Communicating prognosis with parents of critically ill infants: direct observation of clinician behaviors.

OBJECTIVE: Delivering prognostic information to families requires clinicians to forecast an infant's illness course and future. We lack robust empirical data about how prognosis is shared and how that affects clinician-family concordance regarding infant outcomes. STUDY DESIGN: Prospective audiorecording of neonatal intensive care unit family conferences, immediately followed by parent/clinician surveys. Existing qualitative analysis frameworks were applied. RESULTS: We analyzed 19 conferences. Most prognostic discussion targeted predicted infant functional needs, for example, medications or feeding. There was little discussion of how infant prognosis would affect infant/family quality of life. Prognostic framing was typically optimistic. Most parents left the conference believing their infant's prognosis to be more optimistic than did clinicians. CONCLUSIONS: Clinician approach to prognostic disclosure in these audiotaped family conferences tended to be broad and optimistic, without detail regarding implications of infant health for infant/family quality of life. Families and clinicians left these conversations with little consensus about infant prognosis.

Withholding feeding during transfusion: Standardization of practice and nutritional outcomes in premature infants.

OBJECTIVE: To evaluate the nutritional impact of a feed-holding guideline during transfusion for infants <32 weeks gestation. STUDY DESIGN: A pre-/post-interventional study was conducted after introduction of a guideline to hold feeds during transfusion. Demographic variables in addition to nutritional outcomes were collected on all infants admitted within 48 hours of birth with gestational age <32 weeks. Data was collected during a 6 month period pre-intervention and the 6 month period post-intervention. RESULTS: There were 145 eligible infants. Mean birth weight and gestational age were similar in both periods. In total, 98 infants received transfusions, and 82 of those had an active feeding order prior to at least one transfusion. Total transfusions per infant and transfusions ordered while an infant had active feeding orders were similar in both periods. Time to full feedings was decreased post-intervention (p <  0.001). Weight at 34 weeks, incidence of second IV placement, additional IV fluid use, and hypoglycemia were similar between groups.Of 593 total transfusions, 207 were ordered while an infant had an active order for enteral nutrition. Pre-intervention, 64% of transfusions had feeds held during transfusion. Post-intervention, 87% of transfusions had feeds held during transfusion. Feeds were held more often (p <  0.001) and for a shorter duration (p = 0.005) in the post-intervention group. CONCLUSION: Implementing a guideline standardizing feeding practices during transfusions in premature infants increases standardization of care and results in decreased variability in practice. Adverse nutritional consequences were not found after the introduction of the routine practice of holding feedings during transfusion in preterm infants.

The impact of group B Streptococcus prophylaxis on early onset neonatal infections.

OBJECTIVE: To determine if changes have occurred in the causative pathogens and/or antibiotic susceptibility profiles in early onset neonatal infections since initiation of group B Streptococcus (GBS) prophylaxis and to determine risk factors for ampicillin/penicillin resistant microorganisms. STUDY DESIGN: Data on 220 infants with positive blood, urine, or cerebrospinal fluid cultures for bacteria or fungi at ≤seven days of age from 1990-2007 were examined and divided into three epochs, based on intrapartum antibiotic prophylactic (IAP) practices. Pathogens and antibiotic resistance were compared among epochs. RESULTS: A significant decrease in the incidence of GBS infections occurred over time, with no change in the incidence of other pathogens or the emergence of antibiotic resistance, including the very low-birthweight population. In regression analysis, ampicillin resistance was associated with male gender (OR 3.096). CONCLUSIONS: No emergence of antibiotic resistant pathogens was found following IAP use. Changing microorganisms and increasing antibiotic resistance found in prior studies are likely multifactorial. Further study is needed to continue to reduce the rates of common early onset pathogens.

The impact of group B streptococcus prophylaxis on late-onset neonatal infections.

OBJECTIVE: To determine trends in late-onset neonatal infections and risk factors for ampicillin/penicillin-resistant microorganisms. STUDY DESIGN: Data on 584 infants with positive blood, urine or cerebrospinal fluid cultures for bacteria or fungi at 8-30 days of age from 1990 to 2007 were examined and divided into three epochs, based on intrapartum antibiotic prophylactic (IAP) practices. Pathogens and antibiotic resistance were compared among epochs. RESULT: The number of candidal infections increased over time for the entire population (P=0.006). There was an increased incidence of Gram-negative (P=0.009) and candidal infections (P=0.014) among very low-birthweight infants. Only Escherichia coli infections showed increasing ampicillin resistance over epochs (P=0.006). In regression analysis, ampicillin/penicillin resistance increased with IAP use (odds ratio 2.05). CONCLUSION: Changing microorganisms and increasing antibiotic resistance in late-onset neonatal infections are likely multifactorial but are increased with IAP use, which may identify an at-risk population. Increasing Candida infections require further investigation.

