Neonatal Hypertension 

Newborn / By

Neonatal Hypertension 

Description

  • neonatal hypertension refers to repeated, persistently high blood pressure measurements in infants < 1 year old(1,2)
  • unlike hypertension in children and adolescents, most cases of neonatal hypertension are due to underlying etiology rather than primary (essential) hypertension(1,2)

Also Called

  • neonatal high blood pressure
  • newborn hypertension
  • newborn high blood pressure

Definitions

  • definition of neonatal hypertension is not standardized due to factors that make it difficult to establish normative blood pressure cutoffs for neonates including(1,2,3)
    • limited normative data for term and preterm infants
    • changes in blood pressure that occur in first weeks of life
    • dependence on birth weight, postmenstrual age, and gestational age
  • hypertension is most commonly defined as systolic or diastolic blood pressure persistently elevated > 95th percentile for postmenstrual age(1,2,3)
  • severe hypertension may be defined as systolic or diastolic blood pressure persistently elevated > 99th percentile for postmenstrual age(1)

Epidemiology

Who Is Most Affected

  • infants with current or history of neonatal intensive care unit admission(1,2)

Incidence/Prevalence

  • reported incidence of neonatal hypertension
  • incidence of diagnosed neonatal hypertension reported to be 1.8%, however, incidence may be as high as 5.5% when including undiagnosed cases
    •  based on retrospective cohort study
    • 2,162 neonates requiring intensive care were followed through discharge or 120 days of life
    • hypertension identified as
      • definite when documented clinically or discharged home with antihypertensive medication
      • undiagnosed when identified only by retroactive chart review of documented blood pressure measurements (more than half of all lowest measurements throughout admission > 95th percentile for postconceptual age)
    • 5.5% had hypertension identified as either definite or undiagnosed
      • 7.2% in neonates ≥ 36 weeks gestation
      • 3.9% in neonates 30-35 weeks gestation
      • 5.4% in neonates ≤ 29 weeks gestation
    • incidence of definite vs. undiagnosed hypertension by gestational age category (no p values reported)
      • 1.8% vs. 3.7% in entire cohort
      • 2.3% vs. 5% in neonates ≥ 36 weeks gestation
      • 0.6% vs. 3.2% in neonates 30-35 weeks gestation
      • 4% vs. 1.4% in neonates ≤ 29 weeks gestation
    • Reference – AWAKEN study (Pediatr Res 2018 Aug;84(2):279)

Risk Factors

Perinatal and Neonatal Risk Factors
  • prematurity(1,2,3)
  • prolonged umbilical artery catheterization(1,2,3)
  • prenatal drug exposure(2)
  • clinical exposure to phthalates found in IV and ventilator tubing(3)
  • perinatal asphyxia and coagulopathies each associated with development of renal vein thrombosis and associated hypertension (Front Pediatr 2017;5:136full-text)
  • history of bronchopulmonary dysplasia, treatment with steroids, and patent ductus arteriosus each associated with increased risk of neonatal hypertension
    •  based on retrospective cohort study
    • 4,203 neonates < 28 days old (mean gestational age 31 weeks, mean birth weight 2,197 g) admitted or transferred to tertiary neonatal intensive care unit from 2006 to 2009 were evaluated
    • hypertension defined as
      • 3 separate measurements of systolic or diastolic blood pressure > 95th percentile for postmenstrual age
      • ≥ 1 dose of antihypertensive medication administered during hospitalization
    • 1.3% had hypertension
    • factors associated with increased risk of hypertension
      • bronchopulmonary dysplasia (odds ratio [OR] 4.7, 95% CI 2-11.6)
      • steroid treatment for bronchopulmonary dysplasia (OR 3.6, 95% CI 1.2-9.3)
      • patent ductus arteriosus (OR 3.8, 95% CI 2-7.4)
    • Reference – J Pediatr 2013 Jul;163(1):84full-text
Maternal Risk Factors
  • preeclampsia(3)
  • body mass index > 30(3)
  • increased blood pressure(1,2)
  • smoking(3)
  • lower socioeconomic status(3)
  • pregestational and gestational diabetes each associated with development of renal vein thrombosis and associated hypertension (Front Pediatr 2017;5:136full-text)

Etiology and Pathogenesis

Causes

  • neonatal hypertension is idiopathic in reported 50% of cases(1,2)
  • causes of neonatal hypertension are more likely to be secondary to an underlying condition or exposure rather than primary (essential)(1,2,3)
  • most common causes include chronic lung disease, renal disease, and catheter-associated thromboembolism(1,2)
  • iatrogenic causes are common among neonates treated in neonatal intensive care unit(2)

Table

Table 1: Iatrogenic Causes of Neonatal Hypertension

Medications and ExposuresOther Clinical Causes
Steroids including dexamethasone, prednisolone, and hydrocortisoneIndomethacinVasopressorsMethylxanthines (theophylline and caffeine)Phenylephrine eye dropsBronchodilatorsPancuroniumVitamin D or A toxicityMaternal cocaine or heroin useNeonatal opioid withdrawal syndromeUmbilical artery catheterizationHypercalcemia, fluid overload, or hypernatremia caused by parenteral nutritionPerinatal asphyxiaExtracorporeal membrane oxygenationClosure of abdominal wall defect such as gastroschisis and omphalocele

Citation: Reference – Pediatr Nephrol 2019 Jun;34(6):1009, Pediatr Nephrol 2019 May;34(5):787, Pediatr Rev 2020 Jun;41(6):307.

pathophysiologic causes of neonatal hypertension may include pulmonary, renovascular and renal, neurologic, cardiovascular, endocrine, or oncologic disorders

