Exam 2 Flashcards
1
Q
newborn screening
A
Series of blood tests performed on a neonate with the goal of early identification and treatment of disease.
- Individual tests for specific diseases
- Tandem mass spec
- Genetic probes
Hearing screen
Pulse oximetry screening
Note: it is continually evolving
2
Q
history of newborn screenings
A
varies by state; 2000 congress mandated increased federal involvement to correct disparities
- 1961: PKU first screen began in MA
3
Q
features of any screening test
A
High sensitivity
Disease with severity which would warrant early detection
Cheap, easy and fast
Definitive test is available
Early detection can change the course of the illness
Treatment available: historically a requirement, now controversial.
4
Q
sensitivity
A
probability that a person who truly has a disease will have a positive test. This is a “true positive”
- inversely related to specificity
5
Q
specificity
A
probability that a person who really does not have the disease will have a negative test. This is a “true negative.”
- inversely related to sensitivity
6
Q
false negative
A
person who tests as negative but who is actually positive
- results in delayed detection of disease
7
Q
false positive
A
person who tests as positive but who is actually negative.
- results in unnecessary testing and therapeutics
8
Q
positive predictive value
A
likelihood that a person has the disease given a positive test result
9
Q
negative predictive value
A
the likelihood that a person does not have the disease given a negative test result
10
Q
process of newborn screening
A
HHS (federal) now mandates what to screen for and gives states time to comply; trying to make more uniform among states
- all state use public funds
- CO: tests are paid by fees required by and collected by the state (covered by insurance and medicaid)
Blood tests performed at the State Department of Public Health and Environment (CDPHE)
11
Q
newborn screening in CO
A
initial and second blood spot tests for newborns required by law
- some things do not show up as early (endocrine disorders and hypothyroidism)
- CO also gets WY samples
12
Q
what was included on the standard screen prior to 2006 (when mass spec was added)
A
Phenylketonuria
Congenital Hypothyroidism
Hemoglobinopathies
Congenital Adrenal Hyperplasia
Galactosemia
Cystic Fibrosis
Biotinidase Deficiency
B.A.E.R. (hearing test)
Note: top 4 on second NBS as well
13
Q
tests that use drug blood spot samples
A
Phenylketonuria
Congenital Hypothyroidism
Hemoglobinopathies (Sickle Cell Disease)
Cystic fibrosis
14
Q
expanded metabolic screen - added in 2006 (mass spec)
A
With any given sample can detect up to 40 disorders
- Colorado reports on only 23 disorders (those for which are recommended by March of Dimes, for which there is treatment)
- MCADD
Primarily disorders of organic, amino and fatty acid metabolism
Potential for additional diseases
15
Q
what’s new in blood spot screening?
A
SCID
Bart’s Hemoglobin
Potential for spinal muscular atrophy screen
Pompay’s Disease: glycogen storage disease
16
Q
phenylketonuria
A
First and classic congenital disease identified by newborn screen
Disorder of amino acid metabolism; caused by an enzyme deficiency
Occurs in 1 in 10-15,000 live births
between 1979 and 2003
Prevalence Rate: 0.01% or 27,200 people in USA
Untreated, causes developmental delay and often, severe cognitive impairment
17
Q
PKU - untreated
A
Symptoms of PKU include neurodevelopmental problems:
- Developmental delay to severe cognitive impairment
- Seizures
- Autism
- Hyperactivity
- Aggressive behavior
Hair and skin changes incl. hypo pigmentation (melanoma missing)
18
Q
PKU - treated
A
Tx: diet restriction; elimination of specific AA
Children can live healthy life and be developmentally normal
Current recommendation is lifelong diet
NOTE: Children of mom with PKU off diet during pregnancy at risk for congenital heart disease
19
Q
hypothyroidism
A
Most common true positive test
- Incidence is 1 in 3600 to 5000 births
Screen for T4, if abnormal, check TSH
- Timing is important since all newborns have a TSH spike after delivery
- Check as close to or after 24 hours
Main reason why second screen was added in 1996
20
Q
hypothyroidism - treated and untreated
A
untreated:
- causes “cretinism” (severely stunted physical and mental growth)
- cognitive impairment, growth and neurologic abnormalities, fatigue, skin changes, coarse hair, large tongue
Treated with thyroid hormone for life: normal IQ, good health
21
Q
sickle cell disease (hemogloinopathies)
A
primarily a RBC disease but since blood flow is sluggish, spleen gets infarcted early in life and affects WBCs too
Sx: Painful crises Aplastic crises Predisposition to infection Tendency toward infarction Bony changes associated with high blood cell turnover
Incidence of Sickle Cell Disease is 1 in 500 African Americans
22
Q
hemogloinopathies (sickle cell) screen
A
Screening Test is isoelectric focusing, then electrophoresis
Confirmatory Test: Hemoglobin Electrophoresis (not fast enough for screening test - this is a diagnostic test)
23
Q
sickle cell treatment
A
Early immunization against “encapsulated organisms,” (pneumococcus and H.flu) - likely to loose spleen
Penicillin prophylaxis
Early treatment of crises - painful (pain meds)
Attention toward hydration (helps with thick blood)
Avoid triggers such as infection, hypoxia (such as altitude)
Genetic counseling of parents
24
Q
cystic fibrosis
A
Disorder of membrane transport of ions (sodium and chloride)
Presents with:
- Chronic lung disease (secretions can’t be cleared and act as plugs)
- Malabsorption/ malnutrition (secretions are thick and block pancreatic function)
25
cystic fibrosis treatment
Tx:
Managed, not cured
- new medication: Kalydeco (genetic intervention med resolved symptoms in 4% - one strain)
Antibiotics, preventive and therapeutic
Bronchodilators
Exogenous pancreatic enzymes
Attention to nutrition
Life expectancy now 40 years
26
cystic fibrosis diagnosis
Screen measures immunoreactive trypsinogen (1st and 2nd screen)
Definitive test is sweat chloride (older - not babies)
Genetic testing for specific mutation
27
M.C.A.D.D (Medium chain acyl-CoA dehydrogenase deficiency)
metabolic disease detected as part of mass spec test
- disorder of fatty acid oxidation that impairs the body's ability to break down medium-chain fatty acids into acetyl-CoA
28
M.C.A.D.D. - symptoms and treatment
Times of stress and fasting: cause hypoglycemia and shock
Treatment: avoid fasting & dehydration and administer carnitine (plays a crucial role in energy production, as it is responsible for transporting fatty acids (acetyl choline?) to the mitochondria)
29
SCID - Severe Combined Immune Deficiency ("bubble boy disease")
Most debilitating human lymphoid deficiency disease, impairs the differentiation of both T and B lymphocytes
Infants are highly susceptible to recurring infections of viruses, fungi and bacteria
Invariably die within 2yr of birth
30
SCID - testing and treatment
Test is a genetic probe
- some inconsistency yet in the test
- results sent to National Jewish Lab for confirmatory test, a second genetic marker
Treatment: bone marrow transplant
31
Bart's Hemoglobin
Normal adult hemoglobin, Hbg A, has 2 alpha and 2 beta strands - Bart’s hemoglobin is a tetramer of 4 beta strands
Genetic probe used for screening test; hemoglobin electrophoresis confirmatory test
Found in alpha-thalassemia: severity based on # of genes missing (silent carrier v. hydrous fatalis and incompatible with life b/c RBC cannot carry O2)
Found in hemoglobin H disease: RBCs have high binding of O2 so they don't release it to tissues as well - anemia
32
What two diseases can be protective against malaria?
sickle cell disease and alpha-thalassemia
| - worldwide distribution is same as malaria belt
33
SMA (spinal muscular atrophy) - candidate for future screening
2nd most frequently observed autosomal recessive lethal disorder
Clinical presentation ranges from a perinatal lethal to adult onset disease.
- Type I lethal in first year of life
New treatment options and a clearer understanding of the natural history have made SMA a candidate for prospective screening
34
timing of newborn screening test
1st screen 24 to 48 hours
- need several feeds to diagnose galactosemia
- wait until after TSH spike
- normal values on CF and CAH tests vary according to age at time of test
2nd screen 8 to 14 days (range 3 to 30 days)
35
How is newborn screening performed?
Blood is drawn from baby’s heel and allowed to dry on filter paper
Sent to Colorado Dept. of Public Health and Environment where individual tests are run
Results sent to hospital, PCP, specialty follow-up clinics and definitive tests arranged with families
36
newborn screening beyond blood spot
hearing screening
pulse oximetry for critical congenital heart disease
37
congenital hearing loss
American Academy of Pediatrics: recommend that hearing loss in infants be identified prior to 6 months of age - better prognosis for speech and cognitive abilities
BEAR: Brainstem auditory evoked response measures brainwave response to broadband click
- best at 2 wks but newborns usually get screen b/f leave hospital
38
pulse ox screening for C.C.H.D. (critical congenital heart disease - needs tx in 1st month of life)
Method:
- Performed after 24 hours
- Place probe on right hand (pre-ductal) and one foot.
- Room air saturation less than 95% requires further workup
- Definitive test is echocardiogram
Lesions identified:
- Tetralogy of Fallot
- Transposition of Arteries
- Truncus Arteriosis
- Tricuspid Atresia
- TAPVR
- Pulmonic Stenosis
- Hypoplastic Left Heart
- Coarctation of the Aorta
NOTE: will not pick up CHDs that do not cause cyanosis!!
