Purpose: To synthesize all existing literature on the association between sodium disturbances during the first 10 days of life in Extremely-Low-Birth-Weight (ELBW) infants and the risk of developing severe intraventricular hemorrhage (IVH > grade 1) or long-term neurodevelopmental impairment. Methods: Applying systematic review (ID CDR42024622933) principles, five major databases were explored. Any study was included if it reported on ELBW infants, on serum sodium values within the first 10 postnatal days, or was related these to neurocognitive or neurodevelopmental outcomes. Results: Ten studies (13,276 infants) met inclusion criteria. Six studies evaluated the association between hypernatremia (>145 or >150 mmol/L) and severe IVH, and two reported a significant association. Among two studies studying hyponatremia (ranging <130 or <120 mmol/L), one found a significant association with severe IVH. Evidence regarding sodium fluctuations (difference between the maximum and minimum serum sodium values) identified fluctuations >13 mmol/L as a strong risk factor for severe IVH, while another study showed that glucose-corrected sodium fluctuations were independently associated with severe IVH. Long-term neurodevelopmental outcomes were reported in four studies; hyponatremia was significantly associated with hearing loss in one study (OR 5.6 (95% CI 1.1–27.8)), while another study reported that glucose-corrected sodium fluctuations were associated with neurodevelopmental impairment at 18–21 months, although significance disappeared after adjustment for confounding factors. Conclusion: Considering the limitations related to heterogeneity in study design, threshold sodium values and cohort size, this systematic review suggests a possible association between early sodium disturbances and adverse neurodevelopmental outcomes in ELBW infants, emphasizing the need for further high-quality, prospective studies, especially since sodium management can be modulated.

Acute kidney injury (AKI) is a common and serious complication among infants admitted to neonatal intensive care units, affecting up to one-third of hospitalized neonates and contributing to significant short- and long-term morbidity and mortality. The unique physiology of the developing kidney, coupled with diverse neonatal comorbidities, creates both susceptibility to injury and challenges in timely diagnosis. Recent multicenter epidemiologic studies have clarified the incidence, risk factors, and outcomes of neonatal AKI, emphasizing the importance of standardized definitions and early recognition. Advances in monitoring strategies—including near-infrared spectroscopy and early biomarkers of renal stress—offer opportunities for earlier detection, while heightened attention to fluid balance, nephrotoxic stewardship, and targeted pharmacologic interventions support primary and secondary prevention. For infants requiring kidney support, technological innovation has expanded the feasibility and safety of renal replacement therapies, even in the smallest patients. Emerging evidence also highlights strong associations between neonatal AKI, prematurity, and long-term kidney health, prompting new consensus recommendations for risk-stratified outpatient surveillance. This review synthesizes current knowledge and recent advances in neonatal AKI, underscoring the need for proactive, multidisciplinary approaches to preserve kidney health from the earliest stages of life into child- and adulthood.

