NEONATAL

APNOEA

SUBMITTED TO, SUBMITTED BY,

MRS.BINDU.K.SHANKAR ASWATHY.R.C
ASSISTANT PROFESSOR IST YR MSc NURSING
GOVERNMENT COLLEGE OF NURSING GOVT. COLLEGE OF NURSING
THRISSUR THRISSUR
 INTRODUCTION

Apnoea is a common occurrence in preterm infants that is often due to idiopathic apnoea of
prematurity but may also be due to underlying illness or pain. In term infants, apnoea is almost
always due to a pathological cause but they may rarely experience apnoea of prematurity as
well. There are 3 types of apnoea (central, obstructive and mixed), all of which present
differently. The different types of apnoea, how each one presents and which type of
management is most appropriate.

About 30-45% of preterm babies exhibit a periodic breathing pattern characterized by 3 or

more respiratory pauses of greater than 3 seconds duration. Periodic breathing is a normal
event, reflective of immaturity of respiratory control system in these infants and does not merit
any treatment. In contrast, apnea is a pathological cessation of breathing that results in
hemodynamic disturbances and hence merits treatment.

Apnea, defined as cessation of breathing resulting in pathological changes in heart rate and
oxygen saturation, is a common occurrence in sick neonates. Apnea is a common manifestation
of various etiologies in sick neonates. In preterm children it may be related to the immaturity
of the central nervous system. Secondary causes of apnea should be excluded before a diagnosis
of apnea of prematurity is made. Methylxanthines and Continuous Positive Airway Pressure
form the mainstay of treatment of apnea in neonates. Mechanical ventilation is reserved for
apnea resistant to above therapy.

DEFINITION

Apnoea

Apnoea can be defined as “No respiratory effort for greater than 20 seconds or if cessation of
breathing lasts for more than 10 seconds and is accompanied by bradycardia and or
desaturation.”
INCIDENCE

The most common cause of apnoea is apnoea of prematurity; the incidence depends on the
neonate's gestational age

 >60% when born at 28 weeks or below.

 50% when born between 30-31 weeks.
 14% when born between 32-33 weeks.
 10% when born at 34-35 weeks or above.

 Apnoea usually resolves by the time the infant is 36wks postmenstrual age.
 Approximately 50% of infants less than 1500 grams birth weight require either the
pharmacologic intervention or ventilatory support for recurrent prolonged apnoeic
episodes. The peak incidence occurs between 5 and 7 days of postnatal age.
 Apnoea of Prematurity is a specific diagnosis and usually resolves between 34 to 36
weeks postconceptual age.
 The incidence of apnea and periodic breathing in the term infant has not been
adequately determined. Approximately 50-60% of preterm infants have evidence of
apnea: 35% present with central apnea, 5-10% with obstructive apnea, 15-20% with
mixed apnea. Another 30% will have periodic breathing.

TYPES OF APNOEA

There are three types of apnoea:

Central apnoea
Obstructive apnoea
Mixed apnoea
1.Central apnoea:

 (40%) Caused by decreased central nervous system stimuli to respiratory muscles. Both
the respiratory effort and airflow cease simultaneously (absence of chest wall
movement and airflow). A pause in alveolar ventilation due to a lack of diaphragmatic
activity.
 In other words, there is no signal to breathe being transmitted from the central nervous
system to the respiratory muscles. This is due to the immaturity of brainstem control of
the central respiratory drive.
 The premature infant also manifests an immature response to peripheral vagal
stimulation. For example, stimulation of laryngeal receptors in the adult results in
coughing. However, stimulation of these same receptors in the premature infant results
in apnea. Gavages feeds, aggressive pharyngeal suctioning, or the passage of a naso-
gastric tube.

2.Obstructive apnoea:

 (10%) Caused by pharyngeal instability / collapse, neck flexion or nasal

obstruction. Absence of airflow in presence of inspiratory efforts (There is presence of
chest wall movement but no airflow). a pause in alveolar ventilation due to obstruction
of the upper airway (usually at the level of the pharynx).
 The pharynx collapses from negative pressure generated during inspiration because the
muscles responsible for keeping the airway open are too weak in the premature infant
(ex. genioglossus and geniohyoid). Once collapsed, mucosal adhesive forces tend to
prevent the reopening of the airway during expiration. Neck flexion will worsen this
form of apnea.

