Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis.

OBJECTIVE: To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis. STUDY DESIGN: Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations. RESULTS: Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity. CONCLUSION: A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.

The effect of tobacco smoke on oxytocin concentrations and selected oxidative stress parameters in plasma during pregnancy and post-partum - an experimental model.

BACKGROUND: Tobacco smoking is a serious threat to life and health of society. Among the most vulnerable to the toxic effects of tobacco smoke are foetuses and newborns. The objective of the research was to assess the impact of tobacco smoke exposure on oxytocin levels and biochemical oxidative stress parameters during pregnancy and after birth in an experimental model. METHODS: In the experiment, exposure to tobacco smoke of gravid and non-gravid rats was monitored. A reliable biomarker of exposure - cotinine - was used in the process and it was determined by means of high-performance liquid chromatography with diode array detection, which ensured high analytical accuracy and precision. Determination of oxytocin was performed by means of enzyme-linked immunosorbent assay. The levels of selected oxidative stress parameters: total protein concentration, uric acid, trolox equivalent antioxidant capacity, protein S-nitrosylation and lipid peroxidation (thiobarbituric acid reactive substances) were measured by spectrophotometric methods. RESULTS AND CONCLUSIONS: The effect of prenatal and postnatal exposure to tobacco smoke was a lower medium body mass of rat foetuses and pups. Oxidative stress during pregnancy, additionally intensified by tobacco smoke exposure, led to adaptive changes in properties of plasmatic antioxidant barriers. Moreover, the disturbance of oxidoreductive balance by tobacco smoke affects oxytocin fluctuations, what was observed in this study during lactation period. Therefore, women who smoke may breastfeed their children less frequently and for a shorter period.

Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation.

OBJECTIVE: We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation. STUDY DESIGN: A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was > 15 µg kg(-1)min(-1). Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension). RESULT: Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration. CONCLUSION: We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.

Impact of ART on pregnancies in California: an analysis of maternity outcomes and insights into the added burden of neonatal intensive care.

OBJECTIVE: We reviewed the occurrence of prematurity, low birth weight, multiple gestations, frequency of stillbirths and maternity care-associated variables including hospital stay and hospital charges of women conceiving using assisted reproductive technology (ART) or artificial insemination (AI) compared with women with a history of infertility who conceived naturally, and all other naturally conceived pregnancies in California at non-federal hospitals between 2009 and 2011. At a single center, infants born after ART/AI were compared with infants provided care in the normal nursery. STUDY DESIGN: Publically available inpatient data sets from the California Office of Statewide Health Planning and Development for years 2009-2011 using data from all California non-federal hospitals were used to determine the impact of ART on a variety of pregnancy-related outcomes and infant characteristics. Infant data from a single center was used to determine hospital charges for infants delivered over an 18-month period to compare the hospital and physician charges indexed to similar charges for infants admitted to the 'normal' newborn nursery. RESULT: Among ART/AI pregnancies, there was a 4-5-fold increase in stillbirths, compared with a 2-3-fold increase among women with infertility compared with other naturally conceiving women. ART/AI pregnancies underwent more cesarean sections (fourfold), and a near fourfold increase in the rate of preterm deliveries. Multiple gestations were increased 24-27-fold compared with naturally conceived pregnancies. Maternal hospital stay and hospital charges were increased among those undergoing ART/AI. Infant charges were increased multi-fold for singletons, twins and triplets delivered after ART/AI compared with naturally conceived infants. CONCLUSION: Multiple births, preterm births and a higher overall rate of fetal anomalies were found in California after ART/AI for 2009-2011. Cesarean section rates, longer length of maternal stay and hospital charges among women receiving ART/AI could be lowered if emphasis on elective single embryo transfers was a higher priority among providers. Charges for the care of infants delivered after ART/AI are substantially higher than among naturally conceived infants born late preterm or at term. Families seeking ART/AI need to be informed of the impact of these adverse pregnancy outcomes, including neonatal outcomes and charges for medical care for their infant(s), when considering ART/AI.

The impact of assisted reproductive technologies on the genome and epigenome of the newborn.

