A Case of Enterococcal Patent Ductus Arteriosus-associated Endarteritis in a Preterm Neonate.

INTRODUCTION: The persistent patency of the ductus arteriosus frequently occurs in premature neonates and can cause infective endocarditis (IE) or ductal endarteritis (DE) during sepsis. Even though neonatal IE and DE are believed to be a rare eventuality, their incidence has been increasing in the last decades due to the improved survival of even more preterm babies, favored by highly invasive procedures and therapies. In parallel, antimicrobial resistance is another rising problem in neonatal intensive care units, which frequently compels to treat infections with broad-spectrum or last generation antibiotics. CASE PRESENTATION: We report the case of a preterm neonate affected by patent ductus arteriosus-associated DE that followed an episode of sepsis caused by a high-level aminoglycoside-resistant enterococcus. The neonate was successfully treated with the synergistic combination of ampicillin and cefotaxime. DISCUSSION: IE and patent ductus arteriosus-associated DE are rising inside neonatal intensive care units and neonatologists should be aware of these conditions. Enterococcal IE and patent ductus arteriosus-associated DE sustained by high-level aminoglycoside-resistant strains can be successfully treated with the synergistic combination of ampicillin and cefotaxime even in preterm neonates.

Transcatheter closure in preterm infants with patent ductus arteriosus: feasibility, results, hemodynamic monitoring and future prospectives.

Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional closure is needed, it can be achieved with either surgical ligation or a catheter-based approach.Transcatheter PDA closure is among the safest of interventional cardiac procedures and it is the first choice for ductal closure in adults, children, and infants weighing more than 6 kg. In preterm and very low birth weight infants, it is increasingly becoming a valid and safe alternative to ligation, especially for the high success rate and the minor invasiveness and side effects. Nevertheless, being it performed at increasingly lower weights and gestational ages, hemodynamic complications are possible events to be foreseen.Procedural steps, timing, results, possible complications and available monitoring systems, as well as future outlooks are here discussed.

A novel echocardiography method to assess upper body systemic blood flow in preterm infants and comparison with superior vena cava flow measurement.

To evaluate feasibility, reproducibility, and prognostic value of a new echocardiographic method to assess systemic arterial blood flow directed to the upper part of the body (UBAF, upper body arterial flow) alternative to superior vena cava flow (SVCF) measurement. We performed echocardiographic evaluations in 106 infants in the first 2 days of life to obtain SVCF, left ventricle output (LVO), UBAF, and standard parameters of patent ductus arteriosus (PDA) significance. UBAF was calculated by subtracting from LVO the aortic arch blood flow measured immediately distally to the origin of the left subclavian artery. Main outcome measures: UBAF and SVCF agreement was assessed by Bland-Altman analysis in terms of bias, limits of agreement and repeatability index. The Intraclass Correlation Coefficient was used to measure the strength of inter-rater agreement. The agreement between UBAF and SVCF was high. The Concordance Correlation Coefficient (CCC) was 0.7434. (CCC 0.7434, 95% C.I. [0.656, 0.8111]). There was a good absolute agreement between the two raters ICC = 0.747; p value < 0.0001; 95%CI [0.601; 0.845]. Adjusting for confounding factors (BW, GA, PDA) included in the model, there was a statistically significant relationship between UBAF and SVCF. CONCLUSION: UBAF showed a strong agreement with the SCVF with a better reproducibility. Our data support UBAF as a potentially useful marker of cerebral perfusion in the evaluation of preterm infants. WHAT IS KNOWN: • Low SVC (superior vena cava) flow in the neonatal period has been associated with periventricular haemorrhage and unfavourable long-term neurodevelopmental outcome. • Ultrasound measurement of flow in SVC shows relatively high inter-operator variability. WHAT IS NEW: • Our study highlights how much overlap there is between upper-body arterial flow (UBAF) measurement and SCV flow measurement. UBAF is easier to perform and has a strong correlation with better reproducibility. • UBAF may replace measurement of cava flow as a method for haemodynamic monitoring of unstable preterm and asphyxiated infants.

Reply to the comment on "Fluid restriction in management of patent ductus arteriosus in Italy: a nationwide survey".

