Yield of diagnostic testing in evaluating etiology and end organ effects of pediatric hypertension.

BACKGROUND: Current recommendations regarding the utility of diagnostic investigations for pediatric hypertension are based on limited evidence, leading to wide practice variation. The objective of this study was to characterize the cohort of children that may benefit from secondary hypertension workup, and determine the diagnostic yield of investigations. METHODS: This was a single-center, retrospective cohort study of 169 children aged 1-18 years referred between 2000 and 2015, to a tertiary pediatric nephrology center in Canada, for evaluation of hypertension. The number of investigations completed, abnormal findings, and diagnostic findings that helped establish hypertension etiology was determined. RESULTS: 56 children were diagnosed with primary and 72 children with secondary hypertension in the outpatient setting. Secondary hypertension was predominant at all ages except for obese adolescents ≥ 12 years. Half of children with traditional risk factors for primary hypertension, including obesity, were diagnosed with secondary hypertension. Kidney ultrasound had the highest yield of diagnostic results (19.8%), with no difference in yield between age groups (P = 0.19). Lipid profile had a high yield of abnormal results (25.4%) as part of cardiovascular risk assessment but was only abnormal in overweight/obese children. Echocardiogram had a high yield for identification of target-organ effects in hypertensive children (33.3%). CONCLUSION: A simplified secondary hypertension workup should be considered for all hypertensive children and adolescents. High yield investigations include a kidney ultrasound, lipid profile for overweight/obese children, and echocardiograms for assessment of target-organ damage. Further testing could be considered based on results of initial investigations for the most cost-effective management. A higher resolution version of the Graphical abstract is available as Supplementary information.

Child and caregiver perspectives on access to psychosocial and educational support in pediatric chronic kidney disease: a focus group study.

BACKGROUND: Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support. METHODS: Children with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically. RESULTS: We identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child's suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood). CONCLUSIONS: Children with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Etiologies and outcomes of prenatally diagnosed hyperechogenic kidneys.

OBJECTIVES: To determine etiologies and outcomes of fetal hyperechogenic kidneys (HEK). METHODS: We conducted a retrospective chart review of HEK in British Columbia (January 2013-December 2019) and literature review. RESULTS: We identified 20 cases of HEK without other anomalies (isolated) in our provincial cohort, one was lost to follow-up. Eight had testable genetic etiologies (autosomal dominant polycystic kidney disease [ADPKD], autosomal recessive polycystic kidney disease [ARPKD], Bardet-Biedl syndrome [BBS], and HNF1B-related disorder). The remaining seven did not have an identifiable genetic etiology. Of cases without a genetic etiology with postnatal follow-up (n = 6) there were no abnormalities of blood pressure, creatinine/estimated glomerular filtration rate or urinalysis identified with follow-up from 2-71 months. We report 11 cases with extrarenal anomalies (nonisolated), with outcomes and etiologies. We identified 224 reported cases of isolated HEK in the literature. A potentially testable genetic etiology was found in 128/224 (57.1%). The neonatal death rate in those with testable etiologies was 17/128 (13.3%) compared to 2/96 (2.1%) when testable etiologies were excluded. CONCLUSIONS: Genetic etiologies (ARPKD, ADPKD, BBS, HNF1B-related disorder, Beckwith-Wiedemann syndrome, tubular dysgenesis, familial nephroblastoma, and cytogenetic abnormalities) account for approximately half of prenatally isolated HEK; once excluded there are few neonatal deaths and short-term renal outcomes may be normal. There remains a paucity of knowledge about long-term renal outcomes.

Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis.

OBJECTIVES: To determine the recommended blood pressure (BP) measurement methods in neonates after systematically analyzing the literature regarding proper BP cuff size and measurement location and method. STUDY DESIGN: A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on BP in neonates <3 months of age (PROSPERO ID CRD42018092886). Study data were extracted and analyzed with separate analysis of Bland-Altman studies comparing measurement methods. RESULTS: Of 3587 nonduplicate publications identified, 34 were appropriate for inclusion in the analysis. Four studies evaluating BP cuff size support a recommendation for a cuff width to arm circumference ratio of approximately 0.5. Studies investigating measurement location identified the upper arm as the most accurate and least variable location for oscillometric BP measurement. Analysis of studies using Bland-Altman methods for comparison of intra-arterial to oscillometric BP measurement show that the 2 methods correlate best for mean arterial pressure, whereas systolic BP by the oscillometric method tends to overestimate intra-arterial systolic BP. Compared with intra-arterial methods, systolic BP, diastolic BP, and mean arterial pressure by oscillometric methods are less accurate and precise, especially in neonates with a mean arterial pressure <30 mm Hg. CONCLUSIONS: Proper BP measurement is critical in neonates with naturally lower BP and attention to BP cuff size, location, and method of measurement are essential. With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

Ambulatory blood pressure and carotid intima media thickness in children with type 1 diabetes.