The question of genetic alterations resulting from assisted reproductive technologies (ART) in humans is examined within the organization of the human genome. Increased rates of birth defects have been reported among children conceived using ART; however, questions remain and controversy exists regarding how "infertility" predisposes to birth defects. ART has been shown to be associated with an increased number of chromosomal alterations especially in the X chromosome. There is increased risk for embryonal tumors among ART conceived children, as well as, imprinting disorders (Beckwith-Wiedemann and Angelman Syndromes). Genetic studies of children conceived using ART reveal a larger (genome-wide) scale of methylation defects that encompass hundreds of genes. Genes involved in carcinogenesis and developmental pathways appear altered and may impact on later development of chronic illness, although these data are very preliminary. ART may create novel mutations by different chromosomal and molecular mechanisms; however, these techniques also enable propagation of pre-existing mutations that are associated with impaired fertility. While older maternal age is often associated with female infertility and chromosomal aneuploidy, sperm from older men have more new gene mutations. The prevalence of birth defects is increased when ART is used for conception. These data are summarized by large meta-analyses or from multi-year national registries. Whether the increased number of birth defects is due to ART procedures themselves or are a consequence of the impaired fertility of the parents is discussed. Long-term evaluation of children conceived using ART and/or ovarian hyper-stimulation is needed to determine whether alterations during embryonic development may increase the prevalence of chronic diseases in adulthood.

Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of prenatal exposure.

UNLABELLED: Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study. RESULTS: concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns' hair when compared to mothers'. The mean concentrations of diazepam in mothers' hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns' hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers' hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns' hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn's hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers' hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus's ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child's organism. Other metabolites of diazepam--oxazepam and temazepam--were detected in very few cases, in low concentrations.

Prevention of postpartum smoking relapse in mothers of infants in the neonatal intensive care unit.

OBJECTIVE: Approximately 40% of women who smoke tobacco quit smoking during pregnancy, yet up to 85% relapse after delivery. Those who resume smoking often do so by 2 to 8 weeks postpartum. Smoking mothers are more than twice as likely to quit breastfeeding by 10 weeks postpartum. The hospitalization of a newborn, while stressful, is an opportunity to emphasize the importance of a smoke-free environment for babies. Supporting maternal-infant bonding may reduce maternal stress and motivate mothers to remain smoke free and continue breastfeeding. The objective of this study was to reduce postpartum smoking relapse and prolong breastfeeding duration during the first 8 weeks postpartum in mothers who quit smoking just before or during pregnancy and have newborns admitted to the Neonatal Intensive Care Unit (NICU). STUDY DESIGN: This study was an Institutional Review Board-approved prospective randomized clinical trial. After informed consent, mothers of newborns admitted to the NICU were randomized to a control or intervention group. Both groups received weekly encouragement to remain smoke free and routine breastfeeding support. Mothers in the intervention group were also given enhanced support for maternal-infant bonding including information about newborn behaviors, and were encouraged to frequently hold their babies skin-to-skin. RESULT: More mothers were smoke free (81 vs 46%, P<0.001) and breastfeeding (86 vs 21%, P<0.001) in the intervention than in the control group at 8 weeks postpartum. CONCLUSION: Interventions to support mother-infant bonding during a newborn's hospitalization in the NICU are associated with reduced rates of smoking relapse and prolonged duration of breastfeeding during the first 8 weeks postpartum.

Use of propranolol for treatment of hemangiomas in PHACE syndrome.

We report the case of a 29-week preterm infant with PHACE (posterior fossa malformations, hemangionas, arterial anomalies, cardiac anomalies, eye anomalies) syndrome. PHACE syndrome is a neurocutaneous disorder with large facial segmental hemangionas associated with anomalies of the brain, eye, heart and aorta. The hemangiomas in our patient were problematic, distorting the airway and interfering with respirations to the point of requiring mechanical ventilation. Consultation with several different centers with medical expertize in treatment of congenital hemangiomas revealed different views on the best management strategy. In this infant, the hemangiomas progressed with failure to involute despite currently recommended therapy including corticosteroids and vincristine. Therefore, the infant was treated with propranolol and had significant regression of the hemangiomas. The use of propranolol for the treatment of infantile hemangiomas is reviewed.

Pulmonary distribution of lucinactant and poractant alfa and their peridosing hemodynamic effects in a preterm lamb model of respiratory distress syndrome.