Mother-clinician discussions in the neonatal intensive care unit: agree to disagree?

OBJECTIVE: To compare mothers' and clinicians' understanding of an infant's illness and perceptions of discussion quality in the neonatal intensive care unit. STUDY DESIGN: English-speaking mothers with an infant admitted to the intensive care unit for at least 48 h were interviewed using a semi-structured survey. The clinician whom the mother had spoken to and identified was also surveyed. Interviews were audiotaped and transcribed. RESULT: A total of 101 mother-clinician pairs were interviewed. Most mothers (89%) and clinicians (92%) felt that their discussions had gone well. Almost all mothers could identify one of their infant's diagnoses (100%) and treatments (93.4%). Mothers and clinicians disagreed on infant illness severity 45% of the time. The majority of mothers (62.5%) who disagreed with clinician estimate of infant illness severity believed their infant to be less sick than indicated by the clinician. CONCLUSION: Mother-clinician satisfaction with communication does not ensure mother-clinician agreement about an infant's medical status.

Health-related quality of life for infants in the neonatal intensive care unit.

When discussing the benefits and burdens of medical interventions for critically ill infants, clinicians and families are challenged to weigh the uncertainties of treatment success with infant pain and suffering. Concrete measures of infant suffering or quality of life, which could inform infant care and decision-making are lacking. Although consistent and reliable health-related quality of life (HRQOL) definitions and measures have been extensively developed for adults and older children, they have not been relevant to neonates or infants. Advancing HRQOL research methodology is an objective of Healthy People 2020. This paper will review the evidence and practices relevant to HRQOL with a focus on intensive care and pediatric settings. We will highlight existing HRQOL measures, which could be adapted for neonates and existing neonatal intensive care unit measures and practices, which could inform new measures of HRQOL.

Cardiovascular instability after patent ductus arteriosus ligation in preterm infants: the role of hydrocortisone.

OBJECTIVE: Following patent ductus arteriosus (PDA) ligation, preterm infants may develop profound hypotension and respiratory failure. Prophylactic stress hydrocortisone (HC) has emerged as a therapy to prevent complications, postulating these infants do not synthesize steroids because of an immature hypothalamic-pituitary-adrenal axis. The purpose of this study was to compare outcomes in infants who received stress HC before their PDA ligations to those who did not. STUDY DESIGN: A retrospective chart review was performed of infants who underwent PDA ligations at our institution's neonatal intensive care unit. Data were collected on treatment with HC, and respiratory and cardiovascular support. RESULT: Gestational age (GA) and birth weight were lower in the HC group (24 vs 25 weeks, 632 vs 790 g), but age at time of surgery was similar (26 vs 21 days). Cardiorespiratory support was comparable between the groups pre- and post-operatively. In regression models that adjusted for GA, HC treatment was not independently related to respiratory support postoperatively, but was associated with a decrease in postoperative dopamine (2.2 mcg kg(-1) min(-1); P=0.03). Respiratory support postoperatively was predicted by preoperative respiratory support. GA and age at surgery were not independently associated with outcome. CONCLUSION: Preoperative stress HC was not associated with improved cardiorespiratory stability, regardless of GA. Further investigation is needed to identify infants who may benefit from this therapy.

Adolescent mothers in the NICU: how much do they understand?

OBJECTIVE: We aimed to characterize adolescent parents' understanding of their infant's diagnosis, treatment and illness severity in the intensive care unit. STUDY DESIGN: Adolescent mothers were interviewed and neonatal medical records were reviewed. RESULT: Forty-two teens were interviewed. All had spoken with providers: 86% with nurses, 60% with physicians and 45% with both. Most teens could name their infant's diagnosis and treatment but often underestimated the illness severity. Teens reported reluctance to ask providers to clarify technical language. Those who said they spoke with a physician were less likely to understand their infant's illness severity than those who said they had not spoken with a physician (48 vs 82%). Parents' knowledge was better if physicians had documented explicit efforts to communicate with parents. CONCLUSION: Teens often underestimated the critical nature of their infant's illness. Future work should target adolescent willingness to ask questions and provider ability to accurately gauge parent knowledge.

