00:01
Welcome. With this talk, we're going to talk about
elevated bilirubins that occur in the neonatal period.
00:07
This can be pathologic and way too much
bile or heme coming into the system
and not being excreted appropriately
or this can also be physiologic.
00:19
And being able to assure the anxious parents
that their little yellow baby
is going to be fine, that this will
resolve, is very important.
00:28
Or if more needs to be done,
it's also important that you be cognizant
of that and be able to do the appropriate workup.
00:36
So, hyperbilirubinemia of the newborn is
basically just jaundice in the newborn period
and it's again, elevated levels of bilirubin.
The epidemiology of this overall,
interestingly, greater than 50% of term infants
and more than 4/5ths of preterm infants
will have some visible jaundice after birth.
And this is the so called physiologic jaundice.
01:00
It's associated with immaturity.
It's associated with male sex
because the liver is not yet making good levels
of the conjugating enzymes necessary
to metabolize bilirubin into a form
that can be excreted.
01:15
And this will go away relatively quickly as the baby matures and the liver
develops that enzymatic capacity.
01:22
But
term infants, preterm infants are also subject to a substantialamount of trauma coming through the birth canal.
01:30
So, there will be significant bruising
and the absorption of hematomas
will also lead to increased heme burden
that must be metabolized.
01:40
If there are greater causes or more
important causes of hemolysis,
that clearly will cause greater
levels of hyperbilirubinemia.
01:51
And for example, maternal fetal blood group
incompatibility due to erythroblastosis fetalis
due to Rh incompatibility or ABO
incompatibility, hemolytic disorders associated,
say, with spherocytosis or glucose-6-phosphate
dehydrogenase deficiency or infections
that are causing hemolysis will all clearly
impact the heme burden that must be metabolized.
02:17
The overall pathophysiology then, is reasonably straightforward
once you understand how heme is metabolized.
02:24
And I would refer you to the hyperbilirubinemia
talk elsewhere within the Lecturio lexicon.
02:31
Unconjugated or indirect hyperbilirubinemia is physiologic.
Again, in the neonate, the erythrocytes have a shorter lifespan.
02:41
So, it's usually 120 days and it may be half of that in the neonate.
02:45
They also don't have sufficient hepatic bilirubin metabolism.
02:50
So, if it's a relatively immature UDP-glucuronosyltransferase.
02:56
And again, there are the other causes that we talked about,
maternal fetal blood group incompatibility,
hereditary causes of diminished glucuronidation
and in Gilbert Syndrome and in the neonate,
there's also increased enterohepatic circulation,
so, normally, about 20% of the conjugated bilirubin
that's put into the stool is recirculated,
that actually goes up with breastfeeding.
So, you may have a greater burden within the liver.
03:28
That was indirect unconjugated hyperbilirubinemia.
03:33
Conjugated or direct hyperbilirubinemia
actually says the liver's working fine.
03:39
But now, we have some sort of obstruction
and we're not getting that conjugated bilirubin out
of the liver and that really requires intervention.
This is not physiologic.
03:48
So, sepsis or bile duct obstruction,
other disorders and/or really severe hemolysis
with infections or major blood
group incompatibility, etc.
04:00
So, how would your patients present?
Neonatal jaundice is visible even in children of color
because the neonate is not as pigmented as they will be later in life.
04:13
They're also very clearly be scleral icterus.
04:16
Interestingly, as you get higher
and higher levels of hyperbilirubinemia,
different parts of the body will start
showing that cutaneous jaundice.
04:30
So, the face is because of the vasculature
and the relative thinness of the epithelium
will manifest jaundice at a much earlier stage
at about 5 milligrams per deciliter.
04:42
Keep in mind normal, upper limits
of normal, are one to 1.5.
04:47
When you start seeing jaundice in the mid-abdomen
that tends to have more fat
and not as well vascularized as the face is,
when you see jaundice in the mid-abdomen,
that's about 15 milligrams per deciliter.
And then, on the soles of the feet
which have very thick layers of keratin,
that means you're up to about 20 milligrams per deciliter.
05:08
So, you can have a rough ballpark just by
watching which part of the body becomes yellow.
05:14
Kernicterus is what we want to avoid at all costs.