Tracheal instillation of surfactant to premature newborns improves their survivability but may transiently obstruct airways resulting in undesirable acute effects on cerebral blood flow (CBF) and oxygenation. The acute peridosing hemodynamic effects of surfactant administration may be avoided by minimizing the volume of surfactant administered, but smaller surfactant volumes may also result in less even distribution of surfactant throughout the lung. These experiments were undertaken to compare responses to two surfactants with different dose volumes (porcine-derived poractant alfa, 2.5 mL/kg vs peptide-based synthetic lucinactant, 5.8 mL/kg) given to newly delivered lambs at 85% gestation. Both surfactants resulted in similar improvements in blood gas values, a doubling of dynamic compliance, increases in brain tissue oxygen tension, and stable blood pressure with no significant change in CBF. Distribution of surfactant throughout the lungs was more uniform with lucinactant than poractant alfa when assessed by labeled microspheres. We conclude that improvements in lung mechanics, gas exchange, and changes in CBF are comparable for a porcine-derived and peptide-containing synthetic surfactant, despite instilled volumes differing by 2-fold. Intrapulmonary distribution of surfactant is more uniform after a larger volume is instilled.

A critical evaluation of clinical practice guidelines in neonatal medicine: does their use improve quality and lower costs?

Clinical practice guidelines and care pathways have become a focus of quality improvement efforts in Neonatology. Health care administrators believe that using clinical practice parameters reduces health care costs, improves quality of care, and limits malpractice liability. Practice guidelines and surveys of consumer satisfaction have grown in use partly because third-party payers, insurers, and health maintenance organizations, as well as hospital administrators bent on reducing variable costs of care and contracting for capitated care have championed their development, implementation, and monitoring. Overall there is minimal evidence-based medicine to support that neonatal outcomes have benefitted from their implementation, although some studies show affirmative effects in limited populations or in a limited number of centres. For highly autonomous physicians and nurses this standardization of medical decision making may represent a difficult transition into efforts to improve quality, based on evidence-based care, and in some instances into corporate medicine. By realigning the traditional values of patient relationships, including parent involvement, the implementation of guidelines has been fast-tracked in some institutions, without appropriate audit to determine their effectiveness in achieving their goals. However, because guidelines and clinical pathways are here to stay, neonatologists need to think critically about how their content and method of implementation, monitoring and modification may influence medical and nursing teaching and decision making in the future. If guidelines are introduced primarily as a cost savings or containment tool that ignores their impact on the quality of medical care and thereby restricts needed care, then neonatologists must be quick to challenge the potentially damaging and inappropriate use of guidelines and care pathways. Several international efforts are underway to study both the impact of evidence-based guidelines and to determine if they can be imported from one care system into another. Furthermore, there are many medico-legal implications of guideline and clinical pathway implementation that may not favour physicians and other neonatal care practitioners, and leave to hospitals, insurers, and ultimately the courts, decisions regarding evidence-based care. Neonatologists and other practitioners in neonatal care centres should critically analyse the goals of guideline development, implementation and monitoring and should restrict themselves to guideline directed care only at those practices for which there is evidence supporting their implementation and continuous monitoring.

Oxidative inactivation of surfactants.

Reactive oxygen species (ROS) may play an important role in the chronic pulmonary morbidity of preterm infants. We therefore studied the magnitude and mechanisms of oxidative inactivation of a natural lung surfactant (NLS) and of two surfactants used for treatment of respiratory distress syndrome, beractant and KL4 surfactant (KL4). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO-) or 0.5 mM hypochlorous acid (OCl-), resulted in an increased minimum surface tension (MST) of all surfactants; the order of effect on MST was beractant > KL4 > NLS. After incubation with Fenton reagents, NLS contained a higher concentration of conjugated dienes (p < 0.01) but lower concentration of malondialdehyde (p < 0.001) than beractant. Protein carbonyl concentrations after treatment with Fenton reagents were higher in NLS and KL4 than in beractant (p < 0. 05). Surface area cycling for 24 h with 2 mM ONOO- or 0.5 mM OCl- caused both beractant and KL4 to increase the proportion of light subtypes from 8-10% to 26-29%; with Fenton reagents, there was disappearance of the light subtype and formation of ultraheavy subtype 74-91% with poor MST. Natural and therapeutic surfactants differ markedly in their sensitivity to ROS, which may be important for surfactants in therapeutic use because oxidative inactivation may limit their effect. Oxidation of natural surfactant may result in reduced function and contribute to chronic lung disease.

Intensive lifestyle changes for reversal of coronary heart disease.

CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.

Bronchoalveolar lavage with KL4-surfactant in models of meconium aspiration syndrome.