Outcomes of early parenteral nutrition for premature infants.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of early amino acid (early AA) administration in very low birth weight (VLBW) infants. STUDY DESIGN: A pre- and post-intervention study was conducted after initiating an early AA administration protocol. Clinical outcomes were collected for all VLBW infants admitted on the first day of life for 9 months before protocol initiation (standard parenteral nutrition (PN)), and 10 months after initiation of early AA. RESULT: In all, 88 infants met study criteria for standard PN, and 85 infants for early AA administration. The patient characteristics were similar between the groups. There were no differences in mortality, the day birth weight was regained, the day enteral feeds started, the duration of PN, the day full feeds achieved and weight at 32 weeks post-menstrual age. No differences were found for late sepsis, direct hyperbilirubinemia and chronic lung disease. Necrotizing enterocolitis (NEC) occurred more frequently in the early AA administration group (12 vs 1%, P=0.012). CONCLUSION: Early AA administration for VLBW infants was as efficacious as standard therapy, although increased NEC in the early AA period may have negatively affected growth and nutrition in that period.

Early cortisol values and long-term outcomes in extremely low birth weight infants.

OBJECTIVE: Both excess and insufficient levels of glucocorticoid in extremely low birth weight (ELBW) infants have been associated with adverse hospital outcomes, whereas excess glucocorticoid exposure has been associated with long-term adverse neurodevelopment. Our objective was to evaluate the relationship between neonatal cortisol concentrations and long-term outcomes of growth and neurodevelopment. STUDY DESIGN: As part of a multicenter randomized trial of hydrocortisone treatment for prophylaxis of relative adrenal insufficiency, cortisol concentrations were obtained at 12 to 48 h of postnatal age and at days 5 to 7 on 350 intubated ELBW infants, of whom 252 survived and returned for neurodevelopmental follow-up at 18 to 22 months corrected age. Cortisol values from each time point were divided into quartiles. Growth and neurodevelopmental outcome were compared for each quartile. RESULT: Median cortisol value was 16.0 microg per 100 ml at baseline for all infants, and 13.1 microg per 100 ml on days 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 at days 5 to 7 were not associated with impaired growth or neurodevelopment at 18 to 22 months corrected age. High cortisol values were associated with an increase in cerebral palsy, related to the increased incidence of severe intraventricular hemorrhage (IVH) and periventricular leukomalacia. CONCLUSION: Low cortisol concentrations were not predictive of adverse long-term outcomes. High cortisol concentrations, although predictive of short-term adverse outcomes such as IVH and periventricular leukomalacia, did not additionally predict adverse outcome. Further analysis into identifying factors that modulate cortisol concentrations shortly after birth could improve our ability to identify those infants who are most likely to benefit from treatment with hydrocortisone.

Parents' perception of the back-transport of very-low-birth-weight infants to community hospitals.

OBJECTIVE: To characterize parents' perception of back-transport of very-low-birth-weight (VLBW) infants from a regional referral neonatal intensive care unit (RR-NICU) to a community hospital (CH) for convalescent care. STUDY DESIGN: Mixed methods utilizing parental interview and medical record review. RESULT: Overall, 20% of parents selected the CH to which their child was transferred. Less than half of the parents wanted the transfer. Psychological comfort with the RR-NICU was the most frequently reported reason for opposing transfer. At the time of home discharge, most parents were satisfied with the transfer and felt prepared to care for their infant at home. CONCLUSION: Parents want their infants closer to home, but are worried about the unknown. They are willing to forfeit autonomy in decision-making regarding the site of convalescent care. Parents need better preparation for transfer. Including them in an advisory group that reviews transfer policies could ameliorate the transition.

The epidemiology of atypical chronic lung disease in extremely low birth weight infants.

