Neonatology

NEONATOLOGYCHAPTER 1

1.1 Jaundice in the Newborn
Rhishikesh Thakre
1.2 Respiratory Distress Syndrome in the Newborn
Bakul Parekh, Snehal Desai

21.1 JAUNDICE IN THE NEWBORN

Rhishikesh Thakre

INTRODUCTION

Neonatal hyperbilirubinemia, “icterus neonatorum”, is a “transitional” disorder which presents as jaundice characterized by yellowish discoloration of skin, sclera and mucous membrane. It manifests when bilirubin in circulation increases >5 mg/dL. The elevated unconjugated (indirect) bilirubin is most common, usually benign, but in few infants can lead to severe bilirubin-induced encephalopathy, kernicterus and impaired cognition. The rise in conjugated (direct) bilirubin is always pathological and warrants urgent evaluation and will not be detailed in the present chapter.

EPIDEMIOLOGY

Neonatal hyperbilirubinemia is a leading cause of hospitalization and ranked 7th globally among all causes of early neonatal deaths and ranked 9th among all causes of late neonatal deaths.¹ The burden is greatest in low-middle income countries. Up to 60% of term and 80% of preterm infants develop jaundice during the first week of life. In majority, the jaundice is benign but approximately 1 in 10 babies is likely to develop significant hyperbilirubinemia requiring treatment. The incidence of kernicterus ranges from about 0.2 to 2.7 cases per 100,000 live births. Disability-adjusted life year (DALY) represents 1 year of healthy life lost because of the condition at the population level. Globally, neonatal jaundice accounted for 113,401 DALYs [95% uncertainty interval (UI): 96,728–134,352] in 2016 and ranked 7th as a leading cause of DALYs in early neonatal period.²

RISK FACTORS

Knowledge of risk factors (Table 1.1.1) helps identify “at-risk” newborns and helps initiate appropriate measures for early detection and prompt management. Prematurity, hemolytic setting, perinatal infection and exclusive breastfeeding are leading risk factors predisposing to significant hyperbilirubinemia.¹

BILIRUBIN METABOLISM

Nearly 75% of bilirubin is contributed by daily breakdown of red blood cells (RBCs) in reticuloendothelial system and 25% of bilirubin is contributed by nonheme sources and products of ineffective erythropoiesis. Alteration in one or more steps involved in bilirubin metabolism (Flowchart 1.1.1) leads to rise in bilirubin in blood circulation manifesting clinically as jaundice.3

Table 1.1.1 Risk factors for hyperbilirubinemia.

Infant factors Prematurity Intrauterine growth restriction Inadequate breast milk intake Hypothermia Polycythemia Hypoglycemia Hypothyroidism Sepsis Bowel obstruction or ileus	Maternal factors Race or ethnicity Primigravida Exclusive breastfeeding Blood group incompatibility (e.g. ABO, Rh) Drugs (e.g. oxytocin, promethazine) Family history of jaundice Diabetes mellitus
Perinatal factors Assisted delivery Birth trauma (e.g. cephalhematoma, bruises) Asphyxia Delayed cord clamping Congenital infections (e.g. cytomegalovirus)	Genetic factors Glucose-6-phosphate dehydrogenase (G6PD) deficiency RBC defects (e.g. spherocytosis) β-thalassemia Galactosemia Gilbert syndrome Crigler-Najjar syndrome

Flowchart 1.1.1: Bilirubin metabolism.

4Bilirubin overproduction, reduced hepatic uptake or defective bilirubin conjugation leads to unconjugated (indirect) hyperbilirubinemia and bile canalicular transporter defects or impairment of bile flow through the intrahepatic and extrahepatic bile ducts results in conjugated (direct) hyperbilirubinemia.

The functional immaturity in bilirubin metabolism viz. increased fetal RBC breakdown, decreased liver uptake, immature conjugation, increased excretion and increased enterohepatic circulation predisposes to “physiologic hyperbilirubinemia” which is a self-limiting disorder requiring no treatment. It remains a “diagnosis of exclusion”.

BILIRUBIN NEUROTOXICITY

Elevated indirect bilirubin has a potential to cause neurotoxicity which is a complex process not fully understood. Elucidation of structural-functional relationship between bilirubin and the brain, developmental and neurologic processes is needed. There is poor correlation between bilirubin values and neurotoxicity. Areas of the brain most susceptible to bilirubin damage are globus pallidus, hippocampus, lateral ventricular walls, cerebellum, and subthalamic nuclei of auditory and optic nerves. Studies show lipid peroxidation and protein oxidation at cellular level, impaired neuronal arborization, release of proinflammatory cytokines from microglia and astrocytes leading to loss of neurons, demyelination and gliosis.³ The end result is characterized by tetrad of choreoathetoid cerebral palsy, high-frequency central hearing loss, vertical gaze palsy and dental enamel hypoplasia.

EARLY DETECTION OF JAUNDICE

Hyperbilirubinemia may develop both in the absence of risk factors and without clinically significant jaundice being present at the time of discharge. Hence one should remain alert for jaundice during first postnatal week (Box 1.1.1).

Box 1.1.1 : Predischarge assessment.

Examine all the babies for jaundice at every opportunity especially in the first 72 hours
Check whether there are risk factors associated with an increased likelihood of developing significant hyperbilirubinemia soon after birth
Realize that visual inspection alone to estimate the bilirubin level in a baby with jaundice is error prone
Measure and record the bilirubin level when in doubt
Inform parents to report if the baby appears yellow or if there are any concerns
Schedule a follow-up date based on “risk factors”

Table 1.1.2 Suggested follow-up schedule for all newborns.

Scenario	Age at discharge	Follow-up
None of risk factors present	24–72 hours	48 hours after discharge
None of risk factors present	>72 hours	Follow-up optional
Any risk factor present	24–48 hours	24 hours after discharge
	49–72 hours	48 hours after discharge
	73–120 hours	48 hours after discharge

All newborns should be assessed for one or more risk factors at time of discharge following birth. A suggested protocol is given in Table 1.1.2. The more the risk factors present, the greater is the risk of severe hyperbilirubinemia. The risk is extremely low if risk factors are absent.⁴

If facilities exist, all newborns at the time of discharge should undergo transcutaneous bilirubin (TcB) assessment. This serves as an objective screening tool. Babies with TcB >12 mg/dL should undergo serum total bilirubin estimation. The limitations of this approach include poor reliability in the first 24 hours, limited validity in preterm less than 34 weeks gestation and the high cost of the instrument.