As a model of the meconium aspiration syndrome (MAS) of human infants, adult rabbits and newborn rhesus monkeys received intratracheal instillation of human meconium to induce pulmonary injury. Injured rabbits were ventilated with 100% O2 and divided into four treatment groups, receiving: 1) bronchoalveolar lavages (BAL) with dilute KL4-Surfactant; 2) lavages with equal volumes of sterile saline; 3) a single intratracheal bolus of KL4-Surfactant, 100 mg/kg; and 4) no treatment. The untreated rabbits developed atelectasis, a fall in pressure-volume levels and in partial pressure of O2 in arterial blood (PaO2) from approximately 500 to < 100 mm Hg, and severe pulmonary inflammation between 3 and 5 h after instillation of meconium. Rabbits treated by BAL with dilute KL4-Surfactant showed rapid and sustained recovery of PaO2 to approximately 300 mm Hg within minutes, a return toward normal pressure-volume levels, and diminished inflammation. Rabbits receiving BAL with saline failed to show recovery, and rabbits treated with a bolus of surfactant intratracheally exhibited a transient response by 1-2 h after treatment, but then returned to the initial atelectatic state. Newborn rhesus monkeys, after receiving human meconium intratracheally before the first breath, developed severe loss of pulmonary function. Treatment of these monkeys 1-5 h after birth with BAL with dilute KL4-Surfactant produced clearing of chest radiographs and a rapid improvement in pulmonary function with ratios of partial pressure of O2 in arterial blood to the fraction of O2 in the inspired air rising into the normal range where they remained through the 20-h period of study. The studies indicate that pulmonary function in two models of severe meconium injury respond rapidly to BAL with dilute KL4-Surfactant.

Early discharge of premature infants. A critical analysis.

Although significant advances in the medical management of acutely ill preterm infants have resulted in unprecedented rates of survival, issues surrounding the convalescent care, discharge preparation, and readiness of parents or other caregivers have been less well studied and represent the art of medicine. Recent consensus statements provide a degree of content validity; however, important areas of scientific inquiry remain. Much is left to understand about the pathophysiology, management, and outcomes of apnea, bradycardia, and oxygen desaturation episodes continuing at term. Why do the most immature infants have a delay in the maturation of respiratory control? Do breathing studies really provide information that predicts subsequent respiratory control abnormalities? If methylxanthines are used at discharge, what criteria should be adhered to regarding their discontinuation? How is nutrition best provided while transitioning to home? In infants whose mothers desire exclusive breast-feeding, should gavage feeds be used to supplement in order to avoid bottle-feedings? How long should breast milk be fortified, and when should supplemented artificial milks be used and for what period of time postdischarge should these more expensive special-discharge artificial milks be used? What other supplements, such as inositol, vitamins, or antioxidants, should be provided in order to achieve optimal growth and development? Technology-dependent infants pose even greater complexities. Some infants and families adapt to extensive use of technology in the home. In other situations, basic infant care is difficult to achieve. What are the essential components for successful early discharge, and how can the studies involving selected families be made universal? How can NICUs better prepare fathers and mothers for premature parenthood? To what extent are we overwhelming families with additional responsibilities and expectations that may compromise their competency in basic parenting? Furthermore, the degree of provider variation in evaluating and providing for discharge planning is now being more carefully studied. In some circumstances, integrated teams in the NICU have facilitated the discharge process saving days of hospitalization, whereas in others adherence to discharge planning guidelines has lengthened the stay in the NICU and resulted in higher costs. What is the ideal system for achieving coordination of care without co-opting parental choices in assuming more care responsibility than is comfortable? In the design of tertiary care facilities, more attention to space for rooming-in experiences needs to receive greater priority. Furthermore, because of intensity of care, adverse environmental stimuli, and for issues of better resource utilization, should not most previously ill infants be discharged from level II or intermediate care centers? Finally, issues of increasing decision-making responsibility placed on parents (with the reassurance and guiding hand of dedicated physicians and nurses focused on individual infants) must never be made subservient to the economic whims of insurers to decrease costs without understanding the value of the entirety of the care process for critical illness, through convalescence, to it is hoped a supportive and nurturing environment in the home. Our patients deserve no less. The questions posed present a sample of issues yet to be scientifically addressed. These and many other questions need to be answered before we fully understand the optimal process of discharge for the preterm infant.

Inhibitory effects of oxyradicals on surfactant function: utilizing in vitro Fenton reaction.

