Extremely Premature Neonates Research Articles

Obstructive Bilateral Renal Fungal Bezoars in an Extremely Premature Neonate Treated With Antifungals and Urokinase Irrigation: A Case Report and Review of the Literature.

An ex-27-week gestation female infant developed bilateral forearm nodules at 4 weeks of life during treatment for methicillin-sensitive Staphylococcus aureus bacteremia. A pure growth of Candida albicans was isolated on culture of both sterile aspiration of the forearm abscess and urine without evidence of methicillin-sensitive Staphylococcus aureus. The patient went on to develop bilateral obstructive renal fungal bezoars at 11 weeks of life. Bilateral nephrostomies were required to alleviate obstruction with the addition of local irrigation with amphotericin B deoxycholate. Two weeks later, urokinase via the nephrostomy tubes was added due to an unchanged appearance on ultrasound (US) and ongoing candiduria. A significant reduction in the size of bezoars was seen on US after 3 days. Sterilization of urine culture was achieved 7 weeks into treatment, and resolution of bezoars on US was seen 9 weeks after treatment began. No adverse events occurred from the use of local urokinase. Urokinase irrigation via nephrostomy is an effective and safe adjunctive treatment in refractory obstructive renal candidiasis in neonates.

Subpial Hemorrhage in Extremely Premature Neonate: A Rare Finding in a Rare Cohort

Subpial Hemorrhage in Extremely Premature Neonate: A Rare Finding in a Rare Cohort

Hyperbilirubinemia and Choledocholithiasis in an Extremely Premature Neonate.

Cholestasis affects 2% of newborns admitted to the neonatal intensive care unit and 20% of premature infants and requires a thoughtful evaluation and diagnostic workup.There may be a single responsible etiology, or its development may be multifactorial. Premature neonates are especially predisposed because of their increased risk of infections and acute illness, need for parenteral nutrition, and exposure to certain medications. Clinically, an infant may present with jaundice, evidence of hepatic injury, or worsening hepatic function. Diagnosis may be made in consultation with various pediatric subspecialists including gastroenterology, genetics, and surgery. Treatment depends on the etiology but may include medications or surgical interventions. Timely recognition and intervention improve outcomes. [Pediatr Ann. 2023;52(8):e297-e302.].

Exposure to maternal acetylsalicylic acid and the risk of bleeding events in extreme premature neonates.

Exposure to maternal acetylsalicylic acid and the risk of bleeding events in extreme premature neonates.

Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates

Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population. To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates. This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021. Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB. The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death. A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51). In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes. ClinicalTrials.gov Identifier: NCT01378273.

Patient-Ventilator Synchrony in Extremely Premature Neonates during Non-Invasive Neurally Adjusted Ventilatory Assist or Synchronized Intermittent Positive Airway Pressure: A Randomized Crossover Pilot Trial

Introduction: Synchronization of non-invasive ventilation is challenging in extremely premature infants. We compared patient-ventilator synchrony between non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using transdiaphragmatic (Edi) catheter and synchronized intermittent positive airway pressure (SiPAP) using an abdominal trigger. Methods: This study was a monocentric, randomized, crossover trial in premature infants born before 28 weeks of gestation, aged 3 days or more, and below 32 weeks postmenstrual age. NIV-NAVA and SiPAP were applied in a random order for 2 h with analysis of data from the second hour. The primary outcome was the asynchrony index. Results: Fourteen patients were included (median [IQR] gestational age at birth 25.6 (25.3–26.4) weeks, median [IQR] birth weight 755 [680–824] g, median [IQR] postnatal age 26.5 [19.8–33.8] days). The median (IQR) asynchrony index was significantly lower in NIV-NAVA versus SiPAP (49.9% [44.1–52.6] vs. 85.8% [74.2–90.9], p < 0.001). Ineffective efforts and auto-triggering were significantly less frequent in NIV-NAVA versus SiPAP (3.0% vs. 32.0% p < 0.001 and 10.0% vs. 26.6%, p = 0.004, respectively). Double triggering was significantly less frequent in SiPAP versus NIV-NAVA (0.0% vs. 9.0%, p < 0.001). No significant difference was observed for premature cycling and late cycling. Peak Edi and swing Edi were significantly lower in NIV-NAVA as compared to SiPAP (7.7 [6.1–9.9] vs. 11.0 [6.7–14.5] μV, p = 0.006; 5.4 [4.2–7.6] vs. 7.6 [4.3–10.8] μV, p = 0.007, respectively). No significant difference was observed between NIV-NAVA and SiPAP for heart rate, respiratory rate, COMFORTneo scores, apnoea, desaturations, or bradycardias. Discussion/Conclusion: NIV-NAVA markedly improves patient-ventilator synchrony as compared to SiPAP in extremely premature infants.

