Trial Outcomes & Findings for Trial of the Use of Antenatal Corticosteroids in Developing Countries (NCT NCT01084096)
NCT ID: NCT01084096
Last Updated: 2024-12-09
Results Overview
Neonatal deaths before 28 days per 1,000 live births among \<5th %tile birth weight infants. The \<5th %tile birth weight group was a proxy for preterm. Site-specific cutoffs from pretrial data were 2,450g-Argentina, 2,400g-Zambia, 2,267g-Guatemala, 2,000g-Belgaum, India, 2,150g-Pakistan, 2,000g-Nagpur, India, and 2,500g-Kenya. Infants were classified as \<5th %tile on the basis of measured birth weights. Estimated weights by clinical assessment were used when measured weights were unavailable; those missing weights were classified as \<5th %tile (since based on historical data, most of the missing data were for preterm infants). We used birth weight rather than gestational age (GA) for the primary analysis subgroup because many women in the registry had missing or uncertain GA, ultrasound was often unavailable, and the intervention was designed to improve estimation of GA, which could potentially bias GA-based analyses. All live births, including multiple births, are included.
COMPLETED
NA
103117 participants
Birth to 28 days
2024-12-09
Participant Flow
18m, 2-arm, parallel, cluster-randomized trial in 7 Global Network sites from Oct 2011-Mar 2014. Health providers in intervention clusters identified women at high risk of preterm birth for antenatal corticosteroids. Overall, 349 and 360 health facilities served intervention and control clusters, respectively; most (260 in each group) were clinics.
The treatment group for each cluster (and thus all women residing in the cluster) was randomly assigned pretrial (1:1) using a stratified procedure to account for pretrial characteristics. 102 clusters were randomly assigned (51 control:51 intervention). One control cluster withdrew because of unrelated safety concerns prior to study start.
Unit of analysis: Geographic Cluster
Participant milestones
| Measure |
Intervention Group
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Overall Study
STARTED
|
49744 51
|
53373 51
|
|
Overall Study
COMPLETED
|
48219 51
|
51523 50
|
|
Overall Study
NOT COMPLETED
|
1525 0
|
1850 1
|
Reasons for withdrawal
| Measure |
Intervention Group
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1501
|
1833
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
|
Overall Study
Woman had a miscarriage
|
21
|
17
|
Baseline Characteristics
Trial of the Use of Antenatal Corticosteroids in Developing Countries
Baseline characteristics by cohort
| Measure |
Intervention Group
n=48 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=51 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
Total
n=99742 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<20
|
5,412 Participants
n=5 Participants
|
6,622 Participants
n=7 Participants
|
12034 Participants
n=5 Participants
|
|
Age, Customized
20-35
|
41,003 Participants
n=5 Participants
|
42,938 Participants
n=7 Participants
|
83941 Participants
n=5 Participants
|
|
Age, Customized
>35
|
1,741 Participants
n=5 Participants
|
1,895 Participants
n=7 Participants
|
3636 Participants
n=5 Participants
|
|
Age, Customized
Missing
|
63 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
48,219 Participants
n=5 Participants
|
51,523 Participants
n=7 Participants
|
99742 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
2,115 participants
n=5 Participants
|
2,292 participants
n=7 Participants
|
4407 participants
n=5 Participants
|
|
Region of Enrollment
Pakistan
|
7,714 participants
n=5 Participants
|
8,202 participants
n=7 Participants
|
15916 participants
n=5 Participants
|
|
Region of Enrollment
Guatemala
|
5,813 participants
n=5 Participants
|
3,960 participants
n=7 Participants
|
9773 participants
n=5 Participants
|
|
Region of Enrollment
Zambia
|
4,279 participants
n=5 Participants
|
5,739 participants
n=7 Participants
|
10018 participants
n=5 Participants
|
|
Region of Enrollment
Kenya
|
5,900 participants
n=5 Participants
|
7,103 participants
n=7 Participants
|
13003 participants
n=5 Participants
|
|
Region of Enrollment
India
|
22,398 participants
n=5 Participants
|
24,227 participants
n=7 Participants
|
46625 participants
n=5 Participants
|
|
Education
No formal schooling
|
11,005 Participants
n=5 Participants
|
11,258 Participants
n=7 Participants
|
22263 Participants
n=5 Participants
|
|
Education
Primary
|
17,686 Participants
n=5 Participants
|
19,515 Participants
n=7 Participants
|
37201 Participants
n=5 Participants
|
|
Education
Secondary
|
15,528 Participants
n=5 Participants
|
16,170 Participants
n=7 Participants
|
31698 Participants
n=5 Participants
|
|
Education
University
|
3,757 Participants
n=5 Participants
|
4,313 Participants
n=7 Participants
|
8070 Participants
n=5 Participants
|
|
Education
Missing
|
243 Participants
n=5 Participants
|
267 Participants
n=7 Participants
|
510 Participants
n=5 Participants
|
|
Parity
0
|
16,366 Participants
n=5 Participants
|
17,901 Participants
n=7 Participants
|
34267 Participants
n=5 Participants
|
|
Parity
1
|
13,961 Participants
n=5 Participants
|
14,599 Participants
n=7 Participants
|
28560 Participants
n=5 Participants
|
|
Parity
2
|
17,570 Participants
n=5 Participants
|
18,934 Participants
n=7 Participants
|
36504 Participants
n=5 Participants
|
|
Parity
Missing
|
322 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
411 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Birth to 28 daysNeonatal deaths before 28 days per 1,000 live births among \<5th %tile birth weight infants. The \<5th %tile birth weight group was a proxy for preterm. Site-specific cutoffs from pretrial data were 2,450g-Argentina, 2,400g-Zambia, 2,267g-Guatemala, 2,000g-Belgaum, India, 2,150g-Pakistan, 2,000g-Nagpur, India, and 2,500g-Kenya. Infants were classified as \<5th %tile on the basis of measured birth weights. Estimated weights by clinical assessment were used when measured weights were unavailable; those missing weights were classified as \<5th %tile (since based on historical data, most of the missing data were for preterm infants). We used birth weight rather than gestational age (GA) for the primary analysis subgroup because many women in the registry had missing or uncertain GA, ultrasound was often unavailable, and the intervention was designed to improve estimation of GA, which could potentially bias GA-based analyses. All live births, including multiple births, are included.
