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 occasions^1,2. 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

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

Causes of Neonatal Hypertension

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 below^5,9

•  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