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In a multicenter randomized trial comparing nasal high-flow therapy with continuous positive airway pressure (CPAP) as initial respiratory support for newborns in nontertiary special care nurseries, high-flow therapy was not noninferior to CPAP and resulted in a significantly higher incidence of treatment failure.

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.

Endocrine control of cardiovascular function is probably immature in the preterm infant; thus, it may contribute to the relative ineffectiveness of current adrenergic treatments for preterm cardiovascular compromise. This study aimed to determine the cardiovascular and hormonal responses to stress in the preterm piglet. Piglets were delivered by cesarean section either preterm (97 of 115 days) or at term (113 days). An additional group of preterm piglets received maternal glucocorticoids as used clinically. Piglets were sedated and underwent hypoxia (4% FiO2 for 20 min) to stimulate a cardiovascular response. Arterial blood pressure, skin blood flow, heart rate and plasma levels of epinephrine, norepinephrine, angiotensin II (Ang II), angiotensin‐(1–7) (Ang‐(1‐7)), and cortisol were measured. Term piglets responded to hypoxia with vasoconstriction; preterm piglets had a lesser response. Preterm piglets had lower blood pressures throughout, with a delayed blood pressure response to the hypoxic stress compared with term piglets. This immature response occurred despite similar high levels of circulating catecholamines, and higher levels of Ang II compared with term animals. Prenatal exposure to glucocorticoids increased the ratio of Ang‐(1‐7):Ang II. Preterm piglets, in contrast to term piglets, had no increase in cortisol levels in response to hypoxia. Preterm piglets have immature physiological responses to a hypoxic stress but no deficit of circulating catecholamines. Reduced vasoconstriction in preterm piglets could result from vasodilator actions of Ang II. In glucocorticoid exposed preterm piglets, further inhibition of vasoconstriction may occur because of an increased conversion of Ang II to Ang‐(1‐7). e12245 This study aimed to determine if immature hormonal control of the cardiovascular system contributes to preterm cardiovascular compromise. Physiological and hormonal responses of preterm piglets to hypoxia are immature compared with term piglets. This is not due to a lack of endogenous catecholamines or angiotensin II, but may be due to the differences in cardiovascular actions of the renin–angiotensin system.

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. [PUBLICATION ABSTRACT]

Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion–reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29–36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68–71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion–reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period. e12145 A period of high microvascular flow occurs after birth, however, no period of low flow (hypoperfusion stage) precedes this, suggesting that no hypoperfusion–reperfusion cycle exists during early extrauterine life. The data strongly support the use of the preterm guinea pig in future studies to allow further investigation of the interrelationship between cardiac output, preload, afterload, microvascular flow, and SVC flow. Elucidation of these processes may then aid clinicians in managing the circulatory dysfunction of preterm neonates, particularly those at greatest risk, preterm male neonates.

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.

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.

The placental glucocorticoid receptor (GR) is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29) and preterm pregnancies (n = 27). Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001). Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01). Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001). GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02). The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.

ObjectiveTo 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.DesignRetrospective 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 settingTerm, inborn infants cared for in NICUs within the ANZNN.Main outcome measuresThe 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.ResultsA 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.ConclusionsNon-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.

ObjectivesTo determine the influence of burn injuries on childhood performance in national standardised curriculum-based school tests.DesignBirth and health records of 977 children who were hospitalised with a burn injury between 2000 and 2006 in the state of New South Wales, Australia, were linked to performance scores in the National Assessment Program: Literacy and Numeracy test, a compulsory nationwide curriculum-based test (CBT) and compared with children who were not hospitalised for burns and who were matched for birth year, gender, gestation and socioeconomic status.Main outcome measuresTest scores in years 3 (ages 8–9), 5 (ages 10–11) and 7 (ages 13–14) in numeracy, writing, reading, spelling, grammar and punctuation.ResultsMean age at first burn injury was 28 months (median: 20, range: 0–140). Children with burns were significantly more likely to have younger mothers (28.5 vs 29.6 years) (P<0.001), be indigenous (OR 2.5 (95% CI 2.1 to 3.1)) (P<0.001) and have siblings (OR 1.2 (95% CI 1.1 to 1.4)) (P<0.001). They were also less likely to meet national minimum standards in most domains of testing until year 5, even after adjustment for parental education levels, parental smoking, maternal age and indigenous status. Each 10% increase in total body surface area burnt was associated with a decrease in year 5 scores by 37.0% in numeracy and 71.9% in writing.ConclusionsMost childhood burn injuries occur before the start of formal schooling. Children who are hospitalised for burns perform more poorly in CBT even after accounting for family and socioeconomic disadvantage. Rehabilitation of children with burn injuries must address school performance to decrease any long-term negative societal impact of burns.