1. health and fitness
2. disease
3. cancer

Notes compiled for Pediatrics
Reproduction
(Med I, Block 4, RP)
Contents
Class number
Class name
Type
Department
Instructor
RP010
Development of Genito-Urinary
System
Embryology of the GU system
Congenital anomalies and
benign conditions of the Vulva
and Vagina
Congenital anomalies and
benign conditions of the Uterus
and Cervix
Congenital anomalies and
benign conditions of the ovaries
and tubes
Amenorrhea, Oligomenorrhea
and Hyperandrogenic disorders
Perinatal Genetics
Neonatal Recussitation and
assessment
Infections in Pregnancy and the
Neonate
Perinatal Infections and HIV in
Pregnancy
L
AN
Dr. M Torchia
A/GLP
L
AN
RP
Dr. M Torchia
Dr. M Morris
L
RP
Dr. M Morris
L
RP
Dr. M Morris
L
RP
Dr. M Morris
L
L
GN
RP
Dr. B Chodirker
Dr. S Dakshinamurti
L
ID/RP
Dr. J Embree
L
ID/RP
Dr. J Embree
RP011
RP015
RP016
RP018
RP029
RP049
RP051
RP062
RP063
RP 010/KD 2
Dr. M.G. Torchia
Department of Surgery
Lecture Notes
Summary of Developmental Facts
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kidneys are unique in their development - progression of more and more complex
“kidneys” as the embryo/fetus grows and develops
urinary and genital systems come from a common source - intermediate mesoderm
parts of one renal system are incorporated by another during development while others
are lost through apoptotic processes
differentiation, development and growth of many structures are dependent on the
interaction between epithelial and mesenchymal cells
most sex related structures begin as indifferent in structure and under the influence of
hormones and factors differentiate into appropriate male and female structures
the urinary system forms before the gonadal system
Enveloping of the yolk sac is important for the development of the bladder, GI tract etc.
“Renal Systems”
Figure 13-6 Cloaca (formed from the enveloping of the yolk sac) Moore and Persaud
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Pronephros
o
o
o
o
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Epithelial cords differentiate from intermediate mesoderm (day 22)
Pronephric ducts begin to grow down toward the cloaca and has a single nephron
Pronephros in lower animals and fish - find hematopoietic cells
Pronephric cells disappear through the process of apoptosis
Mesonephros
o Pronephric ducts stimulate mesoderm - mesonephric tubules (cranial 4-6 pairs)
o Later mesonephric tubules condense from mesoderm and are composed of
 vascular glomerulus within an epithelial capsule
o Lumen is complete and mesonephric (wolffian) duct connects to cloaca (28 d)
o Urinary function is unclear but in fish and amphibians the mesonephros is capable
of producing a filtrate (no need to conserve water so no concentrating)
o New evidence in humans that yolk sac hematopoietic cells are only transient
while the definitive, long lived adult system hematopoietic cells are found in the
aortic-gonadal-mesonephric region
o Mesonephros is chickens has been shown to be necessary for limb development
o Leftover mesonephric tissue can end up as lesions in the wall of cervix, prostate,
renal pelvis and may be falsely interpreted as adenocarcinoma due to their tubule
Development of the Genito-Urinary System
like structures mimicking glands.
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RP10/KD002
Metanephros (figure 13-6)
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Mesonephric duct forms a ureteric bud (epithelial cells) that grows and
branches (approximately 15 times) into surrounding intermediate
mesoderm (30-34 d)
Buds become the collecting ducts
Inductive interactions between mesoderm and epithelium result in
formation of the metanephros (both must be present for normal
development)
Mesoderm condenses into metanephric blastoma which forms the renal
tubules
Together mesoderm cells, epithelial (bud) cells and ingrowing vascular
endothelial cells from the dorsal aorta (blood supply) form the nephrons
Nephrons start out as rounded group of cells to a comma shaped hollow
and then into an S-shape due to growth and cell differentiation
Portion of nephrons most distal to tubule forms Bowman‟s capsule around
glomerulus while proximal portion of the S shape forms proximal and
distal convoluted tubule and Loop of Henle
There are about 15 generations of nephrons formed with the proximal
maturing faster
While sets of nephrons are forming, kidney is enlarging, ducts enlarge and
form pelvis and calyces (major and minor based on generation of tubule)
to guide urine from kidney to bladder
Kidneys are lobulated in fetus but lobulations disappear soon after birth
Position of kidneys
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Move from pelvis to abdomen due to caudal growth of embryo (4th lumbar to 1st lumbar
to 12th thoracic) with a rotation from ventral facing to anteromedial - brings them
together with adrenals
Retroperitoneal
Vascular lobes of kidney (typically 5) are originally fed from segmental arteries off the
aorta and are usually reduced to a single artery (75% of patients)
Accessory Renal Artery: end arteries
Autosamal recessive polycystic KD: rare, bilateral, 100‟s small uniform cysts; lung hypoplasia
(oligohydramnios); transplant needed; many cysts in the parenchyma, few glomeruli; massive,
non-functional kidneys
Multicystic Dysplastic KD: large cysts within the kidneys; 85% unilateral, the cysts slowly
progress through adulthood (not as life-threatening as the previous condition)
Development of the Genito-Urinary System
RP10/KD002
Horseshoe Kidney: if the budding is close together they end up in the midline in the pelvis
Duplicate Ureters
Ectopic (pelvic) Kidney: one kidney remains in the pelvis area
Urinary Bladder
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Formed during division of the cloaca by the urorectal septum (between hindgut and
allantois) during week 6-7
Cloaca is divided into rectum and urogenital sinus also dividing the cloaca membrane
into anal membrane and urogenital membrane
Area of fusion of urorectal sinus, lateral body folds, and cloacal membrane is the
perineum
Allantois base expands to form the transitional epithelium of bladder while distal ends
forms urachus (median umbilical ligament - bladder to umbilicus)
Other layers of bladder form from mesenchyme
Growing bladder incorporates mesonephric ducts and proximal ureteric buds ending up
with separate openings for both in bladder (figure 13-18)
Area where mesonephric ducts enter elongates and forms urethra
Distal urethra (male only) forms from endodermal downgrowth from surface of penis
Urine
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During changeover from mesonephros to metanephros, amniotic fluid constituents
change with an increase in creatinine, γ-glutamyltransferase, β-2-microglobulin (10-11
weeks)
Urine is excreted into amniotic cavity forming major portion of amniotic fluid
Renal functioning before birth to remove metabolic waste from blood not „necessary‟ due
to placenta
Oligohydramnios (too little fluid) - urethral obstruction, renal agenesis - lung hypoplasia
Polyhydramnios (too much fluid) - usually due to GI obstruction/no swallowing;
premature membrane rupture
Genital system
Germ cells
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Form in posterior wall of yolk sac ( 24 d) and are recognizable by size and alkaline
phosphatase content
Migrate through hindgut and dorsal mesentery (move by ameboid movement, tissue
displacement, and cytoplasmic linkages)
Migration stops as cell reach developing gonadal ridges (5th week)
Number 1000-2000
Aberrant locations form germ cells that survive may produce teratomas
Development of the Genito-Urinary System
RP10/KD002
Gonads
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Form along ventromedial border of mesonephros (cranial portion of mesonephros
becomes the primordia of adrenal cortex - caudal becomes genital ridges (5th wk)
Genital ridges of male/female are indifferent and only under influence of the Sry gene (Y
Xsome, testes-determining factor) and mesonephros signals (which may be a switch for
other genes) does differentiation occur
o Testes
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Testes develop quicker ovaries
When germ cells reach genital ridges, epithelial cells in the ridges
(coelemic) move inward forming primitive sex cords - testis also attract
endothelial and myoepithelial cells from mesonephros
By 6 weeks testes show cell differentiation leading to formation of tunica
albuginea (connective tissue), seminiferous tubules
By 8 weeks Leydig cells within testes synthesize testosterone and
androstenedione but stop this production by about week 17/18 until
puberty
By 8 weeks the Sertoli cells produce Müllerian inhibiting substance
causing involution of the female genital ducts
o Ovaries
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Absence of Sry and therefore, testosterone, leads to formation of ovary
Germ cells must reach genital ridge or “primitive streak ovaries” form
Interior structure is thought to be formed in a similar way to testes
From the time of entry into the genital ridge to about 120 days oogonia
undergo mitosis and gradually begin to undergo first meiotic division to
become oocytes (signals possibly from mesonephros) but stop
development at prophase of 1st meiotic division
Over fifty years may pass until some oocytes complete meiosis resulting
in increased incidence of abnormalities
Sexual duct system
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At the indifferent stage mesonephric (Wolffian) duct and paramesonephric (Müllerian)
ducts along mesonephric ridge
Paramesonephric ducts terminate at urogenital sinus caudally and coelomic cavity in a
funnel shape cranially
o Males
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Müllerian inhibiting substance causes paramesonephric duct cells to undergo
apoptosis leaving only tiny identifiable terminal portions
Development of the Genito-Urinary System
RP10/KD002
 Testosterone causes mesonephric ducts to differentiate into ductus deferens
 Accessory sex glands form from epithelial outgrowth of ducts (seminal
vesicles, prostate, bulbourethral glands) through epithelial - mesenchyme
interaction and androgens
o Female
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Without testosterone the mesonephric ducts regress
Cranial paramesonephric duct become uterine tubes with open fimbriated ends
Caudal end, the paramesonephric ducts approach and fuse forming uterus
Vagina thought to form by the most caudal mesonephric ducts contributing
cells and inducing other changes in surrounding tissues
Descent of Testes
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Testes are retroperitoneal
Three phases to descent
o Enlargement of testes and regression of mesonephric kidneys
o Regression of paramesonephric ducts - descent to inguinal ring
o Testosterone + gubernaculum (mesonephric ligament) - into scrotum
(7th month to birth)
External Genitalia
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Indifferent initially - derived from mesoderm tissue around cloaca forming a
genital tubercle flanked by a pair of genital folds with pair of genital swelling
farther lateral
o Males
 Dihydrotestosterone influences elongation of genital tubercle to
form penis, genital swelling to form scrotal pouches
 Groove on underside of penis formed from genital folds, become a
groove continuous with urogenital sinus, and closes to form penile
part of urethra
 Urogenital sinus closes and forms prostatic part of urethra
o Females
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Causes of Intersex:
Without action of dihydrotestosterone genital tubercle forms
clitoris, genital folds become labia minora, genital swellings
become labia majora
Urethra develops from cranial part of urogenital sinus (i.e.
prostatic urethra)
Development of the Genito-Urinary System
RP10/KD002
o Ovotestes: rare; have both testicular and ovarian tissue
o Congenital adrenal hyperplasia: XX; pseudo-hermaphrodites; enzymatic error  adrenal
gland cannot produce cortisol  thereofore pumps out more and more androgrens 
masculization due to more male phenotypic structures
o Androgen insensitivity syndrome: XY; testosterone receptor error; again it‟s a pseudohermaphrodite; there is a fight between the male and female phenotype
Reproduction 010 and 011 Study Guide
