Pathology of Newborn II

Dr.Muneera Alabdulqader
§ Infections:
61. Definition of 'neonatal sepsis, etiology ,risk factors, clinical course
and how distinguishing between different types.
63. Causative organism for neonatal meningitis.
64. Epidemiology, clinical course, diagnosis and treatment of some
perinatal infection.

§ Neonatal Hypoglycaemia:
46. Describe the changes in glucose homeostasis that occur around the
time of birth.
47. What are the causes and symptoms of neonatal hypoglycaemia?
Neonatal sepsis
 neonate

First 28 days of life

 SEPSIS
Sepsis =
Systemic inflammatory response syndrome (SIRS)
+ Suspected or proven infection
SIRS: 2 of 4 criteria,
1. Core Temperature >38.5°C (101.3°F) or <36°C (96.8°F)
2. Tachycardia or bradycardia over 0.5 hr.
3. Tachypnea or acute need for mechanical ventilation .
4. Leukocyte count elevated or depressed for age or
>10% immature neutrophil
1of which must be abnormal temperature or abnormal leukocyte
count
§ Systemic and local infections (lung, cutaneous,
ocular, umbilical, kidney, bone-joint, and meningeal)
in the newborn period.
Early-onset sepsis
(birth to 7 days)
Late-onset sepsis
(> 7-28 days)
Very Late-onset
sepsis
(>28 days)
duce the rates of late-onset GBS disease and has no
throughwith
of infection thenon-GBS
birth canal and/or
pathogens. Ofenters
concerntheis extrauterine environment. 401-1,500 (respiratory
1,501-2,500 distress,>2,500
shock). Aspiration
All or ingestion of bacteria d
e in The human birth
gram-negative canal is
infections colonized
(especially E. with aerobicAll
coli) in and anaerobic organ- 10.96 the birth process may
1.38 lead to 0.98
0.57 infection after an interval of 1-2 d
bly term infants in spite of a reduction in early GBS Resuscitation at birth,
isms that may result in ascending amniotic infection GBS and/or coloniza- 2.08 0.38 0.35 particularly
0.41 if it involves endotracheal in
tum tion
antibiotics.
of the neonate at birth. Vertical transmission of bacterial agents tion, insertion of an umbilical vessel catheter, or both, is asso
of meningitis is 0.2-0.4/1,000 live births in newborn Escherichia coli
that infect the amniotic fluid and/or vaginal canal may occur in utero 5.09
with an0.54
increased risk 0.07 0.28
of bacterial infection. Explanations includ
her in preterm infants. Bacterial meningitis may be Stoll BJ,Cho-
or, more commonly, during labor and/or
psis or may occur as a local meningeal infection. Up delivery (Fig.
Modified 109-2).
from presence
Hansen NI, Sanchez of
PJ, et al:infection
Early onset at the
neonataltime of birth or acquisition of infe
sepsis: the burden of group B streptococcal and E. coli disease continues,
LBW rioamnionitis resultsmeningitis
infants with late-onset from microbial invasion Pediatrics
have negative of amniotic fluid, often
127(5):817–826, 2011. during the invasive procedures associated with resuscitation.
as a result of prolonged rupture of the chorioamniotic membrane.
Amniotic infection may also occur with apparently intact membranes PATHOGENESIS OF LATE-ONSET
or with a relatively brief duration of membrane rupture. The term POSTNATAL INFECTIONS
chorioamnionitis refers to the clinical syndrome of intrauterine infec- After birth, neonates are exposed to infectious agents in the nu
tion, which includes
Amniotic maternal
fluid fever, with or without local or systemic
Placenta or in the community (including family). Postnatal infections m
Uterus

signs of chorioamnionitis (uterine tenderness, foul-smelling vaginal

discharge/amniotic fluid, maternal leukocytosis, maternal and/or fetal
tachycardia). Chorioamnionitis may also be asymptomatic, diagnosed
only by amniotic fluid analysis or pathologic
Amnion Funisitis
examination of the pla- Amniotic Infection
centa. The rate of histologic chorioamnionitis is inversely related to
Amniotic
gestational age at birth (Fig. 109-3)fluid
and directly related to duration of
infection Aspiration Ingestion
membrane rupture. Rupture of membranes for longer than 24 hr was
once considered prolonged because microscopic evidence of inflam-
Chorioamnionitis In utero
mation of the membranes is uniformly present when the duration of
Chorion Pneumonia Gastrointestinal
rupture exceeds 24 hr. At 18 hr of membrane rupture, however, the colonization
incidence of early-onset disease with group B streptococcus (GBS)
Choriodecidual
infection
Intrapartum
! Bacteremia ! Invasion