Table

Table 2: Causes of Neonatal Hypertension by System

SystemCause
RespiratoryBronchopulmonary dysplasiaPneumothorax
RenovascularThromboembolism/microembolism secondary to umbilical artery catheterRenal vein thrombosisNonatherosclerotic artery stenosis (fibromuscular dysplasia)Renal artery compressionIdiopathic arterial calcificationMidaortic syndromeCongenital rubella syndrome
Intrinsic renal diseaseCongenital causesAutosomal dominant polycystic kidney diseaseAutosomal recessive polycystic kidney diseaseMulticystic dysplastic kidney diseaseRenal dysplasiaUnilateral renal hypoplasiaUreteropelvic junction obstructionCongenital nephrotic syndromeAngiotensin-converting enzyme (ACE) inhibitor fetopathyRenal tubular dysgenesisTuberous sclerosisAcquired causesAcute kidney injuryCortical necrosisAcute tubulointerstitial nephritisHemolytic uremic syndromeObstruction due to stones or tumor
NeurologicIntracranial hypertensionPainSeizuresFamilial dysautonomiaSubdural hematoma
EndocrineCongenital adrenal hyperplasiaHyperaldosteronismHyperthyroidismPseudohypoaldosteronism type 2Glucocorticoid-remediable aldosteronismAdrenal hemorrhage
CardiacPatent ductus arteriosusCoarctation of the aortaInterrupted aortic arch
OncologicWilms tumorPheochromocytomaNeuroblastomaMesoblastic nephromaChorioangioma

Citation: Reference – Pediatr Nephrol 2019 Jun;34(6):1009, Pediatr Nephrol 2019 May;34(5):787, Pediatr Rev 2020 Jun;41(6):307.

  • genetic causes of neonatal hypertension
    • specific genes have been identified as monogenic causes of hypertension
      • CYP11B1 (11-beta hydroxylase gene) associated with congenital adrenal hyperplasia type IV
      • CYP11B2 (aldosterone synthase gene) associated with familial hyperaldosteronism type I
      • WNK1, WNK4 (lysine-deficient protein kinase 1 and 4 genes) associated with pseudohypoaldosteronism type 2 (Gordon syndrome)
      • SCNN1B, SCNN1G (gene encoding subunits of amiloride sensitive sodium channel) associated with Liddle syndrome and pseudoaldosteronism
      • CYP17A1 (steroid 17-hydroxylase/17, 20 lyase gene) associated with congenital adrenal hyperplasia type V
      • HSD11B2 (11-beta-hydroxy steroid dehydrogenase 2 gene) associated with syndrome of apparent mineralocorticoid excess
      • KCNJ5 (potassium inwardly rectifying channel gene) associated with familial hyperaldosteronism type III
      • Reference – Eur Heart J 2013 Apr;34(13):951
    • pathogenic variant in ABC-C6 gene may be associated with generalized arterial calcification of infancy presenting as severe systemic hypertension with heart failure (Front Cardiovasc Med 2022;9:1032519full-text)

