1. Perinatal infections occur during labor and delivery when microbial agents infect the infant. The most common sources are the maternal genital tract and amniotic fluid. 2. The newborn is initially colonized by microbes on the skin and mucosal surfaces, which sometimes cause illness by direct extension or bloodstream invasion. 3. Risk factors for neonatal sepsis include low birth weight, premature rupture of membranes, and maternal infection. The most common causes are Group B Streptococcus and E. coli from the maternal genital tract.

1. TOCUM---- 2008317 Baha D. Moohy Alosy, DCH, FICMSP
Departments of Pediatrics-Collage of Medicine- University of Tikrit -IRAQ
Perinatal infections
(Infection by microbial agent(s) during labor and delivery [intrapartum])
The infant is protected from the microbial flora of the mother's genital tract. Initial
colonization of the newborn and of the placenta usually occurs after rupture of the
maternal membranes. If delivery is delayed after membrane rupture the vaginal
microflora can ascend and in some cases produce inflammation of fetal membranes,
umbilical cord, and placenta. Fetal infections can also occur from aspiration of infected
amniotic fluid. Some viruses are present in the genital secretions (HSV, CMV, or HIV) or
blood (Hepatitis B virus or HIV). If delivery follows shortly after membrane rupture the
infant may be colonized during passage down the birth canal.
The newborn infant is initially colonized on the skin and mucosal surfaces (e.g.
nasopharynx, oropharynx, conjunctivae, umbilical cord, external genitalia). In most
infants the organisms proliferate on these sites without causing any illness. A few infants
may be infected by direct extension (e.g. sinusitis and otitis from the nasopharynx).
Invasion of the bloodstream may then occur. The umbilical cord is an common portal of
entry for systemic infection. Microorganisms may also infect the infant through abrasions
or skin wounds.
Infants who develop sepsis may have certain risk factors that predispose them to
infection. These factors include low birth weight, premature or prolonged rupture of
maternal membranes, septic or traumatic delivery, fetal anoxia and maternal peripartum
infection. Male infants are also more likely to develop sepsis during the newborn period.
Etiologic Agents
The agents responsible for neonatal sepsis are usually found in the maternal birth canal.
Group B Streptococcus (Streptococcus agalactiae), and E. coli are the most common
causes of neonatal sepsis.
Bacteria
Common: Streptococcus pyogenes (Group A Streptococcus), Streptococcus agalactiae
(Group B Streptococcus), Enterococcus spp. (group D Streptococcus), Escherichia coli,
Neisseria gonorrhoeae, Listeria monocytogenes, Chlamydia trachomatis
Uncommon: Staphylococcus aureus, alpha hemolytic Streptococci, various gram negative
rods (ex. Proteus, Salmonella), Haemophilus spp., Bacteriodes spp., Veillonella spp.
Streptococcus pyogenes (Group A Streptococcus)= sepsis, pneumonia, meningitis
Streptococcus agalactiae (Group B Streptococcus)= sepsis, pneumonia, meningitis
Enterococcus spp. (group D Streptococcus)= Urinary tract infections, sepsis

2. Escherichia coli= sepsis, meningitis, pneumonia
Neisseria gonorrhoeae= Opthalmia neonatorium, sepsis
Listeria monocytogenes= Late onset= sepsis, meningitis, diarrhea
Chlamydia trachomatis= pneumonia and/or conjunctivitis
Neonatal Sepsis
1. Epidemiology
1. Incidence: 1 to 8 cases per 1000 live births
2. Meningitis occurs in one third of Sepsis cases
2. Risk Factors
1. Major
1. Maternal prolonged Rupture of Membranes >24 hours
2. Intrapartum maternal fever >38 C (>100.4 F)
3. Chorioamnionitis
4. Sustained Fetal Tachycardia >160 beats per minute
2. Minor
1. Intrapartum maternal fever >37.5 C (>99.5 F)
2. Twin Gestation
3. Premature infant (<37 weeks)
4. Maternal Leukocytosis (White Blood Cell count >15000)
5. Rupture of Membranes > 12 hours
6. Tachypnea (<1 hour)

