Apnoea of Prematurity

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Last updated: March 31, 2026Bookmark

Apnoea of prematurity is a developmental disorder of respiratory control that occurs in preterm infants born at < 34 weeks’ gestational age.

Apnoea of prematurity is defined as:

  • Cessation of breathing (airflow) for ≥ 20 seconds, or
  • Cessation of breathing (airflow) for < 20 seconds with vital changes
    • Bradycardia (< 80 – 100 bpm or a drop in ≥ 30 bpm from baseline)
    • Desaturation (< 85%)

Its prevalence is inversely related to gestational age. At < 28 weeks, almost all neonates are affected.

It usually occurs 2-3 days post-delivery. Apnoea on day 1 of life is not apnoea of prematurity.

Definition of terms

TermDefinition
Periodic breathingCessation of airflow for periods less than 10 seconds occurring at least thrice in succession without change in vitals (no desaturation or bradycardia). Commonly seen in preterms 2 – 6 weeks of life during quiet sleep. Usually resolves by 39 – 42 weeks post-menstrual age. Prominent during active sleep and is eliminated by CPAP.
Intermittent hypoxiaShort and repetitive episodes of hypoxemia and desaturation without bradycardia or apnoea
Apnoea of infancyApnoea occurring in term babies. It is always pathological.
Persistent apnoeaApnoea that continues past 37 weeks post-menstrual age
Extreme apnoea eventApnoea of more than 30 seconds and/or heart rate < 60 bpm for > 10 seconds
Brief Resolved Unexplained Event (BRUE)An acute, frightening event with apnoea, bradycardia, color change, or choking. Low-risk BRUE requires only parental education.