Importance:Blood pressure (BP) is a crucial modifiable risk factor associated with cardiovascular disease in adulthood. The modifiable impact of BP may begin from birth and operate across the whole life span. However, no up-to-date studies have tracked BP from birth onward. Objective:To explore BP trajectory in childhood and evaluate whether the risk of hypertension later in childhood is associated with BP at birth and in early childhood. Design, Setting, and Participants:This cohort study evaluated data from the Belgian ENVIRONAGE birth cohort study with longitudinal follow-up visits in children aged 4 to 6 years (first follow-up [FU1]) and aged 9 to 11 years (second follow-up [FU2]). The study was initiated February 2, 2010, and data were collected and analyzed until August 30, 2024. Exposure:Childhood blood pressure. Main Outcomes and Measures:The main outcomes were incidences of elevated BP and hypertension at the last follow-up (FU1 or FU2). Tracking was assessed using change in mean arterial pressure (MAP) percentiles between 2 visits. Elevated BP and hypertension at childhood were standardized for age, sex, and height following the 2017 American Academy of Pediatrics guideline. Analyses were performed using multivariable-adjusted linear, mixed, and Cox proportional hazards regression models. Results:The study included 500 healthy children (mean [SD] gestational age, 39.2 [1.6] weeks; 266 girls [53.2%]), with 445 having 2 BP measurements and 55 having 3 BP measurements. From birth to FU1, mean (SD) systolic BP (SBP), diastolic BP (DBP), and MAP tracked from 67.3 (8.8) mm Hg, 40.5 (8.3) mm Hg, and (8.2) mm Hg, respectively, to 100.2 (8.5) mm Hg, 57.5 (9.1) mm Hg, and 74.6 (7.8) mm Hg, respectively. At FU2, mean (SD) SBP, DBP, and MAP tracked to 107.7 (9.5) mm Hg, 65.1 (6.4) mm Hg, and 82.1 (6.7) mm Hg, respectively. Per 1-SD increase in initial BP at birth or age 4 to 6 years, for all children in the combined dataset, BP at the last follow-up increased by 2.66 mm Hg (95% CI, 1.65-3.67 mm Hg) for SBP, 1.37 mm Hg (95% CI, 0.28-2.46 mm Hg) for DBP, and 1.97 mm Hg (95% CI, 0.85-3.10 mm Hg) for MAP. In the fully adjusted models, for each 1-SD increase in the initial MAP, the hazard ratios of elevated BP and hypertension were 2.84 (95% CI, 1.50-5.38) and 3.75 (95% CI, 1.79-7.86), respectively. Conclusions and Relevance:This prospective cohort study found that BP tracked consistently from birth through childhood. Higher BP levels at birth and early childhood were associated with an increased risk of elevated BP and hypertension later in childhood. These findings highlight the importance of monitoring and managing BP from birth as a potential strategy to reduce cardiovascular risk later in life.

Acute kidney injury (AKI) is increasingly recognized as a critical and underdiagnosed condition among neonates, with significant short and long-term implications for survival, kidney function, and long-term cardiovascular health. Neonatal physiology, including ongoing nephrogenesis, immature renal haemodynamics, and limited glomerular filtration, makes this population vulnerable to AKI. Advances in consensus definitions, particularly the modified neonatal Kidney Disease Improving Global Outcomes (KDIGO) criteria, have enhanced epidemiologic understanding and facilitated global research collaboration. Despite this, significant variability in AKI surveillance, diagnosis, and follow-up persists. Recent research efforts within Australia emphasize the need to incorporate AKI metrics into quality registries and improve equity of kidney care for infants. Integration of protocolized monitoring, preventative strategies such as nephrotoxin stewardship and methylxanthine therapy, and long-term follow-up for AKI survivors are essential to mitigating progression to chronic kidney disease. This narrative review synthesizes evolving evidence in neonatal renal physiology, AKI definition and biomarkers, epidemiology, management, and policy directions, emphasizing opportunities for education, protocol development, and collaborative improvement across Australia, New Zealand and beyond.

BACKGROUND:Premature birth disrupts the intra-uterine structural and functional maturation of the left ventricle (LV) and arteries. The study investigated the impact of premature birth on ventricular-arterial coupling (VAC), a potential precursor of cardiovascular disease in adulthood. METHODS:This case-control study in Northern Belgium (2011-2016) included 93 extremely-low-birth-weight (ELBW) cases and 87 sex and age-matched term-born controls. Main outcomes included SBP and DBP, central arterial properties, echocardiographic structure and function, and VAC. RESULTS:Compared with controls, cases were shorter by 4.1 cm [95% confidence interval (95% CI): 1.3-7.0] and lighter by 4.1 kg (95% CI: 1.3-6.9). Cases had higher central SBP/DBP (+7.3/3.0 mmHg; 95% CI: 4.7-9.9/1.1-4.8), lower left ventricular end-diastolic and end-systolic dimensions, and 9.2 g (95% CI: 3.7-14.6) lower left ventricular mass. Left ventricular volumes and mass correlated with body size without significant between-group differences ( P  ≥ 0.12). Cardiac output was 0.38 l/min lower in cases, who also had higher arterial resistance (29.5 vs. 24.4 mmHg × min/l) and augmentation ratio (1.10 vs. 1.05). The tension-time index was 231 mmHg × ms (95% CI: 128-335) higher in cases. Ea and Ees were higher in cases (0.40 and 0.65 mmHg/ml, respectively), but VAC did not differ between groups ( P  = 0.48). CONCLUSION:Compensatory mechanisms maintain the anatomical and functional integrity of the cardiovascular system in ELBW youth, but mask their vulnerability to cardiovascular disease in adulthood and necessitate careful follow-up during adolescence.

