Download PaedCh 19_Prematurity RN_4C_ March 2017

PAEDIATRIC HOSPITAL LEVEL ESSENTIAL MEDICINES LIST
CHAPTER 19: PREMATURITY AND NEONATAL CONDITIONS
NEMLC 2 MARCH 2017
Addition of Ballard scoring as appendix
The Paediatric Committee recommended that the assessment of gestational age should be performed.
The Committee recommended that it should be included, as dosing of certain medications are based on
gestational age. The Ballard Scoring assessment will be added as an appendix, and a referral the this
from the prematurity chapter will be added.
New sections added:
The following two sections were added with cross references to other chapters for details:
 19.20 Prevention of Mother to Child Transmission (PMTCT) - with a referral to the HIV Infections
Chapter.
 19.21 Retinopathy of Prematurity - with a referral to the Eye Conditions Chapter.
THE FOLLOWING TEXT WAS ADDED:
19.20 PREVENTION OF MOTHER TO CHILD TRANSMISSION (PMTCT)
Z20.60
See Chapter 9 HIV Infection, section 9.1.1 The HIV Exposed Infant.
19.21 RETINOPATHY OF PREMATURITY
H35.1
See Chapter 16 Eye Conditions, Section 16.8 Retinopathy of Prematurity (ROP).
MEDICINE AMENDMENTS
SECTION
MEDICINE
19.1 Apnoea, Neonatal
Medicine
Doxapram, IV
19.2 Cyanotic Heart Disease in the Newborn
Alprostadil
Prostaglandin Therapy
Dinoprostone
ADDED/DELETED/NOT ADDED
Removed
Amended to be initiated under
specialist consultation
Amended to be initiated under
specialist consultation
19.3 Enterocolitis, Nectotising
Medicine Treatment
Amoxicillin
Gentamicin
Gentamicin
Duration amended
Duration amended
Therapeutic Drug Monitoring
PaedCh19_Prematurity _ 4N_March 2017
added
19.5 Heart Failure in Neonates
Medicine Treatment
Digoxin
Removed
19.8.1 Hypoxia/Ischaemia of the newborn (Perinatal hypoxia/hypoxic-ischaemic encephalopathy)
Ampicillin
Added
Medicine Treatment - Antibiotics
Gentamicin
Added
Medicine Treatment - Seizure
Phenobarbitone, oral
Added
control
19.9.2 Hyperbilitubinaemia, conjugated
Product, dose, frequency and
Medicine Treatment
Multivitamin
duration specified
19.10 Jaundie, Neonatal, Prolonged
Product, dose, frequency and
Medicine Treatment
Multivitamin
duration specified
19.12 Patent Ductus Arteriosus (PDA) in the newborn
Specified that confirmed cases
Medicine Treatment
General
are to be treated in
consultation with a specialist
19.14 Respiratory Distress in the Newborn
Medicine Treatment - Metabolic
Removed
Sodium Bicarbonate 4%
acidosis, suspected
Gentamicin
Duration amended
Medicine Treatment - Infection
Ampicillin
Duration amended
19.15 Resuscitation of the Newborn
Newborn resuscitation
Updated algorithm added
Algorithm
algorithm
19.16 Seizures, Neonatal
Medicine Treatment
Phenobarbitone, oral
Added
19.17 Septicaemia of the Newborn
Medicine treatment - Empiric
Cefotaxime
Removed
treatment
Ampicillin
Added
Piperacillin/Tazobactam
Added
Medicine Treatment deteriorating child
Amikacin
Added
19.19 Tetanus, Neonatal
Medicine treatment
All medicine treatment
Removed
19.1 Prematurity and Neonatal Conditions
Doxapram: Removed
A Cochrane review evaluating the effect of doxapram on apnoea and the use of intermittent positive
airways pressure (IPPV) in preterm infants with recurrent apnoea concluded that doxapram may reduce
apnoea in the first 48 hours of treatment, however this was non-significant (RR 0.45, 95% CI 0.2 to 1.05).
