View
214
Download
0
Category
Tags:
Preview:
Citation preview
NEONATAL NEONATAL HYPERTENSIONHYPERTENSION
MARIFI DE JESUS U. CABALUNA, MDMARIFI DE JESUS U. CABALUNA, MD
PL-2PL-2
NOVEMBER 28, 2006NOVEMBER 28, 2006
QUESTIONS TO BE QUESTIONS TO BE ANSWEREDANSWERED
What is the proper way of obtaining What is the proper way of obtaining
BP in the neonate?BP in the neonate? Does the device used in getting the Does the device used in getting the
BP matters?BP matters? What is the primary determinant of What is the primary determinant of
BP in both Term and Preterm infants? BP in both Term and Preterm infants?
QUESTIONS TO BE QUESTIONS TO BE ANSWEREDANSWERED
What are the common causes of What are the common causes of
Hypertension among the neonates?Hypertension among the neonates? Does catheter tip placement play a Does catheter tip placement play a
role in the incidence of Hypertensionrole in the incidence of Hypertension
among the neonates?among the neonates? What are the “RED FLAGS” in historyWhat are the “RED FLAGS” in history
and PE that points to neonatal and PE that points to neonatal
hypertension?hypertension?
QUESTIONS TO BE QUESTIONS TO BE ANSWEREDANSWERED
What initial laboratory studies are What initial laboratory studies are
important?important? Who should receive treatment ?Who should receive treatment ? How do we choose a suitable agent?How do we choose a suitable agent? Are there any medications to avoid?Are there any medications to avoid? Long term outcome and prognosis Long term outcome and prognosis
depend on which factor?depend on which factor?
DEFINITIONDEFINITION
Systolic and/or diastolic BP >/= Systolic and/or diastolic BP >/= 95%95%
(> 2 SD above the mean)(> 2 SD above the mean) Stage 1 : BP at 95 to < 99 %Stage 1 : BP at 95 to < 99 % Stage 2 : BP >/= 99% + 5 mm Stage 2 : BP >/= 99% + 5 mm
HgHg
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Nwankwo et alNwankwo et al LBW and PT infantsLBW and PT infants
BP is significantly lower in the BP is significantly lower in the proneprone than than supine supine positionposition
First reading is significantly First reading is significantly higherhigher than than
the third reading.the third reading.
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
STANDARDIZED PROTOCOLSTANDARDIZED PROTOCOL Check blood pressure 1.5 hours Check blood pressure 1.5 hours
after after
the last feeding or interventionthe last feeding or intervention
Apply appropriately sized cuff Apply appropriately sized cuff 2/3 the length of the limb segment2/3 the length of the limb segment 75% of the limb circumference75% of the limb circumference
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Wait 15 minutes or more of Wait 15 minutes or more of stillnessstillness
3 successive readings at 2-3 successive readings at 2-minuteminute
interval.interval.
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Intra-arterial catheters Intra-arterial catheters most accurate techniquemost accurate technique placed in aorta or radial arteryplaced in aorta or radial artery continuous readingscontinuous readings
Oscillometric devicesOscillometric devices non-invasive ; continuousnon-invasive ; continuous measure systolic and mean and calculate measure systolic and mean and calculate
diastolic pressure.diastolic pressure.
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
INTRA-ARTERIAL CATHETERS VS. INTRA-ARTERIAL CATHETERS VS.
OSCILLOMETRIC DEVICESOSCILLOMETRIC DEVICES
Low et al (study on 31 newborns)Low et al (study on 31 newborns) Average oscillometric pressures Average oscillometric pressures
significantly significantly
lower than intra-arterial pressures.lower than intra-arterial pressures. Systolic lower by 1 mm HGSystolic lower by 1 mm HG Mean pressure lower by 5.3 mm HgMean pressure lower by 5.3 mm Hg Diastolic pressure lower by 4.6 mm HGDiastolic pressure lower by 4.6 mm HG
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Leg pressures are higher than armLeg pressures are higher than arm
pressurespressures
Normal BP increases with Normal BP increases with gestationalgestational
age, post-conceptual age and age, post-conceptual age and
birthweight.birthweight.