The Authors Chang Liu B.S and Yuan Shi commented our paper on Fluid restriction in management of patent ductus arteriosus (PDA) in Italy. With our study, we conducted a prospective cross-sectional survey among all Italian Neonatal Intensive Care Units (NICUs) to address conservative management of patent ductus arteriosus (PDA) in preterm infants below 29 weeks' gestational age (GA), with specific regard to fluid restriction (FR). The Authors wondered if the heterogeneity of use of fluid restriction both as a prophylactic tool and as a conservative tool when a hemodynamically significant PDA is diagnosed, was due to economic disparities among areas of the included centers. Conducting a secondary analysis of our data, we observed that if we separately consider the responses of two areas, northern and central-southern Italy, FR is slightly more frequently applied in Central and Southern regions (82%) as compared to Northern regions (78%), although this finding does not reach statistical significance. No correlation between the likelihood to adopt conservative measures and the amount of allowed fluid intake was found. The hypothesis that "less fluid intake resulted in milder clinical and echocardiographic presentations of PDA, and thus a lower rate of pharmacological treatment" cannot be supported by our current study design and might deserve future investigations.

Fluid restriction in management of patent ductus arteriosus in Italy: a nationwide survey.

We aimed at establishing the state of the art in fluid restriction practice in our national setting and providing a foundation for future research efforts. A prospective cross-sectional survey was conducted among all 114 Italian Neonatal Units in order to address conservative management of patent ductus arteriosus (PDA) in preterm infants below 29 weeks' gestational age (GA), with specific regard to fluid restriction. Response rate was 80%. Conservative measures for PDA management are provided in the majority of NICUs and 80% of centers reduce fluid intake in neonates with PDA. No relationship can be found among pharmacologically or surgically treated patients per year and the approach to fluid restriction. The minimum intake administered at regimen when fluid restriction is applied is associated to the ratio between the maximum number of neonates managed pharmacologically and number of admitted < 29 weeks' GA newborns. CONCLUSION: Our survey shows an extreme variability among centers in terms of use of fluid restriction as a prophylactic tool but also in terms of its use (both opportunity and modality) when a hemodynamically significant PDA is diagnosed. This variability, that can be also found in randomized trials and observational studies, suggests that further evidence is needed to better understand its potential beneficial effects and its potential harms such as dehydration, hypotension, decreased end-organ perfusion, and reduced caloric intake. WHAT IS KNOWN: • The lack of demonstrable improvement following the treatment of patent ductus arteriosus has recently paved the way to a more conservative approach. • Fluid restriction is the most commonly applied conservative treatment of PDA. WHAT IS NEW: • Among Italian NICUs an extreme variability in terms of indications, timing and modalities of application of Fluid restriction can be found. • This variability reflects the lack of standardization of this practice and the contrasting evidence on its efficacy.

Cor Triatriatum Dexter: Contrast Echocardiography Is Key to the Diagnosis of a Rare but Treatable Cause of Neonatal Persistent Cyanosis.

Cor triatriatum dexter (CTD) is an extremely uncommon and underreported congenital cardiac anomaly in which the persistence of the embryonic right venous valve separates the right atrium into two chambers with varying degrees of obstruction to antegrade flow and variable degree of right to left shunt at atrial level. Depending on the size of the valves, clinical manifestations vary from absence of symptoms to severe hypoxia, requiring urgent surgical correction. We herein describe the diagnostic difficulties in a case of neonatal CTD, who developed increasingly severe and unresponsive cyanosis, first interpreted as postnatal maladjustment with pulmonary hypertension. The failure to respond to oxygen and pulmonary vasodilators led us to reconsider a different diagnosis. The use of contrast echocardiography improved the diagnostic performance of transthoracic echocardiogram (TTE) and revealed a massive right-to-left shunt secondary to the presence of an atrial membrane that required urgent surgery.

Patent ductus arteriosus and spontaneous intestinal perforation in a cohort of preterm infants.

