Last Updated 08-Feb-2006. Authorised by: Neonatal Handbook Editorial Board. Enquiries: Ellen Bowman & Simon Fraser.

webmaster. RWH.

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DisclaimerThe neonatal guidelines presented on this site were developed by clinicians primarily for use by medical and nursing personnel working in newborn special care units throughout Victoria. They detail the initial assessment and management of many common (and some rare but important) conditions encountered during the early newborn period. They do not constitute a textbook, rather, they are designed to acquaint the reader rapidly with the clinical problem and provide practical advice regarding assessment and management. These guidelines have been developed, where possible, by achieving consensus between practicing clinicians. They do not however necessarily represent the views of all neonatologists working in Melbournes Neonatal Intensive Care Units. The recommendations contained in these guidelines do not indicate an exclusive course of action, or serve as a standard of medical care. Variations, taking individual circumstances into account, may be appropriate. The authors of these guidelines have attempted to ensure the information upon which they are based is accurate and up to date. Users of these guidelines should confirm that the information contained within them, especially drug doses, is correct by way of independent sources. No responsibility is accepted for any inaccuracies or information perceived as misleading.

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Neonatal Handbook Index1. Abdominal Wall Defects........................................................................................................................... 05 2. Ambiguous Genitalia ................................................................................................................................06 3. Apnoea .......................................................................................................................................................09 4. Bleeding Disorders In The Neonate ........................................................................................................12 5. Blood Gas Interpretation ..........................................................................................................................14 6. Blood Pressure .........................................................................................................................................16 7. Bowel Obstruction ....................................................................................................................................19 8. Breastfeeding Issues ................................................................................................................................21 9. Bronchopulmonary Dysplasia .................................................................................................................26 10. Chickenpox (Varicella Zoster) ...............................................................................................................30 11. Cleft Lip And Palate ................................................................................................................................31 12. Common Limb Problems .......................................................................................................................33 13. Congenital Adrenal Hyperplasia ............................................................................................................35 14. Congenital Diaphragmatic Hernia .........................................................................................................36 15. Congenital Infection .39 A. Toxoplasmosis ..39 B. Rubella 41 C. Cytomegalovirus (CMV) Infection 42 D. Herpes Simplex Virus (HSV) .....44 E. Syphilis 45 16. Cyanosed Infant Assessment ....47 17. Developmental Care .....51 18. Developmental Dysplasia Of The Hip ..53 19. Dysmorphology Assessment Of The Newborn .54 20. Immediate Management Of The Tiny Baby (1,000g>) ..58 21. Fetal Hydronephrosis ...60 22. Gastro-Oesophageal Reflux ...63 23. Prevention Of Gbs Sepsis ...64 24. Glucose-6-Phosphate Dehydrogenase Deficiency ..66 25. Headbox Oxygen Set-Up .....67 26. Hypoglycaemia...69 27. Hypospadias ...72 28. Hypothyroidism .73 29. Immunisation Of Preterm Infants .....75 30. Incubator To Cot Transfer ...80 31. Infant Of The Chemically Dependent Woman ...81 32. Infant Of The Diabetic Mother (IDM) .....84 33. Inguinal Hernia And Hydrocele .....86 34. Intramuscular (Im) Injection 87 35. Intraosseous Needle Insertion ...89

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36. Intravenous Electrolyte Correction ..91 37. Intravenous Infusion For Scn Admissions ....92 38. Intubation .94 39. Jaundice In The First Two Weeks Of Life ...97 40. Listeria Monocytogenes Infection ..101 41. Meconium Aspiration Syndrome ....102 42. Meconium Stained Liquour, Delivery Room Management ..104 43. Meningomyelocele ..105 44. Metabolic Disease A Neonatal Approach .106 45. Necrotising Enterocolitis ......109 46. Normal Laboratory Values ....112 47. Osteopenia Of Prematurity ...116 48. Parvovirus Infection ...117 49. Percutaneous Central Venous Catheter Insertion .........................................................................118 50. Persistent Pulmonary Hypertension Of The Newborn ..121 51. Pneumothorax Drainage 123 52. Polycythaemia ..125 53. Respiratory Distress Syndrome (RDS) ..126 54. Resuscitation 128 55. Retinopathy Of Prematurity ..131 56. Small For Gestational Age Infants ..134 57. Shock ..136 58. Seizures .140 59. Sepsis .143 60. Single Umbilical Artery .....148 61. Small For Gestational Age Infants ..149 62. Supraventricular Tachycardia .....151 63. Surfactant Replacement Therapy ...154 64. Thrombocytopenia ..155 65. Thrombosis In Newborns ..157 66. Tracheo-Oesophageal Fistula/Oesophageal Atresia .159 67. Transfer Guidelines ....161 68. Transfusion ...164 69. Tuberculosis (TB) ...166 70. Umbilical Artery Catheterization ....167 71. Umbilical Cord Care ...169 72. Umbilical Hernias ....170 73. Umbilical Vein Catheterisation ....171 74. Undescended Testes (Cryptorchidism) ....173 75. Vomiting In The Newborn Infant .....174

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1. ABDOMINAL WALL DEFECTSA. B. C. D. E. F.Summary Introduction Gastroschisis Exomphalos Investigation Management

A. Summary: - the abnormality should be covered with cling wrap - pay careful attention to thermoregulation and fluid management - refer early via NETS to tertiary referral centre with surgical facilities B. Introduction: - The diagnosis of exomphalos and gastroschisis is often but not invariably made antenatally by ultrasound. - These babies will usually be delivered at a tertiary referral centre. C. Gastroschisis: - small defect of the anterior abdominal wall to the right of the umbilicus through which bowel herniates - occurs in between 1:10,000-30,000 births - no covering sac, the surface of the bowel is usually oedematous and matted - associated anomalies are reported in up to 15% (mainly gastrointestinal) - prematurity and growth restriction are frequent - necrotising enterocolitis and malabsorption may occur - survival rates are about 90% D. Exomphalos: - a protrusion of intestinal contents through the abdominal wall at the umbilicus - covered by a thin membrane of amnion and peritoneum - herniation of the liver accompanies intestine if a large sac, omentum and intestine are present if a smallsac associated anomalies occur in 45 67% (eg trisomies, cardiac defects, G.I. and renal anomalies) survival rates are mainly dependent on whether other anomalies are present necrotising enterocolitis and malabsorption are associated complications

E. Investigation: - look for associated problems: remember exomphalos can be associated with Beckwith-Wiedemann Syndrome (includes macroglossia, pathognomonic horizontal ear crease and hypoglycaemia) cardiac malformations renal abnormalities karyotype infants with exomphalos

F. Management: - wrap abdomen of baby in cling film with gut lying well supported either on the abdomen if a small lesion orsupported by a foam rubber "doughnut". If in one position a length of bowel appears to have impaired blood supply or drainage i.e. looks purple or black, try gentle manipulation of the bowel into other positions to see if the circulation can be improved the bowel may need to be rotated on its pedicle to achieve a better circulation cotton wool covering or the use of moist packs is contraindicated. (Cotton wool adheres to the bowel wall, cannot be fully removed and causes peritoneal granulomas; moist packs rapidly become cold and lead to hypothermia) pass size 8 NG tube, place on continuous low-pressure suction or leave on free drainage and aspirate every 60 minutes place nil by mouth start IV infusion - Give usual Day 1 fluids infants with gastroschisis may loose large amounts of colloid fluid into the inflamed gut requiring vigorous colloid fluid replacement (eg Albumin 5% 10-20 mL/kg). Watch blood pressure

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check blood glucose immediately and monitor closely because of the association of Beckwith-Wiedemann syndrome with exomphalos monitor temperature frequently. Patients with a ruptured exomphalos sac or gastroschisis may have major problems with temperature control due to evaporative heat loss contact paediatric surgeon and NETS to arrange transfer to surgical centre give antibiotics: Penicillin, Gentamicin (preferably after blood culture) take blood for FBE, electrolytes, blood culture, group and hold for cross match of blood

2. AMBIGUOUS GENITALIAA. B. C. D. E. F. G. H.Summary Introduction Management Clinical Evaluation Investigation

Differential diagnoses Ongoing ManagementFurther Reading

A. Summary:Be very careful in your choice of words during the diagnostic period and do not sign the birth certificate until a definite decision as to the sex of rearing has been reached. - be aware of associated metabolic problems - palpable gonads imply the presence of testicular tissue - decisions as to sex of rearing may have no relationship to karyotypic, gonadal or genital status in isolation - there is some ongoing controversy as to when is the appropriate time to make decisions as to sex of rearing and who should be party to those decisions

B. Introduction:Approximately 1 in 4,500 births are complicated by ambiguous genitalia. This situation is rarely anticipated and can be a source of great distress for parents, delivery room and nursery staff. Often there can be pressure on medical staff to "make it better" and assign a gender to the child arbitrarily in the first few hours after birth. This must be avoided at all costs. Staff must be careful in their choice of words when discussing the baby with parents. It is unnatural not to discuss a baby without using the terms "he" or "she" and it is easy to accidentally refer to the baby in a gender-orientated way. Parents who are often greatly distressed may assume that medical and nursing staff "know" what the gender of the baby "really is". Consequently any terminology used (deliberately or accidentally) will be given great emphasis by parents. This may lead to confusion and distress later if the suggested sex of rearing is at odds with initial "off the cuff" remarks. Parents may seek advice regarding the naming of their infant. The usual advice is to select non-ambiguous names (ie using gender specific names) since it is thought that by encouraging the use of ambiguous (non-gender specific) names, one is implying an ongoing sense of "ambiguity".

C. Management: - Be very careful in your use of terms when discussing the baby with ambiguous genitalia. Appropriate,non-gender orientated terms are listed in Table 1. Never refer to the baby in question as "it" Table 1: Suggested phenomenology when dealing with babies with ambiguous genitalia.