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Zubrow et al (695 PT infant)Zubrow et al (695 PT infant) D1 – Systolic and Diastolic correlateD1 – Systolic and Diastolic correlate
strongly with BW and GAstrongly with BW and GA First 5 days after birth – First 5 days after birth –
Systolic increase by 2.2-2.7 mm Hg/day Systolic increase by 2.2-2.7 mm Hg/day Diastolic increase by 1.6-2 mm Hg/ Diastolic increase by 1.6-2 mm Hg/
day regardless of BW and GA day regardless of BW and GA
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Zubrow et al (695 PT infant)Zubrow et al (695 PT infant)
After 5After 5thth Day – more gradual Day – more gradual
incrementsincrements Systolic – 0.24-0.27 mm Hg/daySystolic – 0.24-0.27 mm Hg/day Diastolic – 0 – 0.15 mm Hg/dayDiastolic – 0 – 0.15 mm Hg/day
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Zubrow et al (695 PT infant )Zubrow et al (695 PT infant ) generated standard curves for mean generated standard curves for mean BP + upper and lower 95%BP + upper and lower 95% confidence limitsconfidence limits regression lines developed based on regression lines developed based on
BirthweightBirthweight Gestational ageGestational age Postconceptual agePostconceptual age
BLOOD PRESSURE BLOOD PRESSURE MEASUREMENTMEASUREMENT
Postconceptual age/Postmenstrual Postconceptual age/Postmenstrual
age (GA + postnatal age) – age (GA + postnatal age) – primary primary
determinantdeterminant of BP in this population of BP in this population
RECOMMENDATIONRECOMMENDATION BP consistently > 95% confidence BP consistently > 95% confidence
limit by ZUBROW CURVES.limit by ZUBROW CURVES.
INCIDENCEINCIDENCE
General NICU populationGeneral NICU population .08% (26/3,179).08% (26/3,179)
NICU admissionsNICU admissions 2% ( 20/988)2% ( 20/988) 0.7 to 3 % in three studies0.7 to 3 % in three studies
INCIDENCEINCIDENCE
More common in patients with More common in patients with certain certain
diagnoses :diagnoses : BPD – 6 %BPD – 6 % PDA – 3 %PDA – 3 % IV hemorrhage – 3 %IV hemorrhage – 3 % Umbilical catheterization – 9 %Umbilical catheterization – 9 %
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
RENOVASCULARRENOVASCULAR most commonmost common
thromboembolismthromboembolism umbilical artery catheters as theoretical sources umbilical artery catheters as theoretical sources
of of
thomboembolic events thomboembolic events studies established an association between local studies established an association between local
thrombi and development of hypertensionthrombi and development of hypertension
renal artery stenosisrenal artery stenosis renal venous thrombosisrenal venous thrombosis compression of renal arterycompression of renal artery
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
THROMBOEMBOLISMTHROMBOEMBOLISM COCHRANE STUDYCOCHRANE STUDY
analysis of 11 randomized clinical trialsanalysis of 11 randomized clinical trials one study using alternate assignments one study using alternate assignments
To compare the incidence ofTo compare the incidence of
morbidity and mortality for HIGH Vs. morbidity and mortality for HIGH Vs.
LOW catheter tip placement.LOW catheter tip placement.