3.Mixed apnoea:

 (50%) Has a mixed aetiology. Central apnoea is either preceded (usually) or followed
by obstructed respiratory effort. a combination of central and obstructive apnoea (50 -
75% of all apnoea).
 Short episodes of apnoea are usually central whereas prolonged ones are often mixed.
Periodic breathing may be mistaken for apnoea. Apnoea may be a symptom of seizure
activity.
Other types:

 Periodic breathing: Three or more respiratory pauses lasting > 3 seconds separated by
normal respiratory intervals not >20 seconds and not associated with bradycardia.
Periodic breathing can occur in 2-6% of healthy term neonates and in up to 25% of
preterm infants.
 Apnoea of infancy: “An unexplained episode of cessation of breathing for 20 second
or longer or a shorter respiratory pause associated with bradycardia, cyanosis, pallor,
or marked hypotonia in an infant > 37 weeks of gestational age.
 Apnoea of prematurity: Sudden absence of breathing that last at least 20 seconds or
is associated with bradycardia or cyanosis in an infant <37 weeks of gestational age. It
is most commonly central or mixed apnoea.
 Persistent apnoea: Apnoea persist in a neonate >37 weeks postmenstrual age. It
usually occurs in infants born <28 weeks of gestational age.

Secondary cause of apnoea: Apnoea that has a specific cause like sepsis , anemia, asphyxia,
temperature instability, pneumonia, and others.

CAUSES OF APNOEA

 Apnoea of prematurity: The most common cause of apnoea, attributable to the

immaturity of the respiratory centre in the brain. Onset is from days 2-7 of life. Apnoea
beginning immediately after birth suggests another cause. Term or near term babies
may rarely experience apnoea of prematurity but a pathological cause should be sought
before making this diagnosis in this group.
 Airway obstruction: Assess position of head and neck to ensure neutral alignment.
 Infections: Sepsis, necrotising enterocolitis, meningitis.
 Pain: Acute and chronic.
 Drugs: Maternal drugs (consider neonatal abstinence syndrome), opiates, prostin, high
levels of phenobarbitone, chloral hydrate or other sedatives, general anaesthetic.
System wise causes

 Central nervous system: Intraventricular haemorrhage, drugs, seizures, hypoxic

injury, neuromuscular disorders, brainstem infarction or anomalies, birth trauma,
congenital malformations.
 Respiratory: Pneumonia, intrinsic / extrinsic mass or lesions causing airway
obstruction, upper airway collapse, atelectasis, phrenic nerve paralysis, respiratory
distress syndrome, pneumothorax, hypoxia, malformations of chest, pulmonary
haemorrhage, aspiration.
 Cardiovascular: Anaemia, hypotension, hypertension, patent ductus arteriosus,
cardiac failure, hypovolaemia.
 Gastrointestinal: Oral feeding, bowel movement, oesophagitis, intestinal perforation,
gastro oesophageal reflux, abdominal distension.
 Metabolic: Hypoglycaemia, hypocalcaemia, hyponatraemia, hypernatremia,
hyperammonaemia, low organic acids, high ambient temperature, hypothermia,
hyperthermia.

Causes of apnoea according to age

Apnoea on day 1 is not normal and a sudden increase in severity/frequency of episodes

suggests new pathology. The following lists important potential causes of apnoea according to
age of occurrence

 Day 1-2
o sepsis
o hypoglycemia
o impending respiratory failure
o polycythemia
 Days 3-6
o sepsis
o impending respiratory failure
o Patent ductus arteriosus
o massive Intraventricular hemorrhage
o apnoea of prematurity
 Late
 o sepsis
o progressive post-extubation atelectasis
o out grown dose of theophylline/caffeine
o Presenting symptom of RSV infection
o Apnea Pathophysiology

There are currently thought to be three mechanisms of apnea of prematurity:

PHYSIOLOGIC EFFECTS OF APNEA

 Decrease in arterial oxygen tension

 Decrease in heart rate
 Decrease in peripheral blood flow
 EEG changes suggesting CNS depression if apnea is severe
 Increase in venous pressure
 Decrease in muscle tone

INVESTIGATIONS

 A thorough physical examination is mandatory with emphasis on cardiorespiratory and

neurological status.
 Further tests are determined by the need to look for specific conditions causing or
aggravating apnoea.

