Blood volume reduction due to rapid plasma loss after birth in preterm piglets.

BACKGROUND: Understanding changes in blood volume after preterm birth is critical to preventing cardiovascular deterioration in preterm infants. The aims were to determine if blood volume is higher in preterm than term piglets and if blood volume changes in the hours after birth. METHODS: Paired blood volume measurements were conducted in preterm piglets (98/115d gestation, ~28wk gestation infant) at 0.5-5 h (n = 12), 0.5-9 h (n = 44) and 5-11 h (n = 7) after birth, and in a term cohort at 0.5-9 h (n = 40) while under intensive care. RESULTS: At 30 min after birth, blood volume was significantly lower in preterm piglets compared to term piglets. By 9 h after birth, blood volume had reduced by 18% in preterm piglets and 13% in term piglets. By 5-9 h after birth, preterm piglets had significantly lower blood volumes than at term (61 ± 10 vs. 76 ± 11 mL/kg). CONCLUSIONS: In contrast to clinical resources, preterm piglets have a lower blood volume than at term. Substantial reductions in blood volume after birth leave some preterm piglets hypovolemic. If this also occurs in preterm infants, this may have important clinical consequences. Modern studies of blood volume changes after birth are essential for improving preterm outcomes. IMPACT: Preterm piglets do not have a higher blood volume than their term counterparts, in contrast to current clinical estimates. Rapid reduction in blood volume after birth leads to hypovolemia in some preterm piglets. There is a critical need to understand blood volume changes after birth in preterm infants in order to improve clinical management of blood volume.

Red cell infusion but not saline is effective for volume expansion in preterm piglets.

BACKGROUND: A common first-line treatment for supporting cardiovascular function in preterm infants is volume expansion using saline, but this does not improve outcomes. This study aimed to determine if volume expansion with saline increases blood volume, blood pressure and cerebral oxygenation; and if volume expansion with packed red blood cells (RBC) is more effective. We hypothesized that RBC infusion is more effective than saline for increasing blood volume and maintaining cardiovascular function and cerebral oxygenation. METHODS: Five groups of preterm piglets (98/115d gestation) were infused with saline (10 or 20 mL/kg) or RBC (10 or 20 mL/kg) or no treatment. Blood volume, blood pressure, central venous pressure, heart rate, carotid flow, cerebral oxygenation, arterial pH, base excess, and lactate levels were assessed for 6 h after treatment started. RESULTS: Both RBC groups had significant increases in blood volume, and improved measures of cardiovascular function, cerebral oxygenation and metabolic acidosis. Saline infusion did not increase blood volume or measures of cardiovascular function, cerebral oxygenation or metabolic acidosis. CONCLUSIONS: The results suggest that the deteriorating cardiovascular function in the hours after birth in preterm piglets, and possibly in premature babies, may be reversed or halted by more effective support of blood volume. IMPACT: Blood volume decreases after birth in preterm piglets and this decrease is associated with deteriorating cardiovascular function and cerebral oxygenation. Infusion of saline does not increase blood volume nor prevent deterioration in cardiovascular function. Infusion of packed red blood cells results in an increase in blood volume and improvements in cardiovascular function and cerebral oxygenation. Deteriorating cardiovascular function in the hours after birth in preterm piglets, and possibly in human preterm neonates, may be reversed or halted by more effective support of blood volume.

Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries.

BACKGROUND: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown. METHODS: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points. RESULTS: A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval [CI], 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups. CONCLUSIONS: Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).

Food anthocyanins decrease concentrations of TNF-α in older adults with mild cognitive impairment: A randomized, controlled, double blind clinical trial.

