Arvind Sehgal

Towards rational management of the patent ductus arteriosus : the need for disease staging

Perspective on the review by Bose and Laughon (see page 498)

Does echocardiography facilitate determination of hemodynamic significance attributable to the ductus arteriosus

IntroductionThe assignment of hemodynamic significance to a patent ductus remains a challenge for neonatal intensivists. The impact is medical uncertainty and ongoing debate as to when treatment should be provided if ever.DiscussionPatent ductus arteriosus is associated with significant neonatal morbidities including necrotizing enterocolitis and brain injury; causality has not been proven. In addition, there are limited data suggesting a beneficial effect of therapeutic intervention. The inability to accurately differentiate the pathological ductus arteriosus from the innocent ductus arteriosus may contribute, in part, to the lack of scientific evidence of benefit or causality. Our group has previously proposed the need for a staging system to characterize the clinical and echocardiography impact of the ductus arteriosus. This approach requires comprehensive echocardiography evaluation to assess ductal size and the degree of pulmonary overcirculation/systemic hypoperfusion related to the transductal shunt.ConclusionIn this review, we will highlight the evidence for echocardiography markers of hemodynamic significance and speculate as to how they may facilitate improved decision making in the neonatal intensive care unit.

Cardiac Function and Arterial Biophysical Properties in Small for Gestational Age Infants: Postnatal Manifestations of Fetal Programming

OBJECTIVE To investigate the differences in cardiac function and arterial biophysical properties between term-born appropriate for gestational age (AGA) infants and small for gestational age (SGA) infants. Our hypothesis was that adaptation to intrauterine growth restriction induces changes in cardiac and arterial indices. STUDY DESIGN This was a prospective observational echocardiographic evaluation of cardiac and arterial indices in SGA infants and AGA infants. Demographic and echocardiographic data were compared between 20 inborn term SGA infants with birth weight <3rd percentile for gestational age and 20 AGA infants. RESULTS The Ponderal index was significantly lower and blood pressure was significantly higher in the SGA infants compared with the AGA infants. Left ventricular output was lower in the SGA infants (170 ± 31 mL/kg/min vs 197 ± 39 mL/kg/min). Diastolic dysfunction was greater in the SGA infants (ie, reduced E and A wave velocities, higher E/A ratio [1.08 ± 0.16 vs 0.85 ± 0.07], and prolonged isovolumic relaxation time [73 ± 6.2 ms vs 62.6 ± 3.6 ms]). Aortic intima-media thickness was significantly greater in the SGA infants (822 ± 105 μm vs 694 ± 52 μm), as were arterial wall stiffness index and input impedance. CONCLUSION Cardiac function and arterial biophysical properties were altered in the SGA infants. The findings complement the information on the association between in utero growth and cardiovascular morbidity in later life.

The Ductus Arteriosus: A Refined Approach!

Although ongoing patency of the ductus arteriosus is common in small extremely preterm infants, consensus is lacking regarding its clinical significance and treatment strategies. Literature regarding likelihood of spontaneous closure, impact on neonatal morbidity and long-term outcomes, and adverse effects of intervention has led to uncertainty as to the best course of action. Enhancing the determination of hemodynamic significance and refining patient selection for therapeutic intervention will streamline the decision-making process. Targeted neonatal echocardiography performed by the clinician has gained popularity worldwide, and preliminary data show that it has the potential to optimize patient outcomes. We review the arguments for and against medical and surgical therapy, explore how targeted neonatal echocardiography used in conjunction with biomarkers may refine the treatment approach, and consider future directions in the field.

Delayed versus Immediate Cord Clamping in Preterm Infants

Background The preferred timing of umbilical‐cord clamping in preterm infants is unclear. Methods We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late‐onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention‐to‐treat basis, accounting for multiple births. Results Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed‐clamping group and 9.0% in the immediate‐clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. Conclusions Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088.)

