30
1 Neonatal Infection . . 1. 2. 3. 4.
1
Neonatal Infection
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Infection
Host
OrganismTrans
mission
Neonatal Host Defense Mechanism
Humoral immunity Immunoglobulin: IgM, IgA �() Complement, opsonin �()Cellular immunity
Neutrophil storage pool �() Defect in PMN function
Chemotaxis
Phagocytosis
Barrier
Skin
Umbilicus
3
Transplacental Infection
Ascending infection
*��#��+('��%�������,-% ����+.$/ �+�������,-% ��,% colonization $%'��,-% &�'�-)��()�����%��"%������� 18 ��. (PROM > 18 h)&�'�-)��()�����,-% (chorioamnionitis)���������%��)��� �����������)���� ���� gastroschisis, meningocele ��$�%%�H���� �"%�� I�/���,(%'�,%����"%���,% prolonged second stage of labor ��I��������'N ���� umbilical catheter��I����%�"%�"��% ��I�/���,(%'����I� ��I�/��%���'�"%��",%� (parenteral nutrition)
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Neonatal Bacterial Infection
� Early-onset infection
� Late-onset infection
"#��!��'�"����$%'�������,-%I�����������Characteristic Early-onset Late-onset
Time of onset (days) < 3 > 3
Complication of pregnancy
and delivery + +
Source of organism mother’s genital tract postnatal environment
Common organism Streptococcus (GBS) Staphylococcus coag +/-
E.coli E.coli, other gram neg.
Clinical presentation fulminant slowly progressive
multisystem focal
pneumonia frequent meningitis frequent
Mortality rate (%) 5-50 2-6
5
Classification
of Triple I
Terms Definition
Isolated maternal
fever
• Oral temperature > 39oC
• Oral temperature 38-38.9oC x 2 times of
at least 30 minutes apart
Suspected triple I Fever without a clear source and any of the
following;
• Baseline fetal heart rate > 160 bpm for >
10 minutes
• Maternal WBC > 15,000/mm3 (in the
absence of corticosteroids
• Definite purulent fluid from the cervical
os
Confirmed triple I All of the above + objective evidence of
an intrauterine infection
Amniotic fluid
• Positive gram stain
• Positive culture
• Low glucose level (< 14 mg/dL)
• Increased WBC > 30/mm3 in the
absence of bloody tap
Histopathological evidence of
infection/inflammation in placenta, fetal
membrane, umbilical cord vessels
Clinical
Microbiolo
gical
Biochemi
cal
Histological
Diagnosis of Chorioamnionitis
Presence of
inflammatory
biomarkers
Maternal fever >38oC
and
• Tachycardia
• Fetal tachycardia
• Maternal
leukocytosis: WBC
> 15000/mm3
• Foul smell
amniotic fluid
• Uterine tenderness
Positive H&E stain
of the membrane or
umbilical cord on
light microscopy
Positive
culture or
PCR
Polin RA. CANN Conference 2018
6
%���"�%�����'$%' neonatal sepsis
Signs and Symptoms %
LethargyLethargy 8080
Poor feedingPoor feeding 6868
HypothermiaHypothermia 6060
FeverFever 4747
DyspneaDyspnea 6060
JaundiceJaundice 3838
Abdominal distensionAbdominal distension 3737
CyanosisCyanosis 3636ApneaApnea 3636
%���"�%�����'$%' meningitis
Clinical Signs %
HyperthermiaHyperthermia 6161
LethargyLethargy 5050
VomitingVomiting 4949
RespiratoryRespiratory distressdistress 4747
ConvulsionsConvulsions 4040
IrritabilityIrritability 3232
BulgingBulging oror fullfull fontanellefontanelle 2828
JaundiceJaundice 2828
ApneaApnea 77
7
��������Bacterial Infection
� Presenting signs and symptoms may
range from minor complaints to shock
� Infants with fever >38oC should always
prompt a full evaluation for sepsis
� Risk factors: preterm, GBS, PROM,
chorioamnionitis
Puopolo KM, et al. Pediatrics 2011;128:e1155-63
8
Risk Factors: EOS
ConditionCondition Incidence of Proven SepsisIncidence of Proven Sepsis
PROM PROM >> 18 18 hourshours 11%%
Maternal GBS + (preMaternal GBS + (pre--prophylaxis era) prophylaxis era) 00..55--11..00%%
Maternal GBS + (prophylaxis era)Maternal GBS + (prophylaxis era) 00..11--00..22%%
ChorioamnionitisChorioamnionitis 33--88%%
Maternal GBS + & Other risk factors e.g. PROM Maternal GBS + & Other risk factors e.g. PROM 44--77%%
Maternal GBS + & Maternal GBS + & ChorioamnionitisChorioamnionitis 66--2020%%
PROM & PretermPROM & Preterm 44--66%%
PROM & Low PROM & Low ApgarApgar scoresscores 33--44%%
Gerdes JS. Pediatr Clin N Am 2004
Verani JR, et al.
