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Blood pressure - hypertension in neonates

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Definition

Hypertension is defined as elevation in systolic blood pressure in a neonate which is ≥95th percentile for age, weight and gender on 3 separate occasions1,2. This is a statistical definition. Clinically we are likely to investigate and / or treat hypertension only if the blood pressure is persistently ≥99th percentile. Other factors such as pain control etc. need to be taken into consideration before commencing investigation.

Normal blood pressure (BP) in neonates

BP in neonates (preterm and term) admitted to NICU varies with gestational age, chronological age, post-conceptual age (corrected gestation), and birth weight. Hence it is difficult to define normal BP and hypertension in neonates.

  • On day 1, systolic and diastolic BP correlates strongly with gestational age and birth weight
  • BP decreases within first 3 hours of life and then spontaneously increases by 0.2 mm Hg/hour (mean BP) over the first 24 hours3. BP continues to rise rapidly in the first 1 or 2 weeks before the rate of rise slows down (see below)4.
  • The primary determinant of BP is the post-conceptual age4
  • BP in healthy term infants have a different pattern and is not discussed here. Again, the primary determinant here is the post-conceptual age. Refer to table below for BP values from beyond 2 weeks of age in infants from 26 to 44 weeks postconceptional age5. For normal BP values on day 1 of life and subsequently, see the figure and table below4.

Epidemiology

By definition, 5% of neonates will have hypertension, but the reported incidence in infants admitted to neonatal units ranges from 0.2-3.0%5. Hypertension is unusual in otherwise healthy term infants and routine BP measurement is not advocated. Hypertension is much more common in infants with BPD, PDA or those with indwelling UACs, with up to 9% developing hypertension5. Other risk factors for hypertension are antenatal steroids, maternal hypertension, and postnatal ARF6.

The gold standard for blood pressure measurement is an appropriately calibrated intra-arterial catheter. Both umbilical and radial arterial blood pressure correlate with aortic blood pressures7. However, for babies who do not have or require invasive monitoring, the most frequently used technique is via an oscillometric manometer (e.g Dinamap). Blood pressure should be taken preferably in right upper arm, when babies are quietly awake and not feeding (systolic BP is 5mmHg lower in sleeping babies and is higher after a feed) with an appropriate sized cuff8. The cuff bladder should measure 2/3rd of the length of the extremity, and 0.44 to 0.55 of the arm circumference8. If the choice is difficult, err on the side of choosing a larger as compared to a smaller cuff. After cuff placement, infant is left undisturbed for 15 minutes. 3 successive BP readings are obtained at 2-min intervals.

Table 1. Estimated BP values in well infants > 2 weeks of age from 26 - 44 weeks postconceptional age5

Postconceptional age 50th percentile 95th percentile 99th percentile
44 weeks SBP
DBP
MAP
88
50
63
 105
68
80
 110
73
85
42 weeks SBP
DBP
MAP
85
50
62
98
65
76
 102
70
81
40 weeks SBP
DBP
MAP
80
50
60
95
65
75
 100
70
80
38 weeks SBP
DBP
MAP
77
50
60
92
65
75 
 100
70
80
36 weeks SBP
DBP
MAP
72
50
60
87
65
72
92
70
71
34 weeks SBP
DBP
MAP
70
40
50
85
55
65
90
60
70
32 weeks SBP
DBP
MAP
68
40
48
83
55
62
88
60
69
30 weeks SBP
DBP
MAP
65
40
48
80
55
65
85
60
68
28 weeks SBP
DBP
MAP
60
38
45
75
50
58
80
54
63
26 weeks SBP
DBP
MAP
55
30
38
72
50
57
77
56
63

Figure 1. Systolic and diastolic blood pressures (Mean and 95% confidence intervals) on Day1 at various gestational ages4

Blood pressure graph

Causes of Neonatal Hypertension

Renal

• Renal artery thrombosis (particularly if a UAC has been in place)
• Renal vein thrombosis
• Renal artery stenosis or compression (e.g. from tumour, post tight abdominal wall closure)
• Parenchymal renal disease - congenital (ARPKD and ADPKD) or acquired (ATN from inadequate perfusion e.g. sepsis, asphyxia)
• Renal hypoplasia
• Severely obstructed urinary tract
• Idiopathic arterial calcification
• Congenital rubella syndrome
• Haemolytic uraemic syndrome
• VLBW babies - low renal mass / impaired nephrogenesis / nephrocalcinosis

Cardiovascular

• Coarctation of the aorta
• Interrupted aortic arch
• Distal aortic thrombosis (particularly if a UAC has been in place)
• Fluid overload

Endocrine

• Congenital Adrenal Hyperplasia
• Hyperaldosteronism
• Hyperthyroidism
• Adrenal haemorrhage
• Hypercalcaemia

Chronic Lung Disease

• May manifest late after discharge from NICU

Medications

• Dexamethasone
• Adrenergic agents
• Bronchodilators
• Caffeine
• Neonatal TPN through salt and water overload or hypercalcaemia

Neurological

• Pain
• Seizures
• Intracranial hypertension
• Drug Withdrawal
• HIE

Miscellaneous / multifactorial

• ECMO

Investigations

First Line Investigations

  • Repeat your clinical examination
    -  Are there any abdominal masses? Can you feel the kidneys? Are the genitalia normal (CAH)?
    -  Feel the pulses! Are the femoral pulses the same as the brachial pulses?
           - Are the fontanelle and sutures normal?
           - Review UAC position
           - Review medications
  • 4-limb blood pressures
    (Note: Dinamap BP can be normal in the lower limbs in a baby with coarctation)
  • Electrolytes, urea, and creatinine
  • Urinalysis - protein, creatinine, microalbumin
  • Renal and aortic ultrasound scan with dopplers (mention hypertension on the request form)
  • Chest radiograph (if cardiac murmur or signs of congestive cardiac failure)

