Version May 2024
| Diagnosis | Distinguishing features | Diagnostic tests |
| Other systemic neonatal infections | ||
| Viral infections: | ||
| Mucocutaneous vesicles, CSF pleocytosis, elevated CSF protein, thrombocytopenia, hepatitis | HSV PCR; viral culture |
| Fulminant systemic disease, myocarditis, hepatitis, encephalitis | EV PCR |
| Encephalitis/meningitis, rash on palms and soles | HPeV PCR (available through CDC) |
| Thrombocytopenia, periventricular intracranial calcifications, microcephaly, sensorineural hearing loss, chorioretinitis | CMV PCR; viral culture |
| Respiratory symptoms, rhinorrhea, gastrointestinal symptoms | Influenza PCR, rapid molecular assay, or antigen detection test |
| Respiratory symptoms, rhinorrhea, cough, apnea, pneumonia | RSV PCR or antigen detection test |
| Respiratory symptoms, cough, tachypnea, gastrointestinal symptoms | SARS-CoV-2 PCR or antigen detection test |
| Spirochetal infections: | ||
| Skeletal abnormalities (osteochondritis and periostitis), pseudoparalysis, persistent rhinitis, maculopapular rash (particularly on palms and soles or in diaper area) | RPR or VDRL |
| Parasitic infections: | ||
| Anemia, splenomegaly, jaundice | Detection of parasitemia on blood smear |
| Intracranial calcifications (diffuse), hydrocephalus, chorioretinitis, mononuclear CSF pleocytosis, elevated CSF protein | Toxoplasma gondii serology |
| Fungal infection: | ||
| Persistent hyperglycemia, thrombocytopenia, multiorgan failure | Isolation of Candida in blood, urine, or CSF culture |
| Noninfectious causes of temperature instability in neonates | ||
| Altered environmental temperature | Transient; no other systemic symptoms; resolves with simple nonpharmacologic measures | |
| Dehydration | Clinical history of poor feeding or fluid losses (eg, vomiting and/or diarrhea) | |
| Neonatal abstinence syndrome | History of maternal drug use; sweating, sneezing, nasal stuffiness, and yawning | Positive drug screening tests |
| CNS insult (eg, anoxia or hemorrhage) | History of perinatal asphyxia; focal neurologic findings or seizures | Abnormal neuroimaging studies |
| Hypothyroidism | Hypotonia, lethargy, hypothermia, large fontanels | Abnormal T4 or TSH level on newborn screen |
| Congenital adrenal hyperplasia | Ambiguous genitalia (females), adrenal insufficiency and salt-wasting (hyponatremia, hyperkalemia, dehydration) | Abnormal 17a-hydroxyprogesterone level on newborn screen |
| Noninfectious causes of respiratory and cardiocirculatory symptoms in neonates | ||
| Transient tachypnea of the newborn | Onset of symptoms within two hours after delivery; symptoms usually resolve within 24 hours | CXR findings include increased lung volumes, mild cardiomegaly, prominent vascular markings, fluid in the interlobar fissures, and pleural effusions |
| Respiratory distress syndrome | Most common in preterm infants; rare in term infants; onset of symptoms within first few hours after delivery, progressively worsens over first 48 hours of life | CXR findings include low lung volume and diffuse reticulogranular ground glass appearance with air bronchograms |
| Meconium aspiration | History of meconium-stained amniotic fluid; respiratory distress occurs immediately after birth | Initial CXR may show streaky, linear densities; as the disease progresses, the lungs may appear hyperinflated with diffuse patchy densities |
| Pneumothorax | Asymmetric chest rise, decreased breath sounds on affected side; hypotension (in cases of tension pneumothorax) | CXR will usually detect symptomatic pneumothoraces |
| Congenital anomalies (including tracheal-esophageal fistula, choanal atresia, and diaphragmatic hernia) | Often occur with other congenital anomalies including VACTERL and CHARGE associations; choanal atresia is characterized by noisy labored breathing while feeding | CDH is often diagnosed by routine antenatal ultrasound screening; postnatal CXR shows herniation of abdominal contents into hemithorax; TEF is diagnosed with upper gastrointestinal series and/or bronchoscopy |
| Neonatal abstinence syndrome | History of maternal drug use; sweating, sneezing, nasal stuffiness, and yawning | Positive drug screening tests |
| Cardiac arrhythmias (eg, supraventricular tachycardia) | Abrupt onset and termination of rapid heart rate | Abnormal ECG |
| Congenital heart disease | Infants with ductal-dependent lesions may initially lack symptoms then develop cyanosis and rapid clinical deterioration as the PDA closes in the first few days of life | Abnormal pulse oximetry screen; abnormal echocardiography |
| Noninfectious causes of neurologic symptoms in neonates | ||
| Hypoglycemia | Common in infants who are large for gestational age and/or infants of diabetic mothers | Abnormal blood glucose level |
| Hypercalcemia | Increased neuromuscular irritability and seizures; associated with prematurity, maternal diabetes, and perinatal asphyxia | Abnormal serum calcium level |
| Hypermagnesemia | Generalized hypotonia, respiratory depression and apnea; typically results from maternal treatment with magnesium sulfate | Abnormal serum magnesium level |
| CNS insult (eg, anoxia or hemorrhage) | History of perinatal asphyxia; focal neurologic findings or seizures | Abnormal neuroimaging studies |
| Congenital CNS malformations (eg, hydrocephalus) | Abnormal head circumference | Abnormal neuroimaging studies |
| Neonatal abstinence syndrome | History of maternal drug use; sweating, sneezing, nasal stuffiness, and yawning | Positive drug screening tests |
| Inborn errors of metabolism | Otherwise unexplained acid-base disorders, hyperammonemia, hypoglycemia, hematologic abnormalities, liver dysfunction, and renal disease | Positive newborn screen for inborn errors of metabolism |
| Pyridoxine deficiency | Refractory seizures | Abnormal plasma pyridoxal-5-phophate level |
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