OBJECTIVE: To determine the incidence and associated complications of atypical chronic lung disease (ACLD) in extremely low birth weight infants. STUDY DESIGN: All infants born at Johns Hopkins Hospital between 1996 and 2001, with birthweight <1000 g, gestational age <31 weeks, no major anomalies or genetic syndromes, and living at least 21 days were eligible for inclusion. Data pertaining to demographics, hospital course, diagnosis of atypical chronic lung disease, patterns of surfactant use, complications of prematurity and severity of lung disease were collected. RESULT: Using inclusion criteria, 215 eligible infants were identified, of which 185 had hospital charts available for review. Twenty-eight infants (15%) met the criteria for atypical chronic lung disease. Of the remaining 157 infants, 57 patients met the criteria for mild bronchopulmonary dysplasia (BPD) (supplemental oxygen requirement at 28 days of life), 38 patients had moderate/severe BPD (supplemental oxygen requirement at both 28 days of life and 36 weeks post-menstrual age), and 38 infants did not have chronic lung disease. Infants with ACLD had much higher rates of sepsis (46%) and pneumothorax (18%) than infants in the comparison groups. CONCLUSION: Infants with respiratory distress syndrome in the first week of life, which initially resolves are still at risk for an atypical form of chronic lung disease. The prolonged respiratory support they require as a result of this type of lung disease increases their risk for complications of prematurity, which may outlast their lung disease. We speculate that inflammation secondary to infection acquired shortly after birth may be an important step in the pathogenesis of ACLD.

Earlier markers for cerebral palsy and clinical research in premature infants.

The diagnosis of cerebral palsy is based on evidence of impairment of the motor system, but symptoms become evident only as a premature infant matures. The diagnosis is made typically at 18 to 24 months of age, corrected for gestational age at birth. An earlier and more accurate way to identify infants destined to develop cerebral palsy may help improve the prognosis for this vulnerable population. For now, no antenatal, perinatal or postnatal test can predict cerebral palsy with a degree of certainty high enough to help providers or parents plan for an infant's future or make the best use of early intervention resources.

Microbiological assessment of bile during cholecystectomy: is all bile infected?

AIMS: To determine the prevalence of bactibilia in patients undergoing cholecystectomy and to relate the presence or absence of organisms to the preoperative and postoperative course. PATIENTS AND METHODS: Patients undergoing cholecystectomy under the care of a single consultant surgeon during a continuous 5-year period were identified from a prospectively maintained departmental database. Symptoms, clinical signs, findings of investigations, details of treatment and postoperative care were noted. Risk factors for bactibilia (acute cholecystitis, common duct stones, emergency surgery, intraoperative findings and age > 70 years) were documented. Patients were divided according to the presence (B + ) or absence (B-) of bacteria on culture of their bile. RESULTS: In all, 128/180 (70%) of cholecystectomies had full data available for analysis. Bacteria were identified in the bile of 20 (15.6%) patients (B+ group). The B+ group was significantly older at 63.78+/-9.7 versus 61.62+/-13.9 (p<0.05) and contained significantly fewer females than the B- group (p<0.05). All 20 patients (100%) in the B+ group had > or = 1 risk factor, while these factors were present in only 29/108 (30.3%) of patients in the B- group (p<0.05). The overall incidence of infective complications was 20% in the B+ group compared with 0.9% in the B- group (p<0.05) and the bile-related infections were higher in the B+ group (p<0.05). CONCLUSIONS: The study demonstrated that while patients with complicated gallstone disease frequently exhibit bactibilia, patients with uncomplicated cholelithiasis have aseptic bile. The findings would suggest that prophylactic antibiotics should be limited to patients with risk factors for bactibilia.

Monte Carlo simulations on the effect of substrate geometry on adsorption and compression.

Canonical Monte Carlo simulations were used to study the adsorption and compression of fluid layers on model substrates with cubic, (111) fcc, and graphite geometries. The effect of the relative size of the fluid and substrate molecules on adsorption was considered for strong molecule-surface interactions. In the case of monolayer formation, it was found that the surface geometry and the size of the adsorbate molecules had a significant effect on the structure of the adsorbed layer. These structures varied from well-ordered, commensurate layers to liquid-like structures. Lateral compression was observed for certain fluid to substrate molecule sizes. For the interactions studied in this work, it was found that maximum lateral compression occurred on the cubic surface when adsorbate molecules had a diameter approximately 15% larger than the substrate diameter. In the case of multilayer formation, it was found that second and higher adsorbed layers could compress into the adsorbed layers below them. For cubic substrates, the interlayer compression was predicted analytically with reasonable accuracy, with maximum interlayer compression found for fluid diameters approximately 90% the size of substrate molecule diameters.

Oxygen saturation as a screening test for critical congenital heart disease: a preliminary study.

