Subject: Fetal, Preterm and Neonatal

Series: Clinics in Developmental Medicine

Publication date: 04/12/2020

ISBN: 9781911488965

Edition: 1st

Pages: 256

Extremely Preterm Birth and its Consequences

The ELGAN Study

Olaf Dammann, Alan Leviton, T Michael O’Shea, Nigel Paneth (Editors)

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The ELGAN (Extremely Low Gestational Age Newborns) Study was the largest and most comprehensive multicentre study ever completed for this population of babies born before 28 weeks’ gestation. The authors’ presentation and exploration of the results of the research will help clinicians to prevent adverse health outcomes and promote positive health for these children. They have focused on the exposures and outcomes related to the developing brain, inflammation and infection as major risk factors for developmental adversity.

  • Identifies potentially modifiable risk factors and pathways leading to a broad range of neurodevelopmental impairments in middle childhood, as well as to other conditions such as asthma, obesity, cerebral palsy and autism spectrum disorder.
  • With a focus on pre-, peri-, and post-natal inflammation and the methods used to assess it.
  • Covers antenatal and postnatal risk factors, then structural and functional indicators of damage to the brain.

From the Foreword

“The ELGAN Study is an important contribution and not only clarifies, but also signposts their work and future research directions … one of the most important large detailed and prospective longitudinal studies in our field.”

Neil Marlow

Professor of Neonatal Medicine, University College London


It will be a valuable and comprehensive resource for practising neonatologists, developmental paediatricians, child neurologists and psychiatrists, as well as to researchers studying population health.

Clinics in Developmental Medicine

Olaf Dammann
Olaf Dammann

Olaf Dammann is Professor and Vice-Chair Department of Public Health, Tufts University School of Medicine, Boston. He trained in linguistics and informatics (U Hamburg), medicine (U Hamburg), epidemiology (Harvard), and philosophy (U Johannesburg). He worked as a pediatrician until he started doing research full-time in 1995. His main research topics are perinatal epidemiology with a focus on brain/retina damage in preterm newborns, and philosophy of science with a focus on causation and explanation. He has received research funding from the NIH, the European Union, and several private foundations. His bibliography includes more than 200 papers and the book “Causation in Population Health Informatics and Data Science” (Springer, 2019).

Alan Leviton
Alan Leviton

Alan Leviton is Professor of Neurology, Harvard Medical School, Emeritus head of the neuro-epidemiology unit, Boston Children’s Hospital. He has clinical training in neurology and research training in epidemiology, and devoted himself to identifying the exposures that most likely contribute to neurocognitive and physical limitations in high-risk children.

Thomas Michael O’Shea
Thomas Michael O'Shea

Thomas Michael O’Shea, MD, MPH, C. Richard Morris Distinguished Professor of Pediatrics and Division Chief for Neonatal-Perinatal Medicine at the University of North Carolina. For the past 35 years he has studied the epidemiology and prevention of neurodevelopmental impairments and related child health outcomes among individuals born prematurely. He was awarded the AAP Section on Neonatal-Perinatal Medicine Landmark Award in recognition of his study of the relationship of treatment with postnatal glucocorticoids to the risk of cerebral palsy among very low birth weight infants. He currently is the co-principal investigator for the third phase of the ELGAN Study.

Nigel Paneth
Nigel Paneth

Nigel Paneth, MD MPH is University Distinguished Professor, Departments of Epidemiology & Biostatistics and Pediatrics & Human Development, Michigan State University. He is a pediatrician and perinatal and child health epidemiologist with a particular interest in the causes and prevention of childhood neurodevelopmental handicap, especially cerebral palsy.

Other books by Nigel Paneth

Author Appointments

1. Introduction
Alan Leviton, Olaf Dammann, T Michael O’Shea, and Nigel Paneth

PART I Placenta and Perinatal Risk Factors

2. Placental Microorganisms in ELGAN with Correlation to Pregnancy Outcomes, Intrauterine Inflammation, and Postnatal and Later-life Outcomes
Martha Scott Tomlinson and Rebecca C Fry

3. Correlations of Placental Histology in ELGANS With Delivery Indications, Placental Microbiology, and Childhood Morbidity
Jonathan L Hecht

4. Signal Initiators of Early Preterm Birth
Asha N Talati and Tracy A Manuck

5. Maternal Adiposity 43
Jelske W van der Burg and Elizabeth T Jensen

PART II Neonatal Exposures and Outcomes

6. Illness-Severity and Outcomes among Children Born Extremely Preterm
J Wells Logan and Olaf Dammann

7. Bacteremia
H Reeve Bright and Kikelomo Babata

8. Retinopathy of Prematurity
Mari Holm, Deborah Van der Veen, and Olaf Dammann

9. Bronchopulmonary Dysplasia
Wesley M Jackson and Matthew M Laughon

PART III Structural Brain Disorders

10. Ultrasound
Genevieve Taylor and T Michael O’Shea

11. Multispectral Quantitative MRI: Techniques and Preliminary Results
Hernán Jara and T Michael O’Shea

PART IV Function Brain Disorders

12. Cerebral Palsy among Children Born Extremely Preterm: The ELGAN Study
Stephanie Watkins and T Michael O’Shea

13. Cognitive and Behavioral Functioning
Lauren Bush, Megan N Scott, and Scott J Hunter

14. Autism, Social Impairment, and Social Communication Deficits in Children Born Prior to the 28th Week of Gestation
Steven J Korzeniewski

15. Psychiatric and Behavioral Outcomes at Age 2 and 10 Years in Individuals Born Extremely Preterm
Jean A Frazier, Hannah Zamore, and Stephen R Hooper

16. Concluding Chapter: Please Draw Your Own Conclusions
Alan Leviton, Olaf Dammann, T Michael O’Shea, and Nigel Paneth


This new book in the Clinics in Developmental Medicine series summarizes and reviews childhood findings (up to age 10y) from the Extremely Low Gestational Age Newborn (ELGAN) study. The ELGAN study, which is still ongoing, is one of the largest prospective longitudinal studies of individuals born extremely preterm, with a large number of North American centres contributing. It was designed and is conducted by a large group of distinguished researchers from multiple specialities, who are all experts in their respective field.
The main goal of the ELGAN study – and this is what sets it apart from other existing studies on extremely preterm birth and long-term outcomes – has been to investigate how inflammatory processes in parts of the body other than the brain affect the risk for brain injury in infants born extremely preterm.