BACKGROUND & AIMS: Vascular function, blood pressure and inflammation are involved in the pathogenesis of major chronic diseases, including both cardiovascular disease (CVD) and mild cognitive impairment (MCI). This study investigated the effects of food anthocyanins on microvascular function, 24-h ambulatory blood pressure (ABP) and inflammatory biomarkers in older adults with MCI. METHODS AND RESULTS: Thirty-one participants with MCI [19 female, 12 male, mean age 75.3 (SD 6.9) years and body mass index 26.1 (SD 3.3) kg/m2], participated in a randomized, controlled, double-blind clinical trial (Australian New Zealand Clinical Trials Registry: ACTRN12618001184268). Participants consumed 250 mL fruit juice daily for 8 weeks, allocated into three groups: a) high dose anthocyanins (201 mg); b) low dose anthocyanins (47 mg); c) control. Microvascular function (Laser Speckle Contrast Imaging combined with a post-occlusive reactive hyperaemia test), 24h ABP and serum inflammatory biomarkers were assessed before and after the nutritional intervention. RESULTS: Participants in the high anthocyanins group had a reduction in serum tumor necrosis factor alpha (TNF-α) (P = 0.002) compared to controls and the low anthocyanins group (all P's > 0.05). Serum IL-6, IL-1ß, c-reactive protein, and parameters of microvascular function and 24h ABP were not altered by any treatment. CONCLUSION: A daily high dose of fruit-based anthocyanins for 8 weeks reduced concentrations of TNF-α in older adults with MCI. Anthocyanins did not alter other inflammatory biomarkers, microvascular function or blood pressure parameters. Further studies with a larger sample size and longer period of follow-up are required to elucidate whether this change in the immune response will alter CVD risk and progression of cognitive decline.

The impact of maternal asthma during pregnancy on offspring retinal microvascular structure and its relationship to placental growth factor production in utero.

Asthma is a common chronic disease in pregnancy that affects placental function and fetal growth and associated with cardio-metabolic disorders in the offspring but the mechanisms are unknown. This study explored whether maternal asthma in pregnancy is associated with the development of offspring microvascular structure and whether it was related to biomarkers of angiogenesis in utero. Children aged 4 to 6 years, born to either asthmatic mothers (n = 38) or healthy controls (n = 25), had their retinal microvascular structure examined. Maternal plasma PlGF concentrations at 18 and 36 weeks' gestation were measured. There was a significant global difference in all retinal microvascular measures between children of asthmatic mothers relative to controls and increased retinal venular tortuosity in children born to asthmatic mothers (7.1 (95% CI 0.7-13.5); P = .031). A rise in plasma PlGF from 18 to 36 weeks' gestation was observed in the control population which was significantly lower in the asthma group by 190.9 pg/mL. PlGF concentrations were correlated with microvascular structure including arteriolar branching and venular tortuosity. These exploratory findings indicate that exposure to maternal asthma during pregnancy is associated with persistent changes in microvascular structure in childhood that may be driven by alterations to angiogenic mechanisms in utero.

Predicting Nasal High-Flow Treatment Success in Newborn Infants with Respiratory Distress Cared for in Nontertiary Hospitals.

OBJECTIVE: To evaluate demographic and clinical variables as predictors of nasal high-flow treatment success in newborn infants with respiratory distress cared for in Australian nontertiary special care nurseries. STUDY DESIGN: A secondary analysis of the HUNTER trial, a multicenter, randomized controlled trial evaluating nasal high-flow as primary respiratory support for newborn infants with respiratory distress who were born ≥31 weeks of gestation and with birth weight ≥1200 g, and cared for in Australian nontertiary special care nurseries. Treatment success within 72 hours after randomization to nasal high-flow was determined using objective criteria. Univariable screening and multivariable analysis was used to determine predictors of nasal high-flow treatment success. RESULTS: Infants (n = 363) randomized to nasal high-flow in HUNTER were included in the analysis; the mean gestational age was 36.9 ± 2.7 weeks and birth weight 2928 ± 782 g. Of these infants, 290 (80%) experienced nasal high-flow treatment success. On multivariable analysis, nasal high-flow treatment success was predicted by higher gestational age and lower fraction of inspired oxygen immediately before randomization, but not strongly. The final model was found to have an area under the curve of 0.65, which after adjustment for optimism was found to be 0.63 (95% CI, 0.57-0.70). CONCLUSIONS: Gestational age and supplemental oxygen requirement may be used to guide decisions regarding the most appropriate initial respiratory support for newborn infants in nontertiary special care nurseries. Further prospective research is required to better identify which infants are most likely to be successfully treated with nasal high-flow. TRIAL REGISTRATION: ACTRN12614001203640.

Microvascular circulatory dysregulation driven in part by cystathionine gamma-lyase: A new paradigm for cardiovascular compromise in the preterm newborn.

