History

In most newborns, hypertension is discovered on routine monitoring of vital signs. Other presentations of neonatal hypertension to be aware of in acutely ill infants include congestive heart failure (CHF) and cardiogenic shock,^[14]which are potentially life threatening. Fortunately, these consequences of hypertension gradually resolve with appropriate blood pressure (BP) reduction.^[15]

In the less acutely ill infant, feeding difficulties, unexplained tachypnea, apnea, lethargy, irritability, or seizures may constitute symptoms of unsuspected hypertension.^[5]In older infants who have been discharged from the nursery, unexplained irritability or failure to thrive may be the only manifestations of hypertension.

Focus the history on discovering any pertinent prenatal or postnatal exposures, as well as to the particulars of the infant's nursery course and any concurrent conditions. Review the procedures that the infant has undergone, especially umbilical catheter placement, and analyze the baby's current medication list. If the infant has been discharged from the nursery, the history should also cover symptoms related to possible underlying causes of hypertension (similar to the evaluation of hypertension in older children).

Physical Examination

The physical examination should begin with 4-extremity blood pressure (BP) measurements in order to rule out aortic coarctation. Assess the general appearance of the infant and pay particular attention to the presence of dysmorphic features that may indicate an underlying genetic syndrome. Perform careful cardiac and abdominal examinations to rule out congestive heart failure (CHF) or renal anomalies. Examine the genitalia to rule out congenital adrenal hyperplasia (CAH). Neurologic examination may also be helpful, particularly in infants with intraventricular hemorrhage.

Normal blood pressure levels

BP in newborn infants is influenced by various factors, including birth weight, gestational age, and postconceptual age.^{[16, 17]}Excellent data illustrating the importance of these factors were generated by Zubrow et al, who prospectively obtained serial BP measurements from nearly 700 infants admitted to several NICUs in a large metropolitan area over 3 months.^[18]The investigators used these data to define the mean plus upper and lower 95% confidence limits for BP; their data clearly demonstrated increases in BP with increasing gestational age, birth weight, and postconceptual age.

A of hemodynamically stable premature and term infants admitted to the NICU showed that BPs on day 1 of life correlated with gestational age and birth weight.^[19]However, another study of more than 400 term infants admitted to a postnatal ward in Australia showed no difference in BP on day 1 of life based on birth weight, length, or gestational age.^[20]Thus, there appears to be physiologic differences in premature infants with respect to BP level that need to be taken into consideration when considering whether a particular BP value is normal or elevated.

Data from these studies have been summarized by Dionne et al,^{[21, 22]}who generated a table of BP values that can be used in assessing if a neonate’s BP is normal or elevated (see Table 1 below). For older infants, the percentile curves generated by the 1987 Second Task Force on Blood Pressure Control in Childhood remain the most useful reference of normal BP values (see the image below).^[23]These curves allow BP to be characterized as normal or elevated not only by age and sex but also by size, albeit to a somewhat limited extent.

Neonatal Hypertension. Normal blood pressure percentile curves for older infants. From the Second (1987) Task Force on Blood Pressure Control in Childhood; National Heart, Lung, and Blood Institute.

Defining hypertensive-level BP

Hypertension in adults is defined based upon occurrence of hard cardiovascular endpoints such as myocardial infarction, stroke, and death. Since these events occur rarely in the pediatric age group, the definition of hypertension in infants, children, and adolescents is a statistical one based on databases of BP readings obtained in healthy subjects. Thus, BP in the young is considered normal if less than the 90th percentile for age, sex, and height, and is considered hypertensive if it is greater than or equal to the 95th percentile.

For infants, the same definitions should probably be applied, although the available data on normal BP values in infancy is limited. The table summarized below is a useful reference for premature infants, while the Second Task Force curves (see image above) can be used for term and older infants. However, there are obvious shortcomings for both of these references, highlighting the need for additional studies of normal BP in infancy.