Placental lesions and SARS-Cov-2 infection: Diffuse placenta damage associated to poor fetal outcome

IntroductionPregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. MethodWe collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. ResultsWe report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers’ infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. DiscussionSARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.

Normative Echocardiographic Values for Right and Left Ventricular Function in Extremely Premature Neonates

To identify the measures of biventricular function and surrogates of pulmonary vascular resistance that can be expected in relatively stable extremely premature neonates, and evaluate maturational changes in myocardial performance in this patient population. This was a prospective observational study. Clinically stable extremely preterm newborns were divided into 3 cohorts based on gestational age: cohort 1 (240/7-256/7weeks), cohort 2 (260/7-276/7weeks), and cohort 3 (280/7-296/7weeks). Serial echocardiograms were obtained on day of life 3-5, 7-10, and just prior to discharge. In total, 46 subjects met the criteria aimed at capturing only the most clinically healthy and stable newborns less than 296/7weeks of gestational age. Myocardial performance was reliably assessed by echocardiography with high inter-reader correlation. Normative values were identified for right ventricular function, left ventricular function, and surrogates of pulmonary vascular resistance. Biventricular systolic performance is significantly different in the clinically stable extremely premature neonate when compared with healthy full-term newborns. All participants had evidence of poor biventricular compliance at birth which improved with maturation. Extreme prematurity does not appear to adversely affect myocardial functional maturation at the time of term corrected age and/or discharge.

Objective Assessment of Physiologic Alterations Associated With Hemodynamically Significant Patent Ductus Arteriosus in Extremely Premature Neonates.

Delay in closure of ductus arteriosus in postnatal life may lead to serious consequences and complications in an extremely premature neonate secondary to hemodynamic alterations in regional blood flow pattern in various organs. Despite the widespread recognition amongst neonatologists to identify a hemodynamically significant patent ductus arteriosus (hsPDA) early in the postnatal course, there is lack of consensus in its definition and thus the threshold to initiate treatment. Echocardiographic assessment of PDA shunt size and volume combined with neonatologists' impression of clinical significance is most frequently used to determine the need for treatment of PDA. Common clinical signs of hsPDA utilized as surrogate for decreased tissue perfusion may lag behind early echocardiographic signs. Although echocardiogram allows direct assessment of PDA shunt and hemodynamic alterations in the heart, it is limited by dependence on pediatric cardiologist availability, interobserver variation and isolated time point assessment. Electrical cardiometry (EC) is a non-invasive continuous real time measurement of cardiac output by applying changes in thoracic electrical impedance. EC has been validated in preterm newborns by concomitant transthoracic echocardiogram assessments and may be beneficial in studying changes in cardiac output in premature newborns with hsPDA. Alterations in perfusion index derived from continuous pulse oximetry monitoring has been used to study changes in cardiac performance and tissue perfusion in infants with PDA. Near infrared spectroscopy (NIRS) has been used to objectively and continuously assess variations in renal, mesenteric, and cerebral oxygen saturation and thus perfusion changes due to diastolic vascular steal from hsPDA in preterm neonates. Doppler ultrasound studies measuring resistive indices in cerebral circulation indicate disturbance in cerebral perfusion secondary to ductal steal. With recent trends of change in practice toward less intervention in care of preterm newborn, treatment strategy needs to be targeted for select preterm population most vulnerable to adverse hemodynamic effects of PDA. Integration of these novel ways of hemodynamic and tissue perfusion assessment in routine clinical care may help mitigate the challenges in defining and targeting treatment of hsPDA thereby improving outcomes in extremely premature neonates.

