Trial Outcomes & Findings for Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial (NCT NCT01222247)

NCT ID: NCT01222247

Last Updated: 2023-03-28

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 2831 participants
• Primary outcome timeframe: 72 hours of life
• Results posted on: 2023-03-28

Participant Flow

Participants were recruited from October 2010 to February 2015 at 17 university-based clinical centers. Women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period were eligible to be enrolled.

Participant milestones

Measure	Betamethasone A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	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.
Overall Study STARTED	1429	1402
Overall Study Received 2 Doses	860	826
Overall Study Received 1 Dose	568	571
Overall Study Did Not Receive Assigned Medication	1	5
Overall Study COMPLETED	1427	1400
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Betamethasone A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	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.
Overall Study Lost to Follow-up	2	2

Baseline Characteristics

Antenatal Late Preterm Steroids (ALPS): A Randomized Placebo-Controlled Trial

Baseline characteristics by cohort

Measure	Betamethasone n=1429 Participants 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.	Placebo n=1402 Participants 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.	Total n=2831 Participants Total of all reporting groups
Age, Customized Mean maternal age	28.6 years STANDARD_DEVIATION 6.3 • n=5 Participants	27.8 years STANDARD_DEVIATION 6.1 • n=7 Participants	28.2 years STANDARD_DEVIATION 6.2 • n=5 Participants
Sex: Female, Male Female	1429 Participants n=5 Participants	1402 Participants n=7 Participants	2831 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black	376 Participants n=5 Participants	381 Participants n=7 Participants	757 Participants n=5 Participants
Race/Ethnicity, Customized White	828 Participants n=5 Participants	800 Participants n=7 Participants	1628 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	168 Participants n=5 Participants	182 Participants n=7 Participants	350 Participants n=5 Participants
Race/Ethnicity, Customized Other, unknown, more than one race	57 Participants n=5 Participants	39 Participants n=7 Participants	96 Participants n=5 Participants
Region of Enrollment United States	1429 participants n=5 Participants	1402 participants n=7 Participants	2831 participants n=5 Participants
Indication for trial entry Preterm labor with intact membranes	400 Participants n=5 Participants	392 Participants n=7 Participants	792 Participants n=5 Participants
Indication for trial entry Ruptured membranes	316 Participants n=5 Participants	304 Participants n=7 Participants	620 Participants n=5 Participants
Indication for trial entry Exp delivery for gestational HTN or preeclampsia	370 Participants n=5 Participants	385 Participants n=7 Participants	755 Participants n=5 Participants
Indication for trial entry Expected delivery for fetal growth restriction	46 Participants n=5 Participants	48 Participants n=7 Participants	94 Participants n=5 Participants
Indication for trial entry Expected delivery for oligohydramnios	50 Participants n=5 Participants	42 Participants n=7 Participants	92 Participants n=5 Participants
Indication for trial entry Expected delivery for other indication	247 Participants n=5 Participants	231 Participants n=7 Participants	478 Participants n=5 Participants
Gestational age at trial entry ≤34 weeks 6 days	369 Participants n=5 Participants	399 Participants n=7 Participants	768 Participants n=5 Participants
Gestational age at trial entry 35 weeks 0 days to 35 weeks 6 days	571 Participants n=5 Participants	532 Participants n=7 Participants	1103 Participants n=5 Participants
Gestational age at trial entry ≥36 weeks 0 days	489 Participants n=5 Participants	471 Participants n=7 Participants	960 Participants n=5 Participants
Smoking during pregnancy	204 Participants n=5 Participants	186 Participants n=7 Participants	390 Participants n=5 Participants
Nulliparous	457 Participants n=5 Participants	448 Participants n=7 Participants	905 Participants n=5 Participants
Preeclampsia or gestational hypertension	433 Participants n=5 Participants	440 Participants n=7 Participants	873 Participants n=5 Participants
Gestational diabetes	153 Participants n=5 Participants	153 Participants n=7 Participants	306 Participants n=5 Participants
Major congenital anomaly in infant	11 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: 72 hours of life

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonatal Composite Outcome Mechanical ventilation	34 Participants	43 Participants
Neonatal Composite Outcome Primary Outcome Composite	165 Participants	202 Participants
Neonatal Composite Outcome CPAP or high-flow cannula ≥2 continuous hrs	145 Participants	184 Participants
Neonatal Composite Outcome Fraction of inspired O2 of ≥0.30 for ≥4 cont hrs	48 Participants	61 Participants
Neonatal Composite Outcome Extracorporeal membrane oxygenation (ECMO)	0 Participants	0 Participants
Neonatal Composite Outcome Stillbirth or neonatal death ≤72 hr after birth	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 72 hours of life

Population: 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).