The inhibitory effects of reactive oxygen species (ROS) on the surface tension-lowering abilities of three surfactants were compared: natural lung surfactant (NLS), KL4 surfactant containing synthetic peptide resembling the hydrophobic/hydrophilic domains of SP-B in an aqueous dispersion of phospholipids, and Survanta (SUR) containing SP-B and SP-C. The inhibitory concentrations of Fenton reactants (i.e. 0.65 mM FeCl2, 0.65 mM EDTA, 30 mM H2O2), deduced from dose-response plots of FeCl2 on minimum surface tension (MST) of SUR, were used to assess the Fenton effect on biophysical properties of various surfactants. Neither H2O2 (30 mM) nor FeCl2 with EDTA (both 0.65 mM) alone affected surfactant function, but when mixed together significantly increased (p < 0.01) the MST of SUR compared with KL4 (p < 0.05) in a FeCl2 concentration-dependent manner. This effect on NLS was not significant (p = 0.05) at similar phospholipid concentrations. Also, the range of increases in surface adsorption in mN/m at equilibrium surface tension (EST) was 27-40 for SUR, 36-44 for KL4, and 24-25 for NLS. We speculate that the presence of SP-A and the catalase content in NLS may have protective effects on inactivation of NLS by ROS. We conclude that the in vitro Fenton effect could be a valuable test system for comparing the inactivation range of surfactants by oxyradicals.

A review of guidelines for the discharge of premature infants: opportunities for improving cost effectiveness.

Although significant advances in the medical management of acutely ill preterm infants has resulted in unprecedented rates of survival, issues surrounding the convalescent care, discharge preparation, and readiness of parents or other caregivers has been less well studied and represents the art of medicine. We have summarized various guidelines for early discharge of the premature infant and provide our own recommendations for physiologic stability, social requirements, teaching needs of caregivers, and the coordination of community resources. Technology-dependent infants pose even greater complexities. Some infants and families adapt to extensive use of technology in the home. In other situations, basic infant care is difficult to achieve. What are the essential components for successful early discharge, and how can the studies involving selecting families be made universal? How can NICUs better prepare fathers and mothers for premature parenthood? To what extent are we overwhelming families with additional responsibilities and expectations that may compromise their competency in basic parenting? Furthermore, the degree of provider variation in evaluating and providing for discharge planning is now being more carefully studied. In some circumstances, integrated teams in the NICU have facilitated the discharge process, saving days of hospitalization, whereas in other circumstances, adherence to discharge planning guidelines have lengthened the stay in the NICU and resulted in higher costs. Failure to back transport infants to community NICUs has contributed to deregionalization efforts in some regions and increased cost of care. Efforts to establish regional referral networks with common guidelines and developmentally focused care should lead to a reduction in NICU costs and charges.

Recombinant human superoxide dismutase reduces lung injury caused by inhaled nitric oxide and hyperoxia.

We previously demonstrated that 48 h of 100 ppm inhaled nitric oxide (NO) and 90% O2 causes surfactant dysfunction and pulmonary inflammation in mechanically ventilated newborn piglets. Because peroxynitrite (the product of NO and superoxide) is thought to play a major role in the injury process, recombinant human superoxide dismutase (rhSOD, a scavenger of superoxide) might minimize this insult. Four groups of newborn piglets (1-3 days of age) were ventilated with 100 ppm NO and 90% O2 for 48 h. Piglets received no drug, 5 mg/kg rhSOD intratracheally at time 0, 5 mg/kg rhSOD intratracheally at 0 and 24 h, or 10 mg/kg rhSOD by nebulization at time 0. At 48 h, bronchoalveolar lavage (BAL) was performed, and lung tissue was analyzed for markers of inflammation, oxidative injury, acute lung injury, and surfactant function. There were significant differences between rhSOD-treated piglets and untreated controls with respect to BAL neutrophil chemotactic activity, cell counts, and protein concentration as well as lung tissue malondialdehyde concentrations. Minimum surface tension of BAL surfactant from all groups studied was increased, with no differences found among groups. These data suggest that rhSOD, at the doses used, mitigated the inflammatory changes, oxidative damage, and acute lung injury from exposure to 100 ppm NO and 90% O2 but did not appear to improve surfactant function. This has important clinical implications for infants treated with hyperoxia and NO for neonatal lung disorders.

High endothelin-1 in the airways of preterm infants is associated with less severe respiratory distress during the early postnatal period.

OBJECTIVE: To study the relationship between endothelin-1 (ET-1) in the airways and respiratory distress in preterm infants. METHODS: ET-1 was determined in 60 tracheal aspirates from 11 preterm intubated infants (gestational age 28.0 +/- 2.5 weeks) during the first week of life. RESULTS: The concentration of ET-1 of the aspirates was 6 to 2760 pg/mL (median 293 pg/mL). Negative correlations existed between mean log ET-1 and mean airway pressure (R2 = .812) and fraction of inspired oxygen (R2 = .591), whereas a positive correlation was found between the arteriolar/alveolar oxygenation ratio within 3 hours of birth and mean log ET-1 on the first day (R2 = .555). CONCLUSION: The association of high ET-1 in the airways with less severe respiratory distress in the early postnatal period may be attributable to effects of ET-1 on surfactant secretion or development of airway epithelium.

