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Recognition of the seriously unwell neonate and young infant

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    PIC Endorsed

  • See also

    Sepsis
    Febrile child
    Sepsis in neonates
    Acceptable range of physiological variables

    Key points

    1. Infections are the most likely cause of illness in neonates (<28 days corrected age) and young infants (<3 months), however several other serious conditions can have similar initial presentations
    2. A fever in any neonate (≥38°C) warrants initial investigation and empiric IV antibiotics
    3. Unwell infants can present with non-specific findings and may not have a fever; a period of observation, serial examinations and investigations are often helpful
    4. Early review by senior clinician is essential

    Background

    • Infection is the most common cause of illness, with urinary tract infections (see UTI) being the most common bacterial infection
      • Fever is not always present. Neonates and young infants can present with a normal or low temperature (<36.5°C)
    • Neonates and young infants at particular risk include
      • Low birth weight and premature babies
      • Those with a known medical condition eg congenital anomaly
      • Babies from socially disadvantaged families
    • Other causes of an unwell neonate or infant include cardiac, metabolic and surgical causes

    Assessment

    History

    • Irritability
    • Fever
    • Lethargy or increased sleepiness
    • Poor feeding (volume taken in previous 24 hours <50% of normal)
    • Urine output (<4 wet nappies in 24 hours)
    • Vomiting, particularly bilious
    • Apnoea
    • History of brief resolved unexplained event (BRUE) or seizures
    • Growth history and trajectory
    • Maternal and perinatal history
      • Antenatal complications: intrauterine growth restriction (IUGR), gestational diabetes, congenital abnormality, maternal infections or sexually-transmitted infections, medication and toxin exposure
      • Birth history: prematurity, maternal Group B strep (GBS) colonisation, perinatal stress, prolonged rupture of membranes, maternal fever, Apgars and resuscitation requirements, history of postnatal investigations and antibiotics, vitamin K after birth
      • Family history: previous child with early onset sepsis, history of immunodeficiency
    • Immunisation history
    • Sick contacts
    • Exposure to herpes simplex virus
    • High level of parental concern

    Examination

    General aspects of the neonate or young infant's behaviour and appearance provide the best indication of whether serious illness is likely

    Features suggestive of an unwell neonate or young infant

    Airway Signs of acute upper airway obstruction
    Anatomical abnormality, anticipated airway difficulty
    Breathing Grunting
    Tachypnoea
    Increased work of breathing
    Hypoxia

    Apnoea
    Any chest deformity
    Circulation

    Colour: pallor, mottling, cyanosis
    Tachycardia or bradycardia
    Central capillary refill time ≥3 seconds
    Cardiac murmur, weak peripheral pulses, enlarged liver, reduced femoral pulses
    Increased weight gain (fluid overload)
    Hypotension
    Disability/neuro Lethargy or decreased activity
    Poor feeding
    Irritability
    Not responding normally to social cues

    Difficult to wake
    Weak, high-pitched or continuous cry
    Reduced tone
    Abnormal movements
    Focal neurological signs
    Focal, complex or prolonged seizures

    Exposure

    (ensure full exposure for examination,

    while minimising heat loss)

    		 Jaundice
    Swelling of a limb or joint
    Not using an extremity
    Distended abdomen
    Enlarged liver (cardiac, metabolic)
    Fluids/hydration Dry mucous membranes, reduced skin turgor, sunken fontanelle
    Reduced urine output
    Poor weight gain
    Glucose Apnoea
    Jitteriness
    Altered conscious state
    Haematological

    Non-blanching rash
    Bruising
    Bleeding
    Infection Fever or hypothermia
    Bulging fontanelle
    Neck stiffness
    Vesicular rash, encephalopathy (HSV)