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.

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Severe Respiratory Complication, Severe Respiratory Complication Composite	114 Participants	169 Participants
Number of Neonates With Severe Respiratory Complication, CPAP or high-flow cannula ≥12 continuous hrs	93 Participants	147 Participants
Number of Neonates With Severe Respiratory Complication, Fraction of inspired 02 of ≥0.30 for ≥24 cont hrs	20 Participants	34 Participants

SECONDARY outcome

Timeframe: Within the first 30 minutes of birth

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

Outcome measures

Measure	Betamethasone n=1422 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1390 Participants 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.
Neonates Needing Immediate Resuscitation After Birth	206 Participants	260 Participants

SECONDARY outcome

Timeframe: Delivery

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Respiratory Distress Syndrome	79 Participants	89 Participants

SECONDARY outcome

Timeframe: by 72 hours after delivery

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Transient Tachypnea of the Newborn	95 Participants	138 Participants

SECONDARY outcome

Timeframe: 72 hours of life

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Infants With Neonatal Apnea	33 Participants	37 Participants

SECONDARY outcome

Timeframe: 28 days of life

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Infants withChronic Lung Disease / Bronchopulmonary Dysplasia (BPD) Requiring Supplemental Oxygen	2 Participants	9 Participants

SECONDARY outcome

Timeframe: by 72 hours of life

Population: 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).

Neonatal pneumonia

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonates With Pneumonia	6 Participants	13 Participants

SECONDARY outcome

Timeframe: Delivery

Population: 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).

Administration of surfactant for neonatal respiratory treatment

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates Needing Surfactant Administration	26 Participants	43 Participants

SECONDARY outcome

Timeframe: 72 hours of life

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonatal Outcome Composite	198 Participants	249 Participants

SECONDARY outcome

Timeframe: 72 hours post delivery

Population: 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).

Neonatal pulmonary air leak syndrome

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Pulmonary Air Leak	5 Participants	6 Participants

SECONDARY outcome

Timeframe: 72 hours after delivery through hospital discharge up to 3 weeks

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonatal Death After 72 Hours of Delivery	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Delivery

Population: 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).

Weight in grams at delivery

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Birth Weight	2637 grams Standard Deviation 480	2654 grams Standard Deviation 484

SECONDARY outcome

Timeframe: Delivery

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Birth Weight Less Than 10th Percentile	255 Participants	220 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Gestational Age at Delivery ≤34 weeks 6 days	193 Participants	213 Participants
Gestational Age at Delivery 35 weeks 0 days to 35 weeks 6 days	394 Participants	386 Participants
Gestational Age at Delivery 36 weeks 0 days to 36 weeks 6 days	609 Participants	568 Participants
Gestational Age at Delivery 37 weeks 0 days to 38 weeks 6 days	202 Participants	185 Participants
Gestational Age at Delivery ≥39 weeks 0 days	29 Participants	48 Participants

SECONDARY outcome

Timeframe: Delivery

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.

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Necrotizing Enterocolitic (NEC)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Delivery

Population: 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).

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.

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Infants With Neonatal Sepsis	9 Participants	11 Participants

SECONDARY outcome

Timeframe: Delivery

Population: 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).

Grade 3 or 4 Intraventricular Hemorrhage

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Intraventricular Hemorrhage	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Delivery

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonatal Morbidity Composite	81 Participants	90 Participants

SECONDARY outcome

Timeframe: Delivery through hospital discharge up to 3 weeks

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Hypoglycemia	343 Participants	210 Participants

SECONDARY outcome

Timeframe: Delivery to 36 hours post delivery

Population: 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).

Median length of time from delivery until the first neonatal feeding

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Time Until First Neonatal Feeding	5.5 hours Interval 1.4 to 24.7	9.9 hours Interval 1.7 to 29.1

SECONDARY outcome

Timeframe: Delivery to 36 hours post delivery

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonatal Feeding Difficulty	211 Participants	223 Participants

SECONDARY outcome

Timeframe: Delivery

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Neonatal Hyperbilirubinemia	167 Participants	140 Participants

SECONDARY outcome

Timeframe: Delivery through discharge up to 3 weeks

Population: 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).

