Contributors:
Reviewer:
- ► Neonatal Hypoglycemia
- ► Neonatal Jaundice
- ► Perinatal Asphyxia
- ► Respiratory Distress
1.1. NEONATAL HYPOGLYCEMIA
Rhishikesh Thakre, Naveen Jain
CLINICAL PRESENTATION
Hypoglycemic neonates present with subtle nonspecific signs such as irritability, jitteriness, tachypnea, apnea, seizures, cyanosis or lethargy. The signs and symptoms are not specific to hypoglycemia or to a particular blood sugar value and may be seen with other neonatal disorders such as sepsis, asphyxia, meningitis, seizures, etc. At times, the neonate may be asymptomatic but still have hypoglycemia. Presence of hepatomegaly, cataract, midline defects (cleft lip, palate, macroglossia, abnormal genitalia, septo-optic dysplasia), dysmorphism, visceromegaly, hyperpigmentation, abnormal odor to the urine, should alert the clinician to an underlying metabolic or endocrine cause. Hypoglycemia is, thus, not a clinical diagnosis but a ‘chemical’ diagnosis based on screening by glucometer.
DIAGNOSTIC WORK-UP
Screening ‘at risk’ (Box 1.1.1) and ‘all sick’ newborns by glucometer is currently advocated to diagnose hypoglycemia. The operational threshold for managing hypoglycemia is the value less than 40 mg/dL (plasma glucose 45 mg/dL). Management is initiated depending upon lab glucose results. The maximum risk for hypoglycemia is in the first 24 hours and definitely not after 72 hours, unless it is multifactorial in origin.
Confirmation is by lab analysis (glucose oxidase or glucose electrode method) in a sample collected in fluoride bulb. Whole blood glucose is 10–15% less than plasma glucose. The sample should be analyzed quickly as blood glucose levels may fall 15–20% by 1 hour.
IDENTIFYING THE CAUSE
Hypoglycemia may be an isolated problem or may be a part of other disease process. For isolated hypoglycemia occurring in well-appearing ‘at risk’ neonate, which is a transient event, no further work-up is required. For hypoglycemia, which is recurrent, persistent (>72 hours) or documented in sick newborn, workup is required (Table 1.1.1).
MANAGEMENT GUIDELINES
Supportive Care
Newborn must be nursed in neutral thermal environment. Hypo- and hyperthermia should be avoided. Airway is kept patent by positioning, suctioning (if required) and breathing supported if is irregular or absent. Continuous monitoring of vital parameters, blood oxygen saturation and noninvasive blood pressure, provide a trend of hemodynamic status.
Symptomatic versus Asymptomatic Hypoglycemia
The first step in managing hypoglycemia is based on whether the newborn is symptomatic or asymptomatic. Asymptomatic newborn with sugar 20–40 mg/dL is offered a supervised feed of 10 cc/kg of human milk or formula, orally or by tube feed, and sugar value is assessed within 30–60 minutes. Values of more than 40 mg% are managed with oral feeds with sugar monitoring every 3–6 hours. At any time if the newborn becomes symptomatic or the sugar is less than 20 mg dL, intravenous line is secured and sugar is managed by glucose infusion rate (GIR).
Glucose infusion rate is initiated in all symptomatic newborns, with B glucose less than 20 mg% or where enteral feeding is not feasible. GIR is initiated with 6–8 mg/kg/min and glucose evaluated 30–60 min later with an aim to keep it more than 40 mg%. If it is less, GIR is increased by 1–2 mg/kg/min every 30–60 minutes. Once glucose is stabilized for 24 hours, tapering of GIR by 1–2 mg/kg/min is done every 6–12 hours. The maximum glucose that can be infused via peripheral line is 12 mg/kg/min or 12.5% dextrose. If the GIR is more, a central venous access is gained. Oral feeds are gradually introduced when glucose infusion is being tapered depending upon infant condition.
Treatment of the underlying cause is equally important as managing hypoglycemia. Specific measures for sepsis, meningitis (antibiotic), polycythemia (partial exchange transfusion), pneumonia (oxygen, antibiotics, respiratory support), fungemia (anti-fungal), etc. should be promptly instituted.4
Flow chart 1.1.1: Management of refractory hypoglycemiaAbbreviation: GIR, glucose infusion rate
*GIR = Fluids (mL/kg/day) x % Dextrose/144
Management of refractory hypoglycemia is considered when GIR of more than 15 mg/kg/min is required to maintain glucose levels. The most common cause is hyperinsulinemia followed by metabolic or endocrine disorder. Expert consultation should be taken (Flow chart 1.1.1).
