Neonatal Sepsis: Early and Late Onset

• Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia during the first month of life

Definition & Incidence

• Incidence of neonatal sepsis ranges from 1-8/1000 live births
• Incidence is 13-27/1000 live births for infants under 1500g
• Mortality rate is 13-25%
• Mortality rates are higher in premature infants and those with early fulminant disease

Early Onset

• Early-onset sepsis occurs within the first 3 days of life
• Characterized as a multisystem fulminant illness with prominent respiratory symptoms
• This is possibly due to the aspiration of infected amniotic fluids
• Mortality rate for early onset sepsis is 5-20%
• Typically acquired during the intrapartum period from the maternal genital tract
• Frequently associated with maternal chorioamnionitis

Late Onset

• Late-onset sepsis can occur as early as 4 days, but most commonly presents after the first week
• Exhibits less correlation with obstetric complications compared to early-onset sepsis
• Typically has an identifiable focus, such as meningitis or sepsis
• Can be acquired from the maternal genital tract or human contact

Nosocomial Sepsis

• Occurs in high-risk newborns
• Pathogenesis is related to the infant's underlying illness, the flora in the NICU environment, and invasive monitoring
• Occurs when breaks in the skin and intestine barrier functions lead to opportunistic infections

Causative Organisms

• Primary sepsis is commonly caused by Group B Streptococcus
• Other causes include gram-negative enterics (especially E. coli), Listeria monocytogenes, Staphylococcus, other streptococci, anaerobes, and H. flu
• Nosocomial sepsis organism varies by nursery
• Common organisms are Staphylococcus epidermidis, Pseudomonas, Klebsiella, Serratia, Proteus, and yeast

Risk Factors

• Prematurity and low birth weight increase risk
• Premature and prolonged rupture of membranes are risk factors
• Maternal peripartum fever increases risk
• Amniotic fluid problems (e.g., meconium, chorioamnionitis) are risk factors
• Resuscitation at birth and fetal distress increase risk
• Multiple gestation increases risk
• Invasive procedures increase risk
• Galactosemia is a risk factor
• Other factors include sex, race, variations in immune function, and inadequacy of hand washing in the NICU

Clinical Presentation

• Clinical signs and symptoms of neonatal sepsis are nonspecific
• Differential diagnoses to consider include RDS, metabolic disease, hematologic disease, CNS disease, cardiac disease, and other infectious processes like TORCH
• Temperature irregularity (high or low) can be observed
• Changes in behavior, like lethargy, irritability, or changes in tone are important observations
• Skin changes such as poor perfusion, mottling, cyanosis, pallor, petechiae, rashes, and jaundice may occur
• Feeding problems like intolerance, vomiting, diarrhea, and abdominal distension are noted
• Cardiopulmonary signs include tachypnea, grunting, flaring, retractions, apnea, tachycardia, and hypotension
• Metabolic irregularities, such as hypo- or hyperglycemia, and metabolic acidosis, may be present

Diagnosis

• Blood cultures confirm sepsis
• 94% of blood cultures grow by 48 hours of age
• Urine cultures are typically unnecessary for infants under 24 hours old, because UTIs are rare in early infancy
• CSF cultures may be useful in clinically ill newborns or those with positive blood cultures, however, this is deemed controversial

Adjunctive Lab Tests

• Neutropenia may be an ominous sign on a white blood cell count and differential
• An I:T ratio > 0.2 is a sign of good predictive value
• Serial values can establish a trend
• Platelet count changes are a late and nonspecific sign
• CRP rises early in acute phase reactants, so monitor serial values, as ESR rises late
• Other tests to consider are bilirubin, glucose, and sodium

Radiology

• CXR (chest X-ray) is obtained in infants with respiratory symptoms
• Difficult to distinguish Group B Streptococcus or Listeria pneumonia from uncomplicated RDS
• Renal ultrasound and/or VCUG should be performed in infants with accompanying UTI