Pathogenesis

  • in normal physiologic setting, regulation of blood pressure is complex and influenced by many physiologic processes and hormones including
    • neurogenic control
      • vasomotor center including nucleus tractus solitarius in dorsal medulla, rostral part of ventral medulla, and other centers in pons and midbrain
      • arterial baroreceptors that respond to vessel wall distention by increasing afferent impulse activity which decreases efferent sympathetic activity and augments vagal tone and ultimately leads to bradycardia and vasodilation
    • renin-angiotensin system
      • plays important role in control of arterial pressure including sodium balance
      • primary source of renin is juxtaglomerular apparatus of kidney which senses renal perfusion pressure and sodium concentration in distal tubular fluid
      • renin cleaves angiotensin to yield inactive peptide angiotensin I which is converted to angiotensin II by angiotensin-converting enzyme
      • high angiotensin II concentrations suppress renin secretion via a negative feedback loop
      • angiotensin II acts on specific angiotensin receptors causing smooth muscle contraction and release of aldosterone, prostacyclin, and catecholamines
    • atrial natriuretic peptide
      • released from atrial granules in cardiac muscles in response to atrial stretch receptors
      • produces natriuresis, diuresis, and reduced blood pressure
      • decreases plasma renin and aldosterone
    • eicosanoids, such as arachidonic acid metabolites, affect blood pressure through effects on vascular smooth muscle tone and interactions with autonomic nervous system, renin-angiotensin system, and other humoral pathways
    • kallikrein-kinin system
      • tissue kallikreins, such as the vasodilator bradykinin, act on kininogen to form vasoactive peptides
      • kinins are involved in regulating renal blood flow and excretion of water and sodium
    • vascular endothelial cell mechanisms
      • endothelium synthesizes endothelins which are powerful vasoconstrictors
      • endothelium releases nitric oxide which inhibits endothelins and mediates vasodilatation produced by acetylcholine, bradykinin, sodium nitroprusside, and nitrates
    • adrenal steroids, such as mineralocorticoids and glucocorticoids
      • increase blood pressure with effect mediated by sodium and water retention (mineralocorticoid effect) or increased vascular reactivity (glucocorticoid effect)
      • increase vascular tone by upregulating receptors of hormones that raise blood pressure, such as angiotensin II
    • renomedullary vasodepression
      • renomedullary interstitial cells secrete inactive medullipin I which is transformed in the liver into medullipin II
      • medullipin II has prolonged hypotensive effect possibly by vasodilation, inhibition of sympathetic drive in response to hypotension, and diuretic action
    • sodium and water excretion
      • sodium and water retention cause an increase in blood pressure
      • sodium may, via the sodium-calcium exchange mechanism, increase intracellular calcium in vascular smooth muscle which results in increased vascular tone
    • Reference – Cont Ed Anaesthesia Crit Care Pain 2004 Jun;4(3):71
  • physiology of neonatal blood pressure
    • blood pressure at birth is directly related to gestational age and birth weight(1,2,3)
    • blood pressure increases rapidly in first few days of life and then more slowly until age two months when systolic blood pressure levels off and diastolic blood pressure continues with slower rate of rise(1,3)View full sizeTable 3: Neonatal Blood Pressure Rate of Rise Birth to Age 90 DaysAgeChange in Systolic Blood PressureChange in Diastolic Blood PressureBirth – 4 days2.2-2.7 mm Hg/day*1.6-2 mm Hg/day*5-90 days0.25 mm Hg/day0.15 mm Hg/dayCitation: * Daily rates of rise may be higher with decreasing gestational age.Reference -Pediatr Nephrol 2012 Jan;27(1):17
    • normative blood pressure values beyond age 2 weeks are based on postmenstrual age
  • pathophysiology of select causes of neonatal hypertension
    • bronchopulmonary dysplasia
      • pathophysiologic mechanism leading to hypertension is not fully understood, but may be related to
        • hypoxemia causing changes in arterial wall thickness and vasomotor response(2)
        • compensatory increase in systemic blood pressure to maintain pulmonary perfusion in light of pulmonary hypertension(1)
      • medications to treat bronchopulmonary dysplasia may also lead to hypertension including(1)
        • corticosteroids
        • diuretics which may induce nephrocalcinosis
    • renal artery stenosis
      • leads to renal hypoperfusion resulting in decreased glomerular filtration and ischemia
      • renal hypoperfusion activates renin-angiotensin-aldosterone system, leading to
        • increased renin secretion resulting in an increase in angiotensin II; this increase in angiotensin II results in
          • vasoconstriction via sympathetic adrenergic pathways
          • release of aldosterone causing renal sodium reabsorption with subsequent water retention
        • hypertension and associated cardiovascular complications
      • Reference – Med Clin North Am 2017 Jan;101(1):65
    • thromboembolism associated with umbilical artery catheter
      • disruption of vascular endothelium of umbilical artery leads to
      • thrombi propagate or embolize to renal artery where they may be partially or completely occlusive causing renal ischemia or infarction(1)
    • renal vein thrombosis
      • factors that contribute to the development of neonatal renal vein thrombosis include
        • diminished vascular blood flow
        • injury to vascular endothelium as with the use of central venous catheters
        • hypercoagulability secondary to developmental hemostasis
      • propagation of developing thrombosis into renal vein may result in renal congestion and infarction which in turn may result in hypertension
      • References – Curr Pediatr Rev 2014;10(2):101, Front Pediatr 2017;5:136
    • renal artery compression(2)
      • external compression of renal artery leads to release of catecholamines
      • causes of compression include
        • tumor (may also directly release catecholamines)
        • closure of abdominal wall defects (leads to increased intraabdominal pressure)
        • hydronephrosis
        • hematoma
    • parenteral nutrition may cause hypertension via salt or volume overload, or hypercalcemia due to excess intake of vitamin D or A(2)

History and Physical

Clinical Presentation

  • neonates with hypertension are usually asymptomatic and hypertension is detected during routine blood pressure assessment(1,2)
  • nonspecific signs include
    • irritability(2)
    • feeding intolerance(1,2)
    • poor weight gain or failure to thrive(1)
  • clinical presentation of end-organ dysfunction associated with severe hypertension may include signs of
    • left ventricular hypertrophy resulting in heart failure or cardiogenic shock including respiratory distress, tachypnea, and hypoxemia(1,2)
    • neurologic dysfunction including
    • acute kidney injury(1)
    • retinopathy(2)
  • intermittent severely elevated blood pressures may indicate thromboembolism or pheochromocytoma(1)

History

History of Present Illness (HPI)

  • review history for gestational age, birth weight for gestational age, and current postmenstrual age(1,2,3)
  • review current or previous neonatal hospital course for(1,2,3)
    • duration of time in neonatal intensive care
    • interventions such as
      • umbilical artery catheter
      • total parenteral nutrition
      • mechanical ventilation
      • extracorporeal membrane oxygenation
      • closure of abdominal wall defect such as gastroschisis and omphalocele
    • neonatal opioid withdrawal syndrome

Medication History

  • review for use of medications associated with neonatal hypertension including(1,2,3)
    • steroids including dexamethasone, prednisolone, and hydrocortisone
    • indomethacin
    • vasopressors
    • phenylephrine eye drops
    • bronchodilators
    • methylxanthines (theophylline and caffeine)
    • pancuronium
    • vitamin D or A toxicity

Past Medical History (PMH)

  • review prenatal course for
    • prenatal imaging assessing for renal, cardiac, or other congenital anomalies associated with neonatal hypertension(1)
    • prenatal exposures such as(1,2,3)
      • maternal use of cocaine, opiates, or other substances
      • prenatal corticosteroids
    • perinatal events such as birth asphyxia or events that may cause acute kidney injury(1,2,3)
  • review for history of respiratory distress syndrome and subsequent bronchopulmonary dysplasia(1,2)