Laboratory studies

1.Immediate studies

a. Arterial blood gas: To rule out hypoxia and acidosis.

b. Complete blood count with differential count: May suggest infection, anaemia, or
polycythaemia.

c. Culture of blood, urine and cerebrospinal fluid: C-Reactive protein at 36-48 hours after birth
may be useful as an infection screen. Polymerase chain reaction analysis and viral cultures are
appropriate if a viral infection is suspected. Lumbar puncture and CSF analysis if meningitis is
suspected or if increased intracranial pressure from hydrocephalus is causing apnoea or
bradycardia.

d. Serum electrolyte, calcium, magnesium, and glucose levels: To rule out metabolic
abnormalities.

2.Additional studies

a. If an inborn error of metabolism is suspected: Test for organic acid levels, aminoacid profiles,
ammonia, pyruvate and lactate. Ketone in the urea may indicate an organic acidemia.

b. Stool analysis: To rule out infant botulism or other organisms.

3.Imaging and other studies

Chest radiograph: Should be performed immediately if there is any suspicion of lung of heart
or lung disease.

Electrocardiogram: If cardiac disease is suspected.

Abdominal radiograph: Should be performed immediately if indicated. It may detect sign of

NEC.

Ultrasonography of the head: To rule out periventricular-intraventricular hemmorhage,

hydrocephalous, or any congenital abnormalities.

Echocardiography and cardiac consultation: ECG can reveal changes in the R- wave amplitude
and QRS duration, appearing at the onset and termination of apnoea and bradycardia episodes.
Also rule out prolonged QT syndrome.

Electroencephalography: Apnoea and bradycardia may be a manifestation of seizure activity.

Computed tomography of head : To detect cerebral infarction and subarachnoid hemorrhage.

Use adjacent scanning protocol to limit radiation exposure. Term infants may require an MRI
for a more extensive workup.

Barium swallow: To rule out GER. It is helpful if the infant has a swallowing dysfunction or
you suspect trachea oesophageal fistula or oesophageal web.
Pneumography: A pneumogram is another essential tool in the diagnosis of apnea. Chest leads
provide a tracing that gives a continuous recording of both heart rate and chest wall movement
and can detect periods of central apnea and periodic breathing.

MANAGEMENT

 All neonates less than 34 weeks completed gestation should be routinely monitored
with cardio-respiratory and oxygen saturation monitors for at least the first week of life
or until there has been an absence of apnoeic episodes for at least 7 days.
 Above 34 weeks completed gestation neonates only need to be monitored if they are
unstable: all neonates in the NICU, PICU and Cardiac Ward at the Continuous cardio-
respiratory and pulse oximetry monitoring should occur as per Observation and
Continuous Monitoring Nursing Guideline.

ACUTE MANAGEMENT

1. Observe event: Assess. Does the apnoea appear to be obstructive, central or mixed? Is
the apnoea self-limiting or will the infant require intervention?
2. Tactile stimulation: Gentle rubbing of soles of feet or chest is usually all that is required
for episodes that are mild and intermittent.
3. Position airway: Ensure the neonate's head and neck are positioned correctly (neutral
position) to maintain a patent airway. Gently suction mouth and nostrils if necessary.
Be mindful that deep suction may stimulate a vagal response.

NB: It is important to note that although there are different types of Apnoeas, acute
management is always the same.

ONGOING TREATMENT

 Pulse oximeter / cardiorespiratory monitor:

Allows for observation of heart rate, respiratory rate and oxygen saturation. As well as
monitoring trends and patterns.

 Identify cause:
If apnoea is not physiologic, investigate to identify underlying cause and treat appropriately.
Differential diagnoses are outlined above.

 Apnoea monitor:

This detects abdominal wall movement and may alarm falsely with normal periodic breathing.
It will not detect obstructive apnoea.

 Prone positioning:

Has been shown to improve thoracoabdominal synchrony and stabilize the chest wall. Several
studies have demonstrated that prone position reduces apnoea of prematurity.

 Caffeine citrate:

From the methylxanthine group of drugs; it can be given orally or intravenously and is usually
routinely given to neonates <34 weeks gestation. It acts as a smooth muscle relaxant and a
cardiac muscle and central nervous system stimulant.