FEMALEShe Clitoris Labia Ovaries Vagina, urethra

AMBIGUOUSYour baby Phallus Folds Gonads Urogenital sinus

MALEHe Penis Scrotum Testes Urethra

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The situation should be treated as a medical emergency, with paediatric endocrine advice being sought immediately

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D. Clinical Evaluation:Genital ambiguity can be quantified according to the Prader scale (Figure 1). Other relevant clinical details include: - gonads palpable in the labioscrotal or inguinal regions - size of the phallus - pigmentation of the genitalia - syndromic features - metabolic condition of the baby (paying particular attention to glucose, sodium and potassium) The baby's mother should also be examined for signs of hyperandrogenism. Care should be taken in the interpretation of examination findings in growth retarded or premature female neonates. These children may exhibit atrophic labia and clitoral oedema giving them an appearance of "pseudoambiguity". It is a moot point where the boundary lies between severe perineal hypospadias and genital ambiguity. Inability to palpate the gonads in this situation may be indicative of a diagnosis other than isolated hypospadias. Figure 1: Prader staging system for the degree of virilisation of the external genitalia.

Prader 0: Normal female external genitalia.

Prader 1: Female external genitalia with clitoromegaly.

Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus.

Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening.

Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus.

Prader 5: Normal male external genitalia.

(Prader Von, A. (1954). "Der genitalbefund beim Pseudohermaproditismus femininus des kongenitalen adrenogenitalen Syndroms. Morphologie, Hausfigkeit, Entwicklung und Vererbung der verschiedenen Genitalformen." Helv. Pediatr. Acta. 9: 231-248.)

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E. Investigation:Blood should be sent for: - electrolytes - gonadotropins (LH, FSH) - testosterone - urgent karyotype - serum 17-hydroxyprogesterone (17OHP) levels (after day 3 of life) Pelvic ultrasound (carried out by an experienced sonographer) should be undertaken as soon as possible. Other investigations which may or may not be subsequently relevant include: - sinugram - human chorionic gonadotropin stimulation test (to assess testosterone and dihydrotestosterone synthesis capability)

F. Differential diagnoses:a) Gonads palpable, 46XY:gonadal dysgenesis partial androgen insensitivity biosynthetic defect in either testosterone or dihydrotestosterone production b) Gonads impalpable, 46XX: - Congenital adrenal hyperplasia - gonadal dysgenesis - exogenous androgen exposure c) Mosaic karyotype: - gonadal dysgenesis

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G. Ongoing Management:Decision as to sex of rearing is made after opinions have been sought from the endocrine and surgical teams. It should be undertaken with the baby's parents after all the relevant investigation results have been discussed. The decision that will be influenced by an amalgam of:

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the baby's karyotype gonadal status internal and external genital duct status potential for fertility and adequate sexual function cultural influences

Do not complete the baby's birth certificate until the sex of rearing has been decided. There is a 60 day period of grace between the birth of a child and when their birth certificate needs to be completed - hence there is no rush. If the "wrong" sex is entered on the form it is extremely difficult to correct and requires judicial intervention. Long term care:

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families require long term medical and psychological support corrective surgery is usually undertaken within the first year of life infants with CAH and congenital syndromes have additional requirements for ongoing medical therapy disclosure to the patient as to their diagnosis is usually undertaken in mid to late adolescence when they have the ability to understand complex issues such as chromosomes, hormones etc, and possess some degree of emotional maturity

H. Further Reading: Reiner WG Assignment of sex in neonates with ambiguous genitalia. Curr Opin Pediatr 1999 Aug;11(4):363-5. Ahmed SF, Hughes IA The genetics of male undermasculinization.Clin Endocrinol (Oxf) 2002 Jan;56(1):118

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3. APNOEAA. B. C. D. E. F. G.Summary Introduction Differential Diagnosis Investigations Management Areas of Uncertainty in Clinical Practice References

A. Summary:initially monitor all infants 7.4 is an alkalosis pH < 7.3 is an acidosis

The pH is proportional to HCO3 (or base excess), therefore: an abnormal increase in HCO3 (or base excess) increases the pH (metabolic alkalosis) an abnormal fall in HCO3 (or base excess) decreases the pH (metabolic acidosis)

The pH is inversely proportional to pCO2, therefore: an abnormal increase in pCO2 decreases the pH (respiratory acidosis) an abnormal decrease in pCO2 increases the pH (respiratory alkalosis)

C. Acid (H+):Many organic acids are produced during normal metabolism. Sometimes they can accumulate in the blood (e.g. lactic acid). The hydrogen ion (H+) may be 'mopped up' by buffers including bicarbonate (HCO3). Bicarbonate is unique because it can be converted to CO2, which can be blown off by the lungs (provided the baby is not in respiratory failure). The following bi-directional equation demonstrates this:

D. Respiratory Acidosis: (e.g. pCO2 >= 50 mmHg, pH < 7.30)This occurs when the pCO2 is abnormally high and is due to inadequate alveolar ventilation. Causes include depression of the breathing centre in the brain, upper airway obstruction, stiffness of the chest wall or significant ventilation/perfusion imbalance. If the respiratory acidosis is chronic, the body will respond by trying to excrete acid and retain bicarbonate in the urine resulting in a compensatory rise in serum bicarbonate (metabolic alkalosis). The treatment of a respiratory acidosis is to treat the underlying cause and to consider the need for or increase mechanical ventilation. The latter is achieved by either increasing the tidal volume (increasing PIP or decreasing PEEP) or by increasing the respiratory rate.

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E. Respiratory Alkalosis: (e.g. pCO2 < 35 mmHg, pH > 7.40)This occurs when the pCO2 is abnormally low and is usually due to excessive mechanical ventilation or to abnormal control of ventilation (e.g. during hypoxic-ischaemic encephalopathy). The baby may also be trying to compensate for a primary (intracellular or extracellular) metabolic acidosis, although the pH will never become alkalotic (as the baby will never over-compensate). The treatment of a respiratory alkalosis is to wean the mechanical ventilation by reducing PIP or tidal volume, then respiratory rate.

F. Metabolic Acidosis: (e.g. HCO3 < 17 mmol/L or B.E. < minus 6.0 mEq/L, pH < 7.30)This may occur where there is a rise in free H+ ions that cannot be totally buffered. In this case the anion gap is increased. Causes include lactic acidosis secondary to tissue hypoxia (e.g. hypotension, sepsis and PDA) or the inability to excrete/buffer accumulated organic acids (e.g. protein loading and renal immaturity). Another common cause of metabolic acidosis, particularly in the extremely premature infant is excessive loss of HCO3 in the urine or gut. In this case the anion gap is normal. Metabolic acidosis is rarely due to an inborn error of metabolism. The treatment of a metabolic acidosis is to treat the underlying cause, consider volume expansion (e.g. 10 mls/kg of normal saline) if the baby is thought to be hypovolaemic or to administer NaHCO3 if the metabolic acidosis is severe (controversial) or refractory (e.g. bicarbonate wasting). Bicarbonate should not be given if the pCO2 is elevated as the pH will not change (according to the above formula, a metabolic acidosis is merely being replaced by a respiratory acidosis).

G. Metabolic Alkalosis: (e.g. HCO3 > 28 mmol/L or B.E. > plus 4.0 mEq/L, pH > 7.40)This occurs where the plasma HCO3 or base excess is abnormally high. Causes include hypochloraemia (the level of bicarbonate and chloride in plasma are reciprocally related), which may be due to diuretic therapy or upper gastrointestinal obstruction (e.g. pyloric stenosis). The baby may also be trying to compensate for a respiratory acidosis, although the pH will never become alkalotic (as the baby will never over-compensate). The treatment of a metabolic alkalosis is to treat the underlying cause (e.g. chloride replacement) or the underlying cause of the respiratory acidosis.

H. Base Excess:This is one way of looking at the metabolic component. It refers to the 'amount of base that would have to be added to one litre of the baby's blood at 40 mmHg pCO2 to return the pH to normal. It is a calculated value and will be erroneous if the pCO2 is not normal. In these circumstances, the 'metabolic' component of the blood gas should be assessed using the plasma HCO3 level.

I. Acid-Base Disorders:Any one of the above four scenarios can occur in isolation, with or without compensation. These are classified as simple acid-base disorders. When a combination of simple acid-base disturbances occurs, the baby has a mixed acid-base disorder. When there is a mixed disorder, it is sometimes difficult to know which is the primary and which is the compensatory component. In such circumstances a helpful principle is that normal physiological processes never over-compensate. The pH can be relatively normal in the following situations - respiratory acidosis with metabolic compensation - metabolic acidosis with respiratory compensation - metabolic alkalosis with respiratory compensation - respiratory alkalosis with metabolic compensation The fourth is extremely unusual in neonates.

G. The Blood Gas Machine:This measures pH, pCO2 and pO2 and may measure glucose and lactate. It calculates HCO3, base excess and oxygen saturation. Measurements that are inaccurate, including Hb and oxygen saturation, should not be used to decide therapy (although newer machines contain co-oximetry and are very accurate).

K. Areas of Uncertainty in Clinical Practice:The main controversy relates to the use of bicarbonate (HCO3) for the treatment of a metabolic acidosis a) There is no evidence that the correction of an acute metabolic acidosis improves survival or long term neurodevelopmental outcome. b) The extra pCO2 produced (in the above equation) can cross cell membranes and paradoxically worsen the intracellular acidosis (as it combines with intracellular water, and with the equation in reverse, produces excess H+, which can't cross back out). c) Sodium bicarbonate is hyper-osmolar and if given rapidly, particularly to premature babies, may cause intraventricular haemorrhage. d) The exact reference ranges for pH, pCO2, HCO3 and base excess will vary from unit to unit. The above ranges are given for practical demonstration only.