3. 7. Maternal Group B Streptococcus Colonization
8. Low APGAR (<5 at 1 minute)
9. Low birth weight (<1500 grams)
10. Foul lochia
3. Etiologies
1. Most common
1. Group B Beta-hemolytic Streptococcus (Group B Strep)In 2002,
CDC, the American College of Obstetricians and Gynecologists (ACOG),
and the American Academy of Pediatrics (AAP) issued revised
guidelines for prevention of perinatal invasive group B streptococcal
(GBS) disease. These guidelines recommend universal screening of
pregnant women for rectovaginal GBS colonization at 35--37 weeks'
gestation and administering intrapartum antimicrobial prophylaxis to
carriers. which determined that incidence of GBS disease in infants aged
0--6 days (i.e., early-onset disease) in 2004 had decreased by 31% from
2000--2001, the period immediately before universal screening was
implemented. Incidence of GBS disease in infants aged 7--89 days (i.e.,
late-onset disease) remained unchanged during the 9-year period
reviewed. Continued monitoring is needed to assess the impact of the
2002 guidelines on early-onset disease and the long-term effect of
widespread intrapartum use of antimicrobial agents on neonatal GBS
diseaseIncidence of early-onset disease remained stable during 1999--
2001, averaging 0.47 cases per 1,000 live births incidence declined to
0.32 in 2003 and was stable at 0.34 in 2004 . During 1996--2004, late-
onset disease incidence varied little, averaging 0.35 per 1,000 live births,
with annual rates ranging from 0.29--0.39 per 1,000 live births
2. Escherichia coli K1 (ECK1)
3. Listeria monocytogenes
1. Rare in the United States
2. Predominant in Spain
2. Other pathogens
1. Haemophilus Influenzae
2. Coagulase-negative staphylococci (Nosocomial)
4. Signs
1. Respiratory distress (90%)
1. Tachypnea
2. Apnea
3. Hypoxia
4. Flaring or grunting
5. Irregular respirations
2. Temperature instability sustained over 1 hour (30%)
1. Newborn Temperature < 97 F (36 C)
2. Newborn Temperature > 99.6 F (37 C)
3. Gastrointestinal symptoms
1. Vomiting
2. Diarrhea
3. Abdominal distention
4. Ileus
5. Poor feeding
6. Splenomegaly

4. 4. Neurologic
1. Activity decreased or lethargy
2. Irritability
3. Tremor or Seizure
4. Hypo reflexia or hypotonia
5. High pitched cry
6. Swelling of Fontanel
5. Cardiovascular
1. Hypotension
2. Metabolic Acidosis
3. Tachycardia
6. Skin
1. Pallor or skin mottling
2. Petechiae or Purpura
3. Cold or clammy skin
4. Cyanosis
5. Jaundice
5. Labs
1. Complete Blood Count (findings suggestive of Sepsis)
1. White Blood Cell Count
1. Decreased below 5000 /mm3
2. Increased above 25000 /mm3
2. Absolute Neutrophil Count (ANC) < 1000 /mm3
3. Bands to total Neutrophil Count ratio > 0.2
4. Immature to mature Neutrophil Count ratio > 0.2
2. Blood Culture (positive in 5-10% of Neonatal Sepsis)
3. Arterial Blood Gas
1. Indicated for signs or symptoms of Hypoxia
4. Lumbar Puncture
1. Indications
1. Sepsis is considered primary diagnosis
2. Blood Culture positive
3. Neurologic signs or symptoms
2. Specific Tests
1. CSF Examination
2. CSF Culture
3. CSF Antigens
5. Urinalysis and Urine Culture
1. Indicated for late-onset Neonatal Sepsis
2. Not useful in perinatal period (age <3 days old)
6. Consider Urine antigens
1. Escherichia coli
2. Neisseria Meningitis
3. Streptococcal Pneumoniae
4. Group B Streptococcus
6. Radiology