Fate of the Left Pulmonary Artery and Thoracic Aorta After Transcatheter Patent Ductus Arteriosus Closure in Low Birth Weight Premature Infants

Transcatheter patent ductus arteriosus closure (TCPC) is an emerging treatment for low birth weight extremely premature neonates (EPNs). Left pulmonary artery (LPA) and descending aorta (DAO) obstruction are described device-related complications, however, data on mid- and long-term vascular outcomes are lacking. A retrospective analysis of EPNs who underwent successful TCPC at our institution from 03/2013 to 12/2018 was performed. Two-dimensional echocardiography and spectral Doppler velocities from various time points before and after TCPC were used to identify LPA and DAO flow disturbances. A total of 44 EPNs underwent successful TCPC at a median (range) procedural weight of 1150 g (755–2500 g). Thirty-two (73%) patients were closed with the AVP II and 12 (27%) with the Amplatzer Piccolo device. LPA and DAO velocities on average remained within normal limits and improved spontaneously in long-term follow up (26.1 months, range 1–75 months). One patient, who had concerning LPA flow characteristics immediately after device implant (peak velocity 2.6 m/s) developed progressive LPA stenosis requiring stent placement 3 months post-procedure. In the remaining infants, including 7 (16%) who developed LPA and 3 (7%) who developed DAO flow disturbances (range 2–2.4 m/s), all had progressive normalization of flow velocities over time. TCPC can be performed safely in EPNs with a low incidence of LPA and DAO obstruction. In the absence of significant progressive vascular obstruction in the early post-procedure period, mild increases in LPA and DAO flow velocities tend to improve spontaneously and normalize in long-term follow-up.

Assessment of initial vancomycin trough levels and risk factors of vancomycin-induced nephrotoxicity in neonates

ObjectivesVancomycin is a glycopeptide antibiotic commonly used in neonatal intensive care units (NICUs) to treat late onset sepsis. It is recommended that vancomycin trough levels at steady state following intermittent...

Tracheostomy in the Extremely Premature Neonate: A Multi-Institutional Study.

(1) To describe characteristics associated with tracheostomy placement and (2) to describe associated in-hospital morbidity in extremely premature infants. Pooled retrospective analysis of charts. Academic children's hospitals. The patient records of premature infants (23-28 weeks gestational age) who underwent tracheostomy between January 1, 2012, and December 31, 2017, were reviewed from 4 academic children's hospitals. Demographics, procedural morbidity, feeding, respiratory, and neurodevelopmental outcomes at the time of transfer from the neonatal intensive care unit (NICU) were obtained. The contribution of baseline characteristics to mortality, neurodevelopmental, and feeding outcomes was also assessed. The charts of 119 infants were included. The mean gestational age was 25.5 (95% confidence interval, 25.2-25.7) weeks. The mean birth weight was 712 (671-752) g. Approximately 50% was African American. The principal comorbidity was chronic lung disease (92.4%). Overall, 60.5% of the infants had at least 1 complication. At the time of transfer, most remained mechanically ventilated (94%) and dependent on a feeding tube (90%). Necrotizing enterocolitis increased the risk of feeding impairment (P = .002) and death (P = .03). Tracheostomy in the extremely premature neonate is primarily performed for chronic lung disease. Complications occur frequently, with skin breakdown being the most common. Placement of a tracheostomy does not seem to mitigate the systemic morbidity associated with extreme prematurity.