PROGNOSIS
There is no single value below which brain injury definitely occurs. More the depth of hypoglycemia and longer its duration, more adverse is the neurologic squeal. Cognitive deficits, motor delay, cortical blindness, learning difficulties, microcephaly and seizure disorders have been reported.
Follow-up for all hypoglycemic newborns, symptomatic or asymptomatic, should be carried out for neurodevelopmental evaluation at least till 2 years of age. The absence of overt symptoms at low glucose levels does not rule out brain injury.
BIBLIOGRAPHY
- Adamkin DH, Neonatal hypoglycemia. Curr Opin Pediatr. 2016;28(2):150–5.
- Rozance PJ, Hay Jr WW. New approaches to management of neonatal hypoglycemia. Maternal Health, Neonatology, and Perinatology. 2016;2:3.
1.2. NEONATAL JAUNDICE
Rhishikesh Thakre, Naveen Jain
CLINICAL PRESENTATION
Jaundice manifests as yellowness of the sclera, skin and mucous membranes. In majority of the cases, the newborn is well and asymptomatic. Close attention should be paid to timing of appearance of jaundice (early <24 hours or prolonged >3 weeks), gestation (preterm or term) and adequacy of feeding (checking for frequency of feed, color of urine, and frequency of stool and weight pattern). Sick appearing, jaundice in first 24 hours, extension up to soles and feet, associated high colored urine or clay stools suggests ‘danger signs’ for jaundice. Feeding difficulty, irritability, lethargy, shrill cry, abnormal movements or posture and apnea suggest complications of jaundice. Presence of pallor, rash, hepatosplenomegaly, plethora, bleeding tendency, vomiting, unstable vital parameters, suggest a pathological cause, and merit admission and evaluation.
DIAGNOSTIC WORK-UP
Screening for jaundice needs to be done clinically for all newborns at least once a day in the first 72 hours, at the time of discharge and if there are any parental concerns. Newborns, especially ‘at risk’ (Box 1.2.1) for jaundice, should have close surveillance and preferably a transcutaneous bilirubin evaluation.
Clinical evaluation is unreliable in estimating the severity of jaundice and is subjective.
Total serum bilirubin (TSB) is gold standard for diagnosis of jaundice. Certain situations warrant bilirubin evaluation (Box 1.2.2).
Role of Investigations (Box 1.2.3)
Not all newborns need lab evaluation as history and physical examination often give a clue to the cause of jaundice.
MANAGEMENT GUIDELINES
The decision making is based on simultaneous evaluation of infants’ gestation, weight, well or sick status, age of onset (in hours) and type and severity of jaundice.
Supportive Care
Breastfeeding is the preferred mode for feeding. Monitoring for adequacy of breastfeeds should be ongoing. Intravenous fluids are initiated only if oral intake is poor, weight loss is significant (>10%) or there are signs of dehydration. Hypoxia, hypothermia, hypoglycemia, acidosis and sepsis are aggravating factors, and if present, need to be treated aggressively.
Phototherapy
Phototherapy (PT) is the mainstay of treatment. It is initiated based on age-specific thresholds based on TSB (Tables 1.2.1 and 1.2.2).
Technique
- The infant is nursed naked with genitalia and eyes covered with frequent posture changes.
- The light source is placed as close to the baby as possible provided the infant does not get overheated.
- Phototherapy is administered continuously and interrupted only for nursing and feeding purpose.
Choice of Phototherapy Device
The choice of device depends upon the severity of jaundice:
- For majority of infants, standard PT [special blue lights, (Philips TL52, 20 W) or special blue CFT (compact fluorescent tube) lamps (Osram, 18 W), fiber-optic PT] is effective, which emits irradiance of 8–10 mW/cm2/nm.
- When the bilirubin is rapidly rising or nearing exchange transfusion (ET) range, intensive PT (multiple surface PT units, combination of compact fluorescent lamp (CFL) and fiber-optic PT or high intensity LED PT is effective, which emits irradiance more than 30 mW/cm2/nm.
Monitoring
- Close attention is paid to the infant's temperature, daily weight and intake output.
- Total serum bilirubin is monitored every 4–12 hours depending on the patient's age and bilirubin level. PT is usually discontinued when TSB levels reach a level below PT threshold.