5. 1. Chest XRay
7. Management: General
1. Monitor infant for signs of Sepsis
2. Antibiotic indications (contrast with observation only)
1. Symptomatic infants
2. Asymptomatic infants with >2 risk factors (see above)
3. Continue monitoring and antibiotics for 48 to 72 hours
1. Indications to continue antibiotics 14 to 21 days
1. Symptomatic newborn
2. Blood Culture positive
2. Discontinue antibiotics and monitoring if
1. Blood Cultures negative at 48 to 72 hours and
2. No signs of Sepsis on examination
4. Signs of Sepsis with negative culture
1. Consider Neonatal HSV infection
8. Management: Antibiotics for Early Onset (age <1 week)
1. Bacterial spectrum
1. Group B Streptococcus
2. Escherichia coli
3. Klebsiella
4. Enterobacter
5. Staphylococcus aureus (not common)
6. Listeria (rare in United States)
2. Primary Antibiotic Protocol
1. Ampicillin (Meningitis dose often used empirically)
1. Sepsis: 50 mg/kg/dose IV or IM q12 hours
2. Meningitis: 100 mg/kg/dose IV or IM q12 hours
2. Gentamicin
1. Gestation <28 weeks: 2.5 mg/kg/dose IV/IM q24 hours
2. Gestation <34 weeks: 2.5 mg/kg/dose IV/IM q18 hours
3. Gestation >34 weeks: 2.5 mg/kg/dose IV/IM q12 hours
3. Alternative Options
1. Alternative Protocol 1
1. Ampicillin (dosed as above)
2. Cefotaxime 50 mg/kg/dose IV or IM q12 hours
2. Alternative Protocol 2
1. Ampicillin (dosed as above)
2. Ceftriaxone 50 mg/kg IV or IM q24 hours
9. Management: Antibiotics for Late Onset (age 1-4 weeks)
1. Coverage broadened over early onset Sepsis
1. Haemophilus Influenzae
2. Staphylococcus epidermidis
2. Antibiotic Dosing for infant over 7 days old
1. Ampicillin (the higher dose in possible Meningitis)
1. Weight <2 kg: 25-50 mg/kg/dose IV or IM q8 hours
2. Weight >2 kg: 25-50 mg/kg/dose IV or IM q6 hours

6. 2. Gentamicin
1. Gestation <37 weeks: 2.5 mg/kg/dose IV/IM q12 hours
2. Gestation >37 weeks: 2.5 mg/kg/dose IV/IM q8 hours
3. Primary Protocol 1
1. Ampicillin (dosed as above)
2. Cefotaxime 50 mg/kg/dose IV or IM q8 hours
4. Primary Protocol 2
1. Ampicillin (dosed as above)
2. Ceftriaxone 75 mg/kg/dose IV or IM q24 hours
5. Alternative Protocol
1. Ampicillin (dosed as above)
2. Gentamicin (dosed as above)
10. Prevention
1. Prolonged Rupture of Membranes GBS Prophylaxis
2. Routine Group B Strep Screening in pregnancy (36 weeks)
Pregnant women should avoid contact with ill people, particularly if the women is
seronegative or has no prior exposure to the disease. Pregnant women should avoid
eating raw or undercooked lamb, pork, and beef because such products contain T.
gondii, Campylobacter fetus, Listeria monocytogenes, and/or Salmonella spp. They
should also avoid contact with cat feces because it contains highly infectious T.
gondii oocyts. Pregnant women should avoid sexual intercourse with their sexual
partner if he has had genital herpes or HIV. Human immune serum globulin can be
given to seronegative pregnant women exposed to rubella, varicella, measles, or
hepatitis A virus. Proof of efficacy is undetermined and the immune serum globulin
may not protect the fetus. Giving HIV positive pregnant women AZT during
pregnancy and delivery followed by treatment of the newborn significantly lowers
the chances the newborn will be infected. Discouraging breastfeeding of the
newborn in HIV (especially symptomatic mothers and mothers with low CD4 T
cell counts) and Hepatitis B infected mothers will lower the child's chances of
being infected following birth. Treat pregnant women that are culture positive for
Group B Streptococcus during labor and delivery. Treat the eyes of newborns with
erythromycin to prevent opthalmia neonatorium. Immunizations for Rubella,
Hepatitis, and VZV should be given to women thinking of trying to become
pregnant if they are seronegative. Live viral vaccines should be give 3-6 months
before conception. Please note it is too late to give live viral vaccines to a
seronegative woman that is already pregnant. No live attenuated viral vaccine
should be given to a pregnant woman for fear of causing congenital infections.
Effect of Infection on the Fetus and Newborn Infant
Organism or
disease
Prematurity In utero
Growth
Retardation
Developmental
Anomalies
Congenital
Disease
Persistant
Postnatal
Infection