BACKGROUND/OBJECTIVE: Blood pressure abnormalities may play an important role in macrovascular damage in type 1 diabetes. Little is known about blood pressure abnormalities and macrovascular damage in children with type 1 diabetes. METHODS: Children with type 1 diabetes (n = 57) for a short (3 months-2 years; n = 24) or long duration (≥5 years; n = 33) and a group of control children without diabetes (n = 29) completed 24-h ambulatory blood pressure monitoring (ABPM). Carotid intima media thickness (cIMT), a subclinical indicator of atherosclerosis, was assessed by carotid ultrasound. RESULTS: ABPM abnormalities were more prevalent (57% vs 24%, respectively), and daytime, nighttime and 24-h systolic, diastolic, and mean arterial blood pressure indices were higher in children with type 1 diabetes compared to control children. The odds estimate of an ABPM abnormality was 6.68 (95% confidence interval: 1.95, 22.9; P = .003) in children with type 1 diabetes compared to controls after adjusting for age, sex, and BMI standardized for age and sex (zBMI). An interaction between ABPM and zBMI on cIMT was observed. In children with type 1 diabetes and ABPM abnormalities, every 1 SD increase in zBMI was associated with a 0.030 mm increase in cIMT (95% confidence interval: 0.002, 0.041; P = .031). This was not observed in control children with ABPM abnormalities or in children with normal ABPM, regardless of type 1 diabetes status. CONCLUSIONS: Children with type 1 diabetes have a high prevalence of ABPM abnormalities independent of disease duration and this is related to early indicators of cardiovascular damage.

Factors influencing the timing of initiation of renal replacement therapy and choice of modality in children with end-stage kidney disease.

BACKGROUND: Decision-making in pediatric end-stage renal disease (ESRD) is a complex process for patients, families, and physicians. We evaluated the factors influencing the timing of initiation of renal replacement therapy (RRT) and choice of modality in children with ESRD. METHODS: We retrospectively reviewed the RRT decision-making process for all children up to 19 years of age with ESRD, who underwent RRT over an 11-year period (2004 to 2014), at a Canadian pediatric tertiary care center. RRT modalities included peritoneal dialysis (PD), hemodialysis (HD), pre-emptive kidney transplant (PKT), and continuous renal replacement therapy (CRRT). RESULTS: Ninety-two patients progressed to ESRD. RRT was started electively for 58 patients, and urgently for 34 patients. For elective patients, modalities included PD (34%), HD (19%), and PKT (47%). The glomerular filtration rate at initiation of RRT was higher in patients who underwent PKT as opposed to dialysis (11.7 vs. 9.1 ml/min/1.73m2). Medical and quality of life factors, including fatigue and poor concentration, influenced the timing of initiation of elective RRT. Medical factors were primarily important in urgent RRT, including oligoanuria and metabolic disturbances. Medical factors, patient/family preference, and contextual factors such as location of residence influenced choice of modality. CONCLUSIONS: Our study found that the decision-making process in ESRD is multifactorial and involves not only medical factors, but also assessment of social factors, quality of life, and patient/family preference. Bettering our understanding of this decision-making process will positively impact patients and families through more informed decision-making.

Exome Sequencing and the Management of Neurometabolic Disorders.

BACKGROUND: Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. METHODS: To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patient's clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. RESULTS: We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). CONCLUSIONS: Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Children's Hospital Foundation and others.).