PaedCh19_Prematurity _ 4N_March 2017
The primary outcome of severity of apnoea was measured by failed treatment, apnoea frequency, use of
IPPV or mortality. In addition there was insufficient data on long-term outcomes and adverse effects.1
Additionally intravenous doxapram and intravenous methylxanthines were shown to be similar for the
short term treatment of apnoea in preterm infants.2
The Paediatric Committee recommended that doxapram should be deleted, as there is no difference
when compared to methylxanthines.
The text was amended as follows:
If central apnoea is unresponsive to therapeutic doses of caffeine or aminophyline:

Doxapram, IV, 2 mg/kg/hour by continuous infusion.
Level of evidence: I Cochrane
19.2 Cyanotic Heart Disease in the Newborn
Alprostadil: Amended to be initiated under specialist consultation
Dinoprostone: Amended to be initiated under specialist consultation
All patients with cyanotic heart disease in the newborn would need to be referred, however treatment
would need to be started prior to referral. The Paediatric Committee recommended that this be
emphasised, and the initiation of treatment be done under specialist consultation.
The text was amended as follows:
Referral is needed in all patients.
Prior to referral:
To keep ductus arteriosus open if a duct dependent cyanotic heart lesion is suspected:
 Prostaglandin therapy, i.e.:
 Alprostadil, IV, 0.05–0.1 mcg/kg/minute, initial dose. (under specialist consultation)
o
Maintenance dose : 0.01–0.1 mcg/kg/minute.
OR
 Dinoprostone, via naso/orogastric tube. (under specialist consultation)
o For babies < 2.5 kg: 0.125 mg 1–2 hourly (1/4 tablet suspended in 2 mL sterile water), or 50
mcg/kg/dose 1–2 hourly.
o For babies > 2.5 kg: 0.25 mg hourly (½ tablet suspended in 2 mL water).
Continue with prostaglandin therapy until corrective or palliative surgery can be done or until patency of
the duct is not deemed essential for survival of the infant.
Babies on prostaglandin therapy: inspiratory oxygen not more than 40 %. If ductal dependant lesion
suspected maintain oxygen saturation just above 75%
1
Henderson-Smart DJ, Steer PA. Doxapram treatment for apnea in preterm infants (review). The Cochrane Collaboration. The
Cochrane Library. 2009.
2 Henderson-Smart DJ, Steer PA. Doxapram versus methylxanthine for apnea in preterm infants (review). The Cochrane
Collaboration. The Cochrane Library. 2000; 4.
PaedCh19_Prematurity _ 4N_March 2017
19.3 Enterocolitis, Necrotising
Ampicillin: Duration amended
Gentamicin: Duration amended
Most sources recommended an antibiotic regimen consisting of an aminoglycoside plus a penicillin as
first line empiric therapy, and then amended depending on what is cultured/suspected or based on unit
pathogen profiles. 3, 4, 5, 6 It was outlined that each unit should have empiric antibiotic treatment
guidelines tailored to the most common nosocomial infections found in the neonatal intensive care unit
(NICU).
The majority of the NICUs using the Standard Treatment Guideline recommendations, however, may not
be aware of their own susceptibility patterns. In the majority of units, e-coli and klebsiella would the
most likely isolates. In South Africa, ithe vast majority of e-coli and klebsiella isolates may be penicillin
resistant.
The
Paediatric
Committee
recommended
that
the
empiric
therapy
of
ampicillin/gentamicin/metronidazole should be retained as recommended regimen, and sent out for
comment. The Committee additionally recommended that text be added indicating that the empiric
regimen should be amended based on local susceptibility patterns. The duration of therapy was aligned
with other guidelines, and therapeutic drug monitoring recommendations were added for gentamicin.7
The text was amended as follows:
Empiric antibiotic therapy
Ampicillin, IV, 50 mg/kg/dose for 10 7days.
o If age < 7 days:
50 mg/kg 12 hourly.
o If 7 days – 3 weeks of age:
50 mg/kg 8 hourly.
o If > 3 weeks of age:
50 mg/kg 6 hourly.
3
Fox, T. and Godavitarne, C. (2012). What Really Causes Necrotising Enterocolitis?. ISRN Gastroenterology, 2012,
pp.1-9.
4
Necrotizing Enterocolitis Risk. (2012). Advances in Neonatal Care, 12(2), pp.88-89.
Springer, S. and Annibale, D. (2016). Necrotizing Enterocolitis: Practice Essentials, Background, Etiology.[online]
Emedicine.medscape.com. Available at: http://emedicine.medscape.com/article/977956-overview [Accessed 10
Oct. 2016].Sydney Local Health District. (2016). Necrotising Enterocolitis. [online] Available at:
http://www.slhd.nsw.gov.au/rpa/neonatal%5Ccontent/pdf/guidelines/nec.pdf [Accessed 10 Oct. 2016].
5
Wójkowska-Mach, J., Różańska, A., Borszewska-Kornacka, M., Domańska, J., Gadzinowski, J., Gulczyńska, E.,
Helwich, E., Kordek, A., Pawlik, D., Szczapa, J. and Heczko, P. (2014). Necrotising Enterocolitis in Preterm Infants:
Epidemiology and Antibiotic Consumption in the Polish Neonatology Network Neonatal Intensive Care Units in
2009. PLoS ONE, 9(3), p.e92865.
6 Zvizdic, Z., Heljic, S., Firdus, A., Jonuzi, A. and Zvizdic, D. (2014). Relationship of Nosocomial Infections with the
Development of Necrotizing Enterocolitis in Preterm Infants. Materia Socio Medica, 26(1), p.4.
7 Division of Clinical Pharmacology. University of Cape Town. South African Medicines Formulary. 12th Edition.
2016.
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PLUS
 Gentamicin, IV, 6 mg/kg once daily for 107 days.
Where available, gentamicin doses should be adjusted on the basis of therapeutic drug levels.
 Trough levels (taken immediately prior to next dose), target plasma level < 1 mg/L.
 Peak levels (measured 1 hour after commencement of IV infusion or IM/IV bolus dose), target
plasma level > 8 mg/L.
PLUS
Metronidazole, IV, for 7 days.
o
Loading dose: 15 mg/kg over 60 minutes.
o
Post natal age < 4 weeks: 7.5 mg/kg/dose 12 hourly.
o
Postnatal age ≥ 4 weeks: 7.5 mg/kg/dose 8 hourly.
Reassess choice of antibiotics when the culture and sensitivity results become available.
Units to adjust regimen according to local susceptibility patterns and suspicion of nosocomial infection.
Where possible in accordance with a microbiologist or infectious diseases specialist.
19.5 Heart failure in neonates
Digoxin: Removed
The Canadian Cardiovascular Society Guidelines for Heart Failure in children indicate that in the adult
setting there is some evidence of acute haemodynamic benefit for patient with congestive heart failure.
In children however, digoxin has not been reported to result in improved contractility or improved
clinical symptoms, and there is no data supporting the use of digoxin children with structurally normal
hearts and systolic dysfunction.8
The Clinical Practice Guidelines from the European Journal of Paediatrics indicates that institutional
practice has been to avoid the use of digoxin except in situations where ventricular rate control is
required. 9
The Committee recommended since digoxin is not safe and no efficacy benefit has been demonstrated
in children, it should be removed.
The following text was deleted:
Digoxin
Consider in consultation with paediatrician or cardiologist
Monitor digoxin blood levels and ECG.
Digoxin is contraindicated in bradycardia, heart block, cardiac tamponade or hypertrophic
cardiomyopathy.
8
Kantor PF, et. al. Presentation, diagnosis, and medical management of heart failure in children: Canadian
Cardiovascular Society Guidelines. Canadian Journal of Cardiology. 2013, 29: 1535-1552.
