The Distribution of Clinical Phenotypes of Preterm Birth Syndrome: Implications for Prevention | Global Health | JAMA Pediatrics | JAMA Network
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Original Investigation
March 2015

The Distribution of Clinical Phenotypes of Preterm Birth Syndrome: Implications for Prevention

Author Affiliations
  • 1Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas, Pelotas, Rio Grande do Sul, Brazil
  • 2Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil
  • 3Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, England
  • 4Department of Engineering Science, University of Oxford, Oxford, England
  • 5School of Public Health, Peking University, Beijing, China
  • 6Department of Obstetrics and Gynecology, Ohio State University, Columbus, Ohio
  • 7Department of Obstetrics and Gynecology, Columbia University, New York, New York
  • 8Department of Pediatrics and Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
  • 9Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya
  • 10Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland
  • 11Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Detroit, Michigan
  • 12Department of Family and Community Health, Ministry of Health, Muscat, Sultanate of Oman
  • 13Dipartimento di Scienze Pediatriche e dell’Adolescenza, Cattedradi Neonatologia, Università degli Studi di Torino, Torino, Italy
  • 14University of Washington School of Medicine, Seattle
  • 15Centre for Statistics in Medicine, University of Oxford Botnar Research Centre, Oxford, England
  • 16Nagpur INTERGROWTH-21st Research Centre, Ketkar Hospital, Nagpur, India
  • 17Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington
  • 18Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan
  • 19Center for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
JAMA Pediatr. 2015;169(3):220-229. doi:10.1001/jamapediatrics.2014.3040
Abstract

Importance  Preterm birth has been difficult to study and prevent because of its complex syndromic nature.

Objective  To identify phenotypes of preterm delivery syndrome in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.

Design, Setting, and Participants  A population-based, multiethnic, cross-sectional study conducted at 8 geographically demarcated sites in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States. A total of 60 058 births over a 12-month fixed period between April 27, 2009, and March 2, 2014. Of these, 53 871 had an ultrasonography estimate of gestational age, among which 5828 were preterm births (10.8%). Pregnancies were prospectively studied using a standardized data collection and online data management system. Newborns had anthropometric and clinical examinations using standardized methods and identical equipment and were followed up until hospital discharge.

Main Outcomes and Measures  The main study outcomes were clusters of preterm phenotypes and for each cluster, we analyzed signs of presentation at hospital admission, admission rates for neonatal intensive care for 7 days or more, and neonatal mortality rates.

Results  Twelve preterm birth clusters were identified using our conceptual framework. Eleven consisted of combinations of conditions known to be associated with preterm birth, 10 of which were dominated by a single condition. However, the most common single cluster (30.0% of the total preterm cases; n = 1747) was not associated with any severe maternal, fetal, or placental condition that was clinically detectable based on the information available; within this cluster, many cases were caregiver initiated. Only 22% (n = 1284) of all the preterm births occurred spontaneously without any of these severe conditions. Maternal presentation on hospital admission, newborn anthropometry, and risk for death before hospital discharge or admission for 7 or more days to a neonatal intensive care unit, none of which were used to construct the clusters, also differed according to the identified phenotypes. The prevalence of preterm birth ranged from 8.2% in Muscat, Oman, and Oxford, England, to 16.6% in Seattle, Washington.

Conclusions and Relevance  We identified 12 preterm birth phenotypes associated with different patterns of neonatal outcomes. In 22% of all preterm births, parturition started spontaneously and was not associated with any of the phenotypic conditions considered. We believe these results contribute to an improved understanding of this complex syndrome and provide an empirical basis to focus research on a more homogenous set of phenotypes.

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