Outcome measures
| Measure |
Intervention Group
n=2 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=2 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Neonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity)
|
566 Participants
|
524 Participants
|
SECONDARY outcome
Timeframe: 48 hours after identification of risk for preterm birthPopulation: Among women with a less-than-5th-percentile for birth weight infant and with data on administration of antenatal corticosteroid data available.
Antenatal corticosteroids provided antepartum assessed in women with a less-than-5th-percentile for birth weight infants. Site-specific cut offs were determined from pretrial data.
Outcome measures
| Measure |
Intervention Group
n=2 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=2 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Use of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters
|
1,052 Participants
|
215 Participants
|
SECONDARY outcome
Timeframe: Pregnancy through 6 weeks postpartumPopulation: Women with infection data available from all data sources
Maternal safety was assessed through the frequency of suspected maternal infection, a composite of process outcomes including receipt of antibiotics plus hospital admission or referral, and receipt of intravenous fluids, surgery, or other treatment related to infection. The definition also included evidence of antepartum or post-partum infection for mothers with infants with a birthweight less than 2500 g. Additionally, use of antenatal corticosteroids, neonatal and perinatal mortality, and suspected maternal infection were measured for all births, irrespective of birthweight.
Outcome measures
| Measure |
Intervention Group
n=48 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=51 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Suspected Maternal Infection
|
1,207 Participants
|
867 Participants
|
SECONDARY outcome
Timeframe: Pregnancy through 42 days postpartumPopulation: All maternal deaths and pregnancy ending in live birth.
The denominator for maternal deaths through 42 days is pregnancy ending in live birth + all maternal deaths. Maternal mortality includes all maternal deaths through 42 days postpartum, irrespective of cause.
Outcome measures
| Measure |
Intervention Group
n=46 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=50 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Maternal Mortality Rate
|
106 participants
|
97 participants
|
SECONDARY outcome
Timeframe: Birth to 28 daysPopulation: All live births, including multiples
Number of neonatal deaths before 28 days per 1,000 live births
Outcome measures
| Measure |
Intervention Group
n=47 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=50 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Neonatal Mortality Rate
|
1300 Participants
|
1211 Participants
|
SECONDARY outcome
Timeframe: 20 weeks' gestational age to birthPopulation: All births, including multiples.
Number of stillbirths per 1,000 births
Outcome measures
| Measure |
Intervention Group
n=48 Participants
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=52 Participants
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Stillbirth Mortality Rate
|
1304 Participants
|
1264 Participants
|
Adverse Events
Intervention Group
Control Group
Serious adverse events
| Measure |
Intervention Group
n=48698 participants at risk
Women and their babies residing in geographic clusters assigned to the intervention group. If the woman was identified as high-risk for preterm birth from 24 - 36 weeks' gestational age by the intervention she received one course of four doses of 6 mg of dexamethasone every 12 hours. If identified outside the intervention, she received standard of care.
|
Control Group
n=52007 participants at risk
Women and their babies residing in geographic clusters assigned to the control group. If the woman was identified as high-risk for preterm birth, she received standard of care.
|
|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Maternal death
|
0.10%
50/48219 • During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
|
0.10%
49/51523 • During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
|
|
Pregnancy, puerperium and perinatal conditions
Stillbirth/neonatal death
|
5.3%
2604/48698 • During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
|
4.8%
2475/52007 • During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
|
|
Pregnancy, puerperium and perinatal conditions
Congenital anomaly
|
0.57%
278/48698 • During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
|
0.48%
250/52007 • During the period that the trial was active in a particular cluster, serious adverse events were captured on each woman from the time the woman was enrolled in the MNH registry until 6 weeks after delivery for each pregnant woman enrolled in the MNH registry and her babies.
Total number of serious adverse events is out of all participants (i.e. the number of women plus the number of babies (stillbirths and live births)).
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Elizabeth McClure, Data Coordinating Center PI
NICHDGlobal
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place