If in doubt about the extent of jaundice or possibility of infant loss to follow-up, total serum bilirubin (TSB) should be done at discharge and hour-specific bilirubin nomogram used to predict “risk”.

During the hospital stay and at every opportunity during first week of life, all newborns should be examined for jaundice (already detailed in Box 1.1.1). Jaundice is assessed by inspecting the baby's skin, sclera or mucous membranes preferably in natural light. The skin is blanched by digital pressure over bony parts to reveal underlying yellowing. The extent of jaundice can be estimated by Kramer's criteria. However, the clinical estimation is error prone, subjective, influenced by light, experience of the examiner and pigmentation of the infant.⁵ Presence of bruising, cephalhematoma, lethargy, vomiting, excessive weight loss, pallor, plethora and hepatosplenomegaly points toward pathological jaundice. Abnormalities in tone, cry or sensorium must alert to the possibility of bilirubin neurotoxicity (Fig. 1.1.1). Certain features alert to the likelihood of pathological jaundice (Box 1.1.2).

Acute Bilirubin Encephalopathy

Acute bilirubin encephalopathy (ABE) describes the acute manifestations of neurologic dysfunction and can be reversible if corrected early enough. A bilirubin-induced neurologic dysfunction (BIND) score is used to assess the severity of jaundice (Table 1.1.3). A BIND score ≥4 is predictive of adverse outcome at 3–5 months of age with a specificity of 87.3% and sensitivity of 97.4%.⁶6

Fig. 1.1.1: Focused evaluation of newborn with jaundice.

Table 1.1.3 Bilirubin-induced neurologic dysfunction (BIND) score.

Score	Mental status	Muscle tone	Cry
0	Normal	Normal	Normal
1	Poor feeding Sleepy-arousable	Mild hypotonia	High pitched
2	Lethargy Poor suck Irritability	Moderate hypo- or hypertonia	Shrill
3	Seizures Apnea Coma	Retrocollis (Fig. 1.1.2) Opisthotonus Bicycling	Inconsolable Weak Absent
BIND score		Action		Outcome
0–3		Intensive phototherapy		Good
4–6		Exchange transfusion		Fair, reversible
7–9		Exchange transfusion		Guarded, irreversible

INVESTIGATIONS

Not all jaundice infants need investigations (Box 1.1.3).7

Fig. 1.1.2: Signs of bilirubin encephalopathy. Note the sun setting sign, retrocollis, and tightening of limbs in jaundiced newborn.

In all neonates with jaundice that is severe, prolonged or nonphysiologic, investigations are done to assess the severity of jaundice (for planning treatment) and etiology of the jaundice.

Box 1.1.4 summarizes the important investigations. The role of cord blood is limited for typing the baby blood group if mother's blood group is not known or is Rh negative or O Rh positive. The cord blood is collected for direct Coombs’ test, TSB, reticulocyte count, peripheral smear and hemoglobin if there is setting of Rh incompatibility.⁴ End-tidal carbon monoxide (ETCO) measurement in exhaled air may serve as indirect marker of ongoing 8hemolysis as equimolar concentrations of carbon monoxide and bilirubin are formed following breakdown of RBCs.

TREATMENT OF NONCONJUGATED HYPERBILIRUBINEMIA

The decision-making in jaundice management is based on gestation, weight, well-being and age in hours of baby. Supportive care is offered in addition to specific therapy. Flowchart 1.1.2 provides an algorithm for diagnosis and management of neonatal jaundice including investigations.

Flowchart 1.1.2: Algorithm showing approach to the diagnosis and management of neonatal jaundice.

(PCV: packed cell volume; G6PD: glucose-6-phosphate dehydrogenase; USG: ultrasonography; TSH: thyroid stimulating hormone)

Fluid Supplementation

Subclinical dehydration due to evaporative losses and poor intake of breast milk can lead to an increased incidence and severity of jaundice in newborns. Intravenous (IV) fluid administration has been reported to be a risk factor for development of nosocomial infection. There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy, kernicterus or cerebral palsy in healthy term newborn infants with unconjugated hyperbilirubinemia.⁷

Phototherapy

Phototherapy is an effective tool and must be considered as a key “drug” for jaundice management.⁸ When bilirubin is exposed to blue light in the range of 420–480 nm, it undergoes change in structure to a product called lumirubin which can be excreted in urine without undergoing conjugation in the liver. The choice of device depends on the severity of jaundice. Table 1.1.4 provides a comparison of various devices used in phototherapy and their advantages and disadvantages. The rule of thumb is to start phototherapy when TSB is 0.5% and 0.75% of the body weight in grams in sick and healthy infants respectively and to do an exchange transfusion when TSB is ≥1% of the body weight in grams.

Phototherapy is administered continuously and interrupted only for nursing and feeding purpose. The infant is placed naked with genitalia and eyes covered.

Table 1.1.4 Comparison of phototherapy (PT) devices.

Device	Advantages	Disadvantages
Blue-white PT	User friendly	Variable dose Blue hue Intensity reduces with time Risk of overheating
Fiberoptic PT	No parental separation No heat generated No eye patches Consistent intensity Portable	Not recommended for terms due to size
Halogen PT	Compact Consistent intensity	Generate heat Area of focus and infant distance specifications Fragile with heat
Light-emitting diode (LED) PT	Long use up to 3,000 hours Less heat Consistent intensity	-

Table 1.1.5 Choosing phototherapy device.

Phototherapy	Conventional	Intensive
Wavelength (μW/cm²/nm)	Up to 10	>30
Devices	Blue white tubes, CFL, Halogen bulb, Fiberoptic, LED	Combination of PT LED
When?	Bili in PT range	Rapidly rising bili Bili in ET range
(LED: light-emitting diode; PT: phototherapy; CFL: compact fluorescent lamp; ET: exchange transfusion)

Table 1.1.6 Supportive care during phototherapy.

Supportive care
	Conventional PT	Intensive PT
Diaper	Use	Remove
IV fluids	Not routinely	Supplement
Duration	Intermittent	Continuous
Lactation support	Yes	Yes
Hydration check	Yes	Yes
Eye care	Yes	Yes
Thermal check	Yes	Yes
Adjuncts	No	White cloth, aluminum foil
(IV: intravenous; PT: phototherapy)

Close attention is paid to the infant's temperature, daily weight, intake and output. Breastfeeding is continued frequently. Hypoxia, hypothermia, hypoglycemia, acidosis and sepsis need to be prevented and if present and treated aggressively.

Table 1.1.5 details the choices of various phototherapy devices for conventional and intensive phototherapy. Table 1.1.6 describes the differences in conventional and intensive phototherapy.

