Alison L. Kent

Accelerated Maturation and Abnormal Morphology in the Preterm Neonatal Kidney

Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life.

Mortality and adverse neurologic outcomes are greater in preterm male infants

Objective: To determine whether male gender has an effect on survival, early neonatal morbidity, and long-term outcome in neonates born extremely prematurely. Methods: Retrospective review of the New South Wales and Australian Capital Territory Neonatal Intensive Care Unit Data Collection of all infants admitted to New South Wales and Australian Capital Territory neonatal intensive care units between January 1998 and December 2004. The primary outcome was hospital mortality and functional impairment at 2 to 3 years follow-up. Results: Included in the study were 2549 neonates; 54.7% were male. Risks of grade III/IV intraventricular hemorrhage, sepsis, and major surgery were found to be increased in male neonates. Hospital mortality (odds ratio 1.285, 95% confidence interval 1.035–1.595) and moderate to severe functional disability at 2 to 3 years of age (odds ratio 1.877, 95% confidence interval 1.398–2.521) were more likely in male infants. Gender differences for mortality and long-term neurologic outcome loses significance at 27 weeks gestation. Conclusions: In the modern era of neonatal management, male infants still have higher mortality and poorer long-term neurologic outcome. Gender differences for mortality and long-term neurologic outcome appear to lose significance at 27 weeks gestation.

Neonatal acute kidney injury

In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.

Increasing ambient operating theatre temperature and wrapping in polyethylene improves admission temperature in premature infants

Aim:  To improve admission temperatures of preterm infants ≤31 weeks gestation by increasing the ambient temperature in the operating theatre and wrapping in polyethylene wrap at caesarean section.

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia

Objective:  To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use.

Antenatal steroid exposure and outcomes of very premature infants: a regional cohort study.

Objective To compare mortality, short-term morbidity and long-term neurodevelopmental outcomes of <29 week premature infants with antenatal steroid exposure (none, incomplete and complete). Patients and methods Multicentre retrospective cohort study, within a geographically defined area in Australia served by a network of 10 neonatal intensive care units (NICUs), of infants <29 weeks gestational age, admitted to NICUs between 1998 and 2004. Outcome measures included hospital survival, perinatal complications and functional disability at 2–3 years follow-up. Results 2549 neonates were included; 319 (12.5%) received no exposure to steroids. Hospital mortality (OR 0.59, 95% CI 0.45 to 0.76, p<0.001, intraventricular haemorrhage (IVH) (OR 0.58, 95% CI 0.42 to 0.81, p=0.001) and necrotising entercolitis (NEC) (OR 0.62, 95% CI 0.42 to 0.91, p=0.018) was less likely in infants with any steroid exposure. Any steroid exposure was associated with less need for surfactant (OR 0.41, 95% CI 0.30 to 0.57, p<0.001) and mechanical ventilation (OR 0.30, 95% CI 0.17 to 0.52, p<0.001). Subgroup analyses demonstrated differences in outcomes only with complete steroid coverage and not with incomplete coverage. Survival benefit and reduction in the incidence of severe IVH was evident from 24 to 28 weeks. Long-term neurodevelopmental data available for 1473 survivors showed no significant difference in outcomes with steroid exposure after multivariate analysis. Conclusions Exposure to a complete course of antenatal steroids is associated with higher infant survival rates, lower rates of severe IVH and NEC compared to an incomplete course or no exposure. Any exposure to steroids reduces the risk of moderate cerebral palsy, however, long-term neurodevelopmental outcome may not be affected by steroid exposure.

Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: Neurodevelopmental outcome and chorioamnionitis in premature infants

Objective:  To examine the effect of antenatal steroid exposure and in utero inflammation on the development of severe intraventricular haemorrhage, periventricular leukomalacia and long‐term neurological outcome in infants less than 30 completed weeks gestation.