39
malformation
complete or partial absence or abnormal formation of a structure caused by environmental or genetic factors which interfere with development
Most originate during the period of organogenesis, the 3rd to 8th weeks of gestation.
- ex. Congenital heart defect
MOST common cause of infant mortality in the U.S. (more than prematurity and SIDS)
Can be minor or major (see below)
40
syndrome
groups of anomalies occurring together with a common cause
41
association
groups of anomalies occurring together more often than chance alone would allow but cause is unknown
42
sequence
one primary defect causes the next, which causes the next
Example: Pieere Robin sequence:
- small chin causes tongue to be pushed up and back (glossoptosis)
- position of tongue prevents normal closure of palate, causing cleft palate
- results in obstruction of airway and feeding difficulties
43
deformation
body part which was forming normally but was acted upon by environment to be distorted; most often musculoskeletal and fixable
- ex. clubfoot
44
disruption
body part was forming normally when an event occurs that changes it dramatically and irreversibly– often amniotic bands or vascular accident
- often not fixable (more disruptive than deformation)
45
minor malformations
Occur in less than 4% of population; no major intrinsic medical significance
- 70% found on face or hands
- ex. syndactyly (fingers connected)
Significance: more minor anomalies = more likely to have major anomaly
Note: 3 minor anomalies = 20% inc. major anomaly
46
transverse palmar crease
Single, uninterrupted horizontal crease on palm
- previously called “simian crease”
Occurs in 45% of babes with Down Syndrome
4% of Caucasians (minor anomaly)
16% of Chinese (normal variant)
47
major malformation
congenital defect of surgical, medical or functional significance
- ex. omphalocele (intestines protrude from stomach) or congenital heart disease (Tetralogy of Fallot)
48
types of genetic defects
chromosomal disorders:
- abnormalities of number (e.g. Trisomy (3 copies of 1) v. triploidy (3 copies of all))
- abnormalities of structure (e.g. Deletions or duplications of portions of chromosome)
Single gene disorders
- deletions
- duplications
- substitutions
autosomal dominant
autosomal recessive
X-linked
49
genomic defects
Genomics is a subset of genetics in which we look at the turning on or off of specific genes
- can be caused by environmental factors
- explains how normal tissues vary from organ to organ
- also explains how teratogens can effect the expression of an individual’s genetic makeup
50
prenatal diagnosis of genetic defects - two techniques
Two techniques:
- amniocentesis
- chorionic villus sampling
```
Can be used for:
- biochemical screening
- genetic screening
Karyotype
FISH probe
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51
amniocentesis
Under ultrasound guidance, a spinal needle is inserted through the maternal abdominal wall and uterine wall, into a pocket of amniotic fluid (contains cells from skin and kidney)
Risks: greater in first trimester than second
- fetal loss
- damage to fetal structures
- leakage of amniotic fluid
52
chorionic villus sampling
best performed at 11-13 weeks (adv: can do earlier than amniocentesis; if later would just do amnio)
- Requires ultrasound guidance
- approach may be trans-vaginal or trans-abdominal (depending upon location of the placenta)
- Needle biopsies a portion of the chorion
Risks: 2-3% risk of fetal loss, very low if any fetal abnormalities if after 10 weeks
53
diagnosis of genetic diseases
```
history
physical exam
laboratory
- Karyotyping
- FISH probe
- Microarray (genomic)
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54
Why make diagnosis of a syndrome in a neonate?
External signs give clues to serious, internal malformations
Enables provider to help family plan early interventions for expected issues
Genetic counseling; incl. likelihood of recurrence
Helps family to deal with uncertainty / get support
55
karyotyping - definition and indications
Visual inspection of chromosomes and their banding (ID’s all types of specific abnormalities)
Indications:
- Confirmation of a known syndrome
- Infants with multiple congenital anomalies
- Child with developmental delays and morphologic changes
- Ambiguous genitalia
- Still born infant with malformation (5-15% of babies will have a chromosomal abnormality)
Advantage: can see structure of chromosomes
Disadvantage: needs to grow in culture - takes a week
56
FISH Probe
Fluorescent In Situ Hybridization
- DNA probe + label
- Hybridize with sample cells
- Fluorescent detector
Disadvantage: Asks a specific question; ie. You have to have the disorder in mind when selecting which probe to use
- helpful for genital ambiguity
Advantage: results in 24 hours
57
microarray
mainstay in genetic analysis!
Microarray analysis involves breaking open a cell, isolating its genetic contents, identifying all the genes that are turned on in that particular cell, and generating a list of those genes.
A DNA micorarray allows scientists to perform an experiment on thousands of genes at the same time.
Each spot on a microarray contains multiple identical strands of DNA.
The DNA sequence on each spot is unique.
Each spot represents one gene.
Thousands of spots are arrayed in orderly rows and columns on a solid surface (usually glass).
The precise location and sequence of each spot is recorded in a computer database.
Microarrays can be the size of a microscope slide, or even smaller.
58
Trisomy 21 - Down Syndrome
Babies are born with three copies of chromosome 21
- complete: 100% of cells involved
- mosaic: varying percentage of cells involved
NOTE: % of cells is proportional to severity of symptoms
Incidence: 1:600- 1000; MOST common syndrome in man
59
clinical feature of down syndrome at birth
```
Hypotonia
- tongue protrudes, more due to tone than size
- hyperflexibility of joints
Typical facies
- microcephaly
- up slanting palpebral fissures
- inner epicanthal folds
Typical features of hands and feet
- transverse palmar crease
- sandal toe / flat feet
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60
hidden features of down syndrome
40% have congenital heart disease (endocardial cushion defect, VSD)
Skeletal abnormalities (atlanto-axial subluxation, hip problems)
66% hearing loss (at birth or later)
Hypothyroidism
White blood cell abnormalities (susceptibility to infection
Increased risk of leukemia)
61
diagnosis of down syndrome
```
Prenatal "quad screen":
- dec. alpha-fetoprotein (AFP)
- Inc. Human gonadotropin (hCG)
- Dec. Unconjugated estriol (uE3)
- Inc. Inhibin A
NOTE: detects 85%
```
Prenatal ultrasound:
- increased nuchal width
Amniocentesis for karyotyping:
- encouraged in moms over 35
Genetic testing:
1. FISH probe – looking specifically for chromosome 21; fast results
- however, does not tell you what type which is important for additional children from mom (Robertsonian translocation – much higher likelyhood in next sibling); also does not provide mosaic
2. Karyotype (from tissue culture) – this looks for everything but takes a week
62
"Quad" Screen
4 things tested: AFP, HCG, uE3, Inhibin
Neural tube defect (NTD):
-AFP up (rest normal)
Trisomy 21:
- AFP and uE3 down
- HCG and inhibit up
Trisomy 18
- all down
63
Turner's Syndrome
chromosomal abnormality
- XO - females only!
Clinical features:
- Short stature
- Lack of secondary sex characteristics
- Shield chest / Webbed neck
- Wide carrying angle of arms
- Normal intellect (problems with math)
Unseen problems:
- Cardiac disease (coarctation of aorta, aortic valve anomalies)
- Infertility/lack of sexual development
- Renal disease
64
Prader-Willi Syndrome
chromosomal abnormality
- deletion of a portion of a chromosome
Clinical presentation at birth:
- Severe hypotonia
- Poor feeding
- Micropenis
- Small hands and feet
Symptoms later:
- Short stature
- Mild to moderate mental retardation
- Food related behavior issues
65
achondroplasia
Example of a single gene mutation
Passed on in an autosomal dominant fashion
What you see (midget)
Large head
Short stature
Bony abnormalities: curvatures of spine, short hands, abnormally formed pelvis
Normal intelligence and fertility
66
autosomal recessive disorders
Occur if both parents, though clinically normal, carry the same gene
When combined present with the disease in question
Increased likelihood if parents are related or in small, closed communities
Many diseases, including sickle cell disease, cystic fibrosis, Crigler-Naajar
67
X-linked disease
Gene for trait is carried by mother on the X chromosome
- expressed in male children only
- classic examples are hemophilia, Duchenne’s muscular dystrophy and red-green color-blindness
68
teratogens
agent or factor that causes a malformation
- thalidomide (drug for morning sickness): babies with flipper limbs
- fetal alcohol syndrome: typical facies (smooth philtrum), microcephaly; developmental delay, behavior problems
69
Viruses - Main Issues
Important cause of prenatal and neonatal morbidity and mortality
Frequency of viral infections in fetus and newborn may be as much as 6 to 8% (compared to 1 to 2% for bacterial disease)
More likely than bacteria to cross the placenta and cause disease in fetus
70
congenital infection
acquired in utero
can result in malformations, fetal loss, prematurity, IUGR, neurological sequellae
71
natal infections
acquired at the time of birth
- infection did not cross membranes or placenta
wide variety of outcomes from asymptomatic disease to chronic disease or death
72
postnatal infection
acquired during the neonatal period
73
vertical transmission
the transfer of a disease, condition, or trait from one generation to the next either genetically or congenitally
Eg. Passing on an inherited trait (sickle cell disease)
Eg. Passing on an infection (early onset GBS infection) (either during pregnancy or during delivery)
74
horizontal transmission
the spread of an infectious agent from one individual to another, usually through contact with bodily excretions or fluids, such as sputum or blood, that contain the agent.
Eg. Spreading the common cold or spreading avian flu
Eg. Infant developing late onset GBS sepsis from his mother.
