A Randomized Trial Comparing the Impact of One Versus Two Courses of Antenatal Steroids (ACS) on Neonatal Outcome

Obstetrix Medical Group

Status and phase

Completed

Phase 4

Conditions

Preterm Delivery

Treatments

Drug: Placebo

Drug: Betamethasone or Dexamethasone (2nd course of ACS)

Study type

Interventional

Funder types

Industry

Identifiers

NCT00201643

OBX0001 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

437 patients

Sex

Female

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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