Our Neonatal Aim

Accumulating evidence shows that your baby’s development and early life exposures during pregnancy and the newborn period together have a profound impact on overall health throughout their lifetime. Many diseases and disorders that occur in childhood and adulthood are based upon problems with metabolic function that originate in utero (during fetal development) and during the first 1000 days of life. In order to better understand the critical role that metabolism plays in setting a life-course of human health, we’re studying the metabolism of babies and pregnant women. Our aim is to develop therapies that will “cure disease through prevention.”

Metabolism describes chemical reactions that make the energy that we need to live; it plays a critical and previously under-recognized role in human health and disease. Metabolic disorders are many and varied; they include some that are relatively rare, like Phenylketonurea and Niemann Pick disease, and others that are familiar to you and increasingly commonplace in the U.S., like obesity and diabetes. In fact, it’s likely that every disease has a metabolic component.

Indeed, metabolism plays a key role in both genetic (inherited) and acquired human disease. The Metabolic Health Center (MHC) is very interested in investigating the molecular basis for genetic and acquired metabolic diseases, including diseases of unknown origin (in an effort led by Dr. Michael Snyder). We also believe that studying the metabolism of pregnant women and newborns will provide important insights and opportunity for understanding risk of acquired diseases and their prevention. Based on prior research, we understand there is likely an association between the acquired major diseases of prematurity and the under-developed metabolism of preemies. Moreover, we now recognize that variables early in newborn life like frequency of antibiotic usage, route of delivery (i.e. C-section or vaginal birth) and early diet (especially maternal breast milk and formula feedings) can profoundly impact metabolism with both short and long-term consequences. Thus, one of the major goals of the MHC is to help ensure optimal health with metabolic profiling and therapies beginning at birth. To do this, we intend to measure metabolic function in newborns born or admitted to Lucile Packard Children’s Hospital Stanford, starting with the neonatal intensive care unit (NICU) and intermediate care nursery (PICN) while aiming to reach "every" newborn at the hospital. Drs. Karl Sylvester and David Stevenson are leading this effort.

What we’ve learned about metabolism from routine newborn screenings?

Being born early or late, big or small, imparts different biologic vulnerability to your baby for acquired diseases, both of the newborn period as well as into childhood and adulthood. We have discovered that many of these early diseases of the newborn manifest as abnormalities in metabolism. The MHC is expanding the use of blood samples collected at birth that have historically been used to screen all babies for genetic disease that are quite rare. California began to screen newborns in 1966 for just one disorder, and has since developed its Newborn Screening Program to test for 80 different genetic and congenital disease. We are introducing the innovation of re-purposing the newborn screen in several profound ways. Since the newborn screen tells us a lot about a baby’s metabolic profile, we will use collected blood samples for:

  1. Determining risks of a baby developing acquired diseases of prematurity
  2. Forecasting the effects of being born too small (small for gestational age) or too early (premature) on overall health and development

Some of the diseases and consequences of being born too small or too early that we are interested in studying the metabolic basis of include:

  1. Neurodevelopmental impairment (brain capacity and function)
  2. Retinopathy or prematurity (eye disease)
  3. Respiratory distress or chronic lung disease
  4. Necrotizing Enterocolitis [NEC] (intestinal inflammatory condition) 
  5. Sepsis

Dr. Sylvester’s prior work has demonstrated that current newborn screening metabolites can be used in place of gestational age and birthweight to assess a baby’s risk for developing NEC (PMID: 27836286). Moreover, we believe that metabolic profiles will provide great insights to disease origins and potential preventative “cures.”

How has modern medicine influenced metabolism at birth?

Medical advances and changes in routine newborn care have brought about unintended consequences for the natural development of the newborns gastrointestinal tract and immune system. The last century saw the widespread use of perinatal antibiotics in both mom and baby, a rise in C-sections as a route of delivery, and the introduction of newborn and infant formulas that were used in place of maternal breastmilk. Despite their many benefits, these medical advances have altered the bacterial ecosystem of newborns gastrointestinal tract. A newborn’s gut relies on the presence of helpful bacteria to digest many nutrient molecules. Bacteria that line the newborn GI tract co-evolved with humans to aid in digesting these important nutrients to provide additional mediators of gut health and immunity that humans cannot otherwise produce. Thus, nature selected for a delicate interplay between biology, nutrition, and the bacterial lining of the GI tract (fast fact: this is also known as the gut microbiome). Medical care has in-advertently introduced changes that have profoundly worked against human evolution that requires a close symbiotic relationship between humans and their bacterial counterparts. There is emerging evidence that these changes are resulting in a much higher incidence of acquired diseases like asthma and eczema that are much less prevalent in the developing world.

Our Nutrition, our Bacteria, our Health

There is ample evidence of the importance of breast feeding for optimizing a newborn baby’s health. Breast milk is made up of water and nutrients including carbohydrates, lipids, and proteins. Some of the carbohydrates of breast milk are known as HMOs, or human milk oligosaccharides. Yet, humans alone have no ability to digest and process HMOs—why would nature include them in breast milk? As it turns out, HMOs are the food for the good bacteria in our gut. We need these bacteria, and these bacteria have the enzymes that digest HMOs and promote overall immune health and gut functional maturity. Babies born today, especially those born preterm, may be lacking this good gut bacteria. For babies born premature or ill, receiving good gut bacteria may be even more difficult when their earliest developmental process are interrupted by necessity of care in the NICU.

At Stanford Children’s Health, Dr. Sylvester is leading the way in developing the tools and possible therapeutic strategies involving repopulating babies’ GI tract with good bacteria. He is working on strategies that seek to pair the use of “probiotics” (or a food additive of live bacteria) to be given as a supplement to breast-fed babies that will restore the evolutionary “good bacteria” and nurture a healthy beginning through optimized metabolism, lower inflammation, and the avoidance of many diseases that have their origin in the earliest weeks of life. In fact, research has shown that babies who are given specific probiotics can restore their normal gut bacteria. It only takes a couple weeks of exposure to the probiotic to make this change durable. Thus, we are developing plans to “engineer” gut and overall health through a therapeutic approach using bacteria.

Why are we invested in profiling “every” newborn at Lucile Packard Children’s Hospital Stanford?

We are guided by the belief that if we intervene early with care that is nutritionally and metabolically based, we can impact growth, development, and health, both now and in the future. By taking positive steps toward health in infancy, the impact on reducing the overall disease risk over a lifetime is greater. We even may be able to improve the health of subsequent generations.

Metabolic disease is truly a global problem, where neonatal conditions account for 9% of worldwide disease burden. In North America and in other developed nations babies suffer from acquired diseases as a result of being born too soon (prematurity), whereas in other parts of the world pregnant women and their babies face food insecurity, resulting in babies being born too small and at ongoing risk of severe malnutrition that compromises overall health, immunity, and cognitive development. We believe there are similar metabolic problems at play in these very diverse settings with their own unique challenges. Thus, while we act locally here at Stanford, we are thinking globally to extend the benefits of our work that may have profound benefits for women and children the world over.

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