Antenatal Late Preterm Steroids (ALPS): A Randomized Plac... | NCT01222247

ID	Type	Link
U10HD021410	U.S. NIH Grant/Contract	View source
U10HD027869	U.S. NIH Grant/Contract	View source
U10HD027917	U.S. NIH Grant/Contract	View source
U10HD053118	U.S. NIH Grant/Contract	View source
U10HD027915	U.S. NIH Grant/Contract	View source
U10HD034116	U.S. NIH Grant/Contract	View source
U10HD034208	U.S. NIH Grant/Contract	View source
U10HD053097	U.S. NIH Grant/Contract	View source
U10HD040500	U.S. NIH Grant/Contract	View source
U10HD040485	U.S. NIH Grant/Contract	View source
U10HD040544	U.S. NIH Grant/Contract	View source
U10HD040545	U.S. NIH Grant/Contract	View source
U10HD040560	U.S. NIH Grant/Contract	View source
U10HD040512	U.S. NIH Grant/Contract	View source
U10HD036801	U.S. NIH Grant/Contract	View source
U01HL098354	U.S. NIH Grant/Contract	View source
U01HL098554	U.S. NIH Grant/Contract	View source
U10HD068268	U.S. NIH Grant/Contract	View source
U10HD068258	U.S. NIH Grant/Contract	View source
U10HD068282	U.S. NIH Grant/Contract	View source

Status Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	NIH

Description Module

Detailed Description

The rate of preterm birth has steadily increased in the United States over the past 10 years. This increase is driven in part by the rising rate of late preterm birth, defined as those births occurring between 34 and 36 weeks. Late preterm infants experience a higher rate of readmission than their term counterparts, and these infants are more likely to suffer complications such as respiratory distress, kernicterus, feeding difficulties, and hypoglycemia. Late preterm infants also have a higher mortality for all causes when compared to term infants. The use of antenatal corticosteroids has been shown to be beneficial in women at risk for preterm delivery prior to 34 weeks but has not been evaluated in those likely to deliver in the late preterm period. If shown to reduce the need for respiratory support and thus to decrease the rate of special care nursery admissions and improve short-term outcomes, the public health and economic impact will be considerate.This protocol describes a randomized placebo controlled trial to evaluate whether antenatal corticosteroids can decrease the rate of neonatal respiratory support, thus decreasing the rate of neonatal intensive care unit (NICU) admissions and improving short-term outcomes in the late preterm infant.

Two follow-up studies will be conducted concurrently. The first follow-up study will examine if the positive effects of betamethasone on lung function will persist in children at 6 years of age of mothers randomized to betamethasone with an expected late preterm delivery. Neonatal respiratory morbidity is associated with an increased risk of adverse childhood respiratory disease. Thus it is quite plausible that the effect of betamethasone, in reducing neonatal morbidity, particularly TTN, will translate into improved respiratory morbidity in early childhood.The primary outcome is childhood respiratory disease defined by a composite outcome of abnormal pulmonary function test (PFT) measured by spirometry, physician diagnosis of asthma, or other respiratory illnesses with medication.

The second follow-up study will examine whether late preterm antenatal betamethasone treatment is associated with long-term neurocognitive functioning, and whether there are any long-term consequences of what is believed to be transient neonatal hypoglycemia. Cognitive function will be measured by the Differential Ability Scales 2nd Edition (DAS-II) core components of the general conceptual ability (GCA) that includes verbal ability, non-verbal reasoning ability and spatial ability. The primary outcome is defined as a GCA score of <85 (1 standard deviation below the mean) at 6 years of age or greater.

Label	Type	Description	Intervention Names
Betamethasone	Active Comparator	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Drug: Betamethasone
Placebo	Placebo Comparator	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Betamethasone	Drug	The active study drug, betamethasone. 3 mg per ml betamethasone sodium phosphate 3 mg per milliliter betamethasone acetate The first dose of study drug medication will be administered at randomization as 2 ml injection; the next dose of 2 ml will be administered 24 hours later.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Neonatal Composite Outcome	Need for respiratory support: Continuous positive airway pressure (CPAP) or humidified high-flow nasal cannula (HHFNC) for greater than or equal to 2 hours or more in the first 72 hours, or fraction of inspired oxygen (FiO2) greater than or equal to 0.30 for 4 hours or more in the first 72 hours, or mechanical ventilation in the first 72 hours, or Extracorporeal membrane oxygenation (ECMO) Stillbirth, or neonatal death less than 72 hours of age	72 hours of life