Physical

Blood Pressure Measurement

Overview
  • measurement of blood pressure with intra-arterial catheter is considered standard of care, however, use is limited because it is an invasive technique that is often reserved for critically ill neonates who require arterial catheterization for other purposes
  • noninvasive measurement with oscillometric devices is more common, however, accuracy is greatly dependent upon technique
    • collect measurements in prone or supine infant who is sleeping or quietly awake and preferably > 1.5 hours past last feeding or clinical manipulation
    • position appropriately sized cuff on right upper extremity and collect 3 measurements separated by 2 minute intervals
    • discard the first measurement if markedly greater than second and third, and record the average
  • measurement via auscultation may be considered to confirm elevated oscillometric measurements in larger infants outside of neonatal intensive care(2)
  • compare blood pressure measurements against most appropriate normative data for postmenstrual or postnatal age to establish diagnosis of hypertension
Intra-arterial Measurement
  • considered standard of care, however, use is limited by invasive technique and associated risks(1,2,3)
  • umbilical artery catheterization is most commonly used method for intra-arterial measurement in neonatal intensive care, particularly in critically-ill preterm neonates requiring arterial catheterization for frequent blood draws and monitoring for hypotension(1)
  • catheterization of radial or posterior tibial arteries can also be used(1,2)
  • inaccuracy may be caused by arterial spasm during catheterization or improper transducer positioning relative to level of heart(1)
  • risks include(1,3)
    • thrombosis
    • catheter-related blood stream infections
    • ischemia
Oscillometric Measurement
  • most common method of assessing blood pressure in neonates given ease of use and noninvasive measurement(1,2,3)
  • measures mean arterial pressure via oscillations of pulsatile blood flow through artery and calculates corresponding systolic and diastolic blood pressures(1)
  • oscillometric measurements reported to correlate with intra-arterial measurements but may be limited in neonates by(1,2)
    • variable correlation with intra-arterial measurements in small-for-gestational age neonates
    • overestimation of both systolic and diastolic blood pressures in sick neonates
    • variation across different brands of devices
    • variability due to patient being awake or engaged in activity such as crying, feeding, or sucking
    • variability due to clinical interventions and physical manipulation
  • adherence to standardized approach to blood pressure measurement will enhance accuracy of results(2,3)
  • suggested technique for measuring blood pressure with oscillometric device(1,2,3)
    • collect measurements while infant is
      • positioned prone or supine
      • sleeping or quietly awake
      • at least 1.5 hours past last feeding or clinical manipulation (if possible)
    • place cuff on right upper arm if possible and wait 15 minutes without disturbing infant
      • cuff size – cuff width to arm circumference ratio of 0.45-0.7 is recommended (usually 2-4 cm)
      • cuff placement
        • measurements collected from right upper arm are recommended
        • measurements collected from the calf may be acceptable during first few days of life or if arm measurements are contraindicated
        • measurements collected from thigh are not recommended
    • collect 3 blood pressure measurements separated by 2 minute intervals
    • discard first measurement if markedly higher than second and third measurements
    • record average of measurements
  • once elevated blood pressure has been confirmed, blood pressure should be measured in all 4 limbs to assess for coarctation of the aorta, although diagnosis can only be ruled out with echocardiogram(1,2)

General Physical

  • assess remaining vital signs for irregular respiratory rate and bradycardia(1)
  • take anthropomorphic measurements(1)
    • measure height and length and head circumference
    • assess growth patterns for failure to thrive
  • assess for edema suggesting fluid or salt overload(1,2)
  • assess for dysmorphic features that suggest genetic syndrome associated with hypertension including(1,2)
    • Williams syndrome, such as
      • widely spaced teeth
      • broad forehead
      • small jaw
      • prominent earlobes
      • full cheeks
      • short nose with full nasal tip
    • Turner syndrome, such as
      • puffy hands and feet
      • excess folds of skin or webs at neck
      • low posterior hairline
      • broad chest with widely spaced nipples

HEENT

  • assess for retinopathy(2)

Cardiac

Lungs

Abdomen

  • assess for
    • presence of umbilical artery catheter(1,2,3)
    • abdominal bruit (Pediatr Rev 2020 Jun;41(6):307)
    • abdominal distention or mass that suggests(2)
      • urinary tract obstruction
      • tumor
      • polycystic kidney disease
    • surgical wounds from closure of abdominal wall defects(1,2)

Neuro

  • assess for(1,2)
    • altered mental status
    • pain
    • irritability
    • lethargy
    • tremors

Genital Exam

  • assess for abnormalities associated with urinary tract abnormalities or congenital adrenal hyperplasia(1)

Diagnosis

Making the Diagnosis

  • diagnose neonatal hypertension if systolic or diastolic blood pressure is persistently > 95th percentile for postmenstrual or postnatal age using most appropriate normative data

Table

Table 4: Normative Blood Pressure Values for Neonates > 2 Weeks Old

Postmenstrual Age50th Percentile95th Percentile99th Percentile
44 weeksSystolic88105110
Diastolic506873
Mean638085
42 weeksSystolic8598102
Diastolic506570
Mean627681
40 weeksSystolic8095100
Diastolic506570
Mean607580
38 weeksSystolic779297
Diastolic506570
Mean597479
36 weeksSystolic728792
Diastolic506570
Mean577271
34 weeksSystolic708590
Diastolic405560
Mean506570
32 weeksSystolic688388
Diastolic405560
Mean486269
30 weeksSystolic658085
Diastolic405560
Mean486568
28 weeksSystolic607580
Diastolic385054
Mean455863
26 weeksSystolic557277
Diastolic305056
Mean385763

Citation: Reference – Pediatr Nephrol 2012 Jan;27(1):17.

for neonates ≤ 2 weeks postnatal age, pooled 95th percentile blood pressure values may be used for diagnosis of neonatal hypertension

Table

Table 5: Pooled 95th Percentile Blood Pressure Values for Neonates ≤ 2 Weeks Old

Gestational AgePostnatal AgeSystolic Blood Pressure (mm Hg)Diastolic Blood Pressure (mm Hg)
22-24 weeksDay 1 of life5532
Day 4 of life5535
Week 16338
Week 27545
25-29 weeksDay 1 of life6035
Day 4 of life6035
Week 16338
Week 27545
30-31 weeksDay 1 of life6238
Day 4 of life6540
Week 17545
Week 28050
32-33 weeksDay 1 of life6542
Day 4 of life7045
Week 17548
Week 28050
34-36 weeksDay 1 of life6545
Day 4 of life7050
Week 18555
Week 29255
≥ 37 weeksDay 1 of life7850
Day 4 of life8855
Week 19060
Week 29060