OBJECTIVE: To assess whether either duration and magnitude of ductal shunt or medical treatment for patent ductus arteriosus (PDA) are related to spontaneous intestinal perforation (SIP). STUDY DESIGN: Clinical charts of infants <29 weeks' gestation born from 2006 to 2018 were reviewed. Echocardiographic examinations were evaluated according to McNamara and Sehgal's staging system. RESULTS: A higher percentage of patients with SIP had a hemodynamically significant PDA (HSPDA) and was treated with either NSAIDs or paracetamol (79% vs 53% and 81% vs 54%, respectively). Among non-treated patients, we found a 1.32 increase in the odds of SIP per day of persistence of HSPDA. In the cohort of patients treated despite the absence of HSPDA, we found a 2.35 increase in the odds of SIP per dose of drug administered. CONCLUSION: Both treating a non-HSPDA and leaving a HSPDA to its natural history seem to be associated with SIP.

Association between Hemodynamically Significant Patent Ductus Arteriosus and Bronchopulmonary Dysplasia.

OBJECTIVE: To assess whether the duration and magnitude of the shunt with patent ductus arteriosus (PDA) are related to a higher incidence of bronchopulmonary dysplasia (BPD) or death. STUDY DESIGN: A total of 242 infants ≤ 28 weeks gestational age were evaluated retrospectively between 2007 and 2012; 105 (43.3%) developed BPD or died (group 1) and 137 (56.6%) did not (group 2). A review of all echocardiographic evaluations performed from birth up to 36 weeks of postconceptional age or final ductal closure was carried out, to detect the presence of PDA, and estimate the severity of ductal shunt through the "PDA staging system" proposed by McNamara and Sehgal. RESULTS: Group 1 presented with a hemodynamically significant ductus arteriosus (DA) (E3 and/or E4-PDA) for a longer period of time vs group 2: 4.8 vs 2.3 days, respectively (P < .001). Persistence of a nonsignificant DA (E2) was not associated with development of BPD (P = .16). Each week of a hemodynamically significant DA represented an added risk for BPD (OR 1.7), and the duration of a small, nonsignificant DA (E2) did not. Surgical ligation of PDA itself was not found to be an independent risk factor for BPD. In the subgroup of patients who received ligation, a later ligation (33 vs 23 days) and a prolonged PDA were the only factors associated to BPD or death. CONCLUSIONS: A shared scoring system of the severity of ductal shunt is helpful to correctly evaluate the association between PDA morbidities, to compare scientific studies, and to guide treatment.

"The Original Sound": a new non-pharmacological approach to the postnatal stress management of preterm infants.

OBJECTIVE: To evaluate the effect of the exposure to "The Original Sound" (TOS), an original track composed of different sounds such as fetal heartbeat, breathing, blood flow, and ambience sounds, specifically created for this study, on physiological stability of preterm infants during a 10-d hospitalization. METHODS: Thirty-four preterm infants (32-37 weeks of gestation) were randomized to receive either TOS or environmental noise. TOS was provided for a 20-min period, three times a day, using two speakers and a MP3 player placed in the cradle. Cardiorespiratory and behavioral parameters were recorded. RESULTS: Heart rate in the treated group was positively correlated with TOS exposure, showing a significant reduction on day 2 and lower values during the first day. A decrease in RR is also recorded on day two in the TOS group, although not significant. CONCLUSION: This study provides preliminary evidence for short-term improvements in the physiological stability of preterm infants using TOS. Future studies are needed to investigate the potential of this non-pharmacological approach and its clinical relevance to postnatal stress management in neonatal intensive care units.

A case report of aorto-pulmonary window in an infant born to a diabetic mother.

Several studies have described the association between pre-gestational maternal diabetes and cardiac disease in the newborn. Infants of diabetic mothers have an increased incidence of congenital heart disease, reported between 3% and 6% compared to 0.8% of the general population. A particularly high prevalence of conotruncal defects has been recently described among congenital heart diseases. This group of malformations affects ventricular outflows, aorta, and pulmonary artery and shares a common embryogenic origin. They include persistence of the truncus arteriosus, transposition of great arteries, tetralogy of Fallot, interruption of the aortic arch, and double outlet right ventricle. Aorto-pulmonary window, a rare congenital heart disease belonging to conotruncal malformations, has never been previously described in association with maternal diabetes. We describe the case of a male infant born to a mother suffering from a poorly controlled type 1 diabetes during pregnancy. In the early postnatal life the infant showed respiratory distress, tachycardia, and failure to thrive. He was found to be affected by aorto-pulmonary window that required corrective surgical intervention. .