Side Effects
Hypo- or hyperthermia, skin rash, loose stools, insensible water loss and bronze baby syndrome (with direct jaundice).
Failure of Phototherapy
Failure of PT is defined by an inability to observe a decline in bilirubin of 1–2 mg/dL after 4–6 hours and/or to keep the bilirubin below the ET level.
EXCHANGE TRANSFUSION
Indication
Exchange transfusion is indicated for infants, whose bilirubin levels cross the threshold indicated in Tables 1.2.1 and 1.2.2, or those who have clinical features of bilirubin encephalopathy (lethargy, poor feeding, hypertonia, arching, retrocollis, opisthotonus, fever, high-pitched cry).
Choice of Blood
Packed red blood cells reconstituted with plasma with citrate-phosphate-dextrose anticoagulant, less than 7 days old is used for ET (Table 1.2.3).
Technique
- Under aseptic conditions a ‘two-volume’ exchange is performed, i.e. twice the infant's blood volume (160 cc/kg) is exchanged in small aliquots (10% of patient's blood volume) and replaced by donor blood.
- The procedure is performed from peripheral or umbilical arterial catheter and infusing the same amount into a venous line simultaneously. The first aliquot of blood drawn from the neonate is sent for various lab tests. The syringe should be held vertical while pushing donor blood in order to avoid air embolism. The entire procedure is done under close multichannel monitoring with aseptic precautions over 45 minutes to 60 minutes.
| ||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||
Complications
Complications (1–5%) include—hypothermia, fluid overload, infection, electrolyte imbalance, hypoglycemia, thrombocytopenia, thrombosis and death.9
Post-procedure Care
Administer vitamin K, if already on antibiotics, the doses need to be repeated, monitored for blood sugar for next 3 hours and initiate early enteral feeding. Keep a sample of blood (from the last aliquot) for repeat crossmatch if need be for a repeat ET.
Adjunct Therapies
- Intravenous immunoglobulin 500 mg/kg is used when serum bilirubin is rising despite intensive PT or the value is within the ET range in antibody-mediated hemolysis (Rhesus, ABO) settings.
- Phenobarbitone 5–8 mg/kg/day is indicated for treating hyperbilirubinemia of Crigler-Najjar syndrome (Type I).
PROGNOSIS
Prognosis is excellent for uncomplicated newborn jaundice. Prognosis is more guarded if jaundice is severe requiring ET or the bilirubin is near the ET threshold. The mortality from kernicterus is less than 10% with chronic irreversible sequelae in the form of choreoathetoid cerebral palsy, hearing loss and cognitive deficits seen with survivals.
FOLLOW-UP
All neonates requiring ET or having bilirubin in exchange threshold range or with bilirubin encephalopathy are at ‘high risk’ and need follow-up. Hearing assessment [brainstem-evoked response audiometry (BERA)] is done before 6 months of age. Neurodevelopmental assessment is performed at 3, 6, 9 and 12 months of age.
BIBLIOGRAPHY
- Muchowski KE. Evaluation and treatment of neonatal hyperbilirubinemia. Am Fam Physician. 2014;89(11):873–8.
- Wells C, Ahmed A, Musser A. Strategies for neonatal hyperbilirubinemia: a literature review. Am J Matern Child Nurs. 2013;38(6):377–82; quiz 383-4.
1.3. PERINATAL ASPHYXIA
Rhishikesh Thakre, Naveen Jain
CLINICAL PRESENTATION
‘Baby did not cry at birth’ and ‘needed resuscitation at birth’ are unpleasant outcomes of a pregnancy; severe asphyxia is associated with high risk (>50%) of death and disability. In half the cases of asphyxia, perinatal risk factors are present, e.g. antepartum hemorrhage, decreased fetal movements, meconium-stained liquor, fetal tachycardia or bradycardia, abnormal biophysical profile, etc. Some conditions increase risk of perinatal asphyxia—gestational diabetes, pregnancy-induced10 hypertension, multiple gestations, etc. In half the cases, asphyxia is not expected because the pregnancy and labor were progressing normally. Babies with severe asphyxia have neurologic symptoms and multiorgan dysfunction. They may have lethargy or irritability or hypotonia or seizures or poor respiratory efforts. Decrease in urine output, shock, gut injury, hypoglycemia, hypocalcemia, hyponatremia indicate hypoxic–ischemic injury to every organ of the body.