Table 1. Neonatal Blood Pressures and Potential Treatment Parameters. Adapted from Dionne et al.* (Open Table in a new window)

Postconceptual Age	50th Percentile	95th Percentile	99th Percentile
44 weeks
SBP	88	105	110
DBP	50	68	73
MAP	63	80	85
42 weeks
SBP	85	98	102
DBP	50	65	70
MAP	62	76	81
40 weeks
SBP	80	95	100
DBP	50	65	70
MAP	60	75	80
38 weeks
SBP	77	92	97
DBP	50	65	70
MAP	59	74	79
36 weeks
SBP	72	87	92
DBP	50	65	70
MAP	57	72	77
34 weeks
SBP	70	85	90
DBP	40	55	60
MAP	50	65	70
32 weeks
SBP	68	83	88
DBP	40	55	60
MAP	49	64	69
30 weeks
SBP	65	80	85
DBP	40	55	60
MAP	48	63	68
28 weeks
SBP	60	75	80
DBP	38	50	54
MAP	45	58	63
26 weeks
SBP	55	72	77
DBP	30	50	56
MAP	38	57	63

*Estimated values for blood pressures after age 2 weeks in infants from 26-44 weeks postconceptual age. The 95th and 99th percentile values serve as a reference to identify infants with persistent hypertension that may require treatment. SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure.

