Perinatal Infections

Adane Abera, MD University of Addis Ababa Faculty of Medicine

Perinatal Infections

• Outline– Epidemiology– Route of infections– Classifications– Diagnosis– Treatment– Prevention

Why do newborns die?

• Three causes together account for 88% of newborn deaths in Africa– Infections including sepsis/pneumonia, tetanus &

diarrhea(39%)– Preterm birth, 25%– Asphyxia, 24%

• These causes are highly preventable, especially tetanus and neonatal infections

Estimated direct causes of neonatal deaths in Ethiopia as of year 2000 E.C

Preterm, 15%pneumonia & sepsis, 34%

Diarrhoea, 4%

Tetanus, 15%

Other, 6%

Congenital, 4%

Asphyxia, 22%

Infections account 53% of neonatal death in Ethiopia

Where do newborns die?

• Most die at home, unnamed and uncounted• Traditional taboos prevent access to care and

promote acceptance of newborn deaths • But new data used well can make newborns

count

• Progress towards MDG4 in Ethiopia,– NMR 39/ 1000 live births– Neonatal mortality percentage of under 5

mortality 32%– IMR 77/ 1000 live births– 94% home delivery in Rural area.

When do newborn die?

• The first days of life are the riskiest• Up to 50% of all newborn deaths are on the

first days of life(500,000 African babies die on their birth day)

• 75% of newborn deaths are in the first week

Infections in the Newborn

The fetus and the newborn are very susceptible to infections.

There are three major routes of perinatal infection.

Blood borne transplacental infection of the fetus ( e.g., CMV, rubella, syphilis)

Infections in the Newborn

Ascending infection with disruption of the barrier provided by amniotic membranes ( e.g., bacterial infections after 12-18 hours of ruptured membranes)

Infection on passage through an infected blood at delivery ( e.g., herpes simplex, hepatitis B, HIV, bacterial infections).

Intrauterine infection

• Trans-placental infection may occur at any time during gestation, & signs & symptoms may be present at birth or delayed for months or years.

• The timing of infection during gestation affects the outcome.

• 1st trimester infection may alter embryogenesis, with resulting congenital malformations (congenital rubella)

Intrauterine infection

• 3rd trimester infection often results in active infection at the time of delivery (toxoplasmosis, syphilis) and

• Infections that occur late in gestation may lead to a delay in clinical manifestations until some time after birth (syphilis).

Suspected intrauterine infection

• CMV & HSV require culture or polymerase chain reaction (PCR) methods, whereas syphilis, toxoplasmosis and rubella are diagnosed by specific serologic methods (pathogen specific IgM assays) high specificity but only moderately sensitive.

Suspected intrauterine infection

• The total IgM value is important because the normal fetal IgM value is <5mg/dl.

• IgM tests are useful only when the results are strongly positive. IgM levels > 20 mg/dl at birth suggests an intrauterine infection.

Ascending infection

• The human birth canal is colonized with aerobic and anaerobic organisms that may result in ascending amniotic infection &/or colonization of the neonate at birth.

• > 24hrs was once considered PROM because microscopic evidence of inflammation of membranes is uniformly present when duration of rupture exceeds 24hr.

Ascending infection

• At 18hr of membrane rupture, however, the incidence of early onset disease with GBS increases significantly; longer than 18hr is appropriate cutoff for increased risk of neonatal infection.

Late onset postnatal infection

• After birth, neonates are exposed to infectious agents in the nursery or in the community.

• The most common source of postnatal infections in hospitalized newborns is hand contamination of health care personnel.

Late onset postnatal infection

• Most cases of neonatal meningitis result from hematogenous dissemination.

• Abscess formation, ventriculitis, septic infarcts, hydrocephalus, & subdural effusions are complications of meningitis that occur more often in newborn than in older children.

Susceptibility of the newborn to infection

Related to immaturity of both the cellular and humoral immune systems at birth.

Decreased function of neutrophils (defective adherence & chemotaxis), ( term & preterm), under conditions of stress the release of marrow reserves of PMN is impaired markedly (Hence neutropenia is more likely to develop)

Susceptibility of the newborn to infection

Neonatal T cells appear to be relatively deficient in most of their major function, including CD8 T cell mediated cytotoxicity, delayed hypersensitivity and B cell differentiation because of diminished cytokine production by neonatal T cells.

Susceptibility of the newborn to infection

Low concentrations of immunoglobulin (preterm)

Quantitative and qualitative defects of complement system ( both term & preterm)

In premature newborns cord IgG levels are directly proportional to GA.

Susceptibility of the newborn to infection

IgA is virtually absent at birth ( usually <5mg/dl)

Newborn usually lack antibody mediated protection against Escherichia coli & other Enterobacteriaceae. ( Because no IgM is transferred to fetus)

Character-x Early onset Late onset Late, late onset

Age at onset Birth-7days 7-30 days >30days

Maternal obs cxs

common uncommon varies

prematurity frequent varies usual

Organism source

Maternal genital tract

Maternal genital tract/e

Environment/ community

manifestation systemic Systemic or focal

Multisystem or focal

site Nursery, NICU, community

NICU, community

NICU, community

Bacterial infection

Bacterial sepsisEssential diagnosis and typical featuresMost newborns with early onset of sepsis

present at < 24 hours of age.Respiratory distress is the most common

presenting symptom.