Second (and Third) Line Investigations (when clinical picture is suggestive)

  • Echocardiogram to exclude coarctation or interrupted aortic arch.
    Also useful to assess cardiovascular function and complications in long-standing or severe hypertension
  • Plasma renin activity
    Renin levels are higher in newborn infants than in older children and adults and an elevated PRA may not indicate underlying renal disease. Renin levels might be falsely elevated by medications such as caffeine
  • Plasma cortisol, aldosterone, or thyroxine (as indicated)
  • Urine VMA/HVA
  • Cranial ultrasound or MRI if any suspicion of an intracranial cause
  • Renal radionucleotide study
  • Renal angiography may be required for ongoing suspicion of renovascular disease

Treatment

  • Removal of any iatrogenic cause
  • Treatment of underlying cause - e.g. cardiac, endocrine etc.
  • Antihypertensive treatment should be commenced after discussion with the on-call neonatologist. Some commonly used medications and their doses are listed in the table below5,9
Class Drug Recommended Dose Comments Reference
Alpha / Beta -
adrenergic  antagonists 
Labetolol
Oral
  Doses from one month of  age 
1 - 2 mg/kg three to four times a day 
Ref 9
But doses are  from
1 month of age
 
Labetolol
IV 
  IV Hypertensive emergencies
 
500 micrograms/kg/hour  adjusted at intervals of at  least 15 minutes, according to response; to a maximum  of 4 mg/kg/hour 
 Ref 9,10
Beta-adrenergic antagonists Propranolol
Oral 
  250 micrograms/kg three  times daily, increasing if  necessary to a maximum of  2 mg/kg three times daily    Ref 9
Calcium channel blockers  Amlodipine
Oral 
  Doses from one month of age
100 - 200 micrograms/kg  once daily  increasing if necessary at  intervals of 1-2 weeks up to  400 micrograms/kg  once daily.   
Ref 9 
Vasodilators   Hydralazine
Oral 
  250 -500 micrograms/kg  every 8 - 12 hours, increase
as necessary to a maximum  of 2 - 3 mg/kg every 8 hours   
Ref 9,10 
Hydralazine
IV 
  IV Slow IV Injection
100 - 500 micrograms/kg  every 4 - 6 hours,  as necessary.
Maximum of 
3 mg/kg daily.
Continuous IV Infusion
preferred route for cardiac patients
12.5 - 50 micrograms/kg/hour.  Maximum 2 mg/kg daily. 
Ref 9
Ref 10
states that IV labetalol
is more effective
in the initial urgent
control of acute
hypertensive crisis 
  •  Acute severe hypertension (>99th centile) - avoid too rapid fall in BP in order to avoid cerebral ischemia and haemorrhage. Useful drugs for IV infusion are nicardipine, esmolol, labetalol and nitroprusside. Treatment should be monitored via an indwelling arterial line or frequent (every 10-15 min) oscillometric measurements. Intermittent IV administration of hydralazine or labetalol may be an alternative.
  • Less severe hypertension (or chronic therapy after control of acute severe hypertension) is with oral treatment using isradipine, amlodipine, hydralazine, minoxidil, propranolol or captopril.
      - Avoid beta-blockers in babies with chronic lung disease
      - Nifedipine should be avoided as effect is unpredictable
      - Captopril might cause an exaggerated fall in BP and impair nephrogenesis and use is best avoided until 44 weeks corrected gestation
  • Consider discussing with either a paediatric nephrologist or a paediatric cardiologist (depending on underlying cause).

References

  1. Watkinson M. Hypertension in the newborn baby. Archives of Disease in Childhood Fetal and Neonatal Edition. 2002;86(2):F78-F81.
  2. National High Blood Pressure Education Program Working Group on High Blood Pressure in C, Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl 4th Report):555-76.
  3. Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, et al. Evolving blood pressure dynamics for extremely preterm infants. J Perinatol. 2014;34(4):301-5.
  4. Zubrow AB, Hulman S, Kushner H, Falkner B. Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia Neonatal Blood Pressure Study Group. Journal of perinatology: official journal of the California Perinatal Association. 1994;15(6):470-9.
  5. Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatric nephrology. 2012;27(1):17-32
  6. Seliem WA, Falk MC, Shadbolt B, Kent AL. Antenatal and postnatal risk factors for neonatal hypertension and infant follow-up. Pediatr Nephrol. 2007;22(12):2081-7.
  7. Gevers M, Hack WW, Ree EF, Lafeber HN, Westerhof N. Calculated mean arterial blood pressure in critically ill neonates. Basic Res Cardiol. 1993;88(1):80-5.
  8. Flynn J. Etiology, clinical features and diagnosis of neonatal hypertension. 2014 [cited 2015, March 29th.]. Available from: http://www.uptodate.com/contents/etiology-clinical-features-and-diagnosis-of-neonatal-hypertension.
  9. New Zealand Formulary for Children. http://www.nzfchildren.org.nz/
  10. Neonatal Formulary 6: Drug Use in Pregnancy and the First Year of Life (ed. Hey). http://onlinelibrary.wiley.com/book/10.1002/9781444329773

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Document Control

  • Date last published: 25 January 2016
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Author(s): Newborn Services Clinical Practice Committee
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse