Perinatal Infections

Goitom Gebreyesus, MD

Perinatal Infections

• Important causes of morbidity and mortality

• Newborn infections are UNIQUE due to a number of factors:

• Diverse mode of transmission of infectious agents from mother to fetus or newborn

• Less capable of responding to infection due to one or more immunologic deficiencies involving

RES, complement, PMN leucocytes, cytokines, antibodies or cell mediated immunity

Perinatal…

• Co-existing diseases complicate diagnosis and management of newborn infections, e.g:Hyaline Membrane disease and bacterial

pneumonia

• Extremely variable manifestations depending on:Time of exposure, etiology, inoculum size

and immune status

Immunity

• Decreased concentration and function of immunologic factors• Immunoglobulin

• Active transport of IgG antibody across placenta with concentration at term like that of the mothers

• In premature NB cord IgG levels are directly proportional to gestational age

• Cord to maternal serum IgG level ratios are: Term – 1 32 weeks – 0.5 28 weeks – 0.3

Immun…

• IgG provide protection against infections due to e.g tetanus, encapsulated bacteria…

• Bactericidal and opsonic Abs against enterobacilli are in IgM class ➞ susceptibility

• Complement • No transfer from maternal circulation• In terms slightly low classical and 35-60%

alternative pathway compared to adult• In prematures markedly decreased• Decreased complement derived Chemotaxis and

opsonization of certain organisms e.g. GBS and E.coli

Immun…

• Neutrophils • Chemotaxis, adherence, aggregation and deformability are

decreased delayed response➞• Microbicidal activity impaired in RD, hypoglycemia,

hyperbilirubinemia and sepsis• Neutrophils storage pool is 20 – 30% of adult ➞depleted in

infectionA major factor leading to poor outcome in bacterial SEPSIS

• Monocyte – macrophage system • Chemotaxis impaired ➞ poor inflammatory response in

tissue

Etiology: according to time of acquisition

Transplacental Perinatal Postnatal

CytomegalovirusHerpes simplex virusMycobacteriumRubellaT. PallidiumVaricella zoster virus

AnaerobesChlamydiaCytomegalovirusGBSH. InfluenzaeListeria monocytogensmycoplasma

AdenovirusCandida speciesCoaglase negative staph aureusstaph aureusCytomegaloviruspseudomonas

Epidemiology

• Prevalence of organisms vary geographically• Dietary practice important (e.g. toxoplasmosis)• Socio-economic status, maternal age, race and

sexuality influence maternal infection• Status of immunity during pregnancy e.g. to

Rubella• Hospital to hospital variability depending on:

• Rate of prematurity, prenatal care, conduct of labor and environmental condition in nurseries

Epidem…

• Prematurity – most important risk factor, in addition to low birth weight

• Three to four fold higher incidence of infection than full terms due to the following factors:Maternal genito-urinary tract infection is main

cause of premature laborHave less developed immunityMore likely to have HMD and NECMay require IV access or endotracheal tube ➞provide portal of entry

Pathogenesis

• Infected at different time via 3 routes:• In utero (transplacental)• Intrapartum (ascending)• Post partum (nosocomial or community

acquired)

Clinical manifestation

General: Fever, temperature instability, poor feeding, edema

CVS: Pallor, mottling, cold skin, tachycardia, hypotension, bradycardia

Gastro-intestinal: Abdominal distension, vomiting, diarrhea, hepatomegaly

CNS: Irritability, lethargy, tremors, seizure, hyporeflexia, hypotonia, abnormal Moro reflex, irregular respiration, full fontanel

Respiratory: Apnea, dyspnea, tachyhpnea, retractions, flaring, grunting, cyanosis

Hematologic: Jaundice, splenomegaly, pallor, petechia, purpura, bleeding

Renal: oliguria Metabolic: hypoglycemia, acidosis

Laboratory studies

• Evidence for infection• Culture (blood, CSF, others)• Demonstration of microorganisms in tissue or

fluids• Antigen detection (urine, CSF)• Autopsy

• Evidence for inflammation• Leucocytosis, increased immature to total

Neutrophils ratio• Acute phase reactants (CRP, ESR)• Pleocytosis in CSF, synovial or pleural fluid• Fibrin split products in DIC

