An interventional study of Increasing use of Antenatal Corticosteroids (ACS) in Preterm Birth, sponsored by NICHD Global Network for Women's and Children's Health. Completed at 7 sites in 6 countries. Open to female participants, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-09.
Sponsored by NICHD Global Network for Women's and Children's Health · Not applicable, Interventional, and Treatment
Multi-country two-arm, parallel cluster randomized controlled trial to reduce neonatal mortality through increasing the rate of antenatal corticosteroid administration to eligible women.
One of the United Nations Millennium Summit goals is to reduce the deaths of children \<5 years by two-thirds for 2015 (UN, 2000). Given that 38% of all under-five deaths worldwide occur in the first four weeks of life, the goal seems unattainable unless a significant fraction of the neonatal deaths are prevented (Darmstadt et al., 2005). Thus, the provision of health care during the perinatal period in developing countries is a top priority. Preterm birth is a major cause of neonatal mortality, currently responsible for 28% of the deaths overall. As the contribution of preterm birth to neonatal deaths is well above 50% (MacDorman et al., 2005) in middle and high income countries, it is expected that as low income countries improve their development, the relative importance of this cause will increase. One of the most powerful perinatal interventions to reduce neonatal mortality is the administration of antenatal corticosteroids to pregnant women at high risk of preterm birth.
The primary objective will be to evaluate whether a cluster-level multifaceted intervention, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, reduces neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six African, Asian, and Latin American countries.
2,550 studies on the registry are indexed under Premature Birth; 500 are open to participants now.
This study's enrollment of 103,117 is above the median of 84 across 1,666 interventional studies indexed under Premature Birth.
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This is an intent-to-treat design and thus all pregnancy outcomes of women who deliver in the study clusters and provide consent will be collected. Cluster-level inclusion criteria include
Participant-level inclusion criteria include all pregnant women living in and delivering in the study cluster who:
Exclusion Criteria:
Eligible women at high risk for preterm birth will be identified and four 6 mg doses of dexamethasone will be administered before delivery.
Behavioral: Increasing use of Antenatal Corticosteroids (ACS)
Control arm will not receive a specific intervention for comparison.
Intervention clusters: * Increasing administration of ACS to pregnant women at high risk of preterm birth (HRPB) by providing health providers with kits containing dexamethasone, syringes, and instructions. Eligible women receive four injections of 6 mg dexamethasone from the kit or regimen of choice at the site. * Improving identification of women at HRPB by diffusing recommendations for ACS use to health care providers, training health care providers to identify signs of preterm labor and eligibility criteria for ACS use, providing reminders to healthcare providers on the use of the kits, and using a color-coded tape to measure uterine height to estimate gestational age in women at HRPB with unknown gestational age. Control clusters: no specific intervention for comparison. Both intervention and control clusters: Birth attendants trained in essential newborn care of LBW infants and instructed to teach mothers how to provide care to premature infants.
Also known as: Four 6 mg doses of dexamethasone
Neonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity)
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.
Time frame: Birth to 28 days
Use of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters
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.
Time frame: 48 hours after identification of risk for preterm birth
Suspected Maternal Infection
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.
Time frame: Pregnancy through 6 weeks postpartum
Maternal Mortality Rate
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.
Time frame: Pregnancy through 42 days postpartum
Neonatal Mortality Rate
Number of neonatal deaths before 28 days per 1,000 live births
Time frame: Birth to 28 days
Stillbirth Mortality Rate
Number of stillbirths per 1,000 births
Time frame: 20 weeks' gestational age to birth
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.
| Milestone | Intervention Group | Control Group |
|---|---|---|
| Started | 49744 | 53373 |
| Completed | 48219 | 51523 |
| Not completed | 1525 | 1850 |
| Withdrew: Lost to follow-up | 1501 | 1833 |
| Withdrew: Withdrawal by subject | 3 | 0 |
| Withdrew: Woman had a miscarriage | 21 | 17 |
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.
| Participants | Intervention Group | Control Group |
|---|---|---|
| Neonatal Mortality Rate at 28 Days in <5th Percentile Birth Weight Infants (as a Proxy Measure for Prematurity) | 566 | 524 |
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.
| Participants | Intervention Group | Control Group |
|---|---|---|
| Use of Antenatal Corticosteroids in Women at Risk of Preterm Birth in All the Study Clusters | 1,052 | 215 |
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.
| Participants | Intervention Group | Control Group |
|---|---|---|
| Suspected Maternal Infection | 1,207 | 867 |
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.
| participants | Intervention Group | Control Group |
|---|---|---|
| Maternal Mortality Rate | 106 | 97 |
Number of neonatal deaths before 28 days per 1,000 live births
| Participants | Intervention Group | Control Group |
|---|---|---|
| Neonatal Mortality Rate | 1300 | 1211 |
Number of stillbirths per 1,000 births
| Participants | Intervention Group | Control Group |
|---|---|---|
| Stillbirth Mortality Rate | 1304 | 1264 |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intervention Group | — | 2,932/48,698 (6%) | 0/48,698 (0%) |
| Control Group | — | 2,774/52,007 (5.3%) | 0/52,007 (0%) |
| Event | Intervention Group | Control Group |
|---|---|---|
| Stillbirth/neonatal deathPregnancy, puerperium and perinatal conditions | 2604/48698 | 2475/52007 |
| Congenital anomalyPregnancy, puerperium and perinatal conditions | 278/48698 | 250/52007 |
| Maternal deathPregnancy, puerperium and perinatal conditions | 50/48219 | 49/51523 |
Women enrolled in the Global Network Maternal Newborn Health Registry (MNHR) during the Antenatal Corticosteroid Trial period with delivery and outcome data available from MNHR.
| Age, Customized(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| <20 | 5,412 | 6,622 | 12034 |
| 20-35 | 41,003 | 42,938 | 83941 |
| >35 | 1,741 | 1,895 | 3636 |
| Missing | 63 | 68 | 131 |
| Sex: Female, Male(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| Female | 48,219 | 51,523 | 99742 |
| Male | 0 | 0 | 0 |
| Region of Enrollment(participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| Argentina | 2,115 | 2,292 | 4407 |
| Pakistan | 7,714 | 8,202 | 15916 |
| Guatemala | 5,813 | 3,960 | 9773 |
| Zambia | 4,279 | 5,739 | 10018 |
| Kenya | 5,900 | 7,103 | 13003 |
| India | 22,398 | 24,227 | 46625 |
| Education(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| No formal schooling | 11,005 | 11,258 | 22263 |
| Primary | 17,686 | 19,515 | 37201 |
| Secondary | 15,528 | 16,170 | 31698 |
| University | 3,757 | 4,313 | 8070 |
| Missing | 243 | 267 | 510 |
| Parity(Participants) | Intervention Group | Control Group | Total |
|---|---|---|---|
| 0 | 16,366 | 17,901 | 34267 |
| 1 | 13,961 | 14,599 | 28560 |
| 2 | 17,570 | 18,934 | 36504 |
| Missing | 322 | 89 | 411 |
The record gives a start of Oct 2011, a primary completion of Mar 2014 and a completion of Apr 2014. It does not say whether these dates are actual or estimated.
Results were first posted in Dec 2024, 10 years 9 months after primary completion.
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