Oral versus intravenous paracetamol for patent ductus arteriosus closure in preterm infants.

BACKGROUND: To examine whether oral administration of paracetamol as a first-line agent had a greater effect on the closure of a patent ductus arteriosus than the intravenous route. METHODS: We performed a retrospective study of preterm infants (<37 weeks of gestation) between 2012 and 2020 treated with oral or intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction and compared rates of ductal closure, course duration, cumulative dose, PDA characteristics, and serum levels. RESULTS: Over the study period, 80 preterm infants received paracetamol, of which 50 received paracetamol as first-line treatment to augment constriction of the PDA. Closure rate was higher in the oral group (n = 15/19, 79%) compared to the intravenous group (n = 8/20, 40%, p < 0.01), and remained significant after adjusting for gestational age, length of treatment, and postnatal age (OR 0.14, 95% CI 0.03-0.67, p = 0.014, RR 0.51, 95% CI 0.28-0.91). Eleven preterm infants received a combination of both oral and intravenous paracetamol with a closure rate of 45% (n = 5). CONCLUSIONS: Oral administration of paracetamol as a first-line agent is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. IMPACT: Our retrospective study comparing the use of oral versus intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction in preterm infants demonstrates that oral administration of paracetamol is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. To our knowledge, this is the first published study (prospective or retrospective) to compare the efficacy of oral versus intravenous paracetamol as a first-line treatment for PDA closure in preterm infants. Our finding may improve the rate of PDA closure when paracetamol is used as a first-line agent.

A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly.

Tel Hashomer camptodactyly syndrome is a long-known entity characterized by camptodactyly with muscular hypoplasia, skeletal dysplasia, and abnormal palmar creases. Currently, the genetic basis for this disorder is unknown, thus there is a possibility that this clinical presentation may be contained within another genetic diagnosis. Here, we present a multiplex family with a previous clinical diagnosis of Tel Hashomer camptodactyly syndrome. Whole exome sequencing and pedigree-based analysis revealed a novel hemizygous truncating variant c.269_270dup (p.Phe91Alafs*34) in the FGD1 gene (NM_004463.3) in all three symptomatic patients, congruous with a diagnosis of Aarskog-Scott syndrome. Our report adds to the limited data on Aarskog-Scott syndrome, and emphasizes the importance of unbiased comprehensive molecular testing toward establishing a diagnosis for genetic syndromes with unknown genetic basis.

Movement Imitation Therapy for Preterm Babies (MIT-PB): a Novel Approach to Improve the Neurodevelopmental Outcome of Infants at High-Risk for Cerebral Palsy.

To improve the neurodevelopmental outcome in infants with high grade intraventricular haemorrhage and cramped-synchronised (CS) general movements (GMs). Four very preterm infants with intraventricular haemorrhage grade III (n = 3) or intraventricular haemorrhage with apparent periventricular haemorrhagic infarction (n = 1) were diagnosed with CS GMs at 33 to 35 weeks postmenstrual age. A few days later MIT-PB [Movement Imitation Therapy for Preterm Babies], an early intervention programme, was commenced: the instant an infant showed CS movements, the therapist intervened by gently guiding the infant's limbs so as to manoeuvre and smoothen the movements, thereby imitating normal GM sequences as closely as possible (at least for 10 min, 5 times a day, with increasing frequency over a period of 10 to 12 weeks). After a period of consistent CS GMs, the movements improved. At 14 weeks postterm age, the age specific GM pattern, fidgety movements, were normal in three infants, one infant had abnormal fidgety movements. At preschool age, all participants had a normal neurodevelopmental outcome. This report on four cases demonstrates that mimicking normal and variable GM sequences might have a positive cascading effect on neurodevelopment. The results need to be interpreted with caution and replication studies on larger samples are warranted. Nonetheless, this innovative approach may represent a first step into a new intervention strategy.

Long term follow-up of Palivizumab administration in children born at 29-32 weeks of gestation.