Characterization of surfactant subtypes of beractant and a synthetic peptide containing surfactant KL4 following surface area cycling and addition of fibrinogen.

Surfactant is not a homogeneous material and can be separated into subtypes. Subtype conversion is clinically important because it is thought to occur naturally and because surface activity varies depending on the subtype. Fibrinogen, a naturally occurring serum protein, is known to affect this conversion. In this study we studied two surfactants, beractant and KL4, to examine their subtype characteristics. Surface area cycling, an in vitro method, was used in conjunction with sucrose gradient ultracentrifugation to separate subtypes in both surfactants. Activity, expressed as minimum surface tension of these subtypes, was measured using a pulsating bubble surfactometer. The effect of fibrinogen on subtype conversion and subsequent change in activity was elucidated. Our results indicate that following surface area cycling, beractant and KL4 have different subtypes and different responses to fibrinogen. Cycling of beractant resulted in two bands, representing a heavy and a light subtype. In the presence of fibrinogen, cycling resulted in two separate heavy subtypes. Cycling of KL4 surfactant also yielded light and heavy subtypes. However, in the presence of fibrinogen, cycling of KL4 resulted in ultraheavy subtypes. These ultraheavy subtypes retained minimum surface tension comparable to that of native KL4 surfactant. We conclude that these two surfactant preparations have different subtype conversions when subjected to surface area cycling and in the presence of fibrinogen. These conversions result in different activities toward lowering surface tension. We speculate that endogenous fibrinogen will also affect these two surfactants differently in vivo and thus affect their clinical effectiveness.

Clinical practice guidelines in pediatric and newborn medicine: implications for their use in practice.

Clinical practice guidelines are becoming pervasive in pediatrics and newborn medicine. They have spanned a wide range of primary care practice parameters from treating otitis media with effusion, to performing complex surgery for congenital heart disease, and management of respiratory distress syndrome and coordinating discharge from the neonatal intensive care unit. Administrators believe that using clinical practice parameters reduces health care costs, improves quality of care, and limits malpractice liability. Practice parameters and guidelines have grown in use because powerful interests-third-party payers, insurers, and health maintenance organizations, as well as hospital administrators bent on reducing variable costs of care and contracting for capitated care-champion their development, implementation, and monitoring. Economic credentialing of physicians with excessive variances without risk-adjusting for other than average patients is problematic and remains unchecked partly because of the fundamental characteristics of the evolving health care industry in which costs are more easily measured than quality. For highly autonomus physicians this standardization of medical decision making may represent a difficult transition into corporate practice by realigning traditional values of the doctor-patient relationship. However, because guidelines are almost certainly here to stay, pediatricians and neonatologists need to think critically about how their content and method of implementation, monitoring, and modification may influence medical teaching and decision making in the future. If guidelines are introduced primarily as a cost savings or containment tool that ignores the impact on the quality of care and restricts necessary care for infants and children, especially those with chronic illness or who are developmentally at risk, then neonatologists and pediatricians must be quick and determined to challenge the potentially damaging use of practice parameters or guidelines. Furthermore, there are many medicolegal implications of guideline implementation that may not favor physicians and leave to hospitals, insurers, and ultimately the courts decisions regarding evidence-based practice. In this review article, we pay special attention to the guidelines developed in newborn medicine. We discuss why and how guidelines are developed and critically evaluate the available evidence describing potential benefits and drawbacks of guidelines in general. There are legal implications to the implementation of guidelines, and guidelines may increase provider susceptibility to malpractice allegations. Neonatologists and pediatricians should critically analyze the following questions when guidelines are being developed: Are clinical practice parameters the most effective means to reduce the costs of health care, or improve the quality of health care services while reducing the need for and protecting physicians from malpractice suits? Or do clinical practice guidelines more closely resemble an audit system developed by health care organizations, insurers, and others including government-sponsored health care to appease powerful interests-with limited evidence for promise and perhaps potential negative cost, quality, and malpractice liability implications? In pediatric and newborn medicine there is limited evidence that guidelines have achieved the desired goals and further analysis of their process of care and the costs of implementation is warranted.