• (1) Vertical: from mother to infant (Intrauterine)
• Maternal Hematogenous Infection (in spite of placental barrier there are pathogens that due cross)
• Transcervical (Ascending infections): through the birth canal, involves the membranes and then the fetus.
• (2) Horizontal: from baby (or other person) to baby

• Clinical Syndrome: Occurs in 1^st month of life
• Signs and symptoms of infection (Characterized by temperature instability, may be Ý or ß ); most symptoms vague:
• Poor feeding, irritability – non-consolable, lethargy, abd. distention, apnea and bradycardia (can be normal), jaundice
• Labs: Culture of blood and CSF (from LP) diagnostic (infant do have a PMN response). WBC Ý , protein ß , glucose ß . Also look at peripheral WBC and differential.
• Meningitis occurs in 1/3 of bacteremic (bacteria in blood) infants. Bacterial count in blood usually Ý due to ß immunity.
• Ý bacterial count predisposes infants to meningitis.
• Neonates are Immunocompromised Hosts: Complement, PMNs, Phagocytosis/bacterial killing, Humoral immunity
• these systems are in place but function sluggishly. (e.g. pre-term infants have ß IgG; Term infants have ß IgM, IgA)
• Also, procedures in NICU on pre-term infants predispose them to infection (e.g. intubation).
• Blood Brain Barrier: brain microvascular, endothelial barrier that separates the vascular from the subarachnoid space
• is immature in neonates: they have a Ý level of protein and cells in CSF. So already less protective without infection
• during infection:
• (1) bacteria can move through tight junctions
• (2) organism can be phagocytized so WBCs enter
• (3) receptor-mediated pathogen transcytosis through endothelial cells.
• Epidemiology of Meningitis: ~ 1-10/1000 infants.
• Relative Risk in Preterm infants is 10 fold higher than term.
• Other risk factors:
• Premature rupture of membranes (PROM), especially > 18h.
• Maternal fever
• Major Pathogens:
• (1) Genital/urinary colonizers: Group B strep, E. coli.
• E coli with K₁ Ag has a Ý risk of causing meningitis than say a UTI. K₁ Ag is also on Nisseria meningitisis (in older patients).
• K₁ Ag is an adhesion receptor that probably facilitates crossing BBB.
• (2) secondary to maternal bacteremia: Listeria
• Diagnosis: See Signs and symptoms of infection under Clinical Syndrome above. Due lumbar puncture, take blood, run labs.
• Treatment: Antibiotic needs to cover several bugs, mainly Group B strep, E. coli. and Listeria.
• Ampicillin and Gentamicin (30 years experience) is used but Ampicillin and Cefotaxime (15yrs) is preferred in meningitis because beta-lactams dose can be doubled to get enough drug through the BBB.
• Supportive Therapy: for septic shock, hypoxia and/or DIC, which require intensive care.
• Prevention: Particularly Group B strep. See Epidemiology of Meningitis for risk factors.
• Prevent prematurity and you prevent a lot of these infections.
• Maternal Vaccines: we don’t know how to do this yet.
• Intrapartem Antibiotics this is the best approach at present. GBS has been the main target. We will run into this on wards.
• Maternal colonization with GBS is a risk factor as is previous delivery of infant with GBS (also see risk factors above)
• Eliminating GBS from colonized mothers proved impossible with antibiotics (eliminating carrier state is different than treating an infection)
• study in 80’s Þ major ß in GBS colonization and bacteremia in infants of mothers given antibiotics during pregnancy.
• Pediatric and Obstetric groups made recommendations, then CDC developed a widely used consensus regulation.
• (1) All moms (symptomatic or not) with GBS bacteriuria or who had previous infant with GBS should be treated.
• (2) One of 2 strategies should be adopted
• Screen all women at 35-37 weeks
• or treat all who are colonized with GBS (not just women with risk factors)
• (3) Rates of infection have tended to drop as this recommendation is implemented. Metro has gone from 5 to 0/yr.

Intrauterine Infections – see Vertical Infections above.

• These are the "STORCH" infections: Syphilis, Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, Herpes simplex.
• important Others include HIV, Lime disease, etc.
• Pathogenesis: Transplacental > Ascending
• Host immune factors
• depend on Maternal Immunity (e.g. Rubella, if mother is immune then fetus is protected)
• Timing of infection is important (e.g. syphilis is more likely to transmit during certain periods in pregnancy, Toxoplasmosis only causes problems if transmitted during 1^st and 2^nd trimester, 3^rd is possible but less severe)
• Viral Load concept is most clearly worked out in HIV: maternal viral load correlates with risk of transmission.
• Clinical Features: Though there are many different bugs, they have similar clinical features
• Infection may be Inapparent at birth and many important sequelae are Late Sequela (e.g. syphilis, rubella )
• Asymptomatic maternal infection
• Intrauterine Growth Retardation (often associated with a baby small for gestational age)
• Petechia, palpable purpura: multi-systemic disease Þ thrombocytopenia Þ hematologic systemÞ blueberry muffin baby
• Hepatosplenomegally: due to liver and spleen involvement.
• Microcephally: due to CNS involvement Þ severe intrauterine encephalitis
• Chorioretinitis due to CNS involvement of the 2^nd Nerve Þ blindness
• Hearing impairment due to CNS involvement of the 8^th Nerve
• Owl Eye cells seen in Herpes virus infection (CMV)
• Epidemiology is pathogen specific,
• CMV is the most common of the intrauterine infections (40,000/yr) \ is the most important one to know
• Occurs in 1-2% of infants. Compared to Toxo: 1/3000; HSV 1/3000; Rubella only 10/yr nationwide.
• 10% of total will have severe Sequella, the rest can be quite mild.
• Most important (#1) infectious cause of mental retardation, visual and hearing loss.
• because this is a herpes virus there is a primary infection which can be followed by a secondary infection upon reactivation
• The maternal primary infection is the one to worry about due to lack of maternal immunity to attenuate infection.
• therefore highest risk is in young teen mothers or older mothers with children in daycare.
• Etiologic Diagnosis of Intrauterine Infections (difficult because relies on combo of PCR, cultures and Ab test)
• CMV is the exception because it grows readily in culture (can be picked up in urine), PCR available but not needed.
• Toxoplasmosis: harder because it’s a protozoa. Use IgM Ab (too many women have been exposed to it to use IgG), PCR
• HVS: Culture, specific Ab to IgM
• Rubella: Culture, specific Ab to IgM
• Syphilis: VDRL, RTA (Ab test)
• It is almost never helps to look for IgG Ab to TORCH pathogens = "TORCH Titers" - this test is over used
• Prevention:
• Rubella Þ Vaccine, it works, Rubella is about gone
• HSV Þ No vaccine or screening; rely on judicious use of C-section in women who have history and active lesions
• New approach has been to put women who have had an active lesion on acyclovir to prevent reactivation.
• Syphilis Þ easily treated, is screened in 1^st and 3^rd trimester. Should be less of a problem than it is.
• Toxplasmosis Þ transmitted by exposure to litter box or eating uncooked meat, Can be treated by Spiramycin
• HIV Þ use anti-retrovirals during pregnancy and C-section. Screen baby and treat.
• Treatment:
• Syphilis Þ penicillin
• HSV Þ Acyclovir
• Toxo Þ Pyrimethamine/ sulfa drugs cross placenta
• CMV Þ Gnaciclovir
• HIV Þ Anti-retroviral therapy (HAART) 3 drug combination including protease inhibitors.