Reproduction 010 L
Development of the Genito-urinary System 2
Learning Objectives
1. Describe the role of the intermediate mesoderm in the development
of the urinary system.
2. Discuss the development of the three sets of human excretory
organs, with special emphasis on the permanent kidneys.
3. Describe congenital abnormalities relating to positional changes of
the kidneys during development of the renal vessels.
4. Explain the formation of the urogenital sinus, urinary bladder and
urethra.
5. Briefly discuss the following: duplication of the upper urinary tract,
renal ectopia, horseshoe kidney, congenital polycystic disease of the
kidney, urachal malformations and exstrophy of the bladder.
Learning Outcomes for Reproduction
The student will be able to provide counseling and care for a patient with
congenital anomalies of the reproductive tract, including counseling on
future fertility and sexual function.
Reproduction 011 LP
Embryology of the Genito-urinary System
Learning Objectives
1. Understand how the three sets of excretory organs develop and
change.
2. Describe the process of nephrogenesis (development of nephrons).
3. Describe the partitioning of the cloaca and the derivatives formed
from the urogenital sinus.
4. Describe the development of the gonads and genital ducts.
5. Describe the formation of external genitalia.
6. Relate the effects on the uro-genital system to normal and deficient
excretion of testes-determining factor, mullerian inhibiting
substance, and testosterone.
7. Understand the basic principles involved in the histogenesis of the
adrenal glands.
8. Describe the pathogenesis of urogenital defects including renal
agenesis, ectopic kidney, horseshoe kidney, exstrophy of the bladder,
intersexuality, cryptorchidism, and inguinal hernia.
Text: Hacker and Moore Chapter 3 pages 20-28.
Key Study Points
A sound understanding of the normal anatomy and development of the
genito-urinary tract is an important cornerstone for understanding clinical
problems in caring for those with congenital abnormalities or disease
processes in the genito-urinary tract.
The urogenital system develops from the:
 Intermediate mesoderm
 Mesothelium lining the abdominal cavity
 Endoderm of the urogenital sinus.
The urinary system begins to develop about 3 weeks before the genital
system is evident. Three successive kidney systems develop:
 The pronephri which are vestigial and nonfunctional
 The mesonephroi whihc serves as temporary excretory organs.
 The metanephros which become the permanent kidneys.
The metanephri or permanent kidneys develop from 2 sources:
 The metanephric diverticulum or ureteric bud which gives rise to the
ureter, renal plevis, calices and collecting tubules.
 The metanephric mass of intermediate mesoderm which gives rise to
the nephrons.
 The kidneys develop in the pelvis but migrate up during normal
development.
 Abnormalities in development of the metanephros and
paramesonephric ducts can accompany each other for example in
patients with a left hemi-uterus and an absent right kidney.
For reproduction the embryology can be divided into:
1. Development of the external genitalia
2. Development of the internal genitalia
3. Development of the ovaries and testes.
The reason for this division is simple.
 Each of these has a separate origin; clinically this means that
abnormalities in the different areas are usually not related. For
example abnormalities in development of the uterus are not
usually accompanied by abnormalities of the external genitalia
or abnormalities of ovarian development.
 The appearance of the external genitalia is heavily influenced
as well by hormonal stimulation in utero, an abnormality of the
external genitalia may actually be endocrine in origin (for
example testicular feminization or congenital adrenal
hyperplasia) and not be related to any abnormality in the
embryologic development.
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Embryos are unisex on visual inspection until ~ 7 weeks
gestation.
Female genitalia are readily distinguishable by 12 weeks and
visible on ultrasound (as absence of a phallus at 18-20 weeks)
The urogenital sinus development results in a
i. Small vaginal contribution (likely the lower third but
controversial)
ii. Hymen
iii. Skene’s glands
iv. Bartholin’s glands
v. Prostate, prostatic utricle, Cowper’s gland in male
The medial urogenital fold results in development of clitoris,
prepuce of the clitoris and the labia minora (penis in male)
The lateral genital folds result in development of the labial
majora (Scrotum in male).
See next page for image of the adult vulva and try and compare the
structures.
Think about what an abnormality of central fusion of the urogenital folds
would look like. We see this in patients who are born with bladder exstrophy,
an example of failure of midline fusion. They will have a normal vagina past
the lower third, a normal cervix and normal uterus.
Internal Genital Development
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The upper vagina, cervix, uterus and fallopian tubes are formed from
the paramesonephric (Mullerian) ducts.
The male homologous structure is the hydatid testis.
Paramesonephric development will occur at the expense of
mesonephric development in the absence of the Y chromosome.
o With a Y chromosome present mullerian inhibiting substance is
produced and the mesonephric duct develops instead.
Female sexual development does not depend on the presence of
ovaries or hormones, in contrast to the male who needs the
testosterone production to develop normally.
Most anomalies of the uterus and vagina result from abnormal fusion
of the paramesonephric ducts.
Early embryologic development of the genital tract and vaginal
plate.
o PD= paramesonephric duct
o MD= mesonephric duct
o US= urogenital sinus
o MT=mullerian tubercle
o UVP=utero-vaginal primordium
o VP= vaginal plate.
Ovaries:
 At 4 weeks post-conception thickening of coelomic (peritoneal)
epithelium on the ventro-medial surface of the genital ridge
occurs.
 A bulging genital ridge is subsequently produced by rapid
proliferation of the coelomic epithelium an area that is medial but
parallel to the mesonephros.
 After 5 weeks projections from the germinal epithelium extend
into the mesenchyme to form primary sex cords.
 Definite ovarian characteristics do not appear until 10-12 weeks.
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At 3 weeks large primordial germ cells appear intermixed with
other cells in the endoderm of the yolk sac wall of the primitive
hindgut.
These germ cell precursors migrate along the hindgut dorsal
mesentery and are all contained in the mesenchyme of the
undifferentiated urogenital ridge by 8 weeks.
The oogonia are incorporated into the cortical sex cords of the
genital ridge.
The first histologic evidence of follicles is seen at ~ 20 weeks with
germ cells surrounded by flattened cells derived from the cortical
sex cords/. These cells are recognizable as granulosa cells of
coelomic epithelial origin and theca cells of mesenchymal origin.
Their origin is separate from the paramesonephros and urogenital sinus,
abnormalities in the ovaries will be independent of these systems.
Clinical cases:
1. A 19-year-old female presents with primary amenorrhea. She has a
mosaic XO/XX chromosome pattern. Serum estrogen levels are low
and breast development is absent. (Turner’s syndrome) Would you
expect her internal genitalia to be normal?
2. A 16-year-old female presents to the clinic with primary amenorrhea.
She has normal female external genitalia but a small blind vagina. She
does not have any axillary or pubic hair. Her chromosome pattern is
XY. What has happened here?
3. A 20-year-old woman comes to see you about her future fertility. She
was born with bladder extrophy and has had multiple surgeries with
construction of a continent bladder stoma. She is sexually active
without difficulty and is on an oral contraceptive for family planning.
Answers on next page.
Answers:
1. Her internal genitalia would be normal but would be small as her
ovaries may not have been able to make sufficient estrogen to
complete growth of the uterus that occurs after onset of puberty.
2. This is a case of complete androgen insensitivity. The testes would be
normal and healthy and able to produce mullerian inhibiting substance
but the tissues in this disorder do not respond to testosterone. The
male appearance of external genitalia is dependant on testosterone
action.
3. Bladder extropy is a severe developmental abnormality of the
urogenital sinus. AS the internal genitalia develop from para
mesonephric ducts they should not be affected. Her fertility would be
normal except for the possibility that some of her surgical procedures
may have interfered with tubal patency. She also probably wants to
know the risk of her infant being affected by the same disorder.
Learning Objectives:
Reproduction 015
Congenital Anomalies and Benign
Conditions of the Vulva and Vagina
Congenital abnormalities of the vulva
• Congenital adrenal
hyperplasia in a
female fetus.
• Most important to
recognize clinically in
the newborn period as
can be life
threatening.
Congenital abnormalities of the vulva
• Vulva
1. Describe the congenital abnormalities of the vulva
and outline the clinical importance of the differential
diagnosis.
2. List 6 common structural and benign conditions of
the vulva.
3. Describe 2 types of vulvar trauma.
4. Describe 6 common benign epithelial conditions of
the vulva.
Congenital abnormalities of the vulva
• Very important to deal with at birth as gender
assignment can be difficult.
– Sensitivity and avoidance of hasty decisions
important.
• Careful physical examination, pelvic
ultrasonography, hormonal studies, buccal
smear, karyotyping and consultation
necessary.
Benign Conditions of the Vulva: Noninfectious
• Female pseudohermaphroditism
– Virulized female.
– Caused by masculinization in utero.
• Male pseudo hermaphroditism
– Inadequately virulized male.
– For example in androgen insensitivity.
• True hermaphroditism
– Very rare, needs both ovarian and testicular material.
• Labial agglutination
• Thin atrophic labia minora
adhere if irritated or
traumatized.
• Treatment with topical
estrogens.
• Good local care to prevent
recurrences.
1
Benign Conditions of the Vulva: Noninfectious
• Fox-Fordyce Disease
• Epidermal inclusion cysts and sebaceous cysts.
– Pruritic raised yellowish retention cysts
•
•
•
•
Benign Conditions of the Vulva: Noninfectious
Often inflamed
Can occur in axilla, mons, or labia
Keratin plugged apocrine glands.
Treatment difficult.
Clinical Case
– Located below the epidermis
– Mobile, nontender, spherical and slow growing.
– Excision if symptomatic.
Benign Conditions of the Vulva: Noninfectious
• Vulvar varicosities
• 7 year old female with
a 1 year history of
painless swelling on
vulva, previous history
of straddle injury to
the area.
• Diagnosis?
• Inclusion cyst.
• More common multiparous women.
• Urethral caruncle
– Small fleshy outgrowths of the urethral mucosa.
• In children results from prolapse of mucos.
• In postmenopausal women occurs when
hypoestrogenic vaginal mucosa contracts away from
urethral mucosa.
Benign Conditions of the Vulva: Noninfectious
• 4 year old with history
of urinary frequency
and dysuria, MSU
showing no growth
• Diagnosis?
• Urethral prolapse
Benign Conditions of the Vulva: Noninfectious
• Vulvar vestibulitis
– Inflammation of one or more of the minor
vestibular glands.
– Severe introital dyspareunia
– 1-4mm erythematous dots that are very tender
when touched with a Q-tip.
– Difficult to treat, some response to
corticosteroids.
2
Benign growths of the vulva
• Lentigo and nevi can be found on the vulva and may
need to be biopsied to exclude the possibility of
melanoma.
• Fibromas
• Form in deeper connective tissue of the vulva and may become
large requiring excision.
Benign growths of the vulva
• Hidradenoma
– Apocrine gland tumor
• Neurofibroma
– Associated with Von Recklinghausen’s disease
• Angiomata
– Small cherry angioma can appear during life, larger
congenital angiomas require more complex investigation
and possibly surgery.
• Lipomas
• are slow growing tumors composed of adipose tissue and may
require excision.
Vulvar trauma
• Straddle injuries
• Female genital mutilation.
• Obstetric injuries
Epithelial Conditions of the Vulva
