title: The global network antenatal corticosteroids trial: impact on stillbirth.
abstract: BACKGROUND
  Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention.
  
  
  METHODS
  The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5(th) percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth.
  
  
  RESULTS
  After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p-0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04-1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters.
  
  
  CONCLUSIONS
  In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial.
  
  
  BACKGROUND
  clinicaltrials.gov (NCT01084096).
authors.affiliation: Columbia University, New York, NY, USA. rlg@columbia.edu.|Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA. rlg@columbia.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goldenberg
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Thorsten
authors.affiliation: IECS, Buenos Aires, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Althabe
authors.affiliation: Columbia University, New York, NY, USA.|Aga Khan University, Karachi, Pakistan.
authors.forename: Sarah
authors.initials: S
authors.lastname: Saleem
authors.affiliation: , Guatemala, Guatemala.
authors.forename: Ana
authors.initials: A
authors.lastname: Garces
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Carlo
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Omrana
authors.initials: O
authors.lastname: Pasha
authors.affiliation: University Teaching Hospital, Lusaka, Zambia.
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.affiliation: KLE University's JN Medical College,, Belgaum, India.
authors.forename: Shivaprasad
authors.initials: S
authors.lastname: Goudar
authors.affiliation: Moi University, Eldoret, Kenya.
authors.forename: Fabian
authors.initials: F
authors.lastname: Esamai
authors.affiliation: University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Krebs
authors.affiliation: Christiana Care, Newark, DE, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Derman
authors.affiliation: Indiana University, Indianapolis, IN, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Liechty
authors.affiliation: Lata Medical Research Foundation, Nagpur, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Patel
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Hibberd
authors.affiliation: Tulane School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Pierre M
authors.initials: PM
authors.lastname: Buekens
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Marion
authors.initials: M
authors.lastname: Koso-Thomas
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
authors.forename: Menachem
authors.initials: M
authors.lastname: Miodovnik
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Wallace
authors.affiliation: IECS, Buenos Aires, Argentina.
authors.forename: José M
authors.initials: JM
authors.lastname: Belizán
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McClure
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005865:Gestational Age; D006801:Humans; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy*; D050497:Stillbirth / Q000453:epidemiology*
chemical_list: D000305:Adrenal Cortex Hormones