Secondary Outcomes

Measure	Description	Time Frame
Number of Neonates With Severe Respiratory Complication,	A severe respiratory complication was defined as any of the following occurrences within 72 hours after birth: CPAP or high-flow nasal cannula for at least 12 hours, supplemental oxygen with a fraction of inspired oxygen of 0.30 or more for at least 24 hours, mechanical ventilation, stillbirth or neonatal death, or the need for ECMO. Except for the duration of CPAP or high-flow nasal cannula and the duration of a fraction of inspired oxygen of 0.30 or more, the criteria for a severe respiratory complication overlap with those of the primary outcome.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Singleton Pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14,0 weeks by project gestational age is acceptable

Gestational age at randomization between 34,0 weeks and 36,5 weeks confirmed by study criteria

High probability of delivery in the late preterm period (any one of the following):

Membrane rupture as defined by the occurrence of any two of the following: pooling of fluid in the vaginal vault, positive Nitrazine test, ferning of vaginal fluid, positive AmniSure test; or any one of the following: indigo carmine pooling in the vagina after amnioinfustion, visible leakage of amniotic fluid from the cervix

Preterm labor with intact membranes. Preterm labor is defined as at least 6 regular uterine contractions in an observation period of no more than 60 minutes and at least one of the following: cervix greater than or equal to 3cm dilated or at least 75% effaced

Planned delivery by induction of labor or cesarean section in no less than 24 hours and no more than 7 days, as deemed necessary by the provider. An induction must be scheduled to start by 36,5 weeks at the latest, whereas a cesarean delivery must be scheduled by 36,6 weeks at the latest. Therefore the latest gestational age for randomization is 36,4 weeks for a planned induction. The planned delivery may be for any indication, such as the following: prior myomectomy, prior classical cesarean, intrauterine growth restriction (IUGR), oligohydramnios, preeclampsia, nonreassuring fetal heart rate tracing warranting delivery, abruption, placenta previa

Exclusion Criteria:

Any prior antenatal corticosteroid course during the pregnancy because of potential contamination of the placebo group
Candidate for stress dose corticosteroids because of chronic steroid therapy to prevent suppression of adrenal gland, because of potential contamination of the placebo group
Twin gestation reduced to a singleton gestation at or after 14 weeks 0 days by project gestational age either spontaneously or therapeutically
Fetal demise, or known major fetal anomaly, including cardiac anomaly and hydrops
Maternal contraindication to betamethasone: hypersensitivity reaction to any components of the medication, idiopathic thromboycytopenic purpura, systemal fungal infection in case of exacerbation by betamethasone, use of amphotericin B due to the possibility of heart failure with concomitant betamethasone
Pre-gestational diabetes - exclude if the patient was on medication (insulin, glyburide) prior to pregnancy
Delivery expected within 12 hours of randomization, because of insufficient time of corticosteroids to confer benefit, including any of the following:

A. Rupture of Membranes (ROM) does not satisfy protocol criteria - exclude if the patient being evaluated for Preterm Premature Rupture of Membranes (pPROM), does not have preterm labor or planned delivery and does not satisfy the spontaneous membrane rupture criteria (any 2 of: positive Nitrazine test, pooling of fluid in the vaginal vault test or ferning of vaginal fluid; or indigo carmine pooling in the vagina after amnioinfusion; or visible leakage of amniotic fluid from the cervix) B. Rupture of the membranes in the presence of more than 6 contractions per hour or cervical dilation of 3 cm or more, unless oxytocin was withheld for at least 12 hours (other induction agents allowed) C. Chorioamnionitis - exclude if patient is diagnosed with chorioamnionitis D. Cervical dilation ≥ 8 cm E. Evidence of non-reassuring fetal status requiring immediate delivery
Participation in another interventional study that influences neonatal morbidity and mortality
Participation in this trial in a previous pregnancy
Delivery at a non-network hospital
At 36, 0 weeks to 36, 5 weeks and quota for 36 weeks already met. To ensure there is an adequate proportion of women presenting at 34 to 35 weeks of gestation, enrollment will be restricted so that no more than 50% of the women in the trial present at 36 weeks.

Name	Affiliation	Role
Monica Longo, MD	NICHD Project Scientist	Study Director
Rebecca Clifton, PhD	George Washington University	Principal Investigator
Cynthia Gyamfi Bannerman, MD	Columbia University	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama - Birmingham		Birmingham	Alabama	35233	United States
Stanford University

PubMed Identifier	Type	Citation	Retractions
16549207	Background	Davidoff MJ, Dias T, Damus K, Russell R, Bettegowda VR, Dolan S, Schwarz RH, Green NS, Petrini J. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol. 2006 Feb;30(1):8-15. doi: 10.1053/j.semperi.2006.01.009.
16951017	Background	Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006 Sep;118(3):1207-14. doi: 10.1542/peds.2006-0018.

