Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol

Abstract

Background: Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births.

Methods: We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color-coded tape to measure uterine height to estimate gestational age in women with unknown gestational age. In both intervention and control clusters, health providers will be trained in essential newborn care for low birth weight babies. The primary outcome is neonatal mortality at 28 days of life in preterm infants.

Trial registration: ClinicalTrials.gov NCT01084096.

Figure 1

Trial Design. Design of the cluster randomized controlled trial to increase the use of antenatal corticosteroids to improve neonatal survival in developing countries.

Figure 2

Preterm Kit. Ready-to-use treatment kits containing a full course of antenatal corticosteroids (4 vials with 6-mg of dexamethasone), 4 reuse prevention syringes, 4 pairs of gloves, and detailed instructions on when, how, and to whom to administer antenatal corticosteroids.

Figure 3

Poster Reminder. Poster to be placed in areas of care, including recommendations emphasizing the importance of providing antenatal corticosteroids to eligible women and why and whom to treat.

Figure 4

Color-codedz tape. Both sides of the tape to measure uterine height and estimate gestational age in women with unknown gestational age. Women with uterine height on the red zone are eligible to receive antenatal corticosteroids.

Figure 5

Obstetric Disk. Disk to assess gestational age and facilitate the detection of eligible women. Women with gestational age in the red zone are eligible to receive antenatal corticosteroids.