Susan W. Aucott

Prophylaxis of Early Adrenal Insufficiency to Prevent Bronchopulmonary Dysplasia: A Multicenter Trial

Background. Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks’ postmenstrual age, particularly in infants exposed to histologic chorioamnionitis. Methods. Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks’ postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation ≥90%). Results. Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect. Conclusions. Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.

Increased morbidity in severe early intrauterine growth restriction.

OBJECTIVE: To determine the relative frequencies of complications in severe early intrauterine growth-restricted (IUGR) infants.METHODS: All infants 32 weeks gestation or less with birth weight less than the fifth percentile admitted from January 1991 to December 1998 were identified retrospectively. Two infants were identified for each IUGR case: the subsequent admission with birth weight ±100 g of the case, and the subsequent admission with the same gestational age. Infants with multiple congenital anomalies, congenital infections or admission after 48 hours of age were excluded. Maternal and neonatal demographic data, neonatal morbidity and mortality until discharge were gathered by chart review.RESULTS: A total of 39 IUGR identified infants met criteria, with 41 gestational age infants and 33 birth weight infants. Mean birth weights and gestational ages for the IUGR group, gestational age group, and birth weight group were 744 g and 29.6 weeks, 1370 g and 29.7 weeks, and 781 g and 25.5 weeks respectively. Mortality was higher for IUGR infants than gestational age infants (20.5 vs 0%), but less than the birth weight infants (30%). In surviving infants, total ventilator days, total oxygen days, days to full feeds, and patent ductus arteriosis, were higher for IUGR infants than gestational age infants, but less than birth weight infants. Hypoglycemia, direct hyperbilirubinemia, necrotizing enterocolitis (NEC), thrombo-cytopenia, chronic lung disease and feeding difficulties occurred more frequently in IUGR infants than in both other groups. Length of stay for survivors and incidence of retinopathy of prematurity (ROP) was similar for the IUGR and birth weight infants.CONCLUSIONS: Infants born prematurely who are also severely IUGR have higher neonatal morbidity and mortality when compared to infants of similar gestational age. The surviving IUGR infants had less intraventricular hemorrhage and periventricular leukomalacia than less mature infants of comparable birth weight, but a similar incidence of ROP and length of stay. They had a higher incidence of NEC, direct hyperbilirubinemia and chronic lung disease, probably due to end-organ damage in utero from chronic placental insufficiency. These findings highlight the unique pattern of mortality and morbidity seen in infants with severe early IUGR.

Prevention and management of procedural pain in the neonate: An update

The prevention of pain in neonates should be the goal of all pediatricians and health care professionals who work with neonates, not only because it is ethical but also because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor, yet painful procedures. Therefore, every health care facility caring for neonates should implement (1) a pain-prevention program that includes strategies for minimizing the number of painful procedures performed and (2) a pain assessment and management plan that includes routine assessment of pain, pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and measures for minimizing pain associated with surgery and other major procedures.

Chlorhexidine use in the Neonatal Intensive Care Unit: Results from a National Survey

Infection prevention guidelines do not endorse chlorhexidine gluconate (CHG) use in neonates who are less than 2 months old. A survey of US neonatology program directors revealed that most neonatal intensive care units use CHG, often with some restrictions. Prospective studies are needed to further address concerns regarding the safety of CHG in patients in the neonatal intensive care unit.

Safety of chlorhexidine gluconate used for skin antisepsis in the preterm infant.

Chlorhexidine gluconate (CHG) is a widely used topical antiseptic that is recommended by the Centers for Disease Control and Prevention for skin cleansing before central venous catheter insertion in adults and children. Because of limited safety data, CHG is not recommended for use in children <2 months of age. CHG is, however, frequently used in Neonatal Intensive Care Units across the United States. Here, we will review the safety of CHG use in preterm infants.

Do cortisol concentrations predict short-term outcomes in extremely low birth weight infants?

OBJECTIVE. Relative adrenal insufficiency in extremely low birth weight infants may contribute to significant morbidity and death. Our objective was to evaluate the relationship between cortisol concentrations and short-term outcomes. METHODS. Cortisol concentrations were obtained for 350 intubated, extremely low birth weight infants at postnatal age of 12 to 48 hours and at day 5 to 7, as part of a multicenter, randomized trial of hydrocortisone treatment for prophylaxis of relative adrenal insufficiency. Death and short-term morbidity were monitored prospectively. Cortisol levels at each time point were divided into quartiles. The incidence rates of outcomes were determined for each quartile and for infants with cortisol values of <10th percentile or >90th percentile. RESULTS. Median cortisol values were 16.0 μg/dL at baseline and 13.1 μg/dL on day 5 to 7 in the placebo group. Outcomes did not differ in each quartile between treatment and placebo groups. Low cortisol values at baseline or day 5 to 7 were not associated with increased morbidity or mortality rates and were not predictive of open-label hydrocortisone use. In fact, vasopressor use was lower for infants with lower cortisol values at baseline. Severe intraventricular hemorrhage was more frequent in infants with cortisol levels in the upper quartile at baseline, and values of >90th percentile were significantly associated with higher rates of death, severe intraventricular hemorrhage, periventricular leukomalacia, gastrointestinal perforation, and severe retinopathy of prematurity. CONCLUSIONS. Low cortisol concentrations were not predictive of adverse short-term outcomes, but high cortisol concentrations were associated with severe intraventricular hemorrhage, and extremely elevated values were associated with morbidity and death. Low cortisol concentrations alone at these 2 time points did not identify the infants at highest risk for adverse outcomes. In contrast, high cortisol values were associated with increased morbidity and mortality rates.