Identifying Important Outcomes for Young People With CKD and Their Caregivers: A Nominal Group Technique Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers. STUDY DESIGN: We used the nominal group technique whereby participants identified and ranked outcomes and explained their priorities. SETTINGS & PARTICIPANTS: Young people with CKD (stages 1-5, dialysis, or transplantation) and their caregivers were purposively sampled from 6 centers across Australia, the United States, and Canada. ANALYTICAL APPROACH: Importance scores were calculated (scale of 0-1), and qualitative data were analyzed thematically. RESULTS: 34 patients (aged 8-21 years) and 62 caregivers participated in 16 groups and identified 48 outcomes. The 5 highest ranked outcomes for patients were survival (importance score, 0.25), physical activity (0.24), fatigue (0.20), lifestyle restrictions (0.20), and growth (0.20); and for caregivers, kidney function (0.53), survival (0.28), infection (0.22), anemia (0.20), and growth (0.17). 12 themes were identified reflecting their immediate and current priorities (wanting to feel normal, strengthening resilience, minimizing intrusion into daily life, imminent threats to life, devastating family burdens, and seeking control over health) and considerations regarding future impacts (protecting health/development, remaining hopeful, concern for limited opportunities, prognostic uncertainty, dreading painful and invasive procedures, and managing expectations). LIMITATIONS: Only English-speaking participants were recruited. CONCLUSIONS: Kidney function, infection, survival, and growth were the highest priorities for patients with CKD and their caregivers. Young people with CKD also prioritized highly the outcomes that directly affected their lifestyle and sense of normality, while caregiver's highest priorities concerned the long-term health of their child, current health problems, and the financial and family burdens of caring for a child with CKD.

In support of point-of-care social needs screening: The effects of five social determinants on the health of children with chronic diseases in British Columbia.

BACKGROUND: Prior to introducing social needs screening into our subspecialty clinics, we first wanted to understand the health effects of the major social challenges facing children with chronic diseases in British Columbia. METHODS: Using a strict prospective methodology, avoiding use of health databases and proxy end points, we studied the effects of five social health determinants (distance from care, family income, gender, ethnicity, caregiver education), on health outcomes in three groups of children with chronic diseases: cystic fibrosis (CF), type 1 diabetes (T1D), chronic kidney disease (CKD). Social determinant data were collected at a face-to-face interview during a clinic visit. These were correlated with diagnosis-specific health outcomes, measured at the same visit. Main outcomes were: forced expired volume in 1 second (FEV1) (CF group), HbA1c (T1D group), estimated glomerular filtration rate (CKD group). RESULTS: We studied 270 children: 85 CF, 89 T1D and 96 CKD. In all three groups, children from families with annual income less than $45,000 had significantly worse health than those from families above this cut-off. Lower caregiver education was related to worse health in the CKD and T1D groups. We found no adverse health effects associated with distance from subspecialty care, patient ethnicity or gender. CONCLUSION: Even in a prosperous province, family poverty and lack of caregiver education still impose measurable adverse effects on the health of children with chronic diseases. We hope these results help support the integration of social needs screening into routine multidisciplinary outpatient clinics. Early detection of social problems and targeted interventions will hopefully help to equalize health outcomes between children from different social groups.

Child and Parental Perspectives on Communication and Decision Making in Pediatric CKD: A Focus Group Study.

BACKGROUND & OBJECTIVES: Effective communication and shared decision making improve quality of care and patient outcomes but can be particularly challenging in pediatric chronic disease because children depend on their parents and clinicians to manage complex health care and developmental needs. We aimed to describe the perspectives of children with chronic kidney disease (CKD) and their parents with regard to communication and decision making. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: Children with CKD (n=34) and parents (n=62) from 6 centers across 6 cities in Australia, Canada, and the United States participated in 16 focus groups. ANALYTICAL APPROACH: Transcripts were analyzed thematically. RESULTS: We identified 4 themes: (1) disempowered by knowledge imbalance (unprepared and ill-informed, suspicion of censorship, and inadequacy as technicians), (2) recognizing own expertise (intuition and instinct unique to parental bond, emerging wisdom and confidence, identifying opportunities for control and inclusion, and empowering participation in children), (3) striving to assert own priorities (negotiating broader life impacts, choosing to defer decisional burden, overprotected and overruled, and struggling to voice own preferences), and (4) managing child's involvement (respecting child's expertise, attributing "risky" behaviors to rebellion, and protecting children from illness burden). LIMITATIONS: Only English-speaking participants were recruited, which may limit the transferability of the findings. We collected data from child and parent perspectives; however, clinician perspectives may provide further understanding of the difficulties of communication and decision making in pediatrics. CONCLUSIONS: Parents value partnership with clinicians and consider long-term and quality-of-life implications of their child's illness. Children with CKD want more involvement in treatment decision making but are limited by vulnerability, fear, and uncertainty. There is a need to support the child to better enable him or her to become a partner in decision making and prepare him or her for adulthood. Collaborative and informed decision making that addresses the priorities and concerns of both children and parents is needed.

Updated Guideline May Improve the Recognition and Diagnosis of Hypertension in Children and Adolescents; Review of the 2017 AAP Blood Pressure Clinical Practice Guideline.