Bacterial infection

Hypotension, acidemia, and neutropenia are associated with clinical finding.

Bacterial sepsis

Early onset• Appear <7days of life

• Most commonly on day 1 of life

• Respiratory distress due to pneumonia is the most common

• Caused by GBS and G-negative enteric pathogens ( most commonly E. coli)

Early onset

• 60-80 % PRESENT AT FIRST 24 HRS• MEDIAN AGE AT ONSET

– TERM 8 HOURS– PRETERM 6 HOURS

RISK FACTORS FOR INFECTION

• PREMATURE ONSET OF LABOR• PROLONGED RUPTURE OF MEMBRANES > 18

H BEFORE DELIVERY

• MATERNAL CHORIOAMNIONITIS• EARLY POST PARTUM FEBRILE MORBIDITY• MULTIPLE BIRTHS

Late onset• Appear > 7days of age• Presents in more subtle manner( poor

feeding, lethargy, hypotonic, temperature instability , altered perfusion, increased 02 requirement & apnea).

• More often associate with meningitis or other localized infections

• Coagulase negative staph, S. Aureus, GBS, Enterococcus, pseudomonas & gram negatives.

Investigations

• WBC (absolute neutropenia < 1000/ml)• Ratios of immature to mature neutrophils

elevated(>0.2) Normal < 0.15• ESR normal 1-2mm/hr at 12hrs of age & 17-

20mm/hr at 14 days of age• Platelet count ( thrombocytopenia)

• Blood glucose (hypoglycemia)• pH ( un explained acidosis)• Urine examinations collected by

catheterization or suprabubic aspiration• Chest x-ray ( pneumonia is invariably present)

Diagnosis

Definitive diagnosis is made by positive cultures from blood, CSF, urine and joint fluid.

Obtaining 2 blood culture specimens by venipuncture from different sites avoids confusion caused by skin contamination & increases the likelihood of bacterial detection.

Treatment

Early onset• Ampicillin and amino glycoside or third

generation cephalosporin• Supportive therapy

i. IV glucoseii. Volume expansion & electrolyte balanceiii. 02

iv. Ventilator supportv. Nutritional support

Late onset infectionsCoverage include above and staphylococci

• Cephalosporin are not active against Listeria or enterococci and should not be used without concomitant administration ampicillin.

• More over, when used with ampicillin, cephalosporins do not offer the advantage of synergism that aminoglycosides do against strains of enterococci.

The duration of antimicrobial therapy for neonatal sepsis usually is 7 to 10 days or for approximately 5 to 7 days after clinical signs & symptoms of infection have disappeared

Guidelines for evaluation of bacterial infection

Risk factor Clinical signs Evaluation & Rx

Delivery 18hrs after rupture of membranes

none Observation

> 18hrs & chorioamnionitis

none CBC, blood culture and broad spectrum antibiotics for 48-72hrs

Continued

Delivery > 18hrs after rupture of membranes, chorioamnionitis & maternal antibiotics

No clinical

signs

CBC, blood culture & broad spectrum antibiotics for 48-72hrs.

With or without risk factors

With clinical

signs

CBC, blood culture and CSF & antibiotics

CSF examination

An examination of CSF should be performed when infection is highly suspected on clinical basis( e.g., associated hypotension, persistent metabolic acidosis, neutropenia) or if the blood culture is positive.

CSF examination

The diagnosis of meningitis is confirmed by examination of CSF, & identification of a bacterium, virus, or fungus by culture, antigen or the use of PCR

Normal, uninfected neonate from 0-4 wk of age may have elevated CSF protein levels of 84+/ – 45mg/dl, glucose of 46+/- 10mg/dl, & leukocyte count of 11+/-10 with 90th percentile being 22.

Preventions of neonatal infections (sepsis, meningitis, pneumonia,

diarrhea & tetanus)

• Prevention through identifying and treating maternal infections (e.g., syphilis) and through clean delivery and cord hygiene

• Chemoprophylaxis- women with GBS genital colonization: Intrapartum prophylaxis with benzyl penicillin during labor significantly reduced the rate of transmission of GBS from mother to their babies from 45 % (untreated control) to 3% (p<0.001).

• Prevention through early, exclusive breast feeding and feeding hygiene

• IMNCI[integrated management of neonatal and childhood illnesses]

– management & care of LBW babies including kangaroo mother care

– Emergency newborn care for illness, especially sepsis

• Maternal health programs such as antenatal care ( malaria control, tetanus immunization, PMTCT)

• Post natal care (Assess for danger signs, measure weight, temperature, check feeding) & promote hygiene, & skin, eye, cord care