DIAGNOSTIC WORK-UP
Pulse Oximetry
Babies requiring resuscitation at birth must be monitored with a pulse oximeter strapped to right-upper limb, as soon as resuscitation starts. If heart rate improves, saturations gradually increase from 65% to 90% over 10 minutes. Target saturations are 90–95% after 10 minutes of life. Resuscitation must be done with room air (21% oxygen) unless heart rates do not increase after 90 seconds of effective resuscitation. Use of a t-piece resuscitator allows better control of pressures and hypocarbia can be avoided. Hyperoxia and hypocarbia worsen the neurodevelopment outcomes.
Arterial Blood Gas
Cord pH must be obtained from the clamped cord. If not available, arterial blood gas must be obtained as early as possible; low pH (<7.0), base excess less than −12 and respiratory acidosis are expected.
Blood Glucose Monitoring
Hypoglycemia is probably the most important modifiable comorbidity of asphyxia. Uncorrected hypoglycemia increases risk of mortality and neurodisability severalfold. Baby's blood sugar must be checked by glucometer immediately after stabilization after resuscitation in labor room and periodically (6th hourly) after that till baby is medically stable. More frequent checks may be required in case of seizures. Although hypoglycemia is defined as glucose less than 40 mg/dL, target values of 60–125 are desirable. In case of hypoglycemia, blood sugars must be checked every 30 minutes till target values are reached.
Urine Examination
Urine output must be measured by using a urobag or diaper weights. Target urine output is 1–3 mL/kg/hr. If urine output remains low, baby may have to be catheterized for accurate monitoring. Urine examination may show hematuria, proteinuria, pyuria, etc. Serum creatinine and blood urea may be raised.
Complete Blood Count
Nucleated red blood cell (falsely reported as leukocytosis by automated counters) thrombocytopenia.
Liver Function Tests
Neuroimaging
Ultrasound is a bedside test and, hence, easy to use in a sick baby. But, it has limitations in detecting brain injury. Abnormal Doppler, hyperintense basal ganglia, incidental discovery of malformations such as hydrocephalus, absent corpus callosum.
Computerized Tomography
Computerized tomography scan is the neuroimaging of choice when intracranial hemorrhage is suspected (pallor, bulging fontanel) and birth trauma.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) has best resolution for brain injury, but requires that the sick baby be shifted out of intensive care unit to radiology room for at least 1 hour, limiting its utility early in the course of disease. Basal, ganglia hyperintensity and altered signal from posterior limb of internal capsule are poor prognostic signs.
Electroencephalogram
Electroencephalogram (EEG) should be recorded within 24 hours of clinical seizures. Continuous monitoring with an EEG may detect seizures with no clinical correlates. They must be treated.
MANAGEMENT
- Therapeutic cooling
- Supportive care
Therapeutic Cooling
Hyperthermia increases risk of neurodisability. The radiant warmer must be switched off (passive hypothermia) and core temperature measured, ideally using a rectal probe. Target core temperature is 34°C. Cooling can be initiated with devices like gel packs, fans or water bottles. Close monitoring of temperature is critical to avoid temperatures lower than 33°C.
Close monitoring of vitals is important for physiological instabilities of asphyxia and complications of cooling.
Supportive Care
- Management of seizures: Seizures lasting 3 minutes or more or repeated brief seizures must be treated. Rule out metabolic causes such as low blood sugar, low calcium before starting antiepileptic drug (AED)—phenobarbitone is the AED of choice. Further seizures may require fosphenytoin, midazolam, etc. Close monitoring of blood pressure (BP) and respiration is required when AEDs are administered.
- Management of blood pressure or perfusion: Cause of low BP or poor perfusion may be hypovolemic or cardiogenic. If functional echo can be performed, the treatment may be chosen as per echo findings. A saline bolus of 10 mL/kg over 30 minutes followed by dopamine (for hypotensive shock) and dobutamine for12 poor perfusion with normal BP. Steroids, sodium bicarbonate and milrinone may be required in refractory shock.
- Ventilation: Ventilation may be required for sick lung (secondary respiratory distress syndrome or meconium aspiration syndrome or pulmonary infarct), persistent pulmonary hypertension of the newborn or poor respiratory efforts. The strategy of ventilation will be adapted according to the underlying problem.
- Management of hypoglycemia: Dextrose infusion is started at 6 mg/kg/min. Increase in glucose infusion rate by 2 mg/kg/min may be made every 30 minutes till blood sugar values are in range.