•
•
•
•
Squamous cell hyperplasia
Lichen sclerosis
Lichen planus
Common skin conditions appearing on the
vulva
• Eczema
• Psoriasis
• Pemphigus
Management
Atrophic and hypertrophic vulvar dystrophies
• Biopsy
• Biopsy
• Biopsy
• Cannot visually rule out a premalignant or malignant
lesion in an adult!
• Topical corticosteroids mainstay of therapy.
3
Contact Dermatitis
Vulvar Symptoms
• Lichen sclerosus
• Thin atrophic epithelium on biopsy
• Symptoms controlled by application
of steroid cream to affected area
• Erythema and burning, exam can also reveal edema
and excoriations in severe cases.
• Treatment;
–
–
–
–
Learning Objectives:
1. Describe 2 congenital abnormalities of the vagina
and outline their clinical significance.
2. Describe 5 structural and benign conditions of the
vagina.
3. Describe 2 causes for vaginal trauma and outline
the treatment.
4. Describe one functional disorder of the vagina.
Congenital abnormalities of the Vagina
• Canalization abnormalities
– Imperforate hymen
– Transverse vaginal septum
– Upper genital tract normal
• Mullerian associated anomalies
– Longitudinal vaginal septum
– Vaginal agenesis or atresia.
– Often associated with uterine and cervical anomalies.
Embryonic Remnants
• Gartner Duct cysts
– Thick walled soft cysts resulting from mesonephric
remnants(vas deferens , seminal vesicle in the male)
– Can vary in size from 1-5 cm.
– Usually found on the anterior and lateral walls
high in the vagina or laterally lower in the vagina.
– Excision if symptomatic
Biopsy of any thickened or white areas.
Removal of the irritant
Topical mild or moderately strong corticosteroids
Antihistamines and bland emollients.
Structural and Benign Conditions
•
•
•
•
Urethral diverticula
Inclusion cysts
Bartholin duct cyst
Loss of pelvic supports:
• Cystocoele
• Rectocoele
• Enterocoele.
4
Bartholin duct cyst
Vaginal Trauma
• Commonest cause
sexual assault
• 1-year-old female
brought to emergency
department after a 2
day history of vaginal
bleeding.
Dermtologic conditions
• Condyloma accuminata
• Herpes simplex virus
• Lichen planus
Vaginismus
• Painful involuntary contraction of the vaginal
introital and levator ani muscles.
– Can preclude or prevent vaginal penetration
during coitus, pelvic examination or tampon use.
– Sexual dysfunction clinic after ruling out pathology
that is treatable.
5
7/22/2009
Objectives
Reproduction 016
Congenital Anomalies and Benign
Conditions of the Uterus and Cervix
Objectives
3. Describe 2 common benign neoplastic lesions of the cervix.
a. Define Nabothian cyst
b. Endo and ectocervical polyps
4. Define endometrial hyperplasia and outline its risk
factors.
5. Outline a treatment plan for a patient with endometrial
hyperplasia.
6. Describe functional conditions of the uterine corpus and
cervix.
Variations in uterine and cervical
development
1. Describe the common congenital anomalies of the
uterus and cervix, and outline their clinical
importance.
2. Discuss the symptoms, differential diagnosis,
investigation and management of uterine
leiomyomas and endometrial polyps.
Congenital Anomalies of the Uterine
Corpus and Cervix
• Remember: absence of a Y chromosome leads to regression of the
mesonephric system and development of the paramesonephric system.
• The most common anomalies result from either
– incomplete fusion of the paramesonephric ducts,
– incomplete fusion of the ducts
– formation failures.
• Uterus didelphys is the most extreme failure of fusion.
• Cervical anomalies most commonly associated with fusion defects in the
uterus.
• Normal karyotype but need to rule out associated renal anomalies.
Clinical Significance
• Defects associated with obstruction can cause
dyspareunia, hematocolpos or hematometra,
as well as infertility.
• Defects associated with abnormalities in the
size and shape of the uterine cavity can cause
preterm labor and increased need for C/S due
to malpresentation.
1
7/22/2009
Uterine Leiomyomas
Structural and Benign Neoplastic Conditions
• Uterine Leiomyomas
– Benign tumors derived from smooth muscle cells of the
myometrium.
– At least 45% of women will have them by the fifth decade
of life.
– Most are asymptomatic
– Can cause:
• excessive uterine bleeding,
• pelvic pressure and pain,
• infertility.
• Uterine Leiomyomas (fibroids)
–
–
–
–
–
–
Rare before menarche, can regress in menopause.
May enlarge dramatically in pregnancy.
Calcification may occur
Degeneration may be a source of pain.
Location crucial in understanding symptoms.
Malignant leiomyosarcomas rare.
Uterine Leiomyomas
Uterine Leiomyomas
• Symptoms
• Submucosal
• Subserosal
• Intramural
– Majority are asymptomatic
– Mass effect can cause pelvic pressure, congestion
and bloating, as well as constipation and urinary
frequency from pressure on the bladder.
– Urinary retention a rare complication.
– Menorrhagia a major risk with intramural and
submucosal fibroids.
Uterine Leiomyomas
• Case History
A 45-year-old woman presented with menorrhagia
resulting in chronic anemia. (Hgb 79). Pelvic
examination showed a slightly bulky anteverted
uterus with normal adnexa.
She failed to respond to hormonal suppression
therapy. Pelvic ultrasound showed a 2 cm. fibroid
intramurally in the cornual area of the uterus.
Differential Diagnosis
• The differential diagnosis must include other pelvic
masses and other causes of menorrhagia.
–
–
–
–
–
–
–
Most common differential is an ovarian neoplasm
tubo-ovarian inflammatory mass
Pelvic kidney
Diverticular or inflammatory bowel mass
Cancer of the colon.
Pregnancy
Adenomyosis
2
7/22/2009
Treatment
• Based on
• Medical Management
– Hormonal
• Progestin-only therapy
• Combination hormonal contraceptive methods
• GnRH agonists
• Surgical Management
•
•
•
•
Patient Choices
Myomectomy
Hysterectomy
Embolization of uterine arteries
Ablation of submucosal fibroids via hysteroscopy.
Hysteroscopy
– Informed consent
– Desire for future fertility
– Willingness to undergo a surgical procedure
– Willingness to undergo medical therapy and any
potential side effects.
Fibroids via the Hysteroscope
• Dextrose 5% and
saline in water
• Office or OR
• Diagnostic or
therapeutic
Endometrial Polyps
• Endometrial polyps form from the
endometrium to create abnormal protrusions
of friable tissue into the endometrial cavity.
• Can cause unpredictable bleeding and
menorrhagia.
• Source of post-menopausal bleeding.
• Benign.
Diagnosis and treatment
• Diagnosis can be made on
– Ultrasonography
– Hysteroscopy
• Treatment
– Endocervical and endometrial polyps that
protrude from the endocervix can often be
removed in the office.
– Remainder require D&C or operative
hysteroscopy.
3
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Hysteroscopic Image
Benign Conditions of the Cervix
• Endo and ecto-cervical polyps
• Hysteroscopic image
of an endometrial
polyp
• This would be
accessible to excision
using electrocautery
at the time of
hysteroscopy.
Nabothian Cysts
–
–
–
–
Commonest benign growth of the cervix.
Cause post-coital or coital bleeding or menorrhagia
Local proliferation of cells
Narrow based polyps can be removed by twisting them off
at the base in the office.
– Broader base polyps require removal with cautery in an
operative setting.
– All specimens must be sent for pathology, as early
adenocarcinomas may present this way.
Epithelial conditions of the uterine
corpus and cervix
• Endometrial Hyperplasia
• Very common
• Result from the process of
squamous metaplasia
• Layer of superficial
squamous cells cover over
an invagination of
columnar cells under the
cervix.
• May cause dyspareunia.
Treatment
• Simple hyperplasia (no atypia)
– Medroxyprogesterone acetate 5-10mg orally for 10 days each
month
• Repeat endometrial biopsy to confirm successful treatment
• Treat the underlying cause
• Complex hyperplasia
– Needs formal evaluation of endometrium with fractional D&C
– Treat with daily progesterone therapy for 3 months.
• Complex hyperplasia with atypia
– Hysterectomy or careful follow-up after 3 months of
progesterone.
– Seen at times of unopposed estrogen stimulation
•
•
•
•
PCOS
Obesity
Estrogen therapy
Use of tamoxifen.
• Diagnosis by endometrial biopsy
– Suspect in intermenstrual bleeding,
Dysfunctional uterine bleeding and menorrhagia.
Asherman’s syndrome
• Iatrogenic
• Loss of a large component of the functional
endometrial lining.
• Case History
– A 22-year-old woman underwent a D&C in the postpartum
period for retained products of conception, and
subsequently developed prolonged amenorrhea.
• Commonest cause D&C in high risk setting.
• Endometrial ablation a deliberate intent to cause this
to ameliorate menorrhagia.
4
7/22/2009
Functional Conditions of the uterine
corpus and cervix
• Cervical stenosis
– Usually as a result of trauma
• Endocervical curettage, dilation or conization
– or hypoestrogenism
• Cervical incompetence
– Cervix is unable to maintain pressure under the increasing
demands of a pregnant uterus.
– Can be intrinsic
– Can be due to cervical surgery.
5
7/22/2009
Objectives
Reproduction 018
Congenital Anomalies and Benign
Conditions of the Ovaries and Tubes
Congenital Anomalies of the Ovaries
• Rare!
– Congenital duplication or absence of one ovary can occur and is not
associated with paramesonephric abnormalities.
• Genetic chromosomal disorders such as Turner’s (XO) are
associated with abnormal gonadal development.
– (small, early loss of function)
• Y chromosome predominant in situations like Kleinfelter’s
(XXY)
• XY gonadal genesis or testicular feminization
– Presence of the Y chromosome necessitates removal after puberty
because of risk of germ cell tumors.
Neoplastic Tumors of the Ovaries
• Premenarchal years
– 10% are malignant.
– 90% benign.
• Reproductive or menstrual years
– 15% are malignant
• Menopausal years
1. Outline the congenital abnormalities of the ovaries
and tubes.
2. Describe the common functional and benign
tumors of the ovary.
3. Discuss the clinical management of these tumors.
4. Describe 3 benign conditions of the fallopian tubes
and their management.
Benign Conditions of the Ovaries
• Functional
– Follicular cysts
– Lutein cysts
– Polycystic sclerotic ovaries
• Inflammatory
– Salpingo-oophoritis
– Pyogenic oophoritis
– Granulomatous oophoritis
• Metaplastic
– Endometriomas
The Ovary
• Amazing ability to develop a wide variety of tumors,
the majority of which are benign.
• Need to be able to recognize when a malignancy is
more likely to exist.
• During childbearing years 70% of ovarian masses are
functional
– Remainder are neoplastic or metaplastic (endometriomas)
– 50% are malignant.
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Functional Cysts
• Dozens of follicles form each cycle.
• If one persists and is larger than 3 cm it is defined as
a functional cysts.
• If it is a persistent follicle it is classified as a follicular
cysts and may produce estrogen.
– Lined by granulosa cells
• If it is a persistent corpus luteum, it is defined as a
lutein cyst and may produce progesterone, delaying
onset of menses.
Symptoms
Functional Cysts- continued
• Hemorrhagic cysts
• Hemorrhage occurs into the cysts as a result of invasion of ovarian
vessels into the functional cysts
• More likely to be symptomatic
• Theca-lutein cysts
– Associated with high levels of HCG
– Also can be associated with ovarian hyperstimulation
(inducing ovulation in IVF)
• Luteomas of pregnancy
• Polycystic ovarian syndrome
Torsion of Ovarian Cyst
• Often asymptomatic
• Can reach sizes up to 15 cm.
• Lutein cysts more likely to delay menses than
follicular cysts
• Hemorrhagic cysts more likely to be symptomatic
with severe pain
• Torsion
– surgical emergency
• Rupture
– May be a surgical emergency.
Diagnosis
• Pelvic examination
– In the non-obese patient palpable after reaching a
size of 5-6 cm.
– Cysts are mobile unilateral and not associated
with ascites. (Except PCOS which will be bilateral)
• Pelvic ultrasound very useful in trying to
differentiate between functional and
neoplastic cysts, but not infallible.
Management
• Reproductive age patient presenting with < 6 cm cyst
ok to wait and reexamine after next menses. (pelvic
exam or U/S)
• If > 6 cm, or feels solid or fixed ultrasound imaging is
appropriate.
• If lesion is painful, multilocular or partially solid (on
US) surgical exploration is indicated.
• Laparoscopy/laparotomy
• Spontaneous regression will occur in up to 70% of
