Narrowing the DHA Gap
The Baack lab has a general interest in docosahexaenoic acid (DHA), a long chain polyunsaturated fatty acid (LCPUFA) that is important in normal growth, brain development and vascular health. Our goal is to improve the health and long term outcomes of infants who are born with a relative deficiency of this important fatty acid, through optimal nutritional provisions during pregnancy and infancy.
Making Babies Better with Lipids
Over 550,000 infants are born prematurely each year in the United States. Given advancements in medicine, survival is improving, but the absolute number of survivors with disabilities is increasing. Premature infants are at high risk of developing inflammatory diseases including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP) that can have lasting effects on the lungs, bowel and vision respectively. They also have a higher risk of learning and visual problems throughout life. Interestingly, these risks seem to be unique to this population of infants. We believe this is, in part, due to a deficiency in important fats that are required for normal brain, eye and organ development.
Figure 1. The important role of DHA in the health of premature babies is highlighted.
Omega-3 fatty acids, a group of essential dietary fats, are necessary building blocks of cell membranes that also act as signaling molecules and keep a balance between normal health and inflammation. The most commonly known omega-3 fatty acid is docosahexaenoic acid or DHA. DHA accumulation occurs in the last trimester of pregnancy from maternal sources. Premature infants, born before this accumulation can occur, have a relative deficiency of this essential fatty acid. This “DHA Gap” persists due to a baby’s inability to make this fatty acid on its own, compounded by a limited ability to provide this through nutritional sources in babies who are in the Neonatal Intensive Care Unit. Animal and epidemiologic evidence now show that DHA improves neurodevelopmental outcomes and vision and may decrease the risk of inflammatory illness like BPD, NEC and ROP. The goal or our clinical research in the NICU at Sanford Children’s Hospital is to find the optimal dose and source for these tiniest babies during a critical time of growth and development, leading to better outcomes for premature infants.
Diabetes and Obesity During Pregnancy: Implications for the Baby
The effects of gestational diabetes and obesity during pregnancy can extend beyond those of the mother and include devastating consequences in the developing fetus. Gestational diabetes is increasing at an astounding rate of 10% each year, affecting up to 14% of all pregnancies. Additionally, 35% of women of child bearing age are now obese. Babies born to mothers who are overweight or have diabetes during pregnancy are at higher risk of birth defects and neonatal illness. They also have an increased risk of developing diabetes, high cholesterol, obesity and cardiovascular problems later in adolescence and adulthood. Our lab investigates the role of altered circulating fuels that cross the placenta and affect the embryo or fetus during a critical window of development. This exposure may alter cell growth and function, leading to lifelong changes in the structure and function of the body. When this causes fetal loss or major birth defects it is called “embryopathy”, but when it affects function on a cellular level that increases the risk of disease later in life it is called “fetal programming”.
Figure 2. Diabetes causes increased circulating fuels in maternal circulation, many of which cross the placenta, exposing the developing fetus to abnormal amounts of these fuels. Depending on the timing of exposure, this can lead to CV disease in the ODM. If this exposure is early, during organogenesis, it may cause birth defects such as congenital heart defects. If it is late in gestation is can be associated with overgrowth and hypertrophic cardiomyopathy. Exposure throughout the pregnancy increases the risk of adult onset obesity, hyperlipidemia, insulin resistance and cardiovascular disease.
Our work in the basic science lab supports the idea that diabetes during pregnancy is associated with both abnormal glucose and fat exposure to the developing fetus. Glucose seems to be a mediator of embryopathy, or early loss and birth defects. Using a unique rodent model that exposes half of the developing embryos to glucose during different stages of organ development, we can further study how exposure to different fuels cause pregnancy loss and birth defects such as brain abnormalities, neural tube defects, skeletal or cardiac malformations. See figures below.
Figure 3. (Below) Excessive glucose exposure during early embryo development is associated with significant birth defects and early pregnancy loss.
Pregnancy itself increases circulating fats in mom’s bloodstream to support the needs of the developing baby. Diabetes further increases this circulation of fats to abnormal levels. A high fat diet also makes the effects of gestational diabetes much worse and imposes greater risk to the fetus. The Baack lab has discovered that abnormal fat exposure causes an increased risk of infertility, stillbirth and heart and lung disease in offspring early in life. Using state of the art equipment to explore the role of fatty acids in heart and kidney development we found that fats may build up in the heart of a developing fetus causing poor function right after birth. See Angela Wachal’s work under lab members. Exposure to excess fuels during in utero development also increases the risk of cardiovascular disease, obesity and diabetes of offspring even into adult life. Our next step is to determine exactly how this happens and what interventions can be done throughout pregnancy to prevent these risks. Understanding disease at it’s very origin will allow researchers and doctors to prevent these devastating consequences and decrease the escalating rise in cardiovascular disease seen in the growing U.S. population.
Figure 4. Using state of the art equipment at Sanford Research Center, we can use echocardiography to measure the heart function of newborn rat pups born to mothers affected by diabetes or a high fat diet during the pregnancy.
Contact Information for Baack Lab:
Michelle L. Baack, MD
Assistant Scientist, Sanford Children’s Health Research Center
Sanford Health Research Center - USD
Assistant Professor, Department of Pediatrics
Sanford School of Medicine of the University of South Dakota
Sanford Research Center
2301 E 60th Street N
Sioux Falls, SD 57104