Patent Ductus Arteriosus in Preterm Infants.

Despite a large body of basic science and clinical research and clinical experience with thousands of infants over nearly 6 decades,1 there is still uncertainty and controversy about the significance, evaluation, and management of patent ductus arteriosus in preterm infants, resulting in substantial heterogeneity in clinical practice. The purpose of this clinical report is to summarize the evidence available to guide evaluation and treatment of preterm infants with prolonged ductal patency in the first few weeks after birth.

The apgar score

The Apgar score provides an accepted and convenient method for reporting the status of the newborn infant immediately after birth and the response to resuscitation if needed. The Apgar score alone cannot be considered as evidence of, or a consequence of, asphyxia; does not predict individual neonatal mortality or neurologic outcome; and should not be used for that purpose. An Apgar score assigned during resuscitation is not equivalent to a score assigned to a spontaneously breathing infant. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists encourage use of an expanded Apgar score reporting form that accounts for concurrent resuscitative interventions.

Herpes Simplex Virus Infections in Preterm Infants

OBJECTIVE. Neonatal herpes simplex virus infections cause significant neonatal mortality and morbidity, but the course and prognosis in preterm infants is not well documented. We performed a retrospective review of herpes simplex virus infections at out institution within the first 30 days after birth in infants who were born at <37 weeks to help better define the symptoms and signs of herpes simplex virus infections in preterm infants and to assist in prognosis. METHODS. Hospital databases were reviewed to identify culture- or polymerase chain reaction–proven cases of herpes simplex virus-1 or herpes simplex virus-2 infections that occurred in preterm newborns between 1989 and 2003. Maternal and neonatal histories, clinical features, and laboratory results were reviewed systematically. RESULTS. Ten preterm singletons and a set of twins were infected with herpes simplex virus-2 during the first month after birth. No mother had herpes simplex virus lesions at delivery, but a history of genital herpes simplex or other sexually transmitted infections was prevalent among the mothers. Infants presented with either disseminated disease or encephalitis. All infants with disseminated disease (n = 9) died, whereas the 3 infants with encephalitis survived. All infants in the cohort developed respiratory distress, and consistent with the prominence of respiratory symptoms, viral cultures of the respiratory tract were consistently positive. Ten of 12 infants received acyclovir, but despite treatment within 48 hours of symptoms, infants with disseminated disease deteriorated rapidly and died. Two of 3 infants who received high-dosage (60 mg/kg per day) acyclovir survived. CONCLUSIONS. Herpes simplex virus infections in preterm infants usually present during the first 2 weeks of life with respiratory distress and a high incidence of disseminated disease. Viral respiratory cultures have a high yield for documentation of infection. The morbidity of herpes simplex virus in this population may be attributable to a relatively immature immune system in this population. Additional studies are necessary to delineate the evolution of herpes simplex virus disease in preterm infants and the role of antiviral therapy in mitigating the sequelae of herpes simplex virus infections in this population.

Absorption and tolerability of aqueous chlorhexidine gluconate used for skin antisepsis prior to catheter insertion in preterm neonates

Objective:To assess chlorhexidine absorption and skin tolerability in premature infants, following skin antisepsis with 2% aqueous chlorhexidine gluconate (CHG) prior to peripherally inserted central catheter (PICC) placement.Study Design:Neonates less than 32 weeks gestation had skin cleansed with CHG prior to PICC placement. CHG concentrations were measured on serial blood samples. Skin integrity was evaluated for 2 weeks after CHG exposure.Result:Twenty infants were enrolled; median gestational age was 28 2/7 weeks (range 24 3/7 to 31 4/7). Ten infants had detectable serum chlorhexidine concentrations (range 1.6 to 206 ng ml−1). Seven of these infants had their highest serum concentration 2 to 3 days following exposure. No CHG-related skin irritation occurred in any infant.Conclusion:CHG was detected in the blood of preterm infants receiving CHG skin antisepsis for PICC insertion. Highest serum concentrations occurred 2 to 3 days after exposure. Further investigation is needed to determine the clinical relevance of CHG absorption in preterm infants.