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
HIGH – in the descending aortaHIGH – in the descending aorta above the diaphragm (T6 and T9)above the diaphragm (T6 and T9) LOW – above the bifurcation but below the renal LOW – above the bifurcation but below the renal arteries (L3 and L5)arteries (L3 and L5)
CONCLUSIONCONCLUSION High catheter positions caused fewer High catheter positions caused fewer ischemic complications and possibly decreased ischemic complications and possibly decreased
the the frequency of aortic thrombosis frequency of aortic thrombosis
Hypertension appears with equal frequencyHypertension appears with equal frequency
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
RENAL ARTERY STENOSISRENAL ARTERY STENOSIS caused by fibromuscular caused by fibromuscular
dysplasiadysplasia if present there also may be mid- if present there also may be mid-
aortic coarctation and cerebral aortic coarctation and cerebral
vascular stenosisvascular stenosis may be due to congenital rubellamay be due to congenital rubella
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
RENAL VEIN THROMBOSISRENAL VEIN THROMBOSIS HypertensionHypertension gross hematuriagross hematuria abdominal/flank massabdominal/flank mass thrombocytopeniathrombocytopenia
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
CONGENITAL RENAL DISEASECONGENITAL RENAL DISEASE Polycystic kidney diseasePolycystic kidney disease
autosomal dominant and recessiveautosomal dominant and recessive enlarged kidney and hypertensionenlarged kidney and hypertension
multicystic-dysplastic kidney multicystic-dysplastic kidney diseasedisease non-functionalnon-functional
ureteropelvic junction obstructionureteropelvic junction obstructionActivation of Renin-angiotensin systemActivation of Renin-angiotensin system
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
ACQUIRED RENAL DISEASEACQUIRED RENAL DISEASE ATN/Interstitial nephritis/cortical ATN/Interstitial nephritis/cortical
necrosisnecrosis due to volume due to volume
overload/hyperreninemiaoverload/hyperreninemia HUSHUS Obstruction by a tumorObstruction by a tumor
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
BRONCHOPULMONARY DYSPLASIABRONCHOPULMONARY DYSPLASIA 13- 43% of infants develop systemic 13- 43% of infants develop systemic
hypertensionhypertension cause unclear : chronic hypoxiacause unclear : chronic hypoxia severity (greater need for diuretics) of BPD severity (greater need for diuretics) of BPD
related to likelihood of developing related to likelihood of developing
increased BP.increased BP. sickest infant require the closest monitoringsickest infant require the closest monitoring
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
COARCTATION OF THE AORTACOARCTATION OF THE AORTA early repair improves the long early repair improves the long
term term
outcome outcome hypertension may persist even hypertension may persist even
after after
surgical repairsurgical repair
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
ENDOCRINEENDOCRINE seizures and increased seizures and increased
intracranialintracranial
pressure are common causes of pressure are common causes of
episodic hypertensionepisodic hypertension CAHCAH HYPERALDOSTERONISMHYPERALDOSTERONISM HYPERTHYROIDISM HYPERTHYROIDISM
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
IATROGENICIATROGENIC NICU medsNICU meds
DexamethasoneDexamethasone TheophyllineTheophylline CaffeineCaffeine PancuroniumPancuronium PhenylephrinePhenylephrine
Prolonged TPNProlonged TPN lead to salt and water lead to salt and water
overload/hypercalcemiaoverload/hypercalcemiaUnder treatment of painUnder treatment of pain
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
MATERNAL CAUSESMATERNAL CAUSES Cocaine useCocaine use
harm the developing kidneysharm the developing kidneys Heroine useHeroine use
with neonatal withdrawalwith neonatal withdrawal
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