9
Kantor PF, et. al. Clinical Practice: Heart failure in children. Part II: current therapy and new therapeutic
approaches. European Journal Pediatrics. 2010. 169: 403-410.
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
Digoxin, oral, 0.01 mg/kg/dose 8 hourly for 3 doses, then:
o Maintenance: oral, 0.005 mg/kg/dose for as long as needed to control heart failure:
For infants < 37 weeks gestational age: 24 hourly.
For infants ≥ 37 weeks gestational age: 12 hourly.
When oral route is contraindicated:

Digoxin, IV, 75% of oral dose. .
Level of Evidence: III- Guidelines.
19.8.1 Hypoxia/ischaemia of the newborn (perinatal hypoxia/hypoxic-ischaemic
encephalopathy)
Ampicillin: Added
Gentamicin: Added
Cefotaxime: Removed
No evidence could be found with the use of specifically third generation cephalosporins for first line
therapy in cerebral hypoxia/ischaemia.
It was proposed that the empiric antimicrobial cover of penicillin and gentamicin be used. The
Paediatric Committee discussed that gentamicin may not be favourable due to the concomitant renal
injury as a result of renal ischaemia. It was discussed that gentamicin for short-term use would have
minimal renal injury.
A study evaluating the aminoglycoside toxicity in neonates showed that the trough levels are higher in
younger neonates, however the older the neonate gets the lower the trough level becomes.10
The Paediatric Committee proposed that the treatment be brought in line with the general empiric
therapy recommendations for early onset sepsis of ampicillin and gentamicin; if no renal dysfunction is
present. This Chapter will still be sent for comment, and thus can be addressed again if comment is
received.
The text was amended as follows:
If infection is suspected or confirmed:
Treat as follows (if no renal dysfunction is present):
 Cefotaxime, IV, 50 mg/kg/dose.
o 12 hourly for first 7 post natal days and 8 hourly thereafter.
o If infection is excluded, antibiotics can be stopped in 72 hours.
10
Engler D, et. al. A pilot study on the use of amikacin in neonates: who should be monitored for ototoxicity?
Southern African Journal of Infectious Diseases. 2015; 1(1):1-5.
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Ampicillin, IV, 50 mg/kg/dose.
o If age < 7 days:
50 mg/kg 12 hourly.
o If 7 days – 3 weeks of age:
50 mg/kg 8 hourly.
o If > 3 weeks of age:
50 mg/kg 6 hourly.
PLUS
 Gentamicin, IV, 6 mg/kg once daily.
Where available, gentamicin doses should be adjusted on the basis of therapeutic drug levels.
 Trough levels (taken immediately prior to next dose), target plasma level < 1 mg/L.

Peak levels (measured 1 hour after commencement of IV infusion or IM/IV bolus dose), target
plasma level > 8 mg/L.
Phenobarbitone, oral: Added
The Paediatric Committee recommended that phenobarbitone maintenance therapy can be given orally.
It was therefore recommended that the phenobarbitone maintenance treatment section be amended to
indicate either intravenous or oral administration.
The text was amended as follows:
Maintenance:
 Phenobarbitone, IV or oral
o 4 mg/kg/day beginning 12–24 hours after the loading dose.
19.9.2 Hyperbilirubinaemia, conjugated
Multivitamin: Product, dose, frequency and duration specified
Fat soluble vitamins (A, D, E and K) were previously recommended, however there was no guidance on
how to administer these vitamins. The Paediatric Committee recommended that it would be more
practical to give a multivitamin. The Committee recommended multivitamins be administered as per
standard recommendations.
The text was amended as follows:
 Fat soluble vitamins (A, D, E and K).
All premature babies, day 15 to 1 year:
Multivitamin, oral, 0.6 mL daily.
19.10 Jaundice, Neonatal , Prolonged
Multivitamin: Product, dose, frequency and duration specified
Fat soluble vitamins (A, D, E and K) were previously recommended, however there was no guidance on
how to administer these vitamins. The Paediatric Committee recommended that it would be more
practical to give a multivitamin. The Committee recommended multivitamins be administered as per
standard recommendations.