Differential Diagnoses

Singh HP, Hurley RM, Myers TF. Neonatal hypertension. Incidence and risk factors. Am J Hypertens. 1992 Feb. 5(2):51-5. [QxMD MEDLINE Link].
Friedman AL, Hustead VA. Hypertension in babies following discharge from a neonatal intensive care unit. A 3-year follow-up. Pediatr Nephrol. 1987 Jan. 1(1):30-4. [QxMD MEDLINE Link].
Blowey DL, Duda PJ, Stokes P, Hall M. Incidence and treatment of hypertension in the neonatal intensive care unit. J Am Soc Hypertens. 2011 Nov-Dec. 5(6):478-83. [QxMD MEDLINE Link].
Neal WA, Reynolds JW, Jarvis CW, Williams HJ. Umbilical artery catheterization: demonstration of arterial thrombosis by aortography. Pediatrics. 1972 Jul. 50(1):6-13. [QxMD MEDLINE Link].
Hassan R, Verma RP. Neonatal hypertension. StatPearls [Internet]. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Abman SH, Warady BA, Lum GM, Koops BL. Systemic hypertension in infants with bronchopulmonary dysplasia. J Pediatr. 1984 Jun. 104(6):928-31. [QxMD MEDLINE Link].
Alagappan A, Malloy MH. Systemic hypertension in very low-birth weight infants with bronchopulmonary dysplasia: incidence and risk factors. Am J Perinatol. 1998 Jan. 15(1):3-8. [QxMD MEDLINE Link].
Nickavar A, Assadi F. Managing hypertension in the newborn infants. Int J Prev Med. 2014 Mar. 5(Suppl 1):S39-43. [QxMD MEDLINE Link]. [Full Text].
Sahu R, Pannu H, Yu R, Shete S, Bricker JT, Gupta-Malhotra M. Systemic hypertension requiring treatment in the neonatal intensive care unit. J Pediatr. 2013 Jul. 163(1):84-8. [QxMD MEDLINE Link].
Seliem WA, Falk MC, Shadbolt B, Kent AL. Antenatal and postnatal risk factors for neonatal hypertension and infant follow-up. Pediatr Nephrol. 2007 Dec. 22(12):2081-7. [QxMD MEDLINE Link].
Cho MH. Hypertension in adulthood is programmed during the perinatal period. Clin Exp Pediatr. 2022 Oct. 65(10):494-5. [QxMD MEDLINE Link]. [Full Text].
Altemose K, Dionne JM. Neonatal hypertension: concerns within and beyond the neonatal intensive care unit. Clin Exp Pediatr. 2022 Aug. 65(8):367-76. [QxMD MEDLINE Link]. [Full Text].
Shah AB, Hashmi SS, Sahulee R, Pannu H, Gupta-Malhotra M. Characteristics of systemic hypertension in preterm children. J Clin Hypertens (Greenwich). 2015 May. 17(5):364-70. [QxMD MEDLINE Link]. [Full Text].
Sharma D, Farahbakhsh N, Shastri S, Sharma P. Neonatal hypertension. J Matern Fetal Neonatal Med. 2017 Mar. 30(5):540-50. [QxMD MEDLINE Link].
Xiao N, Tandon A, Goldstein S, Lorts A. Cardiogenic shock as the initial presentation of neonatal systemic hypertension. J Neonatal Perinatal Med. 2013. 6(3):267-72. [QxMD MEDLINE Link].
Starr MC, Flynn JT. Neonatal hypertension: cases, causes, and clinical approach. Pediatr Nephrol. 2019 May. 34(5):787-99. [QxMD MEDLINE Link]. [Full Text].
Harer MW, Kent AL. Neonatal hypertension: an educational review. Pediatr Nephrol. 2019 Jun. 34(6):1009-18. [QxMD MEDLINE Link].
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. J Perinatol. 1995 Nov-Dec. 15(6):470-9. [QxMD MEDLINE Link].
Pejovic B, Peco-Antic A, Marinkovic-Eric J. Blood pressure in non-critically ill preterm and full-term neonates. Pediatr Nephrol. 2007 Feb. 22(2):249-57. [QxMD MEDLINE Link].
Kent AL, Kecskes Z, Shadbolt B, Falk MC. Normative blood pressure data in the early neonatal period. Pediatr Nephrol. 2007 Sep. 22(9):1335-41. [QxMD MEDLINE Link].
Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. 2012 Jan. 27(1):17-32. [QxMD MEDLINE Link].
Dionne JM, Abitbol CL, Flynn JT. Erratum to: Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. 2012 Jan. 27(1):159-60. [QxMD MEDLINE Link].
Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children--1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics. 1987 Jan. 79(1):1-25. [QxMD MEDLINE Link].
Crossland DS, Furness JC, Abu-Harb M, et al. Variability of four limb blood pressure in normal neonates. Arch Dis Child Fetal Neonatal Ed. 2004 Jul. 89(4):F325-7. [QxMD MEDLINE Link].
Batisky DL. Neonatal hypertension. Clin Perinatol. 2014 Sep. 41(3):529-42. [QxMD MEDLINE Link].
Brierley J, Marks SD. Treating the causes of paediatric hypertension using non-invasive physiological parameters. Med Hypotheses. 2010 Nov. 75(5):439-41. [QxMD MEDLINE Link].
Costa HTML, Costa TX, Martins RR, Oliveira AG. Use of off-label and unlicensed medicines in neonatal intensive care. PLoS One. 2018. 13(9):e0204427. [QxMD MEDLINE Link]. [Full Text].
Pillai A, Sharma D, Kadam P. Hypertension in the neonatal period: an update. Curr Hypertens Rev. 2016. 12(3):186-95. [QxMD MEDLINE Link].

Media Gallery

Neonatal Hypertension. Normal blood pressure percentile curves for older infants. From the Second (1987) Task Force on Blood Pressure Control in Childhood; National Heart, Lung, and Blood Institute.

of 1

Table 1. Neonatal Blood Pressures and Potential Treatment Parameters. Adapted from Dionne et al.*

Postconceptual Age	50th Percentile	95th Percentile	99th Percentile
44 weeks
SBP	88	105	110
DBP	50	68	73
MAP	63	80	85
42 weeks
SBP	85	98	102
DBP	50	65	70
MAP	62	76	81
40 weeks
SBP	80	95	100
DBP	50	65	70
MAP	60	75	80
38 weeks
SBP	77	92	97
DBP	50	65	70
MAP	59	74	79
36 weeks
SBP	72	87	92
DBP	50	65	70
MAP	57	72	77
34 weeks
SBP	70	85	90
DBP	40	55	60
MAP	50	65	70
32 weeks
SBP	68	83	88
DBP	40	55	60
MAP	49	64	69
30 weeks
SBP	65	80	85
DBP	40	55	60
MAP	48	63	68
28 weeks
SBP	60	75	80
DBP	38	50	54
MAP	45	58	63
26 weeks
SBP	55	72	77
DBP	30	50	56
MAP	38	57	63