 High flow nasal cannula (HFNC):

As treatment for mixed and obstructive apnoeas. Often used when caffeine has failed.

 Nasal CPAP:

As a treatment for mixed and obstructive apnoeas and when caffeine and or HFNC has failed.

 Mechanical ventilation:

This is used when caffeine and HFNC and CPAP have been tried and there are still significant
apnoeas. It is effective in all types of apnoea.

Symptomatic management

Various methods can be used to provide symptomatic control of apnoea until the infant 'out
grows' this problem.
The following suggestions fall within the spectrum accepted at most neonatal units:

 Episodes needing brief stimulation for cyanosis + bradycardia: >6 every 12hrs.
 Episodes needing vigorous stimulation +/- oxygen: >1 every 24hrs.
 Episodes needing PPV +/- oxygen: >1 episode every 24hrs.

Pharmacological management

Both caffeine and theophylline are effective in short term reduction of symptoms.

Caffeine has advantages because of its higher therapeutic ratio, once daily dosing, lack of need
to assay blood levels and fewer adverse events.Caffeine has been more rigorously evaluated in
clinical trials compared with theophylline/aminophylline. Caffeine improves survival without
neurodevelopmental disability in VLBW infants at 18-21 months of age.

DOSAGES THEOPHYLLINE / AMINOPHYLLINE CAFFEINE

CITRATE

Loading dose 6mg/kg 20mg/kg

Maintenance dose 2.5-4.0mg/kg/dose 12hourly (2.5mg wk1, 3mg 5mg/kg 24 hrly

wk2,4mg>wk2) Increase up to
Commence maintenance 24hrs after loading 10mg/kg 24 hourly
dose for infants =</1kg, 12hrs after loading dose if no response
for infants =/>1kg and after 12 hours in infants
>1kg

Methylxanthines block adenosine receptors. Adenosine inhibits the respiratory drive, thus by
blocking inhibition, the methylxanthines stimulate respiratory neurons resulting in an
enhancement of minute ventilation, chemoreceptor sensitivity to CO2, and cardiac output.

Side effects include:

 jitteriness
 irritability
  vomiting
 abdominal distension/feeding intolerance
 seizures
 hyperglycaemia
 electrolyte imbalances

 In general, the side effects of caffeine predominantly involve the central nervous system
(eg irritability and seizures).
 Medication is usually stopped when the infant is >=34wks gestation and apnoea free
for 1 to 2 weeks. Monitoring is continued for a further week after medication is
stopped.
 Since elimination of caffeine is affected by postnatal age, it is suggested that infants
receiving caffeine are observed for 7-10 days after cessation of treatment.
 In the most premature infants (< 28 weeks gestation) apnoea frequently persists beyond
36 weeks post menstrual age and may persist beyond 40 weeks post menstrual age.

Doxapram

If theophylline therapy fails to reduce the frequency of apneic spells, a trial of the
respiratory stimulant doxapram may be considered. Doxapram is administered only as a
continuous infusion, initially at a rate of 1.0 to 1.5 mg/kg per hour. Once control is obtained,
the infusion is decreased. Although increased doses up to 2.5 mg/kg per hour may be
effective in infants who continue to have apnea at lower doses, the risk of toxicity is
considerably increased.

Toxicity includes hyperactivity, jitteriness, seizure, hyperglycemia, mild liver dysfunction,

and hypertension. Although these abnormalities resolve following discontinuation of the
drug, toxicity and the need for continuous parenteral administration limit is widespread use.

Continuous Positive Airway Pressure (CPAP)

CPAP is effective in treating both obstructive and mixed apnea, but not central apnea.
CPAP is most commonly delivered by nasal prongs or by an endotracheal tube placed in
the nasopharynx. Candidates for CPAP consideration would be infants with moderate to
severe apnea i.e. >8 episodes in a 12 hour period or 2 episodes in 24 hours requiring bag
and mask ventilation.

Apnea that continues in spite of optimum methylxanthine treatment may respond to low-
level CPAP. Accordingly, a trial of CPAP (4-5 cmH2O) is warranted in addition to or as
an alternative to ineffective methylxanthine treatment. Frequent apnea associated with
marked bradycardia and/or arterial oxygen desaturation refractory to methylxanthines
and/or CPAP should be treated with positive pressure ventilation.