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L. References: Ganong WF. Review of Medical Physiology, 19th Ed. 1999, p. 697-704. Appleton & Lange, Stanford, Connecticut Taeusch HW, Ballard RA (Eds). Avery's Diseases of the Newborn 7th Ed. W.B. Saunders Company, Philadelphia. 1998

6. BLOOD PRESSUREA. B. C. D. E.Introduction Method of Blood Pressure Measurement 'Normal' Blood Neonatal Blood Pressure Values Areas of Uncertainty in Clinical Practice References

A. Introduction:The recognition and treatment of hypotension are particularly important to avoid complications such as cerebral ischaemic injury or intraventricular haemorrhage. On the other hand, hypertension in the newborn is increasingly seen as a complication in infants with bronchopulmonary dysplasia and who are receiving steroid treatment. Arterial blood pressure (BP) is determined by: cardiac output peripheral vascular resistance In general hypotension indicates inadequate systemic blood flow or left ventricular output and therefore inadequate tissue perfusion, although this is not always the case.

B. Method of Blood Pressure Measurement:Unless the baby has an in-dwelling arterial line, the only reliable and accurate way of measuring blood pressure indirectly is by using the oscillometric method (e.g. Dynamap). To minimise errors of noninvasive BP measurements, the following guidelines are recommended: cuff width to arm (or calf) circumference ratio as indicated on cuff if possible, obtain BP measurement during quiet or sleep state obtain average of two or three measurements if making management decisions use mean BP to monitor changes as less likely to be erroneous noninvasive BP may overestimate BP measurements in VLBW To minimise errors when using in-dwelling arterial lines, the following factors should be noted: narrow catheters will underestimate systolic BP occlusion of the tip of the catheter (vessel wall or clot) may dampen wave and underestimate BP even small air bubbles may have an effect on measurement peripheral lines read higher than umbilical lines

C. 'Normal' Blood Neonatal Blood Pressure Values:Blood pressure increases with: gestation birth weight postnatal age There is no significant difference between arm and calf blood pressure in normal infants. It is difficult to define 'normal' BP values in ELBW infants.

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In clinical practice, the infant's blood pressure is generally considered to be adequate as long as urine output (> 1ml/kg/hr) and capillary refill (< 3 seconds) are within normal limits and there is no metabolic acidosis. However, these are not reliable indicators of tissue perfusion. Arbitrary definitions of hypertension are as follows: term infant: systolic > 90 mmHg, diastolic > 60 mmHg preterm infant: systolic > 80 mmHg, diastolic > 50 mmHg

Low birthweight infants

Birthweight (g) Systolic range (mmHg) Diastolic range (mmHg)

501-750 751-1000 1001-1250 1251-1500 1501-1750 1751-2000

50-62 48-59 49-61 46-56 46-58 48-61Preterm infants

26-36 23-36 26-35 23-33 23-33 24-35

Gestation (wk) Systolic range (mmHg) Diastolic range (mmHg)

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48-63 48-58 47-59 48-60Preterm infants

24-39 22-36 24-34 24-34

Day

Systolic range (mmHg)

Diastolic range (mmHg)

1 2 3 4 5 6 7

48-63 54-63 53-67 57-71 56-72 57-71 61-74

25-35 30-39 31-43 32-45 33-47 32-47 34-46

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Term infants

Age

Systolic (mmHg)

Diastolic (mmHg)

Mean (mmHg)

1 hour 12 hour Day 1 (Asleep) Day 1 (Awake) Day 3 (Asleep) Day 3 (Awake) Day 6 (Asleep) Day 6 (Awake) Week 2 Week 3 Week 4

70 66 70+/-9 71+/-9 75+/-11 77+/-12 76+/-10 76+/-10 78+/-10 79+/-8 85+/-10

44 41 42+/-12 43+/-10 48+/-10 49+/-10 46+/-12 49+/-11 50+/-9 49+/-8 46+/-9

53 50 55+/-11 55+/-9 59+/-9 63+/-13 58+/-12 62+/-12

D. Areas of Uncertainty in Clinical Practice:Definitions of 'normal' blood pressure in low birthweight and preterm infants are based on small numbers. Although these are 'healthy' infants, a variety of devices have been used to produce the measurements. There is very good evidence to suggest that blood pressure cannot necessarily be equated with normal systemic flow or a normal circulating blood volume.

E. References: Nuntnarumit P, Yang W, Bada-Ellzey HS. Blood pressure measurements in the newborn. Clin Perinatol 1999;26:981-996 Rennie JM, Roberton NRC (Eds). Textbook of Neonatology, 3rd Ed. Churchill Livingstone, Edinburgh, 1999. Taeusch HW, Ballard RA. Avery's Diseases of the Newborn 7th Ed. W.B. Saunders Company, Philadelphia. 1998

Other Reading/Web links Bauer K, Linderkamp O, Versmold. Systolic blood pressure and blood volume in preterm infants. Arch Dis Child 1993;69:521-2 Kluckow M, Evans, N. Relationship between blood pressure and cardiac output in preterm infants requiring mechanical ventilation. J Pediatr 1996;129:506-12

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7. BOWEL OBSTRUCTIONA. B. C. D. E. F. G. H. I. J.Summary Introduction Differential Diagnosis Duodenal Atresia Midgut Malrotation and Volvulus Jejunoileal Atresia Meconium Ileus Hirschsprungs Disease Investigation of Bowel Obstruction Management

A. Summary:delay in carrying out surgery may result in the loss of large amounts of bowel not all infants with bowel obstruction require transfer by the NETS team. Infants diagnosed early and without fluid or electrolyte problems may be safely transferred with local ambulance services. However, it is advisable to discuss such infants with the receiving hospital or the NETS team

B. Introduction:Signs of bowel obstruction can include:

vomiting with or without bile stained material, therefore never ignore bile-stained vomiting in the newborn gastric residuals before feedings failure to pass meconium in the first 24 hours of life abdominal distension (particularly with low level obstruction)

C. Differential Diagnosis: Intestinal obstruction without bilious vomiting: duodenal atresia (if obstruction proximal to Ampulla of Vater 20% of cases) duodenal stenosis annular pancreas pyloric stenosis (usually presents at 4-6 weeks of life but may present as early as the first week) Intestinal obstruction with bilious vomiting: malrotation and volvulus duodenal atresia (if obstruction distal to Ampulla of Vater 80% of cases) jejunoileal atresia meconium ileus necrotising enterocolitis (see Necrotising Enterocolitis) Intestinal obstruction with marked abdominal distension: ileal atresia Hirschsprung disease meconium ileus meconium plug imperforate anus

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D. Duodenal Atresia:Duodenal atresia may take the form of either a membranous or interrupted-type lesion at the level of the papilla of Vater. In 80% the papilla of Vater opens into the proximal duodenum causing the vomiting to be bilious:

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obstruction due to failure of recanalisation of the 2nd part of the duodenum during foetal development occurs in 1:5,000-10,000 live births commoner in males associated with Down syndrome in 25% hydramnios is seen antenatally X-ray usually shows a characteristic "double-bubble" appearance

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E. Midgut Malrotation and Volvulus:most patients with midgut malrotation develop volvulus within the first week of life bilious vomiting is the initial symptom and abdominal distention minimal until at a late stage bowel can be involved in strangulation at any time and age. Once midgut ischaemia occurs, unstable haemodynamics, intractable metabolic acidosis and necrosis with perforation develop malposition of the superior mesenteric vessels demonstrated by ultrasound examination is diagnostic upper gastrointestinal contrast studies should be performed by experienced practitioners only. Features include: obstruction at the second portion of the duodenum spiral configuration of the jejunum or a duodenojejunum that occupies the right hemi-abdomen symptomatic infants require immediate surgery

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F. Jejunoileal Atresia:caused by a mesenteric vascular accident during fetal life abdominal distention with bilious vomiting is observed within the first 24 hours after birth. The more proximal the lesion, the earlier the bile-stained vomiting X-ray shows air-fluid levels proximal to the lesion. Calcification due to meconium peritonitis may be present

G. Meconium Ileus:thick tenacious meconium in the bowel (ileum, jejunum or colon) causes obstruction 50% have associated: volvulus jejunoileal atresia bowel perforation and/or meconium peritonitis meconium ileus occurs in 15% of newborns with cystic fibrosis, and at least 90% of patients with meconium ileus have cystic fibrosis presentation includes: early marked bowel distension bilious vomiting remarkable abdominal distention, tenderness and/or erythema of the abdominal skin may indicate perforation on rectal examination mucus plugs may be evacuated after withdrawal of the examination finger (fifth finger) X-ray shows: distended loops of intestine with thickened bowel walls a large amount of meconium mixed with swallowed air produces the so-called "ground-glass" sign typical of meconium ileus, a characteristic feature but often absent calcification, free air or very large air-fluid levels suggest bowel perforation

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Patients with uncomplicated meconium ileus may be successfully treated with hypertonic enemas performed while adequate intravenous fluid is maintained. Immediate surgery is indicated for infants with complicated meconium ileus or where conservative treatment fails.