Table 2. Intravenous Drugs for Severe Hypertension in Neonates ^[21]

Drug	Class	Intravenous (IV) Dosage	Comments
Esmolol	Beta blocker	100-300 mcg/kg/min IV infusion	Very short acting; constant IV infusion necessary
Hydralazine	Vasodilator (arteriolar)	0.15-0.6 mg/kg/dose IV bolus or 0.75-5mcg/kg/min IV constant infusion	Tachycardia is frequent adverse effect; must administer every 4 hours when administered as IV bolus
Labetalol	Alpha blocker and beta blocker	0.2-1 mg/kg/dose IV bolus or 0.25-3 mg/kg/h IV constant infusion	Heart failure, bronchopulmonary dysplasia (BPD), relative contraindications
Nicardipine	Calcium channel blocker	1-5 mcg/kg/min IV constant infusion	May cause reflex tachycardia
Sodium nitroprusside	Vasodilator (arteriolar and venous)	0.5-10 mcg/kg/min IV constant infusion	Thiocyanate toxicity can occur with prolonged use (>72 h) or in renal failure; usual maintenance dose is below 2 mcg/kg/min; may use 10 mcg/kg/min for short duration (ie, < 10-15 min)

Table 3. Oral Antihypertensive Agents Useful for Treatment of Neonatal Hypertension ^[21]

Drug	Class	Oral Dosage	Comments
Captopril	Angiotensin-converting enzyme (ACE) inhibitor	Under age 3 months: 0.01-0.5 mg/kg/dose 3 times daily; not to exceed 2 mg/kg/day At or above age 3 months: 0.15-0.3 mg/kg/dose 3 times daily; not to exceed 6 mg/kg/day	Monitor serum creatinine and potassium levels
Clonidine	Central agonist	0.05-0.1 mg/dose 2-3 times daily	Adverse effects include dry mouth and sedation; rebound hypertension with abrupt discontinuation
Enalapril	ACE inhibitor	0.08-0.6 mg/kg/day, given once or twice daily	Monitor serum creatinine and potassium levels
Hydralazine	Vasodilator (arteriolar)	0.25-1 mg/kg/dose 3-4 times daily; not to exceed 7.5 mg/kg/day	Suspension stable up to 1 wk; tachycardia and fluid retention are common adverse effects; lupuslike syndrome may develop in slow acetylators
Isradipine	Calcium channel blocker	0.05-0.15 mg/kg/dose 4 times daily; not to exceed 0.8 mg/kg/d or 20 mg/day	Suspension may be compounded; useful for both acute and chronic hypertension
Amlodipine	Calcium channel blocker	0.1-0.3 mg/kg/dose twice daily; not to exceed 0.6 mg/kg/d or 20 mg/d	Less likely to cause sudden hypotension than isradipine
Minoxidil	Vasodilator (arteriolar)	0.1-0.2 mg/kg/dose 2-3 times daily	Most potent oral vasodilator; excellent for refractory hypertension
Propranolol	Beta-blocker	0.5-1 mg/kg/dose 3 times daily	Maximal dose depends on heart rate; may administer as much as 8-10 mg/kg/d if no bradycardia; avoid in infants with BPD
Labetalol	Alpha and beta blocker	1 mg/kg/dose 2-3 times daily, up to 12 mg/kg/d	Monitor heart rate; avoid in infants with BPD
Spironolactone	Aldosterone antagonist	0.5-1.5 mg/kg/dose twice daily	Potassium-sparing diuretic; monitor electrolytes; several days necessary to observe maximum effectiveness
Hydrochlorothiazide	Thiazide diuretic	2-3 mg/kg/d orally every day or divided twice daily	Monitor electrolytes
Chlorothiazide	Thiazide diuretic	5-15 mg/kg/dose twice daily	Monitor electrolytes