This document discusses apnea of prematurity (AOP), which refers to cessation of breathing seen in premature infants due to immaturity of respiratory control systems. AOP is defined as absent breathing accompanied by bradycardia and desaturation. The risk is highest in infants born before 28 weeks gestation, with over 60% affected. Treatment involves identifying/treating underlying causes, caffeine therapy to increase breathing drive, and respiratory support like CPAP if needed. AOP generally resolves by 37 weeks but can persist longer in more premature infants. Prompt treatment is important to avoid hypoxia-related risks.

1. APNEA OF
PREMATURITY
(AOP)
-DR. ASIF BAGWAN
JUNIoR RESIDENT
DR. PDMMC AMRAVATI

2.  Definition
 Apnea is defined as cessation of breathing. It is
pathologic when absent breathing is accompanied by
bradycardia (HR <100 bpm), hypoxemia (detected
clinically by cynosis or by oxygen saturation
monitouring SpO2 <80%), hypotonia or pallor.
Bradycardia and desaturation are usually present after 20
seconds of apnea, although they typically occur more
rapidly in the small premature infant. As the spell
continues, pallor and hypotonia are seen, and infants may
be unresponsive to tactile stimulation.

3.  Apnea is usually related to immaturity of respiratory control
system in preterm infants and hence called as apnea of
prematurity (AoP).
𝑖𝑛𝑐𝑖𝑑𝑒𝑛𝑐𝑒 𝑜𝑓 𝑎𝑝𝑛𝑒𝑎 ∝
1
𝑤𝑒𝑒𝑘𝑠 𝑜𝑓 𝑔𝑒𝑠𝑡𝑎𝑡𝑖𝑜𝑛
 The incidence of AoP is inversely proportional to
gestational age. Incidence varies from 10% in infant born at
gestation of 34 wk and move to >60% in infant born at or
less than 28 wk of gestation.
 Apnea can also be a manifestation of many other diseases in
neonates.

4.  Classification of apnea is based on whether absent
airflow is accompanied by continued inspiratory efforts
and/or upper airway obstruction.
1. Central apnea (40%) occurs when inspiratory efforts are
absent.
2. Obstructive apnea(10%) occurs when inspiratory efforts
persist in the presence of airway obstruction, usually at
the pharyngeal level.
3. Mixed apnea(50%) occurs when airway obstruction with
inspiratory efforts precedes or follows central apnea.

6.  Incidence
Apneic spells occur frequently in premature infants.
Essentially, all infants <28 wk gestational age have apnea.
As many as 25% of all premature infants who weigh<1,800
g (~34 wk gestational age) have at least one apneic episode.
1. Onset. Apneic spells may be noted even at birth (due to
RDS); if they do not occur during the first 7 days, they are
unlikely to occur later.
2. Duration. Apneic spells persist for variable periods
postnatally and usually cease by 34 to 37 wks of cGA in
infants born at 28 wks gestation or more. In infants born
before 28 wks gestation, however, spells often persist
beyond that.

7. 3. Term infants. Apneic spells occurring in infants at or
near term are always abnormal and are nearly always
associated with serious, identifiable causes, such as birth
asphyxia, intracranial hemorrhage, seizures, or depression
from medication.
 The source of obstruction in preterm neonate is generally
abnormal neck position and/or secretion.
 Monitouring for all neonates less than 35 wks of
gestation should be done for apnea in first wk of life.

8.  Etiopathology
AoP is related to immaturity
of brainstem and peripheral
chemoreceptors resulting in
abnormal ventilatory
response to hypercarbia and
hypoxia, along with
immature reflex responses.

10.  This condition usually presents after 1-2 days of life
(may be missed in case of ventilatory support in initial
days) and within the first 7 days of life.
 Apnea occurring in first 24 hrs and beyond 7 days of life
is more likely associated with secondary causes than
associated with AoP.

11. Secondary Causes
Temprature Insatability
Hypothermia, Hyperthermia,
Frequent Fluctuation In Body
Temperasture
01 Hematological
Aneamia,
Polycythemia
03
Metabolic
Acidosis, Hypoglycemia,
Hypocalcemia, Hyponatremia,
Hypernatremia
02 Pulmonary
RDS, Pulmonary Hemorrhage, obstructive
airway, pnumothorax, hypoxemia,
hypercarbia, airway obstruction due to neck
flexion
04

12. Secondary Causes
Gastrointestinal
Gastroesophageal Reflex,
Abdominal Distention,
Necrotising Enterocolitis
07 Infection
Sepsis, Pneumonia,
Meningitis, Necrotising
Enterocolitis
08
05 Neurological
Intracranial Infection, ICH, Seizure,
Perinatal Asphaxia, Placental Transfer
Of Drugs such as Narcotics, MgSO4,
Or Drugs used for General Anesthesia
06 Cardiac
Congenital Heart Disease,
hypo/hypertention, CHF,
PDA

14.  MONITORING AND EVALUATION
 All infants <35 wks gestational age should be monitored
for apneic spells for at least the first 7 days after birth
because of the risk of development of apnea.
 Monitoring should continue until no significant apneic
episode has been detected for at least 5 days. Pulse
oximetry should be monitored to detect episodes of
desaturation and bradycardia.
 When a monitor alarm sounds, one should remember to
respond to the infant, not the monitor, checking for
bradycardia, cyanosis, and airway obstruction.