Update on lipid and protein intakes in the critical newborn.

The influence of critical illnesses on adverse outcomes in newborn infants seems to be mediated by nutritional intakes during the first week or few weeks of life. Changes in amounts and ratios of protein and energy, fat quality (medium chain triglycerides, and n-3 long-chain polyunsaturated fatty acids), maintaining normoglycemia during full or partial parenteral nutrition, rate of feeding advancements and avoidance of postnatal growth retardation represent the main items whose roles in critically ill preterm infants have been considered so far. In a condition such as extreme prematurity, feeding higher amounts of amino acids since the first day of life has been shown so far to be safe and effective in terms of metabolic balance, body growth and neurodevelopment outcome. In other clinical conditions and as far as other nutrients are concerned, available data are still limited and do not allow for firm conclusions in most cases.

A rare genetic disorder causing persistent severe neonatal hypoglycaemia the diagnostic workup.

We report a case of familial glucocorticoid deficiency (FGD), a rare genetic autosomal-recessive disorder with typical hyperpigmentation of the skin and mucous membranes, severe hypoglycaemia, occasionally leading to seizures and coma, feeding difficulties, failure to thrive and infections. A newborn child was admitted, on his second day of life, to our neonatal intensive care unit because of seizures and respiratory insufficiency. Hyperpigmentation was not evident due to his Senegalese origin. The clinical presentation led us to consider a wide range of diagnostic hypothesis. Laboratory findings brought us to the diagnosis of FGD that was confirmed by molecular analysis showing an MC2R:p.Y254C mutation previously reported as causative of type 1 FGD and two novel heterozygous non-synonymous single-nucleotide polymorphisms in exon 2 and 3 of melanocortin 2 receptor accessory protein-α, whose role in the disease is currently unknown. The importance of an early collection and storage of blood samples during hypoglycaemic event is emphasised.

Double-blind, placebo-controlled trial comparing effects of supplementation of two micronutrient sprinkles on fatty acid status in Cambodian infants.

BACKGROUND: Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown. OBJECTIVES: To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants. METHODS: A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared. RESULTS: At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians. CONCLUSIONS: Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

Double-blind, placebo-controlled trial comparing effects of supplementation with two different combinations of micronutrients delivered as sprinkles on growth, anemia, and iron deficiency in cambodian infants.

OBJECTIVES: To assess and compare efficacy of two micronutrient sprinkle supplementation on growth, anemia, and iron deficiency in Cambodian infants. METHODS: A total of 204 infants aged 6 months and living in Kompong Chhnang Province, Cambodia were randomly assigned to receive daily supplements of either iron (12.5 mg) plus folic acid (150 mug) plus zinc (5 mg) (MMN, n = 68), or iron (12.5 mg) plus folic acid (150 microg) alone (FFA, n = 68), or placebo (n = 68) for a 12 month period in powder form as sprinkles. Anthropometrics was evaluated bimonthly. Biochemical assessment was performed at baseline and at the end of intervention period. RESULTS: At baseline, the overall mean (SD) of hemoglobin concentration was 101 g/L. No difference among groups was found for growth pattern. Significant decline was observed for weight-for-age and height-for-age z-scores in any group (P < 0.0001). The rate of recovery from anemia was significant (P < 0.001) and comparable between MMN (54%) and FFA (53%) groups and higher than in the placebo group (22%, P < 0.0001). Through the study period, no significant change in the rate of iron deficiency was found in MMN and FFA groups, whereas it increased in the placebo group (31%, baseline vs. 52%, end of study; P < 0.0001). CONCLUSION: Both MMN and FFA supplements were effective for preventing or treating anemia in Cambodian infants and stabilizing plasma levels of ferritin. Use of micronutrients in a controlled home setting, as sprinkled daily supplements, may be promising in preventing and treating anemia in developing countries.