NEOPLASMSNEOPLASMS from compression of renal vessels from compression of renal vessels
and and uretersureters production of vasoactive production of vasoactive
substancessubstances NeuroblastomaNeuroblastoma Wilm’s tumorWilm’s tumor Mesoblastic nephromaMesoblastic nephroma
CAUSES OF NEONATAL CAUSES OF NEONATAL HYPERTENSIONHYPERTENSION
MISCELLANEOUS CAUSESMISCELLANEOUS CAUSES closure of abdominal wall defectclosure of abdominal wall defect adrenal hemorrhageadrenal hemorrhage hypercalcemiahypercalcemia ECMOECMO birth asphyxiabirth asphyxia
EVALUATIONEVALUATION
Life-threatening presentationLife-threatening presentation CHFCHF Cardiogenic shockCardiogenic shock SeizuresSeizures
Presentation of less ill infantsPresentation of less ill infants feeding difficultiesfeeding difficulties unexplained tachypneaunexplained tachypnea lethargy, apnea, irritabilitylethargy, apnea, irritability mottling of the skinmottling of the skin
EVALUATIONEVALUATION
RED FLAGS IN THE HISTORYRED FLAGS IN THE HISTORY prenatal exposures to heroin and prenatal exposures to heroin and
cocainecocaine predisposing conditions – BPD, CNSpredisposing conditions – BPD, CNS
disorders, PDA, hypervolemia (post disorders, PDA, hypervolemia (post
BT)BT) Medications/ Umbilical artery Medications/ Umbilical artery
catheterizationscatheterizations
EVALUATIONEVALUATION
RED FLAGS IN THE PHYSICAL RED FLAGS IN THE PHYSICAL
EXAMINATIONEXAMINATION BP in lower extremities/non-palpable BP in lower extremities/non-palpable
femoral pulses – CoAfemoral pulses – CoA dysmorphic features – CAH/Turner Sydysmorphic features – CAH/Turner Sy Flank mass – UPJ obstructionFlank mass – UPJ obstruction Epigastric bruit – renal artery Epigastric bruit – renal artery
stenosisstenosis
EVALUATIONEVALUATION
RED FLAGS IN THE PHYSICAL RED FLAGS IN THE PHYSICAL
EXAMINATIONEXAMINATION Abdominal distention – obstructive Abdominal distention – obstructive
uropathy, PKD, tumorsuropathy, PKD, tumors Peripheral thrombi – UAC related HTNPeripheral thrombi – UAC related HTN Tachycardia/flushing/LBW – Tachycardia/flushing/LBW –
hyperthyroidismhyperthyroidism Ambiguous genitalia - CAHAmbiguous genitalia - CAH
LABORATORY LABORATORY EXAMINATIONSEXAMINATIONS
UrinalysisUrinalysis CBCCBC Electrolytes, BUN, Crea, CaElectrolytes, BUN, Crea, Ca Urine culture if UTI is suspectedUrine culture if UTI is suspected Plasma renin level – significantly Plasma renin level – significantly
elevated level indicates elevated level indicates renovascular renovascular
diseasedisease
LABORATORY LABORATORY EXAMINATIONSEXAMINATIONS
Additional testsAdditional tests Thyroid studiesThyroid studies VMA/Homovanillic acidVMA/Homovanillic acid AldosteroneAldosterone CortisolCortisol
IMAGING STUDIESIMAGING STUDIES
CXRay/2D echo – CHFCXRay/2D echo – CHF US of genitourinary tract US of genitourinary tract
should be performed in all hypertensive should be performed in all hypertensive infantsinfants
to rule out UPJ obstruction, renal veinto rule out UPJ obstruction, renal vein
thrombosis thrombosis
Doppler flow studies Doppler flow studies Abdominal/pelvic US Abdominal/pelvic US VCUGVCUG
IMAGING STUDIESIMAGING STUDIES
Radionuclide imaging - Abnormal Radionuclide imaging - Abnormal kidney displays:kidney displays: decreased effective renal plasma flowdecreased effective renal plasma flow decreased urine flow ratedecreased urine flow rate increased isotope concentrationincreased isotope concentration
MRA – gold standard for diagnosis of MRA – gold standard for diagnosis of
reno vascular hypertensionreno vascular hypertension must be 3 kgmust be 3 kg
MANAGEMENTMANAGEMENT
optimal management uncertainoptimal management uncertain threshold for starting threshold for starting
antihypertensive antihypertensive
has not been well definedhas not been well defined idiosyncratic responses to certain idiosyncratic responses to certain
drugs due to developmental drugs due to developmental
immaturity of liver and kidney immaturity of liver and kidney
function.function.