adnexal cysts.
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7/22/2009
Epithelial Ovarian Neoplasm
Benign Neoplastic Ovarian Tumors
• Ovarian Neoplasms
– Divided into
• Epithelial – ovarian surface
• Stromal
• Germ cell
• Benign cystic teratoma ( dermoid) is the most
common, from the germ cell group.
Epithelial Ovarian Tumors
• Serous tumors
– 70% will be benign
– 5-10% borderline malignant potential
– 20-25% are malignant.
• Mucinous tumors can attain a massive size
– 85% are benign
– Rarely complicated by pseudomyxoma peritoneii
• Brenner tumors
– Cells resemble transitional cells of the bladder
– Rare, benign
Germ cell tumors
• Make up ~ 60% of ovarian neoplasms in
children.
• Benign cystic teratoma the most common.
(aka dermoid cyst)
• 10-15% bilateral
• Ectodermal tissue
– Sweat and sebaceous glands, hair follicles, teeth
– Some mesodermal and rarely endodermal elements
• All tissue benign in nature.
• Derived from the mesothelium lining the peritoneal
cavity
• Maintain their ability for example to develop the
different types of histologic tissue seen in the
mullerian tract.
–
–
–
–
Serous
Mucinous
Endometrioid
Brenner - bladder mucosa
Sex-cord stromal tumors
• Granulosa-theca cell tumors
– Feminizing tumors due to their ability to produce estrogen
• Precocious puberty in the child
• Menorrhagia and endometrial hyperplasia in the adult
– Sertoli-Leydig cell tumors
• Less common but can cause virulizing symptoms
• All have low malignant potential
• Fibromas
• Smooth solid tumor made of interlacing bundles of fibrocytes
• Benign but can be associated with ascites
• Meigs syndrome: trans thoracic flow thru lymphatics of the
fluid can cause ascites and hydrothorax.
Diagnosis
• Again most asymptomatic unless torsion or
rupture occur.
• Bimanual examination in the non-obese patient.
• Pelvic ultrasonography, particularly transvginal in
obese patient
• Tumor markers
• CA 125 – tumour marker for ovarian cancer but not sense or
spec enough for screening; useful for following malignancy
• Hormone markers
• Laparoscopy – if unsure by US
3
7/22/2009
Management
• Solid tumours generally treated with unilateral
salpingo-oophorectomy
• Ovarian cystectomy in younger women a possibility if
it is unilocular.
• Ovarian fibromas an exception, although solid can be treated
with cystectomy.
• Dermoids can also be treated with cystectomy.
• Ascitic fluid needs to be sent for cytology
• TAH –BSO for the older woman may be appropriate.
• Total hysterectomy and bilateral salpingo-oopherectomy
• Due to large risk of malignancy
Benign Conditions of the Fallopian Tube
• Most lesions inflammatory in nature
– Hydrosalpinx – tube distended with fluid
– Pyosalpinx – tube distended with pus
• Tubes have less tendency towards neoplastic
transformation  Rare
• Neoplasms that do occur
–
–
–
–
–
Epithelial adenomas
Polyps
Myomas
Inclusion cysts
Angiomas.
Benign Ovarian Cyst Operative View
• A 15-year-old female
presented with abdominal
pain and a larges simple
cyst on ultrasound. The
mass did not have a solid
component.
• Operative laparoscopy
performed for ovarian
cystectomy, lower picture
is the post-op view!
Management
• Pyosalpinx is aggressively treated with IV
antibiotics as for salpingitis
• Surgical excision may be required.
• Instant infertility and early menopause
• Hydrosalpinx may be managed conservatively
if it is asymptomatic
– Salpingectomy if symptomatic. (it doesn’t serve
any function anyway)
• Benign growths may be excised via
laparoscopy.
Objectives
1. Outline the congenital abnormalities of the ovaries
and tubes.
2. Describe the common functional and benign
tumors of the ovary.
3. Discuss the clinical management of these tumors.
4. Describe 3 benign conditions of the fallopian tubes
and their management.
4
7/22/2009
Objectives
RP029
Amenorrhea, Oligomenorrhea and
Hyperandrogenic Disorders
Definition of Primary Amenorrhea
1. No period by age 14 in the absence of growth or
development of secondary sexual characteristics.
2. No period by age 16 regardless of the presence of
normal growth and development with the
appearance of secondary sexual characteristics.
Diagnostic Strategy Using the
Compartment System
• Compartment 1
• Disorders of the outflow tract or uterine target organ.
• Compartment 2
• Disorders of the ovary
• Compartment 3
• Disorders of the anterior pituitary
• Compartment 4
• Define primary amenorrhea and state when a
patient should be investigated for it.
• Classify primary amenorrhea disorders based
on presence or absence of secondary sexual
characteristics and presence of mullerian
anomalies.
Rule # 1
• Rule out pregnancy first
– This is never a wrong answer!
Compartment 1 disorders
• Disorders of the outflow tract or uterus
– Obstructive Mullerian tract anomalies
– Agenesis of the Mullerian tract (MRK)
– Hypoplastic Mullerian anomalies
– Imperforate Hymen
– Complete androgen insensitivity (XY)
– Rare forms of CAH (XY)
• Disorders of the central nervous system.
1
7/22/2009
Compartment 2 Disorders
• Disorders of the ovary
– Gonadal agenesis or dysgenesis
• XO, XXX, Mosaic
Compartment 3 Disorders
• Disorders of the anterior pituitary
– Pituitary tumor
• Producing excess PRL, TSH,
– Growth hormone (can initially present with high PRL and
amenorrhea).
Compartment 4 Disorders
Puberty Milestones Review
• Disorders of the central nervous system
– Hypogonadotropic hypogonadism
• Kallmann’s syndrome-accompanying anosmia.
• Stress related amenorrhea
– Exercise
– Chronic illness
• Anorexia nervosa
• Hypothyroidism
• Craniopharyngioma can present as primary amenorrhea,
hypogonadotropic hypogonadism and delayed puberty warrant an
MRI to rule out
Puberty Milestones Review
Puberty Milestones Review
2
7/22/2009
Puberty Milestones Review
Presence of Secondary Sexual Characteristics
• Puberty has been initiated normally
• Look for :
– Mullerian tract anomalies
• Obstructive
• Hypoplastic
• Agenesis
Puberty Milestones Review
Absence of Secondary Sexual Characteristics
• Puberty has not been initiated normally
– Look for:
• Hypothalamic causes
• Pituitary causes
• Ovarian agenesis or dysgenesis.
– Complete androgen insensitivity
– Rare forms of CAH
Objectives
• Define secondary amenorrhea.
• Discuss the differential diagnosis for secondary
amenorrhea associated with hypoestrogenism.
• Discuss the etiology, diagnosis and treatment of
amenorrhea associated with hyperprolactinemia.
• Define mild hypothalamic dysfunction causing
amenorrhea and outline its treatment.
Definition of Secondary Amenorrhea
1. In a woman who has been menstruating, the
absence of periods for a length of time equivalent
to a total of at least three of the previous cycle
intervals or 6 months of amenorrhea.
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7/22/2009
Rule # 1
• Rule out pregnancy first
– This is never a wrong answer!
Diagnostic Strategy Using the
Compartment System
• Compartment 1
• Disorders of the outflow tract or uterine target organ.
• Compartment 2
• Disorders of the ovary
• Compartment 3
• Disorders of the anterior pituitary
• Compartment 4
• Disorders of the central nervous system.
Compartment 1 disorders
• Disorders of the outflow tract or uterine target
organ.
– Asherman’s syndrome
Compartment 3 Disorders
• Disorders of the anterior pituitary
– Pituitary tumors
• PRL, TSH
– Sheehan’s syndrome
Compartment 2 Disorders
• Disorders of the ovary
– Premature ovarian failure
• Autoimmune
• Chromosomal mosaicism
• Partial CAH (adrenal as well)
Compartment 4 Disorders
• Disorders of the central nervous system
– Hypogonadotropic hypogonadism
• Stress related amenorrhea
– Exercise
– Chronic illness
• Anorexia nervosa
• Hypothyroidism
4
7/22/2009
Secondary amenorrhea associated with
hypoestrogenism.
• Hypothalamic-pituitary dysfunction
– Includes patients with severe weight loss or excessive
exercise, anorexia nervosa, severe systemic diseases,
pituitary or CNS lesions and pituitary failure.
• Premature ovarian failure
– Ovarian failure before the age of 40.
• Hyperprolactinemia
– If not explained by drug use or hypothyroidism, a CT or
MRI of the sella turcica should be performed.
Mild hypothalamic dysfunction
• Patients with adequate estrogen levels but who are
anovulatory may have a mild form of hypothalamic
anovulation.
–
–
–
–
–
Nutrition/exercise mismatch
Psychological stress
Recent use of DepoProvera
Recent pregnancy or lactation.
When pregnancy not desried, observation and periodic
withdrawal bleeds with progesterone appropriate.
Case History
• A 25-year-old female presents with secondary amenorrhea.
BMI is 22.
• Her TSH and Prolactin are normal.
• She has a withdrawal bleed on progesterone.
Amenorrhea associated with hyperprolactinemia.
• Treatment objectives
– Elimination of lactation
• Medical with bromocriptine (dopamine agonist)
• Surgical for visual field defects or failure to improve on medical
therapy.
– Establishment of normal estrogen secretion
– Induction of ovulation when fertility is desired.
– Treatment of tumors as indicated.
• Mass effects of prolactinomas
• Craniopharyngiomas.
Case History
• A 16-year-old female comes to your clinic with a diagnosis of
primary amenorrhea.
• She has had breast development at age 12
• TSH and Prolactin are normal.
• She has been on an oral contraceptive ( for contraception)
with no withdrawal bleed.
Case History
• A 23-year-old competitive track and field athlete presents
with a 6 month history of amenorrhea.
• Her TSH and prolactin are normal
• She fails to bleed after a Progesterone challenge.
• After being placed on an OCP she does have regular
withdrawal bleeds.
• FSH is low.
5
7/22/2009
Case History
• An 18-year-old female presents with
oligomenorrhea. She has a BMI of 29. TSH is
elevated and her prolactin is mildly elevated.
She has a withdrawal bleed after
progesterone.
Objectives
Case History
• A 17-year-old female presents with secondary
amenorrhea. Her TSH and prolactin are
normal. She fails to have a withdrawal bleed
on progesterone, but does bleed after one
cycle on an OCP (combined).Her FSH is high.
Ovarian ultrasound
• Outline the medical treatment for a patent
with a diagnosis of polycystic ovarian
syndrome.
Treatment Aims
• Correct the hyperandrogenisim and its effects
• Correct the anovulation and its adverse effects
– Protect the endometrium from hyperplasia
– Restore fertility when desired.
• Identify and treat insulin resistance. hyperlipidemias
and hypertension when present.
Hyperandrogenism
• Hirsuitism and acne
– Combination oral contraceptive therapy or Depo-Provera
• Need mechanical methods to remove pre-existing hair.
• Diane 35 containing cyproterone acetate is best available product
for treatment of androgen symptoms.
– Spironolactone (aldosterone antagonist) also indicated for
treatment of hirsuitism when ovarian suppression therapy
fails.
– Weight loss
6
7/22/2009
Differential Diagnosis for hyperandrogenic
disorders
•
•
•
•
Congenital adrenal hyperplasia
Cushing’s syndrome
Adrenal neoplasms
Racial differences in expression of androgenic effects
in the skin can lead to difficulties in diagnosis (excess
hair with normal androgens, minimal hirsuitism in
the face of elevated androgens)
Treatment
• Insulin resistance
– Weight loss
– Oral hypoglycemics
• Hyperlipidemias
– Weight loss
– Medical therapy.
7
RP049 - Perinatal Genetics
Learning Objectives
Perinatal Genetics:
Metabolic / Genetic Disorders
in Pregnancy
After this lecture the student should be able to
 Describe the effects of genetic/ metabolic diseases
in the mother on the mother or pregnancy and
provide examples
 Describe the effects of genetic/ metabolic diseases
in the mother on the fetus and provide examples
 Describe the effects of genetic/metabolic diseases
in the fetus on the mother and provide an example
Bernie Chodirker
Definitions: Mother = Mother and pregnancy and delivery
Fetus = Fetus, placenta and baby
Effects of Metabolic / Genetic Disorders in Pregnancy
 Four
1
2
3
Main categories
Effects of disease in the mother on the mother/pregnancy
Effects of disease in the mother on the fetus
Effects of disease in the fetus on the mother/pregnancy
Effects of disease in the fetus on the fetus
4
Genetic Disorders Affecting Fertility
 GALACTOSEMIA
 -females
with classical galactosemia develop
hypergonadotrophic hypogonadism
 fertility is rare
 CYSTIC FIBROSIS-
CBAVD in males
 CONG. ADRENAL HYPERPLASIA
 HOMOCYSTINURIA-?
S.A.

