Title

A Randomized Trial Comparing the Impact of One Versus Two Courses of Antenatal Steroids (ACS) on Neonatal Outcome
A Randomized Double-Blinded Study Comparing the Impact of One Versus Two Courses of Antenatal Steroids on Neonatal Outcome
  • Phase

    Phase 4
  • Study Type

    Interventional
  • Intervention/Treatment

    urea betamethasone ...
  • Study Participants

    437
The hypothesis is that administration of two courses of antenatal corticosteroids, compared to one course, will show a 40% reduction in the incidence of composite neonatal morbidity in patients delivering prior to 34 weeks' gestation.
This is a randomized double-blinded placebo-controlled trial. The objective of this study is to evaluate the impact of one versus two courses of antenatal steroids on the incidence of major neonatal morbidity including respiratory distress syndrome in patients delivering prior to 34 weeks' gestation in a randomized prospective fashion.

Preterm delivery occurs in approximately 10% of all deliveries in the United States. Preterm birth is the cause of 75% of neonatal mortality not mentioning the significantly increased morbidity from respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis. Numerous studies have evaluated the safety and efficacy of antenatal corticosteroid (ACS) administration in threatened preterm labor.

National Institutes of Health (NIH) first consensus conference in 1994 evaluated the research in this field. Conclusions included the clear evidence that antenatal corticosteroids decrease the incidence of RDS in infants born at 29-34 weeks gestation, with a decrease in RDS severity for infants born at 24-28 weeks gestation and a decrease in the incidence of intraventricular hemorrhage in infants born at 24-28 weeks gestation without harm to mother or fetus. Their recommendation was to give a single course of corticosteroids to all pregnant women between 24 and 34 weeks gestation who are at risk of preterm delivery within 7 days.

Since the studies on the duration of the effects of antenatal corticosteroids in the fetus are not conclusive, many obstetricians repeat corticosteroids weekly or bi-weekly to patients continuing to be at risk for preterm delivery. Lacking scientific evidence, many investigators have performed retrospective analyses regarding the effects of single-course versus multiple-course antenatal corticosteroids.

The NIH consensus panel reconvened in 2000 and concluded that studies regarding repeated courses of corticosteroids are suggestive of possible benefits, especially in reduction of RDS, however, design flaws limit their validity.

The more recent publication from Caughey and Parer examined the literature for evidence regarding a dose response of the benefits and detriments of antenatal corticosteroids. Based on their complex mathematical analysis they recommend all fetus' between 24 and 34 weeks' gestation at risk for preterm delivery should be given a first course of ANC. If the risk of preterm delivery persists the next course should be given 2 weeks later, for a maximum of two courses. Consistent with all previous articles, the call for a well designed randomized, controlled trial is made.
Study Started
Nov 30
2003
Primary Completion
Feb 29
2008
Study Completion
Feb 29
2008
Results Posted
Mar 01
2011
Estimate
Last Update
Jan 07
2015
Estimate

Drug Betamethasone or Dexamethasone (2nd course of ACS)

Course of Betamethasone or Dexamethasone

  • Other names: Beta, Dex

Drug Placebo

Course of Placebo (NS)

  • Other names: Placebo, Normal Saline.

1 Test group Active Comparator

Receive 2nd Course = Study drug (betamethasone or dexamethasone)

2 - Control Placebo Comparator

Placebo group = received placebo course

Criteria

Inclusion Criteria:

25 to 32 6/7 weeks gestation
Singleton or twin gestation
Received 1st course of betamethasone prior to 30 weeks' gestation
Began 1st course of betamethasone at least 14 days prior to randomization
Risk of delivery in next 7 days due to either maternal or fetal complication (e.g. preterm labor, severe preeclampsia, IUGR, etc.)
Intact membranes

Exclusion Criteria:

Known major fetal anomalies (eg: anencephaly, renal agenesis etc…)
High order multiple gestation (triplets or higher)
Cervical dilation > 5 cm
Clinical chorioamnionitis prior to initiation of second course (two or more of the following; antepartum temperature > 38ºC (100.4ºF), uterine tenderness, foul smelling vaginal discharge or amniotic fluid, maternal tachycardia (>100beats/min), fetal tachycardia (>160 beats/min), or white blood cell count >20x109/L.define)
Ruptured membranes prior to initiation of second course of betamethasone
Already receiving corticosteroids for other conditions (e.g. Lupus, asthma)
Maternal condition contraindicating the use of steroids (e.g. HIV, active Tuberculosis)
Participation in conflicting study

Summary

"Rescue" Course of Betamethasone or Dexamethasone

Placebo (Normal Saline)

All Events

Event Type Organ System Event Term "Rescue" Course of Betamethasone or Dexamethasone Placebo (Normal Saline)

Composite Neonatal Morbidity < 34 Weeks Gestation at Time of Birth.

This outcome measured the total number of neonates with Composite Neonatal morbidity who delivered at < 34 weeks gestation. Composite Morbidity consisted of respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death

"Rescue" Course of Betamethasone or Dexamethasone

71.0
participants

Placebo (Normal Saline)

105.0
participants

Gestational Age at (@) Delivery

Reported the average/mean Neonatal gestational age (GA) (reported in weeks of pregnancy) at the time of birth for both groups (ACS vs. Placebo).

"Rescue" Course of Betamethasone or Dexamethasone

33.1
Weeks (Mean)
Standard Deviation: 3.1

Placebo (Normal Saline)

33.0
Weeks (Mean)
Standard Deviation: 3.1

Neonatal Birth Weight Reported in Grams

Measured mean Birth weights of Neonates in each arm as reported in grams on the birth record.

"Rescue" Course of Betamethasone or Dexamethasone

1905.0
grams (Mean)
Standard Deviation: 738

Placebo (Normal Saline)

1920.0
grams (Mean)
Standard Deviation: 667

Interuterine Growth Restriction (IUGR) or Small for Gestational Age(SGA)in Babies Delivering at < 34 Weeks Gestation.

Noted as the total number of Neonates delivering at < 34 weeks gestation for which their weights fell within the 10th percentile at time of birth.

"Rescue" Course of Betamethasone or Dexamethasone

25.0
paticipants

Placebo (Normal Saline)

20.0
paticipants

Neonatal Head Circumference Taken at Time of Birth.

Reported as the average of all neonatal head circumferences (HC) taken at time of birth in each group.

"Rescue" Course of Betamethasone or Dexamethasone

30.2
centemeters (cm) (Mean)
Standard Deviation: 3.0

Placebo (Normal Saline)

30.0
centemeters (cm) (Mean)
Standard Deviation: 2.9

Number of Babies Who Required Ventilatory Support Within the First 28 Days of Life.

The number of babies who required ventilatory support within the first 28 days of life. Equal to or great than 12 hours was considered one day.

"Rescue" Course of Betamethasone or Dexamethasone

70.0
participants

Placebo (Normal Saline)

95.0
participants

Number of Neonates Who Required Surfactant Therapy After Birth.

The Number of neonates who required surfactant therapy within the first 28 days after birth.

"Rescue" Course of Betamethasone or Dexamethasone

70.0
participant

Placebo (Normal Saline)

99.0
participant

Number of Neonates With Pneumothorax

Total number of neonates with pneumothorax diagnosed postpartum.

"Rescue" Course of Betamethasone or Dexamethasone

4.0
participants

Placebo (Normal Saline)

4.0
participants

Maternal Infectious Morbidity.

Total number of Mothers having Maternal infectious morbidity (e.g. endometritis & maternal sepsis) noted from birth through 28 days after birth

"Rescue" Course of Betamethasone or Dexamethasone

8.0
participants

Placebo (Normal Saline)

10.0
participants

Total

437
Participants

Age, Continuous

29
years (Mean)
Standard Deviation: 6

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study

"Rescue" Course of Betamethasone or Dexamethasone

Placebo (Normal Saline)

Drop/Withdrawal Reasons

"Rescue" Course of Betamethasone or Dexamethasone

Placebo (Normal Saline)