, United States, 10019
      • St. Luke's - Roosevelt Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Memorial Hospital, Wake Forest University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0794
      • The University Hospital, University of Cincinnati
    • Cleveland, Ohio, United States, 44109
      • Case Western University
    • Columbus, Ohio, United States, 43210
      • Dept of OB/GYN, Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • MCP Hahnemann University
    • Pittsburgh, Pennsylvania, United States, 15213
      • Dept of OB/GYN Magee Womens Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905-2499
      • Women and Infants Hospital
  • Texas
    • Dallas, Texas, United States, 75235-9032
      • Dept of OB/GYN, Southwestern Medical Center, University of Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch - Galveston
    • Houston, Texas, United States, 77030
      • University of Texas - Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant with diagnosis of preterm labor
• Membrane rupture or delivery definitely planned within 24 hours
• Gestational age > 24.0 and < 31.6 wks, viable fetus

Exclusion Criteria:

• Prior IV magnesium sulfate therapy within 12 hours of screening
• Delivery expected <2 hrs
• Cervical dilation > 8 cm
• More than 2 fetuses
• Known major fetal anomalies
• Hypertension or preeclampsia
• Maternal medical complications contraindicating magnesium sulfate treatment
• Participation in any intervention study which influences infant neurological outcome
• Previous participation in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: TRIPLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Composite outcome of death or moderate to severe cerebral palsy

Secondary Outcome Measures

Outcome Measure
Birth weight
Intraventricular hemorrhage
Maternal
Chorioamnionitis
Endometritis
Other infectious morbidity
Pulmonary edema
Placental abruption
Neonatal
Stillbirth and neonatal death
Neonatal infectious morbidity
Neonatal noninfectious morbidity
Days in NICU

Collaborators and Investigators

• Sponsor: The George Washington University Biostatistics Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Dwight Rouse, MD, University of Alabama at Birmingham; Study Director: Menachem Miodovnik, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

General Publications

• Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics. 1995 Feb;95(2):263-9.
• Schendel DE, Berg CJ, Yeargin-Allsopp M, Boyle CA, Decoufle P. Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA. 1996 Dec 11;276(22):1805-10.
• Hallak M, Berry SM, Madincea F, Romero R, Evans MI, Cotton DB. Fetal serum and amniotic fluid magnesium concentrations with maternal treatment. Obstet Gynecol. 1993 Feb;81(2):185-8.
• Aziz K, Vickar DB, Sauve RS, Etches PC, Pain KS, Robertson CM. Province-based study of neurologic disability of children weighing 500 through 1249 grams at birth in relation to neonatal cerebral ultrasound findings. Pediatrics. 1995 Jun;95(6):837-44.
• Pinto-Martin JA, Riolo S, Cnaan A, Holzman C, Susser MW, Paneth N. Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. Pediatrics. 1995 Feb;95(2):249-54. Erratum In: Pediatrics 2001 Aug;108(2):238.
• Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Alexander JM, Harper M, Thorp JM Jr, Ramin SM, Malone FD, Carpenter M, Miodovnik M, Moawad A, O'Sullivan MJ, Peaceman AM, Hankins GD, Langer O, Caritis SN, Roberts JM; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008 Aug 28;359(9):895-905. doi: 10.1056/NEJMoa0801187.
• Costantine MM, Weiner SJ; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet Gynecol. 2009 Aug;114(2 Pt 1):354-364. doi: 10.1097/AOG.0b013e3181ae98c2.
• Buhimschi CS, Jablonski KA, Rouse DJ, Varner MW, Reddy UM, Mercer BM, Leveno KJ, Wapner RJ, Sorokin Y, Thorp JM Jr, Ramin SM, Malone FD, Carpenter MW, O'Sullivan MJ, Peaceman AM, Saade GR, Dudley D, Caritis SN, Buhimschi IA; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial. EClinicalMedicine. 2019 Mar 22;9:11-18. doi: 10.1016/j.eclinm.2019.03.009. eCollection 2019 Mar.
• Hirtz DG, Weiner SJ, Bulas D, DiPietro M, Seibert J, Rouse DJ, Mercer BM, Varner MW, Reddy UM, Iams JD, Wapner RJ, Sorokin Y, Thorp JM Jr, Ramin SM, Malone FD, Carpenter MW, O'Sullivan MJ, Peaceman AM, Hankins GD, Dudley D, Caritis SN; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Antenatal Magnesium and Cerebral Palsy in Preterm Infants. J Pediatr. 2015 Oct;167(4):834-839.e3. doi: 10.1016/j.jpeds.2015.06.067. Epub 2015 Aug 5.
• Twickler DM, McIntire DD, Alexander JM, Leveno KJ. Effects of magnesium sulfate on preterm fetal cerebral blood flow using Doppler analysis: a randomized controlled trial. Obstet Gynecol. 2010 Jan;115(1):21-25. doi: 10.1097/AOG.0b013e3181c4f7c1.

Helpful Links

• Click here for more information on the NICHD MFMU Research Network.

Study record dates

Study Major Dates

• Study Start: December 1, 1997
• Primary Completion (ACTUAL): February 1, 2007
• Study Completion (ACTUAL): June 1, 2007

Study Registration Dates

• First Submitted: April 17, 2001
• First Submitted That Met QC Criteria: April 17, 2001
• First Posted (ESTIMATE): April 18, 2001

Study Record Updates

• Last Update Posted (ACTUAL): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Cerebral palsy; Preterm delivery; Magnesium sulfate
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Brain Damage, Chronic; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Placenta Diseases; Infant, Premature, Diseases; Encephalomalacia; Cerebral Palsy; Hemorrhage; Pulmonary Edema; Leukomalacia, Periventricular; Abruptio Placentae; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Magnesium Sulfate
• Other Study ID Numbers: NICHD-0800; U10HD036801 (U.S. NIH Grant/Contract); U10HD021410 (U.S. NIH Grant/Contract); U10HD027869 (U.S. NIH Grant/Contract); U10HD027917 (U.S. NIH Grant/Contract); U10HD027860 (U.S. NIH Grant/Contract); U10HD034116 (U.S. NIH Grant/Contract); U10HD034208 (U.S. NIH Grant/Contract); U10HD034136 (U.S. NIH Grant/Contract); U10HD040500 (U.S. NIH Grant/Contract); U10HD040485 (U.S. NIH Grant/Contract); U10HD040544 (U.S. NIH Grant/Contract); U10HD040545 (U.S. NIH Grant/Contract); U10HD040560 (U.S. NIH Grant/Contract); U10HD040512 (U.S. NIH Grant/Contract); U10HD053097 (U.S. NIH Grant/Contract); U10HD027915 (U.S. NIH Grant/Contract); U10HD021414 (NIH); U10HD027905 (NIH); U10HD027861 (NIH); U10HD034122 (NIH); U10HD034210 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be shared after completion and publication of the main analyses in accordance with NIH policy. The dataset can be obtained by email at mfmudatasets@bsc.gwu.edu.