Citation: Reference – Pediatr Res 2018 Aug;84(2):279.

for infants < 1 year old, the American Academy of Pediatrics recommends the use of blood pressure values found in 1987 National Heart, Lung, and Blood Institute Report of the Second Task Force on Blood Pressure Control in Children (Pediatrics 2017 Sep;140(3):doi:10.1542/peds.2017-1904)

Table

Table 6: Normative Blood Pressure Values for Infants < 1 Year Old

Hypertensive CategorySystolic Blood pressure (mm Hg)Diastolic Blood Pressure (mm Hg)
95th-99th percentile≥ 112≥ 74
> 99th percentile≥ 118≥ 82

Citation: Reference – Pediatrics 1987 Jan;79(1):1.

pooled normative blood pressure values for infants collected via oscillometric devices may be more accurate than those suggested by the AAP measured by Doppler devices(1)

Table

Table 7: Pooled Normative Blood Pressure Values for Infants by Oscillometry

Postnatal AgeSystolic Blood Pressure (mm Hg)Diastolic Blood Pressure (mm Hg)
1 month50th percentile7750
95th percentile8758
6 months50th percentile10263
95th percentile12075

Citation: Reference – Pediatr Nephrol 2019 Jun;34(6):1009.

  • upon diagnosis of persistently elevated blood pressure, perform careful history and physical exam to guide testing and imaging needed to identify underlying cause

Differential Diagnosis

  • differential diagnosis of neonatal hypertension is large and has many potential causes, most of which involve an underlying condition(1,2)
  • other possible causes of elevated blood pressure readings should be assessed such as improper measurement technique(1,2)
  • elevated intra-arterial measurements may be due to arterial spasm or improper transducer placement(1)
  • elevated oscillometric measurements may be due to(1,3)
    • awake and active or crying neonate
    • elevated head position during measurement
    • use of improperly sized cuff

Testing Overview

  • initial evaluation is focused on identifying most common causes of hypertension(1,2)
  • initial evaluation should include
    • blood tests including complete blood count and basic metabolic profile with calcium
    • urine studies including urinalysis and urinary albumin to creatine ratio
    • imaging including renal Doppler ultrasound, chest x-ray, and echocardiogram
  • subsequent evaluations depending upon clinical presentation and results of initial testing may include additional
    • blood tests such as thyroid studies, serum cortisol levels, and plasma renin and aldosterone
    • urine studies such as urinary vanillylmandelic acid (VMA) and homovanillic acid (HMA) concentrations
    • imaging such as renal scintigraphy

Blood Tests

  • initial blood tests include
    • basic metabolic profile with calcium(1,2)
      • serum creatinine and blood urea nitrogen to assess kidney function
      • hyponatremia may suggest renovascular cause of hypertension
      • hypokalemia and metabolic alkalosis may suggest hyperaldosteronism
      • hypercalcemia may result from excessive intake from parenteral nutrition or vitamin A or D toxicity
    • complete blood count with platelets to assess for thrombosis or thrombophilia(1,2)
  • additional blood tests to consider depending upon clinical presentation and results of initial testing may include
    • thyroid studies(1,2)
    • serum cortisol(1,2)
    • plasma renin and aldosterone(1,2)
      • should be considered if patient has hypokalemia and metabolic alkalosis suggestive of monogenic hypertension due to hyperaldosteronism
      • should be obtained prior to the initiation of antihypertensives or other medications that may alter results

Urine Studies

  • initial urine studies include
    • urinalysis to assess for proteinuria and hematuria that suggest intrinsic renal abnormality not detectable by ultrasound(1,2)
    • urinary albumin to creatinine ratio(1)
  • additional urine studies to consider depending upon clinical presentation and results of initial testing may include urinary vanillylmandelic acid (VMA) and homovanillic acid (HMA)(1,2)

Imaging Studies

  • initial imaging tests include
    • renal Doppler ultrasound
      • first-line imaging used to identify genitourinary and adrenal anatomy including renal arteries and veins(1,2)
      • may identify most common congenital and acquired causes of hypertension including(1)
        • congenital anomalies of the kidney or urinary tract (CAKUT)
        • urinary tract obstruction
        • cystic kidney disease
        • arterial or venous thrombosis
        • renal masses
    • chest x-ray to assess heart size(2)
    • echocardiogram
      • should be performed to rule out coarctation of the aorta and aortic thrombus(1,2)
      • may not detect coarctation outside aortic arch; additional chest or abdominal ultrasonography may be required to confirm or exclude diagnosis(1)
  • additional imaging studies to consider depending upon clinical presentation and results of initial testing may include
    • renal angiography
      • considered standard of care in neonates > 3 kg for evaluation of extremely elevated blood pressure presumably due to renovascular causes such as thrombus or renal artery stenosis (Radiol Clin North Am 2003 Sep;41(5):931)
      • use in neonates is limited by
        • need for general anesthesia
        • risk of catheter-induced injury to vasculature
        • radiation exposure
        • possibility that identified thrombus is incidental finding as presence of thrombus correlates poorly with clinical signs and symptoms and is common in neonates with history of umbilical artery catheterization
        • Reference – Radiol Clin North Am 2003 Sep;41(5):931
      • advantages include
        • ability to assess hemodynamic significance of lesion through functional testing such as infusion of epinephrine (Radiol Clin North Am 2003 Sep;41(5):931)
        • greater resolution compared to computed tomography (CT) and magnetic resonance (MR) angiography(2)
      • given procedural risks and limitations in neonates, medical management is suggested until infant is old enough to undergo angiography(2)
    • renal scintigraphy with Tc-99m-dimercaptosuccinic acid (DMSA)
      • for renovascular hypertension, considered standard of care to assess renal parenchymal function before and after angioplasty or surgical intervention
      • may also be used to assess parenchymal function following renal vein thrombosis
      • following injection, DMSA is slowly absorbed by proximal renal tubules with only small amount excreted in urine
      • imaging generally performed 2-4 hours after administration of DMSA
      • use of dynamic scintigraphy with diagnostic administration of an angiotensin-converting enzyme (ACE) inhibitor such as captopril is no longer routinely recommended in the evaluation of renovascular hypertension due to reported poor sensitivity
      • Reference – Br Med Bull 2017 Sep 1;123(1):127
    • CT and MR angiography
      • limited data for use in neonates and infants
      • advantages of CT angiography include
        • speed of image acquisition may reduce need for procedural sedation
        • minimally invasive compared to angiography
      • disadvantages of CT angiography include
        • inability of neonates to hold breath during imaging
        • limited ability to identify lesions of accessory, segmental, or intrarenal arteries which are often involved in neonates with renal artery stenosis
        • higher doses of IV contrast required than used in digital subtraction endovascular arteriography
        • exposure to radiation
      • advantages of MR angiography include lack of exposure to iodinated intravenous contrast and radiation
      • disadvantages of MR angiography include need for sedation, motion artifact, and diagnostic limitations in assessing small renal artery branches
      • Reference – Radiol Clin North Am 2003 Sep;41(5):931
    • head ultrasound can be used to assess for intracranial abnormalities such as hemorrhage or mass(1)
    • voiding cystourethrogram may be indicated for assessing obstructive anomalies of the urinary tract that may result in hypertension, such as uteropelvic junction (UPJ) obstruction(1,2)