Turner Syndrome
 Pregnancy possible if mosaic or with assisted reproduction
 2 patients died of aortic dissection in third trimester
Myotonic Dystrophy
Myotonic Dystrophy CTG repeats
24/69
none
adult
5/845/75
13/300
juvenile
congenital
13/112
5/160
13/205
14/2100
13/730
16/200
Myotonic Dystrophy
 Mother on Mother
 Prolonged labor



due to maternal weakness
post-partum hemorrhage, pre-term labor
respiratory distress with small amounts of resp depressants
Mother on Fetus
 Old
1
theory was maternal non-genetic factor
 fetus on mother
 hydramnious
(10% of idiopathic hydramnious)
 fetus on fetus
 Congenital
myotonic Dystophy
Genetic Disorder in Mother
Affecting Mother
Genetic Disorder in Mother Affecting Mother
 Neurofibromatosis
NF1 (Dugoff
1996)
 Marfan
 21
Syndrome (Rossiter 1995)
women, 45 pregnancies
 aortic root < 40, tolerate pregnancy well
 2 aortic dissections
 105
women 247 pregnancies
livebirths, 44 SA’s, 21 TA’s, 2
ectopic
 7 C-section due to NF (eg. Pelvic
neurofibroma
 no increase in pregnancy
complications eg. Preeclampsia
 60% new neurofibromas, 52%
enlargement of neurofibromas
 182
Genetic Disorder in Mother Affecting Mother
 Ehlers
Danlos Syndrome IVVascular type
 Thin,
translucent,fragile,premature
aged skin
 minimal joint hypermobility
 Spontaneous rupture of arteries
and internal organs
 colon,
uterus
 average
life span 40
 Autosomal Dominant
Genetic Disorder in Mother Affecting Mother
 Skeletal
dysplasia (Allanson, 1986)
women (26 Achondroplasia)
pregnancies (70 to term)
 9 women had resp distress in last 2/12
 63/70 deliveries were C-Section
 epidural successful in 23
 Suggest
baseline pulmonary function
careful with general anesthetic
small trachea, spine instability,
lower body mass,
Genetic Disorder in Mother Affecting Mother
 Ehlers
Danlos Syndrome IV- Vascular type
(NEJM, 2000)
83 pregnancies
12 deaths
5 uterine rupture during labor
2 of blood vessel rupture at delivery
5 of blood vessel rupture within 2 weeks
after delivery
 Pepin
unknown
if CS would help
More Genetic disorder in mother affecting mother
 46
 89
Genetic Disease in Mother affecting Mother
 CF:
1/2 have serious /progress lung decompensation
- 43% no change, 43% worse, 14% better
 Multiple Sclerosis- relapse rate similar to non-pregnant
 Epilepsy
 Asthma
 if
 if
1 seizure/month prior, most worse
0 seizure/ 9 months prior, 25% worse
Metabolic Disease in Mother affecting Mother
 Metabolic
 Metabolic
disease causing further organ damage
during pregnancy
 Glycogen
storage disease I (renal)
 Cystinosis (renal)
decompensation after delivery
Cycle Disorders
(OTC Deficiency)
CPS deficiency
Urea
 Glycogen
Maternal
 Poryphyria
Maternal
Storage Disease III (cardiomyopathy)
( 50% had attacks during pregnancy, 1
maternal death)
High
Maple Syrup Urine Disease
Homocystinuria
risk for postpartum
thromboembolism
Maternal Disease Affecting Fetus
PKU
phenylalanine
2
-------x--------->Tryosine
Autosomal recessive
 1/ 12,000 Caucasian births
carrier frequency 1/50
Disease can range from Classic to mild
hyperphenylalanemia
Maternal Disease Affecting Fetus
Maternal PKU
MATERNAL PKU
routine NB screening began in 1960’s, early rx women are
now fertile,
 ~2800 fertile women with normal IQ in U.S. (~300 in
Canada) by 1990.
 Rouse et al (2000) 413 offspring to 354 women with PKU
 31 CHD,
 17 microcephaly with MR,
 no control before 4-8 weeks.
 Need for metabolic control prior to pregnancy


 Developmental
Follow-up
et al (2000) –FU in 149
offspring
Waisbren
 Good
control= mean score 99
without control by 20 weeks IQ<2SD
 Overall 30% of children have social /behavioral problems
 Treatment at any stage may be helpful
 47%
Nutritional Rickets
Maternal PKU
 Vitamin
Do we know all the moms with PKU?
 Hanley et al (1999) retrospective survey, of 414
women with maternal PKU,
 17 diagnosed for 1st time in pregnancy, including 6
only after birth of the affected offspring
 Recommendations
 Diet life long ; consider PKU embryopathy in children
with microcephaly, MR, CHD if firstborn, other
affected, mom with MR
 “Consider Prenatal screening for any woman born
before 66”
D Deficiency

