Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)

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.

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