Compact Fluorescent Lamp

The response to phototherapy depends on cause, severity of hyperbilirubinemia and the light dose. A decrease in bilirubin levels of 6–20% of initial levels can be expected in the first 24 hours of standard phototherapy. Bilirubin levels decline most quickly in the first 4–6 hours of phototherapy. Intensive phototherapy can cause bilirubin drop by 30–40% within 24 hours and up to 10 mg/dL in first 6 hours when TSB levels are more than 30 mg/dL.

During phototherapy, depending on severity of hyperbilirubinemia, TSB should be monitored every 4–12 hours. Following discontinuation of phototherapy, a rebound increase in TSB levels of 1–2 mg/dL is most commonly seen in preterm, infants with hemolytic disease, or in infants treated with phototherapy in first 72 hours of age.11

The treatment thresholds for phototherapy and exchange transfusion are in Table 1.1.7.⁹

Several factors affecting phototherapy are depicted in Table 1.1.8.

Table 1.1.7 Treatment thresholds for phototherapy and exchange transfusion of indirect hyperbilirubinemia.⁹

	Phototherapy	Exchange transfusion
Age	Healthy newborns >35 weeks gestation	Newborns <35 weeks gestation	Healthy newborns >35 weeks gestation	Newborns <35 weeks gestation
Day 1	Any visible jaundice		15 mg/dL	10 mg/dL
Day 2	15 mg/dL	10 mg/dL	25 mg/dL	15 mg/dL
Day 3	18 mg/dL	15 mg/dL	25 mg/dL	20 mg/dL

Table 1.1.8 Evidence for issues in phototherapy (PT).¹⁰

Continuous or intermittent PT	No evidence to support the safe use of intermittent PT at moderate or high levels of serum bilirubin
Prophylactic PT for preterm/low birth weight (LBW)11	Helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. Efficacy and safety on long-term outcomes including neurodevelopmental outcomes need to be determined
Light-emitting diode (LED) PT12	Efficacious in bringing down levels of serum total bilirubin at rates that are similar to PT with conventional [compact fluorescent lamp (CFL) or halogen] light sources
Reliability of transcutaneous devices with PT13	Moderate correlation between TcB and TSB during PT
Effect of positioning14	Unnecessary to alternate positions of the jaundiced neonates when conventional PT is delivered to lighten nurses’ workload
Reflective materials around a PT15	Addition may be therapeutic for neonates with physiologic jaundice
Home- or hospital-based PT for term16	Inconclusive evidence
Blue light PT and melanocyte count17	No evidence
Fiberoptic PT18	Safe alternative to conventional PT in term infants with physiological jaundice
Chest shielding for preventing patent ductus arteriosus (PDA) under PT19	Very low-quality evidence
(TcB: transcutaneous bilirubin; TSB: total serum bilirubin)

Exchange Transfusion

Exchange transfusion is indicated for infants whose bilirubin levels cross the threshold indicated in Table 1.1.6 or those who have clinical features of bilirubin encephalopathy. During exchange transfusion twice the infant's blood volume (160 mL/kg) is exchanged; this procedure can decrease the bilirubin level by approximately 50%. The procedure is invasive and carries a small risk of complications (1–5%)—fluid overload, infection, electrolyte imbalance, hypoglycemia, thrombocytopenia, thrombosis and death.

Intravenous Immunoglobulin

Routine use is not recommended. 500 mg/kg is used when serum bilirubin is rising despite intensive phototherapy or the value is within the exchange transfusion range in antibody-mediated hemolysis (Rh, ABO) settings.²⁰

Phenobarbitone

Phenobarbitone by inducing the activity of uridine diphosphate-glucuronyl transferase enzyme can blunt the bilirubin rise seen in neonatal period. A meta-analysis of three studies has concluded that phenobarbitone reduces peak serum bilirubin, duration and need of phototherapy and need of exchange transfusion in preterm very low birth weight (VLBW) neonates. Although no major adverse events have been reported, reporting on neurodevelopmental outcome is lacking.²¹

Other Modalities

Several other interventions which have been studied for jaundice management are summarized in Table 1.1.9.

OUTCOME

Prognosis is excellent for uncomplicated newborn jaundice. Prognosis depends on gestation, age of onset, underlying cause, comorbid conditions and timing of intervention. Several other outcomes have been studied are summarized in Table 1.1.10.

SUMMARY

Jaundice is a sign and not a diagnosis. All newborns in first week of life and at every opportunity must be assessed for jaundice and risk factors. A structured follow-up and evaluation is mandatory to prevent significant jaundice. All efforts must be made to investigate the cause of jaundice. Phototherapy is the mainstay and should be used like a drug. All newborns with significant jaundice must have a long-term follow-up.13

Table 1.1.9 Evidence for management of jaundice.

Use of bilirubin nomogram22	Transcutaneous bilirubin nomograms had the same predictive value as TSB nomograms. Result should be interpreted cautiously due to methodological limitation
Screening for bilirubin encephalopathy23	No robust evidence to suggest that screening is associated with favorable clinical outcomes
Preterm transcutaneous bilirubin reliability24	Reliable and could be used in clinical practice to reduce blood sampling
Prebiotics for prevention25	Not enough evidence
Prophylactic calcium during exchange transfusion (ET)26	Difficult to support or reject the continual use of prophylactic intravenous calcium
Clofibrate in combination with phototherapy627	Insufficient data
Oral zinc for prevention28	Limited evidence with no effect on incidence or need of PT
Clofibrate29	Short-term benefits in term infants and infants without hemolytic diseases
Probiotics30	Routine use of probiotics to prevent or treat neonatal jaundice cannot be recommended
Yinzhihuang31	Yinzhihuang oral liquid combined with phototherapy seemed to be safe and superior to phototherapy alone for reducing serum bilirubin in neonatal jaundice
Meconium evacuation by per rectal laxative32	No significant clinical advantage for neonatal jaundice
Single- versus double-volume ET33	Insufficient evidence to recommend change from current use of double-volume ET
Metalloporphyrins34	Routine treatment cannot be recommended
(TSB: total serum bilirubin; PT: phototherapy)

Table 1.1.10 Evidence for association with hyperbilirubinemia.