H. Hirschsprungs Disease:causes 15-20% of newborn intestinal obstructions 80% of cases present in the first 6 weeks of life 4:1 male:female ratio presents with failure to pass meconium in the first 24 hours plus gradual onset of abdominal distension and vomiting. Distal short segment disease can present later in life with persistent and progressive constipation the most serious complication is enterocolitis. This occurs as a result of progressive colonic dilation with decreased ileal and colonic fluid resorption, stasis with bacterial overgrowth and mucosal ischaemia which may lead to massive acute fluid loss into the bowel with diarrhoea, shock and dehydration. Enemas should be avoided during episodes of enterocolitis because of the possibility of perforating the colon definitive diagnosis is made by a full thickness rectal biopsy showing a lack of ganglion cells in the myenteric plexus of the colon

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I. Investigation of Bowel Obstruction:thorough physical examination and assessment of the circulation bowel obstruction may be a part of multiple anomalies, therefore look for associated abnormalities eg Vertebral Anal Cardiac TracheoEsopageal atresia Renal Limb (VACTERL) sequence with imperforate anus, trisomy 21 with duodenal atresia plain abdominal X-rays contrast studies and ultrasound examinations are best undertaken in centres with paediatric surgical services

J. Management:place infant in an incubator for close observation and temperature control nurse supine or on the right side with the head elevated place an orogastric tube (8 - 10FG) on low pressure suction (or aspirate with a syringe every 60 minutes and leave on free drainage). The amount and type (eg bile-stained, faeculent) of fluid aspirated should be recorded place nil by mouth commence IV fluids. Give maintenance fluids plus ml for ml replacement of NG aspirate with normal saline obtain abdominal x-rays (include supine and erect or decubitus view). Note that a relatively gasless abdomen is compatible with mid-gut volvulus consult with a paediatric surgeon or NETS to arrange transfer to an appropriate surgical centre it may be appropriate to commence antibiotics preferably after blood culture taken(discuss with the receiving unit or NETS) obtain blood for FBE, electrolytes, blood grouping and hold for X match (and blood cultures if commencing antibiotics) frequently, these infants have associated problems of acidosis and shock

8. BREASTFEEDING ISSUESA. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.Summary Introduction Benefits of breast milk Storage of Breast milk for Infant Use Maintenance of supply of breast milk Developmental issues Prematurity and nutritional adequacy of human milk Human Milk Fortifier Breast milk substitutes Infections Maternal medications Drugs of addiction Herbal preparations Jaundice Drugs in pregnancy and/or lactation References

A. Summary:Breast milk is the milk of first choice in neonates, whether term or preterm there are significant clinical benefits to providing breast milk in the preterm infant expressed breast milk can be safely frozen for later use human milk fortification should be considered in babies < 1500g or < 30 weeks' gestation very few maternal medications contraindicate breastfeeding maternal Hepatitis C does not preclude breastfeeding (unless nipples are cracked)

B. Introduction:The Innocenti Declaration (WHO/UNICEF, 1990) recognised that breastfeeding is a unique process that provides ideal nutrition for infants and contributes to their healthy growth and development. The Paediatrics and Child Health Division of the Royal Australasian College of Physicians encourages and supports the promotion of breastfeeding (see website).

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C. Benefits of breast milk:

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The many benefits of mother's own milk are well known. Breastmilk is a unique 'living" fluid. It contains: anti-infective factors hormones enzymes specialised growth factors anti-inflammatory mediators specific nutrients Colostrum is a high density; low-volume feed high in immunoglobulins, which evolves into mature milk between 3 and 14 days postpartum. Breastmilk feeding for both preterm and unwell term infants assists recovery and has major health benefits. As the unwell or preterm infant may not be able to breastfeed mothers are encouraged to provide fresh expressed milk daily; if this is not possible breast milk can be stored in a refrigerator or freezer.

D. Storage of Breastmilk for Infant Use:Guidelines for collecting and storing breast milk are more stringent for sick and preterm babies than for healthy babies at home. - sterilised containers are recommended - refrigeration at 40C for 48 hours results in minimal loss of nutrients and bacterial count is reduced - freshly expressed milk should be chilled in refrigerator before adding to frozen milk - thaw breast milk by placing in cool or warm water - thawed milk should be used within 24 hours - never refreeze or re-warm breast milk

Time to keep milk in various conditions

Breast milkFreshly expressed into closed container

Room Temperature Refrigerator6 - 8 hours (d260C ) If refrigeration is available store milk there 3 - 5 days (d40C) Store in back of refrigerator where it is coldest

Freezer2 weeks in freezer compartment inside a refrigerator 3 months in freezer section of refrigerator with separate door 6 - 12 months in deep freeze (- 180C) Do not refreeze

Previously frozen thawed in refrigerator but not warmed

4 hours or less i.e. next feeding

Store in refrigerator 24 hours

Thawed outside For completion of refrigerator in warm water feeding Infant has begun feeding Only for completion of feeding then discard

Hold for 4 hours or until Do not refreeze next feeding Discard Do not refreeze Discard

There is controversy regarding the use of sterile vs clean washed containers for storage of expressed breast milk (EBM) intended for preterm infants. There is limited published evidence to support the use of clean containers One Level 3 nursery in Melbourne does provide sterile containers which families re-use after washing in the dishwasher and air-drying.

E. Maintenance of supply of breast milk: The long-term commitment of expressing breast milk for a preterm infant is stressful and may result in reduced volumes of EBM. Strategies that assist in maintaining a good supply of milk include: the provision of a comfortable environment within the special care nursery if expression at the cotside is impractical reminders that it is the regular emptying of the breasts that stimulates formation of more mature milk the continuing discipline of expressing at least once overnight to ensure the longevity of supply kangaroo care (the practice of mother holding her baby skin to skin between her breasts). The close contact triggers

-

22

the enteromammary pathway by which a mother produces antibodies in response to antigens in the infant's environment If supply lags, technique and frequency of expression needs review before resorting to galactogues. Commencement of an oral contraceptive agent may also contribute to reduction in supply. In addition

Galactogues:These are substances, which stimulate the supply of breast milk. Both pharmacological and herbal preparations are available. - Published evidence supportive of herbal preparations is limited. Fenugreek is the most widely recognised however there is no data regarding transmission in breast milk or safety for preterm infants. - Metoclopramide (Maxalon) will stimulate breast milk supply in the lactating mother. The safety of this medication has been established for preterm infants. Mothers should be advised about the possibility of dystonic reactions. In some women use exacerbates symptoms of depression. Controversy exists over the dosage regime and duration. A suggested regime is 10mg tds for 5 days and then tapering over the next 5 days. Some women benefit from repeated courses but little data exists on the safety of such practice. Metoclopramide often results in dramatic increase in supply, which may not be sustained once medication is withdrawn. - Domperidone also acts a galactogue and is safe for preterm infants. There appears to be a slower onset of action but the increase in supply is better maintained than with Metoclopramide. Unfortunately Domperidone is not approved as a galactogue on the Australian Pharmaceutical Benefits Scheme and the quantity required can prove costly. The dose required is 10 - 20 mg qid. Domperidone is better tolerated by mothers as a long term stimulant of breast milk supply.

F. Developmental issues:Initiating breast-feeding in preterm infants does not require a demonstrated ability to breastfeed. Kangaroo care is a good introduction to mother's breasts for the preterm or unwell infant. Studies have shown that preterm infants show greater cardio-respiratory stability when breast feeding than bottle feeding. Infants exhibit sucking movements as early as 11 weeks gestation. By 32 weeks there is coordination of sucking and swallowing, but this is not sustained until closer to term. Controversy exists over the issue of nipple confusion. Ultrasonography has shown that the sucking action used at the breast is different from that used for an artificial teat. A randomised controlled trial comparing artificial teats and cup feeding in preterm infants did not demonstrate any difference in time to achieve breastfeeding. (personal communication). If it is to be mentioned then the technique of cup feeding needs brief explanation Similarly controversy exists between the advantages of indwelling naso-gastric feeding tubes and intermittent orogastric tube feeds. Sandra Lang in her book "Breastfeeding Special Care Babies" addresses these issues in depth.

G. Prematurity and nutritional adequacy of human milk:Preterm breast milk differs from term milk, not only in nutritional composition but also in immuno-protective factors. Preterm infants given breast milk have significantly reduced rates of sepsis and necrotising enterocolitis compared with infants fed breast milk substitutes. Preterm infants exclusively breastfed have been found to have an IQ several points greater than infants fed breast milk substitutes. Is this difference real world significant? Should the degree of difference be stated? Mother's own milk may not meet the increased nutritional demands of the preterm infant whose birthweight is below 1500g. These needs persist to term postmenstrual age. There is considerable variation in the energy content of expressed breastmilk largely due to separation of the fat whilst standing. Use of hind-milk, with a two to threefold greater fat content than foremilk will provide significantly more energy for growth. The content of protein and sodium declines throughout lactation. Calcium and phosphorous content is also insufficient for the growing preterm infant.

H. Human Milk Fortifier:Mother's own milk can be supplemented by combining with a commercially prepared fortifier to provide increased protein, energy and minerals. All human milk fortifiers contain similar amounts of protein, energy, calcium and phosphorous. The differences relate to the type of protein and the amounts of lactose, sodium and vitamins. Dr K Simmer has prepared comparative tables indicating the composition of breast milk and fortifiers available in Australia. In general infants with a birthweight less than 1500g and less than 30 weeks gestation will benefit from addition of fortifier, which should continue to discharge, when the infant is not breastfeeding. In practice fortification of breast milk is best delayed until the infant demonstrates tolerance of a reasonable volume of enteral feeds (150 mls/kg/day). Breast milk fortification is often commenced at half strength for 2 days and if tolerated full strength

23

supplementation is introduced. However, there are a number of potential complications with fortification. These include:

-

an increase in regurgitation an increase in feed intolerance glycosuria in extremely of preterm infants hypercalcemia in extremely preterm infants

As the fortifier is usually cow's milk based there is a theoretical advantage in using a product in which the protein has been hydrolysed. Infants fed fortified human milk receive less volume, but greater intakes of protein and minerals and experience greater weight gain and incremental linear growth than infants fed unfortified milk. The growth of infants fed fortified breastmilk is still less than infants fed on preterm formula. However the quality of the milk and its many advantages far outweigh any growth disadvantage. In general, fortifier can be discontinued once the infant reaches a corrected age of term and prior to discharge from hospital.

I. Breast milk substitutes:When there is insufficient breast milk available for an infant tolerating enteral feeds parents should give consent for the use of formula. If the intention is to primarily breastfeed then use of a protein hydrolysed or semi-elemental formula may be appropriate. If the infant is not tolerating full volume feeds then the formula should be standard 67 kcal per 100 mls. Most preterm formulae are 85 kcal per 100mls and are fed once the infant is tolerating volumes of 150mls/kg/day as they provide better nutrition. Dr K Simmer has prepared comparative tables indicating the composition of preterm formulae available in Australia. Donor human milk is not an option as there are no human milk banks in Australia. In general, preterm formulas can be discontinued once the infant reaches a corrected age of term and prior to discharge from hospital.