75
effect of material immune response on fetus
When mother is infected - immune system first makes IgM
- large molecule
- does not cross the placenta
- spike in IgM indicates current infection
As the immune response continues, maternal antibody is primarily IgG
- small molecule
- freely crosses placenta (especially during the third trimester)
- indicates convalescent of past infection
Term baby is essentially born with a copy of his mom’s IgG which persists for 4 to 6 mos
- why premature babies are more prone to infection
76
effect of viral infection varies with trimester of pregnancy
1st trimester: viral infections act as teratogens (period of organogenesis)
2nd trimester: baby gets infection and immunity
3rd trimester: baby can pick up infection without antibody (if come to delivery)
77
congenital viral infections - what happens when mom gets virus while pregnant?
most maternal infection are self-limiting and have no effect on fetus (Influenza, RSV, rhinovirus, Norwalk)
maternal viremia (virus in blood) - usually placenta protects fetus
some viruses cross placenta and cause:
- replication and infection of placenta
- damage to vessels of placenta so it is “leaky”
- infection of maternal leukocytes which sneak through inflamed placenta
78
common viral pathogens - TORCH
```
Toxoplasmosis
Other- primarily syphilis
Rubella- aka “German measles”
Cytomegalovirus
3 H's:
- Herpes
- Hepatitis B & C
- HIV
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Note: There is no such thing as a “Torch Titer”- provider needs to consider each possible infection and order specific antibody titers separately
79
toxoplasmosis - not a virus at all
Caused by an intracellular protozoan parasite
Most natural infections are acquired by ingesting undercooked meat or food contaminated by cat feces
Cat - definitive host
Severity of fetal disease is inversely proportional to gestational age
- 1st trimester: fetal death or baby with severe neurologic (calcified lesions in brain) or eye disease (calcifications on retina); also see ASYMMETRIC IUGR
- 2nd or 3rd: mild or subclinical disease
80
syphilis ("other") - not a virus at all
Sexually transmitted infection caused by Treponema pallidum
In adult, 4 stages:
- Primary: ulcerative lesion on genitals, non-painful and easily missed
- Secondary: systemic illness with fever, sore throat, headache and diffuse rash
- Latent: treponemes present but without symptoms
- Tertiary syphilisL neurologic and cardiac symtoms
more recent mom’s infection, the more likely the transmission to fetus; (i.e. 100% transmission in primary and secondary syphilis infection;
after secondary, i.e. during latent phase, infection rate drops)
Baby more likely infected if mom is infected during second or third trimester
- if baby gets in 1st trimester - full blown congenital syphilis (bad!)
81
syphilis - congenital infection
May result in stillbirth, hydrops fetalis, prematurity, IUGR, microcephaly, blistering rash
Or, baby may be asymptomatic at birth, develop characteristic symptoms in first 3 months:
- Hepatomegaly, splenomagaly, skeletal & dental abnormalities ()Hutchinson teeth), anemia, snuffles, saddle nose
Treat with PENICILLIN
Untreated, will develop neurosyphilis and bony changes
82
congenital syphilis
we do not see a lot of it here, but screen for it since it can be devastating and is preventable with PENICILLIN
83
rubella
Classic example of viral teratogen if infection occurs during the first 8 weeks of pregnancy
Symptoms: heart defects, cataracts, cognitive impairment, hearing loss, IUGR, blueberry muffin rash
- these are malformations (occur early)
Infection in third trimester: causes myocarditis (pathology of an already formed structure - deformation)
NOTE: there is an effective vaccine - so rare in US
- WE STILL SEE IT IN OTHER PARTS OF WORLD!
84
congenital rubella - familiar rash
“Blueberry muffin rash” - consists of raised purplish bumps on the skin which reflect extramedulary hematopoiesis (RBC formation on the skin; outside of the bone marrow)
NOTE: also see with congenital CMV
85
CMV (cytomegalovirus)
MOST common cause of intrauterine infection in US (1% of all neonates infected)
Mom is asymptomatic, as are most babes
Early childhood infections are common and mild - often spread in daycare settings (25% of population has CMV antibody)
NOTE (1st trimester): 20-30% risk of fetal loss if occurs during first trimester; other bad effects
86
congenital CMV - symptoms at birth
Symptoms are most severe when they occur in first trimester:
- Prematurity
- Corioretinopathy
- Hepatic failure
- Microcephaly (i.e., OFC (head circumference) less than 5%tile)
"Blueberry muffin” appearance (petechiae & purpura)
87
blueberry muffin rash
Usually on trunk
Can be seen in rubella, CMV, congenital leukemia, neuroblasoma, etc.
- any intrauterine condition in which there is severe anemia
Magenta coloured papulonodular lesions suggestive of dermal hematopoiesis (RBC formation)
88
CMV - long term symptoms
MOST COMMON cause of congenitally-acquired sensoirneural hearing loss
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Intracranial calcifications
Cerebral palsy
Seizures
Cognitive impairment
Dental defects
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89
CMV diagnosis
Urine specimen is best source for culture (though virus present in other body fluids also)
90
viral infections acquired during time of delivery: all of the H's
HIV
Hepatitis B
Hepatitis C
Herpes Simplex virus
91
HIV (Human Immunodeficiency Virus)
virus responsible for AIDS
Routine testing for HIV is recommended for all pregnant women
RISK OF TRANSMISSION of HIV from untreated mom to baby is 25%
TREAT!
- antiretroviral drugs (ATZ) (not teratogenic to the developing fetus)
92
HIV positive mom - how to treat
Mom with low titers (good t cell count):
- can delivery vaginally; begin AZT tx to baby
- reduced risk of HIV to baby down to 1%
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Mom with high titers:
- vaginal v. c-section
AZT during labor and delivery
- baby gets multi-drug therapy
- 2% likelihood of infection in newborn
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CONTACT CHIP program - follow mom and baby once born
93
HIV and breastfeeding
Depends on where in world (HIV can pass through breast milk and cause newborn infection.)
In “first world,” better to use formula
In developing world, particularly Africa, better to continue to breast feed (likelihood of newborn death due to diarrheal illness outweighs death due to HIV)
94
HBV (hepatitis B)
Picked up at time of delivery; does not dross placenta
Babies present with a variety of signs and symptoms, including:
- CHRONIC INFECTION (90%)
- Clinical hepatitis with jaundice
- Fatal fulminant hepatitis
- Chronic hepatitis - Predisposition for hepatocellular CA (carcinoma).
Note: More than 90% of perinatally infected infants will develop chronic infection whereas only approximately 10% of infected adults do
95
HBV positive mom - management
All pregnant women are screened for HBV as part of prenatal labs
- Immediate bath
- Hep B vaccine
- HBIG (Hepatitis B Immune Globulin)
note: Breastfeeding poses no threat to baby -BREASTFEED
95% EFFECTIVE in preventing HBV infection in baby!
96
HCV - hepatitis C
Not part of routine prenatal screening
Signs and symptoms of hep C virus are indistinguishable from Hep B and Hep A
Acute disease is mild; children have low chance of chronic disease (opposite Hep B - HBV)
management for baby of HCV positive mom:
- test bay at 18 months (after maternal antibody gone)
- BREASTFEEDING OK
97
herpes simplex virus (HSV)
HSV-2 is more commonly the cause of neonatal infection than HSV-1
most often transmitted during birth through an infected maternal genital tract
Risk to babe
- 33-50% if mom’s primary infection
- 5% if result of reactivation shedding
Neonatal herpes infections are severe
- High morbidity and mortality rates
Consider diagnosis in neonates with fever, irritability, abnormal CSF findings and seizures
98
HSV - manifestations
Manifestations
- 1/3 disseminated disease involving multiple organs (sepsis): presents in 1st week
note: vesicular rash will kill - must catch!
