Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21st Newborn Case-Control Study protocol

Stephen Kennedy ,James A Berkley,Rachel Craik,Alan Stein,Shama Munim,Rose Mcgready,Ann Lambert,Michelle Fernandes,Fernando C Barros,Ricardo Uauy,Ghulam Zainab,Krina T Zondervan,Cecilia M Lindgren,Leila Cheikh Ismail,Eleonora Staines Urias,Christoffer Nellåker,William Stones,Manu Vatish,Hellen C Barsosio,Katharina Wulff,Eric O Ohuma ,J Alison Noble ,François Nosten ,José Villar,Chrystelle O O Tshivuila-Matala ,Maria Carvalho,Shane A Norris ,Stephen Ash,Cesar G Victora ,Zulfiqar Ahmed Bhutta ,A.t Papageorghiou

doi:10.12688/gatesopenres.12869.1

Abstract

Background: INTERBIO-21st is Phase II of the INTERGROWTH-21st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.

Highlights

The International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Project is a large, multicenter, population-based, research initiative, coordinated by the University of Oxford and being carried out by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide
The study directly addresses one of the principal impediments to progress in this field: namely that clinical and public health practice continue to rely upon the use of rudimentary terminology to describe high-risk newborns, e.g. LBW and preterm birth
Interventions should no longer be recommended without a detailed investigation of the prevalence of the etiological factors at country and regional levels

Summary

Introduction

The International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Project is a large, multicenter, population-based, research initiative, coordinated by the University of Oxford and being carried out by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. INTERBIO-21st is Phase II of the INTERGROWTH-21st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment

Objectives

Methods

Findings

Conclusion