MANAGEMENTMANAGEMENT
RECOMMENDATIONRECOMMENDATION Asymptomatic /Mild HypertensionAsymptomatic /Mild Hypertension (Systolic 95(Systolic 95thth to < 99 to < 99thth %) %)
observationobservation resolves in timeresolves in time
Moderate to Severe Moderate to Severe (Systolic >/= 99(Systolic >/= 99thth %) %)
antihypertensive therapyantihypertensive therapy
MANAGEMENTMANAGEMENT
Address correctible causes ofAddress correctible causes of
hypertensionhypertension treat paintreat pain correct volume overloadcorrect volume overload wean inotropic infusionwean inotropic infusion
Choose a suitable agentChoose a suitable agent depends on specific clinical depends on specific clinical
situationsituation
TREATMENTTREATMENT
ACUTELY ILL INFANTSACUTELY ILL INFANTS continuous IV infusioncontinuous IV infusion
intermittently administered agents intermittently administered agents cause cause
wide fluctuation in BP wide fluctuation in BP PT are at increased risk for cerebral PT are at increased risk for cerebral
ischemia and hemorrhage from rapidly ischemia and hemorrhage from rapidly falling BP’s.falling BP’s. allows titration for desired effectallows titration for desired effect
TREATMENTTREATMENT
ACUTELY ILL INFANTSACUTELY ILL INFANTS continuous IV infusioncontinuous IV infusion
Nicardipine - DOCNicardipine - DOC Nitroprusside Nitroprusside Labetalol – cathecholamine and CNS Labetalol – cathecholamine and CNS mediated hypertensionmediated hypertension - avoid in BPD- avoid in BPD
monitor BP Q 10-15 minutesmonitor BP Q 10-15 minutes
TREATMENTTREATMENT
NICARDIPINE NICARDIPINE calcium channel blockercalcium channel blocker peripheral vasodilatorperipheral vasodilator short half life : 10-15 minutesshort half life : 10-15 minutes IV infusion 0.5 mcg/kg/min if normal BP IV infusion 0.5 mcg/kg/min if normal BP not achieved in 15 minutes increase not achieved in 15 minutes increase infusion to max of 3 mcg/kg/min. If still infusion to max of 3 mcg/kg/min. If still elevated, add Sodium nitroprussideelevated, add Sodium nitroprusside then stop Nicardipine.then stop Nicardipine.
TREATMENTTREATMENT
NITROPRUSSIDENITROPRUSSIDE potent vasodilator potent vasodilator rapid onset of action short rapid onset of action short
duration ofduration of
effect effect complications : hypotension and complications : hypotension and
thiocyanate toxicity.thiocyanate toxicity.
TREATMENTTREATMENT
LABETALOL LABETALOL combined alpha-1 and beta-blockercombined alpha-1 and beta-blocker rapid onset of actionrapid onset of action duration of action : 2-3 hoursduration of action : 2-3 hours do not cause tachycardia, cerebraldo not cause tachycardia, cerebral
vasodilatation or changes in vasodilatation or changes in
intracranial pressure.intracranial pressure.
TREATMENTTREATMENT(NeoReviews)(NeoReviews)
LESS SEVERE HYPERTENSION NOT LESS SEVERE HYPERTENSION NOT READY FOR ORALREADY FOR ORAL
Intermittent IV agentsIntermittent IV agents HydralazineHydralazine LabetalolLabetalol
sometimes doses at lower end of sometimes doses at lower end of recommended range cause recommended range cause
significant significant hypotensionhypotension
TREATMENTTREATMENT
HYDRALAZINEHYDRALAZINE peripheral vasodilatorperipheral vasodilator relaxes vascular smooth musclerelaxes vascular smooth muscle
TREATMENTTREATMENT(NeoReviews)(NeoReviews)
INFANT READY TO BE WEANED INFANT READY TO BE WEANED FROM IV / READY FOR ORALFROM IV / READY FOR ORAL
ORAL ANTIHYPERTENSIVE AGENTSORAL ANTIHYPERTENSIVE AGENTS CaptoprilCaptopril Diuretic - can be added if captopril is Diuretic - can be added if captopril is
ineffectiveineffective B Blocker – should be avoided (BPD)B Blocker – should be avoided (BPD)
TREATMENTTREATMENT
CAPTOPRIL CAPTOPRIL Drug of choiceDrug of choice ACE inhibitorACE inhibitor .017 mg/kg/dose PO BID –TID.017 mg/kg/dose PO BID –TID Extremely low doses (0.01 Extremely low doses (0.01 mg/kg/dose or 0.03 mg/kg/dose or 0.03
mg/kg/day)mg/kg/day) may be effective in newbornsmay be effective in newborns
TREATMENTTREATMENT
CAPTOPRIL CAPTOPRIL more potent in newborns more potent in newborns
than older children because of than older children because of
higher renal vascular higher renal vascular resistanceresistance
longer duration of actionlonger duration of action
TREATMENTTREATMENT
BETA BLOCKERBETA BLOCKER effective in newborns effective in newborns side effects uncommonside effects uncommon avoided in infants with BPD avoided in infants with BPD
because of because of bronchoconstrictionbronchoconstriction
TREATMENTTREATMENT
DIURETICSDIURETICS reduce extracellular and plasma reduce extracellular and plasma
volumevolume use in newborns limited to mild use in newborns limited to mild
hypertension resulting from fluid hypertension resulting from fluid
overload or as an adjunctive overload or as an adjunctive
medication. medication.
