Neonatology and the Developmental- Evolutionary Parallel

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Neonatology and the Developmental- Evolutionary
Parallel

• Endodermal and Ectodermal Tissues follow a common
  developmental sequence throughout all vertebrates
• Disruption of this developemental sequence
  results in predictable consequences
• In the surviving neonate, the consequences of
  developmental disruption equal congenital
  anomalies (e.g. holoprosencephaly, pulmonary
  hypoplasia) or morbidities of prematurity (e.g.
  RDS, apnea of prematurity).
• We can flip this logic around by asking
  ourselves, how can the developmental
  evolutionary parallel be used to better
  understand these diseases?

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What is the Developmental- Evolutionary Parallel?
The mesoderm is unfaithful in terms of the
developmental evolutionary parallel. By 21
days, the mesoderm of the human fetus has created
the basic form of a salamander, but it takes
another 21 weeks before the endoderm and ectoderm
mature sufficiently for viability (at the
saccular stage of lung development). But
endoderm and ectoderm are faithful because of
growth factor ontogeny (more later).
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Notochordata (lampreys, lancets, hagfish)
Larvea
Pineal gland (the 3rd eye)
Polymicrogyria
Ram Jet Ventilation
2 the notochord
-/- PAX 6 (no pineal gland and)
Does he have 3 eyes too?
GI tract stoma gut tube
The lamprey gives us our hypothalamus, pituitary
/ pineal tracts and basal brain stem nuclei.
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Elasmobranchs part 1
proximal to distal gut development
Elasmobranchs have 13 cranial nerves 13 the
nervous terminalis (an accessory olfactory nerve)
The brain follows the nose holoprosencephaly
BMP
Elasmobranchs have keen smell and well developed
olfactory cortex
IGF-I IGF-II
FGF10
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Elasmobranchs part 2
If a fetus cant breath in fluid (due to a
swallowing defect, neuro or muscular defects, or
insufficient amniotic fluid) the result is
pulmonary hypoplasia
Some Elasmobranchs develop the first gill
chambers (operculums) and along with it they
develop primary respiratory drive (a brain stem
function). In parallel with evolution, fetal
breathing starts in the first trimester.
Elasmobranchs gave us our brainstem, cranial
nerves and first highly developed lobe of cortex
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Boney Fish
metanephric kidney
IGFs TGFa
BMPs FGFs
Fish bring two crucial things to the
developmental-evolutionary parallel 1st they
evolve the first high resolution, complex eye
into being (which comes with the optic
cortex). 2nd elasmobranchs convert ammonia to
urea and permeate their tissues with it for
buoyancy. Fish evolve the swim bladder for
buoyancy as well as metanephric kidneys. They
excrete all their ammonia. This become the basis
for the terrestrial kidney.
Pop Quiz what is this syndrome?
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Amphibians part 1
TH
The limit of gestational viability is the late
cannicular phase of lung development. Artificial
surfactant has little effect on the surface
tension of lungs that have no air sacks but can
almost completely normalize saccular lung.
Amphibians stop here
Mature type II pneumocytes are required to
recycle surfactant and may explain why older
infants (gt30 weeks) require fewer repeat doses.
BMP, EGF, FGF, TGFb, VEGF, SPARC
Surfactant deficiency respiratory distress
syndrome
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Amphibians part 2
Optic cortex and retinal density reach the
optimum now that amphibians have to track flying
prey (Bufo Marinus).
Proximal Distal effect
Cloaca evolves as amphibians must hide their
feces from predators carry their eggs to water
(precurser to colon and 1st durable gut
modification since elasmobranchs).
SIP occurs because the distal small intestine
(ileum) is under grown in comparison to the
proximal bowel, which distends it and perforates
it with bowel gas
The skin becomes keratinized and semi- permeable
to water as amphibians forage onto land.
KGF
ELBW infants have extreme insensible water loss.
If poorly managed it leads to hypernatremia and
is associated with IVH
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Reptiles
Reptiles have aveolar lungs and aveolar histology
emerges after 34 weeks of development, coincident
with final maturation of type II pneumocytes
Keritinization is more complete after 28 weeks of
gestation and water loss is less profound.
Keritinization can be accelerated by stress.
Apnea of Prematurity resolves around 30-32 weeks
of gestation when the nuclei of the respiratory
drive centers mature fully. Reptiles are the 1st
vertebrates fully dependent upon active
respiration
SNO
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Mammals part 1
Transient Tachypnea is a disease of term infants
that results from failure of clara cells and type
II cells to insert ENaC in the cell surface
(associated with c-sections / rapid progression)
due to insufficient cortisol exposure.
More Proximal Distal effect
Long gestations require large meconium resevoirs
Development 20 weeks 30 weeks
40 weeks
Preterm NEC
Term NEC
Pre- ileocecal valve bacterial overgrowth formula
feeds functional ileus
Post ileocecal valve isechemic preconditions
formula feeds rapid feeding advances
scortisol during pregnancy
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Mammals part 2
The phenomenon of postnatal brain development in
higher mammals (primates) has created additional
opportunity for developmental perturbation. There
are two primary mechanisms of insult 1)
hypoxia-ischemia, which can occur either
secondary to anoxic birth injury or in concert
with prematurity and the combination of low O2
tensions low flow states 2) Inflammatory
cytokines associated
with sepsis make premature infants
even more vulnerable to PVL PVL is
associated with
cerebral palsy
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So What?