OBJECTIVE: H2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition. METHODS: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H2 S, was determined by high-performance liquid chromatography. Real-time H2 S production was assessed using a microrespiration system in fetal and postnatal (10, 24 hours) skin and heart samples. CSE contribution was investigated by inhibition via propargylglycine. RESULTS: In preterm animals, postnatal H2 S production capacity in peripheral vasculature increased significantly and was significantly reduced by the inhibition of CSE. Urinary thiosulfate correlated with both microvascular blood flow and capacity of the vasculature to produce H2 S. H2 S produced via CSE did not correlate directly with microvascular blood flow. CONCLUSIONS: In preterm neonates, H2 S production increases during fetal-to-neonatal transition and CSE contribution to total H2 S increases postnatally. CSE-dependent mechanisms may therefore underpin the increase in H2 S production over the first 72 hours of life in preterm human neonates, associated with both central and peripheral cardiovascular instability.

Supporting preterm cardiovascular function.

Preterm infants are at higher risk of adverse neurodevelopmental outcomes. Inadequate cerebral oxygen delivery resulting from poor cardiovascular function is likely to be a significant contributor to preterm brain injury. In this context, improved support of cardiovascular function is integral to improving preterm outcomes. Many of the treatments used to support preterm cardiovascular function are based on adult physiology and may not be appropriate for the unique physiology of the preterm infant. The preterm heart is structurally immature with reduced contractility and low cardiac output. However, there is limited evidence that inotropic support with dopamine and/or dobutamine is effective in preterm babies. Hypovolemia may also contribute to poor preterm cardiovascular function; there is evidence that capillary leakage results in considerable loss of plasma from the circulation of newborn preterm babies. In addition, the vasoconstrictor response to acute stimuli does not develop until quite late in gestation and is limited in the preterm infant. This may lead to inappropriate vasodilatation adding to functional hypovolemia. The first line treatment for hypotension in preterm infants is volume expansion with crystalloid solutions, but this has limited efficacy in the preterm infant. More effective methods of volume expansion are required. Effective support of preterm cardiovascular function requires better understanding of preterm cardiovascular physiology so that treatments can target mechanisms that are sufficiently mature to respond.

Reduced blood volume decreases cerebral blood flow in preterm piglets.

KEY POINTS: Preterm infants often have poor cardiovascular function that is associated with adverse neurodevelopmental outcomes. Preterm infants may be vulnerable to hypovolaemia due to excessive vasodilatation and leaky capillaries. Following reduction in blood volume, cardiac output and mean arterial pressure were reduced to the same extent in term and preterm piglets. Cerebral blood flow was maintained following blood volume reduction in term but not in preterm piglets. Effective detection and treatment of functional hypovolaemia may reduce the risk of brain injury in preterm infants. ABSTRACT: Preterm infants often have impaired cardiovascular function that may contribute to poor neurodevelopmental outcomes. The study aimed to determine the effects of reduced blood volume on cardiovascular function, including cerebral blood flow, in preterm and term piglets. In preterm (97/115 days) and term piglets, up to 10% of the estimated blood volume was removed. Removal of blood was stopped if MAP dropped below 20 mmHg. Heart rate, cardiac contractility and relaxation, cardiac output, mean arterial pressure (MAP), and cerebral blood flow were measured at baseline and again after blood volume reduction. The volume of blood removed was less in preterm piglets than in term piglets (5.1 ± 1.8 vs. 7.7 ± 0.9 mL kg-1 , mean ± SD, P < 0.001). Cardiac output and MAP decreased to the same extent in term and preterm piglets. Cerebral blood flow decreased in preterm but not term piglets and cerebral vascular conductance increased in term piglets only. Compensatory responses to maintain cerebral blood flow after blood volume reduction are active in term piglets but not in preterm piglets. As a result, even a small reduction in blood volume, or an increase in the capacity of the circulatory system leading to functional hypovolaemia, may lead to a significant reduction in cerebral blood flow and contribute to brain injury in preterm neonates.

Influence of sympathetic activity in the control of peripheral microvascular tone in preterm infants.

