The first week of a newborn's life is a time of the most rapid biological change in life as the baby adapts to living outside the womb, suddenly exposed to new challenges including bacteria and viruses. Yet surprisingly little is known about these early changes.
An international research team co-led by the University of British Columbia has pioneered a technique to get huge amounts of data from a tiny amount of newborn blood--less than a quarter teaspoon--allowing for the most comprehensive data analysis yet.
The technique, described in new research published today in Nature Communications, reveals molecular changes in the first week of newborn life, including what genes are turned on, what proteins are being made and how metabolism changes. The findings establish a common developmental pathway for the first week of a newborn's life, providing a baseline to further our understanding of newborn health and, in particular, the impact of vaccines.
"It's quite amazing," said Amy Lee, co-lead author of the study and research associate at UBC. "We were able to capture a tremendous amount of information about newborns in that first week of their development, all from less than a quarter of a teaspoon of blood."
Tiny sample, big knowledge
Previous efforts to gather data on newborn development have been limited by the challenge of obtaining a large enough blood sample from a tiny newborn.
The team overcame this challenge by developing methods that minimize the amount of blood needed, followed by analyzing the complex data using sophisticated software.
"We found thousands of changes over the first week of life, including changes in gene expression and components of immune defense such as interferons, neutrophil function and complement pathways," said Casey Shannon, co-lead author and a computational biologist at the PROOF Centre in Vancouver.
"Contrary to the relatively steady biology we see in healthy adults, we found that the first week of human life for newborns is highly dynamic," said Robert Hancock, one of the study's senior authors and the Canada Research Chair in Health and Genomics at UBC. "Through advanced computational analyses of diverse data from this tiny sample of blood, we discovered dramatic biological changes in newborns, but these molecular changes also follow a common and highly interconnected developmental pattern."
An inter-continental effort
The researchers piloted their technique with a group of infants from The Gambia in West Africa after first obtaining permission from village elders and informed consent from mothers in local languages. They then validated their approach with a second group of Australasian newborns.
They found that the two independent infant groups showed a common, highly dynamic developmental trajectory--suggesting that the molecular changes do not occur at random, but instead follow an age-specific pathway.
"This common trajectory is exciting as it allows us to ask bigger questions about the differences between different populations and the impact of biomedical interventions such as vaccines on development," said Dr. Ofer Levy, one of the study's senior authors and director of the Precision Vaccines Program at Boston Children's Hospital.
Optimizing vaccines in early life
The study establishes a baseline for health and disease in early life that can help measure responses to key medical interventions and the impact of factors such as diet, disease and maternal health.
The researchers are especially interested in studying the impact of immunization. Newborns' responses to immunization are distinct from those of older individuals, and much needs to be learned to optimize the use and benefit of vaccines in early life.
"These findings will guide us to develop better infant vaccines in the future," said Dr. Tobias Kollmann, one of the study's senior authors, professor in the UBC faculty of medicine and an investigator and pediatric infectious disease consultant at BC Children's Hospital. "Newborns are especially susceptible to infection early in life, and at most risk of serious complications during that critical first week of life."
The researchers say this study would not have been possible without international collaboration amongst experts in their respective fields.
Those involved included scientists from UBC, the BC Cancer Agency, BC Children's Hospital, the Centre for Heart Lung Innovation (HLI) at St. Paul's Hospital, and the PROOF Centre of Excellence. The study also involved researchers at Boston Children's Hospital, the London School of Hygiene & Tropical Medicine, and the Medical Research Council Unit - The Gambia, the Papua New Guinea Institute of Medical Research, the University of Melbourne and the University of Western Australia as well as Telethon Kids Institute in Perth, Australia.
The Expanded Program on Immunization Consortium (EPIC) contributed collectively to this study. EPIC is an association of academic centers around the world partnering to conduct systems biology studies in newborns and infants.
The study was supported in part by the NIH's National Institute of Allergy and Infectious Diseases as part of the Human Immunology Project Consortium and by the Precision Vaccines Program.