In neonates, estimation of the glomerular filtration rate is problematic, and assessment of renal impairment is challenging. Serum creatinine is a widely used marker, and urine output is an important vital parameter monitored in intensive care settings, particularly in unwell neonates. However, the rapid changes after birth with adaptation to the extrauterine environment is a unique situation in which absolute serum creatinine is not a reliable indicator of renal function. A rise in serum creatinine from the previous value during the neonatal period can be a result of worsening renal function in neonates but is dependent on many other factors. In addition, urine output can be difficult to measure in sick neonates during their intensive care stay. Despite a high prevalence of acute kidney injury (AKI) in preterm and/or unwell infants, the current definitions are not straightforward and do not take postnatal adaptation processes into account. The management of AKI is challenging in very young and small patients because the assessment of fluid status as well as balancing nutritional needs with fluid restriction can be problematic. The Australian Neonatal Medicines Formulary provides advice on drug dosing in the face of reduced renal function in neonates. Predictors (or long-term outcome, or recovery) after AKI diagnosis are still poorly described. Therefore, the diagnosis of neonatal AKI needs to be documented and transferred to the paediatrician responsible for the follow-up of the child. This educational review aims to give a perspective on neonatal kidney function and AKI, the relation of fluid balance and creatinine, the management of neonatal AKI and the consequences for drug dosing and long-term outcomes.

Background: Sodium regulation is critical in extremely low birth weight (ELBW, < 1000 grams) in-fants. In a recent systematic review, a sodium pattern over postnatal age and its variables (care factors, fluid regimens, maturational factors) has been summarized. However, this systematic re-view also illustrated the shortages and limitations of reported cohorts, and the need to report on additional datasets. This study therefore aims to describe the postnatal sodium patterns and its variables in a cohort of ELBW neonates in their first 10 days of life. Methods: Data on 1704 serum sodium observations in the first 10 days of life from 211 ELBW infants admitted to a single neonatal intensive care unit were available to explore associations between serum sodium and perinatal variables. Multivariate linear models with sodium as response variable and postnatal day as factor were hereby applied. Baseline and treatment characteristics were included as variables, applying an unstructured covariance matrix to account for the longitudinal data. Results: Gestational age, birth weight, and length, showed variable correlations with serum sodium concentrations over postnatal age. Interesting, the analysis on sodium patterns in this ELBW cohort also revealed significant as-sociations between prenatal betamethasone use, delivery mode, ibuprofen, or the use of inotropics and the postnatal serum sodium concentrations patterns. Multivariate analyses confirmed that gestational age and birth weight independently impacted sodium concentration patterns, and that ibuprofen use remained a significant variable after adjusting for these variables. Conclusions: Gestational age and birth weight complexities emphasize the need for nuanced understanding and standardized methodologies. Sodium patterns in the current ELBW cohort provide support for previously published sodium reference patterns in this population. New variables associated with sodium levels include ibuprofen administration, and the use of inotropic agents.