15.  Most apneic spells in preterm infants respond to tactile
stimulation.
 Infants who fail to respond to stimulation should be
ventilated during the spell with bag and mask, generally
starting with a fractional concentration of inspired
oxygen (FiO2).
 After the first apneic spell, the infant should be evaluated
for a possible underlying cause and if a cause is
identified, specific treatment can then be initiated.

16.  One should be particularly alert to the possibility of a
precipitating cause in infants who are >34 weeks’
gestational age because secondary causes are most likely.
 Therefore evaluation with a detailed history and physical
examination and may include arterial blood gas
measurement complete blood count; and measurement of
blood glucose, calcium, and electrolyte levels

18.  Treatment
 A. General Measures-
1. Specific therapy should be
directed at an underlying cause,
if one is identified.
2. The optimal range of oxygen
saturation for preterm infants is
not certain.

19. However, supplemental oxygen should be provided if
needed to maintain SpO2 in the targeted range (90% to
95%). Hyperoxia should be avoided.
3. Care should be taken to avoid reflexes that may trigger
apnea. Suctioning of the pharynx should be done carefully,
and tolerance of oral feedings when appropriate should be
closely monitored.
4. Positions of extreme flexion or extension of the neck
should be avoided to reduce the likelihood of airway
obstruction. Prone positioning stabilizes the chest wall and
may reduce apnea.

20.  B. Management (Mx) Therapy- for AoP is indicated if
apneic episodes are frequent and the baby requires PPV
for apnea that is unresponsive to tactile stimulation
 Mx therapy is initiated as IV and can be shifted to oral
after infant is stable and tolerating oral feeds
 Recurrent or persistent apnea of prematurity is
effectively treated with methylxanthines.
Methylxanthines increase central respiratory drive by
lowering the threshold of response to hypercapnia as well
as enhancing contractility of the diaphragm and
preventing diaphragmatic fatigue.

21.  Caffeine and theophylline are similarly effective, but
caffeine is preferred because of its longer half-life and
lower potential for side effects (less tachycardia and
feeding intolerance). In preterm infants, caffeine reduces
the incidence and severity of apnea of prematurity,
facilitates successful extubation from mechanical
ventilation, reduces the rate of bronchopulmonary
dysplasia (BPD), and improves neurodevelopmental
outcomes.

23.  Despite its high
frequency in preterm
infants, long term
harm associated
with apnea of
prematurity is
unknown.
 Apnea of prematurity does not appear to alter an infant’s
prognosis unless it is severe, recurrent, and refractory to
therapy. Prompt, effective therapy and careful monitoring are
vital to avoid prolonged, severe hypoxia, which may increase
the risk of death and neurodevelopmental impairment.

24.  Continuous positive airway
pressure (CPAP)- is usually
administered using nasal prongs with
PEEP of 5 cm of H2O in case of
persistent episode of apnea despite
Mx therapy.with CPAP infant will
have fever episodes of apnea. This
reduction is primarily related to
significant reduction in episodes of
obstructive and mixed apneas and
has effect in securing and keeping
upper airway open by positive
airway pressure.

25.  Heated Humidified high-
flow nasal cannula
(HHHFNC) use for apnea is
on the rise; the parents and
staff find the HFNC much
friendlier and as effective as
CPAP.
 Both are used widely, but
CPAP may be preferred in
extremely preterm infants
because of its proven
efficacy and safety.

26.  The neonate should be
ventilated if significant
apnea persists even after
Mx therapy and
CPAP/HHHNFC. (As
there is no underlying
disease in AoP, only
minimal setting like PIP
10 to 12 cm of H2O and
PEEP of 3-5 cm of H2O).

27.  DISCHARGE CONSIDERATIONS
 We typically require that preterm infants have no apnea
spells recorded for 5 to7 days prior to discharge, although
this may be extended for extremely low- gestational-age
infants or those with severe events.
 Because of the long half-life of caffeine (50 to 100 hours)
and even longer effects in some infants, we typically start
this “countdown” period several days to 1 week after
caffeine is stopped.

28.  REFERENCES
1. NELSON TEXTBOOK OF PEDIATRICS (21ST
EDITION),
2. CLOHERTY AND STARK’S MANUAL OF
NEONATAL CARE (SOUTH ASIAN
EDITION),
3. AIIMS PROTOCOLS IN NEONATOLOGY
(2ND EDITION).