BACKGROUND: Microvascular dysregulation following preterm birth is associated with increased illness severity and hypotension, particularly in males. Sympathetic nervous vascular regulation is evident in females. We hypothesized that sympathetic dysfunction in male preterm infants may contribute to a failure of peripheral microvascular vasoconstriction. METHODS: Microvascular blood flow of infants 24-43 wk gestational age was assessed at 6, 24, and 72 h of age by laser Doppler. Blood flow Fourier transformed frequency distribution spectra (low frequency/high frequency ratio) were used to assess the influence of sympathetic tone on microvascular regulation. Total sympathetic output was assessed as urinary normetanephrine. RESULTS: Microvascular sympathetic activity at 24 h postnatal age decreased in early preterm males, but not females. Peripheral sympathetic activity increased with advancing postnatal age in females, but decreased in males. In early preterm infants, total normetanephrine outputs increase significantly with postnatal age, in both sexes. CONCLUSION: Sympathetic activation following preterm birth is sexually dimorphic, with preterm males having reduced sympathetic tone and reduced upregulation of sympathetic tone following birth. There is evidence of a disconnect between central sympathetic activity and local peripheral microcirculatory sympathetic drive. This may relate to autonomic nervous immaturity and highlights the need to understand how preterm birth may affect autonomic function.

Inotropes do not increase cardiac output or cerebral blood flow in preterm piglets.

BACKGROUND: The preterm newborn is at high risk of developing cardiovascular compromise during the first day of life and this is associated with increased risk of brain injury. Standard treatments are volume expansion and administration of inotropes, typically dopamine and/or dobutamine, but there is limited evidence that inotropes improve clinical outcomes. This study investigated the efficacy of dopamine and dobutamine for the treatment of cardiovascular compromise in the preterm newborn using a piglet model. METHODS: Preterm and term piglets were assigned to either dopamine, dobutamine or control infusions. Heart rate, left ventricular contractility, cardiac output, blood pressure, and cerebral and regional blood flows were measured during baseline, low (10 µg/kg/h), and high (20 µg/kg/h) dose infusions. RESULTS: At baseline, preterm piglets had lower cardiac contractility, cardiac output, blood pressure, and cerebral blood flow compared to term piglets. The response of preterm piglets to either dopamine or dobutamine administration was less than in term piglets. In both preterm and term piglets, cardiac output and cerebral blood flow were unaltered by either inotrope. CONCLUSION: In order to provide better cardiovascular support, it may be necessary to develop treatments that target receptors with a more mature profile than adrenoceptors in the preterm newborn.

Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future.

Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients.

Extra-uterine renal growth in preterm infants: oligonephropathy and prematurity.

BACKGROUND: Nephron number in humans is determined during fetal life. The objective of this study was to investigate the effects of preterm birth on nephron number using renal volume as a surrogate for nephron number. METHODS: This observational study was conducted over 12 months in a tertiary perinatal center. Preterm babies less than 32 weeks of gestation were recruited and followed until discharge. Term infants were recruited for comparison. The babies underwent renal sonography and renal function measurements at 32 and 38 weeks corrected age. The primary outcome measurement was total kidney volume at 38 weeks and the secondary outcome was estimated glomerular filtration rate (eGFR). RESULTS: Forty-four preterm infants and 24 term infants were recruited. At 38 weeks corrected age, premature infants had lower total kidney volume than term infants (21.6 ± 5.7 vs. 25.2 ± 5.7 ml; p = 0.02) and a significantly lower eGFR (73.6 [IQR 68.1-77.6] vs. 79.3 [IQR 72.5-86.6] ml·min(-1)·1.73 m(-2); p = 0.03). There was a significant correlation between total kidney volume and eGFR in premature and term babies. CONCLUSIONS: Premature infants have smaller kidney volume and likely decreased nephron number and lower estimated glomerulofiltration rate relative to infants born at term.

Measuring cystatin C to determine renal function in neonates.

OBJECTIVES: The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortality rate. The purpose of this review was to determine the feasibility of using serum cystatin C measurements to assist clinicians in making early and accurate diagnoses of acute kidney injury in neonates. DATA SOURCE: We searched for the following seven key words within the PubMed database and the Cochrane Database of Systematic Reviews: cystatin C, neonates, newborn, preterm, premature, kidney failure, and kidney injury. STUDY SELECTION: The selected studies included neonates within their study populations and were published in English. We reviewed literature published between January 1990 and May 2012. DATA EXTRACTION: Ten studies had conducted serum cystatin C measurements in neonates. DATA SYNTHESIS: The cystatin C level in neonates is not influenced by the maternal level and is highest at birth. In most studies, cystatin C levels on day 1 of life ranged between 1 and 2 mg/L, gradually declined during the first year and then remained relatively stable thereafter. Cystatin C levels did not differ between male and female infants, and no significant gestational age-dependent differences were found. Cystatin C levels were increased in cases of sepsis, acute kidney injury, and congenital renal abnormalities. CONCLUSIONS: Cystatin C has all of the theoretical properties needed to be an ideal marker of renal function. It can be used to determine baseline renal function on day 1 and is increasingly being used to determine renal function in sick neonates. In the majority of studies, the day 1 cystatin C level ranged between 1 and 2 mg/L, which gradually declined in the first year of life. However, the number of available studies evaluating cystatin C in sick neonates is currently limited, and there are also no studies linking cystatin C levels in sick babies with short-term and long-term outcomes.