PURPOSE OF REVIEW: Hypertension in children and adolescents is under-recognized and under-diagnosed in clinical practice. The 2017 AAP Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents provides updated recommendations that may improve hypertension identification and management. RECENT FINDINGS: The AAP blood pressure guideline recommends annual screening for hypertension in children at preventive care visits and targeted routine screening in high-risk populations. A simplified blood pressure screening table is provided for easier recognition of blood pressures that may require attention. Normative blood pressure tables have been revised to include only data from normal-weight children as more representative of a healthy population. Classification of blood pressure in adolescents has been simplified to threshold values consistent with adult guidelines. The updated AAP blood pressure guideline has clarified and simplified recommendations for hypertension screening, diagnosis, and management based on a systematic review of current best evidence.

Can office blood pressure readings predict masked hypertension?

BACKGROUND: Studies in children with chronic kidney disease indicate a high prevalence of masked hypertension detected by ambulatory blood pressure monitoring (ABPM). However, it is not well known if the frequency of masked hypertension is related to the level of normal casual blood pressure (BP). METHODS/RESULTS: We hypothesized that lower levels of normal casual BP are associated with a lower prevalence of masked hypertension. Data from the chronic kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple visits. The majority of children with normal casual BP also had normal wake and sleep ABP (60 %), even at the highest percentiles of casual BP. The frequency of masked hypertension was lower in children with casual BP ≤25th percentile versus those with casual BP in 26-50th percentile and casual BP in 51-90th percentile during both wake and sleep periods. In children with the lowest normal casual BP levels (≤25th percentile), the frequency of abnormal mean wake or sleep ABP was 2-7 %, and of abnormal BP load was 6-16 %. CONCLUSIONS: These data suggest that masked hypertension is unlikely if the casual BP is found to be in the low normal range.

Vitamin D insufficiency and deficiency in pediatric renal transplant recipients.

Vitamin D deficiency is prevalent in the pediatric CKD population. Recognizing that renal transplant recipients have CKD, we assessed the prevalence of vitamin D insufficiency and deficiency in pediatric renal transplant recipients, compared to a healthy pediatric population. We prospectively studied 25(OH)D levels in 29 pediatric renal transplant recipients and 45 control patients over one yr. The overall prevalence of vitamin D insufficiency and deficiency was common in both populations, at 76% (95% CI: 61, 87%) in the pediatric renal transplant recipients and 91% (95% CI: 80, 98%) in the control group. In the paired renal transplant samples, the mean 25(OH)D level was 52.3 ± 17.9 nmol/L in the winter and 65.6 ± 18.8 nmol/L in the summer (95% CI diff.: 3.9, 22.7), in keeping with a significant seasonal difference. The mean dietary intake of vitamin D in the renal transplant recipients, assessed by three-day dietary record, was 5.7 µg/day, with a vitamin D intake below the EAR in the majority. We did not find an association between vitamin D intake and 25(OH)D levels in this study, likely due to the low dietary intake of vitamin D within the transplant population, identifying a potential area for intervention and improvement.

Evidence-based guidelines for the management of hypertension in children with chronic kidney disease.

Hypertension is common in children with chronic kidney disease and early evidence suggests that it is a modifiable risk factor for renal and cardiovascular outcomes. Recommendations for blood pressure management in children with chronic kidney disease can be found in various clinical practice guidelines including the 4th Task Force Report, the European Society of Hypertension pediatric recommendations, and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the management of blood pressure in chronic kidney disease. Unfortunately, as pediatric trial evidence is limited, there are discrepancies in the recommendations that may lead to inconsistent clinical care and practice variation. This article reviews the strength of evidence behind each of the clinical practice guideline recommendations regarding blood pressure assessment, treatment targets, and first-line antihypertensive medications. The benefits and cautions of use of clinical practice guidelines are described with emphasis on the importance of reading beyond the summary statements.

Sustaining life or prolonging dying? Appropriate choice of conservative care for children in end-stage renal disease: an ethical framework.