    Causes that need to be considered in an unwell neonate and young infant

    Condition Salient features
    Infective: bacterial  UTI/pyelonephritis Fever vomiting, poor feeding
    Bacteraemia/sepsis
    Pneumonia
    Meningitis    		 Fever, tachycardia, tachypnoea, increased work of breathing
    Irritable, neck stiffness or bulging fontanelle
    Bone or joint Reduced movement of limb +/- swelling
    Skin Skin erythema, swelling, tenderness or lesions
    Infective: viral Bronchiolitis Tachypnoea, increased work of breathing, wheeze or crackles on auscultation
    Primary HSV, in first 1 month of life Skin vesicles (not present in 1/3 of neonates and can be afebrile), seizures or encephalopathy
    Influenza and other respiratory viruses Fever, poor feeding, lethargic, nasal congestion
    Enterovirus or parechovirus Fever, rash, poor feeding, irritable, possible seizures, persistent or marked tachycardia (myocardial involvement)
    Surgical Malrotation with volvulus Bile-stained vomit, abdominal distension
    Pyloric stenosis Progressive, non-bilious and projectile vomiting, pyloric olive-shaped mass, hypochloraemic hypokalaemic metabolic alkalosis
    Incarcerated hernia Irreducible inguinal swelling
    Hirschsprung's disease and meconium ileus Abdominal distention with absent or infrequent bowel motions
    Necrotising enterocolitis (NEC) Abdominal distention, tenderness, vomiting, blood in stool, discolouration or erythema of abdominal wall
    Intussusception Intermittent severe abdominal pain, vomiting, pallor, lethargy and rectal bleeding (red currant stool, a late sign)
    Cardiac Congenital cardiac disease Cyanosis, murmur (not always present), diaphoresis (sweating) with feeding, cardiac failure (tachypnoea, enlarged liver, hypoperfusion), poor or absent peripheral pulses
    Supraventricular tachycardia (SVT) and other arrhythmias Persistent marked tachycardia, pallor, poor feeding
    Respiratory Meconium aspiration Meconium-stained liquor, tachypnoea, increased work of breathing, cyanosis
    Transient tachypnoea of the newborn (TTN) and respiratory distress syndrome Tachypnoea, increased WOB, possible cyanosis, radiological findings
    Pneumothorax Tachypnoea, hyper-resonance, decreased breath sounds
    Endocrine and metabolic Congenital adrenal hyperplasia Ambiguous genitalia, hypotension, dehydration, hyponatraemia, and hyperkalaemia, hypoglycaemia
    Hypoglycaemia
    Inborn errors of metabolism    		 Altered level of consciousness, hypotonia, seizures, jaundice, organomegaly, dysmorphism
    Hypoglycaemia, metabolic acidosis
    Non-accidental injury (NAI) Child abuse Bruising, unexplained injury, signs of intracranial injury, signs of neglect
    Other Acute bilirubin encephalopathy Jaundice
    Brief resolved unexplained event (BRUE)
    Toxin
    Electrolyte abnormalities Eg iatrogenic, from diluted formula water ingestion

    Management

    Any neonate or young infant who appears unwell should be assessed promptly and discussed with a senior doctor

    Investigations

    • For unwell neonates and young infants: Perform BGL, consider VBG if available, FBE, UEC, LFT, CRP, blood culture, urine MCS (see SPA)
    • Lumbar puncture in neonates <28 days (if not contraindicated), consider in young infants
    • Investigate according to likely cause (see table above) consider
      • Ammonia level
      • Viral swabs eg HSV
      • ECG
    • Consider imaging, depending on the cause
      • CXR
      • Abdominal imaging
      • Neuroimaging

    Treatment

    • Involve senior clinician
    • Early referral to paediatric, surgical and/or sub-specialist team as indicated
    • All seriously unwell neonates and young infants should receive:
      • Prompt management of sepsis with early administration of empiric antibiotics (IV/IM/intraosseous)
      • Aciclovir if indicated
      • Adequate analgesia and sedation
    • Careful fluid management:
      • See Neonatal intravenous fluids for neonates
      • See Intravenous fluids for infants
      • Fluid resuscitation as required
      • Maintenance fluids, account for oral intake
      • Restrict fluid rate in meningitis or respiratory infections to two-thirds of maintenance rate
      • Judicious fluid management in cardiac causes
    • Treatment targeted to underlying suspected cause
    • Nasogastric tube on free drainage if bowel obstruction is suspected
    • In neonates with suspected duct dependent congenital cardiac condition, early discussion with cardiology/ICU/retrieval team, consider IV prostaglandin

    Consider consultation with local paediatric team when

    Assessing any unwell neonate or young infant

    Consider transfer when

    Child requiring care beyond the comfort level of the hospital

    For emergency advice and paediatric or neonatal ICU transfers, see Retrieval services

    Parent information

    Fever in children
    Crying and unsettled children
    Meningitis
    Urinary tract infections and Urine samples
    Interacting with your baby

