As many more premature infants survive, the numbers of these infants with health problems also has increased. The rate of cerebral palsy in extremely premature infants is approximately 20%. Magnesium sulfate, the most commonly used drug in the US used 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.

Condition	Treatment or Intervention	Phase
Cerebral Palsy Intraventricular hemorrhage Periventricular Leukomalacia Pulmonary Edema Abruptio Placentae	Drug: magnesium sulfate	Phase III

Further Study Details: 

Expected Total Enrollment:  2000

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). 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.

Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• Pregnant with diagnosis of preterm labor
• Membrane rupture or delivery definitely planned with 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

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

Study chairs or principal investigators

Dwight Rouse, MD,  Principal Investigator,  University of Alabama, Birmingham   

Study ID Numbers:  NICHD-0800; U10-HD40473; U10-HD21410; U10-HD27905; U10-HD27917; U10-HD27860; U10-HD27915; U10-HD34116; U10-HD34208; U10-HD34136; U10-HD40462
Record last reviewed:  December 2004
Last Updated:  December 1, 2004
Record first received:  April 17, 2001
ClinicalTrials.gov Identifier:  NCT00014989
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08