MMWR Recomm
Rep 2010;59:1-36.
9
�������'�/%' P�Q#����
CBC
- WBC
- Total neutrophil
- Immature neutrophil
- I:T ratio
- Platelets count
CRP, ESR
Lumbar puncture
Gastric content examination
Gold standard:
Culture
- Blood
- CSF
- Urine
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%� WBC PMN
(%)
Band
(%)
Lymphocyte
(%)
������� 18,100
(9,000-30,000)
52 9 31
7 �#� 12,200
(5,000-21,000)
39 6 41
14 �#� 11,400 34 5 48
10
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Term Preterm
WBC (cells/mm3) 8 (0-32) 9 (0-29)
PMN (%) 61 57
Protein (mg/dL) 90 (20-170) 115 (65-150)
Glucose (mg/dL) 52 (34-119) 50 (24-63)
���#��Early onset : ampicillin/PGS + gentamicin
Late onset : cloxacillin + gentamicin
vancomycin + amikacin
GBS : high dose penicillin 200,000 u/kg
ampicillin 200 mg/kg
Meningitis : double dose of ampicillin +
gentamicin
cefotaxime
Duration : sepsis 10 �#�
meningitis 14-21 �#�
11
� Full sepsis evaluation
� CBC
� Blood culture
� Urinalysis
� Urine culture (catheterized or suprapubic
specimen)
� CXR (respiratory distress)
� LP (late-onset sepsis, early-onset sepsis with
symptoms that suspected meningitis, positive
blood culture, respiratory distress: exclude
RDS or MAS)
� Broad-spectrum antibiotics
Neonatal Sepsis Risk Calculator
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Prior probability
GA >34 wks
Escobar GJ, et al.
Pediatrics 2014;
133:30-6.
13
Prior probability
Posterior probability
Stratification of Risk of EOS in NBs
>34 Weeks’ Gestation
Escobar GJ, et al. Pediatrics 2014;133:30-6
14
Infants born to mother
with intrapartum fever
GA < 34
weeks
GA > 34
weeks
Suspected or
Confirmed
triple I
Isolated
maternal
fever
Isolated
maternal
fever
Confirmed
triple I
Suspected
triple I
Sepsis
screen labs
If labs
normal,
closely
observed
• Blood
culture
• Sepsis
screen
labs
• Start
antibiotics
Closely
observed
• Individualiz
ed care
• If infant
remains well
����
observation
• Sepsis
calculator?
• Blood
culture
• Sepsis
screen labs
• Antibiotics
Higgin RD, et al. Obstet Gynecol. 2016;127:426-36
Congenital Infection
Intrauterine infection
Etiology :
Toxoplasma gondii
Others: syphilis, HIV, varicella, etc.