- 1/3 localized CNS disease: presents in 2nd or 3rd week
- 1/3 localized to skin, eyes and mouth: presents in 2nd week
99
HSV at delivery
active lesions: many OBs elect C-section
AVOID USING FETAL SCALP ELECTRODE (common site for introduction of infection)
Do NOT RUPTURE MEMBRANES, if possible
100
Care of newborn at risk for HSV (due to maternal lesions)
isolation
cultures from many areas
treatment:
- controversial if asymptomatic
- ACYCLOVIR if has any symptoms
101
Parvovirus B19 (aka Fifth disease)
Causes mild, self-limited illness with typical rash in young children
- “slapped cheeks”
- lacy rash on extensor surfaces of joints
Contagious before rash appears; typically a preschool disease
Like many viruses, causes bone marrow suppression
102
varicella (aka chicken pox)
Caused by Herpes Varicella Zoster virus
Like all herpesviruses, characterized by an acute infection with recurrences (shingles)
Initial infection is “chicken pox”
Lesions at different stages (unlike small pox)
NOTE: vaccine now exists (1995)
103
effect of varicella virus on fetus and newborn
First trimester: serious but not common (limb atrophy, CNS, eye manifestations)
Second trimester: unapparent infection
Varicella infection occurring 5 days before to 2 days after birth: can be fatal since no IgG
More then 5 days before delivery in 3rd trimester: no problem b/c maternal antibody
104
bacteremia
The presence of bacteria in the bloodstream
can be a transient, self-limited phenomenon, cleared by immune system
can “seed” other sites such as bone, lung, meninges
can progress to sepsis
105
sepsis
Bacteremia coupled with inadequate perfusion and end-organ involvement
- decreased blood flow causing damage to important organs
106
Two types of neonatal sepsis
Early-onset sepsis (EOS): Sepsis which occurs in a neonate within the first 3 days of life
- vertical transmission
Late-onset sepsis (LOS): Sepsis which occurs after the first 3 days until 2 to 3 months of life (definitions vary)
- horizontal transmission
107
signs and symptoms of sepsis - can be difficult in babies
Temperature elevated or depressed (normal range is 36.5 to 37.5)
Tachypnea (RR >60/min BPM)
Signs of respiratory distress:
- Poor color
- Decreased responsiveness
- Poor feeding
- Irritability or sleepiness
108
effect of sepsis (EOS and LOS) on neonates
EOS neonatal sepsis has a mortality rate of approximately 15%
- Higher mortality in pre-term babies
LOS more likely to be complicated by meningitis with its attendant morbidity
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bacterial organisms that cause sepsis
1. Group B Strep
2. E. coli (#1 in preterm babies)
3. Other strep species (most commonly Pneumococcus)
4. Enterococcus
5. Staph
6. Listeria
7. Klebsiella
NOTE: these organisms all come from vagina or GI tract (aka rectum)
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how does transmission of bacteria from mom to baby occur
During labor membranes rupture or become leaky
Organisms can ascend from the birth canal (vagina)
Fluid becomes infected, fetus inhales or swallows it and also becomes infected
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Risk factors for early onset sepsis (EOS)
```
Major risk factors:
CHORIOAMNIONITIS
Maternal Group B Strep carriage
Prolonged rupture of the membranes (> 18 hours)
Prematurity
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chorioamnionitis
Maternal temperature during labor > 38.o C or 100.4 F
At least 2 other features:
1. maternal leukocytosis: WBC > 15,000 in blood
2. maternal tachycardia: > 100 beats/min
3. fetal tachycardia- baseline: > 160 beats/min
4. uterine tenderness
5. foul smelling amniotic fluid
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Group B Strep (GBS)
GRAM POSITIVE BACTERIA
- Carrier state in mother (part of normal flora)
- Not sexually transmitted
- 50% vertical transmission
- 1% of babies born to mothers with GBS will develop early onset sepsis
Note: Late onset disease is horizontal transmission
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history of GBS in USA
There as been a 87% reduction from the 1990’s rate!
- due to doing GBS cultures on moms between 35 and 37
- treating GBS positive moms with Penicillin when in labor
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risk factors for GBS
Previous child who had early-onset GBS sepsis
GBS bactiuria during current pregnancy
Maternal fever/chorio
Preterm labor
Note: based on 1996 criteria for Penicillin; still use if do not have GBS culture results
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PROM - prolonged rupture of membranes
> 18 hours
The longer the membranes are ruptured, the higher the likelihood of ascending infection
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prematurity (gestational age
Very high risk for EOS
Higher risk for mortality associated with sepsis
Possibly premature labor was prompted by brewing infection
Premature babies are more vulnerable because of less adequate immune system
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diagnosing sepsis - difficult!
Amer. Academy of Pediatrics (AAP): . available DIAGNOSTIC TESTING IS NOT HELPFUL in deciding which neonate requires empirical antimicrobial therapy but can assist with the decision to discontinue treatment
The only truly specific laboratory test in the workup of neonatal sepsis is the BLOOD CULTURE. If it is positive we can say that the baby is bacteremic
- coupled with a suggestive history and physical exam, the diagnosis of sepsis can be made.
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septic workup - tests to consider
Blood culture (mandatory)
Chest X-ray (almost always done)
Lumbar puncture, aka “spinal tap” (varies)
Complete blood count (CBC)
C-reactive protein
NOTE: Urine culture is not indicated in septic workup of a newborn in the first 3 days of life (include in workup of late onset sepsis)
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septic workup - blood culture
In a newborn, 1.0-2.0 ml of blood is inoculated into culture
Almost ALL pathogens will grow within 48hrs
Sensitivity is 50- 80%
NOTE: Positive blood culture is DIAGNOSTIC of neonatal sepsis but negative culture does NOT rule it out
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septic workup - chest x-ray
Include whenever baby has significant respiratory symptoms.
Recall that respiratory distress is one of the most common signs of sepsis
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septic workup - spinal tap
Meningitis is uncommon but devastating
Weigh risks and benefits of the spinal tap since it is invasive and stressful
Best performed before starting antibiotics, can be delayed if baby is unstable
When to do LP with CSF culture:
- symptoms of meningitis (lethargy, abnormal tone, excessive irritability, bulging fontanel, or septic shock)
- symptomatic babies in whom sepsis is the leading diagnosis (that is, not MAS, simple RDS)
- all babies with positive blood cultures
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septic workup - CBC
Can be a clue, not diagnostic
There are several features to consider:
- total WBC count
- absolute neutrophil count
- immature/total ratio (I/T) - neutrophils
- immature leukocyte count
NOTE: Normal ranges are broad and depend upon timing (best time is at least 6 hours after birth)
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absolute neutrophil count
Note: neutrophils are the cell line most responsible for managing bacterial infections
calculate by multiplying the total percentage of all neutrophils x total white blood cell count
total neutrophils = polys + bands+ myelocytes + metamyelocytes
Abnormal if less than 1750 - a low neutrophil count reflects an overwhelmed immune system
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septic workup - C-reactive protein
CRP is a protein synthesized by the liver in response to, and as part of, the inflammatory response
Poor specificity: other perinatal conditions confound (asphyxia, fetal distress, MAS, etc.)
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current recommendations - GBS and sepsis prevention
prophylaxis against GBS: Penicillin during labor (GBS is “exquisitely sensitive” to Penicillin)
Ideally, mother needs 2 doses of PCN prior to delivery
- acceptable: at least one dose, at least 4 hours prior to delivery
If adequate prophylaxis, eliminates risk of EOS GBS sepsis, can go home in 24 hours
If inadequate, needs a 48 hours observation period to watch for evidence of EOS.
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current recommendations - chorio and sepsis prevention
Mothers who have fever or signs of chorio are treated with antibiotics during labor to prevent sepsis in newborn
Baby must be observed for 48 hours after birth
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treatment for newborns with sepsis
IV antibiotics
- Ampicillin & Gentamicin
Duration
10 full days for sepsis
2 weeks if meningitis
NOTE: The trick is deciding who truly has sepsis and who is at risk but not infected
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actions when sepsis is suspected in newborn - current recommendations
AAP and CDC Recommend:
- babies born to mothers with diagnosis of chorio should have a sepsis workup
- i.v. antibiotics (Ampicillin and Gentamicin) for 48 hours until cultures are negative
NOTE: If you follow this closely, it means that 10 to 15% of newborns will have blood drawn and IV antibiotics
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actions when sepsis is suspected in newborn - risk-based options
must look at whole picture to prevent overuse of antibiotics and stress to neonate!
Consider gestational age (34 to 42 weeks)
Highest maternal temperature during labor
Length of time membranes were ruptured
GBS carrier status
Type of intrapartum antibiotics used
Risk-based analysis: Kaiser Sepsis Risk Calculator
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gastrointestinal (GI) problems in newborn - general principles
All significant pathology of GI tract in newborn results in obstruction (block in passage of material along tract)
Presentation of pathology depends upon where the obstruction occurs
When intervention is needed, immediate steps are all the same (can intervene b/f know cause)
Resolution of significant pathology nearly always requires surgery
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4 types of obstruction
Atresia: non-formation resulting in discontinuous lumen and complete obstruction
Stenosis: formation with restriction; i.e., limitation of diameter of lumen with partial obstruction
Blockage: contents of lumen harden to cause obstruction or external compression of tract occurs
Dysmotility: peristalsis, the rhythmic contraction of tract is abnormal leading to functional obstruction
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symptoms of GI problems depends on location of problem
upper tract: from mouth to end of duodenum
- presents with vomiting
- closer to mouth, sooner the emesis
- belly will be flat or scaphoid (concave)
lower tract: duodenum to anus
- presents with decreased or no stooling
- belly will be distended
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radiology of GI system
Can help define location of problem:
- Plain x-ray
- Ultrasound
- Contrast studies
Air is present in the stomach immediately after birth; by 24 hours of life air should appear in the rectum.
Gasless abdomen: decreased swallowing, decreased GI motility, vomiting or gastric decompression.