Types of apnoea

ClassificationDescription
Mixed apnoea (40 – 50%)Contains elements of both central and obstructive apnoea
Central apnoea (30 – 40%)Cessation of both airflow and respiratory effort
Obstructive apnoea (10 – 20%)Cessation of airflow in the presence of continued respiratory effort. Due to secretions or the collapse of pharyngeal muscles
  • Pathophysiology
    • Immature respiratory control
      • Poor brainstem development
      • Reduced CO2 sensitivity
      • Hypoxia → apnoea (instead of tachypnoea)
    • Abnormal reflexes
      • Laryngeal reflex → apnea with feeds or secretions
      • Vagal dominance → bradycardia
    • High levels of GABA and adenosine → suppression of the central urge to breathe
    • Poor pharyngeal tone and reduced chest wall compliance → airway collapse during sleeping
  • Differentials – other causes of apnoea
    • Maternal sedation
    • Magnesium use peripartum
    • Birth asphyxia
    • Hypoglycaemia
    • Early-onset sepsis
    • Respiratory distress: apnoea might indicate worsening disease
    • Causes of secondary apnoea
      • Temperature instability
      • Intraventricular hemorrhage
      • Sepsis
      • Necrotizing enterocolitis
      • Pneumonia
      • Gastroesophageal reflux or aspiration
      • Electrolyte disturbances
  • Investigations
    • Sepsis screen
    • Blood glucose
    • Electrolytes
    • Chest radiograph to rule out lung disease
    • Cranial ultrasound to rule out intraventricular haemorrhage
    • EEG to rule out seizures in some cases
    • Polysomnography
  • Treatment
    • Positioning with the neck neutral
    • Thermoneutral environment
    • Minimal stimulation
    • Gentile tactile stimulation during episodes
    • Caffeine citrate
      • Blocks adenosine receptors → increases respiratory drive
      • Has a longer half-life and a higher therapeutic index than theophylline
      • It also has fewer side effects
    • Theophylline is rarely used
    • CPAP if apnea persists despite caffeine
    • Mechanical ventilation for severe or refractory cases
    • Caffeine can be stopped once the neonate is apnea-free for 5 – 7 days (usually at 34 – 35 weeks postmenstrual age)
    • Observe for 5 – 7 days before discharge
  • Clinical course of apnoea of prematurity
    • Starts day 2 – 3
    • Peaks at 1 – 2 weeks
    • Resolves by 34 – 36 weeks postmenstrual age
Reference Intervals ›
Biochemistry
ACTHP: <80 ng/L
ALTP: 5–35 U/L
AlbuminP: 35–50 g/L
AldosteroneP: 100–500 pmol/L
Alk. phosphataseP: 30–130 U/L
α-AmylaseP: 0–180 IU/dL
α-FetoproteinS: <10 kU/L
Angiotensin IIP: 5–35 pmol/L
ADHP: 0.9–4.6 pmol/L
ASTP: 5–35 U/L
BicarbonateP: 24–30 mmol/L
BilirubinP: 3–17 μmol/L
BNPP: <50 ng/L
CRPP: <10 mg/L
CalcitoninP: <0.1 mcg/L
Calcium (ionized)P: 1.0–1.25 mmol/L
Calcium (total)P: 2.12–2.60 mmol/L
ChlorideP: 95–105 mmol/L
CholesterolP: <5.0 mmol/L
VLDLP: 0.128–0.645 mmol/L
LDLP: <2.0 mmol/L
HDLP: 0.9–1.93 mmol/L
Cortisol AMP: 450–700 nmol/L
Cortisol MidnightP: 80–280 nmol/L
CK ♂P: 25–195 U/L
CK ♀P: 25–170 U/L
CreatinineP: 70–100 μmol/L
FerritinP: 12–200 mcg/L
FolateS: 2.1 mcg/L
FSHP: 2–8 U/L ♂; >25 menopause
GGT ♂P: 11–51 U/L
GGT ♀P: 7–33 U/L
Glucose (fasting)P: 3.5–5.5 mmol/L
Growth hormoneP: <20 mu/L
HbA1C (DCCT)B: 4–6%
HbA1C (IFCC)B: 20–42 mmol/mol
Iron ♂S: 14–31 μmol/L
Iron ♀S: 11–30 μmol/L
Lactate (venous)P: 0.6–2.4 mmol/L
Lactate (arterial)P: 0.6–1.8 mmol/L
LDHP: 70–250 U/L
LHP: 3–16 U/L
MagnesiumP: 0.75–1.05 mmol/L
OsmolalityP: 278–305 mosmol/kg
PTHP: 0.8–8.5 pmol/L
PotassiumP: 3.5–5.3 mmol/L
Prolactin ♂P: <450 U/L
Prolactin ♀P: <600 U/L
PSAP: 0–4 mcg/mL
Protein (total)P: 60–80 g/L
Red cell folateB: 0.36–1.44 μmol/L
Renin (erect)P: 2.8–4.5 pmol/mL/h
Renin (recumbent)P: 1.1–2.7 pmol/mL/h
SodiumP: 135–145 mmol/L
TBGP: 7–17 mg/L
TSHP: 0.5–4.2 mU/L
T4P: 70–140 nmol/L
Free T4P: 9–22 pmol/L
TIBCS: 54–75 μmol/L
TriglyceridesP: 0.50–2.3 mmol/L
T3P: 1.2–3.0 nmol/L
Troponin TP: <0.1 mcg/L
Urate ♂P: 210–480 μmol/L
Urate ♀P: 150–390 μmol/L
UreaP: 2.5–6.7 mmol/L
Vitamin B12S: 0.13–0.68 nmol/L
Vitamin DS: 50 nmol/L
Arterial Blood Gases
pH7.35–7.45
PaCO₂4.7–6.0 kPa
PaO₂>10.6 kPa
Base excess±2 mmol/L
Urine
Cortisol (free)<280 nmol/24h
Hydroxyindole acetic acid16–73 μmol/24h
Hydroxymethylmandelic acid16–48 μmol/24h
Metanephrines0.03–0.69 μmol/mmol cr.
Osmolality350–1000 mosmol/kg
17-Oxogenic steroids ♂28–30 μmol/24h
17-Oxogenic steroids ♀21–66 μmol/24h
17-Oxosteroids ♂17–76 μmol/24h
17-Oxosteroids ♀14–59 μmol/24h
Phosphate (inorganic)15–50 mmol/24h
Potassium14–120 mmol/24h
Protein<150 mg/24h
Protein/creatinine ratio<3 mg/mmol
Sodium100–250 mmol/24h
Haematology
WCC4.0–11.0 ×10⁹/L
RBC ♂4.5–6.5 ×10¹²/L
RBC ♀3.9–5.6 ×10¹²/L
Hb ♂130–180 g/L
Hb ♀115–160 g/L
PCV ♂0.4–0.54 L/L
PCV ♀0.37–0.47 L/L
MCV76–96 fL
MCH27–32 pg
MCHC300–360 g/L
RDW11.6–14.6%
Neutrophils2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes1.0–4.5 ×10⁹/L (20–45%)
Eosinophils0.04–0.44 ×10⁹/L (1–6%)
Basophils0–0.10 ×10⁹/L (0–1%)
Monocytes0.2–0.8 ×10⁹/L (2–10%)
Platelets150–400 ×10⁹/L
Reticulocytes0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time10–14 s
APTT35–45 s
Paediatric
Pulse Rate (bpm)
Neonate140–160
Infant <1yr120–140
1–5 years110–130
5–12 years80–120
>12 years70–100
Respiratory Rate (tachypnoea)
0–2 months≥60/min
2–12 months≥50/min
1–5 years≥40/min
>5 years≥30/min
Blood Pressure (mmHg)
Term65/45
1 year75/50
4 years85/60
8 years95/65
10 years100/70
Weight Formulas
3–12 months(a + 9)/2 kg
1–6 years2a + 8 kg
>6 years(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn13–20
1 month11–18
2 months10–15
1–2 years10–13
>2 years11–14
MUAC (6 months–5 years)
Obese>17.5 cm
Normal13.5–17.4 cm
At risk12.5–13.4 cm
Moderate malnutrition11.5–12.4 cm
Severe malnutrition<11.5 cm
Developmental Milestones
Social smile1.5 months
Head control4 months
Sits unsupported7 months
Crawls10 months
Stands unsupported10–12 months
Walks12–13 months
Talks18 months
CSF WBC (/mm³)
Term newborn0–25
>2 weeks0–5
Calculator ›

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