 Inadequate
vitamin D in
diet (milk, liver, fish)
 Inadequate
exposure to
sunlight for dermal vitamin
D synthesis
Congenital Rickets
3
Innes et al 2002,
4 Aboriginal Manitoba babies with Congenital Rickets
whose mothers had evidence of Vitamin D deficiency, did not consume milk,
little prenatal care, no vitamins,
Mirror syndrome
Fetal conditions with Mirror syndrome
 Also
 Placental
called “pseudotoxemia”, “triple edema
syndrome”, “maternal hydrops”, Ballantyne
syndrome”.
 Fluid retention in women with hydropic fetus
Chorioangioma
infections
 Alpha-thalassemia
 Sacrococcygeal teratoma
 Trisomy 13
 Rh erythroblastosis
 Ebstein Anomaly
 Cardiac arrhythmia
 Viral
 complications
 may
include pulmonary edema
also get pre-eclampsia
 Outcome
poor for mother and baby without
prompt delivery or treatment of hydrops
Complete Mole

Histologically, the
hydatidiform mole has
large
avascular villi and areas
of trophoblastic
proliferation.
Diploid karyotype
 85% 46,XX 15% 46,XY
 80-100% paternal only
diandric diploidy
 Diploid
complete moles occasionally go to
choriocarcinoma
15% local invasion, 4% distant
 can
also present with hyperemesis, pre-eclampsia,heavy vag
bleed, RDS, hypertyhroidism due to trophoblastic
hyperplasia and high HCG
Well recognized pregnancy complications
Hyperemesis
Gravidarum : very common
Pre-eclampsia : common (5%)
HELLP
(Hemolysis,
Elevated Liver enzymes, Low
Platelets) syndrome uncommon (1/200)
AFLP
(Acute Fatty Liver of Preg)
jaundice,
Plasma
encephalopathy, (1/10000)
Free Fatty Acids
Cytoplasm
CPT1
Inner Mt. Memb
CPT2
Fatty Acyl-CoA
Acetyl-CoA
 LCHAD (long
chain-3-hydroxylacyl-CoA
dehydrogenase),
 MCAD (medium chain-acyl-CoA dehydrogenase),
CPT-1 (Carnitine Palmitoyltransferase 1) def. &
?others are part of a new class of metabolic disorders
called fatty acid oxidation defects (FAOD)
 FAOD are only recently characterized; in childhood
present as Reye-like syndrome, ALTE,
cardiomyopathy etc
Long Chain
Fatty Acids
Outer Mt. Memb
Mitochondrial
Matrix
Metabolic Fetal Disease Affecting Mother
Signs and Symptoms of
Fatty Acid Oxidation Defects
lethargy
hepatomegaly
myopathy
Reye-like episodes
failure to thrive
seizures
cardiomyopathy
sudden death
coma
hypoketotic hypoglycemia
MCAD
LCAD
LCHAD
Fetal disease affecting mother
 There
Liver Steatosis
in FAOD
Cardiomyopathy
in FAOD
are now well- documented studies showing
association of LCHAD with preeclampsia,
HELLP and esp. AFLP and HELLP
 Ibdah et al.
A fetal fatty acid oxidation disorder as a cause
of liver disease in pregnant women. NEJM.
1999;340:1723-31.
24 children with
hypoketotic hypoglycemia
and fatty liver
Fetal disease affecting mother
?
8 homozygotes
for
glu474gln LCHAD
11 compound
heterozygotes for
glu474gln LCHAD
5 with
cardiomyopathy/neuropathy
no glu474gln mutations
7 had AFLP
and/or HELLP
8 had AFLP
and/or HELLP
0 had AFLP
and/or HELLP
Mechanism
 In
presence of Glu474Gln mutation, metabolites
produced by fetus or placenta accumulate in the
mother and are highly toxic to liver.
 Metabolites overwhelm the mitochondrial oxidation
machinery of the heterozygous mother who is already
under stress from the increased demand for fatty acid
oxidation in later stages of pregnancy..
Signs and Symptoms of
Fatty Acid Oxidation Defects
Fetal disease affecting mother
 Pre-eclampsia
and HELLP also associated with
MCAD deficiency
 hyperemesis
gravidarum HELLP and AFLP also
associated with hepatic CPT-1 deficiency
lethargy
hepatomegaly
myopathy
Reye-like episodes
failure to thrive
seizures
cardiomyopathy
sudden death
coma
hypoketotic hypoglycemia
hyperemesis gravidarum Pre-eclampsia
HELLP syndrome
acute fatty liver of pregnancy
Recommendations
Conclusions
 Strauss
 Some
et al b Seminars in Perinatology (1999):
AFLP / recurrent HELLP
 Maternal
 screen
for common LCHAD mutation in parents
baby for FAOD- glucose, urinary organic
acids, acylcarnitine profile, carnitine, palmitate
oxidation & DNA testing
 investigate
 Yield
will be lower for isolated HELLP
of the disorders mentioned may be modified
prenatally or postnatally by diet e.g.PKU,
 Pregnancies can cause significant complications from
Genetics disorders for mother or baby
 Pregnancy or birth of an affected child may often be
the “presenting symptom” of an inborn error of
metabolism in the family
Learning Objectives
After this lecture the student should be able to
 Describe the effects of genetic/ metabolic diseases
in the mother on the mother or pregnancy and
provide examples
 Describe the effects of genetic/ metabolic diseases
in the mother on the fetus and provide examples
 Describe the effects of genetic/metabolic diseases
in the fetus on the mother and provide an example
7/22/2009
Objectives
Newborn Assessment
and Resuscitation
Med II RP051
Shyamala Dakshinamurti
Section of Neonatology
• 5 million neonatal deaths per year worldwide
• Birth asphyxia accounts for 19% of neonatal deaths
and is a major source of perinatal mortality
At the end of this lecture, you will be responsible to
know the following:
•
•
•
•
Immediate assessment of the newborn
Apgar score: its elements and implications
Major complications of term delivery
Physiology of perinatal depression and of basic
resuscitative measures
• Common causes of failed resuscitation
• Principles of gestational age assessment
• Major complications of prematurity
You Are Called to Attend a Delivery…
• 10% of newborns require some respiratory assistance
at birth
• 1% of newborns require extensive resuscitation at
birth
• 30,000 deliveries a year in Manitoba
• This means 300 newborn resuscitations per year
• You will be doing some of these!
Newborn Assessment
• You are called to attend this delivery
• Maternal history: 26 yr G1 P0, medically healthy, swabs
and serologies normal, in spontaneous labour at term (39
wks GA)
• Intrapartum fetal tracing has shown deep variable
decelerations, but these have resolved with changes in
maternal position
• Mild shoulder dystocia, otherwise delivery uneventful
• Baby is born flat, blue, not breathing
• Now what?
Newborn Assessment
• Immediate questions:
• Is the baby breathing?
• What is the baby’s heart rate?
• What is the baby’s colour?
• Why are you asking these questions?
Basic Physiology of Neonatal Transition:
•
•
•
•
•
Oxygenation switches from placental to pulmonary
Respiratory drive needs to be stimulated
High vagal tone controlling heart rate
Hypoxia is a vagal stimulant
Almost all cardiorespiratory depression is therefore
respiratory in origin. Almost.
1
7/22/2009
Respiratory Adaptation
Circulatory Adaptation
• During fetal life, high
pulmonary vascular
resistance means blood
from the right ventricle
bypasses the lung
circulation
• Blood enters aorta via
the ductus arteriosus
• After birth, lungs are oxygenated with first breaths
and pulmonary vascular resistance falls
• Ductus closes; Blood enters the lungs via pulmonary
artery, and is oxygenated
• Alveolar fluid is absorbed by the lung (active Na+ ion transport at
birth, stimulated by O2)
• Lung inflation initially requires very negative intrathoracic pressure
to recruit alveolar expansion
• Stimuli for respiratory effort include rising PO2 at birth and hormonal
changes associated with birth, including decreased prostaglandin
production
• A supraphysiologic PCO2 also stimulates peripheral chemoreceptors;
a PCO2 below the apneic threshhold abolishes breathing activity
• Physical stimuli stimulate breathing by increasing arousal
insult
insult continues…
Primary and Secondary Apnea
Primary Apnea
• ‘stunned infant’
• Transient apnea; can be associated with drop in HR
• Spontaneous recovery possible with appropriate stimulation
regular
respiratory
effort
Secondary Apnea
• ‘down for the count’
• Protracted apnea, associated with bradycardia and
desaturation
• Spontaneous recovery not possible; will need resuscitation
gasping
respiration
HR falls;
Sat may fall
HR falls;
Sat falls;
BP falls
BP stable
At first glance, these look the same!
Causes of Neonatal
Cardiorespiratory Compromise
Physiology of Resuscitation
• Primary apnea lasts 1 to 2 min, followed by gasping of
progressively increasing vigour
• Secondary (terminal) apnea can persist for over 10
minutes prior to cardiac arrest
• Hypoxemia itself inhibits respiratory effort
• In severe asphyxia, PaCO2 rises by 10 mmHg/min; pH can
drop from 7.30 to 6.80 in 5 min
• PaO2 drops as low as 30 mmHg within 5 min of severe
asphyxia, with lactic acidosis and onset of hypotension
• Cerebral blood flow decreases with hypoxia
• Reperfusion injury and oxygen radicals cause much of the
CNS damage in perinatal hypoxia/resuscitation
• Respiratory
• Apnea increases vagal tone and causes bradycardia
• Respiratory acidosis can be a direct cause of
hemodynamic compromise
• Cardiac
•
•
•
•
Blood loss (placenta; cord accident)
Arrhythmia
Anemia (high output failure) eg. Rh incompatibility
Septic shock
2
7/22/2009
Decision Tree
Facilitating Neonatal Adaptation
• Place baby in a warm location
• Dry the baby off – and remove the wet linens!
• Clear the airway of mucus and fluid; position for
open airway (sniffing position)
• Stimulate respiration by gentle rubbing of skin
on back
• Watch for onset of respiratory efforts
Dry
Clear airway
observe
Breathing?
Heart rate?
No respir effort
or
Poor respir effort
Good respir effort
HR > 100
observe
Colour pink?
Baby to mom;
You can go
get a coffee
• You have 30 seconds for this stage
PPV
Causes of Perinatal Respiratory Distress
While you’re thinking: Decision Tree
Can’t breathe:
• Mechanical airway obstruction (meconium, blood, mucus)
• Parenchymal lung disease (retained alveolar fluid, pneumonia,
etc)
• Prematurity and hyaline membrane disease
• Space-occupying lesion in pleural space (air, liquid, …gut)
dry, clear airway
Poor respir effort
PPV x 30 sec
observe
Won’t breathe:
• Intrauterine asphyxia
• CNS depressants (narcotics, barbiturates, alcohol,
anaesthetics, magnesium)
• Trauma (cerebral edema, hemorrhage)
• Neurologic disorders; congenital anomalies
Breathing?
Heart rate?
Poor respir effort
HR > 100
Good respir effort
Pinking up
HR > 100
Stop PPV and observe
Keep doing PPV
What is the Apgar at 1 min?
What does APGAR stand for?
Trick question: it’s not an acronym!
It’s named after Dr Virginia Apgar (1953)
• Infant is 60 seconds old… take a second to reassess:
1
Heart
rate
Respir
rate
Colour
Reflex
Tone
2
> 100
Regular
Pink
Grimace,
Sneeze
or Cough
Good
flexor
tone
1
< 100
Irregular
or
Gasping
Acrocyanosis
only
Twitch
Some
tone
0
None
Apnea
Cyanosis
or
Pallor
None
Flaccid
0
0
Apgar
score is
measured
at 1 min
and 5 min
0
0
• Palpating the base of the umbilical cord, you feel a
heart rate of about 8 beats in 6 seconds,
ie. 80
beats/min
• No spontaneous respir effort; you are still bagging at
about 60 breaths/min
• Colour is pale, with acrocyanosis
• No response when nasopharynx is suctioned
• Extremities are limp and flaccid, no spontaneous
movements seen
In sum, the 1 minute Apgar is only 1. How bad is this?
3
7/22/2009
Back to the Decision Tree…
Implications of Low Apgar Scores
Poor respir effort
• At 1 minute, 6% of babies have Apgar score of 0-2; 24%
score 3-7; 70% score 8-10
• This 1 minute Apgar does not correlate with a bad longterm
outcome
• 5 min Apgar < 4 is associated with major neurological
sequelae (cerebral palsy, usually spastic diplegia)
• Combination of pH < 7.0 and Apgar < 4 at 5 min has
specificity and positive predictive value of ~100% (but
poor sensitivity, ~60%) for neurologic abnormality
• pH < 7.0 and Apgar < 4 is also associated with 8-fold
increased risk of neonatal death
PPV x 1 min so far
observe
Breathing?
Heart rate?
while ventilating
HR > 100
HR < 60
Continue PPV
Cardiac compressions
Keep doing PPV
Observe for
onset of
respir effort
… another 30 seconds
then
consider drugs (epinephrine)
NRP and Drugs
NRP and Drugs
Other NRP drugs:
• Volume
– Crystalloid (NS or Ringer’s lactate) usually sufficient to
restore intravascular volume in shock
– In case of blood loss (eg. Placental abruption), emergency
blood transfusion
• Sodium Bicarbonate
– Almost useless
– Can be used to correct a severe metabolic acidosis; but this
is almost always a result of poor perfusion – far better to fix
the perfusion problem
– Route is iv only (need an umbilical central line)
• Narcan
– To reverse effects of recent maternal narcotic therapy, if
you know for a fact that there was no chronic maternal
drug use
• Recall: about 10% of regular term deliveries require
some intervention; about 1% of regular term deliveries
require resuscitation
• Of those infants resuscitated, only about 1% require
more than PPV +/- CPR; you don’t open the drug box
very often
• Epinephrine is the most commonly needed
resuscitation drug in NRP; it can be given iv, or via
endotracheal tube
Which route will you use if you need it in this case?
Most Common Morbidities at Term
• Sepsis
• Commonly Group B Streptococcus
• Can also be enteric Gram Negative bacilli
• Presents as pneumonia or septic shock; but can also be
quite subtle in onset
• Perinatal asphyxia
• Prolonged labour, cord compression, nuchal cord
(usually problems reversible with good resus)
• Placental abruption, placenta previa, vasa previa (can
cause significant blood loss)
• Placental insufficiency (acute on chronic)
Causes of Rescuscitation Failure
•
Inadequate thermoregulation
•
•
•
•
Lack of radiant heat source
Failure to dry infant and remove wet linen
Can stymie all further resus efforts
Poor respiratory support
•
•
•
•
Take care to position head to open airway
Appropriate pressure, appropriate speed !! Ensure
chest inflates with each bagged breath
Is tubing hooked up to an oxygen source?
Good PPV means you rarely need to intubate
4
7/22/2009
What is the Apgar at 5 min?
It’s now time for your 2nd Apgar assessment:
2
1
1
2
1
• With your assiduous efforts at PPV, infant now has a
heart rate of 12 beats in 6 seconds’ count, ie.
120/min
• Making occasional gasping respiratory effort
• Centrally has started to pink up, although extremities
are still blue
• Sneezes with suctioning, grimaces
• Extremities have some tone, but limbs are in an
extended position
The 5 minute Apgar is up to 7. Good resuscitation!
Prematurity: A Special Scenario
A Successful
Resuscitation…
But don’t forget the
after-care:
Monitoring for late
complications of
perinatal depression
(includes failure of
circulatory transition)
• iv, O2, monitor
• to mother when
you are satisfied
all is well
Hyaline Membrane Disease
• Premature infants are considered viable after 23 weeks
gestation, or > 500g
– 23-24 weeks is a grey zone (mortality > 90%)
– At 23 weeks, lungs are still in a canalicular phase of development
(few alveoli, big A/a gradient)
– At 25 weeks, mortality 40-50%
– By 27 weeks, lungs are alveolarizing, and mortality is down to
<20%
• Primary complication of preterm birth is respiratory
distress due to surfactant deficiency and hyaline
membrane disease
• The greatest advance in neonatal care in the last 50 years
is artificial surfactant
Surfactant - Physiology
surfactant
• Surfactant is a product of alveolar type II cells; artificial
surfactant may be synthetic or derived from animal lung
extracts
• Decreases alveolar opening pressure, ie. the pressure at
which the lung parenchyma begins to fill beyond dead
space volume
• Achieved by lowering the surface tension at the gas
liquid interface in the small airways and alveoli
• Surfactant also stabilizes the lung on deflation,
maintaining functional residual capacity by preventing
complete collapse of previously inflated alveoli
Hyaline Membrane Disease
Post Surfactant
High surface tension
Collapsed alveoli
Hypoventilation, V/Q mismatch
Hypoxia
Pulmonary vascular constriction
Decrease in surface tension
Inflation of alveoli
Relaxation of pulmonary vessels
Good gas exchange
Respiratory failure
Metabolic acidosis
Circulatory failure
5
7/22/2009
How Preterm is Preterm?
Major Factors Determining Outcome
• The major determinate of overall perinatal mortality and
morbidity is prematurity
• In developed countries, preventing prematurity would
markedly improve infant mortality figures
• In developing countries, sepsis is still king (and is the major
hazard for term infants in North America)
• The main determinate of quality of life is longterm
neurological function
• Perinatal asphyxia, intraventricular hemorrhage, cerebral
palsy and learning disability are all increased with preterm
birth and low birth weight
Gestational age
assessment
• Based on physical
features and on
neurological devt
• Skin thickness, skin
creases, devt of
cartilage, breast buds,
genital devt
• Muscle tone (flexor vs
extensor), joint laxity
Determining Neurodevelopmental Outcome:
Intraventricular Hemorrhage
Summary
• Principles of cardiorespiratory resuscitation in
the depressed infant:
• Incidence - ~ 20% of infants <1500g
• Pathogenesis
– Highly vascular germinal matrix with tenuous capillary
integrity, poor cerebral autoregulation
– Fluctuating cerebral blood flow
IVH
(especially in infants with
severe RDS)
Periventricular venous congestion
Ischemia
Hemorrhagic infarct
• Temperature regulation
• Resolve respiratory problems first
• Hemodynamic instability and bradycardia often (but not
always) secondary to respiratory issues
•
•
•
•
Apgar scores and their implications
Common causes of failed resuscitation
Resuscitating the premature infant
Determinates of term and preterm outcome
Cerebral palsy, neurologic deficit
6
7/22/2009
RP062 - Infections in pregnancy and the neonate
Goal
To introduce the concept of
the special nature of
infections in pregnancy
Lecture
+
Tutorial
Objectives
Describe
the factors that
specifically affect infections during
pregnancy and the neonatal period
List the most important congenital
and perinatal infections
List the consequences of congenital
and perinatal infections
Describe what determines the
consequences of congenital and
perinatal infections
Outline how to diagnose congenital
and perinatal infections
Congenital infections
Definitions
Perinatal Infections: Occur during
gestation, labour and delivery, or
during the first month of life
Congenital Infections: Occur during
gestation
Vertical Infections: Occur secondary to
infection of sperm or egg
Early Onset Neonatal Infections: Occur
before 7 days of age
Late Onset Neonatal Infections: Occur
from 7 days to 3 months of age










