Ann R. Stark

Optimizing care and outcome for late-preterm (near-term) infants: A summary of the workshop sponsored by the national institute of child health and human development

In 2003, 12.3% of births in the United States were preterm (<37 completed weeks of gestation). This represents a 31% increase in the preterm birth rate since 1981. The largest contribution to this increase was from births between 34 and 36 completed weeks of gestation (often called the “near term” but referred to as “late preterm” in this article). Compared with term infants, late-preterm infants have higher frequencies of respiratory distress, temperature instability, hypoglycemia, kernicterus, apnea, seizures, and feeding problems, as well as higher rates of rehospitalization. However, the magnitude of these morbidities at the national level and their public health impact have not been well studied. To address these issues, the National Institute of Child Health and Human Development of the National Institutes of Health invited a multidisciplinary team of experts to a workshop in July 2005 entitled “Optimizing Care and Outcome of the Near-Term Pregnancy and the Near-Term Newborn Infant.” The participants discussed the definition and terminology, epidemiology, etiology, biology of maturation, clinical care, surveillance, and public health aspects of late-preterm infants. Knowledge gaps were identified, and research priorities were listed. This article provides a summary of the meeting.

Respiratory Distress Syndrome

Increasing knowledge of the pathophysiology of respiratory distress syndrome has led to improvements in clinical management. Future advances in prevention and therapy, including administration of agents to prevent prematurity or to accelerate lung maturation, provision of surfactant replacement, and new techniques of mechanical ventilation, will further decrease mortality and morbidity.

Management and Outcomes of Very Low Birth Weight

With increasing numbers of extremely premature infants surviving, the outcome for these infants has generated much interest and controversy. This article reviews recent progress in the management and outcomes of some of the most common conditions affecting infants with very low birth weight (1500 g or less) and extremely low birth weight (1000 g or less).

Hyperbilirubinemia in the Newborn Infant 35 Weeks' Gestation: An Update With Clarifications

In July 2004, the Subcommittee on Hyperbilirubinemia of the American Academy of Pediatrics (AAP) published its clinical practice guideline on the management of hyperbilirubinemia in the newborn infant ≥35 weeks of gestation,1 and a similar guideline was published in 2007 by the Canadian Paediatric Society.2 Experience with implementation of the AAP guideline suggests that some areas require clarification. The 2004 AAP guideline also expressed hope that its implementation would “reduce the incidence of severe hyperbilirubinemia and bilirubin encephalopathy… .” We do not know how many practitioners are following the guideline, nor do we know the current incidence of bilirubin encephalopathy in the United States. We do know, however, that kernicterus is still occurring in the United States, Canada, and Western Europe.3–7 In 2002, the National Quality Forum suggested that kernicterus should be classified as a “serious reportable event,”8 sometimes termed a “never event,”9 implying that with appropriate monitoring, surveillance, and intervention, this devastating condition can, or should, be eliminated. Although this is certainly a desirable objective, it is highly unlikely that it can be achieved given our current state of knowledge and practice.10 In certain circumstances (notably, glucose-6-phosphate dehydrogenase [G6PD] deficiency, sepsis, genetic predisposition, or other unknown stressors), acute, severe hyperbilirubinemia can occur and can produce brain damage despite appropriate monitoring and intervention. In addition to clarifying certain items in the 2004 AAP guideline, we recommend universal predischarge bilirubin screening using total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) measurements, which help to assess the risk of subsequent severe hyperbilirubinemia. We also recommend a more structured approach to management and follow-up according to the predischarge TSB/TcB, gestational age, and other risk factors for hyperbilirubinemia. These recommendations represent a consensus of expert opinion based on the available evidence, and they are supported by … Address correspondence to M. Jeffrey Maisels, MB, BCh, DSc, Beaumont Childrens Hospital, 3601 W. 13 Mile Rd, Royal Oak, MI 48073. E-mail: JMaisels{at}beaumont.edu

Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring

BACKGROUND New intraparenchymal brain injury on magnetic resonance imaging is observed in 36% to 73% of neonates after cardiac surgery with cardiopulmonary bypass. Brain immaturity in this population is common. We performed brain magnetic resonance imaging before and after neonatal cardiac surgery, using a high-flow cardiopulmonary bypass protocol, hypothesizing that brain injury on magnetic resonance imaging would be associated with brain immaturity. METHODS Cardiopulmonary bypass protocol included 150 mL . kg(-1) . min(-1) flows, pH stat management, hematocrit > 30%, and high-flow antegrade cerebral perfusion. Regional brain oxygen saturation was monitored, with a treatment protocol for regional brain oxygen saturation < 50%. Brain magnetic resonance imaging, consisting of T1-, T2-, and diffusion-weighted imaging, and magnetic resonance spectroscopy were performed preoperatively, 7 days postoperatively, and at age 3 to 6 months. RESULTS Twenty-four of 67 patients (36%) had new postoperative white matter injury, infarction, or hemorrhage, and 16% had new white matter injury. Associations with preoperative brain injury included low brain maturity score (P = .002). Postoperative white matter injury was associated with single-ventricle diagnosis (P = .02), preoperative white matter injury (P < .001), and low brain maturity score (P = .05). Low brain maturity score was also associated with more severe postoperative brain injury (P = .01). Forty-five patients had a third scan, with a 27% incidence of new minor lesions, but 58% of previous lesions had partially or completely resolved. CONCLUSIONS We observed a significant incidence of both pre- and postoperative magnetic resonance imaging abnormality and an association with brain immaturity. Many lesions resolved in the first 6 months after surgery. Timing of delivery and surgery with bypass could affect the risk of brain injury.