Label	URL
(The public website of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network)	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
FG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Mean

Standard Deviation

years

Title

Denominators

Categories

Mean maternal age

Title	Measurements
	BG00028.6± 6.3 BG00127.8± 6.1 BG00228.2± 6.2

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001429 BG0011402 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Black

Title	Measurements
	BG000376 BG001381 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0001429 BG0011402 BG002

Indication for trial entry

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Preterm labor with intact membranes	BG000400 BG001392 BG002

Gestational age at trial entry

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
≤34 weeks 6 days	BG000369 BG001399 BG002

Smoking during pregnancy

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG000204 BG001186 BG002

Nulliparous

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG000457 BG001448 BG002

Preeclampsia or gestational hypertension

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG000433 BG001440 BG002

Gestational diabetes

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG000153 BG001153 BG002

Major congenital anomaly in infant

Although the presence of a major congenital anomaly was an exclusion criterion, these disorders were not discovered until birth. Therefore we report this as a baseline measure on the publication and not an outcome. To be consistent with the publication, we report this as a baseline measure here.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00011 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Neonatal Composite Outcome

Need for respiratory support: Continuous positive airway pressure (CPAP) or humidified high-flow nasal cannula (HHFNC) for greater than or equal to 2 hours or more in the first 72 hours, or fraction of inspired oxygen (FiO2) greater than or equal to 0.30 for 4 hours or more in the first 72 hours, or mechanical ventilation in the first 72 hours, or Extracorporeal membrane oxygenation (ECMO) Stillbirth, or neonatal death less than 72 hours of age

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

72 hours of life

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG0001427 OG0011400

Title

Denominators

Categories

Primary Outcome Composite

Title	Measurements
	OG000165 OG001202

CPAP or high-flow cannula ≥2 continuous hrs

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis for Primary Outcome composite	Chi-squared		0.02		Risk Ratio (RR)	0.80			2-Sided	95	0.66	0.97					Superiority or Other (legacy)
OG000 OG001	Analysis for CPAP or high-flow nasal cannula	Chi-squared

Secondary

Number of Neonates With Severe Respiratory Complication,

A severe respiratory complication was defined as any of the following occurrences within 72 hours after birth: CPAP or high-flow nasal cannula for at least 12 hours, supplemental oxygen with a fraction of inspired oxygen of 0.30 or more for at least 24 hours, mechanical ventilation, stillbirth or neonatal death, or the need for ECMO. Except for the duration of CPAP or high-flow nasal cannula and the duration of a fraction of inspired oxygen of 0.30 or more, the criteria for a severe respiratory complication overlap with those of the primary outcome.

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

72 hours of life

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Secondary

Neonates Needing Immediate Resuscitation After Birth

Need for resuscitation after birth: any intervention in the first 30 minutes other than blow-by oxygen

Posted

Count of Participants

Participants

Within the first 30 minutes of birth

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Respiratory Distress Syndrome

Respiratory distress defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis) with an oxygen requirement and a chest x-ray that shows hypoaeration and reticulogranular infiltrates

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Transient Tachypnea of the Newborn

TTN is defined as signs of respiratory distress, specifically tachypnea, that are resolved by 72 hours of age. TTN may be diagnosed in the absence of a chest X-ray or with a chest X-ray that is normal or shows signs of increased perihilar interstitial markings

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

by 72 hours after delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants

Secondary

Number of Infants With Neonatal Apnea

Neonatal apnea with respiratory pauses of more than 20 seconds duration resulting in bradycardia or oxygen desaturation below baseline.

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

72 hours of life

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Infants withChronic Lung Disease / Bronchopulmonary Dysplasia (BPD) Requiring Supplemental Oxygen

Infants requiring supplemental oxygen of more than 0.21 for the first 28 days of life

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

28 days of life

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Neonates With Pneumonia

Neonatal pneumonia

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

by 72 hours of life

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates Needing Surfactant Administration

Administration of surfactant for neonatal respiratory treatment

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Neonatal Outcome Composite

Transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), and apnea

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

72 hours of life

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Pulmonary Air Leak

Neonatal pulmonary air leak syndrome

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

72 hours post delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Neonatal Death After 72 Hours of Delivery

Neonatal death after 72 hours of life but before hospital discharge.

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

72 hours after delivery through hospital discharge up to 3 weeks

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Birth Weight

Weight in grams at delivery

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Mean

Standard Deviation

grams

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Birth Weight Less Than 10th Percentile

Neonates whose birth weight is less than the 10th percentile at delivery

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Gestational Age at Delivery

Number of neonates delivered at ≤ 34 weeks 6 days, between 35 weeks 0 days and 35 weeks 6 days, between 36 weeks 0 days and 36 weeks 6 days, between 37 weeks 0 days and 38 weeks 6 days, or on or after 39 weeks 0 days

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Necrotizing Enterocolitic (NEC)

Defined as modified Bell Stage 2 or 3. Stage 2: Clinical signs and symptoms with pneumatosis intestinalis on radiographs. Stage 3: Advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Infants With Neonatal Sepsis

Clinical suspicion of systemic infection with a positive blood, cerebral spinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evience of cardiovascular collapse or an X-ray confirming infection.