Delayed cord clamping35	Increased risk of jaundice
Autism spectrum disorders (ASDs)36	Associated with ASD (OR, 1.43, 95% CI 1.22–1.67, random effect model). Not in preterm
Childhood allergic disorders37	Low quality evidence for significant increase in the odds of childhood allergic diseases after jaundice and/or PT
Urinary tract infection (UTI) with prolonged jaundice38,39	Overall prevalence of UTI was 11% in Iranian children. Screening is recommended. In the United Kingdom, the incidence was very low and hence urine screening is not recommended

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161.2 RESPIRATORY DISTRESS SYNDROME IN THE NEWBORN

Bakul Parekh, Snehal Desai

INTRODUCTION

Prematurity is the leading cause of neonatal mortality worldwide. Respiratory distress syndrome (RDS) occurs almost exclusively in premature infants. The incidence and severity are inversely proportional to the gestational age. Modern neonatal pediatrics started in the 1970s with the introduction of assisted ventilation. Other advances that improved the survival of preterm infants included the use of antenatal corticosteroids widely used from the late-1970s onwards, and the exogenous surfactant, which became available from the early 1990s.

ANTENATAL CARE

A detailed discussion of antenatal management while delivering a preterm is beyond the scope of this discussion; however, a few salient points with reference to RDS are enumerated for awareness of the pediatrician.

It is ideal to transport the unborn preterm child in utero and deliver at a center where tertiary neonatal intensive care unit (NICU) facility is available. In a situation of preterm premature rupture of membranes (PPROM), antibiotics delay the preterm delivery and reduce neonatal morbidity. The use of co-amoxiclav should be avoided because it increases the risk of necrotizing enterocolitis (NEC).¹

Magnesium Sulfate Therapy

The most common pathological lesion associated with cerebral palsy in preterm infants is periventricular white matter injury. It is observed that magnesium sulfate (MgSO₄) given to women with imminent preterm delivery reduces cerebral palsy at 2 years of age by about 30%.² Although the evidence is not new, there is no widespread use of MgSO₄ in preterm delivery as yet. The possible reasons include the lack of a statistically significant difference in primary outcome measures from the randomized controlled trials (RCTs); and the large number needed to treat for benefit as compared to the advantage of maternal administration of steroids. However, the use should be encouraged because the meta-analyses clearly show that magnesium reduces cerebral palsy and motor deficits.³

Second, unlike steroids that need to be administered up to 24 hours before preterm birth to have their optimal effect, magnesium has a much more rapid neuroprotective effect, making it more relevant. Finally, obstetricians are 17already familiar with giving a similar magnesium sulfate regime to women at risk of preeclampsia and know that major maternal adverse effects are uncommon. An intravenous 4 g loading dose over 20–30 minutes should be given followed by a 1 g/h maintenance regime to continue for 24 hours or until birth, whichever occurs sooner.⁴

Prenatal Corticosteroids

A single course of prenatal corticosteroids given to mothers with anticipated preterm delivery improves survival, reduces RDS, NEC and intraventricular hemorrhage and does not appear to be associated with any significant maternal or short-term fetal adverse effects.⁵ Therefore prenatal corticosteroid therapy is recommended in all pregnancies with threatened preterm birth before 34 weeks of gestation where active care of the newborn is anticipated. Given the potential for long-term side-effects, steroids are not currently recommended for women in spontaneous preterm labor after 34 weeks.⁶ The optimal treatment to delivery interval is more than 24 hours and less than 7 days after the start of steroid treatment; beyond 14 days, benefits are diminished. Beneficial effects of the first dose of antenatal steroid start within a few hours, so advanced dilatation should not be a reason to refrain from therapy.⁷ WHO recommends that a single repeat course of steroids may be considered if preterm birth does not occur within 7 days after the initial course and there is a high risk of preterm birth in the next 7 days.⁸ It is unlikely that repeat courses given after 32 weeks’ gestation improve outcome.⁹

DELIVERY ROOM MANAGEMENT

Postnatal management of the preterm infant may be regarded simply as supportive care while the immature physiology and anatomy adapt to the postnatal environment independent of the placental circulation.

Umbilical Cord Clamping

Timing of umbilical cord clamping is an important first step. Clamping the cord immediately after delivery before initiation of respiration results in an acute transient reduction in left atrial filling leading to an abrupt drop in left ventricular output. Delayed “physiological” clamping after lung aeration results in much smoother transition and less bradycardia in animal models.¹⁰ In premature infants, Cochrane review found that delayed (30–180 seconds) cord clamping versus early (within seconds) was associated with fewer infants requiring transfusions for anemia [relative risk (RR): 0.61], less intraventricular hemorrhage (RR: 0.59), lower risk for NEC compared with immediate clamping (RR: 0.62). For healthy women with term births, the National Institute for Health and Care Excellence (NICE) recommends 18that the cord is not clamped in the first 60 seconds, except where there are concerns about the baby's heart rate.¹¹

In emergency situations where delayed cord clamping was not feasible, cord milking could be an alternative. There have been two RCTs suggesting that cord milking was equivalent to delayed clamping.¹² However, animal studies have shown that cord milking causes considerable hemodynamic disturbance leading to increased incidence of intraventricular hemorrhage raising concerns about the safety of this procedure.¹³

Continuous Positive Airway Pressure

Multiple animal studies and observational studies in humans have proved beyond doubt that positive pressure ventilation induces lung injury and triggers an inflammatory cascade immediately after delivery more so in a surfactant deficient lung.¹⁴ Continuous positive airway pressure (CPAP) support is seen as a potentially “gentler” and less invasive modality to stabilize preterm neonates in the delivery room.¹⁵ CPAP is to be used for infants born with a good heart rate but who are slow to establish a functional residual capacity (FRC) and effective spontaneous respiration. CPAP support with a pressure of at least 5–6 cm H₂O helps stabilize expanded or recruited alveoli and also works in synergy with endogenous surfactant by conserving the surfactant on the alveolar surface.¹⁶

Pragmatically, there is now increasing emphasis on minimizing ventilation-induced lung injury (VILI) and its consequence, chronic lung disease (CLD), starting in the delivery room.^15–17 Spontaneously breathing babies started on CPAP rather than intubation in the delivery room have a reduced risk of bronchopulmonary dysplasia (BPD).¹⁸ The ideal level of CPAP is unknown, but most studies have used levels of at least 6 cm H₂O with some as high as 9 cm H₂O. Sustained inflation which is using pressures of 20–25 cm H₂O for 10 seconds at initiation of respiration to avoid intubation was considered, but subsequently abandoned because of excess death in infants.¹⁹

A T-piece resuscitator will be required to provide measurable CPAP in the delivery room from birth.²⁰ A self-inflating bag will not be able to give CPAP. In babies who are apneic or bradycardic, gentle, positive ventilation will need to be given which can also be delivered by a T-piece resuscitator.