Bilirubin can cross the immature blood-brain barrier
and then, cause a whole host of CNS complications.
And that's the main thing.
05:25
Otherwise, the bilirubin is relatively benign
but once it gets above 25 milligrams per deciliter,
there may be permanent, irreversible damage
to the baby's central nervous system.
05:38
In physiologic jaundice, and remember,
this is the unconjugated jaundice
because we have a relatively immature
hepatocyte conjugation apparatus.
05:47
The jaundice usually appears within 24 hours and it peaks
by days two to four and then, goes away by one week.
05:54
And by two weeks, 10 to 14 days,
it's back to normal completely.
05:59
And this is the one being able to tell the very
anxious parents, your baby's going to be okay.
06:03
He/she won't be yellow in about a week
or so will do a lot to alleviate their anxieties.
06:10
So, that's the physiologic jaundice. Non-physiologic.
So, it's either unconjugated or conjugated bilirubin.
06:16
There's then, again, different pathologies.
With the unconjugated hyperbilirubinemia
due to increased hemolysis and increased
heme burden, the total serum bilirubin
will get up to about 15 milligrams per deciliter,
so, the abdomen will be yellow.
06:33
And this is due to things where we see
hemolysis, hereditary spherocytosis, elliptocytosis,
glucose-6-phosphate dehydrogenase
deficiency, pyruvate kinase deficiency.
06:45
There are a whole bunch
of hemolytic disorders.
06:47
There is a heme talk somewhere in the Lecturio
collection that you can refer to for hemolysis.
06:56
You can also have, because of breastfeeding
and increased enterohepatic circulation,
higher levels of bilirubin than you would expect
and this falls in the non-physiologic category.
07:05
And then, there are genetic causes because of
mutations or defects in the conjugating enzymes.
07:13
The conjugated hyperbilirubinemia in the non-physiologic
category are going to be due to biliary tract disease.
07:21
So, obstruction due to primary atresia or cysts
or an early cholangitis of a neonate can be infectious
such as some of the torch pathogens,
so, toxoplasmosis, rubella, cytomegalovirus
and herpes can be required - other acquired
perinatal infections can be genetic,
apha1 antitrypsin deficiency or metabolic
galactosemia and this is just a partial list.
07:48
So, all of these things are potentially
causing outflow obstruction.
07:53
The hepatocytes are generally working okay.
They're conjugating appropriately.
07:58
They're trying to release the bilirubin
into the common bile duct
and that's being frustrated by
a variety of potential causes.
08:07
How are we going to make our diagnosis?
It's going to be important to distinguish physiologic
versus non-physiologic and then, whether it's
conjugated or unconjugated, indirect or direct, etc.
08:18
The laboratory testing is very important.
So, we want to assess whether it's indirect bilirubin
in which case, we're probably not getting good metabolism or it's direct, in which case, you probably have obstruction.
08:28
We want to make sure that there's not a lot of hemolysis
going on, raising the specter of potential infection.
08:33
In terms of hemolytic causes, autoimmune
or antibody-driven hemolysis is a biggie.
08:41
So, we would do coombs
testing looking for that.
08:44
We can get a sense or for whether there's biliary obstruction
by whether the alkaline phosphatase is elevated
and ultrasound is clearly going to be important
for identifying dilated bile ducts.
08:55
Management. The key thing is to avoid the
neurotoxicity associated with kernicterus.
09:01
That's what we want to do above all else.
09:04
And remember, kernicterus is going to occur
when we have bilirubin in excess of
about 25 milligrams per deciliter.
09:12
It turns out that we can administer just simple light
at a particular wavelength shown there
that converts the bilirubin into lumirubin
which can be excreted directly in the urine,
so, without any conjugation or anything else,
we can get rid of that.
09:28
So, we can take what's in the skin and in
the circulation and with this very passive light
that doesn't hurt the infant or anything else,
we can get rid of it by peeing it away.
09:39
For immune hemolysis, we clearly want to stop
that process that's also going to cause severe anemia.
09:43
We'll have other developmental consequences.
So, we can get intravenous immune globulin.
09:48
We can do plasmapheresis to remove
the autoantibodies that are causing hemolysis
or we can do a complete exchange transfusion.
09:57
With that, the hyperbilirubinemia of the neonate.