Management

Management Overview

  • treatment decisions should be made by neonatologist in consultation with pediatric nephrologist, cardiologist, and pharmacist given complexity of decisions and limited evidence for threshold for initiating pharmacologic intervention, safety, and efficacy(1,2)
  • management of neonatal hypertension may be determined by blood pressure percentile for age and presence of signs of end-organ dysfunction
  • surgery may be needed to treat underlying cause of hypertension in some infants

Initial Management

  • evaluate and treat underlying cause of hypertension prior to initiating antihypertensive medications, if applicable
    • correct fluid overload and electrolyte abnormalities(2)
    • treat pain(2)
    • discontinue or adjust medications associated with hypertension(2)
    • correct hypoxemia in those with bronchopulmonary dysplasia(2)
    • treat intracranial hypertension prior to attempting to reduce systemic hypertension(1)
    • treat endocrine disorders with appropriate hormone replacement(2)
    • measure serum aldosterone and renin levels if underlying cause of hypertension is not yet known as antihypertensive medications may reduce their diagnostic accuracy(1)
  • plan for surgical correction for neonates with operable conditions such as coarctation of aorta and urinary tract obstruction

Antihypertensive Medications

  • CLINICIANS’ PRACTICE POINT: Evidence-based guidelines and recommendations to define the clinical indication, selection, route of administration, and dosing of antihypertensive medications for the management of neonatal hypertension are lacking. The use of antihypertensive medications for neonates is largely guided by clinical expertise.
  • medication is generally indicated for hypertensive neonates with either
  • selection of antihypertensive medication may be directed by severity of hypertension, presence of end-organ dysfunction, and comorbid conditions
    • continuous infusion of IV antihypertensive medication
      • may be considered for severe hypertension, particularly with acute evidence of end-organ dysfunction(1,2)benefits of continuous infusion include ease of titration to effect(2)requires admission to intensive care with continuous monitoring of blood pressure, preferably via intra-arterial catheterization(2)avoid precipitous drop in blood pressure which may decrease cerebral perfusion increasing risk of cerebral hypoxemia, seizures, ischemia, or bleeding(1,2)reduction of blood pressure to < 95th percentile is generally recommended; titrate IV antihypertensive treatment to reduce blood pressure by
        • one-third of targeted reduction during first 6 hours of treatmentadditional one-third of targeted reduction during following 24-36 hours of treatmentfinal one-third of targeted reduction during following 48-72 hours of treatmentReference – Arch Dis Child 2017 Dec;102(12):1176

Table

Table 8: Dosing and Administration of IV Antihypertensives Administered as Continuous Infusion in Management of Severe Neonatal Hypertension*

MedicationDrug ClassSuggested DosingNotes
NicardipineCalcium channel blocker0.5-2 mcg/kg/minute IVAdminister via central line if possibleCaution use in perinatal asphyxiaMay cause mild tachycardia
LabetalolAlpha- and beta-blocker0.25-3 mg/kg/hour IVContraindicated in sinus bradycardia, heart block > first degree, and overt heart failureCaution use in chronic lung diseaseMonitor for phlebitis
EsmololBeta-blockerPNA ≤ 7 days: 50 mcg/kg/minute IV increased by 25-50 mcg/kg/minute every 20 minutes until SBP ≤ 87 mm HgPNA ≥ 8 days: 75 mcg/kg/minute IV increased by 50 mcg/kg/minute every 20 minutes until SBP ≤ 101 mm HgContraindicated in sinus bradycardia, heart block > first degree, and overt heart failureCaution use in chronic lung diseaseMonitor for phlebitis
Sodium nitroprussideVasodilator0.3 mcg/kg/minute IV increased every few minutes to target blood pressure (maximum 10 mcg/kg/minute)Contraindicated in compensatory hypertension due to aortic coarctation or arteriovenous shuntingCaution use in renal or hepatic failure and in neonates < 2 weeks oldMonitor for cyanide toxicity

Citation: * Evidence-based guidelines and recommendations to define the clinical indication, selection, route of administration, and dosing of antihypertensive medications for the management of neonatal hypertension are lacking. The use of antihypertensive medications for neonates is largely guided by clinical expertise.Abbreviations: PNA, postnatal age; SBP, systolic blood pressureReferences – Arch Dis Child 2017 Dec;102(12):1176, Pediatr Nephrol 2019 May;34(5):787, Pediatr Nephrol 2019 Jun;34(6):1009, Merative Micromedex, Neofax Pediatrics (accessed 2024 Jun 6).

intermittent dosing of IV antihypertensive medications

  • may be considered for those with blood pressure < 99th percentile without evidence of end-organ dysfunction who cannot tolerate enteral administration(2)
  • may be used to determine daily antihypertensive medication requirement to allow for transition to oral administration(1)

Table

Table 9: Dosing and Administration of Intermittent IV Antihypertensives in Management of Neonatal Hypertension*

MedicationDrug ClassSuggested DosingNotes
LabetalolAlpha- and beta-blocker0.2-1 mg/kg/dose IV every 10 minutes until effect to maximum total dose of 4 mg/kgContraindicated in sinus bradycardia, heart block > first degree, and overt heart failureCaution use in chronic lung diseaseMonitor for phlebitis
HydralazineVasodilator0.1-0.5 mg/kg/dose IV every 6-8 hours (maximum 2 mg/kg/dose IV every 6 hours)May cause tachycardia, fluid retention, diarrhea, and emesisRarely causes agranulocytosis
EnalaprilatACE inhibitor10 mcg/kg/dose IV every 24 hours; subsequent doses may be titrated based on responseUse extreme caution in neonates with impaired renal functionNot recommended if < 44 weeks PMA due to increased risk of severe hypotension and oliguric AKI and concerns for impaired nephron developmentMonitor potassium and serum creatinine

Citation: * Evidence-based guidelines and recommendations to define the clinical indication, selection, route of administration, and dosing of antihypertensive medications for the management of neonatal hypertension are lacking. The use of antihypertensive medications for neonates is largely guided by clinical expertise.Abbreviations: ACE, angiotensin-converting enzyme.References – Arch Dis Child 2017 Dec;102(12):1176, Pediatr Nephrol 2019 May;34(5):787, Pediatr Nephrol 2019 Jun;34(6):1009, Merative Micromedex, Neofax Pediatrics (accessed 2024 Jun 6).

oral antihypertensive medications

  • should be avoided in severe hypertension and those with end-organ dysfunction due to variable onset and duration of effect, and unpredictable response(2)
  • may be considered in those with less severe hypertension or those with persistent hypertension adequately controlled with IV medications(1,2)
  • calcium channel blockers or vasodilators may be considered first-line options(2)
  • diuretics may be considered for neonates with comorbid bronchopulmonary dysplasia due to additional pulmonary benefits(2)
  • beta-adrenergic blockers should be avoided in neonates with chronic lung disease due to potential to cause bradycardia and bronchospasm(2)
  • angiotensin-converting enzyme (ACE) inhibitors should be avoided until infant reaches age 44 weeks postmenstrual age due to potential for impairment of renal maturation leading to acute kidney injury as well as other side effects, such as prolonged hypotension, ischemia, and seizures(1,2)
  • if initiating antihypertensive treatment in outpatient setting, begin with lowest recommended dose to avoid hypotension(1)

Table

Table 10: Dosing and Administration of Oral Antihypertensives Used in Management of Neonatal Hypertension*

MedicationDrug ClassSuggested DosingNotes
IsradipineCalcium channel blocker0.05-0.15 mg/kg/dose orally every 6-8 hours (maximum 0.8 mg/kg/day)Caution use in congestive heart failureMay cause mild tachycardiaRequires extemporaneous formulation
AmlodipineCalcium channel blocker0.05-0.3 mg/kg/dose orally every 12-24 hours (maximum 0.6 mg/kg/day)May cause feeding intolerance, flushing, reflex tachycardia, hypotension, peripheral edema, and altered liver function testsCaution use with CYP3A4 enzyme-inducing medicationsCommercial solution and suspension available
LabetalolAlpha- and beta-blocker0.5-1.5 mg/kg/dose orally every 8-12 hours (maximum 10 mg/kg/day)Contraindicated in sinus bradycardia, heart block > first degree, and overt heart failureCaution use in chronic lung diseaseRequires extemporaneous formulation
PropranololBeta-blocker0.25-1 mg/kg/dose every 6 hours, increased as needed to maximum 3.5 mg/kg orally every 6 hoursContraindicated in premature neonates with corrected age < 5 weeks and neonates < 2 kg, and in those with sinus bradycardia, heart block > first degree, and overt heart failureMay cause AV block, bradycardia, and hypoglycemiaCommercial solution available
ClonidineCentral alpha agonist0.5-2.5 mcg/kg/dose orally every 6 hoursMay cause sedation, somnolence, and xerostomiaRebound hypertension may occur upon abrupt discontinuationRequires extemporaneous formulation
CaptoprilACE inhibitor0.01 mg/kg/dose orally every 12 hours;incrementally increase dose to 0.1-0.4 mg/kg orally every 6 hours based upon responseNot recommended if < 44 weeks PMA due to increased risk of severe hypotension and oliguric AKI and concerns for impaired nephron developmentCaution additive risk of hypotension with diureticsMonitor potassium and serum creatinineRequires extemporaneous formulation
HydrochlorothiazideDiuretic1-2 mg/kg/dose orally every 12 hours with feedingAvoid use in neonates with significant renal or hepatic impairmentMay cause hyperglycemia, hypokalemia, and other electrolyte disordersMay be second-line or adjunctive therapy for neonates with BPDRequires extemporaneous formulation
SpironolactoneDiuretic1-3 mg/kg/dose orally every 24 hoursContraindicated in neonates with hyperkalemiaMay be considered second-line or adjunctive therapy for neonates with BPDMonitor electrolytesCommercial suspension available