Lab…

• Evidence for multi-organ system diseases

• Metabolic acidosis: PH, PCO2, HCO3

• Pulmonary function: PO2, PCO2

• Renal function: BUN, creatinine• Liver function: bilirubin, SGPT, SGOT, ammonia,

PT, PTT• Bone marrow function: neutropenia, anemia,

thrombocytopenia

Group B Streptococcus (GBS)

• Major cause of severe systemic & focal infection in NB

• Common inhabitant of maternal genital & GI tract

• Colonizes 4 – 40% of pregnant women who are mostly asymptomatic – UTI, chorioamnionitis, or endometritis

• Major cause of chrioamnionitis & puerperal infection

GBS (continued)

• Early onset GBS disease occur in the 1st wk usually <72 hrs•50% are symptomatic at birth

• C/M: Ranges from asymptomatic bacteremia to septic shock

• CXR: • Reticulogranular pattern (50%)• Patchy infiltrates (30%)• Less commonly – pleural effusion, pulmonary

edema, cardiomegally, pulmonary vascular markings

GBS (continued)

• Treatment: sensitive to penicillin G – empiric penicillin (Ampicillin) + Aminoglycoside• Mortality 5 – 15%, highest in VLBW & septic shock• Neurologic complications in those with meningitis are

severe in 20 – 30%

• Prognosis: principal predictor of mortality & morbidity is septic shock

• Prevention: selective intra-partum chemoprophylaxis & treatment of chorioamnionitis

Listeria monocytogens

• Widespread in nature, associated with food-borne transmission• Unpasturized milk & milk products, contaminated

raw meat & vegetables

• Perinatal infections predominate (secondary to maternal inf. or colonization)

• C/M: depends on age of patient & circumstances of infection• 2nd &3rd TM infection

• fetal inf, • onset of premature labor & delivery, • infected premature infant or• still birth

Listeria mon…

• Neonatal listeriosis (transplacental, ascending)• Early onset (< 5 days) septicemic form with a

mortality of 30%• Late onset meningitic form

• Post neonatal infection in the immuno compromised

• Increased peripheral blood monocytes alerts to the possibility of listeriosis

• Treatment: Ampicillin alone or in combination with aminoglycosides

L. ‘monocytogens’

Listeria mon…

• Prognosis: • Mortality > 50% in premature infection in utero• 30% in early neonatal sepsis• 15% in late onset disease (meningitis)

• Prevention: • avoid consumption of contaminated food & contact

with domestic animals• Hand washing

Mycoplasma hominis & Ureaplasma urealiticum

• Human urogenital pathogen, often associated with STD such as non-gonococcal urethritis & puerpral infection

• Mainly colonize GUT of post pubertal females & males

• Colonization in pregnancy 40 – 90% with 25 – 60% vertical transmission rate to NB

• C/M: variety of fetal & neonatal infection, silent chorioamnionitis may result in 8 fold in fetal death or premature delivery

• Treatment: Clindamycin, Doxycycline (CNS inf.)

Chlamydiae trachomatis

• Genital infection in 5 –30% of pregnant women• NBs acquire at parturition• Risk of vertical transmission is 50%• C/M: ~70% nasopharyngeal infection

• Conjunctivitis in 30 – 50% of infants (50% with NP inf); symptoms develop 5 –14 days after delivery;

• varies from mild conjunctival injection with mild mucoid discharge to severe form with copious purulent discharge

Chlamydiae trac…

• Pneumonia: onset b/n 1 & 3 months• Other sites: rectum, vagina

• N.B.: may persist for 3 yrs

• Treatment: Erythromycin• Prevention: prenatal screening & treatment of

pregnant women

N. Gonorrhea

• Gonococcal ophthalmitis (Ophthalmia Neonatrum)

• Appear 1 – 4 days after birth• C/M:

• starts as mild inflammation with serosanguinous discharge and within 24 hrs it becomes thick and purulent with tense edema

• If not treated, it progresses to corneal ulceration, rapture and blindness

• Treatment:• Ceftriaxone + saline irrigation

H. Influenzae (non typable)

• Follow maternal genital colonization• Causes chorioamnionitis of premature rapture

of membrane• Vertical transmission up to 50%• C/M:

• Invasive infection – from pneumonia to septic shock• Conjuctivitis, scalp abscess and cellulitis

• Treatment:• Ceftriaxone or chloramphenicole + Ampicillin