Infections transmitted during
Labour/Delivery













HSV
Hepatitis B
HIV
HPV
Enterovirus
Varicella
CMV
Gonococcus/Meningococcus
Chlamydia
Ureaplasma/Mycoplasma
GBS/E.coli/Listeria
Staph aureus/GAS/Gram negatives
Candida
Syphilis
HSV
Hepatitis B
HIV
Varicella
CMV
Human parvovirus B19
Toxoplasmosis
Malaria
TB
Neonatal Sepsis









Group B  hemolytic Streptococcus
E. coli
Listeria monocytogenes
Group A  hemolytic Streptococcus
Citrobacter, Enterobacter,
Klebsiella, Pseudomonas
Staph aureus
Coagulase negative Staphylococcus
Candida
Tuberculosis
1
7/22/2009
Points about Infections during Pregnancy and
during the Neonatal period




 transplant antigens expressed on cell
surfaces of the fetal/placental unit
 maternal immune responses
selective transfer of immune co-factors
infant immune system develops over
time
Possible Consequences of Congenital
Infections







» 2 months  2 years of age



IgG but not IgM or IgA transplant
across placenta
Placenta (& membranes) act as a
barrier to infection
Neonate is a sterile field for microbial
colonization
Possible Consequences of Congenital
Infections
Intracranial calcifications
and hydrocephalus due to
congenital CMV
Possible Consequences of Congenital
Infections
Hutchison’s Teeth due to
congenital syphilis
Nothing
Fetal Death
Fetal malformations





Chromosomal alterations
Progenitor Cell Death
Scar Formation
Ongoing Infection
Growth disturbances
Microcephaly
Cranial Calcification
Organ system disease
Maternal death
Possible Consequences of Congenital
Infections
Chorioretinitis due to
toxoplasmosis
Possible Consequences of Congenital
Infections
Snuffles
2
7/22/2009
What determines the Consequences