Intermittent Mandatory Ventilation (IMV)

If significant apnea persists despite using both pharmacotherapy and CPAP, the infant
should be intubated and ventilated. Initial settings need to be clinically adjusted to prevent
episodes of desaturation or cyanosis. In order to minimize barotrauma, short inspiratory
times should be used along with minimal peak inspiratory and expiratory pressures. The
infant may need to remain on a minimal rate for a few weeks while the respiratory control
system matures.

 Prone positioning can improve thoracoabdominal synchrony and stabilize the chest wall
without affecting breathing pattern or SpO2. Several studies have demonstrated that
prone position reduces AOP .
 Extension of the neck 15° from the prone position is referred to as the head -tilt position,
which has been found to decrease episodes of oxygen desaturation and it should be
considered as a first-line intervention in infants with AOP .
Other Therapies

KMC

Maternal kangaroo care, also known as skin-to-skin care for premature infants, has calming
effects on the baby’s clinical status and vital signs. It has shown to be effective in reducing
the apnoea.
Sensory Stimulation

Sensory stimulants, including tactile and olfactory stimulation, are useful in the treatment or
prevention of AOP. Tactile stimulation is the most common intervention in response to AOP.
This simple intervention most likely works by generating excitatory, nonspecific neuronal
activity in the brainstem centre to stimulate respiratory activity.

 Cutaneous stimulation often arouses the infant and markedly affects breathing pattern
in premature infants. Systematic review has shown that kinesthetic stimulation is not
effective at preventing AOP.
 Olfactory stimulation has also been used for the treatment of AOP. Pleasant odors
elicited increased respiratory drive, whereas unpleasant odors caused decreased
respiratory effort, during active sleep when apnoea is more common.
 Vanilla, a stimulus known to affect the olfactory nerve, was used to treat refractory
apnoea and bradycardia unresponsive to both caffeine. The presence of a pleasant odour
helped the infants to better regulate their respiratory patterns .
 An increase in upper airway resistance may also play a significant role in AOP.
Nasogastric tubes have been documented to increase nasal airway resistance by 50%.
Therefore, orogastric feeding tubes are sometimes preferred in premature infants with
apnoeic events. Interestingly, transpyloric feedings, especially when limited to human
milk, have recently been shown to be safe and reduce episodes of apnoea and
bradycardia in premature infants with suspected gastroesophageal reflux .
Thermoneutral Range

 A mild increase in body temperature in infants enhances the instability of the breathing
pattern.
 Packed Cell Transfusion

 Anemia can lead to AOP, and a proposed mechanism to treat AOP is transfusion of red
blood cells to increase oxygen carrying capacity. Because of the lack of clear cut
evidence transfusion to treat AOP may not be recommended as a routine unless the
neonate fulfils the recommened transfusion criteria for preterm neonates

Avoidance of Triggering Reflexes:

 Beware of suction catheters

 Avoid nipple feedings (feed by tube or intravenously)
 Avoid hyperinflation and hyperventilation during bagging
 Avoid cold stimuli to the face
 Place infant in the prone position
 Avoid severe flexion of neck
 Treat gastro esophageal reflux

Discharge Planning & Follow Up

A major issue in the management of infants with apnea is deciding when to stop administration
of theophylline and whether or not the infant needs to be discharged on theophylline, a home
monitor, or both.

Discontinuing medications:

Consider stopping theophylline therapy when the apnea has resolved and the infant weighs
between 1800 and 2000 g. If the infants remain asymptomatic following the discontinuation
of theophylline therapy, the child may be discharged without further therapy.

Home Monitors:

 Preterm infants who continue to exhibit symptomatic apnea when they would otherwise
be ready for hospital discharge should have their oxygenation carefully evaluated,
because hypoxia can cause apnea in preterm infants, and relieving it may resolve the
problem. Chronic lung disease is frequently associated with apnea in preterm infants,
In the absence of any identified underlying cause, preterm infants who are still having
clinically apparent episodes of apnea can be discharged on home apnea-bradycardia
monitoring. If theophylline or caffeine reduces the frequency of these episodes, then
these infants can be treated in addition to the home monitor. An additional indication
 for home monitoring is a positive history of an apparent life-threatening event (ALTE)
during the infant's hospital course.