Background: Sodium regulation is critical in extremely low-birth-weight (ELBW, <1000 g) infants. In a recent systematic review, a sodium pattern over postnatal age and its variables (care factors, fluid regimens, and maturational factors) has been summarized. However, this systematic review also illustrated the shortages and limitations of reported cohorts, and the need to report on additional datasets. This study therefore aims to describe the postnatal sodium patterns and their variables in a cohort of ELBW neonates in the first 10 days of postnatal life. Methods: Data on 1704 serum sodium observations in the first 10 days of life from 211 ELBW infants hospitalized in a single neonatal intensive care unit were available to explore associations between serum sodium and perinatal variables. Multivariate linear models with sodium as a response variable and postnatal day as a factor were hereby applied. Baseline and treatment characteristics were included as variables, applying an unstructured covariance matrix to account for the longitudinal data. Results: Gestational age, birth weight, and length showed variable correlations with serum sodium concentrations over postnatal age. Interestingly, the analysis of sodium patterns in this ELBW cohort also revealed significant associations between prenatal betamethasone use, delivery mode, ibuprofen, or the use of inotropes and the postnatal serum sodium concentrations patterns. Multivariate analyses confirmed that gestational age and birth weight independently impacted sodium concentration patterns, and that ibuprofen use remained a significant variable after adjusting for these variables. Conclusions: Gestational age and birth weight complexities emphasize the need for nuanced understanding and standardized methodologies. Sodium patterns in the current ELBW cohort provide support for previously published sodium reference patterns in this population. New variables associated with sodium levels include ibuprofen administration and the use of inotropic agents.

BACKGROUND:Epidemiological evidence suggests higher rates of heart failure in adults born at an extremely low birth weight (ELBW). Reports on the echocardiographic phenotype in this population are inconsistent and do not consider the effect of modifiable contributors such as blood pressure. METHODS:This study reports on the echocardiographic findings of the PREMATurity as predictor of children's Cardiovascular-renal Health (PREMATCH) study, a prospective case-control study evaluating renal and cardiovascular outcomes in children with ELBW in comparison to term-born controls. Left ventricular (LV) mass was the primary outcome. Data were analyzed with multivariable-adjusted regression models considering anthropometric variables and systolic blood pressure as covariates. RESULTS:Eighty cases (median age, 10.8 years) and 72 controls (median age, 11.4 years) were included. Multivariable-adjusted analyses revealed that the adjusted difference in LV mass in cases versus controls was -8.49 g (CI, -13.78 to -3.20; P=0.002). Sex, height, weight, and body fat percentage were significant covariates. There was a positive interaction between ELBW status and systolic blood pressure (Pinteraction=0.039). There was a -6.47 g (CI, -11.7 to 1.28; P=0.016) difference in LV mass between normotensive cases and controls, while the difference disappeared between subjects with increased blood pressure or hypertension. CONCLUSIONS:ELBW children exhibit lower LV mass during childhood in comparison with term-born controls. However, elevations in systolic blood pressure are associated with a steeper increase in LV mass in cases than in controls. Our findings question whether cutoffs for the general population are adequate to evaluate and manage hypertension and LV hypertrophy in children with ELBW.

The prevalence of obesity in adolescents is rising, including in those with kidney failure. Obesity increases the risk of complications during dialysis and may be associated with poorer outcomes after transplantation. Bariatric surgery has been found safe and effective in adults on dialysis. This Clinical Insights is about a 14-year-old female with kidney failure and obesity. She was initially managed on peritoneal dialysis but subsequently gained further weight. Multiple interventions for weight loss were unsuccessful, including the switch to haemodialysis. The patient underwent laparoscopic sleeve gastrectomy after extensive multidisciplinary assessment. She lost > 30 kg over 6 months (BMI decreased from 48 to 32 kg/m2) which made it possible for her to be activated on the deceased donor kidney transplant waiting list. Managing weight gain in patients on peritoneal dialysis is important, especially in obese adolescents. Bariatric surgery should be considered early where morbid obesity is a major impediment to listing for kidney transplantation.

