Premature babies are doing better than ever before, but survival comes with hidden costs.
There are health consequences associated with premature birth. Maurice Frazer/Flickr (CC BY-ND 2.0)
The womb, although it nurtures life until birth, is not the absolute safe-haven that we often imagine. Environmental factors that we experience before birth can have long-term health consequences that follow us into adulthood. It has been well established, for example, that a mother’s lifestyle during pregnancy affects the health of her baby: smoking, malnutrition, and alcohol use can cause developmental defects or increase susceptibility to diseases later in life. We know very little, however, about how the length of pregnancy can affect the long-term health of the offspring.
The environment inside the womb is optimised for the fetus’s cells to multiply and mature. Most of us spend nine full months (or 40 weeks) in the womb — enough time for our organs to develop and prepare for life after birth. This is not the case for the one in 10 babies worldwide who are born premature. Premature birth, defined as birth prior to 37 completed weeks in the womb, has recently been linked to many life-threatening and long-lasting health complications.
Premature babies are born with severely underdeveloped lungs and struggle to breathe without life support. Until about 30 years ago, these babies typically died soon after birth. Back then, mechanical ventilators developed for larger infants would force oxygenated air into a premature baby’s fragile, immature lungs. This technique allowed some of the stronger, more developed babies to survive, but led to fatal airway damage in smaller babies born extremely premature. In the early 1990s, gentler forms of ventilation were developed and premature babies were given a mix of steroids, stimulants and surfactants to help boost lung development and improve respiratory function.
Premature babies also tend to have low blood pressure (known as hypotension), thanks to a weak and underdeveloped heart that is unable to pump enough blood around the body. Doctors often inject blood from the umbilical cord and inotropic drugs into the baby to counteract hypotension. These major advances in neonatal care drastically improved survival rates for premature babies. Nowadays, babies born as early as 20 weeks can survive with the help of these clinical interventions.
Improved medical intervention has increased the survival prospects for premature babies. Yann/Wikimedia Commons (CC-BY-SA 4.0)
However, with these ‘miracle babies’ now in their late 20s, the long-term effects of premature birth are becoming visible. A growing body of epidemiological studies show that premature-born survivors are more likely to develop cardiovascular diseases such as heart failure, stroke and high blood pressure disease (hypertension), compared to adults born at full term. The risk of developing cardiovascular disease is proportional to the severity of prematurity. Premature birth is now considered a novel risk factor for cardiovascular disease, alongside more commonly known factors such as physical inactivity, a high fat diet, smoking, and diabetes mellitus.
Cardiovascular disease is the world’s number one killer, ahead of cancer and traffic accidents. With an increasing number of premature survivors entering adulthood, a greater portion of the population are highly susceptible to developing cardiovascular disease.
Scientists don’t fully understand why premature-born hearts are so prone to cardiovascular disease. We do know that cardiovascular health is driven largely by heart function. The shape and size of the heart dictates how much blood it can pump around the body. Premature-born adults have smaller chambers (called ventricles) with thicker walls and impaired pumping activity, compared to adults born at term. The blood pressure in these ventricles is also abnormally high, meaning these individuals are at higher risk of developing hypertension. This is in stark contrast to early life, when premature babies’ cardiac ventricles have thinner walls and pump less blood. Over time, in response to low blood pressure in infancy, the premature heart undergoes structural remodelling to develop thicker, more muscular ventricles. This short-term compensation may continue throughout life, causing long-term, maladaptive remodelling in the adult heart.
Cardiovascular changes that occur during infancy can influence health outcomes much later in life. Simone D. McCourtie, World Bank/Flickr (CC BY-NC-ND 2.0)
Despite an increasing interest in the long-term impacts of premature birth on the heart, this area of research is still in its infancy, partly because this cohort of premature-born survivors have only recently reached adulthood. In addition, factors such as maternal lifestyle, genetic predisposition to cardiovascular disease, and medical intervention at birth are difficult to control for in large clinical studies. Studies using echocardiography to monitor heart function in babies have found that medical interventions aimed at improving lung function inadvertently change the shape and, therefore, function of the heart in premature-born adults. Assisted ventilation and steroid treatment for premature babies are continually being refined to ensure their side effects on other organs are minimised.
Studies in humans are limited by our inability to study microscopic changes within the heart tissue. This is because it is unfeasible to take small biopsies of the heart to analyse changes in protein and gene expression. Animal studies avoid some of these restrictions, and can be carefully controlled to ensure we’re comparing apples to apples. Furthermore, we can easily and ethically collect animal tissue for lab analysis.
One landmark study showed that, in premature-born sheep, the heart tissue itself had a higher percentage of collagen within its walls. Collagen is a protein that provides all organs in our body with structural support, much like the internal frame of a house. However, too much collagen deposition creates scar tissue and is a common feature in diseased tissue. Excess collagen within the ventricle walls makes them very stiff, meaning they struggle to efficiently pump blood around the body. An increase in collagen production in early life might give the young, premature heart structural stability, but will likely lead to impaired heart function later in life as collagen continues to accumulate within the heart tissue.
If you were born premature, don’t be too alarmed — not all premature babies will develop cardiovascular disease, just like not all cigarette smokers will develop lung cancer. Understanding the underlying mechanism of cardiovascular disease progression in people born premature will allow clinicians to better identify at-risk patients and provide them with personalised medical advice.
Edited by Andrew Katsis