Rectal temperature < 36 C at any time

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Number of Neonates With Hypothermia	132 Participants	112 Participants

SECONDARY outcome

Timeframe: Delivery through hospital discharge up to 3 weeks

Population: 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).

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Length of NICU or Nursery Stay NICU stay of any duration	596 Participants	629 Participants
Length of NICU or Nursery Stay NICU stay of ≥3 days	470 Participants	518 Participants

SECONDARY outcome

Timeframe: Duration of hospital stay following delivery up to 2 weeks

Population: 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).

Median length of maternal hospital stay following delivery

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Median Length of Hospital Stay	7 days Interval 4.0 to 12.0	8 days Interval 4.0 to 13.0

SECONDARY outcome

Timeframe: Labor and delivery through 72 hours post partum

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

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Maternal Outcomes (Participant-based) Chorioamnionitis	20 Participants	32 Participants
Maternal Outcomes (Participant-based) Postpartum Endometritis	16 Participants	16 Participants
Maternal Outcomes (Participant-based) Cesarean Delivery	454 Participants	431 Participants

SECONDARY outcome

Timeframe: Randomization through delivery

Population: 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).

Median interval of hours from randomization to delivery

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Hours From Randomization to Delivery	33.0 Hours Interval 15.2 to 111.6	30.6 Hours Interval 14.6 to 111.0

SECONDARY outcome

Timeframe: Delivery through hospital discharge

Population: 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).

Median length of maternal hospital stay in days

Outcome measures

Measure	Betamethasone n=1427 Participants A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1400 Participants 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.
Median Length of Maternal Hospital Stay	3 days Interval 3.0 to 5.0	3 days Interval 3.0 to 5.0

Adverse Events

Betamethasone

Serious events: 13 serious events

Other events: 223 other events

Deaths: 2 deaths

Placebo

Serious events: 12 serious events

Other events: 352 other events

Deaths: 0 deaths

Serious adverse events

Measure	Betamethasone n=1428 participants at risk；n=1429 participants at risk A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1397 participants at risk；n=1402 participants at risk 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.
Pregnancy, puerperium and perinatal conditions Postpartum Hemorrhage	0.49% 7/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.36% 5/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Vascular disorders Hypotension	0.00% 0/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.07% 1/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Pregnancy, puerperium and perinatal conditions Seizure	0.07% 1/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.07% 1/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Pregnancy, puerperium and perinatal conditions Uterine rupture	0.00% 0/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.07% 1/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Pregnancy, puerperium and perinatal conditions Delayed pre-eclampsia	0.07% 1/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.00% 0/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Cardiac disorders Aortic dissection type 1	0.00% 0/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.07% 1/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Cardiac disorders Cardiomyopathy	0.00% 0/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.14% 2/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Gastrointestinal disorders Obstructed bowel	0.07% 1/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.00% 0/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Musculoskeletal and connective tissue disorders Lumbar plexus stretch injury	0.00% 0/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.07% 1/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
Blood and lymphatic system disorders Neonatal Thrombocytopenia	0.07% 1/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.00% 0/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.
General disorders Neonatal death	0.14% 2/1429 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	0.00% 0/1402 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.

Other adverse events

Measure	Betamethasone n=1428 participants at risk；n=1429 participants at risk A course of two 2mL intramuscular (IM) injections containing 3 mg of betamethasone, 24 hours apart	Placebo n=1397 participants at risk；n=1402 participants at risk 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.
Skin and subcutaneous tissue disorders Skin reaction at injecton site	15.6% 223/1428 • Number of events 223 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.	25.2% 352/1397 • Number of events 352 • Adverse events were collected from the time of randomization into the study through 72 hours after delivery. Adverse events were documented by research nurse coordinators and principal investigators on standardized study protocol forms and reported to the study sponsor. Non-serious adverse events are reported for patients who received 1 or 2 doses of drug or placebo. Not all participants who were randomized received a study injection.

Additional Information

Elizabeth Thom, Ph.D.

The George Washington University Biostatistics Center

Phone: 301-881-9260

Email: e_thom@bsc.gwu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60