“Air-fluid levels” reflect decrease in peristalsis
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acute abdomen
contents of bowel got outside intestine as a result of perforation (peritonitis - inflammation of peritoneum)
Symptoms:
- abdominal distention
- tenderness (tenderness is elicited, versus pain)
- tympanic (percussion)
NOTE: medical / surgical emergency
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GI problems - immediate interventions
All same no matter what the problem is:
1. Make baby N.P.O. (nothing by mouth) until you have identified problem and have decided upon intervention
2. Place nasogastric tube to decompress stomach of air and stomach contents (oral gastric tube more likely in newborns since nose so small)
3. Start I.V. to provide fluid maintenance
4. Call surgeons
NOTE: prophylactic antibiotics only if fear necrosis due to lack of blood supply (bowel rotation)
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gastroesophageal reflux
clinically significant conditions that occurs in newborns due to insufficient tone of the gastroesophageal sphincter (GERD)
clinically significant = baby can't grow since spit everything up; won't eat due to pain (arch back and pull away)
mild form = wet burp; pain
Management:
- feed small amounts
- positioning during feeding
- medications to prevent pain (H2 blockers)
- surgery (fundoplication - wrap funds around duodenum)
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esophageal atresia
Esophagus is discontinuous and there is communication between GI and respirtory tracts (malformation that occurs during organogenesis)
Usually accompanied by tracheoesophageal fistula (TEF)
Note: present few hours after birth (early)
MOST COMMON malformation of esophagus
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esophageal atresia - types and signs / symptoms
Presenting signs:
- Drooling
- Immediate vomiting after eating
- Coughing
- Abdomen may be distended or scaphoid
30-40% have associated anomalies, especially VACTERL; can have history of polyhydramnios
Type III B is most common: esophagus comes out of trachea (slide 16)
- belly is distended since air gets into belly (would never want to resuscitate if you knew baby had this since you would blow up stomach)
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VACTERL association
Formerly known as VATER
Present in 25- 30% of children with EA/TEF
```
Features:
Vertebral anomalies
Imperforate Anus
Cardiac defects (PDA,ASD,VSD)
Tracheoesophageal fistula
Renal anomalies
Limb anomalies (most often of radius)
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pyloric stenosis
hypertrophy of muscular layer of pyloric channel; pyloric sphincter has too much tone and contents cannot pass
Does not present right away (2 days - 2 months) - worsens as baby grows and eats more
Signs:
- Seems hungry
- Vomits - FORCEFUL (few minutes after each feeding)
- Gets worse as days pass
- Often presents with dehydration
- Normal stool
- No fever
- No ill contacts
NOTE: would think gastroenteritis (most common cause of vomiting)
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pyloric stenosis - diagnosis and treatment
diagnosis: abdominal US
Treatment:
- Very minor surgery: “Pyloromyotomy” (consists of incising the hypertrophic muscle from the outside to essentially loosen it up)
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bilious vomiting in newborn - significance
Recall: common bile duct enters the intestine at the ampulla of Vater, located 1/3 of the way along the duodenum.
Bilious vomiting implies obstruction DISTAL to the ampulla.
Usual spitting up or feeding intolerance is not bilious; therefore, consider pathologic until proven otherwise
In newborn, – bilious vomiting is considered an EMERGENCY until proven otherwise
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duodenal obstruction
can be: blockage, stenosis, or atresia – don’t need to find out right away; can be partial or complete
Malformation: caused by incomplete re-canalization of gut during organogenesis (making inner tube of lumen forms as solid tube)
- atresia:complete obstruction of lumen
- stenosis: narrowing of the lumen
NOTE: 30% of babes with duodenal obstruction have DS and other anomalies
Presents with:
- vomiting: location will determine if bilious
- abdominal distention: may be present soon after birth (peaks at 24 to 48 hrs)
May pass meconium
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duodenal obstruction - prenatal clues
Polyhydramnios (excess amniotic fluid) since baby cannot swallow as much
SGA (small gestational age)
Often, preterm
Prenatal ultrasound shows “double bubble” (stomach and duodenom)
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duodenal atresia - evaluation and management
Abdomen is scaphoid or distended
Obtain abdominal film
- Newborn xray may show “double bubble” (stomach is first; duodenum is second since it swells prior to atresia)
- Look for dilated stomach, distal gas (if distal gas present, stenosis rather than atresia)
Can also be diagnosed with ultrasound
Management: usual preliminary steps followed by surgical correction
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midgut (jejunum or ileum) obstruction
Can be atresia, stenosis, or malrotation:
Atresia: 50% of all atresias occur in jejunum or ileum
Stenosis
Malrotation/Midgut Volvulus:
- mesenteric attachments are posterior only
- midgut is free to move
- duodenum and proximal colon are fixed
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Malrotation/Midgut Volvulus
During fetal life, intestines normally herniate into the umbilical cord and return to abdomen
Abnormal rotation results in abnormal position, known as malrotation
In addition to obstruction, malrotation can cause a volvulus which compromises vascular system, resulting in necrosis, peritonitis, sepsis and shock - THIS IS A SURGICAL EMERGENCY
- necrotic intestines allow contents to spill out, causing acute abdomen
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Malrotation/Midgut Volvulus - presentation, diagnosis, treatment
Presentation: apparently well child who presents with sudden onset of bilious vomiting
- may occur at any time postnatally but 80% occur in neonatal period (first month)
- initially intermittent
- abdominal distention
NOTE: ALL BILIOUS vomiting in the newborn is Volvulus until proven otherwise!
- This is a surgical EMERGENCY!
Diagnosis: definitive study uses contrast
Treatment: surgical ("Ladd procedure"_
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meconium ileus
peristalsis of intestine stops; viscous, inspissated meconium obstructs the mid-ileum
- baby has not passed meconium (try suppository first to see if it's just meconium plug)
- abdominal distention at or after birth
- associated with Cystic Fibrosis
Diagnosis and Treatment:
- gastrograffin enema
- surgical clean out
Note: untreated can lead to rupture of bowel, acute abdomen, shock, death (meconium ileum with perforation)
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Hirschprung's Disease
Congenital absence of nervous plexuses of the colon
Peristalsis is abnormal in affected segment (skinny), causes functional obstruction with dilated bowel proximally (toxic megacolon)
Presentation
- constipation, delayed stooling, meconium plug (2 DOL)
- abdominal distention
- can have vomiting after meals
- congenital but rarely diagnosed in neonatal period (diagnosed by 4 months)
Epidemiology
- 75- 80% male
- accounts for 25% of all congenital GI obstruct
Treatment and Repair:
- initial enemas to promote stooling
- Laparoscopic or open “pull-through” of colon containing ganglion cells to the anal verge
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imperforate anus
no anus or abnormal
- 75% have fistula to urethra, vagina, or perineum and may pass meconium
Associated with VACTERL, chromosomal, cardiac, and CNS anomalies.
Treated surgically (use temporary measures until baby is a bit older), long term outcome good
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Managing Newborns with Suspected Intestinal Obstruction - Review
1. Make N.P.O.
2. Decompress obstructed area with nasogastric suction
3. Start intravenous fluids
4. Begin radiologic workup
5. Call the surgeons
6. Consider workup for other associated problems
7. Consider starting antibiotics
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use of antibiotics for suspected intestinal obstruction
Although the causes of intestinal obstruction are mechanical rather than infectious, it is often wise to begin antibiotics prophylactically.
Pressure changes and vascular compromise can result in perforation of bowel, spilling contents into peritoneal cavity.
Acute abdomen: Peritonitis, infection of the peritoneal cavity, a severe infection which results in sepsis and shock.
Think about specific situation:
- Volvulus: definitely begin antibiotics
- duodenal atresia and baby is doing fine: probably no antibiotics
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ventral wall defects
Present at birth
Intestine present outside abdominal wall
Risks include motility problems, fluid loss, infection
```
Immediate response:
Cover with saran wrap to prevent fluid losses
NPO
Start I.V.
Start antibiotics
Surgical intervention
```
Two types:
omphalocele
gastroschisis
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omphalocele
Malformation
Failure of intestine to fully return to abdomen during fetal life
ALWAYS associated with MALROTATION
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gastroschisis
Disruption
Caused by vascular accident during fetal life
Dysmotility because has a thick peel on surface as result of contact with amniotic fluid
- worse then omphalacele
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why do newborns become jaundiced - physiology
Jaundice occurs when an infant is hyperbilirubinemic.
- Bilirubin is a by-product of RBC breakdown (after 120 days, RBCs breakdown and release bili which is excreted in stool when healthy)
- in utero, baby is hypoxic which triggers large production of RBCs (hematocrit is higher in newborn v. adult); upon birth this large pool of RBCs is broken down causing jaundice (can be physiologic or pathologic)
- When not healthy, bilirubin pigments build up in liver and are deposited in the skin and mucous membranes, causing the classic yellow or jaundiced appearance of the skin
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jaundice - initial presentation and distribution
Jaundice in the newborn is a generally mild, transient physiologic increase in bilirubin occurring in a healthy, full-term baby
Jaundice first becomes visible in the face and forehead and progresses caudally to the trunk and extremities
- tell newborn is jaundice by blanching skin and looking for yellow tone
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production of bilirubin - general steps
- RBCs broken down; heme is converted to uncongugated bilirubin
- unconjugated bili released into serous where is is tightly (but reversibly) bound to albumin
- unconjugated bili-albumin complex carried to liver
- in liver, bili-albumin complex converted into bilt salt or conjugated bilirubin (enzyme = glucuronic transferase)
- conjugated bili is pumped out of hepatocytes into canalicular (bile duct) system
- either excreted in stool or deconjugated and reabsorbed back into enterohepatic circulation
NOTE: everything before liver is unconjugated and everything after is conjugated (can be released)
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unconjugated bilirubin
Exists in this form before the liver; the fat soluble product of hemoglobin metabolism
NOTE: prehepatic dysfunction can cause this type of hyperbilirubinemia
Binds tightly and readily to albumin in serum; neither is changed by the union
Known as “free bilirubin” regardless of whether it is bound to albumin or not
Unconjugated = Indirect
NOTE: most bill exists in this form in infants
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conjugated bilirubin
Exists in this form after liver; salts of glucuronic or sulfonic acids; water soluble
(essentially)
Conjugated = Direct
Incorporated in to bile acids which act as a detergent to help in digestion of fats.
