NHLBI Grant Awarded to Study Offspring Cardiometabolic Health

January 03, 2024

Wendy Brickman, MD, Attending Physician in the Division of Endocrinology, and Donald Lloyd-Jones, MD, ScM, at Northwestern University Feinberg School of Medicine, were awarded an NHLBI grant to study the developmental origins of cardiovascular health and disease.  Specifically, does the cardiometabolic health of a mother during pregnancy independently affect the offspring’s cardiometabolic health into adulthood, and if so, are epigenetic changes implicated in this process. The new study is a follow-up study based on two previous projects: the Hyperglycemia and Adverse Pregnancy Outcome Study and the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS).

The first study, Hyperglycemia and Adverse Pregnancy Outcome Study, led by Dr. Boyd Metzger with Dr. William Lowe at Northwestern University Feinberg School of Medicine, began in 2000. This international study enrolled over 25,000 mothers from 15 field centers in 9 countries, with 23,000 of those mothers completing the study. In this study, the investigators evaluated the mother’s glucose response to an oral glucose tolerance test during mid-pregnancy and associations of those glucose levels to adverse pregnancy outcomes including cesarean section rates and birth weight. They found that across increasing maternal glucose levels, even at levels below diagnostic thresholds for diabetes in pregnancy,  cesarean section rates, birth weights and cord blood c-peptide increased.

The follow-up study, The Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS), again led by Dr. Boyd Metzger, began in 2013. The study enrolled over 4,500 mother child pairs from 10 field centers in 7 countries from the original HAPO study. The Chicago field center was led by Drs. Wendy Brickman and Jami Josefson, where 300 of the mother-offspring pairs were studied. The study found that mother’s glucose during pregnancy was independently associated with offspring adiposity and disorders of glucose metabolism at ages 10-14 years.

The current NHLBI-funded research investigates the offspring’s risk for cardiovascular disease now that they are young adults. The team aims to enroll 1,000 young adult offspring participants in the newest study known as HAPO-CVH. The investigators will bring back children that participated in the HAPO follow-up study to evaluate their cardiovascular health, investigating whether the mother’s cardiometabolic health during pregnancy independently impacts the offspring’s cardiometabolic health as adults.  
 
The study uses two main cardiovascular outcomes: 

The first is a construct published by the American Hospital Association (AHA) called cardiovascular health. The construct uses four physical measurements (body mass index, blood pressure, glycemia, and cholesterol) and four behavior measurements (nutrition, physical activity, smoking and sleep) to determine a total score. The team will use the scores to determine if there is an association between the mother’s cardiometabolic health during pregnancy and the offspring’s cardiovascular health.  

The secondary outcome will evaluate an early indicator of heart disease: carotid intima media thickness (cIMT). This measurement is taken using an ultrasound of the carotid artery to evaluate the intima media thickness which has been shown to be a risk factor for cardiovascular disease.

Young adulthood appears to be a pivotal time in one’s overall cardiovascular health.  The outcome of this study could prove valuable in determining whether or not the in utero environment independently affects the offspring’s cardiovascular health at this crucial time in one’s lifespan.  If so, the results may direct future interventions during or before pregnancy with the goal of improving the offspring’s future health outcomes.