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

Indomethacin, ibuprofen, and gentamicin are commonly administered to neonates between 24 and 28 wk gestation when glomerulogenesis is still occurring. Indomethacin is known to cause renal failure in up to 25% of infants treated. Possible morphologic effects of these drugs are largely unknown. The purpose of this study was to determine the type of renal changes found on light (LM) and electron microscopy (EM) following administration of indomethacin, ibuprofen, and gentamicin in a neonatal rat model. Rat pups were exposed to indomethacin or ibuprofen and/or gentamicin antenatally for 5 d before birth or postnatally for 5 d from d 1 of life. Pups were killed at 14 d of age. LM examination in all indomethacin- and ibuprofen-treated pups both antenatally and postnatally showed vacuolization of the epithelial proximal tubules, interstitial edema, intratubular protein deposition but no significant glomerular changes. EM examination showed pleomorphic mitochondria and loss of microvilli in the tubules. The glomeruli showed extensive foot process effacement and irregularities of the glomerular basement membrane. EM changes were most marked in pups treated antenatally with ibuprofen, and indomethacin with gentamicin postnatally. Indomethacin, ibuprofen, and gentamicin cause significant change in glomerular and tubular structure in the neonatal rat model.

Assessment of renal functional maturation and injury in preterm neonates during the first month of life

Worldwide, approximately 10% of neonates are born preterm. The majority of preterm neonates are born when the kidneys are still developing; therefore, during the early postnatal period renal function is likely reflective of renal immaturity and/or injury. This study evaluated glomerular and tubular function and urinary neutrophil gelatinase-associated lipocalin (NGAL; a marker of renal injury) in preterm neonates during the first month of life. Preterm and term infants were recruited from Monash Newborn (neonatal intensive care unit at Monash Medical Centre) and Jesse McPherson Private Hospital, respectively. Infants were grouped according to gestational age at birth: ≤28 wk (n = 33), 29-31 wk (n = 44), 32-36 wk (n = 32), and term (≥37 wk (n = 22)). Measures of glomerular and tubular function were assessed on postnatal days 3-7, 14, 21, and 28. Glomerular and tubular function was significantly affected by gestational age at birth, as well as by postnatal age. By postnatal day 28, creatinine clearance remained significantly lower among preterm neonates compared with term infants; however, sodium excretion was not significantly different. Pathological proteinuria and high urinary NGAL levels were observed in a number of neonates, which may be indicative of renal injury; however, there was no correlation between the two markers. Findings suggest that neonatal renal function is predominantly influenced by renal maturity, and there was high capacity for postnatal tubular maturation among preterm neonates. There is insufficient evidence to suggest that urinary NGAL is a useful marker of renal injury in the preterm neonate.

When birth comes early: effects on nephrogenesis

Preterm birth (birth prior to 37 completed weeks of gestation) may occur at a time when the infant kidney is very immature and nephrogenesis is often ongoing. In autopsied preterm human kidneys and in a baboon model of preterm birth it has been shown that nephrogenesis continues after preterm birth, with a significant increase in the number of glomerular generations and number of nephrons formed within the kidney after birth. Of concern, however, morphologically abnormal glomeruli (with a cystic Bowmans space) are often observed; the abnormal glomeruli are only located in the outer renal cortex, suggesting that it is the recently formed glomeruli (perhaps those formed in the extra‐uterine environment) that are affected. The proportion of abnormal glomeruli within the renal cortex differs between infants with some kidneys appearing normal whereas others are severely affected. This suggests that it may be haemodynamic factors and/or factors in the neonatal care of the infant that lead to the glomerular abnormalities. Indeed, the haemodynamic transition at birth where there is a marked increase in systemic blood pressure and renal blood flow are likely to lead to injury of glomerular capillaries, although further studies are required to elucidate this. In order to optimize renal health at the beginning of life in the preterm infant, it is imperative in future studies to gain an understanding of the causes of the glomerular abnormalities in the preterm neonate.