PaedCh19_Prematurity _ 4N_March 2017
The text was amended as follows:
 Fat soluble vitamins (A, D, E and K).
All premature babies, day 15 to 1 year:
Multivitamin, oral, 0.6 mL daily.
19.12 Patent Ductus Arteriosus (PDA) in the newborn
General: Specified that confirmed cases are to be treated in consultation with a specialist.
The text was amended as follows:
In confirmed cases (in consultation with specialist)
Cardiac failure
Diuretics
 Furosemide, IV/oral, 1 mg/kg/24 hours.
Closure of PDA in preterm infants less than 14 days of age
 Ibuprofen, oral
First dose: 10 mg/kg. After 24 hours follow with 2 doses of 5 mg/kg 24 hours apart.
Contraindications to ibuprofen therapy:
o Thrombocytopaenia (< 50 000/mm3).
o Bleeding disorders.
o Impaired renal function.
o Jaundice approaching exchange transfusion levels.
SURGICAL TREATMENT
Consider, if medicine treatment is contraindicated or fails.
19.14 Respiratory Distress in the Newborn
Shake test
The shake test is a simple procedure to identify those neonates who will develop respiratory distress
syndrome. 11, 12, 13, 14, 15 There is however no evidence that not using it will cause mortality.
11
Babaei, H., Sadeghi, N. and Rezaei, M. (2013). Comparative study of diagnostic value of gastric aspirate shakes
test & lamellar body count for prediction of lung maturity in premature neonates. SJKU, 18(4), pp.8-17.
12
Bajracharya, S. (2014). Comparison of Reliability of Tap Test and Shake Test for Determination of Fetal Lung
Maturity. Nepal Journal of Obstetrics and Gynaecology, 7(2).
13
Mehrpisheh, S., Mosayebi, Z., Memarian, A., Kadivar, M., Nariman, S., Ostadrahimi, P. and Dalili, H. (2015).
Evaluation of specificity and sensitivity of gastric aspirate shake test to predict surfactant deficiency in Iranian
premature infants. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 5(2),
pp.182-186.
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A study indicated that the gastric aspirate shake test has 100% sensitivity, 82% specificity, a 42.4%
positive predictive value and negative predictive value of 100%. According to this study gastric shake
test (GST) is a reliable test and is a simple procedure to identify those neonates who will develop
respiratory distress syndrome (RDS) and therefore to decide prophylactic exogenous surfactant
replacement. This study however only included 46 cases. 16
The Paediatric Committee recommended that firm guidance should be given for results of the shake
test, such as 'if positive - very low risk of hyaline membrane disease". It was additionally queried
whether this test
The Paediatric Committee recommended that the Shake Test could be used as a gatekeeper for
surfactant use. This can be revisited once the chapter has been sent out for external comment and
feedback.
Sodium bicarbonate 4% (if metabolic acidosis suspected): Removed
The Paediatric Committee outlined that the use of sodium bicarbonate, if metabolic acidosis is
suspected, could be potentially harmful. The Paediatric Committee recommended that sodium
bicarbonate should only be administered if severe metabolic acidosis is suspected where the benefits of
would outweigh the risks.
The text was amended as follows:
Metabolic acidosis
If pH ≤ 7.0 and the metabolic acidosis does not respond to normalisation of PaO2, PaCO2, blood pressure,
volume expansion (hydration) and correction of anaemia:
 Sodium bicarbonate, 4.2 %, IV, administered slowly.
1 mmol = 2 mL
HCO3 needed (mmol) = base excess x 0.3 x body mass (kg)
(½ correct base deficit initially)
If blood gas and acid base analysis is not available and metabolic acidosis is suspected:
Sodium bicarbonate, 4%, slow IV, 2 mL.