Decidua Maternal infectionFetal

infection Aspiration
Fetus Ingestion ! Bacteremia

Bloodstream invasionChoriodecidual
infection Cervix
No fetal or placental Placental infection Vaginal secretions
infection
Myometrium Figure
Vagina 109-2 Pathways of ascending or intrapartum infecti
Fetal infection No fetal infection
No effect on growth
or viability Effects on growth and viability n! 70
Nelson textbook of pediatrics 20th ed
261 n!
otential sites of bacterial infection within the uterus. (From Goldenberg RL, Hauth JA, Andrews WW: Intrauterine
n ! infection
200 and
N Engl J Med 342:1500–1507, 2000.Abortion
Copyright 2000, Massachusetts
Premature Medical
Term Society.) 60
 Same as Early onset +

Postpartum acquired infections

Nosocomial acquired infectious diseases.

§ The incidence
§ 1:1,500 in full-term infants and
§ 1:250 in preterm infants.
§ The sixfold-higher rate of sepsis in preterm infants
relates to
§ immature immunologic systems.
§ prolonged periods of hospitalization.
§ Most common organisms in Early onset
sepsis/ Meningitis
§ Group B streptococci
§ E. coli, Klebsiella
§ L. monocytogenes
§ nontypeable H. influenzae.
§ Herpes simplex virus (HSV)-1 or, more often, HSV-
2 also causes ascending infection that at times may
be indistinguishable from bacterial sepsis.
§ Most common organisms in Late onset
sepsis
§ Coagulase-negative staphylococci,
§ Gram-negative bacilli (E. coli, Klebsiella
pneumoniae, Enterobacter, Pseudomonas
aeruginosa),
§ Group B streptococci
§ Enterococci
§ Staphylococcus aureus
§ Enteroviruses
§ Focal infections
§ Meningitis (GBS, Ecoli )
§ Osteomyelitis (group B streptococci,
Staphylococcus aureus),
§ Arthritis (gonococcus, S. aureus, Candida albicans,
gram-negative bacteria),
§ Urinary tract infection (gram-negative bacteria).
§ Vaginal colonization with group B streptococci
§ Prolonged rupture of the membranes (>24 hours)
§ Amnionitis
§ Maternal fever
§ Maternal leukocytosis
§ Fetal tachycardia
§ Preterm birth
§ African American race
§ Male gender
§ CBC.
§ Blood culture.
§ CSF (Gram stain, cell count, protein, glucose
levels).
§ CSF cultures.
§ C-reactive protein levels.
§ Procalcitonin
§ Urine analysis and culture (for Late sepsis).
§ Chest X- ray ( if respiratory symptoms)
§ To reduced the rate of early-onset infection
§ Give Intrapartum penicillin empirical
prophylaxis for:
§ Group B streptococcal colonized
mothers or
§ Mothers with risk factors (fever, preterm
labor, previous infant with group B
streptococci, known colonization, and
amnionitis, PROM).
 Bacteremia or
Pneumonia
(10-14 days)

Meningitis
Culture positive
Suspected Sepsis

3 weeks or
( Treat according to the
cultures) 2 weeks after
–ve CSF culture
Take Cultures
And Start Osteomyelitis
Empirical
antibiotics 4-6 weeks

Clinically no sepsis stop antibiotics

Culture negative

Antibiotics for 10-14

Clinically ill
days
§ Early onset
§ Ampicillin + Aminoglycoside (usually
Gentamicin)
§ Ampicillin + Cefotaxime
§ Late onset
§ Ampicillin + Aminoglycoside (usually Gentamicin)
§ Ampicillin + Cefotaxime ( especially last week of first
month)
§ and Vancomycin if meningitis is present
Congenital infections
§ Congenital Infections: infection acquired transplacentally
during gestation
§ Perinatal Infection: During the birth process.

§ TORCH Infection
 Maternal infection
! Bac
Bloodstream
Bloodstream invasion
invasion ! Bacteremia
Bloodstream invasion
Maternal infection
Maternal
No fetalNo infection
or fetal or placental
placental Placental infection
Placental infection
Aspiration
No fetal or placentalinfectioninfection Placental infection
infection Bloodstream invasion
Bloodstream invasion Figure 10
No fetal or placental Fetal infection
Fetal infection No fetalNo fetal infection
infection
No fetal or placental Fetal infection Placental infection Va
infectionNo effect
No effect on growth Placental infection No fetal infection
infection on growth
No effect on growth or viability
or viability Effects on growth and Figure
viability 109-2 Figure
Pathways 10o
or viability Effects on growth and viability 70 n
Effects on growth and viability
Fetal infection
Fetal infection No fetal infection 2
Embryonic
Embryonic No fetal
Abortion infection
Abortion PrematurePrematureTerm Term
infant infantinfant infant 60
No effect on growth