7. and Low
Birth
Weight
Viruses
Rubella - + + + +
CMV + + + + +
HSV + - - + +
VZV - (+) + + +
Enteroviruses - - (+) + -
Hepatitis B + - - + +
HIV (+) (+) (+) + +
Erythrovirus
B19
(Parvovirus
B19)
- - - + -
Bacteria
Treponema
pallidum
+ - - + +
Mycobacterium
tuberculosis
+ - - + +
Listeria
monocytogenes
+ - - + -
Campylobacter
fetus
+ - - + -
Salmonella
typhosa
+ - - + -
B. burgdorferi - - - + -
Parasites
Toxoplasma
gondii
+ + - + +
Plasmodium
spp.
(+) + - + +
Trypanosoma
cruzi
+ + - + -
+ = evidence for effect; - = no evidence for effect; (+) = association of effect with
infection has been suggested and is under consideration
Syndromes in the Neonate Caused by Congenital Infections

8. Microorganism Signs
Toxoplasma gondii
Hydrocephalus, diffuse intracranial calcification,
chorioretinitis
Rubella virus Cardiac defects, sensorineural hearing loss, cataracts
Cytomegalovirus Microcephalus, periventricular calcification
Herpes Simplex Virus Vesicular lesions, keratoconjunctivitis
Treponema pallidum
Bullous, macular, and eczematous skin lesions
involving the palms and the soles; rhinorrhea,
dactylitis and other signs of osteochrondritis and
periostitis
Varicella-zoster virus Limb abnormalities, cicatricial lesions
Erythrovirus B19 (Parvovirus
B19)
Diffuse edema (in utero hydrops fetalis)
Human Immunodeficiency
virus
Severe thrush, failure to thrive, recurrent bacterial
infections, calcification of the basal ganglia
Clinical Manifestations of Neonatal Infection
Acquired In Utero or at Delivery
Microorganism
Clinical Sign
Rubella
virus
CMV HSV
Toxoplasma
gondii
Treponema
pallidum
Streptococcus
agalactiae
(Grp B) or E.
coli
Hepatosplenomegaly + + + + + +
Jaundice + + + + + +
Adenopathy + - - + + -
Pneumonitis + + + + + +
Skin Lesions
Petechiae/purpura
+ + + + + +
Vesicles - + ++ - + -
Maculopapular
exanthems
- - + + ++ -
CNS Lesions
Meningoencephalitis
+ + + + + +
Microcephaly - ++ + + - -
Hydrocephalus + + + ++ - -
Intracranial
calcifications
- ++ - ++ - -

9. Paralysis - - - - - -
Hearing deficits + + - - + -
Heart lesions
Myocarditis
+ - + + - -
Congenital defects ++ - - - - -
Bone lesions ++ - - + ++ -
Eye Lesions
Glaucoma
++ - - - + -
Chorioretinitis or
retinopathy
++ + + ++ + -
Cataracts ++ - + + - -
Optic atrophy - + - + - -
Microphtalmia + - - + - -
Uveitis - _ - + + -
Conjunctivitis or
keratoconjunctivitis
_ _ ++ - - -
11. References
1. Behrman (2000) Nelson Pediatrics, Saunders, p. 550
2. Cloherty (1991) Neonatal Care, Little Brown, P. 146-58
3. Gilbert (2001) Sanford Guide, ATI, p. 42 .
4. Editors: Rudolph, Colin D.; Rudolph, Abraham M.; Hostetter, Margaret
K.; Lister, George; Siegel, Norman J.Rudolph's Pediatrics, 21st
Edition©2003 McGraw-Hill

10. Paralysis - - - - - -
Hearing deficits + + - - + -
Heart lesions
Myocarditis
+ - + + - -
Congenital defects ++ - - - - -
Bone lesions ++ - - + ++ -
Eye Lesions
Glaucoma
++ - - - + -
Chorioretinitis or
retinopathy
++ + + ++ + -
Cataracts ++ - + + - -
Optic atrophy - + - + - -
Microphtalmia + - - + - -
Uveitis - _ - + + -
Conjunctivitis or
keratoconjunctivitis
_ _ ++ - - -
11. References
1. Behrman (2000) Nelson Pediatrics, Saunders, p. 550
2. Cloherty (1991) Neonatal Care, Little Brown, P. 146-58
3. Gilbert (2001) Sanford Guide, ATI, p. 42 .
4. Editors: Rudolph, Colin D.; Rudolph, Abraham M.; Hostetter, Margaret
K.; Lister, George; Siegel, Norman J.Rudolph's Pediatrics, 21st
Edition©2003 McGraw-Hill