Mortality of Extremely Premature Neonates with Severe Intraventricular Hemorrhage (FR481B)

Mortality of Extremely Premature Neonates with Severe Intraventricular Hemorrhage (FR481B)

Early Clinical Experience of Trans-catheter Closure of Patent Ductus Arteriosus in Extremely Premature Neonates

Early Clinical Experience of Trans-catheter Closure of Patent Ductus Arteriosus in Extremely Premature Neonates

Neonatal periventricular leukomalacia: current perspectives

Neonatal periventricular leukomalacia: current perspectives Kunal P Ahya,1 Pradeep Suryawanshi2 1Department of Neonatology, Maahi Newborn Care Centre, Rajkot, Gujarat, 2Department of Neonatology, BVDU Medical College, Pune, Maharashtra, India Abstract: Significant advances in the neonatal ICU have improved the survival of extreme premature neonates; with this comes the importance of intact survival. Periventricular leukomalacia (PVL) is the commonest white matter brain injury in preterm infants. It has a typical distribution at the watershed areas adjacent to the lateral ventricles. PVL occurs because of ischemic injury to periventricular oligodendrocytes of the developing brain. It can be detected by cranial ultrasonography (CUS) as initial periventricular echodensities, followed later by cystic formation. Recent magnetic resonance imaging studies have shown that it helps in early visualization of PVL and also detection of non-cystic form of PVL, which is not picked up by CUS. It is the commonest cause of cerebral palsy, intellectual impairment or visual disturbances. Currently, no medical treatment is available for PVL; prevention and close developmental follow-up are the only options. Keywords: periventricular leukomalacia, preterm brain injury, cranial ultrasonography

Postnatal Transitional Weight Loss and Adverse Outcomes in Extremely Premature Neonates.

The early postnatal weight loss (EPWL) is highly variable in the extremely low birth weight infants (birth weight <1000 g, ELBW). It is reported to be unassociated with adverse outcomes within a range of 3-21% of birth weight. Its wide range might have contributed to this lack of association. The aim of our paper is to study the effects of maximum EPWL, graded as low, medium and large on clinical outcomes in ELBW infants. In a retrospective cohort observational study EPWL was measured as maximum weight loss from birth weight (MWL) in ELBW infants and grouped as low (5-12%) moderate (18.1-12%) and high (18-25%). The clinical course and complications of infants were compared between the groups. Gestational age (GA) was highest and surfactant administration, peak inspiratory pressure requirement, fluid intake, urinary output, oxygen dependent days and the number of oxygen dependent infants at age 28 days were lower in the low MWL compared to the high MWL group. However, all these significant P-values declined after controlling for GA. Diabetes mellitus and pregnancy associated hypertension were not noted in mothers in high MWL group, whereas 38% of mothers in low MWL group suffered from the latter (P=0.05). Maximum postnatal transitional weight loss, assessed in the range of low, moderate and high, is not associated with adverse outcomes independent of gestational age in ELBW infants. Maternal hypertension decreases EPWL in them.

Intraventricular Hemorrhage and Platelet Indices in Extremely Premature Neonates.

Intraventricular hemorrhage (IVH) is a multifactorial disorder, the most important risk factors of which are prematurity and low birth weight. Disturbances in cerebral blood flow, inherent fragility of the germinal matrix vasculature, and platelet/coagulation disturbances are the 3 major pathogenic mechanisms. In this context, we investigated the role of platelet indices and several maternal and neonatal characteristics in the development of IVH through a retrospective cohort analysis of 130 extremely premature neonates, 24% of whom presented with severe IVH. There was a significant difference in platelet counts between the IVH and the control group on the first day of life (P=0.046). Presence of IVH was linked with lower birth weight (P=0.006) and lower gestational age (P=0.001). Platelet count on the first day of life was positively correlated with survival (P=0.001) and, along with platelet mass, was indicative of the worst IVH grade recorded for each neonate (P=0.002 and 0.007, respectively). Prolonged prothrombin time was also correlated with IVH (P<0.001), but factor analysis supported no prominent role. Maternal medications seem to play a minor role as well. In conclusion, IVH in extremely premature infants cannot be solely explained by platelet parameters, and further studies are required to determine the relationships between IVH, platelet indices, and outcomes.