Rubella
Cytomegalovirus
Herpes simplex
15
�������S#
1. History
2. Clinical manifestation
3. X-ray
4. Serology
5. Quantitative IgM
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Clinical signs Rubella CMV Toxo HSV Syphilis
Hepatosplenomegaly
Jaundice
+
+
+
+
+
+
+
+
+
+
Lesions of skin or mucous membranes
Petechiae or purpura
Vesicels
Maculopapular rash
+
-
-
+
+
-
+
-
+
+
++
+
+
+
++
Lesions of nervous system
Meningoencephalitis
Microcephaly
Hydrocephalus
Intracranial calcified
Hearing deficits
+
-
+
-
+
+
++
+
++
+
+
+
++
++
-
+
+
+
-
-
+
-
-
-
+
Clinical signs Rubella CMV Toxo HSV Syphilis
Lesions of heart
Myocarditis
Congenital defects
+
++
-
-+
-
+
-
-
-
Bone lesions ++ - + - ++
Eye lesions
Glaucoma
Chorioretinitis
Cataracts
Microphthalmia
Keratoconjunctivitis
++
++
++
+
-
-
+
-
-
-
-
++
+
+
-
-
+
+
-
++
+
+
-
-
-
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Microorganism Signs
Rubella virus Cardiac defects, sensorineural hearing loss, cataracts
Cytomegalovirus Microcephalus, periventricular calcification
Toxoplasma gondii Hydrocephalus, diffuse intracranial calcification, chorioretinitis
Herpes simplex virus Vesicular lesions, keratoconjunctivitis
Treponema pallidum Bullous, macular, and eczematous
skin lesions involving the palms and soles; rhinorrhea; dactylitis and other signs of ostechondritis and periostitis
Congenital CMV Infection
Incidence 0.15-2% of LB
Major cause of MR, CP, SNHL
10% Death in symptomatic newborns
Treatable
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Congenital CMV Infection
Transmission
- Via placenta
- Human milk
- Blood transfusion, organ transplantation
- Body fluid: saliva, sexual
Primary maternal CMV infection
- 95% Clinically inappetence
- 35% Transmitted to fetus
Congenital CMV Infection
InvestigationMaternal
- CMV IgM, IgG, IgG avidity
Prenatal- PCR for CMV
- CMV IgM
Postnatal- Isolation of CMV from urine or other body fluid in
first 3 weeks
- CMV IgM (false positive/negative)
- PCR for CMV
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CMV: Antiviral Treatment
Ganciclovir IV or Valganciclovir oral
Total of 6 months for most newborns with symptomatic congenital CMV infection
Whom to treat- Symptomatic infection
- Asymptomatic infection with failed hearing screen
- Primary immunodeficiency: SCID
Uptodate.com
Neonatal Herpes Infection
Route of infection
- Congenital (transplacental) 5%
- Perinatal infection 85%
- Direct contact with maternal genital herpes
- Ascending infection after ROM
- Posnatal infection 10%
40-44% Primary maternal HSV infection
1.3-3% Recurrent maternal HSV infection
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Neonatal Herpes Infection
1. Localized form
- Skin, eye, mouth
- Onset 10-11 �#�
- Recurrence after treatment
Neonatal Herpes Infection
2. Encephalitis form- %��Q�����#Q disseminated form ��,% localized form
- Cortical hemorrhagic necrosis
- HV� �#� poor feeding
- Severe sequelae
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Neonatal Herpes Infection
3. Disseminated form
- Multi-organ involvement
- Onset 1-2 �# ��
- %���"/ bacterial sepsis
- Vesicle �Q.�/ ���! 80%
- Worst prognosis
Neonatal Herpes Infection
Woman in labor with visible genital lesion:
Swab - PCR for HSV and culture
Woman without a history of genital herpes:
HSV1 & HSV2 antibody
22
Neonatal Herpes Infection
Whole blood PCR, CBC, LFT
Viral isolation: oropharynx, nasopharynx, conjunctivae, rectum, CSF
CSF: profile-elevate protein, PCR for herpes
CXR: pneumonitis
EEG: focal or multifocal periodic epileptiform D/C
Brain CT/MRI: parenchymal edema or attenuation,
hemorrhage or destructive lesions involving the
temporal, frontal, parietal or brainstem regions of
the brain