    Updated on May 2025

    Reference List

    1. Edwards MS. Clinical features and diagnosis of sepsis in term and late preterm infants. UpToDate. https://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-sepsis-in-term-and-late-preterm-neonates (viewed May 2024)
    2. Edwards MS. Management and outcome of sepsis in term and late preterm infants [Internet]. UpToDate. https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-neonates (viewed May 2024)
    3. Jefferies AL. Management of term infants at increased risk for early-onset bacterial sepsis. Paediatr Child Heal. 2017;22(4):223--8.
    4. NICE Guidelines. Neonatal infection: antibiotics for prevention and treatment. National Institute of Health and Care Excellence. https://www.nice.org.uk/guidance/ng195/chapter/Recommendations#risk-factors-for-and-clinical-indicators-of-possible-early-onset-neonatal-infection (viewed May 2024)
    5. Puopolo KM, Benitz WE, Zaoutis TE. Management of Neonates Born at ≤34 6/7 Weeks' Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics. 2018;142(6):e20182896.
    6. Safer Care Victoria. Sepsis in neonates. https://www.safercare.vic.gov.au/best-practice-improvement/clinical-guidance/neonatal/sepsis-in-neonates (viewed May 2024)
    7. Smitherman HF, Macias CG. Febrile infant (younger than 90 days of age): Outpatient evaluation. UpToDate. https://www.uptodate.com/contents/febrile-infant-younger-than-90-days-of-age-outpatient-evaluation (viewed May 2024)
    8. Weisman LE, Pammi M. Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation. UpToDate. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bacterial-sepsis-in-preterm-infants-less-than34-weeks-gestation?search=neonatal%20sepsis&source=search_result&selectedTitle=3~101&usage_type=default&display_rank=3#H462631933 (viewed May 2024)

  • Reference List

    1. Edwards MS. Clinical features and diagnosis of sepsis in term and late preterm infants [Internet]. UpToDate. 2019. p. 1–33. Available from: https://www.uptodate.com/contents/clinical-features-evaluation-and-diagnosis-of-sepsis-in-term-and-late-preterm-infants?search=Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants&source=search_result&selectedTitle=1~150
    2. Edwards MS. Management and outcome of sepsis in term and late preterm infants [Internet]. UpToDate. 2019. p. 1–25. Available from: https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants?search=Management and outcome of sepsis in term and late preterm infants&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
    3. Government N. Paediatric Antibiotic guidelines for severe sepsis and septic shock and unwell neonates [Internet]. Clinical Excellence Commission. 2018. Available from: http://www.cec.health.nsw.gov.au/__data/assets/pdf_file/0009/348597/Newborn-Antibiotic-Guide~or-early-and-late-onset-sepsis-during-birth-episode-of-care-Revised-June-2018.pdf
    4. Health Q. Queensland Clinical Guideline: Early onset Group B streptococcal disease [Internet]. Maternity and Neonatal Clinical Guideline. 2016. Available from: http://www.health.qld.gov.au/qcg/documents/g_gbs5-0.pdf
    5. James SH, Kimberlin DW. Neonatal herpes simplex virus infection: Epidemiology and treatment. Clin Perinatol [Internet]. 2015;42(1):47–59. Available from: http://dx.doi.org/10.1016/j.clp.2014.10.005
    6. Jefferies AL. Management of term infants at increased risk for early-onset bacterial sepsis. Paediatr Child Heal. 2017;22(4):223–8.
    7. NICE Guidelines. Neonatal infection (early onset): antibiotics for prevention and treatment [Internet]. National Institute of Health and Care Excellence. 2012. p. 1–40. Available from: https://www.nice.org.uk/guidance/cg149/resources/neonatal-infection-early-onset-antibiotics-for-prevention-and-treatment-pdf-35109579233221
    8. NICE Quality Standard. Neonatal infection [Internet]. National institute for Health and Care Excellence. 2014. Available from: nice.org.uk/guidance/qs75%0A©
    9. Puopolo KM, Benitz WE, Zaoutis TE. Management of Neonates Born at ≤34 6/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics. 2018;142(6):e20182896.
    10. Scarfone RJ, Cho C. Approach to the ill-appearing infant (younger than 90 days of age) [Internet]. UpToDate. 2018. p. 1–65. Available from: https://www-uptodate-com.offcampus.lib.washington.edu/contents/approach-to-the-ill-appearing-infant-younger-than-90-days-of-age?search=approach to ill appearing infants younger than 90 days&source=search_result&selectedTitle=2~150&usage_ty
    11. Smitherman HF, Macias CG. Febrile infant (younger than 90 days of age): Outpatient evaluation [Internet]. UpToDate. 2019. p. 1–37. Available from: https://www.uptodate.com/contents/febrile-infant-younger-than-90-days-of-age-outpatient-evaluation
    12. Strategy S, Is HOW, Hypoglycemia N. Screening guidelines for newborns at risk for. Paediatr Child Heal. 2004;9(10):723–9.
    13. Victoria SC. Neonatal Strategies [Internet]. Vol. 1, Victoria State Government. 2017. Available from: www.safercare.vic.gov.au
    14. Weisman LE, Pammi M. Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation [Internet]. UpToDate. 2019. p. 1–22. Available from: https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-bacterial-sepsis-in-preterm-infants-less-than34-weeks-gestation?search=neonatal sepsis&source=search_result&selectedTitle=3~101&usage_type=default&display_rank=3#H462631933