Background/Objectives: Sodium regulation is critical in extremely low birth weight (ELBW, <1000 g) infants. This study aimed to provide a comprehensive overview of sodium dynamics and related variables in ELBW infants in their first 10 days of life through a structured literature review. Methods: Applying PRISMA guidelines, six databases were searched (1 August 2023) on sodium measurements in ELBW cohorts, with quality assessment (RoB2, ROBINS-1, Newcastle Ottawa scale) of retained papers, and subsequent data extraction in line with these PRISMA guidelines to describe findings. Results: Only eight heterogeneous studies could be retained, including observational cohort studies (n = 5), case–control studies (n = 2, Tegaderm application yes/no, gestational age < 24 or 24–28 weeks), and only one randomized trial (sodium restriction versus no sodium restriction). Definitions of hyper- or hyponatremia were also heterogeneous, with incidence ranges for hyper- (8–92.2%) and hyponatremia (0–52.9%). Peak sodium values were observed on days 2–4 in the individual studies. When pooled and compared to the cohort mean sodium values, the highest increases in mean serum sodium values were observed on day 3 (+4, range, −0.6 to +8.6 mEq). Variables of sodium values were related to care factors [incubator settings (open/closed, double-/not double-walled, humidity), fluid regimens (water volume, sodium supplementation), occlusive skin care], as well as related maturational factors (postnatal age, gestational age, small versus appropriate for gestational age, SGA/AGA). Conclusions: Based on a structured literature review, patterns of sodium changes over postnatal age in ELBW cases were documented. Besides incubator settings, fluid regimens, or occlusive skin care, these patterns also depend on maturational factors of the ELBW infant (gestational age, postnatal age, SGA/AGA). These complexities emphasize the need for nuanced interpretation, the relevance of standardizing clinical practices and research definitions, and the need to report on additional datasets.

Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors for these adverse outcomes which we have investigated in this study. We compared renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal outcome and to unveil associations between kidney function and blood pressure. This study included 93 former ELBW children and 87 healthy controls with a mean age of 11 years at assessment. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children. ELBW children have significantly higher blood pressure (mean SBP percentile 75th vs. 47th, p <0.001) and lower mean eGFR (94 vs. 107 ml/min/1.73 m2, p = 0.005) compared to the control group. Elevated blood pressure did not correlate with perinatal characteristics and none of them had microalbuminuria. ELBW children with eGFR <90 ml/min/1.73 m2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40

Abstract Background Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors and their similarity for these adverse outcomes. Methods We compared cardiovascular-renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal and cardiovascular outcome and to unveil associations between kidney function and blood pressure. This study included 93 ELBW children and 87 healthy controls. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children. Results ELBW children have significantly higher blood pressure and lower eGFR. Elevated blood pressure did not correlate with perinatal characteristics. ELBW children with eGFR < 90 ml/min/1.73m2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40% vs. 15.8%, p = 0.056). There was no association between blood pressure and kidney dysfunction. Conclusions Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney or cardiac dysfunction. These risk profiles could be different for renal and cardiovascular outcome. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk.

There is currently no consensus on the guidelines for vitamin D prophylaxis in healthy children. The purpose of this study was to investigate the prescribing behaviour of vitamin D prophylaxis among Belgian paediatricians. Between June and September 2022, a questionnaire was distributed by email to all Belgian paediatricians who are a member of at least one of three scientific or professional organisations, as well as to the heads of every Belgian paediatric or neonatal hospital ward. We analysed 426 completed questionnaires. All regions, age categories and subspecialties were represented. Vitamin D prophylaxis is always or frequently recommended by 98% of paediatricians. Fifty-eight per cent of paediatricians advise vitamin D prophylaxis up to the age of six years and 66% of paediatricians advise a daily dose of 400 IU. In nearly every hospital in Belgium (96%), there is a specific protocol for vitamin D prophylaxis for newborns; but not for the paediatric unit (only 30%). Nearly all Belgian paediatricians prescribe vitamin D prophylaxis to infants. Although not recommended by guidelines, 25(OH)D is frequently measured by paediatricians. Practices regarding duration and dosing of vitamin D prophylaxis show large variability. Most neonatal wards do have a protocol, whereas most paediatric wards do not.