TREATMENTTREATMENT(UPTODATE)(UPTODATE)
IV EnalaprilIV Enalapril IV administered ACE inhibitor IV administered ACE inhibitor effective in renovascular effective in renovascular
hypertensionhypertension has been used successfully in has been used successfully in
newbornsnewborns lowest dose should be tried firstlowest dose should be tried first
TREATMENTTREATMENT(NeoReviews)(NeoReviews)
IV EnalaprilIV Enalapril avoided because of it’s avoided because of it’s
unpredictable unpredictable
antihypertensive efficacy andantihypertensive efficacy and
potential to cause oligoanuria via potential to cause oligoanuria via
blockade of the renin-angiotensin blockade of the renin-angiotensin
axis.axis.
TREATMENTTREATMENT
Surgical correctionSurgical correction CoACoA UPJ obstructionUPJ obstruction
Medical management + surgeryMedical management + surgery Renal artery stenosis Renal artery stenosis
Nephrectomy Nephrectomy Polycystic kidney diseasePolycystic kidney disease
Chemotherapy + surgeryChemotherapy + surgery Wilm’s tumor and NeuroblastomaWilm’s tumor and Neuroblastoma
PROGNOSISPROGNOSIS
depends on the causedepends on the cause often resolves over timeoften resolves over time persistentpersistent
polycystic kidney diseasepolycystic kidney disease renal parenchymal diseaserenal parenchymal disease renal vein thrombosis – require renal vein thrombosis – require nephrectomynephrectomy
recurrentrecurrent restenosis of renal artery stenosis or CoArestenosis of renal artery stenosis or CoA after repairafter repair
REFERENCESREFERENCES
Ettinger, Leigh et al : Ettinger, Leigh et al : Neoreviews Neoreviews Vol 3 Vol 3 No.8. 2002No.8. 2002 Fanaroff, Jonathan, et al. Fanaroff, Jonathan, et al. Blood pressure disorders in Blood pressure disorders in
the Neonate : Hypotension and Hypertensionthe Neonate : Hypotension and Hypertension. . Seminars in Fetal and Neonatal Medicine Vol 11. No. Seminars in Fetal and Neonatal Medicine Vol 11. No. 3, June 2006, 174-181.3, June 2006, 174-181.
Ettinger, Leigh et al : Ettinger, Leigh et al : Neoreviews. Neoreviews. Vol 3 Vol 3 No. 8, 2002No. 8, 2002 Neonatal Hypertension : Neonatal Hypertension : Uptodate.2006Uptodate.2006 Neonatal Hypertension : Neonatal Hypertension : EmedicineEmedicine. August . August 29, 200629, 2006 Sondheimer, Judith M. (editor) : Sondheimer, Judith M. (editor) : CurrentCurrent Pediatric Diagnosis and TreatmentPediatric Diagnosis and Treatment. 16. 16thth ed. ed. McGraw-Hill Companies,2003McGraw-Hill Companies,2003
Recommended