Oxygen is a potentially toxic gas which can cause direct damage to respiratory epithelium. There is good evidence that 100% oxygen is harmful to most neonates and potentially more so in extremely preterm infants, in whom hyperoxia results in a 20% decrease in cerebral blood flow and a much worse alveolar-arterial oxygen gradient.²¹

During resuscitation, effort should be made to mimic normal transitional saturations, that is rising gradually from 60% to 90% over the first 10 minutes after birth. Therefore, blended air/oxygen should be available at 19the delivery room. For term babies requiring resuscitation, there is reduced mortality when using fraction of inspired oxygen (FiO₂) 0.21 rather than 1.0.²² Observational studies have raised concerns about starting extremely preterm infants in air because of poorer recovery from bradycardia and increased mortality in the smallest babies.²³ Moreover, the combination of bradycardia (<100/min) and lower SpO₂ (<80%) in the first 5 minutes is associated with death or intracranial hemorrhage.²⁴

Further trials are underway to resolve this issue. Presently, it is known that when titrating oxygen, most infants end up in about 30–40% oxygen by 10 minutes, so we believe it is reasonable to start preterm infants <28 weeks in about 30% oxygen until more evidence is available.²² For those between 28 and 31 weeks’ gestation, 21–30% oxygen is recommended.²⁵

Practically, if self-filling resuscitation bag is used during resuscitation; ventilation can be initiated with room air. If oxygen is required, O₂ can be connected providing around 40% FiO₂ without and around 100% FiO₂ with the reservoir in place. However, PEEP cannot be given through this method. Majority of T-piece resuscitators use only oxygen to deliver the required CPAP and also positive pressure if required, thus delivering 100% FiO₂. A built-in air/oxygen blender in the T-piece resuscitator or an external blender in the delivery room is essential for optimum treatment but not very widely available as yet in India.

Preterm babies have immature skin, leading to rapid loss of heat from the body leading to early hypothermia. It is essential to immediately wrap the baby in a polythene bag under a radiant warmer and to increase the environmental temperature in the delivery room to around 26°C, especially for babies born below 28 weeks.

SURFACTANT

In 1959, surfactant deficiency was identified as the principle cause of RDS in preterm. The function of pulmonary surfactant is essentially to lower surface tension, thus preventing collapse of alveoli at the end of expiration. The surfactant is composed of a complex mixture of approximately 90% lipids and 10% proteins. The lipid is majorly a phospholipid, di-palmitoyl-phosphatidyl-choline (DPPC). The proteins are surface proteins (SP), composed of two hydrophobic proteins, SP-B and SP-C, and two hydrophilic proteins, SP-A and SP-D. SP-B and SP-C play significant roles in the adsorption and spread of DPPC to stabilize alveoli.

Surfactants used in clinical practice are either natural or synthetic. The natural surfactants are derived from bovine and porcine minced lungs or lung lavage extracts. The natural surfactants have limitations such as elevated cost and limited availability. They also contain animal proteins that may be potentially immunogenic and infectious. Therefore, to overcome these 20limitations, synthetic surfactants were developed which have evolved over the years. Animal-derived products have been proven superior to first-generation synthetic products demonstrating the significant role of surfactant proteins.

The first-generation synthetic surfactants were SP free, have been proven inferior to natural surfactants in terms of mortality, lower oxygen and ventilation requirements thus demonstrating the significant role of surfactant proteins.^26,27

Currently, first-generation protein-free synthetic surfactants have been removed from most markets. Thereafter, second-generation surfactants were investigated, which are supplemented with peptides or proteins to mimic natural surfactant proteins. Lucinactant contains two phospholipids and a high concentration of sinapultide, a synthetic peptide designed to have similar activity to surfactant protein B. The available literature supports the fact that the newly approved second-generation synthetic surfactant lucinactant is equally effective as animal-derived surfactants.²⁸

CHF5633, a third-generation synthetic surfactant containing SP-B and SP-C analog is also proven effective and safe in a multicenter cohort study for preterm infants.

Timing of Surfactant Administration

The initial clinical trials with surfactant were conducted in preterm intubated and ventilated for RDS. These studies demonstrated that early surfactant administration (FiO₂ < 45%) was superior to late administration (FiO₂ > 45%).^29,30 From this evolved the strategy of early intubation of very preterm infants in the delivery room and administration of prophylactic surfactant from 1990.

What is the Latest Consensus on Prophylactic Surfactant?

Over the years, there have been two major changes in the management of preterm babies. Antenatal corticosteroids have gained widespread acceptance thus reducing the severity of RDS and instead of intubation and ventilation, more and more babies are being managed on CPAP. Both these interventions have been associated with lower rates of BPD. Hence the dilemma is whether to intubate and prophylactically give surfactant or manage them on CPAP and administer surfactant to preterm failed on CPAP.

Several large clinical trials (COIN, SUPPORT, and VON-DRM) have addressed this question.^31–33 It was concluded that it was better to start with CPAP support in the delivery room if possible and intubate and administer surfactant only to infants with signs of RDS.

Studies have compared primary CPAP and surfactant to failed CPAP to prophylactic surfactant treatment with the “Intubate-Surfactant-Extubate (INSURE)” approach. During INSURE, infants are intubated, receive 21surfactant, and are supposed to be immediately extubated to minimize mechanical ventilation. These studies also did not find a benefit of prophylactic surfactant with INSURE over CPAP.³⁴ A possible explanation may be that even short periods of mechanical ventilation can damage the vulnerable lung. Many of the infants in whom INSURE was performed, were ventilated for a longer period thus causing more damage. Many, mainly extremely preterm infants, who were treated with INSURE failed to be extubated after surfactant administration, leading to a longer time on ventilation. Meta-analyses have demonstrated that prophylactic INSURE did not lead to a higher survival without BPD.^35,36

Prophylactic surfactant has a role only in selected cases where antenatal steroids have not been possible and the preterm has needed intubation during resuscitation. If intubation is required as part of stabilization, then surfactant should be given immediately, as the main purpose of avoiding surfactant prophylaxis is to avoid intubation.

If not Prophylactic, at What Stage do we Administer Surfactant?

At present, severity of RDS can only be determined clinically using a combination of FiO₂ to maintain normal saturations, coupled with judgment of work of breathing and degree of aeration of the lungs on chest X-ray, all of which can be influenced by CPAP.

The 2013 Guideline suggested that surfactant should be administered when FiO₂ > 0.30 for very immature babies and > 0.40 for more mature infants based on thresholds used in the early clinical trials. Observational studies have confirmed that FiO₂ exceeding 0.30 in the first hours after birth in babies on CPAP is a reasonably good test for predicting subsequent CPAP failure.³⁷ Therefore, it is recommended that the threshold of FiO₂ > 0.30 is used for all babies with a clinical diagnosis of RDS, especially in the early phase of worsening disease.

