by Soha Usmani
Graphic design by Stephen Nachtsheim
The advances in neonatology—a pediatric subspecialty focused on newborn babies up to 28 days of life—have facilitated high life expectancy and survival rates in developed countries like Canada. Neonatal intensive care units (NICU) have become a staple of hospitals in first-world nations as wards for premature (born less than 37 weeks of pregnancy) and ill newborns. Common neonatal complications include congenital disorders, infections, low birth weight, and organ-related conditions. In the latest Raw Talk Podcast episode, the team discussed current trends and gaps in neonatal care and research with various experts in the field.
Organ-related issues constitute a leading cause of modern NICU admissions. One notable condition is brain damage, caused by complications such as birth asphyxia, which causes low oxygen delivery and blood flow to the brain, and brain hemorrhages, resulting in conditions such as cerebral palsy, epilepsy, and other neurodevelopmental problems. Dr. Pia Wintermark, a physician-scientist from the McGill University Health Centre, expressed indignation about being unable to treat brain injuries compared to other organs due to the lack of available treatments. “As a neonatologist, I always find it frustrating because other organs you can fix, but when you have a brain injury, there is not much you can do to improve [it],” Dr. Wintermark notes. This experience inspired her to start the current research program in her lab, which replicates the pathology of birth asphyxia in rat models. The lab uses these models to test potential new treatments to alleviate organ damage and prevention strategies.
Lung-related issues such as pulmonary hypertension and respiratory distress syndrome (RDS) are also common causes of NICU admission. Pulmonary hypertension prevents proper oxygen delivery due to high blood pressure in the lungs. RDS occurs from fluid buildup and lack of surfactant due to underdeveloped lungs, making breathing more difficult and reducing oxygen intake. Congenital heart defects are also prevalent and cause neonatal cardiovascular disease. All these conditions make up the most cases of neonatal death in Canada, with a 2020 Statistics Canada report ranking congenital malformations and deformations as the leading cause, followed by birth asphyxia, heart disease and respiratory distress.
The Head of the Neonatology division at SickKids, Dr. Estelle Gauda, noted the vast improvements in neonatal survival rates, such as the minimum viable age for premature babies dropping from 24 to 22 weeks of gestation. She attributes this to improved technologies such as pressure ventilators and the development of interdisciplinary NICU teams, including respiratory therapists, nutritionists, occupational therapists, and social workers. However, with the rising survival rates of premature babies, neonatology teams now must care for increased numbers of sick babies with underdeveloped and injured organs alongside other medical conditions unique to premature babies that require NICU admissions.
The lack of available drugs tailored to babies admitted to the NICU is another pressing issue. Pharmaceuticals must undergo expensive and time-consuming phase I to III trials before approval for general use. This is not the case for drugs used to treat NICU patients. “Unfortunately, most drugs have not gone through this rigorous phase 1-2-3 study. Instead, we commonly take medicines approved in adults and older children, and we begin to use them in the NICU without adequate evidence and labeling,” says Dr. Tamorah Lewis, Division Head of Clinical Pharmacology and Toxicology at SickKids. She further relates how this shortcoming resulted in a lack of specialized drugs for neonates and increased use of off-label medications, leaving neonatologists to reuse medicines designed for other patient populations with inaccurate formulations. To Dr. Lewis, this is likely due to NICU patients being a relatively small patient population with rare conditions and pharmaceutical companies incentivizing common conditions affecting larger patient populations.
Drug testing in newborn babies presents unique challenges because of drastic physiological changes developing as babies age throughout the weeks. This impacts drug dosing and raises the ethical question of obtaining consent. One of the treatments the Wintermark lab is researching is sildenafil, commonly used to lower blood pressure in neonatal lungs. Given promising results in safety and animal model trials, the lab is currently testing the efficacy of sildenafil with an ongoing Gates Foundation-funded phase I trial in Uganda. Dr. Wintermark mentioned a ‘tunnel vision’ in neonatology research that leads researchers to focus only on a single organ rather than multi-organ applications of drugs.
Gaps in Developing Countries
One active area of research is analyzing and solving the gaps between developing and developed countries, as the prevalence and severity of the conditions mentioned above are exacerbated in lower-income countries. Dr. Zulfiqar Bhutta, Co-Director of Research at SickKids Centre for Global Child Health, emphasized that the drop in total infant mortality rate from four to two million is unequally distributed, as progress in low-income countries is slower than in other higher-income nations. This is primarily due to the shortage of trained medical professionals and suboptimal resources and infrastructure for neonatal care and complications, alongside external factors: “About 30 to 40% of all neonatal mortality and morbidity is now in geographies affected by conflict, climate change, extreme poverty, population migration and movements,” says Dr. Bhutta, “you cannot construct facilities and have human resources at the same level as you have in normal circumstances.”
These obstacles translate into inadequate health facilities and scarcity of pharmaceuticals we take for granted, such as vaccines and oxygen, driven by exorbitant prices and a lack of cold storage. This scarcity also results in high malnutrition rates, poor sanitation, and a lack of access to electricity and clean water. All these combined factors worsen health outcomes, with a prime example being enhanced susceptibility to infectious diseases, including vaccine-preventable and drug-treatable ones, such as hepatitis B, group B strep, tetanus, HIV, rubella and Zika. These microbes increase the risk of preterm birth, birth defects, miscarriage/stillbirth, chronic illnesses, and other fatal complications.
This episode just scratched the surface of this critical interdisciplinary field. It intersects various specialties, including but not limited to immunology, pharmacology, global health, and physiology. Despite advances, gaps in knowledge and room for improvement on the clinical side still exist. The synthesis of ongoing research from current and future scientists and clinicians from diverse subdisciplines, such as the guests featured in this article and the episode, will translate into enhanced health outcomes for neonates worldwide.
We want to acknowledge the hard work and ideas of the rest of the team and our guests, Drs. Bhutta, Gauda, Lewis and Wintermark, and the Foreman family who shared their NICU experience with us. To learn more about neonatal care and research in Canada, listen to the full episode of Raw Talk Podcast at www.rawtalkpodcast.com/episode/111 or on Spotify.