That any of us survive nine months in the womb is amazing. The level of oxygen available to a developing baby in the uterus is equivalent to the low levels of oxygen available at very high altitudes, such as at the top of Mount Everest. Nonetheless, a developing fetus thrives in these low oxygen (hypoxic) conditions—but how?
Developing fetuses have a low metabolic rate requiring little energy and oxygen to grow. Until birth, most of a baby’s blood flow bypasses the lungs since the mother’s blood provides nutrients and oxygenated blood, essentially doing the work of breathing for the baby.
However, at birth, a baby can no longer rely on the mother’s blood and must suddenly obtain its oxygen by breathing through its lungs, which requires redirecting the heart’s blood flow to the lungs. For this to happen, blood pumped from the heart to the lungs must enter the lungs’ blood vessels to collect oxygen and release carbon dioxide. A clear sign that this rerouting has occurred is when a baby turns pink after its first breath. But that does not always happen because the trigger to direct blood flow to the lungs requires oxygen.
Babies that have a difficult time or are unwell during delivery often suffer from oxygen shortages. These babies are usually perfectly healthy until they undergo a difficult delivery. In this situation, even if a healthy baby tries to breathe, no blood reaches the lungs, and the baby remains blue (a sign of low oxygen levels). These so-called blue babies are the sickest in the neonatal intensive care unit (NICU).
What is Persistent Pulmonary Hypertension of the Newborn?
The lack of oxygen at the critical time of delivery causes a dangerous respiratory disease called Persistent Pulmonary Hypertension of the Newborn (PPHN). PPHN affects about 2–6 out of 1,000 newborns and complicates 10% of admissions to the NICU. PPHN occurs when the blood vessels do not open wide enough, resulting in a shortage of how much oxygen travels to the brain and organs. This is why PPHN is extremely dangerous. These babies are the sickest in NICU. Without treatment, these babies can die within a week of being born. Treatment involves restoring blood flow to the lungs to improve oxygen levels. Despite existing therapies, PPHN has a mortality rate of 4–33%. Furthermore, about 25% of newborns with moderate/severe PPHN can have complications in the development of their nervous system, including a brain disorder caused by a lack of oxygen to the brain, known as hypoxic encephalopathy.
What are the early signs of PPHN?
Newborns with PPHN can present with breathing difficulties and other signs at birth or in the first hours after birth, including fast breathing and heart rate, grunting, blueish skin (cyanosis), cool hands and feet,etc. In the NICU, a neonatologist specializing in newborn care usually diagnoses PPHN using the following tests: chest X-ray, oxygen level, and echocardiogram to visualize the heart.
How is PPHN treated?
PPHN is mainly characterized by low oxygen levels and constricted pulmonary blood vessels. Therefore, the pulmonary circulation should be relaxed as soon as possible to expand the blood vessels and facilitate blood flow to the lungs’ oxygen exchange surfaces. However, even when doctors treat a newborn with PPHN with inhaled oxygen, the lungs’ blood vessels can remain tightly constricted. Vasodilators can also be used to open the blood vessels and treat PPHN, including inhaled nitric oxide (iNO), prostacyclin, milrinone, and sildenafil. Although these treatments are beneficial, they are not always successful and can cause side effects such as slow heartbeat and the production of dangerous toxic gases. Therefore, research to discover new therapies for PPHN is essential.
Some babies may also need aggressive support for heart function and blood pressure, depending on the severity. Most studies on PPHN worldwide focus on increasing blood flow by decreasing the pressure of blood vessels, mainly by administering pulmonary vasodilators. At the University of Manitoba, Dr. Shyamala Dakshinamurti and her team are trying to develop a new mechanism that may be a potential for the treatment of PPHN. Dr. Shyamala Dakshinamurti is a neonatologist and biomedical researcher, heading the Neonatal Pulmonary Biology Lab and anchoring the animal hemodynamics lab at the Children's Hospital Research Institute of Manitoba (CHRIM). “What we are working on now is a bit of a leap of faith," says Dr. Dakshinamurti. "We have found a central molecule that is one of the gatekeepers to get blood vessels to relax. Our long-run goal is to target this molecule and develop a modified drug to activate it in the lung. It would certainly buy us time and may be enough to save more babies with PPHN. This would make me and my team extremely happy.”
This summer I am going to be interviewing Austin Read, a 2020 PH Research Scholarship recipient. Austin’s project aims to identify how cells of the fetal pulmonary arteries and DA sense and respond to oxygen in their environment, in order to identify new molecular targets to treat PPHN.
Stay tuned!
References:
Dakshinamurti S. Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn. Pediatr Pulmonol. 2005;39(6):492-503.
Nair, Jayasree, and Satyan Lakshminrusimha. "Update on PPHN: mechanisms and treatment." Seminars in perinatology. Vol. 38. No. 2. WB Saunders, 2014.
Razzaq A, Quddusi AI, Nizami N. Risk factors and mortality among newborns with persistent pulmonary hypertension. Pakistan journal of medical sciences. 2013;29(5):1099.
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