Current Pediatric Reviews (v.12, #2)

Meet Our Editorial Board Member by P. Puri (77-77).

The clinical management of a patent ductus arteriosus (PDA) in preterm newborns is a controversial topic, and despite nearly three decades of research, varying opinions remain. This dilemma stems from uncertain causal linkage between PDA and neonatal comorbidities, as well as the lack of clear evidence showing that benefits of treatment outweigh risks. There has been a general shift in the management of PDA in preterm newborns from early and aggressive closure to a more conservative approach of watchful waiting and spontaneous closure. However, a firm recommendation cannot be made due to a lack of randomized controlled trials validating either treatment strategies. Although cyclooxygenase inhibitors, namely indomethacin and ibuprofen, are approved pharmacological treatments for PDA, there is a need to explore alternative medical therapies in view of lack of clinical response in many newborns and concerns over adverse effects. One such recent interest is the use of acetaminophen as a pharmacological agent. This present review tries to address the questions at hand, integrate the current evidence, highlight the principles of PDA management in preterm newborns, and suggest areas for possible future research.

Background: Patent ductus arteriosus (PDA) is a common factor complicating the care of the preterm infant, but controversy remains regarding the long term effects of PDA and iatrogenic closure of PDA.
Methods: Studies presenting data relevant to the relationship between PDA and mortality and morbidity were identified via a systematic literature review. These studies were classified based on PDA exposure in the case and control groups. The data was abstracted and summarized using linear modeling, resulting in summary estimates of mean effect size (odds ratio).
Results: Recently published data suggests that a significant relationship between PDA and mortality, bronchopulmonary dysplasia/chronic lung disease, necrotizing enterocolitis, or retinopathy of prematurity is unlikely. However, the data related to mortality leaves room for some debate. Quantitative analysis of the data shows that PDA is a risk factor for intraventricular hemorrhage and related studies suggest this risk may carry over into long term neurological outcomes.
Conclusion: Further efforts to better understand the physiologic consequences of PDA and its closure in preterm infants is necessary. A focus on new biochemical or physiologic factors that mediate or confound any apparent effect of PDA and are themselves amenable to targeted therapy is imperative to further progress in improving the outcomes of these patients.

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.

Management of the patent ductus arteriosus (PDA) represents an ongoing challenge in the care of extremely premature neonates. Determining the optimal treatment strategy requires careful consideration of the potential risks and benefits of available therapies. Surgical ligation results in reliable ductal closure, but may result in numerous short-term complications and have a negative impact on long-term outcome. Intravenous indomethacin was the first pharmacologic agent widely utilized for PDA closure. Intravenous indomethacin effectively closes the ductus arteriosus and prevents pulmonary hemorrhage and severe intraventricular hemorrhage, but fails to mitigate short-term morbidities and improve long-term outcomes. Intravenous ibuprofen represents an alternative therapy with fewer renal adverse effects. However, intravenous ibuprofen does not prevent severe intraventricular hemorrhage and also has concerning adverse effects, including bilirubin displacement and the potential to increase the risk of chronic lung disease. Enteral ibuprofen has also been investigated, although gastrointestinal adverse effects limit widespread utilization. Acetaminophen (paracetamol) represents an enticing novel therapy due to wide availability, low cost, and an appealing safety profile. Ongoing investigation is required to determine the role of this agent in PDA treatment algorithms. Pending these results, clinicians must weigh the potential risks and benefits of each therapy for individual neonates considering all available evidence.

The ductus arteriosus is a muscular artery connecting two elastic arteries with different resistances. It is a normal fetal structure that only becomes pathological if it remains patent after birth. A varied clinical impact is observed as some neonates may be asymptomatic, symptoms may be deferred until later in life, or the infant may be overtly symptomatic and present as early as the first days of life. Prematurity increases the likelihood of persistent ductal patency and is seen in about 30% of preterm infants. In premature neonates, patent ductus arteriosus (PDA) is associated with significant morbidity and mortality [1,2]. This discussion explains the pathophysiology behind the pathological events associated with PDA.

The ductus arteriosus is a fetal vascular connection between the pulmonary and systemic circulations. It fails to close after birth in a small number of term infants, and in a larger number of infants with cyanotic congenital heart disease. In contemporary practice the majority of patients present with a patent ductus arteriosus (PDA) are premature infants before the gestational age of 28 weeks. The surgical management of PDA in preterm infants is critical for optimal outcomes and is discussed in this article.

Clinical signs alone are unreliable in the diagnosis of patent ductus arteriosus (PDA) in preterm infants, and therefore echocardiography remains the mainstay of diagnosis of this common condition. Echocardiography also facilitates understanding of the hemodynamic effects of a PDA, and thus aids in management decisions. Several echocardiographic parameters, including duct size, maximum ductal velocity, left atrial: aorta ratio, mitral inflow E:A ratio, and isovolumic relaxation time, have been utilized in the assessment of PDA, but no single measurement can be used in isolation to inform clinical judgement. Therefore, it is important that echocardiographers on the neonatal unit have a comprehensive understanding of available methods and their limitations.
Newer echocardiographic techniques, such as 3 Dimensional echocardiography, tissue Doppler imaging and strain imaging, are now providing insights into myocardial function in the adaptation of preterm infants to extra-uterine life, and into the effects of a PDA causing systemic-to-pulmonary artery shunting.
Magnetic resonance imaging delivers excellent diagnostic information and accurate hemodynamic evaluation; however this modality is not easily accessible for most preterm infants, in comparison to echocardiography, which is readily available at the cotside in most neonatal units.
Further developments in echocardiography may further refine the contribution it makes to individualized clinical decisionmaking in the management of premature infants with PDA.

Prader-Willi Syndrome: Clinical Genetics and Diagnostic Aspects with Treatment Approaches by Merlin G. Butler, Ann M. Manzardo, Janice L. Forster (136-166).
Background: Prader-Willi syndrome (PWS) is a neuro-developmental genetic disorder due to lack of expression of genes inherited from the paternal chromosome 15q11-q13 region with three main genetic subtypes. These include paternal 15q11-q13 deletion (about 70% of cases), maternal uniparental disomy 15 or both 15s from the mother (20-30% of cases), and defects in the imprinting center (1-3%) which controls the expression of imprinted genes in this chromosome region. Clinical manifestations include infantile hypotonia with a poor suck resulting in failure to thrive, short stature, small hands/feet and hypogonadism/hypogenitalism due to growth and other hormone deficiencies, hyperphagia and excessive weight gain with obesity and cognitive and behavioral problems including obsessive compulsions, tantrums and self-injury. The phenotype is likely related to hypothalamic dysfunction.
Objective: Hyperphagia and obesity with related complications are major causes of morbidity and mortality in PWS requiring accurate diagnosis, appropriate medical management and treatment; the major objective of our report.
Methods and Results: An extensive review of the literature was undertaken including genetics, clinical and behavioral aspects, and updated health-related information addressing the importance of early diagnosis and treatment of individuals with Prader-Willi syndrome. A searchable, bulleted and formatted list of topics related to this obesity syndrome was provided utilizing a Table of Contents approach for the clinical practitioner.
Conclusions: Physicians and other health care providers can use this review with clinical, genetic and treatment summaries divided into sections that are pertinent in the context of clinical practice. Finally, frequently asked questions by clinicians, families and other interested participants will be addressed.