Multiple courses of antenatal corticosteroids for preterm birth study: outcomes in children at 5 years of age (MACS-5).

Abstract

IMPORTANCE:

A single course of antenatal corticosteroid therapy is recommended for pregnant women at risk of preterm birth between 24 and 33 weeks' gestational age. However, 50% of women remain pregnant 7 to 14 days later, leading to the question of whether additional courses should be given to women remaining at risk for preterm birth. The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) was an international randomized clinical trial that compared multiple courses of antenatal corticosteroids with a single course in women at risk of preterm birth.

OBJECTIVE:

To determine the effects of single vs multiple courses of antenatal corticosteroid therapy on death or neurodevelopmental disability (neuromotor, neurosensory, or neurocognitive/neurobehavioral function) at 5 years of age in children whose mothers participated in MACS. Our secondary aims were to determine the effect on height, weight, head circumference, blood pressure, intelligence, and specific cognitive (visual, spatial, and language) skills.

DESIGN, SETTING, AND PARTICIPANTS:

Cohort follow-up study of children seen between June 2006 and May 2012 at 55 centers. In total, 1724 women (2141 children) were eligible for the study, of whom 1728 children (80.7% of the 2141 eligible children) participated and 1719 children contributed to the primary outcome.

INTERVENTION:

Single and multiple courses of antenatal corticosteroid therapy.

MAIN OUTCOMES AND MEASURES:

The primary outcome was death or survival with a neurodevelopmental disability in 1 of the following domains: neuromotor (nonambulatory cerebral palsy), neurosensory (blindness, deafness, or need for visual/hearing aids), or neurocognitive/neurobehavioral function (abnormal attention, memory, or behavior).

RESULTS:

There was no significant difference between the groups in the risk of death or neurodevelopmental disability: 217 of 871 children (24.9%) in the multiple-courses group vs 210 of 848 children (24.8%) in the single-course group (odds ratio, 1.02 [95% CI, 0.81 to 1.29]; P = .84).

CONCLUSIONS AND RELEVANCE:

Multiple courses, compared with a single course, of antenatal corticosteroid therapy did not increase or decrease the risk of death or disability at 5 years of age. Because of a lack of strong conclusive evidence of short-term or long-term benefits, it remains our opinion that multiple courses not be recommended in women with ongoing risk of preterm birth.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00187382.

• Authors: Elizabeth V Asztalos, Kellie E Murphy, Andrew R Willan, Stephen G Matthews, Arne Ohlsson, Saroj Saigal, B Anthony Armson, Edmond N Kelly, Marie-France Delisle, Amiram Gafni, Shoo K Lee, Renee Sananes, Joanne Rovet, Patricia Guselle, Kofi Amankwah, Mariam Saleem, Johanna Sanchez, MACS-5 Collaborative Group
• Journal: JAMA pediatrics (JAMA Pediatr) Vol. 167 Issue 12 Pg. 1102-10 (Dec 2013) ISSN: 2168-6211 [Electronic] United States
• PMID: 24126948 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Betamethasone

Topics

• Abnormalities, Drug-Induced (diagnosis)
• Adult
• Betamethasone (administration & dosage, therapeutic use)
• Child Behavior Disorders (diagnosis)
• Child, Preschool
• Cohort Studies
• Developmental Disabilities (diagnosis)
• Female
• Follow-Up Studies
• Glucocorticoids (administration & dosage, therapeutic use)
• Humans
• Infant, Newborn
• Infant, Premature, Diseases (drug therapy, mortality)
• Injections, Intramuscular
• Maternal-Fetal Exchange (drug effects)
• Pregnancy
• Pregnancy Outcome
• Premature Birth (drug therapy)
• Risk Factors
• Survival Rate
• Treatment Outcome