%
No effect on growth Embryonic Abortion
death and Premature
and Term
or death
viability death 70 n
and infant infant 70

chorioamnionitis
or viability and Effects
and on growth
resorption
resorption and stillbirth
viabilitystillbirth n!
andEffects on growth and viability
resorption stillbirth n! 2 50 261
n ! 200
60

%
Embryonic Abortion Premature Term 60

Histological chorioamnionitis %
Embryonic Abortion Premature Term Develop-Congenital 139Normal
deathIntrauterine Intrauterine
Intrauterineand infant Develop-
infant infantCongenitalNormal

chorioamnionitis
death and Develop-
growth infant
Congenital
mental mental disease Normal
disease infant infant 40 n
and resorption growthstillbirth
and resorption stillbirth
growth mental
restriction disease
anomaliesanomalies infant 50 16
restriction 50
restriction anomalies
30
Intrauterine Develop- Congenital Normal 40

Histological
Intrauterine Develop- Congenital Normal 40
growth mental disease infant
growth mental
Persistent disease
Persistent postnatal
postnatal infection infant
infection Eradication
Eradication of infection
of infection
restriction
Persistent postnatal infection anomalies Eradication of infection 20
restriction anomalies 30
30

Histological
Progressive
Progressive 10
Progressive tissue damage tissue damage
Persistentleading
postnatal infection No apparent
No apparent
Eradication of infection20 Sequelae Sequelae
of 20
of
tissue damage
Persistent postnatalleading
infection to to Eradication of infection
No apparent diseasedisease Sequelae of infection infection
leading to sequelae sequelae
or death or death disease infection 0
sequelae or death
Progressive 10 10 20
Progressive Figure
tissue damage Figure
109-1109-1 Pathogenesis
Pathogenesis of hematogenous
of hematogenous transplacental
transplacental infec- infec-
tissue damage Figure 109-1 Pathogenesis of hematogenous
No apparent transplacental Sequelae infec-
of
leading to tions. tions.
(FromNo (From
Klein Klein
JO,
apparent JO, Remington
Remington JS:
of Current
JS: Current
Sequelae concepts concepts of infections
of infections of Fig
0of
leading to tions. (From
sequelae ortheKlein
fetus
death JO,
theand Remington
fetus and newborn
disease
newborn JS: disease
Current
infant.infant. concepts of
In Remington
infection
In Remington
infection
infections
JS,JO,
JS, Klein Kleinof0
JO,
editors: Figure
editors:
Infec- 109-3
Infec- by
20
sequelae or deaththe fetus and newborn infant. In Remington JS, Klein JO, editors:
Nelson Infec- 20–24by 25 26
hgestationa 2
tious diseases
tious diseases of the of theand
fetus fetus and newborn
newborn infant, edtextbook
infant, ed 5,of pediatrics 21 ed 2002,
Philadelphia,
5, Philadelphia, 2002, fet
 When to suspect
congenital
infections ?
Ø IUGR
Ø Nonimmune hydrops
Ø Anemia
Ø Thrombocytopenia
Ø Jaundice
Ø Hepatosplenomegaly
Ø Chorioretinitis
Ø Congenital
malformations.
 Perinatal congenital infection
Clinical features
Organism Treatments
CNS Liver heart Eyes Ears Skin/ Bone Lung Blood others

Hydrocephalus
Jaundice Chorioretinitis Pyrimethamine
Toxoplasma Anemia
Chorioretinal + Sulfadiazine
gondii Intracranial Thrombocytopenia
HSM scars + leucovorin
calcifications

Microphthalmia
Jaundice Anemia Prevention:
PDA Cataracts
Rubella Microcephaly Blueberry muffin Thrombocytopenia IUGR vaccine
PAS Glaucoma Deafness
virus HSM rash Leukopenia No specific
“salt and pepper”
treatment
Chorioretinitis

Blueberry muffin Sepsis

Cytomegalo Microcephaly Jaundice Anemia
rash Pneumonia
virus periventricular Chorioretinitis Deafness Thrombocytopenia Ganciclovir
Petechiae/Purpura IUGR
CMV calcifications HSM Neutropenia

