for the premature infant. With a blood volume of 90 mL/kg it would
not take long to cause significant anemia in a 1 kg premature baby.
Today, many tests are performed using a drop of blood at the point
of care or by using no blood at all, such as with the determination
of pulse oximetry or end-tidal CO2.
An area that has held the neonatologist’s greatest attention over
the past 60 years has been the search for the perfect mechanical
ventilator. The fetus in utero receives its oxygenation and eliminates
carbon dioxide through the umbilical vessels attached to the placenta.
While the fetus’ basic lung structure is complete at 12 weeks of
gestation, the arborization of alveoli is not sufficient to sustain life
until about 22 weeks. Before that, the distance between the alveolar
duct and the pulmonary capillary is too great to achieve sufficient
oxygen diffusion. In addition, at this stage the lung is physiologically
immature, lacking a key substance called pulmonary surfactant.
Surfactant coats the inner walls of the alveolus and inhibits it from
totally collapsing between breaths. Surfactant production begins
around the 20 th week of gestation, but production is not optimum
until near term. Absent of pulmonary surfactant, the lungs are stiff
and require significant airway pressure to ventilate. The pressure
required, or the tidal volume of air it produces, while needed to
affect survival, often damages the premature baby’s small airways
and immature alveoli leading to chronic lung disease. We now
have artificial surfactants, made of minced calf or porcine lung,
that supplement the premature infant’s own surfactant production
in the first days of life. This often mitigates the need for artificial
ventilation. But the search for the perfect ventilator goes on.
The real holy grail in neonatology would be the artificial placenta.
For no matter how perfect the ventilator, unless the structure
of the lung allows gas exchange, survival is not possible before the
alveoli approximate the pulmonary capillaries at around 22 weeks.
Extra-corporal membrane oxygenation (ECMO) is possible in babies
weighing as little as 2 kg but it is fraught with complications such as
intracranial hemorrhage. Japanese and Australian researchers have
recently made some progress towards achieving an ex vivo uterine
environment therapy for premature lambs. 2
The ability to provide nutrition to the premature infant is also
essential in achieving improved survival. Everything about a premature
infant is immature, including the gastrointestinal system.
Premature infants do not have the neurologic development to
coordinate sucking, swallowing and breathing and need tube feedings.
The stomach does not produce acid well. The intestines lack
digestive enzymes and effective motility. The search for the perfect
formula led us back to human breast milk. But even breast milk
cannot match the placenta’s ability to provide sufficient nutrients
for optimum brain growth and body growth. Since the latter part of
the 20 th century, total parenteral nutrition (TPN) has been helpful in
improving survival but indeed it is not “total” and brain and body
growth still lag behind the optimum intrauterine environment in
both quantitative and qualitative measures.
In the past 60 years, there have been many more technologic
advances addressing the immaturity of all organ systems of the
premature infant. This technology is expensive. Today a basic incubator
can cost several thousand dollars and the most sophisticated,
$20,000. The highest level of care in the modern neonatal intensive
care unit can exceed four to five thousand dollars per day, and the
three-month hospital stay of a premature infant born at 25 weeks
gestation can tally nearly a million dollars.
So, with all this technology and investment, how are we doing?
There is no doubt that most premature babies born between 28 weeks
gestation and term do very well. Many centers now report over
90% survival in those born at 28 weeks, with less than 10% of the
survivors having significant long-term health problems. The length
of their hospital stays are about eight weeks. Survival increases, and
developmental complications decrease, with increasing gestational
age. Many babies born between 26 weeks and 28 weeks also do
well. Those babies born below 26 weeks however present a major
challenge, both practically and ethically, to parents and caregivers.
Recently, the National Institute of Child Health and Human Development
produced an online outcome calculator for these tiniest of
babies: www.nichd.nih.gov/research/supported/EPBO/use.
By entering a baby’s birth information, one can see the outcomes
of similar babies that were born at 22 to 25 weeks gestation
between 2006 and 2012. For example, a baby born as a singleton
male at 22 weeks gestation, weighing 401 g (14 oz), whose mother
received prenatal steroids, and for whom resuscitation and active
management was chosen, would have an average survival of 17%
(range 10% to 28%). And, of the survivors, at 18 months of age,
52% – 78% would have moderate-severe neurodevelopmental delay
and 15% – 22% moderate-severe cerebral palsy.
The field of neonatology has always had it ethical challenges.
Does the sanctity of life demand survival at all costs? Who decides?
Will society’s support for the pursuit of an infant’s survival at earlier
and earlier gestations, so present in the 19 th and 20 th century, apply
to the 21 st ? Will there continue to be future scientific and technological
advances in the field of neonatology equivalent to those of
the 20 th century?
These are questions for society and the next generation of neonatologists.
References
PEDIATRICS
1
Raffel, Dawn. The Strange Case of Dr. Couney: How a Mysterious European
Showman Saved Thousands of American Babies. New York, New York, Penguin
Random House, 2018.
2
Usuda H, Watanabe S, Miura Y, et al. Successful maintenance of key physiological
parameters in preterm lambs treated with ex vivo uterine environment
therapy for a period of 1 week. Am J Obst Gynecol. 2017;217:457.e1-57. e13.
John L. Roberts is a neonatologist and Professor of Pediatrics at the University of
Louisville School of Medicine.
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