J. Infections:Maternal HIV is the only infection in which breastfeeding is contra-indicated in the developed world Hepatitis C has been reported to have a 5% risk of transmission. Most probably this occurs at times of active disease (PCR positive women). It is generally advised that HCV positive mothers do not breastfeed when nipples are cracked. Hepatitis B is not transmitted through breast milk CMV is transmitted through breast milk. The burden of disease acquired from breast milk is not well established. It is presumed that preterm infants are more vulnerable and likely to exhibit more severe clinical illness, such as pneumonitis, than term infants. However women who are CMV positive are not discouraged from breastfeeding as the other benefits are thought to outweigh the risk. Herpes Simplex is not transmitted through breast milk. Should there be an open sore on the breast the mother would be advised to avoid feeding from that breast. With Varicella and Herpes Zoster (shingles) maternal antibodies transmitted through breast milk will be protective. However in the case of Varicella if the mother develops chicken pox within 5 days of birth the infant is at risk and should be protected with VZV immunoglobulin. Breast-feeding can then continue, provided there are no lesions on or near the nipple. (link) bacterial infections almost never transmit disease through breast milk

-

-

K. Maternal medications:absolutely contraindicated: chemotherapeutic agents

radioactive drugs

-

relatively contraindicated: lithium

citalopram cyclosporin

Most psychoactive medications are now generally considered safe, although dosage needs to be considered. Infants should always be carefully monitored for effects of sedation when their mother's are using psychoactive drugs. Be aware that drug companies are very cautious in their recommendation of safety for the breastfed infant. Preferably consult specific reference texts or drug advisory services experienced in lactation.

24

L. Drugs of addiction:Methadone passes in small quantities into breast milk and generally the benefits of breast milk overcome the disadvantages. In situations of very high maternal dosage (e90mg daily) the infant is at risk of sedation. Buprenorphine is a long acting narcotic agonist and antagonist used to replace methadone in opiate addicts. Little information is available regarding the pharmacology of this drug in lactation. Sedative effects are of concern. Marijuana passes into breast milk and the relative dose is concentrated. Infants are at risk of sedation, feeding difficulties and poor weight gain.

M. Herbal preparations:Scientific data is limited. Given the variability in standards of preparation of herbal supplements it is recommended that breastfeeding mothers avoid such products.

N. Jaundice (see also Jaundice in the first two weeks of life):Increased rates of initiating breastfeeding have resulted in an increased incidence of jaundice. There is an inverse correlation between the number of breastfeeds per day and level of jaundice. Increasing the number of breastfeeds per day from 6 to 12 per day for each of the first 3 days of life results in significantly lower serum bilirubin on day 3. Increased number of feeds is associated with significantly greater daily milk intake, better elimination of meconium and thereby reduced entero-hepatic circulation. Commencement of phototherapy should be seen as an opportunity to review breastfeeding frequency and technique. It is not carte blanche to introduce supplemental formula feeds. Preferably mothers will be encouraged to express after feeding and top-up their babies with their own milk rather than formula. Excessive use of formula runs the risk of reducing milk supply, as the infant is less stimulated to empty the breast.

O. Drugs in pregnancy and/or lactation: Medications and Mother's Milk. T Hale. 10th edition, 2002. Pharmasoft publishing, Texas. Drugs in Pregnancy and Lactation. Briggs G et al. 6th edition 2002. Lippincott Williams and Wilkins.

Q. References: J Akre. Infant Feeding: the physiological basis. WHO 1994. Bulletin (Suppl.) 67:25 J Akre. Infant Feeding Guidelines for Health Workers. 1996. NHMRC Sosa R, Barness L. Bacterial growth in Refrigerated Human Milk. Am J Dis Child. 1987: 141; 111-112 Whitelaw A. Kangaroo baby care: just a nice experience or an important advance for preterm infants? Pediatrics 1990; 85: 604-605 Ehrenkranz RA et al. Metoclopramide effect on faltering milk production by mothers of premature infants. Pediatrics. 1986;78:614-20. Da Silva et al. Effect of Domperidone on milk production in mothers of premature newborns: a randomised, double-blind, placebo controlled trial. CMAJ. 2001; 164: 17-21. Blaymore Bier JA et al. Breastfeeding infants who were extremely low birth weight. Pediatrics 1997;100:E3 Lang S. Breastfeeding Special Care Babies. 1997. Bailliere Tindall. London. Schanler RJ, Hurst NM, Lau C. The use of human milk and breastfeeding in premature infants. Clin Perinatol. 1999;26:379 - 398 El-Mohandes AE et al. Use of human milk in the intensive care nursery decreases the incidence of nosocomial sepsis. J Perinatol. 1997;17:130 - 134 Lucas A, Cole TJ. Breast milk and necrotising enterocolitis. Lancet. 1990; 336: 1519-1523 Lucas A, Morely R, Cole TJ et al. Breastmilk and subsequent intelligence quotient in children born preterm. Lancet. 1992; 339:261-264 K Simmer. Choice of formula and human milk supplement for preterm infants in Australia. J Paediatr Child Health. 2000;36:593-595. Ruff. Infection and breastmilk. Semin Perinatol. Howard CR, Lawrence RA. Drugs and breastfeeding. Clin Perinatol. 1999;26: 447 - 478 Maisels MJ, Gifford K. Normal serum bilirubin levels in the newborn and the effect of breastfeeding. Pediatrics. 1986;78:837-843 De Carvalho M, et al. Frequency of breastfeeding and serum bilirubin concentration. Am Dis Child 1982;136:747-748 Clinical Aspects of Human Milk and Lactation. Clin Perinatol June 1999;26:2

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9. BRONCHOPULMONARY DYSPLASIAA. B. C. D. E. F. G. H. I. J. K.Summary Introduction Risk Factors Clinical Features Management of BPD in Level 3 Units Respiratory Criteria for Transfer to a Level 2 Hospital Management in the Level 2 SCN Oxygen Home oxygen Follow up References

A. Summary:the most severely affected babies are the most premature, particularly 23-26 week gestation babies diuretics and corticosteroids are effective in achieving short-term improvement in the status of ventilator dependant babies. Safety issues of steroid use are unresolved. There is no place for long term therapy with diuretics in level 2 SCN's there is no consensus on how to wean oxygen in babies with BPD the transition from a tertiary hospital nursery to a level 2 SCN is a difficult time for parents as they adjust to different staff and practices

B. Introduction:In line with the recommendations from a recent workshop in North America the term bronchopulmonary dysplasia (BPD) will be used in this chapter rather than Chronic Lung Disease. The definition is complicated, however in this chapter BPD refers to a premature baby who has been in oxygen for > 28 days. BPD is the single most important factor determining length of stay in babies born at less than 29 weeks. The most severely affected babies are the most premature, particularly 23 - 26 week gestation babies.

C. Risk Factors:prematurity peripartum inflammation/infection associated with preterm labour and/or clinical or subclinical chorioamnionitis postnatal lung Injury due to volutrauma, oxygen or infection

D. Clinical Features:Tertiary unit babies with BPD (actual or evolving) fall into three broad groups:

-

babies dependant on endotracheal mechanical ventilation (MV) babies dependant of Nasal CPAP babies who are oxygen dependant, usually by nasal prongs

The most common clinical scenario is the 23 - 26 week gestation baby who, over a period of 4 - 10 weeks, progresses from MV, NCPAP through to requiring supplementary oxygen. These babies are usually transferred to a level 2 Special Care Nursery (SCN) for ongoing care. Although some of these babies spend many weeks on NCPAP it is common to see rapid improvement in their respiratory stability once weaned from NCPAP. Respiratory stability off NCPAP is the single most important criterion that determines suitability for transfer to a SCN. It is important to understand the tertiary unit's experience with babies at these gestations as it has a significant impact on decision making with respect to transfer to level 2 SCNs. Issues include:

-

all tertiary units experience late deaths of extremely premature babies due to chronic lung disease when prolonged MVis needed there are often many weeks before one can reassure the family with confidence that the baby is likely to survive. Once a baby is showing consistent growth associated with an oxygen requirement less than 40% the recovery process is likely to be successful some babies cope for many months on NCPAP in high (more than 40%) oxygen concentrations before dying. Fortunately this group is rare

These factors make the care of babies with BPD extremely demanding for babies and their families, as well as for nursing, medical and ancillary staff.

