title: The Antenatal Corticosteroids Trial (ACT)'s explanations for neonatal mortality - a secondary analysis.
abstract: BACKGROUND
  The Antenatal Corticosteroid Trial assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but was associated with an overall increase in neonatal deaths. We aimed to explore plausible pathways through which this intervention increased neonatal mortality.
  
  
  METHODS
  We conducted a series of secondary analyses to assess whether ACS or other components of the multifaceted intervention that might have affected the quality of care contributed to the increased mortality observed: 1) we compared the proportion of neonatal deaths receiving ACS between the intervention and control groups; 2) we compared the antenatal and delivery care process in all births between groups; 3) we compared the rates of possible severe bacterial infection between groups; and 4) we compared the frequency of factors related to ACS administration or maternal high risk conditions at administration between the babies who died and those who survived 28 days among all births in the intervention group identified as high risk for preterm birth and received ACS.
  
  
  RESULTS
  The ACS exposure among the infants who died up to 28 days was 29 % in the intervention group compared to 6 % in controls. No substantial differences were observed in antenatal and delivery care process between groups. The risk of pSBI plus neonatal death was significantly increased in intervention clusters compared to controls (2.4 % vs. 2.0 %, adjusted RR 1.17, 95 % CI 1.04-1.30, p = 0.008], primarily for infants with birth weight at or above the 25(th) percentile. Regarding factors related to ACS administration, term infants who died were more likely to have mothers who received ACS within 7 days of delivery compared to those who survived 28 days (26.5 % vs 17.9 %, p = 0.014), and their mothers were more likely to have been identified as high risk for hypertension and less likely for signs of preterm labor.
  
  
  CONCLUSIONS
  These results suggest that ACS more than other components of the intervention may have contributed to the overall increased neonatal mortality. ACS may have also been involved in the observed increased risk of neonatal infection and death. Further trials are urgently needed to clarify the effectiveness and safety of ACS on neonatal health in low resource settings.
authors.affiliation: Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina. falthabe@iecs.org.ar.
authors.forename: Fernando
authors.initials: F
authors.lastname: Althabe
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Thorsten
authors.affiliation: Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina.
authors.forename: Karen
authors.initials: K
authors.lastname: Klein
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McClure
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Hibberd
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goldenberg
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Carlo
authors.affiliation: Fundación para la Alimentación y Nutrición de Centro América y Panamá, Guatemala City, Guatemala.
authors.forename: Ana
authors.initials: A
authors.lastname: Garces
authors.affiliation: Lata Medical Research Foundation, Indira Gandhi Government Medical College, Nagpur, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Community Health Sciences, 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: University of Colorado School of Medicine, Denver, CO, USA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Krebs
authors.affiliation: KLE University's Jawaharlal Nehru Medical College, Belgaum, Karnataka, India.
authors.forename: Shivaprasad
authors.initials: S
authors.lastname: Goudar
authors.affiliation: Christiana Health Care, Newark, DE, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Derman
authors.affiliation: Moi University School of Medicine, Eldoret, Kenya.
authors.forename: Fabian
authors.initials: F
authors.lastname: Esamai
authors.affiliation: School of Medicine, Indiana University, Indianapolis, IN, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Liechty
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Nellie I
authors.initials: NI
authors.lastname: Hansen
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Sreelatha
authors.initials: S
authors.lastname: Meleth
authors.affiliation: RTI International, Durham, NC, USA.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Wallace
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: Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Tulane School of Public Health & Tropical Medicine, New Orleans, LA, USA.
authors.forename: Pierre M
authors.initials: PM
authors.lastname: Buekens
authors.affiliation: Institute for Clinical Effectiveness and Health Policy (IECS), Buenos Aires, Argentina.
authors.forename: José M
authors.initials: JM
authors.lastname: Belizán
mesh_terms: D003906:Developing Countries; D005240:Feasibility Studies; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D066087:Perinatal Death / Q000209:etiology*; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control; D011295:Prenatal Care / Q000379:methods* / Q000592:standards; D012307:Risk Factors
chemical_list: D005938:Glucocorticoids