Prevention:
Varicella- Microphthalmia,
cutaneous VZIG
zoster virus cataracts,
And bony lesions Treatment:
VZV chorioretinitis,
acyclovir

nonimm
Treponema CSF pleocytosis HSM Pneumonia Anemia une
Interstitial
pallidum & Deafness Hutchinson teeth syphilitic Thrombocytopenia hydrops penicillin
keratitis
(syphilis) Lymphocytosis Hepatitis rhinitis Neutropenia prematu
rity
Herpes Intrauterine infection: chorioretinitis, skin lesions, microcephaly
simplex Perinatal Infections :Skin, eye, and mouth disease (few small vesicles, particularly on the presenting part or at sites of trauma )
acyclovir
virus HSV encephalitis,
§ Transmitted most commonly from cats.
§ Most infants have subclinical infection with no
overt disease at birth.
§ The classic findings of hydrocephalus,
chorioretinitis, and intracerebral
calcifications. IUGR, develop early-onset jaundice,
have hepatosplenomegaly, and present with a
generalized maculopapular rash. Seizures are common,
§ Skull films may reveal diffuse cortical
calcifications
§ For symptomatic and asymptomatic congenital
infections:
§ TTT: Pyrimethamine combined with
sulfadiazine.
 Image 119.6
Young adult male with postrubella thrombo-
cytopenic purpura with large blueberry muffin
skin lesions.

Image 119.7
Newborn w
of Immuniza

Image 119.9

§ Rare in developed countries. (due to routine A 4-year-old

syndrome w
vaccines) Image 119.8
cataract form

This photograph shows the cataracts in an

infant’s eyes due to congenital rubella syndrome.
§ Acquired early gestation can cause severe neonatal Rubella is a viral disease that can affect suscep-
tible persons of any age. Although generally a
consequences. mild rash, if contracted in early pregnancy,
there can be a high rate of fetal wastage or
birth defects, known as congenital rubella
§ The occurrence of congenital defects approaches 85% if syndrome. Courtesy of Centers for Disease
Control and Prevention.
infection is acquired during the first 4 weeks of gestation.
§ The most common characteristic include:
§ Ophthalmologic
§ Cardiac (patent ductus arteriosus and peripheral
pulmonary artery stenosis), Sensorineural hearing
loss, Neurologic , Growth retardation,
hepatosplenomegaly, early-onset jaundice,
thrombocytopenia, radiolucent bone disease, and
purpuric skin lesions (“blue-berry muffin”
appearance from dermal erythropoiesis).
§ The most common congenital infection.
§ Congenital CMV occurs in about 0.5–1.5% of births.
§ More than 90% no clinical evidence of disease at birth.
§ Findings include: Microcephaly, thrombocytopenia,
hepatosplenomegaly, hepatitis, intracranial
calcifications, chorioretinitis, and hearing
abnormalities. Some infants can present with a
blueberry muffin appearance as the result of dermal
erythropoiesis.
§ Skull films may reveal periventricular calcifications.
§ 10% of infected infants may not present until later in
infancy or early childhood ( developmental delay ,
deafness)
§ Treatment: ganciclovir
§ Clinical symptoms vary: include hydrops fetalis ,
hepatosplenomegaly, snuffles, lymphadenopathy,
mucocutaneous lesions, osteochondritis, rash,
hemolytic anemia, and thrombocytopenia.
§ The combination of interstitial keratitis,
eighth cranial nerve deafness, and
Hutchinson teeth is commonly referred
to as the Hutchinson triad
§ Treatment: Parenteral penicillin is the
preferred drug of choice for treatment of
syphilis.
§ Early gestation infection result in :
§ Microphthalmia, cataracts, chorioretinitis,
cutaneous and bony aplasia/
hypoplasia/atrophy, cutaneous scars.
§ Later Infection
§ Infant develops severe neonatal
varicella with maternal illness 5
days before or 2 days after delivery.
§ Prevention: VZIG
§ Treatment: acyclovir
§ 70–85% of neonatal herpes simplex
infections are caused by HSV-2.
§ Intrauterine infection: chorioretinitis,
skin lesions, microcephaly
§ Perinatal Infections: symptoms of
infection develop at 5–10 days of life.
§ Skin, eye, and mouth disease (few
small vesicles, particularly on the
presenting part or at sites of trauma )
§ Encephalitis
§ Disseminated HSV infections (similar
to that of infants with bacterial sepsis)
§ Treatment: Acyclovir
 NEISSERIA GONORRHOEAE CHLAMYDIA TRACHOMATIS

§ Within the first 5 days of life.
§ Transmission during passage
through the birth canal.
§ Infants should be hospitalized and
evaluated for disseminated disease
(sepsis, arthritis, meningitis).
§ One intramuscular dose of
ceftriaxone
§ 5-14 days to weeks after birth.
§ Transmission during passage
through the birth canal.
§ Need to R/O Pneumonia
§ Oral azithromycin for 3 days
or erythromycin for 14 days.