Timing of the maternal infection during
gestation
Timing of the transmission to the fetus
Maternal general health status
Drugs and other treatment given
Virulence of the infecting organism
General health status of the infant
LUCK!!!!
Diagnosis






Neonatal Sepsis



Early: congenital or during labour
Late: Congenital, labour and
delivery, postnatal
Signs: often non-specific
» respiratory distress
» fever
» circulatory collapse
» seizures
» rash
» localizing ms signs
Maternal symptoms
Maternal history of exposure
Isolation of the pathogen from the
mother, placenta and/or infant
Documentation of maternal immune
response (IgM or  IgG)
Infant signs and symptoms
Infant antibody response - IgM, IgA or
sustained IgG
Neonatal Sepsis

Broad Differential Diagnosis
» Primary respiratory disease
» Congenital cardiovascular
disease
» Inborn errors of
metabolism
» Neurovascular accidents
» Sepsis
Management





High index of suspicion
Presume sepsis until proven otherwise
Obtain appropriate cultures THEN start
antibiotics +/- antivirals
Choice of antibiotics based on clinical
situation
Further therapy based on
 results of cultures
 identity of the pathogen
 antimicrobial sensitivities
 clinical condition
 response to therapy
3
University of Manitoba
Faculty of Medicine
Med 2 / Blk 4 / RP063
2008
RP63 TUTORIAL - Perinatal Infections & HIV in Pregnancy
Objectives:
1. Describe the factors that specifically affect infections during pregnancy and in the neonatal period.
2. List the most important congenital and perinatal infections.
3. List the consequences of congenital and perinatal infections.
4. Describe what determines the consequences of congenital and perinatal infections.
5. Outline the clinical & laboratory diagnosis of congenital and perinatal infections.
6. Discuss the prevention and medical management principles for congenital and perinatal infections.
CASE #1 Baby Boy A.
This infant was born at 34 weeks gestation to a 25-year-old gravida 1 para 0 mother. Prenatal course
was uneventful until spontaneous rupture of membranes followed 12 hours later by the onset of labor.
Labor lasted 16 hours. The delivery was difficult and forceps were necessary. The baby was small,
weighing 1900 grams. APGAR scores were 5 at one minute and 9 at five minutes. The baby was well
until 6 hours of age when he was found to be pale and mottled with grunting respirations of 70/minute.
The chest X-ray showed a bilateral reticular infiltrate which had a ground-glass appearance. A CBC was
drawn and the results were as follows: Hemoglobin=124 g/L; Platelet count=18x10e9/L;
WBC=3.2x10e9/L with the differential showing 37% mature and 21% young PMNs.
Comments re case: Normal APGARs of 8 and 8, Hg should be at least 130 in neonates, WBC in first
month of life should be around 20-30.
QUESTIONS:
1. What could be the non-infectious and infectious causes for this child’s illness?
Non-infectious: muconium aspiration
hyaline membrane disease
congenital heart defects
infectious: pneumonia, pneumonitis, sepsis (early onset up to seven days, vs late onset 7 days –
3 months)
- E.coli
- GBS
- Lysteria
- Herpes viruses (HSV, Varicella- especially when lesions present a few days before
and after delivery in which case mom is viremic during delivery)
2. What risk factors
-
could have predisposed this infant to an infection?
prematurity
prolonged rupture of membranes (anything more than 18 hrs is risk for sepsis)
instrumentation
3. When would this infant have probably acquired such an infection?
- exposure during labor and delivery
4. What could have been done to prevent illness due to an infection in this infant?
- Intrapartum Abx for mom if GBS status unknown or positive,
o GBS bacteuria, previous GBS illness in previous baby, GBS swab positive
- If mom has intrapartum fever
- prolonged rupture of membranes
5. Comment on the results of the CBC in terms of the newborn premature infant’s ability to cope with
an infection.
- HgB is low, platelets low (usually same as adults), WBC is very low, significant left
shift (consistent with sepsis and overwhelming sepsis)
Page 1 of 4
University of Manitoba
Faculty of Medicine
Med 2 / Blk 4 / RP063
2008
TX with ampicillin, gentamycin, acyclovir
CASE #2 Baby Boy E.
This infant was delivered ½ hour after this 19-year-old unmarried mother was admitted to hospital in
labor. Gestational age was unknown and the mother had no prenatal care. The mother would give no
information about herself and wanted to sign herself out of the hospital after delivery of her infant.
However, the anesthetist had noted needle marks on her arms when he had started her IV during
delivery.
The infant weighed 1900 grams but appears term. APGARs were 9 at one minute and 9 at five
minutes. The head circumference is less than the 5th percentile for a term infant. The infant is
described by the nurses as jittery and difficult to handle.
QUESTIONS:
1. What congenital or perinatal infections, if any, could this infant have?
- small for gestational age/IUGR type picture
- HIV, syphilis, CMV, toxoplasmosis, HBV, HCV, EBV, parvovirus (tends to cause
hydrops rather than small baby)
2. What are the risk factors which predispose this infant to a congenital infection?
- poor pre-natal care
- high-risk maternal behavior (presumed IV drug use, maybe many sex partners)
- IUGR
3. What other non-infectious problems could this infant have?
- withdrawl
- any other regular baby things – hypoglycemia, hypocalcemia, IUGR stress
4. What other physical findings should one look for to determine if this infant had a congenital
infection?
- vital signs
- constellation of symptoms of specific infections
- Head neck: microcephaly, cataracts (rubella), deafness, Calcifications of brain
seen on CT in CMV, toxoplasmosis,
- SMK: X-ray of long bones for periostitis in syph
5. How could one determine whether this infant had one or more congenital infections?
- toxicology screen
- HIV testing - mom’s serum Ab and baby and do baby HIV PCR at 2 weeks age
o HIV positive mom will hve antibody positive baby
- Hepatitis B – get mom’s status quickly, if positive give baby Anti-HBV Ig and
vaccine, if unknown give vaccine and test baby for Anti-HBV Ab and wait for those
results to decide if Ig should be given
- Blood culture, urine culture, LP for standard pathogens
- LP – Syph, CMV,
- Urine for CMV culture within first 21 days of life
- pathology should look at placenta (infection specific changes)
CASE #3 Baby Boy F.
This infant was born at term to a 23-year-old married gravida 1 para 0 mother. The antenatal course
was uneventful. The infant was born via an uncomplicated vaginal delivery after a 16-hour labor.
Membranes ruptured at delivery. The infant weighed 3600 grams and the APGAR scores were 10 at
both one and five minutes. The post-delivery course was uneventful until the infant was 10 days of age
when his parents brought him to the Emergency Department. He had been well until that day when he
became “fussy” and didn’t feed well. His mother thought he was warm and took his temperature which
was 39.5C. On the way to the hospital, he seemed to become pale and mottled. His mother noted that
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University of Manitoba
Faculty of Medicine
Med 2 / Blk 4 / RP063
2008
he seemed to be arching his back and not responding to her. She thought he might be having a
seizure.
QUESTIONS:
1. What infectious agents acquired perinatally or postnatally could be causing this child’s illness?
- late onset sepsis
- GBS, E.coli, lysteria
- HSV (still within timeframe for disseminated infection)
- enterovirus (GI infections, hand,foot,mouth disease can cause fatal infection in
newborns while generally self-limitting in adulthood)
2. Discuss why infants have “late-onset” perinatal bacterial infections?
- exposed later or with less virulent pathogens
3. What are the risk factors that would predispose this infant to an infection?
- no risk factors
CASE #4 Mother C.
A G1P0 25-year-old married woman seeks prenatal care at 9 weeks gestation. She is well and has no
abnormalities on physical examination. As part of the initial screening investigations, she is found to be
HIV seropositive. Her CD4 count is 400 and her HIV viral load is 55,000 RNA copies per ml. She states
that she has only had one sexual lifetime partner. Her husband is tested and found to be HIV positive.
He denies any risk factors but admits to have had several one night stands while in university before he
was married. The woman elects to continue her pregnancy.
QUESTIONS:
1. What other infectious or non-infectious conditions, if any, could this woman have?
- STI’s come in packs, test for all of them
o syphilis, HPV, GC, Chlamydia, trichomonas, HepB, HepC
2. What are the potential ways that HIV could be transmitted from the mother to her infant?
- transplacental (very small percent), during vaginal delivery, breastmilk
3. What interventions could be used to reduce the risk that the infant will acquire HIV from this
mother?
- Antiretrovirals – start at end of first trimester, triple combo (efaverin is not safe in
pregnancy, the rest are)
- C/S if viral load doesn’t come down below 1,000
- intrapartum IV AZT 2mg/Kg bolus and 1mg/kg/hr after that
- baby gets AZT for a few weeks postpartum
- Baby viral PCR at 2 weeks, and repeat times 2, do antibody screen at 1 year to
confirm
- No breast feeding
CASE #5 Baby Boy H.
This 3-month-old infant is admitted to Children’s Hospital with pneumonia which, on X-ray has a
bilateral interstitial pattern. On physical examination he is distressed and mildly cyanotic with a
respiratory rate of 70 per minute. His weight, height and head circumference are all below the 5 th
percentile for his age. The liver edge is palpable 5 cm below the right costal margin and the spleen is
palpable 2 cm below the left costal margin. He has several palpable lymph nodes 1-2 cm in diameter
bilaterally in the axillar, inguinal and cervical regions.
QUESTIONS:
1. What congenital or perinatal infection, if any, could this boy have?
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University of Manitoba
Faculty of Medicine
Med 2 / Blk 4 / RP063
2008
-
HIV + pneumocystis pneumonia until proven otherwise
Chlamydia
Community acquired pneumonia
RSV
big liver, spleen and lymphnodes : EBV, CMV, Toxoplasmosis, leukemia,
SCID would present at this age but they don’t have lymph nodes
2. How could HIV infection be diagnosed in this circumstance?
- viral PCR (because he’d still have mom’s Ab)
- CD4 count and CD8 counts will come back more quickly (less than 500 is the child
equivalent to the adult less than 200)
3. If this infant were found to be infected with HIV, what other clinical illnesses might this child
develop in the future?
- any opportunistic infection (toxoplasmosis, CMV)
- community acquired infections
- DO ALL IMMUNIZATIONS except BCG or oral polio
4. Generally, how would you treat this boy if he were found to be HIV infected?
- infants are treated at time of diagnosis because there are a subset of kids that will
deteriorate very quickly in first year of life
- kids diagnosed later in life are followed for CD4 and viral loads every three months
o different cell count numbers
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