BACKGROUND: Severe respiratory syncytial virus (RSV) bronchiolitis requiring hospitalization induces long term immunological and respiratory abnormalities. The long-term immunomodulation effect of Palivizumab (RSV monoclonal antibody) prophylaxis and its impact on the development of asthma remain controversial. Our aim was to evaluate airway hyper-reactivity, systemic inflammatory markers, allergic parameters and respiratory morbidity, 5-7 years following Palivizumab administration to children born at 29-32 weeks of gestation (WGA). METHODS: Children born at 29-32 WGA were evaluated at age 5-7 years. Methacholine challenge test (MCT), serum inflammatory cytokines, fractional exhaled nitric oxide (FeNO), blood tests for eosinophil count, IgE and assessment of respiratory morbidity by questionnaire were compared between those born before Palivizumab prophylaxis was extended to 29-32 WGA and those who received Palivizumab prophylaxis. RESULTS: Of 42 children recruited, 27 received Palivizumab and 15 did not. The mean gestational age and weight were lower in the Palivizumab group. Similar values of spirometry, MCT, FeNO and allergic parameters were observed in the two groups. The Palivizumab group had higher IL4, IL5 and IL13 (Th2 cytokines), IL6, IL17α, and G-CSF (Th17 activation), and lower IL12 and higher INF-γ (Th1 cytokines). CONCLUSION: Compared to children who did not receive immunoprophylaxis, among children who received Palivizumab, no beneficial effects on long-term respiratory morbidity, airway reactivity or allergic parameters were observed, and levels of Th2 and Th17 cytokines implicated in the pathogenesis of asthma were higher. These findings cast doubt on the potential long-term beneficial effect of Palivizumab on asthma inception.

Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis.

OBJECTIVES: We performed a systematic review and meta-analysis of all the available evidence to assess the efficacy and safety of paracetamol for the treatment of patent ductus arteriosus (PDA) in neonates, and to explore the effects of clinical variables on the risk of closure. DATA SOURCE: MEDLINE, Scopus and ISI Web of Knowledge databases, using the following medical subject headings and terms: paracetamol, acetaminophen and patent ductus arteriosus. Electronic and manual screening of conference abstracts from international meetings of relevant organisations. Manual search of the reference lists of all eligible articles. STUDY SELECTION: Studies comparing paracetamol versus ibuprofen, indomethacin, placebo or no intervention for the treatment of PDA. DATA EXTRACTION: Data regarding efficacy and safety were collected and analysed. RESULTS: Sixteen studies were included: 2 randomised controlled trials (RCTs) and 14 uncontrolled studies. Quality of selected studies is poor. A meta-analysis of RCTs does not demonstrate any difference in the risk of ductal closure (Mantel-Haenszel model, RR 1.07, 95% CI 0.87 to 1.33 and RR 1.03, 95% CI 0.92 to 1.16, after 3 and 6 days of treatment, respectively). Proportion meta-analysis of uncontrolled studies demonstrates a pooled ductal closure rate of 49% (95% CI 29% to 69%) and 76% (95% CI 61% to 88%) after 3 and 6 days of treatment with paracetamol, respectively. Safety profiles of paracetamol and ibuprofen are similar. CONCLUSIONS: Efficacy and safety of paracetamol appear to be comparable with those of ibuprofen. These results should be interpreted with caution, taking into account the non-optimal quality of the studies analysed and the limited number of neonates treated with paracetamol so far.

Does Haptoglobin Phenotype Influence Postnatal Morbidity in Preterm Neonates?

BACKGROUND: Haptoglobin (Hp) is an acute phase protein with antioxidant, bacteriostatic, and anti-inflammatory activities. Hp proteins associated with the three major phenotypes differ in their proinflammatory and anti-inflammatory action. Inflammation and oxidative stress are both involved in most pathophysiological processes in premature infants. The objective of this study was to determine whether Hp phenotype influences clinical manifestations and sepsis incidence in the premature infants. OBJECTIVE: Infants born before 35 weeks gestational age were prospectively evaluated for Hp phenotype and clinical events, including sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity. The participants were observed until discharge. METHODS: A total of 122 preterm infants were enrolled in the study. Clinical events were not affected by the Hp phenotype. The expression of Hp protein was extremely low in the study population. More septic episodes were found in infants with a birth weight greater than 1,500 g, although, the difference was not statistically significant. RESULTS: Extremely low expression of Hp may explain the lack of a correlation between Hp phenotype and sepsis in preterm infants. Further research involving a larger neonatal population is required to better understand the role of the Hp phenotype in morbidity of premature infants.

[Why perform routine brain sonography in late preterm infants?].

We present a case of a late preterm baby with respiratory distress syndrome (RDS), prolonged jaundice and congenital hypothyroidism. The infant developed late lenticulostriate vasculopathy (LSV). LSV was previously described in association with various neurodevelopmental abnormalities and in this case would have been missed by the current US brain screening recommendations for newborns.

Paracetamol effectiveness, safety and blood level monitoring during patent ductus arteriosus closure: a case series.

Paracetamol was reported to be effective for patent ductus arteriosus (PDA) closure. We present a case series of PDA closure by paracetamol in seven premature infants. During the treatment, paracetamol blood levels did not exceed the recommended levels for analgesia and hyperthermia in six tested infants. None of the patients demonstrated significant disturbances of liver function.