The aim of this study was to assess the utility of arm and leg oxygen saturation as a candidate screening test for the early detection of ductal-dependent left heart obstructive disease. We measured arm and leg oxygen saturation in 2876 newborns admitted to well baby nurseries and 32 newborns with congenital heart disease. Fifty-seven newborns in the well baby nurseries (0.02%) had an abnormal test (leg saturation less than 92% in room air or 7% lower saturation in the leg than in the arm). Four of the 57 had critical congenital heart disease, including 1 with coarctation of the aorta. Of the 32 newborns with congenital heart disease, 11/13 (85%) with left heart obstructive disease had abnormal oxygen saturation tests, as did 15/19 (79%) with other forms of congenital heart disease. Pulse oximetry deserves further study as a screening test for critical congenital heart disease.

An aspartate residue at the extracellular boundary of TMII and an arginine residue in TMVII of the gastrin-releasing peptide receptor interact to facilitate heterotrimeric G protein coupling.

The mammalian bombesin receptor subfamily of G protein-coupled receptors currently consists of the gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor, and bombesin receptor subtype 3. All three receptors contain a conserved aspartate residue (D98) at the extracellular boundary of transmembrane domain II and a conserved arginine residue (R309) near the extracellular boundary of transmembrane domain VII. To evaluate the functional role of these residues, site-directed GRP-R mutants were expressed in fibroblasts and assayed for their ability to both bind agonist and catalyze exchange of guanine nucleotides. Alanine substitution at GRP-R position 98 or 309 reduced agonist binding affinity by 24- and 56-fold, respectively, compared to wild-type GRP-R. Single swap GRP-R mutations either resulted in no receptor expression in the membrane (D98R) or the protein was not able to bind agonist (R309D). In contrast, the double swap mutation (D98R/R309D) had high-affinity agonist binding, reduced from wild-type GRP-R by only 6-fold. In situ reconstitution of urea-extracted membranes expressing either wild-type or mutant (D98A or R309A) GRP-R with G(q) indicated that alanine substitution greatly reduced G protein catalytic exchange compared to wild-type GRP-R. The D98R/R309D GRP-R had both a higher intrinsic basal activity and a higher overall catalytic exchange activity compared to wild-type; however, the wild-type GRP-R produced a larger agonist-stimulated response relative to the double swap mutant. Taken together, these data show that GRP-R residues D98 and R309 are critical for efficient coupling of GRP-R to G(q). Furthermore, our findings are consistent with a salt bridge interaction between these two polar and oppositely charged amino acids that maintains the proper receptor conformation necessary to interact with G proteins.

Pharmacology and cell biology of the bombesin receptor subtype 4 (BB4-R).

Recently, a fourth member of the bombesin (Bn) receptor family (fBB4-R) was isolated from a cDNA library from the brain of the frog, Bombina orientalis. Its pharmacology and cell biology are largely unknown, and no known natural cell lines or tissues possess sufficient numbers of fBB4-R's to allow either of these to be determined. To address these issues, we have used three different strategies. fBB4-R expression in cells widely used for other Bn receptor subtypes was unsuccessful as was expression in two frog cell lines. However, stable fBB4-R cell lines were obtained in CHO-K1 cells which were shown to faithfully demonstrate the correct pharmacology of the related Bn receptor, the GRP receptor, when expressed in these cells. [DPhe6,betaAla11,Phe13,Nle14]Bn(6-14) was found to have high affinity (Ki = 0.4 nM) for the fBB4 receptor and 125I-[DTyr6,betaala11,Phe13,Nle14]Bn(6-14) to be an excellent ligand for this receptor. The fBB4-R had a unique pharmacology for naturally occurring Bn-related agonists, with the presence of a penultimate phenylalanine being critical for high-affinity interaction. It also had a unique profile for six classes of Bn antagonists. The fBB4-R was coupled to phospholipase C with activation increasing [3H]inositol phosphates and mobilizing Ca2+ almost entirely from cellular sources. There was a close correlation between agonist the receptor occupation and the receptor activation. Three of the five classes of Bn receptor antagonists that interacted with higher affinity with the fBB4-R functioned as fBB4-R antagonists and two as partial agonists. fBB4-R activation stimulated increases in phospholipase D (PLD) over the same range of concentrations at which it activated phospholipase C. These results demonstrate that the fBB4 receptor has a unique pharmacology for agonists and antagonists and is coupled to phospholipase C and D. The availability of these cell lines, this novel ligand, and the identification of three classes of antagonists that can be used as lead compounds should facilitate the further investigation of the pharmacology and cell biology of the BB4 receptor.