Recent evidences still demonstrate that early rescue surfactant (<2 hours after birth) as compared to late rescue surfactant (>2 hours after birth) is associated with a reduction in BPD and/or death.³⁸ Therefore, the American Academy of Pediatrics (AAP) and the European guidelines on surfactant administration advise stabilization of preterm infants on CPAP and, if necessary, the administration of surfactant as early rescue therapy, preferably within 2–3 hours after birth if FiO₂ requirement is more than 30% at a pressure of at least 6 cm of H₂O.^39,40

More than one dose of surfactant may be needed. Clinical trials comparing multiple doses to a single dose showed fewer air leaks, although these were conducted in an era when babies were maintained on mechanical ventilation. Today many infants are maintained on noninvasive ventilation even when surfactant is required. Need for redosing can be minimized by using the larger dose of 200 mg/kg of natural porcine lung surfactant (poractant alpha).⁴¹22

A second and occasionally a third dose of surfactant should be given if there is ongoing evidence of RDS such as persistent high oxygen requirement and other problems have been excluded.

Newer Advances in the Pipeline

Lung ultrasound may be a useful adjunct to clinical decision making in experienced hands, with RDS lungs having a specific appearance that can be differentiated from other common neonatal respiratory disorders and it has potential to reduce X-ray exposure.^42,43

Rapid bedside tests to accurately determine presence or absence of surfactant in gastric aspirate are currently being tested in clinical trials.⁴⁴

Dose of Surfactant Administration

The only trial that has so far demonstrated differences between natural surfactant preparations compared two doses of poractant alpha (Curosurf), at either 100 or 200 mg/kg body weight, with beractant (Survanta) at 100 mg/kg body weight.⁴⁵ When the two surfactants were compared at 100 mg/kg body weight, the main outcome data showed no significant differences between the groups.

However, when poractant alpha was increased to 200 mg/kg body weight, it resulted in lower mortality rates at 36 weeks than beractant at 100 mg/kg body weight. At 100 mg/kg body weight, the three natural surfactant preparations mentioned earlier had comparable effects on gas exchange and survival without BPD.⁴⁵

Table 1.2.1 provides the different preparations of surfactant and their source, dose, and formulations.

Method of Surfactant Administration

Surfactant administration requires an experienced practitioner with intubation skills and ability to provide mechanical ventilation if required. Most surfactant clinical trials to date have used tracheal intubation, bolus administration with distribution of surfactant using invasive positive pressure ventilation (IPPV), either manually or with a ventilator, followed by a period of weaning from mechanical ventilation as lung compliance improves.

Table 1.2.1 Different preparations of surfactant: Source, dose, and formulations.

Surfactant	Survanta	Curosurf	Neosurf
Source	Bovine lung extract	Porcine lung extract	Bovine lung lavage
Dose (Phospholipids)	4 mL/kg (100 mg/kg)	2.5 mL/kg (200 mg/kg)	5 mL/kg (135 mg/kg)
Formulations	4 mL and 8 mL	1.5 mL and 3 mL	3 mL and 5 mL

23The disadvantages of mechanical ventilation in preterm, most importantly lung trauma and the importance of early CPAP are being widely recognized. Hence the administration of surfactant to preterm neonates during respiratory support on CPAP has been investigated.

The first was an interruption of CPAP for intubation for surfactant administration followed by a short interval of positive pressure ventilation administered through ventilator or resuscitator bag followed by rapid extubation. That is INSURE, intubation–surfactant–extubation. The INSURE technique allows surfactant to be given without ongoing MV and is endorsed as it reduces BPD.³⁰

Another procedure is less invasive surfactant administration (LISA). In this method a thin small diameter catheter, such as feeding tube is placed in the trachea with the aid of Magill forceps under direct laryngoscopy. The surfactant is delivered intratracheally while the infant is spontaneously breathing supported by CPAP. This method does not require endotracheal intubation nor mechanical ventilation.⁴⁶ The LISA procedure reported a reduction in the need for mechanical ventilation and the rate of BPD compared with the classic procedure of intubation and mechanical ventilation.^47,48

Since the distribution of surfactant is dependent on alveolar recruitment and the CPAP is continued during the surfactant administration, there is optimal distribution of surfactant and thus leads to an immediate increase in end-expiratory lung volume and oxygenation in preterm infants.^49,50

Meta-analyses compared LISA and INSURE for the incidence of severe neonatal complications such as BPD and the rate was lower for neonates treated with the LISA method.⁵¹ Another advantage of LISA is avoidance of large mechanical breaths, which are often required with intubation thus limiting lung trauma.

However, none of the included trials provided data regarding long-term neurodevelopmental outcomes. Recent cohort study using historical controls showed no difference in long-term outcomes at school age with LISA.

It is reasonable to recommend it as the optimal method of surfactant administration for spontaneously breathing babies who are stable on CPAP. Some units also employ strategies of prophylactic LISA for the smallest babies, although this has not yet been tested in RCTs. One of the advantages of LISA is that the temptation to continue MV following surfactant is removed.

Dargaville et al. from Australia described a novel method of administering surfactant to very preterm neonates between 25 and 28 weeks of gestation. They used small stiff vascular catheters, which did not need to be introduced with Magill forceps. They demonstrated that this stiff catheter technique, which they called minimally invasive surfactant therapy (MIST), was effective without increasing neonatal complications.⁵²

Surfactant delivered by nebulization would be truly noninvasive. With development of vibrating membrane nebulizers, it is possible to atomize 24surfactant, although only one clinical trial has shown that nebulizing surfactant when on CPAP reduces need for MV compared to CPAP alone, and this finding was limited to a subgroup of more mature infants of 32–33 weeks.⁵³ Further trials of nebulization are ongoing.

Surfactant has also been administered by laryngeal mask airway, and one clinical trial shows that this reduces need for intubation and MV.⁵⁴ However, the size of currently available laryngeal masks limits the use of the method to relatively mature preterm infants, and routine use for smaller infants at greatest risk of BPD is not recommended.⁵⁵

NONINVASIVE VENTILATION

Continuous Positive Airway Pressure

There is increasing awareness from animal studies and observational studies in human infants that positive pressure ventilation is capable of inducing lung injury and triggering an inflammatory cascade within minutes of birth, especially in a surfactant-deficient lung.¹⁴ It is well-established that respiratory support should be noninvasive as far as possible. The best-known mode of noninvasive neonatal respiratory support is CPAP. CPAP is useful in infants with respiratory distress who are spontaneously breathing, and is widely used both in the early acute and late weaning/recovery phases of RDS. The continuous distending pressure of at least 5–6 cm of H₂O applied to the lung improves oxygenation by decreasing atelectasis, helping establish an FRC and eliminating fetal lung fluid, controlling pulmonary plethora in the presence of a patent ductus arteriosus (PDA) and improving ventilation–perfusion matching.^6,16,17 It may also reduce airway resistance by supporting the non-surfactant dependent upper airways.