Relationship between the retinal microvasculature and renal volume in low-birth-weight babies.

OBJECTIVE: We performed a study to assess whether the development of the retinal microvasculature reflects nephron growth and therefore nephron number. STUDY DESIGN: In our study, we determined the association between kidney volume (nephron number) and the retinal microvasculature of term low-birth-weight (LBW) and normal-birth-weight (NBW) infants (11 LBW and 27 NBW). RESULTS: LBW infants had significantly larger retinal arteriolar and venular diameters (104.2 ± 21.4 versus 87.0 ± 12.7 µm; p = 0.004; 146.8 ± 19.5 versus 128.0 ± 19.5 µm; p = 0.01, respectively) compared with NBW infants. LBW infants also had smaller mean renal volumes (9.3 ± 2.3 versus 12.2 ± 3.1 ml; p = 0.008). There were negative correlations between retinal arteriolar and venular diameters and renal volumes (r = -0.34, p < 0.05; r = -0.37, p < 0.05, respectively). CONCLUSION: The larger the kidney (and, by implication, the greater the nephron number), the smaller are the diameters of retinal arterioles and venules. Thus, the degree of dilation of the retinal microvasculature provides an indirect index of renal growth.

The guinea pig as an animal model for studying perinatal changes in microvascular function.

INTRODUCTION: Microvascular dysfunction, characterized by inappropriate vasodilatation and high blood flow in the peripheral microcirculation, is linked to physiologic instability and poor outcome in neonates. Specifically, preterm neonates have significantly higher levels of baseline microvascular blood flow than term neonates at 24 h postnatal age. Because of similarities between human and guinea pig endocrine profiles and maturity at birth, we hypothesized that preterm guinea pig neonates would provide a suitable model for studying the mechanisms underlying transitional microvascular function. RESULTS: Guinea pigs that were delivered preterm showed immaturity and had markedly reduced viability. Baseline microvascular blood flow was significantly higher in preterm animals than in term animals. No effect of intrauterine growth restriction or birth weight on baseline microvascular blood flow was observed in either preterm or term animals. DISCUSSION: These results are consistent with recent clinical findings and support the use of the guinea pig as a suitable model for future studies of the mechanisms underlying perinatal microvascular behavior. METHODS: Guinea pigs were delivered either prematurely or at term. Laser Doppler flowmetry was used to study microvascular blood flow at 23 h postnatal age.

Protocol for the Women And Their Children's Health (WATCH) study: a cohort of pregnancy and beyond.

BACKGROUND: The developmental origins of health and disease is a conceptual framework that helps explain the links between our early life exposures and later health outcomes, and is a burgeoning field of research. In this report, we describe the study protocol used in a prospective cohort of women recruited during pregnancy, with postnatal follow-up of the mothers and offspring. METHODS: The Women And Their Children's Health (WATCH) cohort (n = 180 women) is being conducted at the John Hunter Hospital, Australia (from June 2006). Women attended study visits during pregnancy at 19, 24, 30, and 36 weeks' gestation. Postnatal follow-up of the women and their offspring occurred at 3-month intervals during the first year after birth and annually thereafter, until age 4 years. Fetal ultrasound scans were performed at each pregnancy visit. Pregnancy and birth data were obtained from hospital records. Data collection has included maternal and child anthropometric, biochemical, dietary, physical activity, socioeconomic, medical, and other variables. CONCLUSIONS: The 2 most novel components of our prospective cohort study are (1) the regular and systematic tracking of fetal and child growth and body composition, starting in the second trimester of pregnancy and continuing to age 4 years, and (2) the detailed maternal and child dietary data collection, including biochemical parameters. Detailed cohorts that collect data on the early nutritional, physiological, and social determinants of health are valuable. Despite its relatively small sample size, many hypotheses on developmental origins can be tested or piloted using data collected from the WATCH cohort.