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Intraventricular Hemorrhage

Grade 3 or 4 Intraventricular Hemorrhage

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Neonatal Morbidity Composite

A composite endpoint of morbidities known to be affected by steroid administration will also be evaluated. Specifically, this composite will include RDS, intraventricular hemorrhage (IVH), and NEC

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Hypoglycemia

Glucose < 40 mg per deciliter (2.2 mmol per liter) at any time

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery through hospital discharge up to 3 weeks

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Time Until First Neonatal Feeding

Median length of time from delivery until the first neonatal feeding

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Median

Inter-Quartile Range

hours

Delivery to 36 hours post delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Neonatal Feeding Difficulty

Inability of the neonate to take all feeds (po), i.e. requiring gavage feeds or IV supplementation.

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery to 36 hours post delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Neonatal Hyperbilirubinemia

Peak total bilirubin of at least 15 mg% or the use of phototherapy.

Posted

Count of Participants

Participants

Delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Number of Neonates With Hypothermia

Rectal temperature < 36 C at any time

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery through discharge up to 3 weeks

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Length of NICU or Nursery Stay

Includes need for NICU or intermediate care admission and length of stay if admitted. For analysis purposes, death before discharge is assigned maximum rank

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Count of Participants

Participants

Delivery through hospital discharge up to 3 weeks

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Median Length of Hospital Stay

Median length of maternal hospital stay following delivery

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Median

Inter-Quartile Range

days

Duration of hospital stay following delivery up to 2 weeks

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Maternal Outcomes (Participant-based)

Chorioamnionitis: clinical diagnosis and a body temperature of at least 100.4 degrees F., Endometritis: persistent postpartum temperature greater than 100.4 degrees F with uterine tenderness, cesarean delivery

Posted

Count of Participants

Participants

Labor and delivery through 72 hours post partum

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Hours From Randomization to Delivery

Median interval of hours from randomization to delivery

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Median

Inter-Quartile Range

Hours

Randomization through delivery

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Secondary

Median Length of Maternal Hospital Stay

Median length of maternal hospital stay in days

The number of participants analyzed accounts for the 4 participants for which baseline measures were obtained but who were subsequently lost to follow-up (2 in each group).

Posted

Median

Inter-Quartile Range

days

Delivery through hospital discharge

ID	Title	Description
OG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart
OG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Postpartum Hemorrhage	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Postpartum Hemorrhage	EG0007 affected1,429 at risk EG0015 affected1,402 at risk
Hypotension	Vascular disorders	Non-systematic Assessment	Low blood pressure	EG0000 affected1,429 at risk EG0011 affected1,402 at risk
Seizure	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Postpartum pregnancy complication	EG0001 affected1,429 at risk EG0011 affected1,402 at risk
Uterine rupture	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Pregnancy complication	EG0000 affected1,429 at risk EG0011 affected1,402 at risk
Delayed pre-eclampsia	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Pregnancy complication	EG0001 affected1,429 at risk EG0010 affected1,402 at risk
Aortic dissection type 1	Cardiac disorders	Non-systematic Assessment		EG0000 affected1,429 at risk EG0011 affected1,402 at risk
Cardiomyopathy	Cardiac disorders	Non-systematic Assessment		EG0000 affected1,429 at risk EG0012 affected1,402 at risk
Obstructed bowel	Gastrointestinal disorders	Non-systematic Assessment	Maternal obstructed bowel	EG0001 affected1,429 at risk EG0010 affected1,402 at risk
Lumbar plexus stretch injury	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	Maternal stretch injury	EG0000 affected1,429 at risk EG0011 affected1,402 at risk
Neonatal Thrombocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment		EG0001 affected1,429 at risk EG0010 affected1,402 at risk
Neonatal death	General disorders	Non-systematic Assessment	Two infants died after 72 hours of life but before hospital discharge.	EG0002 affected1,429 at risk EG0010 affected1,402 at risk

ID	Term
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D012120	Respiration Disorders
D007752	Obstetric Labor, Premature
D007744	Obstetric Labor Complications
D011248	Pregnancy Complications
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart Betamethasone: The active study drug, betamethasone. 3 mg per ml betamethasone sodium phosphate 3 mg per milliliter betamethasone acetate The first dose of study drug medication will be administered at randomization as 2 ml injection; the next dose of 2 ml will be administered 24 hours later.
BG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Betamethasone	A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	2	1,429	13	1,429	223	1,428
EG001	Placebo	A similar course of an identical appearing placebo: two 2 mL IM injections of placebo, 24 hours apart Placebo: Similar course of identical appearing placebo: 2 mL IM injections, 24 hours apart.	0	1,402	12	1,402	352	1,397