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

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

doi:10.12688/gatesopenres.12869.2

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

Gates Open Res. 2019 Feb 5:2:49. doi: 10.12688/gatesopenres.12869.2. eCollection 2018.

Authors

Stephen H Kennedy^#^{1

2}, Cesar G Victora^#³, Rachel Craik^{1

2}, Stephen Ash^{1

4}, Fernando C Barros⁵, Hellen C Barsosio⁶, James A Berkley^{6

7}, Maria Carvalho⁸, Michelle Fernandes^{1

9}, Leila Cheikh Ismail^{1

10}, Ann Lambert^{1

2}, Cecilia M Lindgren¹¹, Rose McGready¹², Shama Munim¹³, Christoffer Nellåker^{1

11}, Julia A Noble¹⁴, Shane A Norris¹⁵, Francois Nosten¹², Eric O Ohuma^{1

16

17}, Aris T Papageorghiou^{1

2}, Alan Stein¹⁸, William Stones^{8

19}, Chrystelle O O Tshivuila-Matala^{1

15

20}, Eleonora Staines Urias^{1

2}, Manu Vatish¹, Katharina Wulff²¹, Ghulam Zainab¹³, Krina T Zondervan^{1

22}, Ricardo Uauy^#^{23

24}, Zulfiqar A Bhutta^#^{17

25}, José Villar^#^{1

2}

Affiliations

¹ Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.
² Oxford Maternal & Perinatal Health Institute, Green Templeton College, Oxford, UK.
³ Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
⁴ Oxford Ludwig Institute, University of Oxford, Oxford, UK.
⁵ Programa de Pós-Graduação em Saúde e Comportamento, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
⁶ KEMRI-Coast Centre for Geographical Medicine and Research, University of Oxford, Kilifi, Kenya.
⁷ Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁸ Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya.
⁹ Faculty of Medicine, Department of Paediatrics, University of Southampton, Southampton, UK.
¹⁰ Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
¹¹ Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
¹² Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
¹³ Department of Obstetrics and Gynaecology, Division of Women and Child Health, Aga Khan University, Karachi, Pakistan.
¹⁴ Department of Engineering Science, University of Oxford, Oxford, UK.
¹⁵ SAMRC Developmental Pathways For Health Research Unit, Department of Paediatrics & Child Health, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK.
¹⁷ Center for Global Child Health, Hospital for Sick Children, Toronto, Canada.
¹⁸ Department of Psychiatry, University of Oxford, Oxford, UK.
¹⁹ Departments of Public Health and Obstetrics & Gynaecology, Malawi College of Medicine, Blantyre, Malawi.
²⁰ Health, Nutrition & Population Global Practice, World Bank Group, Washington, DC, USA.
²¹ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
²² Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
²³ Division of Paediatrics, Pontifical Universidad Catolica de Chile, Santiago, Chile.
²⁴ Department of Nutrition and Public Health Interventions Research, London School of Hygiene and Tropical Medicine, London, UK.
²⁵ Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

^# Contributed equally.

Abstract

Background: INTERBIO-21 ^st is Phase II of the INTERGROWTH-21 ^st 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-21 ^st 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.

Keywords: INTERBIO-21st; INTERGROWTH-21st; SGA; fetal growth; preterm birth.

Grants and funding

The work was supported by the INTERGROWTH-21st grant no.49038 from the Bill & Melinda Gates Foundation to the University of Oxford, for which we are very grateful.