Maternal Studies

• Examination of the placenta and fetal membranes is done for evidence of chorioamnionitis

Management - Antibiotics

• Primary sepsis is treated with ampicillin and gentamicin
• Nosocomial sepsis is treated with vancomycin and gentamicin or cefotaxime
• Antibiotic choice should be changed based on culture sensitivities

Supportive Therapy

• Respiratory: Administer oxygen and ventilation as necessary
• Cardiovascular: Support blood pressure with volume expanders and/or pressors
• Hematologic: Treat DIC with FFP and/or cryoprecipitate
• CNS: Treat seizures with phenobarbital, watch for signs of SIADH (decreased UOP, hyponatremia), and treat with fluid restriction
• Metabolic: Treat hypoglycemia/hyperglycemia and metabolic acidosis

GBS Prophylaxis

• GBS is the most common cause of early-onset sepsis
• Incidence: 0.8-5.5/1000 live births
• Fatality rate: 5-15%
• 10-30% of women are colonized in the vaginal and rectal areas
• Most mothers are screened at 35-37 weeks gestation

Neonatal Respiratory Distress

• Respiratory distress syndrome (RDS) is a general term used to describe respiratory symptoms
• Signs of respiratory distress include, tachypnea, where the respiratory rate exceeds 60/min.

Other Signs of Respiratory Distress Includes:

• Expiratory grunt – breathing against a closed Glottis
• Chest retraction or recession
• Flaring of the nostrils
• Cyanosis or low arterial oxygen saturation in room air

Primary Respiratory Causes

• Transient tachypnea of the newborn
• Pulmonary Air leaks - include Pneumothorax & pneumomediastinum
• RDS due to surfactant deficiency, usually in preterms
• Aspiration syndromes - resulting from meconium, milk, or blood
• Pneumonia
• Pulmonary hypoplasia - with oligohydramnios
• Pulmonary haemorrhage
• Chronic neonatal lung disease - aka BPD

Secondary Problems Causing Respiratory Distress

• Congenital Heart Diseases
• Birth Asphyxia and infections
• Surgical Conditions
• Persistence of fetal circulation (PPHN)
• Anaemia, Polycythaemia
• Metabolic Diseases

Diagnosis of Respiratory Distress- Perinatal History Should Include the Following

• Gestational age
• Polyhydramnios, or oligohydramnios
• Anomalies on ultrasound
• Risk factors for sepsis
• Passage of meconium
• Condition at birth
• Duration of amniotic membrane rupture
• Observation of vital signs and auscultation of the lungs for symmetry of air entry, and heart sounds

Investigation

• Chest radiograph, bacteriological cultures on blood, urine, cerebrospinal fluid including Viral cultures and rapid-yield immunodiagnostic tests
• Haematocrit and full blood count
• Chest transillumination if pneumothorax is suspected
• Passage of nasogastric catheters if choanal or oesophageal atresias are suspected
• Hyperoxia test to differentiate between cardiac and respiratory disease
• Echocardiography

Respiratory Distress Syndrome (RDS)

• The primary cause is inadequate production of surfactant due to prematurity also known as (hyaline membrane disease (HMD))
• The diffuse alveolar atelectasis, edema and cell injury are mainfestations of the disease
• Serum proteins that inhibit surfactant function leak into the alveoli

Advances Made in the Management Include

• Diagnosing infants at risk through prenatal diagnosis
• Antenatal administration of glucocorticoids and improvements in perinatal and neonatal care
• Replacement surfactant therapy
• Mortality from RDS has decreased but remains the main contributary cause of neonatal mortality and morbidity