Retinal microvascular changes in low-birth-weight babies have a link to future health.

BACKGROUND: In utero insults that result in low-birth-weight (LBW) infants are now recognized risk factors for the development of vascular-related diseases in adulthood. Microcirculatory pathologies are believed to form a mechanistic link between fetal insult and the manifestation of illness in adulthood. OBJECTIVES: The challenge has been to investigate microcirculatory changes in vivo. The objective of this review is to determine whether LBW infants and individuals undergo abnormal microvascular changes and, if so, whether these changes can be objectively identified and measured by investigating retinal vessels. METHODS: An online publication search was carried out using the following keywords to identify and review relevant articles: retinal microvasculature, retinal vessels, small for gestation age, growth restriction, and intrauterine growth restriction. Articles published from 1980 to 2011 were considered. CONCLUSIONS: The ability of retinal imaging technology to assess and measure retinal microvasculature makes it a valuable assessment tool. The current tool is, however, unsuitable for non-invasive assessment in infants and young children. Once this hurdle has been overcome, a longitudinal study of LBW individuals from infancy to adulthood, with regular retinal microvascular assessments, would help prove the mechanistic link between LBW and cardiovascular disease in adulthood.

Oligonephropathy of prematurity.

With improved health care, the number of premature babies who survive to adulthood is expected to increase. The objective of this review is to determine whether premature infants have an increased risk of chronic kidney disease (CKD). A literature review was performed by searching PubMed (U.S. National Library of Medicine) and the Cochrane Library, using the keywords "prematurity," "kidney," "nephrogenesis," "oligonephropathy," and "kidney impairment." Articles published in English since 1990 were reviewed. Increasing evidence suggests that prematurity causes oligonephropathy independently of, and coexisting with, intrauterine growth restriction. Animal studies show that nephrogenesis continues for up to 3 weeks in extrauterine life, but with up to 18% abnormal glomeruli. Nephrogenesis is further impaired in preterm infants who develop renal impairment in the early postnatal period, which is estimated to be 8 to 24%. Premature infants are at risk for CKD. A larger longitudinal study is needed that follows up premature infants to determine the exact incidence of CKD. Until then, renal assessment in premature infants should be incorporated into follow-up guidelines, in addition to the current assessment of growth and neurodevelopmental outcomes. The cost implications to a comprehensive program, impact of early identification, and strategies to improve outcomes in this population are needed.

Trends in the use of non-invasive respiratory support for term infants in tertiary neonatal units in Australia and New Zealand.

OBJECTIVE: To determine whether the use of non-invasive respiratory support, such as continuous positive airway pressure and nasal high flow, to treat term infants in Australian and New Zealand tertiary neonatal intensive care units (NICUs) has changed over time, and if so, whether there are parallel changes in short-term respiratory morbidities. DESIGN: Retrospective database review of patient-level data from the Australian and New Zealand Neonatal Network (ANZNN) from 2010 to 2018. Denominator data on the number of term inborn livebirths in each facility was only available as annual totals. PATIENTS AND SETTING: Term, inborn infants cared for in NICUs within the ANZNN. MAIN OUTCOME MEASURES: The primary outcome was the annual change in hospital-specific rates of non-invasive respiratory support per 1000 inborn livebirths, expressed as a percentage change. Secondary outcomes were the change in rates of mechanical ventilation, pneumothorax requiring drainage, exogenous surfactant treatment and death before hospital discharge. RESULTS: A total of 14 656 term infants from 21 NICUs were included from 2010 to 2018, of whom 12 719 received non-invasive respiratory support. Non-invasive respiratory support use increased on average by 8.7% per year (95% CI: 7.9% to 9.4% per year); the number of term infants receiving non-invasive respiratory support almost doubled from 980 in 2010 (10.8/1000 livebirths) to 1913 in 2018 (20.8/1000). There was no change over time in rate of mechanical ventilation or death. The rate of pneumothorax requiring drainage increased over time, as did surfactant treatment. CONCLUSIONS: Non-invasive respiratory support use to treat term infants cared for in NICUs within the ANZNN is increasing over time. Clinicians should be diligent in selecting infants most likely to benefit from treatment with non-invasive respiratory support in this relatively low-risk population of term newborn infants. Analysis of patient-level data by individual NICUs is recommended to control for potential confounding due to changes in population over time.