26

E. Management of BPD in Level 3 Units:1. Respiratory support:

-

-

-

there is an intense focus on minimizing ventilator associated lung injury from the moment a baby is placed on a ventilator. Synchronised modes of MV with close monitoring of tidal volumes are key features of current practice. In addition there is a more liberal approach to carbon dioxide control, allowing CO2 to rise into the 50's and 60's providing the pH remains better than 7.25 oxygen damages delicate lung tissue as well as the immature retina. Pulse oximetry targets are typically setx etween 88 to 93% in the first weeks after birth endotracheal ventilation is being increasingly replaced by NCPAP, even for the tiniest babies while it is clear that the aggressive early use of NCPAP can avoid the need for endotracheal intubation and MV in babies who in the past would have been electively intubated, it is not yet clear what the effects of this practice are on survival and short and long term morbidity. Randomised trials are in progress to determine best practice in this area babies who require endotracheal ventilation are aggressively weaned and extubated to NCPAP often within 1-2 days of birth

2. Drug Therapy for established/evolving BPD:

-

Corticosteroids:

dexamethasone is effective in achieving short-term improvement in the status of ventilator dependant babies there is now low level evidence showing that dexamethasone in the first week of life is associated with an increased risk of cerebral palsy in survivors safety of corticosteroids used later in the course of evolving BPD between 14 - 28 days is unresolved. RCT's are in progress frequency of the use of steroids for BPD in NICUs has dramatically declined in the past 2 years it is recommended that corticosteroids be used only within the context of a RCT. Otherwise a "low" dose regimen (eg 0.15 - 0.25mg/kg/day) weaned and ceased over a 7 - 10 day period is recommended typical clinical scenarios where steroids would be considered are a baby > 2 weeks of age who is unable to be weaned from endotracheal MV there is no place for the use of steroids in the treatment of BPD outside a tertiary neonatal unit early use of inhaled steroids is ineffective in preventing BPD

-

Diuretics:

insufficient studies of suitable size reporting on important outcomes exist to strongly support the use of diuretics for the treatment of BPD diuretics are an effective short term therapy for ventilated babies There is no evidence for efficacy in non ventilated babies therefore diuretic therapy should be weaned and ceased once babies are stable off mechanical ventilation typical combinations include hydrochlorothiazide and spironolactone chronic frusemide administration is generally avoided, as it has been associated with the development of nephrocalcinosis and hyperchloremic metabolic alkalosis NaCl and KCl supplementation are commonly required there is no place for long term therapy with diuretics in level 2 SCN's

3. Nutrition:

-

provision of adequate calories in a nutritionally appropriate form is critical caloric requirements of babies with moderate to severe lung disease can be as high as 130 - 150 calories/kg/day babies are modestly fluid restricted (150 - 160mL/kg/day) and fed fortified breast milk or low birthweight formula growth is closely monitored and caloric intake titrated against growth Vitamin A supplementation has a statistically significant benefit in reducing oxygen requirements at 36 weeks corrected gestational age however most consider this effect to be clinically insignificant babies sufficiently stable to transfer to a level 2 unit should not require a caloric density of > 24 cal/30mls

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4. Oxygen Therapy:

-

-

oxygen is the one constant in the treatment of BPD but it has been poorly studied once weaned from NCPAP, oxygen is delivered by nasal prongs using low flow (86% for 30 minutes the test should be repeated in 48 hours. If a second test is satisfactory the baby is eligible for discharge on home oxygen on respiratory grounds. In other words the baby has demonstrated a reasonable level of respiratory reserve

J. Follow up: These babies require term follow up throughout childhood There is an increased pulmonary morbidity in the first 2 years of life. Parents should be counselled about this morbidity and ways to minimise it. Influenza vaccine is not officially recommended for these babies RSV prophylaxis is not routinely recommended

K. References:Jobe A, Bancalari E. Bronchopulmonary Dysplasia, NICHD/NHLBI/ORD Workshop Summary. Am J Respir Crit Care Med. 163 1723-1729, 2001 Barrington KJ and Finer NN. Treatment of Bronchopulmonary Dysplasia - A Review. Clinics in Perinatology 25 1 March 1998 177-202 Brion L et al. Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Cochrane Neonatal group, Cochrane database of systematic reviews, Issue 3, 2001. Shah V, Ohlsson A, Hallidah HL, Dunn MS. Early administration of inhaled corticosteroids for prevention of chronic lung disease in ventilated VLBW preterm neonates. Cochrane Neonatal group, Cochrane database of systematic reviews, Issue 3, 2001. Halliday HL and Ehrenkranz RA. Early postnatal corticosteroids for the prevention of chronic lung disease in preterm babies. Cochrane Neonatal group, Cochrane database of systematic reviews, Issue 3, 2001. Chronic Lung Disease. Department of Neonatal Medicine Protocol Book, Royal Prince Alfred Hospital, Sydney, NSW. www.cs.nsw.gov.au/rpa/neonatal Oxygen Therapy. Department of Neonatal Medicine Protocol Book, Royal Prince Alfred Hospital, Sydney, NSW. www.cs.nsw.gov.au/rpa/neonatal

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10. CHICKENPOX (VARICELLA ZOSTER)A. Introduction B. Fetal exposure to Varicella Zoster Virus 1. Management 2. Areas of Uncertainty in Practice C. Infant of a mother with perinatal chickenpox 1. Management 2. Areas of Uncertainty in Practice D. Postnatal exposure to VZV (up to 28 days) 1. Management E. Reference

A. Introduction:The Varicella-zoster virus is a herpes virus causing chickenpox as the primary infection or herpes zoster after reactivation from its latent form in dorsal root ganglia.

B. Fetal exposure to Varicella Zoster Virus:Fetal varicella due to primary infection with chickenpox in pregnancy is usually benign Congenital varicella syndrome (CVS) is thought to result from in utero viral reactivation or disseminated zoster infection

Risk is higher when maternal chickenpox occurs before 20 weeks and is estimated at approximately 2%. CVS is associated with:

-

cicatricial skin lesions limb hypoplasia or paresis microcephaly (secondary to cortical atrophy) ophthalmic lesions (chorioretinitis, microphthalmia, atrophy and cataracts)

1. Management:give ZIG (6mL IMI) within 72 hours of significant exposure to the pregnant woman if sero-negative or if there is a negative history and sero-testing is unavailable continue monitoring, including with ultrasound, since ZIG reduces the clinical attack rate in the pregnant woman but may not eliminate fetal risk negative amniotic fluid PCR correlates well with a good outcome but positive PCR correlates poorly with congenital varicella syndrome development

2. Areas of Uncertainty in Practice:

-

termination of pregnancy would not usually be offered but may require discussion

C. Infant of a mother with perinatal chickenpox:When maternal chickenpox develops within 7 days and up to 28 days after delivery the newborn is at risk of developing severe neonatal varicella (reported mortality rates of up to 30%) since the newborn will not have any passive immunity.

1. Management:

-

give the infant ZIG (2mL IMI) as soon as possible after delivery or onset of maternal illness. ZIG must be given within 72 hours while in hospital, a mother and/or infant with lesions should be isolated from other patients. A mother with lesions does not need to be isolated from her own infant continue to encourage breastfeeding unless lesions are on or near the nipple admit infant into hospital isolation room if rash develops give IV aciclovir (20mg/kg every 8hours) to infants who develop chickenpox and:

did not receive ZIG prophylaxis within 24 hours are immunocompromised are premature (less than 28weeks gestation at birth)

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2. Areas of Uncertainty in Practice:

-

The high risk period for severe infection varies between authorities. These conservative recommendations follow the published Australian guidelines

D. Postnatal exposure to VZV (up to 28 days):Chickenpox is a common childhood illness so the commonest situation is of a sibling developing chickenpox. The risk to the infant relates to whether transplacental transfer of maternal antibody has occurred. Significant exposure includes face to face contact for more than 5 minutes, or contact for more than an hour with a person who has uncrusted lesions or develops them within the next 48 hours.

1. Management:

-

give ZIG (2mL IMI) immediately if: mother is seronegative her sero-status cannot be determined and history is negative infant born at less than 28weeks gestation or 2.6mmol/L are obtained. infants with blood glucose < 2.6 mmol/L should have hourly blood glucose determinations until stable >2.6mmol/L. large normally grown and nourished premature infants who can be fed early after birth generally will only require screening before the first two 3 hourly feeds. Other at risk infants require continued screening before every second feed until 24 hours of age. congenital adrenal hyperplasia can present with hypoglycaemia. Failure to investigate and promptly treat these cases of ambiguous genitalia can be disastrous if > 20 mg/kg/min of IV glucose is required for normoglycaemia in the first few days, or if > 12 mg/kg/min is required after that age, initiate diagnostic steps for hyperinsulinism. When the true blood sugar is < 2.0mmol/L, test urine for ketones and send venous or arterial blood for:

glucose insulin growth hormone cortisol free fatty acids

E. Prevention:If able to take enteral feeds, commence by 1-2 hours of age. Feed frequently either 2 hourly or 3 hourly if risk is low. Use full strength formula at 60 mL/kg initially, increase to 90 mL/kg by 24 hours according to tolerance. If only able to have IV fluid, commence 10% dextrose at 60-90mls/kg/24 hours (4-6 mg/kg/min of glucose). If fluid restriction is required increase the concentration of dextrose in the infusion.

F. Management:Oral Feeds. If a hypoglycaemic infant is able to tolerate enteral feed, this should be given and the blood glucose determined an hour later and before next feed. IV Glucose. If the infant is unable to tolerate enteral feeds or if there is no response to the above measure:

- An IV bolus of 200-300 mg/kg glucose (2-3 ml/kg of 10% dextrose) This is followed by a continuous IV infusion of 10% dextrose at 120 mL/kg/d (8 mg/kg/min glucose) to prevent rebound hypoglycaemia. If fluid restriction is necessary, give more concentrated dextrose solution (up to 15% with peripheral IV). IV infusion of solutions with >12.5% dextrose are best given through a central line in order to aviod complications. - Once the blood glucose normalises, enteral feeds can be reintroduced and the infusion tailed off. - Prescription to make up a 50mL solution of various dextrose infusions 70

Infusion Concentration 12.5% 15.0% 17.5% 20.0%

Volume of 10%Dextrose 46.5mL 44.0mL 40.5mL 37.5mL

Volume of 50%Dextrose 3.5mL 6.0mL 9.5mL 12.5mL

Glucagon. In infants with adequate glycogen stores (e.g. hyperinsulinaemic states) whose hypoglycaemia persists in spite of an IV infusion: An IM statim injection of glucagon 0.3 mg/kg (0.3 u/kg). This may be repeated once only if there is good initial response.

-

If hypoglycaemia recurs or persists despite IV infusion of 15% dextrose at 120ml/kg/d (12mg/kg/min glucose), an IV glucagon infusion should be considered (1-2 mg/kg/d) while arrangements are made to transfer the infant to a Level 3 centre for continued treatment.

Other Treatments. Corticosteroids (eg Hydrocortisone, 5-10mg/kg/24hours IM/IV, or Dexamethasone) are required rarely in severe hypoglycaemia to raise blood glucose levels. The use of diazoxide and pancreatic surgery is extremely rare, but may need to be considered in profound intractable hypoglycaemia secondary to hyperinsulinism. The cause of hypoglycaemia (e.g. hypothermia, sepsis) must also be treated.