[Hypothermia as a treatment for hypoxic ischemic encephalopathy after neonatal asphyxia--update].

Hypoxic-ischemic encephalopathy (HIE) due to neonatal asphyxia is an important cause of irreversible bad neurodevelopmental outcomes in children. Understanding the mechanisms causing the central nervous system cell death enabled the development of new treatment strategies that may decrease the severity of neurological damage. This survey includes data on epidemiology, pathogenesis, clinical features and diagnostic criteria of HIE. We discuss the neuro-protective mechanisms of therapeutic hypothermia and provide data on clinical studies conducted to investigate the impact and safety of this treatment in newborn infants affected by HIE. In addition, other therapeutic options of neuro-protective agents are mentioned.

A new method for continuous monitoring of chest wall movement to characterize hypoxemic episodes during HFOV.

INTRODUCTION: Monitoring ventilated infants is difficult during high-frequency oscillatory ventilation (HFOV). This study tested the possible causes of hypoxemic episodes using a new method for monitoring chest wall movement during HFOV in newborn infants. METHODS: Three miniature motion sensors were attached to both sides of the chest and to the epigastrium to measure the local tidal displacement (TDi) at each site. A >20% change in TDi was defined as deviation from baseline. RESULTS: Eight premature infants (postmenstrual age 30.6 ± 2.6 weeks) were monitored during 10 sessions (32.6 h) that included 21 hypoxemic events. Three types of such events were recognized: decrease in TDi that preceded hypoxemia (n = 11), simultaneous decrease in TDi and SpO2 (n = 6), and decrease in SpO(2) without changes in TDi (n = 4). In the first group, decreases in TDi were detected 22.4 ± 18.7 min before hypoxemia, and were due to airway obstruction by secretions or decline in lung compliance. The second group resulted from apnea or severe abdominal contractions. In the third group, hypoxia appeared following a decrease in FiO2. CONCLUSIONS: Monitoring TDi may enable early recognition of deteriorating ventilation during HFOV that eventually leads to hypoxemia. In about half of cases, hypoxemia is not due to slowly deteriorating ventilation.

Benefits of high frequency oscillatory ventilation for premature infants.

BACKGROUND: High frequency oscillatoryventilation based on optimal lung volume strategy is one of the accepted modes of ventilatory support for respiratory distress syndrome in very low birth weight infants. In 1999 itwas introduced in our unit as the primary ventilation modality for RDS. OBJECTIVES: To evaluate if the shift to HFOV influenced the outcome of ventilated VLBW infants in the neonatal intensive care unit of Carmel Medical Center. METHODS: Data were obtained from the medical charts of VLBW infants born at Carmel Medical Center, and late mortality data from the Israel Ministry of Internal Affairs records. A retrospective analysis and a comparison with a historical control group ventilated by the conventional method were performed. RESULTS: A total of 232 VLBW infants with RDS were mechanically ventilated during the period 1995 to 2003: 120 were ventilated using HFOV during 1999-2003 and 102 infants using CV during 1995-1999. The mean gestational age of survivors was 27.4 +/- 2 weeks in the HFOV group and 28.4 +/- 2 in the conventional ventilation group (P = 0.03). The sub-sample of infants with birth weight < 1000 g ventilated with HFOV showed higher survival rates than the infants in the conventional ventilation group, 53 vs. 25 (64.6% vs. 44.6%) respectively (P < 0.05). A trend for lower incidence of pulmonary interstitial emphysema was observed in the HFOV group. CONCLUSIONS: The introduction of HFOV based on optimal lung volume strategy proved to be an efficient and safe method of ventilation support for VLBW infants in our unit.

The anuric preterm newborn infant with a normal renal ultrasound: a diagnostic and ethical challenge.

Diagnosis and treatment of an anuric premature infant with severe respiratory compromise and a normal renal ultrasound (US), is a difficult task that requires a multidisciplinary approach. A 29-week gestation premature male infant, born after 5 weeks of worsening oligohydramnios, was ventilated for respiratory distress and remained anuric. Intensive clinical investigations and pediatric nephrology consultation that predicted very poor prognosis were followed by progressive renal failure, electrolyte imbalance, respiratory failure, ventricular arrhythmia, and finally cardiac arrest and death on day 5. In view of the predicted poor outcome, and after discussion with the parents, a decision was made not to start peritoneal dialysis (PD), and to offer only palliative therapy, with comfort care alone. Pre and postnatal diagnosis lead, in this case, to an ethical challenge that focuses on the question of futility.