UA Physiology Researcher Continues Studies on Nicotine Exposure During Pregnancy with $1.9 Million NIH Grant

Monday, September 17, 2018

Cigarettes contain 4,000 chemicals, including nicotine, which is the highly addictive component. For pregnant women who continue to smoke, some obstetricians have been prescribing nicotine-replacement therapy (NRT), such as e-cigarettes, patches and gum, with the rationale that nicotine alone is a better alternative than exposure to nicotine plus the 3,999 other chemicals in tobacco products.

NRT has been touted as a drug therapy for smoking cessation and considered a potentially safer alternative for women than smoking during pregnancy. However, a growing body of evidence is beginning to show that nicotine exposure in the womb leads to a number of serious developmental abnormalities in rats, and this also may be true for humans.

Ralph F. Fregosi, PhD, professor of physiology at the University of Arizona College of Medicine – Tucson, has been studying the effects of fetal nicotine exposure on motor neuron development in newborn rats for two decades. Results from his published research indicate nicotine exposure in the womb is associated with complications in fetal development, particularly in brain regions that control motor functions, such as breathing and swallowing, which are key to survival.

Dr. Fregosi recently was awarded a $1.9 million, five-year grant from the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, to continue his research to determine if these abnormal changes persist as the animals develop, with studies occurring in the first week of life, when the animals reach sexual maturity, and in adulthood.

"We also will determine if the changes can be reversed if nicotine exposure stops at birth, or worsened if nicotine exposure continues," Dr. Fregosi said. "This is the potential clinical application for newborns that were exposed in the womb."

Animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring, such as impaired fertility, Type 2 diabetes, obesity, hypertension, neurobehavioral defects and respiratory dysfunction, Dr. Fregosi explained. A limited number of short-term human trials have looked at the safety of NRT use during pregnancy, but no information exists on the long-term effects of developmental nicotine exposure in humans.

"Our study will examine the long-term effects of fetal and neonatal nicotine exposure on development of critical motor functions across the lifespan," he said.

Specifically, Dr. Fregosi's research focuses on the effects of nicotine exposure in the womb on the structure and function of hypoglossal motoneurons. These neurons control muscles of the tongue, and therefore are critical elements for normal suckling, swallowing, breathing and vocalization.  

"We are trying to understand how nicotine exposure may underlie the difficulties that some nicotine-exposed infants have with suckling and breathing," Dr. Fregosi said. This is especially important because recently published research has confirmed maternal smoking is the leading risk factor for sudden infant death syndrome (SIDS).

"With increasing numbers of nicotine patch and electronic cigarette users during pregnancy, there is an increasing urgency to better understand the impact of nicotine exposure on the development of the fetal nervous system," he said.

“This is research that really can help people,” said Nicholas A. Delamere, PhD, head of the UA Department of Physiology. “Nicotine is such a powerful drug and has devastating effects on our most vulnerable humans – newborns.”

"It is very important that we fully understand the potential long-term risks of nicotine exposure and nicotine-replacement therapy, particularly so that we have the best health care practices for pregnant mothers,” said UA President Robert C. Robbins, MD. "As technology advances, it is crucial that we continue to refine medical treatments and recommended practices, which is why Dr. Fregosi's research is so significant."

Research reported in this release was supported by National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, under grant No. 2R01HD07130206A1.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the UA College of Medicine – Tucson

The University of Arizona College of Medicine – Tucson is shaping the future of medicine through state-of-the-art medical education programs, groundbreaking research and advancements in patient care in Arizona and beyond. Founded in 1967, the college boasts more than 50 years of innovation, ranking among the top medical schools in the nation for research and primary care. Through the university’s partnership with Banner Health, one of the largest nonprofit health care systems in the country, the college is leading the way in academic medicine. For more information, visit medicine.arizona.edu.

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