14
NooriShadkam, M., Lookzadeh, M., Taghizadeh, M., Golzar, A. and NooriShadkam, Z. (2014). Diagnostic value of
gastric shake test for hyaline membrane disease in preterm infant. Iran J Reprod Med, [online] 12(7), pp.487-491.
Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126253/pdf/ijrm-12-487.pdf [Accessed 11 Oct.
2016].
15
Swarnkar, K. and Swarnkar, M. (2015). PREVALENCE OF HYALINE MEMBRANE DISEASE WITH SPECIAL REFERENCE
TO SIGNIFICANCE OF GASTRIC SHAKE TEST IN PRETERM INFANTS. European Journal of Biomedical and
Pharmaceutical Sciences, [online] 2(5), pp.381-390.
16
Swarnkar, K. and Swarnkar, M. (2015). PREVALENCE OF HYALINE MEMBRANE DISEASE WITH SPECIAL REFERENCE
TO SIGNIFICANCE OF GASTRIC SHAKE TEST IN PRETERM INFANTS. European Journal of Biomedical and
Pharmaceutical Sciences, [online] 2(5), pp.381-390.
PaedCh19_Prematurity _ 4N_March 2017
19.15 Resuscitation of the newborn
Newborn resuscitation algorithm: updated algorithm added
The Paediatric Committee recommended the inclusion of the new algorithm with permission from the
Resuscitation Council of Southern Africa. The previous and new versions were reviewed, with no
fundamental differences noted.
19.16 Seizures, Neonatal
Phenobarbitone, oral: Added
The Paediatric Committee recommended that phenobarbitone maintenance therapy can be given orally.
It was therefore recommended that the phenobarbitone maintenance treatment section be amended to
indicate either intravenous or oral administration.
The text was amended as follows:
Maintenance:
 Phenobarbitone, IV or oral
o 4 mg/kg/day beginning 12–24 hours after the loading dose.
19.17 Septicaemia of the Newborn
Cefotaxine: Removed
Ampicillin: Added
Piperacillin/tazobactam: Added
Amikacin: Added
Guidelines for empiric therapy in neonates with sepsis usually include gentamicin over cefotaxime based
regimens due to the lower levels of susceptibility to cefotaxime, and the need ot avoid exerting selective
pressure for resistance. 17
The Paediatric Committee recommended added a second line regimen where child is deteriorating on
the first line regimen.
Empiric treatment (first line):
 Aminoglycoside, e.g.:
 Gentamicin, IV, for 10 days.
o If < 32 weeks gestation:
o If ≥ 32 weeks gestation:
5 mg/kg/36 hours in the first week of life.
5 mg/kg/24 hours in the first week of life.
17
Muller-Pebody B, et.al. Empirical treatment of neonatal sepsis: are the current guidelines adequate? ADC Fetal
and Neonatal. Volume 96 (1).
PaedCh19_Prematurity _ 4N_March 2017
o Monitor blood levels.
PLUS
 3rd generation cephalosporin, e.g.:
Cefotaxime, IV, for 10 days.
o If < 7 days of age:
o If ≥ 7 days of age:
50 mg/kg 12 hourly.
50 mg/kg 8 hourly.
Ampicillin, IV, 50 mg/kg/dose for 10 days.
o If age < 7 days:
50 mg/kg 12 hourly.
o If 7 days – 3 weeks of age:
50 mg/kg 8 hourly.
o If > 3 weeks of age:
50 mg/kg 6 hourly.
If child is deteriorating on above regimen and there are no culture positive results:
Empiric treatment (second line):
 Piperacillin/tazobactam, IV for 7 days
o If < 7 days of age: 50 - 100mg/kg 12 hourly (1st week of life)
o If > 7 days of age50-100mg/kg 6-8 hourly
PLUS
 Amikacin, IV for 7 days
o 15mg/kg/dose 24 hourly
(therapeutic drug monitoring to be done where available)
Note: Shorter durations of therapy should be used where there is there is no culture confirmed
infection, and child shows clinical improvement.
PaedCh19_Prematurity _ 4N_March 2017