3-Year Survival and Neurodevelopmental Outcomes in Extremely Premature Neonates: A 15-Year Odyssey

Abstract BACKGROUND: For neonates born at limits of viability, CPS recommends resuscitation decisions should occur after detailed discussion with parents, utilizing best available data on survival and neuro-developmental morbidities. There are emerging studies reporting such outcomes beyond 18-24 months. However, there is a notably wide variation in survival and rates of long term morbidity reported in the literature for infants born before 26 weeks of gestation. Centre specific survival rates among actively resuscitated extremely premature neonates and accurate developmental outcome data that truly reflects functional abilities are crucial for both parents and healthcare providers. OBJECTIVES: Assess mortality, neuro-developmental outcomes at 3 years of age and correlate with risk factors predictive of adverse developmental outcomes in neonates born between 23+0-26+6 weeks of gestation at a tertiary care center in Ontario, Canada DESIGN/METHODS: This was a retrospective analysis at a Level 3 center focusing on neonates born at 23+0 to 26+ 6 weeks gestation between January 2000 to December 2014. Data was extracted from Neonatal-Perinatal Database and Developmental Clinic Database. Clinical assessment of motor impairment (GMFCS), sensory impairment(blind or deaf) and a well validated tool Child Development Inventory were used to assess developmental outcomes at 3 yrs of age. Comparative analysis of possible risk factors, extracted from the NICU database , for adverse outcomes were analyzed using multivariate regression. RESULTS: Survival rate among actively treated neonates were 25%, 60.4% and 77.5% at 23, 24 and 25 weeks respectively. 3 year survival rates with no major motor or neuro-sensory impairment were 40% among survivors born at 23 weeks, 47.2% among those born at 24 weeks, 55.6% and 68.6% among those born at 25 and 26 weeks respectively. Those born at 23 weeks had a significantly higher risk of having CP compared to the risk at 26 weeks [OR 9.04 {CI 1.96-41.67}]. Presence of IVH [OR 2.50 {CI 1.20-5.21}] and CSF infections [OR 5.71 {CI 1.03-31.56}] were identified as significant risk factors for adverse motor outcomes. Female neonates across all gestational age groups had significantly lower C P, speech delay and significantly better CDI scores. CDI profile analysis showed that at 3 years, nearly 80% of neonates born between 24-26 weeks have normal General Development Score, while only 40% of neonates born at 23 weeks had normal General Development Score at 3 years. CONCLUSION: Being born at 23 week increased risk of cerebral palsy when compared to risk of birth at 26 weeks. CSF infection and IVH were found to be significant risk factors for adverse motor outcomes. The functional abilities as per the CDI Profiles were remarkably similar among survivors born at 24, 25,26 weeks of gestation.

Nursing Assessment, Education, and Care of Extremely Premature Neonates with Patent Ductus Arteriosus.

The care of extremely premature neonates with suspected or confirmed diagnosis of patent ductus arteriosus (PDA) is a frequent challenge for pediatric nurses. It is important for nurses to have adequate knowledge of the normal postnatal changes in cardiovascular and pulmonary function to recognize any adverse symptoms. Nurses caring for these vulnerable neonates must have a thorough understanding of the pathophysiology of a PDA in order to assess, plan, and implement patient-centered care. Recognition of characteristic symptoms of PDA in a timely manner is essential for optimal management and outcomes. Understanding the science behind treatment options is also imperative for pediatric nurses to provide the best care and effectively educate parents. Pediatric nurses are a significant resource in managing extremely premature neonates through comprehensive assessment, effective parent education, and high-quality patient-centered care.

Proteinuria and hematuria in the neonate.

Neonatal proteinuria and hematuria while not common can have potentially devastating consequences if left undiagnosed and untreated. It is important to distinguish between inherited and acquired causes of proteinuria to initiate appropriate and timely treatment. With regards to hematuria, it is critical to identify true hematuria from pseudo-hematuria to balance between thorough investigation and unnecessary laboratory work up. This review provides an overview of the common causes of hematuria and proteinuria in a neonate. The identification of genetic mutations in nephrotic syndrome has improved our understanding of the role of various proteins that play an important role in maintaining the glomerular filtration barrier. With the advancement in our ability to provide care for extreme premature neonates, the incidence of acute kidney injury has increased in these neonates along with proteinuria and hematuria. Persistent proteinuria after neonatal acute kidney injury would be of interest in regards to the risk of developing future chronic kidney disease and hypertension.