CPAP is also useful in reducing apnea of prematurity which commonly coexists with RDS. This CPAP can be generated using mechanical ventilators, expiratory resistance valves, flow drivers, or underwater bubbling circuits.

Using an underwater seal to generate the pressure or “Bubble CPAP,” generates small fluctuations around the set pressure which some believe offers additional advantage.⁵⁶ Using a flow driver to generate CPAP has the theoretical advantage of offloading expiratory work of breathing (the Coanda effect). There is no evidence that one is better than the other, but the simplicity of bubble CPAP systems allows their use in low-income settings.^57,58 The interface for delivering the continuous pressure through the nose could be nasal prongs, short pharyngeal tubes or nasal mask. Again evidence suggests all are equally effective for delivering the pressure.⁵⁹ Although for prolonged use, nasal masks are the best as they cause the least distortion of the face.⁶⁰ CPAP is now typically delivered via the nose; this can be via a nasal mask or short nasal prongs. Potential disadvantages of CPAP tend to be common to 25most methods of respiratory pressure support and include increased risk of pneumothorax and decreased pulmonary perfusion.

In the weaning/recovery phase of RDS, CPAP is invaluable after extubation from positive pressure ventilation by reducing the need for reintubation due to respiratory failure.⁶¹

Nasal Intermittent Positive Pressure Ventilation

Some infants need more support than CPAP. Nasal intermittent positive pressure ventilation (NIPPV) combines CPAP with intermittent pressure increases through the nasal prongs, generating peak pressures just slightly higher than baseline CPAP.⁶²

In most of the studies comparing NIPPV with CPAP, no difference is found in tidal volumes; however, there is evidence that NIPPV reduces work of breathing.

NIPPV can be generated by ventilators and by the flow drivers used for CPAP. Synchronizing NIPPV with spontaneous breathing is possible but challenging because of air leaking around the prongs and from the mouth. Pneumatic abdominal capsules are most commonly used for synchronization but are only available with a few devices. Other potential synchronization methods include neurally adjusted ventilatory assist (NAVA) which is invasive and expensive and respiratory inductance plethysmography which is currently not readily available.

NIPPV improves extubation success and reduces the risk of BPD and it appears that synchronization improves its effectiveness. Nasal bilevel CPAP is a variant of NIPPV where two pressure levels alternate while the infant breathes independently; however, there is no clear benefit of bilevel CPAP compared with standard CPAP in preterm infants.

Nasal High-flow Therapy

Nasal high-flow therapy is a third noninvasive support mode to deliver heated, humidified gas via small binasal cannula designed not to occlude the nostrils at a rate of 2–8 L/min. Weaning of flow rate is done clinically when FiO₂ requirement reduces and the work of breathing decreases.⁶³

The use of nasal high-flow therapy in neonatal respiratory care has spread rapidly, despite initial concerns that airway pressure is neither controlled nor measured. Nasal high flow (NHF) generates some distending pressure, which varies with leak, gas flow, and infant weight; it probably also improves nasopharyngeal gas washout.⁶⁴

The perceived benefits of nasal high-flow therapy compared with CPAP, which include a simple interface, easy application, improved infant comfort and preference by parents and nurses, fuelled its early uptake in the NICUs despite limited evidence of safety or efficacy.⁶⁴26

However, the use of nasal high-flow therapy post-extubation in preterm infants has now been widely investigated; results of a recent Cochrane review of six RCTs showed that nasal high-flow therapy and CPAP were equally effective for post-extubation support in preterm infants and that infants randomly assigned to receive nasal high-flow therapy had less nasal trauma than infants who received CPAP.⁶⁵

Heated humidified high-flow nasal cannula (HFNC) are increasingly used as an alternative to CPAP. Centers familiar with the use of HFNC argue that with experience it can be used for initial support even in some of the smallest babies.^66,67 In the HIPSTER trial, HFNC was compared with CPAP as a primary mode of support in the delivery room for infants >28 weeks, but the trial was stopped early because more infants started on HFNC needed rescue with CPAP.⁶⁸

At present, CPAP remains the preferred initial method of noninvasive support. There are likely to be further refinements of noninvasive support over the next few years. Better synchronization of ventilator support with the baby's own breathing efforts can be achieved using NAVA, and large clinical trials of these newer modes of support are urgently needed.⁶⁹

MECHANICAL VENTILATION

Despite our best efforts to maximize noninvasive support, many small infants will initially require mechanical ventilation (MV).

The aim of MV is to provide “acceptable” blood gases as our effort to reach normal values leads to higher pressures and higher volumes causing lung injury. Overinflation increases risk of air leaks such as pneumothorax and pulmonary interstitial emphysema and suboptimally low pressure leads to areas of atelectasis during expiration, which generates inflammation. Maintaining an “open lung” is achieved by optimizing PEEP, at which FiO₂ requirement is lowest with acceptable blood gases and hemodynamic stability.⁷⁰

Volume-targeted Ventilation

Conventionally, the volume of gas delivered with each ventilator breath is clinician controlled by adjusting inspiratory pressure and time. The pressure is set to deliver an approximate tidal volume of 5 mL/kg. As the compliance of the lung improves with time or after surfactant administration, the same pressure will now deliver the much larger tidal volume. Much of the lung damage represented by BPD is thought to be mediated through excessive volume delivery—volutrauma. Similarly, if the lung pathology worsens the volume delivered will decrease leading to hypoventilation. Logically, it might be advantageous to allow the ventilator to deliver preset volumes rather than preset pressures. Volume-targeted ventilation (VTV) enables clinicians to 27ventilate with less variable tidal volumes and real-time weaning of pressure as lung compliance improves. VTV compared with time-cycled pressure ventilation results in less time on the ventilator, fewer air leaks and less BPD.⁷¹

This mode allows the ventilator to respond to rapid changes in lung compliance without clinician intervention. VTV mode enables automatic weaning of PIP in real-time as compliance improves facilitating faster weaning from mechanical ventilation.⁷²

Pressure Support Mode

Pressure support mode is where the ventilator supports all the respiratory efforts of the infant and the rate of breathing is determined by the infant itself and the cycling (i.e. ending of inspiration and starting of expiration) is also determined by the patient itself. This is the purest form of patient-controlled ventilation, leading to best synchronization and patient comfort.⁷³ As there is no fixed setting of ventilator breaths, it is important to understand to use this mode only when there is no risk of apnea.