Citation: Abbreviations: ACE, angiotensin-converting enzyme; AKI, acute kidney injury; BPD, bronchopulmonary dysplasia; PMA, postmenstrual age.* Evidence-based guidelines and recommendations to define the clinical indication, selection, route of administration, and dosing of antihypertensive medications for the management of neonatal hypertension are lacking. The use of antihypertensive medications for neonates is largely guided by clinical expertise.Reference -Arch Dis Child 2017 Dec;102(12):1176Pediatr Nephrol 2019 May;34(5):787Pediatr Nephrol 2019 Jun;34(6):1009

Surgery and Procedures

  • surgery may be needed to treat underlying cause of hypertension in a few clinical scenarios(2)
  • corrective surgery may be required for neonates with(2)
    • obstructive abnormalities of the urinary tract
    • coarctation of aorta
  • neonates with suspected renovascular hypertension should be managed with medications until old enough to undergo diagnostic and interventional endovascular arteriography(2)
  • unilateral nephrectomy may be indicated in neonates with hypertension unresponsive to medication management secondary to(2)
    • renovascular hypertension
    • multicystic dysplastic kidney disease
  • tumor debulking may be indicated in(2)
    • Wilms tumor
    • nephroblastoma

Follow-Up

  • infants with resolving hypertension may be weaned from antihypertensive medication by either decreasing dose or not adjusting dose for weight as infant grows; blood pressure should be monitored while weaning(2)
  • follow-up with pediatric nephrologist is recommended(1)
  • infants with chronically elevated blood pressure maintained on antihypertensive medications should have(2)
    • blood pressure and renal function monitored at each office visit
    • home blood pressure measurement device to monitor for safety and allow for medication titration between visits
  • conditions associated with prolonged hypertension which will require long-term monitoring include(1,2)
    • renal parenchymal disease
    • polycystic kidney disease
    • renal vein thrombosis with or without vascular repair
    • renal artery stenosis
    • coarctation of aorta following surgical repair
    • genetic causes of hypertension
  • American Academy of Pediatrics recommends measurement of blood pressure at all visits in children < 3 years old with history or suspicion of
    • prematurity, small for gestational age, or very low birth weight
    • other neonatal complication requiring intensive care with umbilical arterial line
    • family history of congenital renal disease
    • urologic malformations
    • known renal disease
    • hematuria or proteinuria
    • congenital heart disease
    • recurrent urinary tract infections
    • solid-organ transplant
    • malignancy or bone marrow transplant
    • other systemic illnesses associated with hypertension such as neurofibromatosis or tuberous sclerosis
    • treatment with drugs known to raise blood pressure
    • evidence of elevated intracranial pressure
    • Reference – Pediatrics 2017 Sep;140(3):doi:10.1542/peds.2017-1904

Complications

  • severe, prolonged hypertension may damage end-organs and result in cardiovascular, neurocognitive, renal, and ocular complications such as
    • left ventricular hypertrophy resulting in heart failure or cardiogenic shock(1,2)
    • acute kidney injury(1)
    • vascular injury (Pediatr Rev 2020 Jun;41(6):307)
    • retinopathy(2)
    • seizure(2)
    • failure to thrive(1)

Prognosis

  • long-term outcomes of neonatal hypertension are poorly understood due to limited long-term studies(1,2)
  • resolution of neonatal hypertension
    • by age 6 months reported in most neonates(1,2)
    • by age 2 years reported in infants with bronchopulmonary dysplasia; most resolve by age 8 months(1)
  • hypertension more likely to resolve if due to(1,2)
    • iatrogenic causes such as medications or umbilical artery catheterization
    • chronic lung disease
    • idiopathic cause
  • hypertension more likely to be persistent if due to(1,2)
    • renal parenchymal disease
    • polycystic kidney disease
    • renal vein thrombosis with or without vascular repair
    • renal artery stenosis
    • coarctation of aorta following surgical repair
    • genetic causes of hypertension
  • disposition of antihypertensive medication
    • reported median duration of 10 days for neonates with hypertension during intensive care(1)
    • 41% diagnosed with neonatal hypertension during intensive care discharged home with medication(1)
    • most neonates treated for hypertension able to discontinue antihypertensive medication by age 6 months(2)
  • conditions that may increase risk of developing hypertension as child or adult regardless of occurrence of neonatal hypertension include(2)
    • premature birth
    • coarctation of aorta
    • bronchopulmonary dysplasia
    • kidney disease
    • congenital heart disease
    • intrauterine growth restriction

Prevention and Screening

Prevention

  • not applicable

Screening

  • neonatal hypertension is often identified via routine monitoring of vital signs during intensive care(2)

Guidelines and Resources

Guidelines

United States Guidelines

European Guidelines

Review Articles

  • to search MEDLINE for (Neonatal hypertension) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis

Patient Information

  • DynaMed Editors have not identified patient education materials that meet our criteria for inclusion (freely accessible, non-promotional, topic-specific). We will continue to search for acceptable materials and welcome your suggestions.

References

General References Used

The references listed below are used in this DynaMed topic primarily to support background information and for guidance where evidence summaries are not felt to be necessary. Most references are incorporated within the text along with the evidence summaries.

  1. Pediatr Nephrol 2019 Jun;34(6):1009-1018.
  2. Pediatr Nephrol 2019 May;34(5):787-799full-text, correction can be found in Pediatr Nephrol 2019 Sep;34(9):1637.
  3. Hypertension 2021 Mar 3;77(3):781-787.

Related Posts

Related Posts:

15585

Sign up to receive the trending updates and tons of Health Tips

Join SeekhealthZ and never miss the latest health information

15856