In a normal newborn the direct bilirubin should be be
163
bilirubin laboratory results (serum)
Total bili: measures all bilirubin fractions in serum
Direct bili measures 90% of conjugated bili.
Ordering “fractionated” bili will get you total and direct values.
Indirect is a calculated value: (total - direct = indirect)
NOTE: bilirubin should be mostly unconjugated (indirect) in serum; indirect should be 90% or greater!
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unconjugated hyperbilirubinemia - causes
too much unconjugated (indirect) bilirubin
Hemolytic (due to rupture of RBCs):
- Physiologic
- Pathologic
- Immune mediated
- Certain enzyme defects
- Pool of blood outside vascular system
Prematurity
Associated with breastfeeding:
- breast feeding jaundice
- breast milk jaundice
Defects in conjugation step:
- Crigler-Najjar
- Gilbert’s
- Asian descent
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hemolytic hyperbilirubinemia (unconjugated)
physiologic: natural response to increased production of RBCs in utero - jaundice occurs in 1st 2 hours and peaks 3-5 days
Pathologic: maternal antibody (IgG) crosses the placenta to attack fetal RBCs
due to blood type; jaundice in first few days
- mom O and baby A, B, or AB
- mom Rh- and bbay Rh+ (rho-gam prevents - anti IgG)
Breakdown of extravascular blood: blood usually a result of bruising / cephalohematoma due to birth trauma (blood trapped b/t periosteum and skull)
G-6-PD deficiency: Sex-linked disorder of cell membranes which makes them vulnerable to hemolysis
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prematurity hyperbilirubinemia (unconjugated)
80% of premature infants become jaundiced
Premature infants conjugate more slowly (liver is not working well yet)
- higher risk for BIND at lower levels of bilirubin
- leaky blood-brain barriers
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hyperbilirubinemia associated with breastfeeding (unconjugated)
1. Breastfeeding jaundice
- caused by inadequate oral intake
- increases enterohepatic circulation
- essentially, dehydration
- occurs on days 2-5
Baby’s hydration is the urgent problem
Mother needs breastfeeding support
- consider supplementation with pumped milk or formula
2. Breastmilk jaundice
- Begins day 4; can peak weeks 2 to 4
- Persists up to 3 months
- Not all breastfed babies get it
- totally benign (don’t interrupt nursing)
Etiology unclear
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hyperbilirubinemia associated with defect in conjugation (unconjugated)
Gilbert's: defect in glucuronyl transferase
- typically, mild jaundice after puberty
- autosomal dominant: family history (parent turn yellow with stress)
Crigler-Najjar Syndrome: severe, often lethal form of hyperbili.
- clinically looks like kernicterus
- autosomal recessive; ccurs in one in one million live births
- virtual absence of glucuronyl transferase enzyme
```
Two Types (I, II).
I: requires lifelong PTX to avoid BIND and liver transplantation
II: treatable with Phenobarbital.
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169
Gilbert's
Unconjugated hyperbilirubinemia
Caused by defect in glucuronyl transferase
- typically, mild jaundice after puberty
- autosomal dominant: family history (parent turn yellow with stress)
170
Crigler-Najjar Syndrome
Unconjugated hyperbilirubinemia
Severe, often lethal form of hyperbili.
- clinically looks like kernicterus
- autosomal recessive; ccurs in one in one million live births
- virtual absence of glucuronyl transferase enzyme
```
Two Types (I, II).
I: requires lifelong PTX to avoid BIND and liver transplantation
II: treatable with Phenobarbital.
```
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causes of conjugated hyperbilirubinemia
Hepatitis:
Inborn errors of Metabolism
Biliary atresia
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infection hepatitis causing hyperbilirubinemia (conjugated)
- infectious agent (Hep B, Rubella, CMV, toxoplasmosis) attaks canicular cells and makes them leaky
- conjugated / direct bilirubin is dumped into system
- can cause blueberry muffin rash
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inborn errors of metabolisms causing hyperbilirubinemia (conjugated)
Galactosemia: inborn error of galactose metabolism
other inborn errors of metabolism can also cause cholestatic jaundice
- Cholestatic jaundice implies that conjugated bilirubin flow is obstructed
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biliary atresia causing hyperbilirubinemia (conjugated)
Congenital absence of all or part of the biliary tree (ducts that drain bile from liver)
- etiology is uncertain, may be viral
- presents weeks 2 to 8 after birth
- light stools (clay color), dark urine, jaundice, weight loss and irritability
Initially treated with Kasai procedure (intestine attached to liver to bypass biliary tree)
- ultimately need liver transplant
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Management of jaundice - History and Physical
- MOC’s blood type / Rh
- family history of hemolytic disease?
- maternal history of infections during pregnancy (Hep B status)?
- Prematurity?
- Medications?
- Baby’s diet history and stooling patterns
Physical findings consistent with intrauterine infections?
- Hepato- or splenomegaly?
- Hydration status
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Management of jaundice - Bilirubin level
transcutaneous or serum levels
In the first week of life, if there is no cause to suspect hepatitis, obtain a transcutaneous bilirubin level
Indications for a bilirubin level:
Baby appears jaundiced
- very subjective
Compelling risk factors for hyperbilirubinemia:
- ABO or rh “set-up" (risk for immune-mediated hemolysis)
- family history to suggest genetic causes
- history of, or signs which suggest viral infection
- prematurity
- Asian
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transcutaneous bilirubin monitor
Inexpensive, non-invasive
Good screening tool however… no good studies to help you interpret values
Requires developing your own guidelines (vary)
Generally, higher levels) of bilirubin are "allowed" over time (not as much concern for higher at 36 / 48 /72 hours of life)
Level will determine if serum bilirubin level is needed - see NOMOGRAM
- value in high intermediate and above = serum
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serum bilirubin values - managment
High risk zone: begin phototherapy
High intermediate:
recheck 6-12 hrs +/- phototherapy
Low intermediate: recheck based on clinical progress
Low risk: no need to follow up
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phototherapy (PTX) - treatment for unconjugated hyperbilirubemia
Blue light changes molecular structure of bilirubin so it is less tightly bound to albumin and more water soluble
- can be eliminated from the body via the kidneys without conjugation
can be under light (on back with sunglasses) or with light blanket
NOTE: DO NOT USE WITH CONJUGATED HYPERBILIRUBEMIA
- se of PTX in conjugated hyperbili results in “bronze baby”, an unappealing discoloration of skin
- consider fractionated bili prior to starting light therapy if there is doubt
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BIND (Bilirubin Induced Neurologic Dysfunction)
Why we watch jaundice carefully and treat!
Associated with UNCONJUGATED hyperbilirubemia
Acute manifestations: acute bilirubin encephalopathy (ABE)
Chronic and permanent sequelae: Kernicterus
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kernicterus
Form of brain damage associated with greatly elevated unconjugated bili; can be prevented with early tx!
Symptoms:
- abnormalities of tone, high pitched cry, arching of back
- smart baby trapped in spastic body
Pathology: Bilirubin staining of basal ganglia and hippocampus (leaky BBB)
- occurred in babes with erythroblastosis fetalis and has become rare since the advent of rho-gam
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newborn skin at birth - what we may see (normal)
vernix
petechiae
lanugo
mottling
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vernix
thick, pasty covering that protects newborn
184
petechiae
when normal: non-blanching lesions secondary to birth trauma or vigorous resuscitation (scalp, rips, and back)
When abnormal: sign of sepsis in infants ("blueberry muffin rash - systemic"
- be concerned when mom has hx of low platelets or infection risk
185
lanugo
downy hair - presents to varying degrees at birth (on shoulder, etc.)
186
mottling (curtis marmorata)
Lace-like pattern of dusky erythema over trunk and extremities.
- Normal in newborns who are cold (disappears on re-warming)
- Can be a sign of poor perfusion in illness
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Cutis marmorata telangiectatica congenita
Rare congenital vascular malformation.
- Usually presents on one limb.
- Does not go away with heat
- Associated with underlying muscular defects (50%).
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transient skin lesions of newborn (birth - 10 days)
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Erythema Toxicum
Milia
Sebaceous Gland Hyperplasia
Pustular Melanosis
Normal Peeling
Sucking Blisters
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189
erythema toxicum
White to yellow papule on a blotchy erythematous base.
- usually start on DOL 1 or 2.
- contain eosinophils - but etiology poorly understood.
- come and go over first 10 days of life (chameleon rash)
- located everywhere except palms and soles.
CONCERNED: if HSV!!
190
Herpes Simplex Virus (HSV)
Neonatal emergency:
- 1% chance of women with a hx of HSV 2 to be shedding virus at time of delivery
- In babies born with neonatal infection, only 30% have a hx of active lesions
- many mom’s don’t even have an active lesion
- 50% risk of transmission if Mom has a primary infection
191
milia
Keratin filled epithelial cysts.
- often mistaken for neonatal acne which does not appear until 2 weeks of life.
- no inflammatory component
- spontaneously resolve
192
sebaceous gland hyperplasia
More yellow than milia.
- caused by maternal androgen exposure.
- spontaneously resolve
193
transient pustular melanosis
Fragile pustular rash that begins in-utero.
- when pustules break they leave behind a white collarette with a central hyper-pigmented macule.
- no inflammatory component.
- pustules usually removed during resuscitation or bath.
194
peeling of skin and sicking blister
normal findings; no lotion of oils if have cracks or fissures - will absorb into babies blood stream
NOTE: yellow stained peeled skin - sign of meconium
195
harlequin phenomenon
Thought to be caused by an immature hypothalmus.
One side red and one side white (symmetric) – changes with position and only lasts temporarily
196
birthmarks
represent an area of excess of one or more of the normal components of skin per unit areas.
- blood vessels, pigment cells, sebaceous glands, epidermis…
197
mongolian spots
pigmented lesions; blue-black macules commonly located over lumbosacral area.
- congenital Dermal Melanocytosis
- most common in Black, Asian and Hispanic infants.
- fade during first or second year of life (most have disappeared by age 6-10)
NOTE: Important to clearly record location of macules as they are easily confused for bruising.
198
cafe au lait spots
irregularly shaped, evenly pigmented, brown macules.
multiple lesions associated with neurofribromatosis.
- measure size and draw location / count # (most individuals with neurofibromatosis have 6 or more spots that are 1.5 cm or greater in diameter)
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congenital vascular lesions: hemangiomas v. malformations
hemangiomas:
- 40% at birth
- common on face; anywhere
- well delineated
- rapid neonatal growth with slow involution
- arterial
malformations (3):
- 99% present at birth (clinically subtle)
- common on limbs; anywhere
- porly circumscribed
- no change in size (grows with child, no involution)
- venous and capillary
Three vascular malformations:
- nevus simplex (salmon patch, macular stain)
- port wine stain
- cutis marmorata
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hemangiomas
Benign neoplasm resulting from rapid proliferation of endothelial cells.
Superficial (strawberry), deep or mixed.
Proliferate for 8-18 months then regress.
50% gone by age 5, 90% gone by age 9 (10% per year).
When to treat: obstruct vision, in diaper area (ulcerate), facial lesions since can disfigure even if regress down road
Note: baby Ben
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nevus simplex
Light red blanching macule on nape of neck (stork bite) or glabella/eyelids (angel kiss).
- 70% white babies, 60% black babies.
- fade with time but always present - more pronounced when flushed.
Note: lacy looking and can cross midline
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port wine stain
Flat dark pink to red macule found on face or limbs.
- typically do not cross midline.
Can be associated with syndromes:
- On face and involving an eye, may be associated with Sturge-Weber syndrome.
- On legs can be associated with Klippel-Trenaunay-Weber syndrome
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when to suspect an infection based on dermal lesion
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Infection must be considered if vesiculobullous or pustular lesions are found in a newborn.
Viral
- Herpes Simplex
Bacterial
- Staphylococcus
- Bullous Impetigo
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Note: most infectious lesion appear in days to weeks after birth
- see HSV and staph (main one) at birth
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care of newborn skin
newborn skin is thinner and has large surface to body ratio
- do not bath often, no soap, no lotions with chemicals
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Colorado Can Do 5 - Breastfeeding (hospital maternity care practices that will help with successful breastfeeding)
1. Infants are breastfed in the first hour after birth.
2. Infants stay in the same room as their mothers.
3. Infants are fed only breast milk and receive no supplementation.
4. No pacifier is used.
5. Staff gives mothers a telephone number to call for help with breastfeeding.
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Breastfeeding: 3 basic things for health care providers to know
nutritional parameters:
- Weight loss (10%)
- Regain weight by day 10
- A teaspoon (5 mL) at a good feed
- Yellow stools at day 5
hand expression:
- good for engorgement, sore nipples
asymmetrical latch:
- nose of baby pointed at nipple; mouth below nipple; a lot more of the lower portion of nipple and areola in babies mouth; nipple should be way back in babies mouth (b/t hard and soft palate); babies mouth is massaging lower breast tissue stimulating more milk; areola and breast tissue is what is massaged by babies mouth
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indications for formula
As a substitute or supplement for human milk in infants whose mothers choose not to exclusively breastfeed
For infants in whom breastfeeding is contraindicated (mom's with HIV)
As a supplement for breastfed infants whose intake of human milk is inadequate to support appropriate weight gain
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composition - breast milk v. formula
very different in composition:
- human milk has hormones, antibodies, growth factor, live cells, etc.
- formula made from cow's milk (whey in breast milk is primarily lactalbumin, in cow’s milk it is lactoglobulin)
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storing breast milk v. formula
Use thawed room temp breast milk within 4-6 hours (formula 2-3).
Use refrigerated breast milk within 48 hours (formula 24).
Do not freeze formula (breast milk can be frozen for 3-6 months).
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why not use cow milk for infants under age of 1?
Infants fed cow’s milk develop anemia
- low iron concentration and not bioavailable
- cow milk protein can irritate bowl and cause intestinal blood loss
Note: higher concentrations of protein, sodium, potassium and chloride
- inadequate essential fatty acids, Vit E and zinc
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preparing formula
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clean water source
add water first
mix according to package instructions:
- powdered: one scoop of powder to 2 oz of water = 20 cal/oz
- ready to feed: shake well
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daily requirements of baby
for growth, baby needs a minimum of 100cal/kg/day
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goals for growth - newborn
Keep in mind initial weight loss up to 10%
- 4-6% DOL #1 2-3% DOL #2
Surpass birth weight by 2 weeks.
- 0-3 months gain 15-30 grams/day
- 3-6 months gain 15-20 grams/day
- 6-12 months gain 10-15 grams/day
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formula feeding - anticipatory guidance
Vomiting or spitting up is common and does not require formula change unless there is inadequate growth
Stools tend to be pasty and brown, occur one to twice/day
Note: constipation with good wt gain is common with formula!
- constipation with slow weight gain may indicate inadequate calories (volume or concentration – check history)
Blood in stool or vomit - reason to change formula
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types of formula available
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Cow’s Milk Formula (Enfamil and Similac)
- Added iron
- Added ARA and DHA
Soy
Hydrolyzed (for babies allergic to milk and soy) - aka hypoallergenic
Kosher
Organic
Specialty (for PKU, renal disease or premature infants)
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who should have soy formula?
Often, babies with cow's milk intolerance also have soy intolerance (35-60%)
1. Parents who are strict vegans
2. A true diagnosis of lactose intolerance (rare in babies)
3. Congenital galactosemia
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milk allergy
allergy to cow milk protein; most common in infants (most outgrow)
- diarrhea, vomiting, failure to thrive, eczema and respiratory symptoms
- colitis – inflammation of mucosa resulting in GI discomfort and blood in stool
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hypoallergenic formulas
Extensively hydrolyzed formulas: cow's milk proteins that are broken down
Amino acid-based infant formulas: contain protein in its simplest form (amino acids are the building blocks of proteins)
Alimentum, Nutramigen, Pregestamil, Neocate
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dacrostenosis
Congenital obstruction of the nasolacrimal duct causing tears to drain out of the eye, onto the face.
- very common; 90% resolve in 1st yr of life (massage and keep clean)
Note: contact ophthalmologist after 12 months
- associated with mucoid discharge from the lacrimal punctum
- not infected but predisposes to infection
Conjunctiva clear, but mucus can trap bacteria causing an associated conjunctivitis with conjunctival injection
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dacrocystitis
complication of dacrostenosis
Infection of the obstructed nasolacrimal duct
- requires antibiotic management and possible surgical opening of the duct
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goopy eye in newborn: differential
dacrostenosis: likely resolve on own
conjunctivitis: thick, pussy discharge; why we do prophylactic eye tx at brith; caused by STIs
periorbital cellulitis: serious complication - can get into orbit and brain
corneal abrasion: scratch eye with nail; red eye that is painful and watery (see eye doc)
congenital glaucoma: thick, pussy discharge
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circumcision
Surgical removal of the foreskin of the penis to expose all or part of the glans for therapeutic, prophylactic, ritual or religious reasons
1999 AAP: Existing scientific evidence demonstrates potential medical benefits of newborn male circumcision; however, these data are not sufficient to recommend routine neonatal circumcision.
2012 AAP: Evaluation of the current evidence indicates that the health benefits of newborn male circumcision outweigh the risks
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benefits of circumcision
easier hygiene
dec. risk of penile cancer
dec. bacterial colonization
- UTIs, ballantitis (infection of foreskin), phimosis (unretractable foreskin)
dec. risk of STIs (HPV and HSV; likely syphilis; 40-60% HIV)
- none for Gonorrhea or chlamydia
- protection not seen for homosexual males
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paraphimosis
foreskin gets stuck behind the glans and acts as a tourniquet
- surgical emergency
Recurrent balanitis can lead to phimosis
Retraction of a phimosis can result in paraphimosis
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circumcision techniques
Plastibel: uses clamp and string
Gomco: pull up foreskin and use instrument to cut
Mogen: blind cut with scalpel
All rely on crushing of tissue and removal of excess skin
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Complications:
Bleeding
Infection
Injury
Cosmetically unpleasing
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which religion requires circumcision
Jewish (day 8)
| Muslim
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SIDS - Back to Sleep
The sudden death of an infant under 1 year of age, which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination ofthe death scene, and review of the clinical history.
Phenomenon of unknown cause
Leading cause of death - infants 1 month - 12 months (beyond neonate)
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SIDS - risk factors
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Prone sleep position
Sleeping on a soft surface
Maternal smoking and drug use during pregnancy
Second-hand smoke
Overheating
Late or no prenatal care
Young maternal age
Preterm birth and/or low birth weight
Male gender
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pacifiers
Offer a pacifier at nap time and bedtime.
- helps to reduce the risk of SIDS.
- If you are breastfeeding, wait until breastfeeding is going well before offering a pacifier (3 to 4 weeks)
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carseats
Infant: children should face rear until at least 1 and 20 lbs (new recommendation is at least 2)
Convertible: forward-facing until age 4 / 40 lbs
Booster: until 4'9" (8-12)
Backseat: until age 13
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umbilical cord
Baby’s lifeline; i.e., attachment to placenta
- contains 2 arteries and one vein
Clamping: current trend 30 sec to few min after to give any more blood
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cord care
wash cord when baby gets first bath, then allow to air dry
keep diaper folded beneath the cord to keep it dry
Alcohol - used in hospital
Delays cord separation by sterilizing environment (local immune reaction to bacteria helps cord to separate)
Do not put baby into a bath tub until after cord falls off, usually 2 to 3 weeks.
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omphalitis
infection of umbilical stump
Erythema surrounding cord gets progressively worse; thick discharge, foul smell, hot and painful to touch
Dangerous – direct line back to vena cava: peritonitis; babies can get septic
Treatment: full septic workup; IV antibiotics for a week
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umbilical granuloma
small red mass of scar tissue that stays on the belly button after the umbilical cord has fallen off.
- this granuloma will drain a light-yellowish fluid.
usually self-limited, but healing can be hastened with the application of silver nitrate
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umbilical hernia
type of ventral hernia (covered by skin)
- Intestine protrudes through defect in abdominal wall left by the umbilical cord.
Surgery if persist beyond 4 yrs
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birth trauma
molding of head (recovers quickely)
- breech flat on top
- vaginal cone-shaped
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hemorrhages in different spaces of skull
caput succadaneum:
subgaleal hematoma: in large potential space under galeal - can leave to hemorrhage; changes position with gravity
cephalohematoma
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caput succadaneum
collection of edema in scalp; just below skin
- results from banging of baby’s head on mom’s pelvis
- crosses suture lines
- resolves in 1 to 2 days
- completely benign
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cephalohematoma
Collection of blood beneath the periostium which surrounds the bones of the skull (usually parietal)
- limited by suture lines
- results from pounding head on mom’s pelvis during labor
- resolves over days to weeks
- risk of developing jaundice as pool of blood is broken down
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subgaleal hemorrhage
Bleeding into large potential space between the scalp and skull
- result of shearing forces from vacuum or suction tearing bridging vessels
- can be quite dangerous as a large volume of blood can be lost, causing shock, anemia
- feels boggy / water balloon
NOTE: dependent on gravity
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shoulder dystocia
Shoulders get stuck during delivery
Risk factors: big baby, small pelvis
Erb's Palsy: Stretch injury of brachial plexus
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Erb's Palsy
Stretch injury of brachial plexus
Causes characteristic “waiter’s tip” flaccid position of arm
Resolves distally to proximally over course of days to weeks.
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fractures of baby during birth
Most commonly fractured bone at delivery: clavicle
Second most common: humerus
Third: skull
Multiple fractures or fractures of other bones would lead one to consider diagnosis of osteogenesis imperfecta
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How long does AAP recommend mom's exclusively breastfeed
one year; introduce solids 4-6 months
| - as long as mom and baby can
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vast majority of early onset sepsis will present by how many hours of life
12-24
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medicine and desired dosing schedule for prevention of GBS sepsis
Penicillin – at least 2 doses 4 hours apart.
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At this number or less,
an ANC (absolute neutrophil count) would be considered
abnormal
1750
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upper limit of normal for an I/T ratio
0.2
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length of full term gestation
38-42 weeks
Note: 37 treat as term with high level of suspicion
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how to read a chest x-ray (CXR)
RIP ABCDE
R: rotation (check clavicles)
I: inspiration (9 ribs)
P: penetration (correct amount of x-ray material; should see b/t vertebrae)
A: should see two bronchi splitting from airway
B: fractures of anomalies
C: rt and lt heart borders
D: diaphragm borders should be well-defined
E: everything else (lines, leads, foreign bodies)
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APGAR Score
reported 1 and 5 minutes after birth; most effective for term babies; expression of infant's physiological condition and includes subjective components
A: appearance
- blue or pale = 0
- acrocyanotic (hands, lips blue) = 1
- pink = 2
P: pulse (HR) 80-160 BPM
- absent = 0
- 100 = 2
G: grimace / reflex irritability (responce to stimulation)
- none = 0
- weak response to rub = 1
- active withdrawal or cry = 2
A: activity (tone)
- limp = 0
- some flexion = 1
- active motion = 2
R: respiratory, 30-60 breaths/min
- absent = 0
- weak cry/hypoventilation = 1
- good, crying = 2
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Tetralogy of Fallot
MOST COMMON CYANOTIC CHD
A set of congenital cardiac defects including:
- overriding of ascending aorta over ventricular septum and receives venous as well as arterial blood (due to hole in septum)
- ventricular septal defect
- pulmonic valve stenosis (obstruction of RV outflow) - valve is pushed over and compromised
- right ventricular hypertrophy due to inc. pressure since blood can't get through valve; considered part of the tetralogy although it is reactive to the other defects (syn: Fallot tetrad)
Note: degree of cyanosis depends on degree of stenosis of the pulmonic valve
Note: "boot-shaped" heart
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ventricular septal defects (VSD)
acyanotic heart lesion
MOST COMMON CHD
hole in either atrial or ventricular septum; blood will flow in direction of greatest to least pressure, which changes from fetus to newborn
note:
- if on own, will not present with hypoxia since blood goes form lt to rt and to lungs to get oxygenated
- if part of tetralogy of fallot, this is a mixing lesion that presents with hypoxia
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hyperoxitest
Most sensitive tool for differentiating between primary pulmonary and cyanotic congenital heart disease
- measure pO2 by blood gas in room air
- place baby on 100% oxygen for 10 minutes, then re-check blood gas
- note: pulse ox often used, easier but less accurate
Results: a patient with primary pulmonary disease will usually dramatically increase saturation when given oxygen; cardiac etiology will have no improvement
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most common cardiac lesions in newborn (cyanotic vs. acyanotic)
Cyanotic - 5 T's with a P and H
- Transposition of the great vessels
- Truncus arteriosus (single arterial vessel arises from heart, instead of separate aorta and pulmonary artery)
- Tricuspid atresia (absence of tricuspid valve on rt side of heart)
- Tetralogy of Fallot
- Total anomalous pulmonary venous return (TAPVR) (pulmonary viens do not empty into LA)
- Pulmonary atresia / stenosis (passage is closed, narrow, or absent)
- Hypoplastic left heart
Acyanotic
- Patent ductus arteriosus
- Large septal defects
- Critical aortic stenosis
- Coarctation of the Aorta
- Hypoplastic left heart
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definition of neonate
period of birth to 28 days old
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partial pressure of oxygen
partial pressure of any gas is a measurement of how much gas there is in any environment (e.g. liquid, room of air)
- changes with altitude
- changes in fetal lung during transition
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percent saturation
% saturation of oxygen in air is 21% regardless of altitude
- the number of molecules of oxygen are fewer as altitude increases but the percentage of oxygen molecules to total molecules in air is always 21%
% saturation of oxygen in blood - percentage of red blood cells are carrying oxygen
- measured by a pulse oximeter
- this can change with blood
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how can you trust you have an accurate pulse Ox reading
wave-forms on machine and pulse matches the one you took
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pressure changes during transition and effects on shunts
Increase in pO2 in blood when baby begins to breathe air
- dilatation of vessels in pulmonary bed drops pulmonary pressures; therefore, right sided pressures become lower than left (functional shunt gone)
- constriction (closure) of ductus arteriosus
Systemic pressure increases as a result of cutting off umbilical circulation (to and from placenta) with result of increased volume elsewhere
Foramen ovale: pressure effect of having LA pressures greater than RA pressure
Ductus venosus closes because there is no longer flow through it
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three types of operative delivery and risks of each
Cesarean section: - retained lung fluid
- laceration of the fetus
- surgical complications
- prolonged recovery for mom
Forceps assisted birth:
- skull fractures (rare)
- facial nerve palsy (heals quickly / good prognosis)
Vacuum assisted delivery: shearing forces on the scalp
- subgaleal hemorrhage: large potential space where baby can bleed out (extradural hemorrhage) - why we say these can be dangerous (shock)
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what does not cross placenta (hint: glucose-related)
insulin
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benign murmurs (3 common) - common during transition / closing of shunts
Pulmonic flow murmur or “peripheral pulmonic stenosis”
- MOST COMMON
Physiologic ductus arteriosus
Tricuspid Jet
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ways to evaluate newborn
fetal echocardiogram: only most severe cases of CHD can be determined (more accurate at 18-20 weeks)
- most useful for congenital heart lesions, but very expensive!
blood pressure (4 limbs): difference b/t rt arm and leg is indication for coarctation of aorta
pulse oximetry (done as screening test; baby can be low on O2 saturation even if color is good)
chest x-ray: useful for signs of CHF (enlarged heart or pulmonary edema)
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transitional period for newborn
first few hours after birth; period of many changes in the physiological makeup of the newborn, including conversion of cardiac and pulmonary systems to extrauterine life
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risks for premature babies
meconium aspiration syndrome (MAS)
Hyaline Membrane Disease/Respiratory Distress Syndrome (RDS)
patent ductus arteriosus