Range of UK practice regarding thresholds for phototherapy and exchange transfusion in neonatal hyperbilirubinaemia

Objective: To establish the range of opinion regarding thresholds at which phototherapy and exchange transfusion are used to treat neonatal hyperbilirubinaemia in the UK. Design: A survey of existing charts and guidelines collected from around the UK. Threshold levels were extracted from the charts and entered into an Excel spreadsheet. Filters were applied to analyse subsets of guidelines, and calculations were carried out to analyse the rate of rise of bilirubin (in μmol/l/h) between the origin and the plateau, where this was possible. Results: Of 263 hospitals contacted, 163 submitted guidelines, of which most were in the form of individual charts. There was wide variation in the choice of the threshold levels at which treatment was recommended, particularly in preterm babies. At 28 weeks, for example, the range at which phototherapy was recommended extended from 100 μmol/l to 250 μmol/l, and the upper limit was even higher if data from units which used a single guideline for preterm babies of all gestations were included. There was variation in the choice of the origin of the graph and the time at which the plateau commenced (and hence the slope), whether “sickness” criteria should be adopted, and what those criteria should be. Many charts were confusing, poorly presented, sketchily drawn and lacked proper gridlines or axis labels. Conclusions: For such a vitally important topic it is disappointing that there is little existing consensus and no national guidance in the UK. Guidelines for England, Wales and Northern Ireland will be available from 2010, when the National Institute for Health and Clinical Excellence completes its review.

Haemodynamically unstable preterm infant: an unresolved management conundrum

While extremely low-birthweight infants are at a higher risk of haemodynamic instability, management strategies can be highly variable and may lack scientific validation. The aetiology of cardiovascular compromise can be diverse. Volume replacements, cardiotropes (dobutamine, dopamine, epinephrine and milrinone) and hydrocortisone supplementation are common interventions. Most often, therapy is driven by protocol, is based on poorly validated clinical information or is based on the premise that “one therapy fits all”. A physiology-driven approach is most needed during transition from intrauterine to extrauterine life surrounding preterm birth, when rapid changes in cardiovascular adaptation occur. The physiologically important determinants of neonatal haemodynamics include cardiac output and systemic vascular resistance, blood pressure, as well as individual organ vascular resistances and blood flows. Three key variables with impact on neonatal haemodynamics, haemodynamically significant ductus arteriosus, systemic blood flow and left ventricular afterload, as well as related therapeutic dilemmas are addressed. Among the novel technologies and approaches presently available, targeted neonatal echocardiography performed by the clinician, used in conjunction with the clinical context, has the potential to better define pathophysiology. A framework for physiology-driven care is proposed, which has the potential to optimize care.

Indomethacin Impairs Coronary Perfusion in Infants with Hemodynamically Significant Ductus Arteriosus

Background: A haemodynamically significant ductus arteriosus (HSDA) is commonly associated with morbidity in preterm infants. Aim: To study the effect of the first dose of indomethacin on coronary blood flow in preterm neonates diagnosed with an HSDA. Method: A prospective observational echocardiographic study was performed on preterm infants. A single study dose of intravenous indomethacin (0.1 mg/kg) was administered over 1 h. Serial echocardiography was performed before and after indomethacin treatment to study the effect on coronary artery perfusion and cardiovascular performance. Results: Eighteen infants born at a median gestation of 25.8 (24.2, 28.1) weeks and a birth weight of 773 g (704, 1,002) were evaluated. The median age at indomethacin administration was 7.5 days (4, 17). There was no significant change in arterial pressure or ventilatory indices. Left anterior descending artery diastolic velocity and time integral declined from 0.3 ± 0.1 and 3.19 ± 1.2 m/s to 0.22 ± 0.08 and 2.01 ± 0.9 m/s, respectively, within 10 min of completion of infusion. These indices showed partial recovery when reassessed after 60 min. There were no changes in left ventricular output or transductal flow. Conclusions: Intravenous indomethacin was followed by a decline in coronary arterial diastolic blood flow.

Global myocardial function is compromised in infants with pulmonary hypertension

Aim:  Persistent pulmonary hypertension of the newborn is a serious clinical entity with significant mortality and long‐term morbidity. The objective was to study the profile of myocardial function, especially diastolic function, in term infants with pulmonary hypertension treated with nitric oxide.

Cardiac function and arterial indices in infants born small for gestational age: analysis by speckle tracking.

To compare strain indices between small for gestational age (SGA) infants and asymptomatic appropriate for gestational age (AGA) infants and to ascertain correlations with arterial biophysical properties.