Due to technological advances, an increasing number of infants and children are surviving with multi-organ system dysfunction, and some are reaching end-stage renal disease (ESRD). Many have quite limited life expectancies and may not be eligible for kidney transplantation but families request dialysis as alternative. In developed countries where resources are available there is often uncertainty by the medical team as to what should be done. After encountering several of these scenarios, we developed an ethical decision-making framework for the appropriate choice of conservative care or renal replacement therapy in infants and children with ESRD. The framework is a practical tool to help determine if the burdens of dialysis would outweigh the benefits for a particular patient and family. It is based on the four topics approach of medical considerations, quality-of-life determinants, patient and family preferences and contextual features tailored to pediatric ESRD. In this article we discuss the basis of the criteria, provide a practical framework to guide these difficult conversations, and illustrate use of the framework with a case example. While further research is needed, through this approach we hope to reduce the moral distress of care providers and staff as well as potential conflict with the family in these complex decision-making situations.

Long-Term Cardiovascular Outcomes in Children and Adolescents With Hypertension.

Importance: Hypertension affects 6% of all children, and its prevalence is increasing. Childhood hypertension tracks into adulthood and is associated with subclinical cardiovascular disease; however, there is a lack of evidence linking childhood hypertension to cardiovascular outcomes, which may contribute to underdiagnosis and undertreatment. Objective: To determine the long-term associated risk of major adverse cardiac events (MACE) among children diagnosed with hypertension. Design, Setting, and Participants: This was a population-based, retrospective, matched cohort study conducted from 1996 to 2022. The study included all children (aged 3-18 years) alive in Ontario, Canada, from 1996 to 2021, who were identified using provincial administrative health databases. Children with prior kidney replacement therapy were excluded. Exposure: Incident hypertension diagnosis, identified by validated case definitions using diagnostic and physician billing claims. Each case was matched with 5 controls without hypertension by age, sex, birth weight, maternal gestational hypertension, prior comorbidities (chronic kidney disease, diabetes, cardiovascular surgery), and a propensity score for hypertension. Main Outcomes and Measures: The primary outcome was MACE (a composite of cardiovascular death, stroke, hospitalization for myocardial infarction or unstable angina, or coronary intervention). Time to MACE was evaluated using the Kaplan-Meier method and Cox proportional hazards regression. Results: A total of 25 605 children (median [IQR] age, 15 [11-17] years; 14 743 male [57.6%]) with hypertension were matched to 128 025 controls without hypertension. Baseline covariates were balanced after propensity score matching, and prior comorbidities were uncommon (hypertension vs control cohort: malignancy, 1451 [5.7%] vs 7908 [6.2%]; congenital heart disease, 1089 [4.3%] vs 5408 [4.2%]; diabetes, 482 [1.9%] vs 2410 [1.9%]). During a median (IQR) of 13.6 (7.8-19.5) years of follow-up, incidence of MACE was 4.6 per 1000 person-years in children with hypertension vs 2.2 per 1000 person-years in controls (hazard ratio, 2.1; 95% CI, 1.9-2.2). Children with hypertension were at higher associated risk of stroke, hospitalization for myocardial infarction or unstable angina, coronary intervention, and congestive heart failure, but not cardiovascular death, compared with nonhypertensive controls. Conclusions and Relevance: Children diagnosed with hypertension had a higher associated long-term risk of MACE compared with controls without hypertension. Improved detection, follow-up, and control of pediatric hypertension may reduce the risk of adult cardiovascular disease.

Neonatal blood pressure by birth weight, gestational age, and postnatal age: a systematic review.

BACKGROUND: Blood pressure is a vital hemodynamic marker during the neonatal period. However, normative values are often derived from small observational studies. Understanding the normative range would help to identify ideal thresholds for intervention to treat hypotension or hypertension. Therefore, the aim of this study was to assess observed blood pressure values in neonates who have not received any blood-pressure modifying treatments from birth to three months postnatal age and whether these vary according to birth weight, gestational age and postnatal age. METHODS: This was a systematic review. A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on blood pressure in neonates from birth to 3 months of age (PROSPERO ID CRD42018092886). Unpublished data were included where appropriate. RESULTS: Of 3,587 non-duplicate publications identified, 30 were included (one unpublished study). Twelve studies contained data grouped by birth weight, while 23 contained data grouped by gestational age. Study and clinical heterogeneity precluded meta-analyses thus results are presented by subgroup. A consistent blood pressure rise was associated with increasing birth weight, gestational age, and postnatal age. In addition, blood pressure seemed to rise more rapidly in the most preterm and low birth weight neonates. CONCLUSION: Despite blood pressure increasing with birth weight, gestational age, and postnatal age, there was marked blood pressure variability observed throughout. To better define hypotension and hypertension, future studies should develop consistent approaches for factors related to blood pressure variability, including the method and timing of measurement as well as statistical control of relevant patient characteristics.