Family centered care

 Ensure that parents are aware of the cause of the apnoea and how it is being treated e.g.
Apnoea of prematurity treated with Caffeine.
 Ensure the parents of premature babies are aware that Apnoea of Prematurity is a
normal occurrence and should resolve with age.
 Explain all interventions and why they are necessary e.g. Caffeine, Antibiotics, CPAP
or Ventilation.

CONCLUSION

Apnea is pretty dangerous. In order to avoid irreversible damage. Human breathing is

controlled by the brain’s respiratory centre. At the same time, various receptors in the body
monitor the changes in the concentration of carbon dioxide and oxygen in the body. When the
respiratory centre directs the lungs to breathe, it adjusts according to various stimuli in the
body. However, the sensory receptors of premature infants are less sensitive to CO2, and the
sensitivity gradually increases with the increase of gestational age, and can reach adult level at
term. The more immature the new-born, the higher the frequency of periodic breathing.
Periodic breathing may also exist in full-term infants and early infancy, which usually occurs
within 2 days after birth. So far, no direct connection has been found between periodic
breathing and apnea in premature infants.

RELATED RESEARCH STUDIES

1.Caffeine for the Treatment of Apnoea in the Neonatal Intensive Care Unit: A Systematic
Overview of Meta-Analyses

Objective: The aim was to provide a systematic overview of SRs on the use of caffeine for the
management of neonatal apnoea. Such overviews are a recent method used to assess and filter
top evidence among SRs, enabling enhanced access to targeted information of interest.

Methods: A comprehensive literature search was conducted via EMBASE, Cochrane

Database of Systematic Reviews (CDSR), and PubMed since inception to January 2020. Two
reviewers independently conducted study selection and data extraction, and assessed the
quality of methods and the risk of bias in included SRs based on A Measurement Tool to Assess
Systematic Reviews (AMSTAR-2) and Risk of Bias in Systematic Reviews (ROBIS) tools.
Extracted data related to study type, characteristics, patients, intervention, comparator,
regimen, and outcome measures.

Results: Seven SRs with meta-analyses (SRMAs) were included in the current overview,
involving a total of 63,315 neonates. SRMAs included randomized clinical and observational
studies, with various types of patients, comparators, and outcomes. The effectiveness of
caffeine with regard to treatment success and the rate of apnea was not significantly different
from that of theophylline or doxapram in two SRMAs. Against control, in one SRMA, while
caffeine reduced the rate of failure as well as the need for pressure ventilation, it did not
significantly reduce mortality. This comparative effectiveness of caffeine was based on high-
quality SRMAs with a low risk of bias.

CONCLUSION

There is evidence of non-inferior effectiveness of caffeine against other methylxanthines or

doxapram for the management of apnea in neonates. Owing to the limited quality, limited
evidence exists in support of an optimal administration regimen for caffeine. Further controlled
studies are, therefore, needed to confirm the comparative usefulness of caffeine as well as to
assess its different potential regimens, including in relation to safety.

2. High variability in nurses’ tactile stimulation methods in response to apnoea of

prematurity

A prospective observational study was carried out at the NICU of the Leiden University
Medical Center from April to July 2018. Nurses were asked to demonstrate and explain their
current procedures for stimulating preterm infants during a simulated scenario of apnoea of
prematurity using a manikin. At the end of the demonstrations, all nurses were asked how they
had developed their methods of tactile stimulation.

Nurses were asked to demonstrate and explain their methods of tactile stimulation on a
manikin, using an apnoea scenario. All nurses demonstrated their methods three times in
succession, with the manikin positioned either prone, supine or lateral. Finally, the nurses were
asked how they decided on the methods of tactile stimulation used. The stimulation methods
were logged in chronological order by describing both the technique and the location. The
nurses' explanations were transcribed and categorised.

Results

In total, 47 nurses demonstrated their methods of stimulation on the manikin. Overall, 57

different combinations of technique and location were identified. While most nurses (40/47,
85%) indicated they learned how to stimulate during their training, 15/40 (38%) of them had
adjusted their methods over time. The remaining 7/47 (15%) stated that their stimulation
methods were self-developed.

Conclusion

Tactile stimulation performed by NICU nurses to terminate apnoea was highly variable in both
technique and location, and these methods were based on either prior training or intuition.

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