Tests for concomitant infection

Topical prophylaxis with erythromycin, or tetracycline is recommended
for all newborns for the prevention of gonococcal ophthalmia not
neonatal chlamydial conjunctivitis. .
 Neonatal
Hypoglycemia
§ Infant of diabetic mother
§ Neonatal sepsis
§ Inborne error of Metabolism
§ Perinatal asphyxia
§ Others
Pregastational diabetes
Diabetes mellitus that develops during pregnancy
(Gestational diabetes) affects 5% of women.
Effect of diabetes on the fetus depends on :

Duration of Presence of
Severity of Age of onset treatment vascular Control of
the DM of the DM the DM
with insulin disease.
mmon in ill Maternal
e levels but hyperglycemia
pituitary– Placenta
cally euthy-
o difference Fetal hyper- Fetal hyper- Fetal hyper-
practice is glycemia insulinemia glycemia and
hyperthy- hyperinsulinemia
thyroidism
medication. 1. Congenital 1. Neonatal 1. Fetal macrosomia
any of the anomalies hypoglycemia (!20 weeks
(peri-con- (0-7 days postnatal) gestation)
ceptional)
ces, which
during the a. Birth asphyxia
2. Decreased
may occur early growth
2. Surfactant deficiency b. Cardiomyopathy
(neonatal) c. TTN
with over- (0-20 weeks
shock can gestation) 3. Immature 2. Fetal hypoxia
miting, diar- liver metabolism (!30 weeks
3. Hyperinsul-
ambiguous inemia
(neonatal) gestation)
ous genitals (!20 weeks
etermined, gestation)
drenocorti- a. Jaundice a. Polycythemia
s of adrenal
therapy for c. Iron
outcomes. b. Stroke, RVT
abnormalities
to adrenal
Poor neurodevelopmental outcome
atic edema,
Nelson textbook of pediatrics 21th ed
Problems
 Problems
§ Neonatal mortality rate is >5 times
§ Hypoglycemia
§ Congenital anomalies (> 3-fold in infants of diabetic
mothers)
§ Birth injuries
§ Others

The risk of diabetic embryopathy (neural tube

defects, cardiac defects, caudal regression
syndrome) and spontaneous abortions is highest in
those with pregestational diabetes
 HYPOGLYCEMIA SIGN AND SYMPTOMS
DUE to EPINEPHRINE RELEASE DUE to CEREBRAL GLYCOPENIA

Perspiration Headache
Palpitation (tachycardia) Mental confusion
Pallor Somnolence and lethargy
Paresthesia Personality changes
Tremulousness Refusal to feed
Anxiety Inability to concentrate
Weakness Staring
Nausea Hunger
Vomiting Convulsions
Ataxia
Coma
Apnea
 Screening and Management of Postnatal Glucose Homeostasis in Late Preterm
and Term SGA, IDM/LGA Infants
[(LPT) Infants 34–366/7 weeks and SGA (screen 0–24 hrs); IDM and LGA "34 weeks (screen 0–12 hrs)]

Asymptomatic Symptomatic
and !40 mg/dL

Birth to 4 hours of age 4 to to

Birth 244hours
hoursofofage
age
IV glucose
INITIAL FEED WITHIN 1 hour Continue feeds q 2–3 hours
Screen glucose 30 minutes after 1st feed Screen glucose prior to each feed

Initial screen !25 mg/dL Screen !35 mg/dL

Feed and check in 1 hour Feed and check in 1 hour

!25 mg/dL 25–40 mg/dL !35 mg/dL 35–45 mg/dL

IV glucose* Refeed/IV glucose* IV glucose* Refeed/IV glucose*

as needed as needed

Target glucose screen "45 mg/dL prior to feeds

*Glucose dose = 200 mg/kg (dextrose 10% at 2 mL/kg) and/or IV infusion at 5–8 mg/kg per min (80–100 mL/kg per d).
Achieve plasma glucose level of 40–50 mg/dL.

Symptoms of hypoglycemia include: Irritability, tremors, jitteriness, exaggerated Moro reflex, high-pitched cry,
seizures, lethargy, floppiness, cyanosis, apnea, poor feeding.
7-3 Screening for and management of postnatal glucose homeostasis in late-preterm (LPT 34-36
Nelson textbook wk) and
of pediatrics term small-f
20th ed
nfants and infants who were born to mothers with diabetes (IDM)/large-for-gestational age (LGA) infants. LPT and SGA, sc
 Essential Nelson
9th ed.
Chapter :59,65,66