The ELGAN study focuses on potentially modifiable risk factors (in particular prenatal and perinatal inflammation) and a broad range of important neonatal morbidities. These include brain injury, chronic lung disease, retinopathy of prematurity, and sepsis. The study also covers resulting long-term outcomes, such as neuromotor function, global and specific cognitive functions, behaviour, learning, and mental health, as well as some paediatric outcomes (e.g. lung function). The introduction to the book describes the ideas that shaped the ELGAN study, and the planning and implementation of the project. This makes a very interesting read and creates an appetite for the specific research areas of the study and findings.
The ELGAN study findings are divided into four parts. Each part contains concise, short chapters, which are intended to provide a broad perspective rather than going into too much detail. This succeeds for the majority of the chapters. They are easy and enjoyable to read, and the underlying concepts of each topic are presented in sufficient detail. This allows the reader to get a quick overview on the specific topic and main findings. Most chapters in the four sections contain a brief introduction, main findings, and a section where ELGAN findings are discussed in context with other existing work. Each chapter contains an exhaustive reference list with papers from the ELGAN study and research from other studies, pointing the reader to sources for more detailed reading.
The first part of the book describes the ELGAN study work relating to placental and perinatal risk factors, maternal weight, and obesity. Part II deals with neonatal exposures, or, rather, risk factors, and neonatal outcomes (chronic lung disease, retinopathy of prematurity, sepsis). Part III is concerned with structural brain abnormalities assessed with cranial ultrasound in the neonatal period, and touches on early findings from advanced magnetic resonance imaging studies in childhood. Part IV contains chapters that describe toddler age and childhood age outcomes: neuromotor, cognitive, behavioural, psychiatric, and their neural correlates. Antecedents are described for each, that is, associations with perinatal or neonatal inflammation. There is then a concluding chapter, which pulls the themes and concepts of the ELGAN study together and briefly outlines the current and future research streams.

There is something for everybody in this book. It is highly recommended for clinicians in the fields of obstetrics/fetal medicine, neonatology, developmental paediatrics, neurology, and for allied health professionals. It also provides important background information and food for thought for researchers in the field. This is an inspiring book that brings together the many studies that so far have been conducted in the ELGAN project. It provides a good overview of how all the findings from the individual studies fit together overall in the ELGAN study, and how they broaden our understanding of causes and consequences of extremely preterm birth.

Brigitte Vollmer
Clinical Neurosciences, Faculty of Medicine, University of Southampton,
Southampton; Paediatric Neurology, Southampton Children’s Hospital, Southampton,

This book is a summary of the Extremely Low Gestational Age Newborn (ELGAN) study and all of its subsequent papers (>150) in the past 17 years. The original study was an NIH sponsored collaborative effort of 14 hospitals treating over 1,000 neonates of less than 28 weeks gestation between 2002 and 2004. The survivors were studied during their initial hospitalization and then at intervals up to 17 years of age. Harry Gordon once said "neonatologists should be farmers and not firemen," and this book emphasizes the importance of careful long-term follow up of our most vulnerable patients. The book summarizes the findings of antenatal risk factors that lead to prematurity as well as the postnatal factors that may lead to abnormal outcomes.
The purpose of the book is to bring together the extensive literature that this one study has produced in order to prevent adverse health outcomes including severe prematurity and its consequences. This is a very worthy objective since the United States has one of the highest Extremely Low Birth Weight (ELBW) rates in the industrialized world. The book reviews and clarifies the various aspects of this project and gives direction to future research projects in this area.
The book is intended for neonatologists, perinatologists, pediatric neurologists, developmental pediatricians, researchers, and those who study population health. Although it probably will not help with bedside decisions for the practicing physician, it does identify risk factors that may alter some of the adverse outcomes for this vulnerable population. The researchers and authors of the text are world renowned in this field.
The book is divided into four sections, each having two to four chapters. The first two sections deal with antenatal and postnatal risk factors for adverse outcomes. The third and fourth sections deal with brain dysfunction/damage and functional abnormalities. The first section is of particular importance in that it brings together several decades of research of antenatal risk factors from abnormalities of the placenta and other potential risks such as maternal obesity. If the burden of severe prematurity in the U.S. is going to be reduced, this is the area that must be understood.
This book is a well written and concise summary of where we stand with regard to one of the most challenging medical problems in the U.S.: extreme prematurity. It is one of the most important longitudinal studies in the field and should be read by practicing clinicians who deal with the ELGAN baby on a daily basis. Although many texts will discuss the outcomes of ELGAN babies, most will refer to these studies as their references and no book is comparable in its depth and insight.
Jay Goldsmith, MD (Tulane University School of Medicine) 2021 Jay Goldsmith, MD (Tulane University School of Medicine) 2021

Extremely Preterm Birth and its Consequences – Chapter 1: Introduction (free ebook) - £0