Treatment
Acyclovir 20 mg/kg/dose IV q 8 hours
- Localized form 14 days
- Encephalitis form 21 days
- Disseminated form 21 days
or until PCR negative (repeat LP)
Oral Acyclovir suppression 300 mg/m2/dose
q 8 hours for 6 months
(improve neurodevelopmental outcome)
Isolation
23
Congenital Syphilis
Early: < 2 W
2/3 asymptomatic
Late: > 2 W
Clues That Suggest a Diagnosis of
Congenital Syphilis
Maternal history
- Untreated syphilis in the mother
- Mother treated for syphilis during pregnancy with
a drug other than penicillin
- Mother treated for syphilis during pregnancy and
not followed to delivery
- Last dose of treatment <4 weeks prior to delivery
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Clinical Findings
Nonimmune hydrops fetalis
Placental villitis or vasculitis (unexplained
enlarged placenta)
Intrauterine growth retardation; failure to thrive
Snuffles, hemorrhagic rhinitis
Condylomatal lata
Bullous lesions, palmar/plantar rash, mucus
patches
Clinical Findings
Hepatomegaly, splenomegaly
Jaundice
Hemolytic anemia, diffuse intravascular
coagulation, thrombocytopenia
Osteochondritis, periostitis
Generalized lymphadenopathy
Pneumonitis
Nephrotic syndrome
Elevated cell count or protein in CSF
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Suggested Diagnostic Categories of Congenital Syphilis Relative to
Confidence of Diagnosis
Definite Diagnosis
Confirmation of presence of T.pallidum by
dark-field microscopic
or histologic examination or rabbit infectivity
test (RIT)
Probable Diagnosis
1. STS (VDRL) increased fourfold or greater
than maternal STS
2. STS (VDRL) reactive in presence of other
clinical manifestations
3. STS (VDRL) reactive in cerebrospinal fluid
Serum: VDRL mother & baby (at delivery)
CBC, LFT, X-ray long bone, CXR (if indicated)
CSF: profile & VDRL
26
Possible DiagnosisSTS (VDRL) reactive in absence of clinical
manifestations
- Normal lab tests
- Abnormal lab tests
Serum: VDRL mother & baby (at delivery)
CBC, LFT, X-ray long bone, CXR (if indicated)
CSF: profile & VDRL
Less Likely DiagnosisSTS non reactive in absence of clinical
manifestations
Serum: VDRL mother & baby (at delivery)
Others investigation & treatment: not required
27
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���#��
Aqueous penicillin G IV
50,000 u/kg/dose q 12 hours x 7 days
then q 8 hours for a total of 10 days
Procaine penicillin G IM
50,000 u/kg/dose single daily dose x 10 days
Benzathine penicillin IM single dose
- Possible infection ���.���+%��I�N �"��" lab ���
- ���.�/�#Q���#����Q�"���� ��� ���.�����I������ follow
up ��,%.��
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Chickenpox
VZV - DNA virus in herpes family
Transmitted by
- Respiratory droplets
- Contact with vesicle fluid
Primary infection
- Fever
- Malaise
- Pruritic rash
29
Incubation period 10-21 days
The disease is infectious 48 hours before the rash and continues to be infectious until the vesicles crust over
Primary VZV infection is uncommon 3:1000 pregnancies
Following the primary infection, herpes zoster or simply zoster or shingles
Fetal and Neonatal Risks of Varicella Infection
Before 20 weeks
Not increase spontaneous miscarriage
FVS: skin, eye, hypoplasia of limbs, neurological
abnormalities
After 20 weeks and before 36 weeks
No associated adverse fetal effect
After 36 weeks
Severe chicken pox most likely to occur if the
infant is born within 7 days of onset of the
mother’s rash when cord blood VZV IgG is low
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Prevention
- VZIG, IVIG
- Observe sign of infection 14-16 days or 28 days
Treatment
- Acyclovir
References
� UpToDate: www.md.kku.ac.th/library
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