Bronchopulmonary dysplasia: Possible relationship to pulmonary edema

The pathogenesis of bronchopulmonary dysplasia is controversial. Oxygen toxicity, mechanical trauma to the lung secondary to respirator therapy, and congestive heart failure with a left to right shunt through a patent ductus arteriosus have all been implicated. Our data suggest that in addition to these three conditions, all of which are edemagenic, infants with bronchopulmonary dysplasia have a significantly greater mean fluid intake in the first five days of life when compared with infants with respiratory distress syndrome or patent ductus arteriosus alone. We suggest that the addition of a fluid load may potentiate the effects of other factors and increase the risk of bronchopulmonary dysplasia in infants with respiratory distress syndrome who require respiratory support.

Kernicterus: Epidemiological Strategies for Its Prevention through Systems-Based Approaches

Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders.At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

Diabetic nephropathy and perinatal outcome

We studied the effect of diabetic nephropathy on the course of pregnancy, perinatal outcome, and infant development and determined the influence of pregnancy on maternal hypertension and renal function. Maternal proteinuria usually increased during pregnancy (greater than 3 gm/24 hours in 69%), and hypertension was present by the third trimester in 73%. The degree of proteinuria correlated with diastolic pressure and creatinine clearance. After pregnancy, proteinuria declined in 65% of the mothers, hypertension was absent in 43.5%, and the expected rate of fall in creatinine clearance was not accelerated. Among 35 patients, abortion occurred spontaneously or was performed electively in 25.7%, and 71% of the remainder underwent delivery before 37 weeks. Birth weight was related to maternal blood pressure and creatinine clearance. Neonatal morbidity was common, but the perinatal survival rate was 89%. Infants seen at follow-up without congenital anomalies had normal development at 8 to 36 months of age. We concluded that perinatal outcome has significantly improved for diabetic women with nephropathy.

Spontaneous neck flexion and airway obstruction during apneic spells in preterm infants

Forty-three apneic episodes were observed in eight preterm infants, four of whom had a history of spells. Measurements of expiratory airflow and respiratory effort indicated that 36 of 43 spells were mixed, consisting of central apnea preceded or followed by airway obstruction. The episodes occurred more frequently during periods of spontaneous neck flexion. This association can be related to previous studies indicating that neck flexion interferes with neuromuscular regulation of pharyngeal patency and can produce intermittent airway obstruction. Our observations suggest that airway obstruction may be an important factor in the pathogenesis of apnea in certain preterm infants.

Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn.

ObjectiveWe previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether treatment with inhaled NO improves oxygenation and clinical outcomes in infants with persistent pulmonary hypertension of the newborn and associated lung disease who are ventilated with high-frequency oscillatory ventilation (HFOV). DesignSingle-center, prospective, randomized, controlled trial. SettingNewborn intensive care unit of a tertiary care teaching hospital. PatientsWe studied infants with a gestational age of ≥34 wks who were receiving mechanical ventilatory support and had echocardiographic and clinical evidence of pulmonary hypertension and hypoxemia (Pao2 ≤100 mm Hg on Fio2 = 1.0), despite optimal medical management. Infants with congenital heart disease, diaphragmatic hernia, or other major anomalies were excluded. InterventionsThe treatment group received inhaled NO, whereas the control group did not. Adjunct therapies and ECMO criteria were the same in the two groups of patients. Investigators and clinicians were not masked as to treatment assignment, and no crossover of patients was permitted. Measurements and Main ResultsPrimary outcome variables were mortality and use of ECMO. Secondary outcomes included change in oxygenation and duration of mechanical ventilatory support and supplemental oxygen therapy. Forty-two patients were enrolled. Baseline oxygenation and clinical characteristics were similar in the two groups of patients. Infants in the inhaled NO group (n = 21) had improved measures of oxygenation at 15 mins and 1 hr after enrollment compared with infants in the control group (n = 20). Fewer infants in the inhaled NO group compared with the control group were treated with ECMO (14% vs. 55%, respectively;p = .007). Mortality did not differ with treatment assignment. ConclusionsAmong infants ventilated by HFOV, those receiving inhaled NO had a reduced need for ECMO. We speculate that HFOV enhances the effectiveness of inhaled NO treatment in infants with persistent pulmonary hypertension of the newborn and associated lung disease.