UNC School of Medicine researchers are 15 years into a long-term study to learn how to optimize the health of children born at less than 28 weeks gestation, including identifying factors that help them succeed in school and develop social and communication skills.
Michael O’Shea, MD, MPH, C. Richard Morris Distinguished Professor of Pediatrics, and Rebecca Fry, PhD, Carol Remmer Angle Distinguished Professor of environmental sciences and engineering at the Gillings School of Global Public Health, run the Extremely Low Gestational Age Newborn (ELGAN) study, which is now 15 years old. We talked to them about what they have learned and how they are using this information as part of a new national study to explore the impact of the environment on children’s health and improve health outcomes.
Studying Babies Born Before 28 Weeks Gestation
Funded by the National Institutes of Health (NIH), the ELGAN research team has sought to learn more about the causes of medical problems and developmental difficulties that are common in babies born very early. This information has the potential to help make a difference in the care and health outcomes for these children.
The ongoing study started with more than 1,500 children born at least three months early at 14 different hospitals in five states. These children, born between the years 2002 and 2004, were assessed at birth and again when they were two and 10 years old.
“In addition, when the babies had routine blood tests, researchers saved a few drops of blood for later testing,” says Fry, an environmental scientist and co-principal investigator of the study.
“Because they were born at 14 hospitals, we had geographic diversity, as well as diversity in socioeconomic status and in race,” says O’Shea, a neonatal and perinatal specialist and Fry’s co-principal investigator of the study.
The ELGAN study assessed the events before and around the time of these early births and then measured developmental skills as the children grew. Through statistical analyses, researchers are trying to determine if children with health and developmental difficulties during childhood were more likely to have been exposed to something in particular before or around the time of their birth. While the study is ongoing, the researchers determined that inflammation, maternal obesity, and fetal growth impairment play roles in the overall health of premature babies.
The Inflammation Effect
Inflammation is the process through which the body defends itself against infection and other damaging influences, but too much can harm the lungs, intestines, eyes, and brain. Certain proteins that circulate in the blood serve as inflammation signals to alert the body about the presence of potentially damaging influences, such as infections.
The researchers found that the earlier a baby was born, the longer it took for the inflammation-related proteins to disappear from the blood and the more likely these proteins were to reappear. In addition, the longer the inflammation-related proteins stayed in the blood, the higher the risk of damage to the baby’s lungs, intestines and brain.
The study also explored how inflammation early in life is related to brain development. By measuring inflammation-related proteins in the blood of ELGAN participants, obtained during each baby’s first weeks in the neonatal intensive care unit, researchers discovered that:
- Children who were exposed to more than one day of inflammation in the first month of life were more likely to develop cerebral palsy, more likely to have developmental difficulties, and more likely to have an attention problem at age 2 than children without inflammation.
- Children who were exposed to more than one day of inflammation in the first month of life were more likely to have difficulty on tests that assessed thinking and learning skills.
- The amount of gray matter and white matter in the brain appears to be somewhat less among those who had inflammation in their blood after birth.
ELGAN researchers are now using this information to guide the design of clinical trials for medicines and treatments that may help reduce problems from inflammation.
Obesity’s Role in Premature Births
ELGAN researchers also found that whether a mother was obese before pregnancy could have negative impact on her child’s health.
The child is more likely to grow up to be obese if his or her mother is obese before pregnancy, and obesity has many health consequences. A healthy pre-pregnancy body mass index (BMI) was associated with a child being healthier and doing better developmentally later in life.
“The other prenatal factor that seems to be important is how well the fetus grows, because among the ELGAN Study participants, fetuses that did not grow well during pregnancy had a higher risk of an autism spectrum disorder,” O’Shea says.
“We aim to identify modifiable factors that can influence the health of children and make the lives of children better,” Fry says. “Factors such as maternal pre-pregnancy BMI is an example of a factor that is theoretically modifiable.”
The Premature Baby Enters Adolescence
ELGAN has entered its third phase and is once again assessing the study participants, who are now around age 15. Researchers continue to study their health and well-being, including assessing reasoning skills, behavior, emotions, sleep patterns and overall quality of life. In addition, the study tracks the teens’ weight, height and head circumference. Researchers also are collecting baby teeth, saliva and urine samples.
The researchers say they hope to use this information to continue to learn how to help make a difference in the care and health outcomes of children born very early and to help prevent learning and behavior problems in these children.
Understanding Environmental Influences on Children
In 2016, the National Institutes of Health selected ELGAN, along with similar studies in the United States, to join a seven-year study of about 50,000 children called Environmental Influences on Child Health Outcomes (ECHO). ECHO combines about 70 studies, including ELGAN, to focus on environmental impacts. Last year O’Shea and Fry received a five-year, $20.5 million NIH grant to continue their studies.
“As part of ECHO, we will be expanding the health areas being measured,” Fry says. “This will be the largest study of children’s health in the United States, and the goal is that at the end of that seven-year period, we will have a sense of what influences the health of about 50,000 children.”
ECHO will investigate environmental exposures—including physical, chemical, biological, social, behavioral, natural and built environments—on child health and development. The focus will be on four key pediatric outcomes that have a high public health impact: upper and lower airway, obesity, pre-, peri- and postnatal outcomes, and neurodevelopment.
The study is going to greatly broaden researchers’ understanding of environmental influences during pregnancy, Fry says.
“We have umbilical cord specimens from the individuals who are participating in the ELGAN Study that were saved 15 years ago. We can use these specimens to measure environmental factors such as toxic metals,” she says. “And we are gathering the residential information of ELGAN participants to geocode, and that will allow us to get an idea about the air quality to which the mother was exposed.”
For Fry and O’Shea, the ELGAN-ECHO Study is a once in a lifetime opportunity to collaborate with children and their families, outstanding child health researchers, and public health stakeholders to transform our understanding of how the environment influences child health. The knowledge gained from this collaboration can then be used to create a roadmap leading to better health for future generations of children in the United States and beyond.