G. Areas Of Uncertainty In Clinical Practice: - In the 1960s neonatal hypoglycaemia was diagnosed only in symptomatic infants with two true bloodglucose level 30weeks gestation). Infants awaiting transfer to a higher dependency unit or with specialised problems (eg bowel obstruction with vomiting) should have fluid management as indicated for their specific condition or as discussed with an appropriate specialist. The goal of treatment is to maintain hydration and avoid biochemical disturbances, particularly hypoglycaemia and hyponatraemia.

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B. Fluid Infused:Fluid Volume ml/hr 0-24hrs 25-48hrs 49-72hrs >72hrs Bwt x 2.5 Bwt x 2.5 Bwt x 3 Bwt x 4 ml/kg/d 60 60 72 96 10% Dextrose 10% Dextrose 10% Dextrose + NaCl + KCl* 10% Dextrose + NaCl + KCl* Fluid Infused

* Ordered as 10% Dextrose 500 ml & 6.5 mL 20% NaC1 &10 mL 7.5% KCl (giving 22 mmol NaCl and 10 mmol KCl per 500mL)

C. Investigations:0-24hrs 25-48hrs 49-72hrs 73-96hrs >96hrs Check BSL: If1mL/kg/hr) before adding electrolytes Check Na, K if still nil po Consider transfer to a level 3 centre for Parenteral Nutrition if still nil by mouth

D. Introducing enteral feeding:Consider change in clinical condition e.g. resolution of respiratory distress, conscious state. - For term infants Halve IV infusion rate. Offer sucking feeds on demand or at least 4th hourly. After two or three sucked feeds IV access may be bunged off and feeding performance assessed. If intravenous access is not required as a route for medications the cannula should be removed as soon as possible. While the bunged off line is in place flush short extension tubing every 6 hours with 0.5mL 0.9% Sodium Chloride (ordered on the infants medication sheet). Check at least 6 hourly for signs of phlebitis/extravasation and integrity of cannula and extension set.

-

For infants 90 mL/kg/d enteral intake achieved. Thereafter enteral intake is gradually increased to 150 mL/kg/d total.

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E. Inputs ( while nil po):Volume mL/kg/d 0-24hrs 25-48hrs 49-72hrs >72hrs 60 60 72 96 Glucose mg/kg/min 4 4 5 6.6 Na mmol/kg/d 3 4 K mmol/kg/d 1.5 2 Energy KJ/kg/d 100 100 125 160 KCal/kg/d 24 24 30 38

38. INTUBATIONA. B. C. D. E. F. G. H. I.Summary Introduction Equipment Monitoring Endotracheal Tube Size and Length Procedure Confirmation of tube position Areas of Uncertainty in Clinical Practice References

A. Summary:in an emergency oral intubation is the route of choice if unfamiliar with technique of intubation use bag and mask until adequate help arrives. The majority of infants can be managed with bag and mask ventilation muscle relaxants are contraindicated in situations known to be associated with difficult intubation (e.g. Pierre Robin sequence) or when the operator is inexperienced with these medications the commonest reason for the clinical condition not to improve after intubation is because either the oesophagus or the right main bronchus has been intubated

B. Introduction: Endotracheal (ET) intubation is an important procedure in the care of the newborn. C. Equipment:laryngoscope -Handle: Penlon miniature with hook-on fitting blades: 00, 0 (Premature), 1 (Neonatal) introducer (in sterile package) for oral intubation, it must be inserted to 1cm less than the length of the ET tube magills forceps for use during nasotracheal intubation endotracheal tubes: Portex Paediatric, Sizes 2.5, 3.0 and 3.5mm connectors to fit between ET tubes and ventilation bag and circuit, Neopuff or mechanical ventilator tapes for securing ET tubes - Sleek "trousers", Leukoplast or Elastoplast, tie skin prep swabs cotton buds Tinc. Benzoin Co. (optional)

D. Monitoring:During an acute cardiorespiratory arrest or in the delivery room monitoring may not be achievable. In controlled situations, before commencing intubation, place infant under radiant warmer, obtain IV access, attach cardiorespiratory and oxygen saturation monitors and record full baseline observations.

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E. Endotracheal Tube Size and Length:Most babies 38weeks) a 3.5 ID tube.

Baby Weight (kg) 340 mmol/L and likely to exceed that concentration for any length of time and due to haemolysis (for non-haemolytic jaundice, see the Tables)

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-

In preterm or sick infants, lower concentrations of bilirubin may warrant exchange transfusion since exchange transfusions are rarely performed today, especially outside level-III centres, it is advisable that any baby who requires an exchange transfusion be transferred to a level-III centre. It is preferable that the blood is cross-matched prior to transfer so that the baby can be exchanged as soon as possible after arrival

After an exchange transfusion subsequent monitoring of the haemoglobin is necessary because ongoing haemolysis may result in significant anaemia, and the baby may need a top-up simple blood transfusion.

G. Tables:1. Management of non-pathologic jaundice in healthy term infants:For healthy term babies, phototherapy and exchange transfusion can be provided as recommended in the AAP Guidelines (published in Pediatrics 94:558-565, Oct. 1994).

Age (hrs)

Consider Phototherapy

Phototherapy

Exchange Transfusion if Intensive Phototherapy Fails SBR (m mol/L) --> 340 > 430 > 430

Exchange Transfusion and Intensive Phototherapy SBR (m mol/L) --> 430 > 510 > 510

SBR (m mol/L) 72 hours --> 200 > 260 > 290

SBR (m mol/L) --> 260 > 310 > 340

2. Management of jaundice in preterm infants:Phototherapy:

Age

Wt 70 > 120 > 155 > 170

Wt > 2000g SBR (m mol/L) > 85 > 140 > 200 > 240

< 24 hours 24 - 48 hours 49 - 72 hours > 72 hoursExchange Transfusion:

High risk*: all Others: > 70 > 85 > 120 > 140

Age

Wt 255 > 270 > 290

Wt >2000g SBR (m mol/L) > 270 - 310 > 270 - 310 > 290 - 320 > 310 - 340

< 24 hours 24 - 48 hours 49 - 72 hours > 72 hours

> 170 - 255 > 170 - 255 > 170 - 255 > 255

For high risk* premature infants: use lower end of range and weight, next lower weight category, and next lower age category in that order. Use total bilirubin as the exchange criteria unless direct bilirubin is at least 40 mmol/L, then subtract direct from total.

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40. LISTERIA MONOCYTOGENES INFECTIONA. B. C. D. E.Introduction Clinical Manifestations Investigation Treatment References

A. Introduction:Listeria Monocytogenes is a short Gram-positive rod. Transmission to humans occurs via food, especially dairy products contaminated by infected farm animals. In United States, occurrence rates are 13/100,000 live births. It is less common in Australia. The mortality of neonatal listeriosis is about 5-15%. This infection is classified as a notifable disease.

B. Clinical Manifestations:Transplacental infection:

Causes a non-specific influenzal or gastroenteritic illness in pregnant women, during which the organism may infect the fetus either by spread across placenta or through amniotic fluid. First and second trimester infection may cause fetal death. Later in pregnancy infection may precipitate preterm labour with foetal distress and meconium staining of the liquor. Since meconium staining of the liquor is rare below 34 weeks, its presence should raise suspicion of listeriosis. Characteristically, small (2-3mm) pinkish-grey cutaneous granulomas are present and, at autopsy, similar small granulomatous lesions are widespread in the liver, lungs, CNS and many other tissues and organs.

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Early-onset infection:

60% of infants infected intrapartum are preterm and become ill within 24 hours of birth. Most have disseminated infection with pneumonia, meningitis, thrombocytopenia, anaemia and sometimes conjunctivitis. Both blood and stool should be cultured. Most cases are sporadic, but epidemics are described.

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Late-onset infection:

Usually presents as meningitis, probably due to nosocomial infection. Median age of onset is about 2 weeks.

C. Investigation:Gram stain can be variable and the organism slow growing.

D. Treatment: Penicillin or ampicillin and gentamicin. Listeria is resistant to all third generation cephalosporins.

E. References: Feigh, R. D., and Cherry, J. D. Textbook of pediatric Infectious Diseases (3rd Ed.). Philadelphia: Saunders, 1992. Stoll, B. J.Weisman, L.E. Infections in perinatology. Clin. Perinatol. 24:1, 1997.

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41. MECONIUM ASPIRATION SYNDROMEA. B. C. D. E. F. G. H.Summary Introduction MAS Pathogenesis Clinical Features Complications Differential Diagnosis Management References

A. Summary: - MAS is characterised by early onset of respiratory distress and hypoxaemia in a meconiumstained term infant - most babies with MAS require nothing more than oxygen therapy and general supportive care; oxygen shouldbe used liberally in this condition ventilator support should be instituted where there is refractory hypoxaemia or respiratory acidosis

B. Introduction:Meconium aspiration syndrome (MAS) is an important cause of respiratory distress in the term infant, with a local incidence of around 1.5 in 1000 live births. The prelude to MAS is the passage of meconium at or prior to delivery, a circumstance encountered in 10-20% of all deliveries at term, and more frequently beyond term. Meconiumstained amniotic fluid is rarely seen at preterm delivery; its presence raises the possibility of fetal infection (particularly Listeria).

C. MAS Pathogenesis:In an infant born through MSAF, the risk and severity of MAS is influenced by: - the severity of concurrent asphyxia - the degree of contamination of the amniotic fluid with meconium - the presence of meconium in the airways (nasopharynx, trachea) at delivery Of these, asphyxia is the single most important risk factor for MAS, and is presumed to relate to the influx of MSAF into the lung during hypoxic fetal gasping. MAS can occur, however, in meconium-stained infants that are in good condition at birth. The perinatal events leading to the inhalation of meconium are outlined in Fig 1.