Factors Affect Lung Development at Birth Include

• Prematurity, maternal diabetes, and genetic factors (White race, history of RDS in siblings, male sex)
• Thoracic malformations that cause lung hypoplasia, such as diaphragmatic hernia
• Genetic disorders of surfactant production and metabolism ( surfactant protein B or C deficiency cause a severe RDS like picture, often in term infants)
• Perinatal asphyxia in premature infants and Cesarean section before labor starts
• Management includes - Prevent hypoxemia and acidosis, optimise fluid management, reduce metabolic demands, prevent atelectasis and pulmonary edema & minimise lung injury caused by oxygen

Specific Management

• Surfactant replacement therapy.
• Continuous positive airway pressure
• Mechanical ventilation and lastly supportive care

Complications

• Pneumothorax and other air leaks
• Patent ductus arteriosus (PDA
• Subglottic stenosis(causes stridor)
• Chronic lung disease (CLD)
• Necrotizing enterocolitis (NEC)
• Intraventricular-periventricular hemorrhage,
• Periventricular leukomalacia (PVL),
• Retinopathy of prematurity (ROP)

Transient Tachypnea of the Newborn (TTN)

• It is known as Wet Lung this is a relatively mild, self-limited disorder that affects infants that are born at or near full term

• Transient Tachypnea of the Newborn (TTN) occurs in 1–2% of all newborn infants and is due to respiratory mal-adaptation at birth causing retention of fluids in the lungs

• Tachypnea is generally the outstanding feature, usually benign and self-limiting, with symptoms rarely persisting beyond 48hrs Pathophysiology.

• Disruption or delay in clearance of fetal lung liquid from a number of conditions results in an increased risk of transient pulmonary edema that characterizes TTN

• Retained fluid accumulates in the Peribronchiolar, lymphatics and bronchovascular spaces, causing compression and bronchiolar collapse with areas of Air Trapping and Hyperinflation

• These change all results in a net decrease in Lung Compliance

Risk Factors

• Premature birth, precipitous birth, and operative birth without labor, associated with an increased risk of TTN
• Delayed cord clamping, promotes placental-fetal transfusion, which leads to an elevation in the central venous pressure
• Congenital disrupting clearance of fluid from the thoracic duct or pulmonary lymphatics, maternal history of asthma, maternal sedation, or high degrees of IVF
• Male, macrosomia, and multiple gestation have an increased risk

Diagnosis of TTN

• Requires the exclusion of other pathology that may result in these symptoms such as Pneumonia, Cyanotic Congenital ❤️ Disease, Hyaline Membrane Disease (HMD), Pulmonary Hypertension, Meconium Aspiration and Hypoxic-Ischemic Encephalopathy (HIE) and polycythemia

Investigations/Management:

• Sepsis evaluation
• Monitor laboratory data. If respiratory distress does not improve within four hours initiate Antibiotics
• Supportive care with increased oxygen
• In more severe cases CPAP may aid resolution but diuretic therapy has no significant effect

Meconium Aspiration Syndrome (MAS)

• Acute or chronic hypoxia and/or infection can result in the passage of meconium
• gasping by the fetus or newly born infant can cause aspiration of amniotic fluid contaminated by meconium
• MSAF complicates delivery in approximately 8% to 15% of live births and more severely MAS occurs in approximately 5% of neonates born through MSAF
• The incidence of MSAF in preterm infants is very low
• plugging of the airways, and hyperinflation
• chemical Pneumonitis and impairment of surfactant production and function

Risk Factors

• Placenta insufficiency from Preeclampsia or heavy smoking
• These women should be carefully monitored during pregnancy
• Mothers at risk for placental insufficiency include those having preeclampsia or increased blood pressure; those with diabetes, chronic respiratory, or cardiovascular diseases: women with poor uterine growth or post-term pregnancy and/or heavy smokers
• Check fetal heart rate, as well as blood pH level

NICU Management:

• Check depressed infants for chest x-rays for abnormalities
• The classic findings are diffuse, asymmetric patchy infiltrates, areas of consolidation, and hyperinflation
• Blood glucose, calcium, and electrolytes, administer fluids and circulatory support
• Measure ABGs and administer oxygen if necessary