High Frequency Oscillatory Ventilation

High frequency oscillatory ventilation (HFOV) is an alternative strategy to conventional MV allowing gas exchange to be achieved using very small tidal volumes delivered at very fast rates with the lung held open at optimal inflation using a continuous distending pressure (CDP). Studies comparing HFOV to conventional MV show modest reductions in BPD favoring HFOV, although there is a paucity of trials where HFOV is compared with volume targeted ventilation.⁷⁴

Neurally Adjusted Ventilator Assist

It is always beneficial to synchronize the ventilator-derived breath to the patient's effort to take a breath. This reduces work of breathing and fluctuations of pressures. Usually the flow or the negative pressure developed in the ventilator circuit acts as a trigger for the ventilator to deliver the breath. However, there is a lag period between the patient initiating a breath and the ventilator triggering the breath. Now, the act of taking a breath is controlled by the respiratory center of the brain, which decides the characteristics of each breath, timing, and size. The respiratory center sends a signal along the phrenic nerve, excites the diaphragm muscle cells, leading to muscle contraction. In this mode the electrical activity of the diaphragm is captured, fed to the ventilator, and used to assist the patients breathing in synchrony with and in proportion to the patient's own effort. As the work of the ventilator and of the lung is controlled by the same signal synchronization is achieved beautifully.⁷⁵28

Servo-controlled Oxygen Delivery

Modern ventilators now also have the option of servo-controlled oxygen delivery. This means the FiO₂ delivered by the ventilator keeps changing to achieve the set target saturation values. This increases time spent in the desired saturation range and reduces hyperoxia, but there are no trials to show this improves outcomes.⁷⁶

Early extubation of even the smallest babies is encouraged provided it is judged clinically safe. Infant's size, absence of growth restriction, FiO₂ and blood gases are all determinants of extubation success. Extubation may be successful from 7 to 8 cm H₂O MAP on conventional modes and from 8 to 9 cm H₂O CDP on HFOV. Extubating to a relatively higher CPAP pressure of 7–9 cm H₂O or noninvasive positive pressure ventilation (NIPPV) will improve chance of success.⁷⁷

Several other strategies have been used specifically to shorten duration of MV including permissive hypercarbia, caffeine therapy, postnatal steroid treatment, and avoiding overuse of sedation.

Permissive Hypercarbia

Targeting arterial CO₂ levels in the moderately hypercarbic range is an accepted strategy to reduce time on MV.⁷⁸ The PHELBI (Permissive Hypercapnia in Extremely Low Birthweight Infants) trial explored tolerating even higher PaCO₂ up to about 10 kPa (75 mm Hg) compared to 8 kPa (60 mm Hg) in preterm babies <29 weeks for the first 14 days. Follow-up of this cohort and others suggests no long-term adverse sequelae of permissive hypercarbia and it is therefore reasonable to allow moderate elevation of PaCO₂ during weaning provided the pH is acceptable.⁷⁹ This allows for more gentle ventilation at reduced pressures and volumes thus decreasing volutrauma and barotrauma.

OXYGEN TARGET AFTER STABILIZATION

The oxygen target after initial stabilization has undergone a sea change. Oxygen in the earlier times was considered the panacea in the management of respiratory distress but was soon realized as the culprit of an epidemic of retinopathy of prematurity and subsequent blindness. However, targeting lower levels of oxygen has increased death from hypoxia. Hence clinicians soon realized a middle way was needed and thus large multicentric trials were needed to determine the optimum range of oxygen target.

The Neonatal Oxygenation Prospective Meta-analysis (NeOProM) collaboration, was established in 2003 called NeOProM which coordinated a series of international RCTs to be included in a prospective meta-analysis.⁸⁰ These were the SUPPORT trial in the USA,^81,82 the BOOST-2 (Brain Oxygen Optimization in Severe Traumatic Brain Injury, Phase II) trials in the UK,⁸³ New Zealand⁸⁴ and Australia⁸⁵ and the Canadian COT trial.⁸⁶29

The results of a meta-analysis of the composite primary outcome of death or disability in all five trials revealed a higher risk in the low oxygen saturation target group (saturation target: 85–89%) than in the high oxygen saturation group (saturation target: 91–95%), an effect mainly attributable to the difference in mortality between groups.⁸⁷

Hence the recommendation is to target saturations between 90% and 94% by setting alarm limits between 89% and 95% although it is acknowledged that ideal oxygen saturation targets are still unknown.^88,89

At the ground level, while treating a patient, targeting any oxygen saturation range is difficult; compliance is low, alarm limits are often inappropriately set and it is human tendency to maintain oxygen saturations higher than the upper limit.⁹⁰

Linking automated oxygen delivery systems with oxygen saturation monitoring might be an option. A paradigm shift could be to search alternatives to peripheral oxygen saturation measurement have been. One possibility is the use of near infrared spectroscopy (NIRS) to measure regional brain tissue oxygenation, for which some normal values for preterm infants have been established.⁹¹

NIRS has shown that not all desaturations detected peripherally correlate with cerebral hypoxia and common interventions such as handling and airway suctioning cause large fluctuations in cerebral oxygenation.⁹²

SUPPORTIVE CARE

Always maintain body temperature at 36.5–37.5°C. Start parenteral nutrition immediately with amino acids and lipids in initial fluid volumes about 70–80 mL/kg/day for most babies and restrict sodium during the early transitional period. Enteral feeding with mothers’ milk should also be started on day 1 if the baby is stable. Antibiotics should be used judiciously and stopped early when sepsis is ruled out. Blood pressure should be monitored regularly aiming to maintain normal tissue perfusion, if necessary, using inotropes. Hemoglobin should be maintained at acceptable levels. Protocols should be in place for monitoring pain and discomfort and consideration should be given for nonpharmacologic methods of minimizing procedural pain and judicious use of opiates for more invasive.⁸⁸

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Chapter Notes

NEONATOLOGYCHAPTER 1

Box 1.1.1 : Predischarge assessment.

Box 1.1.2 : Factors suggesting pathologic cause of jaundice.

Box 1.1.3 : Indications for measuring total serum bilirubin.

Box 1.1.4 : Investigations for significant hyperbilirubinemia.