Figure 1. The pathogenesis of MAS (modified from ref 1)

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Once in the lung, meconium quickly migrates down the tracheobronchial tree, inducing a complex lung disease that includes large and small airway obstruction, chemical pneumonitis, proteinaceous alveolar oedema, and surfactant dysfunction (Fig 1). The resultant impairment of gas exchange is often severe, and manifests as hypoxaemia with or without hypercarbia. Persistent pulmonary hypertension with right to left ductal and foramen ovale shunt frequently compounds the oxygenation difficulty.

D. Clinical Features:MAS is characterized by early onset of respiratory distress (within 2 hours) in a meconium-stained infant. Tachypnoea, cyanosis and variable hyperinflation are the main clinical findings. Ausculation reveals widespread "wet" inspiratory crackles, occasionally with expiratory noises suggesting ball-valve airway obstruction. Radiologically the typical progression is from global atelectasis in early X-rays to a widespread patchy opacification accompanied by areas of hyperinflation and/or atelectasis. Blood gas analysis invariably shows hypoxaemia, accompanied by hypercarbia in those infants with significant airway obstruction or severe respiratory failure.

E. Complications: - persistent pulmonary hypertension - air leak pneumomediastinum, pneumothorax , cystic lung disease - pulmonary haemorrhage - complications of asphyxia encephalopathy, seizures, oliguria, coagulopathy and thrombocytopenia F. Differential Diagnosis: - birth asphyxia with pulmonary hypertension and/or haemorrhagic pulmonary oedema - transient tachypnoea of the newborn - surfactant deficiency (especially after elective Caesarean delivery) - sepsis/pneumonia - pneumothorax - congenital diaphragmatic hernia G. Management:1. Delivery room management of the infant born through MSAF:This should consist of airway suctioning (oropharyngeal tracheal) followed by respiratory support (oxygen positive pressure ventilation)

2. Management of the infant with established MAS:2.1. Respiratory care: 2.1.1. Oxygen: It cannot be over-emphasised that administration of oxygen is critically important in infants with MAS, and in many infants is the only respiratory therapy needed. The pulmonary vasculature in the term infant is exquisitely sensitive to oxygen tension, and failure to overcome hypoxaemia almost inevitably will lead to progressive pulmonary hypertension. Oxygen should be administered early and liberally in any baby suspected of having inhaled meconium. The suggested target range for oxygen saturation is 94-98%; target PaO2 60 90 mm Hg. Oxygen toxicity is not an important consideration in the term infant. 2.1.2. Nasal CPAP: Consider as an interim measure in infants with MAS where there is moderate respiratory distress and hypoxaemia. 2.1.3. Intubation and positive pressure ventilation: Indications: Persistent hypoxaemia (SaO2 < 90%, PaO2 < 50) in 100% oxygen Respiratory acidosis with pH < 7.20 Method: Other than in the delivery room, term infants with MAS require deep sedation and preferably muscle relaxation prior to intubation. Infants with MAS are frequently very difficult to manage once intubated, and often require high peak inspiratory pressures (30 35 cm H2O) to achieve gas exchange. Most evidence favours a high positive endexpiratory pressure (6-8 cm H2O), and a long expiratory time. The latter can be achieved using ventilator rates of 40 60 breaths per minute, with an inspiratory time of 0.5 0.6 secs. Particularly where there is concomitant pulmonary hypertension, deep sedation should be maintained after intubation, and muscle relaxation should be continued if the disease is severe. 2.1.4. Surfactant therapy: Available evidence does not suggest a consistent benefit from bolus surfactant therapy in MAS; many infants show no response, and some acutely deteriorate. Lung lavage using surfactant is currently being investigated in MAS, but cannot yet be recommended as a therapy for this disease. Supportive therapy for pulmonary hypertension

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2.2. Suctioning: All infants with MAS should have the stomach contents evacuated, and an in-dwelling nasogastric tube inserted. In those intubated, the trachea should be suctioned by small volume saline lavage if there is clinical evidence of build-up of meconium or secretions in the large airways. 2.3. General supportive care:

cardiovascular support volume and inotrope therapy fluid restriction antibiotic therapy should be continued until primary bacterial infection is excluded IV therapy and nil orally until the respiratory distress is resolving

H. References:Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues. Pediatr Clin North Am 1993; 40: 955-81.

42. MECONIUM STAINED LIQUOUR, DELIVERY ROOM MANAGEMENTA. B. C. D.Introduction Management Areas of Uncertainty in Clinical Practice References

A. Introduction:Meconium staining of the liquor complicates approximately 15% of live births. Meconium aspiration syndrome (MAS) may complicate up to 5% of births through meconium stained liquor. MAS carries a significant respiratory morbidity and may be fatal.

B. Management: - At both vaginal and operative deliveries perform thorough suctioning of the mouth and pharynx afterdelivery of the head and before delivery of the shoulders. Guide the catheter into the posterior pharynx via a finger inserted into the infants mouth. Use a size 12Fr catheter set at 100mmHg. Repeat the procedure until no further meconium is obtained. Transfer the infant to the resuscitation area and assess infant vigour. A vigorous infant has: good muscle tone active breathing efforts HR>100BPM IF VIGOROUS - provide standard care (see guidelines for resuscitation) IF NOT VIGOROUS when the operator present is able to perform intubation: place infant under radiant warmer while avoiding stimulation insert laryngoscope suction mouth and pharynx with 12 or 14 Fr catheter (set at 100 mmHg) insert either 3.0 or 3.5 ET into trachea, attach meconium aspirator, apply suction while withdrawing ET or pass suction catheter directly through the vocal cords and apply suction while gradually withdrawing catheter repeat until either little meconium is recovered or HR 3 mmol/L), the differential diagnosis is as follows:

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Severe organ dysfunction leading to decrease tissue perfusion/oxygen delivery, or increased metabolic demand: perinatal asphyxia congenital heart disease (duct-dependent lesions) sepsis untreated seizures Primary lactic acidosis: disorders of pyruvate metabolism mitochondrial disorders Secondary lactic acidoses - other metabolic diseases may be associated with lactic acidosis, for example: fatty acid oxidation defects organic acidoses urea cycle defects sulphite oxidase deficiency)

D. Hypoglycaemia:Low blood glucose in a neonate most usually indicates either:

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glycogen depletion inadequate gluconeongenesis eg premature or SGA infant hyperinsulinism eg infant of a diabetic mother, Beckwith syndrome occasionally hypoglycaemia will be a manifestation of a metabolic disease eg fatty acid oxidation defect, glycogen storage disease

E. Cardiac disease:Cardiac failure and cardiomyopathy can occur in association with mitochondrial, lysosomal or fatty acid oxidation disorders.

F. Liver dysfunction:Persistent hyperbilirubinaemia (conjugated unconjugated) may be indicative of a metabolic disease, in particular galactosaemia, but also hypothyroidism, tyrosinaemia, a1-antitrypsin deficiency, and others.

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G. Dysmorphism:Metabolic diseases associated with dysmorphic features include:

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peroxisomal disorders (Zellweger syndrome and others) disturbances of energy metabolism (eg pyruvate dehydrogenase deficiency) defects in cholesterol biosynthesis (eg Smith-Lemli-Opitz syndrome) storage disorders

H. Fetal hydrops:A number of metabolic diseases, all individually rare, can cause fetal hydrops.

I. Approach To The Diagnosis Of Metabolic Disease:History and clinical information:Perinatal information that should be sought includes: - a history of previous pregnancy losses - consanguinity - any problems during the pregnancy Detailed clinical examination should be performed, focussing in particular on the cardiorespiratory and neurological status of the infant, supplemented by imaging and metabolic testing as appropriate.

"Screening tests" for metabolic disease:

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odour of baby and urine (but most babies with malodorous urine do not have metabolic disease) blood glucose serum ammonia acid-base status anion gap ([Na+ + K+] - [Cl- + HCO3-], normal < 12 mmol) lactate - arterial sample liver function tests urinary reducing substances (Clinitest). Remember that glucose is a reducing substance, so if the Clinitest is positive, check the urine specifically for glucose using a glucose oxidase strip urinary ketones urine metabolic screen. A sample of 5-10 mL of freshly-collected urine is needed for this test; the sample can be frozen prior to analysis if necessary. As much clinical information as possible should be included on the request card to assist in the interpretation of the results

In only a few cases will the results of the above "screening" tests pinpoint the exact metabolic defect. They will, however, identify infants with a high likelihood of having a metabolic disease, in whom further tests would be performed as appropriate. The details of these tests is beyond the scope of this work, see reference 2 for details.

J. Initial Management Of Suspected Metabolic Disease:If a metabolic disease is suspected, it is highly recommended that the case be discussed with a physician conversant with the management of metabolic disease in the neonate. Where the index of suspicion is high, or the infant is significantly unwell, transfer to a tertiary centre should be arranged, with interim treatment measures commenced as outlined below.

General measures:Infants with metabolic disease frequently require vigorous supportive measures to stabilise their physiological state. Examples of commonly encountered problems, and the appropriate responses are: - profound encephalopathy or apnoea - mechanical ventilation - circulatory failure - intravascular volume expansion, inotrope therapy - seizures- anticonvulsant therapy

Specific therapy:In addition to general supportive measures, in some cases specific treatment should be instituted as soon as a metabolic disease is recognised. Examples of the reponse in specific situations are:

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any case where metabolic disease appears likely - cease oral feeds and administer 10% dextrose electrolytes (milk is the source of toxic metabolites in many metabolic diseases). Give dextrose at an infusion rate of at least 5 mg/kg/min (=3 mL/kg/hr of 10% dextrose). Many metabolic diseases are aggravated by tissue catabolism; a higher rate of dextrose infusion may be required beyond 24 hours

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hyperammonaemia - sodium benzoate (250 mg/kg loading dose over 1-2 h