- Blood products: Packed red blood cells transfusion may be required, if blood loss is associated [(cord events or antepartum hemorrhage (APH)], platelet transfusion may be required if platelet counts are less than 30,000 or less than 50,000 in a baby with bleeding manifestations.
- Renal function: Urine output, sodium and potassium must be monitored closely. Saline bolus and diuretic may be required, if oliguria is noted. Severe renal dysfunction may require peritoneal dialysis.
Prognosis
Poor prognosis: Low Apgar at 10 minutes, early onset encephalopathy, difficult to control seizures, MRI findings.
BIBLIOGRAPHY
- Edibe Pembegül Yildiz, Bariş Ekici, Burak Tatli. Neonatal hypoxic ischemic encephalopathy: an update on disease pathogenesis and treatment. Expert Review of Neurotherapeutics. 2016, DOI: 10.1080/14737175.2017.1259567.
- Douglas-Escobar Martha, Weiss MD. Hypoxic-Ischemic Encephalopathy: a reveiw, for the clinical JAMA Pediatr. 2015;169(4):397–403. doi: 10.1001/jamapediatrics. 2014.3269.
1.4. RESPIRATORY DISTRESS
Rhishikesh Thakre, Naveen Jain
CLINICAL PRESENTATION
A newborn with respiratory distress has two or more signs present—tachypnea, i.e. respiratory rate more than 60/minute, grunt, increased work of breathing (e.g. subcostal, intercostal, supraclavicular, sternal in-drawing, flaring of alae-nasi); and or central cyanosis. Special attention should be given to presence of risk factors, timing of onset of respiratory distress, gestation, degree of severity of respiratory distress (assessed by Downes score or Silverman Anderson Score).
The presentation is nonspecific. Presence of certain signs may give a clue to underlying etiology, e.g. large for gestation (birth trauma, asphyxia, polycythemia, respiratory distress syndrome, heart disease, hypoglycemia). Frothing, inability to pass orogastric tube (tracheoesophageal fistula), worsening on bag and mask13 ventilation (diaphragmatic hernia), meconium staining (meconium aspiration syndrome), pallor (anemia, shock), cyanosis (congenital heart disease), plethora (polycythemia), potter facies (hypoplastic lungs), isolated cleft palate (aspiration), features suggestive of heart disease (murmur, hepatomegaly, cardiomegaly, abnormal pulses, differential cyanosis) and features suggestive of sepsis (fever, hypothermia, thermal instability, umbilical sepsis, foul smell, pustules, petechiae, bleeding tendency, sclerema).
DIAGNOSTIC WORK-UP
- Hemoglobin, sepsis screen
- Blood culture
- B glucose
- Arterial blood gas
- X-ray chest.
Further investigations are done based on clinical suspicion (Table 1.4.1).
MANAGEMENT GUIDELINES
Supportive Care
- Ensure normothermia (36.5–37.5°C). Avoid cold stress, hypo-hyperthermic
- Minimal handling
- Ensure airway is clear. Suction if visible secretions
- Ensure adequate hydration. No routine restriction of fluids
- Nil by mouth during the unstable phase. Trophic feeds as early as feasible.
| |||||||||||||||||||||||||||
Oxygen Therapy
- Humidified oxygen be administered by nasal prongs, nasopharyngeal or oxygen hood.
- Monitor arterial oxygen saturation (SpO2). Target SpO2 to 90–95%. Set pulse oximeter alarms.
Antibiotics
- No prophylactic antibiotics. Start if infection cannot be ruled out.
- Cover Gram +ve or -ve organisms with broad-spectrum antibiotics.
- Have an exit policy based on clinical course, sepsis screen and blood culture.
Monitoring
- Assess sensorium, vital parameters, respiratory status and perfusion periodically.
- Review investigations and clinical course to plan action.
Anticipate Complications
Air leak, shock, hypoglycemia, persistent pulmonary hypertension of the newborn, patent ductus arteriosus, etc.
Specific Management
The specific management of respiratory distress is shown in Table 1.4.2.
| |||||||||||||||||||||||||||
INDICATIONS FOR VENTILATION
- Impending respiratory failure
- Respiratory failure
- Cardiopulmonary failure
- Recurrent apnea.
BIBLIOGRAPHY
- Pramanik AK, Rangaswamy N, Gates T. Neonatal Respiratory Distress: a practical approach to its diagnosis and management. Pediatr Clin N Am. 2015;62:453–69.