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The Helping Babies Breathe Global Development Alliance (GDA) was a public-private partnership created simultaneously with the launch of the educational program Helping Babies Breathe to accelerate dissemination and implementation of neonatal resuscitation in low- and middle-income countries with the goal of reducing the global burden of neonatal mortality and morbidity related to birth asphyxia. Representatives from 6 organizations in the GDA highlight the recognized needs that motivated their participation and how they built on one another's strengths in resuscitation science and education, advocacy, frontline implementation, health system strengthening, and implementation research to achieve common goals. Contributions of time, talent, and financial resources from the community, government, and private corporations and foundations powered an initiative that transformed the landscape for neonatal resuscitation in low- and middle-income countries. The organizations describe the power of partnerships, the challenges they faced, and how each organization was shaped by the collaboration. Although great progress was achieved, lessons learned through the GDA and additional efforts must still be applied to the remaining challenges of prevention, widespread implementation, improvement in the quality of care, and sustainable integration of neonatal resuscitation and essential newborn care into the fabric of health care systems., Competing Interests: POTENTIAL CONFLICT OF INTEREST: This article reflects the views of the authors and does not necessarily reflect the views of the US Agency for International Development, the National Institutes of Health, or the US Government., (Copyright © 2020 by the American Academy of Pediatrics.)

Helping Babies Breathe (HBB) changed global education in neonatal resuscitation. Although rooted in the technical and educational expertise underpinning the American Academy of Pediatrics' Neonatal Resuscitation Program, a series of global collaborations and pivotal encounters shaped the program differently. An innovative neonatal simulator, graphic learning materials, and content tailored to address the major causes of neonatal death in low- and middle-income countries empowered providers to take action to help infants in their facilities. Strategic dissemination and implementation through a Global Development Alliance spread the program rapidly, but perhaps the greatest factor in its success was the enthusiasm of participants who experienced the power of being able to improve the outcome of babies. Collaboration continued with frontline users, implementing organizations, researchers, and global health leaders to improve the effectiveness of the program. The second edition of HBB not only incorporated new science but also the accumulated understanding of how to help providers retain and build skills and use quality improvement techniques. Although the implementation of HBB has resulted in significant decreases in fresh stillbirth and early neonatal mortality, the goal of having a skilled and equipped provider at every birth remains to be achieved. Continued collaboration and the leadership of empowered health care providers within their own countries will bring the world closer to this goal., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors are members of the American Academy of Pediatrics Helping Babies Survive Planning Group and members of the editorial committee for the first and second editions of Helping Babies Breathe., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: A comprehensive, well-trained pediatric workforce is needed to ensure high-quality child health interventions around the globe. Further understanding of pediatric workforce training capacity would assist planning at the global and country level. The purpose of this study was to better understand the availability and process of training programs for pediatricians and pediatric subspecialists worldwide, as well as in-country presence of subspecialists., Methods: A survey was developed and distributed by e-mail to national pediatric leaders across the globe. The survey asked about the number of pediatric training programs, duration and logistics of training, and whether practicing pediatric subspecialists and subspecialty training programs were available in their country., Results: We received responses from 121 of the 166 countries contacted (73%). Of these, 108 countries reported the presence of one or more general pediatric postgraduate training programs, ranging from 1 to 500 programs per country. The number of training programs did not vary significantly by gross domestic product but did vary by region, with the fewest in Africa (P < .001). Most countries identified national guidelines for training (82% of countries) and accreditation (84% of countries). Availability of pediatric subspecialists varied significantly by income and region, from no subspecialties available in 4 countries to all 26 queried subspecialties available in 17 countries. Neonatology was most common, available in 88% of countries. Subspecialty training programs were less available overall, significantly correlating with country income., Conclusion: Education for general pediatrics and pediatric subspecialties is quite limited in many of the countries surveyed, particularly in Africa. The creation of additional educational capacity is a critical issue challenging the adequate provision of pediatrics and pediatric subspecialty services., (Copyright © 2019 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

The tracheal aspirate (TA) culture is commonly ordered in the NICU, but it has low sensitivity and specificity, limited by contamination. Interpretation of a TA culture out of context can lead to antibiotic overuse, which should be avoided. Clinicians should practice caution in the diagnosis of congenital pneumonia and use newer, published approaches to the diagnosis of ventilator-associated pneumonia in neonates. A subset of neonatal patients with risk factors of maternal fever or chorioamnionitis requiring intubation may benefit from TA culture performed within 12 hours after birth, to help identify an organism when blood culture may be negative, and tailor antimicrobial therapies. The more invasive, but more sensitive, technique of nonbronchoscopic bronchoalveolar lavage should be considered in older infants when bacterial isolation from the lower respiratory tract is necessary, because TA culture cannot distinguish between colonization and infection in that population., (Copyright © 2019 by the American Academy of Pediatrics.)

Objective: Our primary objective was to examine the global paediatric workforce and to better understand geographic differences in the number of paediatricians globally. Secondary objectives were to describe paediatric workforce expectations, who provides children with preventative care and when children transition out of paediatric care., Design: Survey of identified paediatric leaders in each country., Setting: Paediatric association leaders worldwide., Main Outcome Measures: Paediatrician numbers, provision of primary care for children, age of transition to adult care., Results: Responses were obtained from 121 countries (73% of countries approached). The number of paediatricians per 100 000 children ranged from a median of 0.5 (IQR 0.3-1.4) in low-income countries to 72 (IQR 4-118) in high-income countries. Africa and South-East Asia reported the lowest paediatrician density (median of 0.8 paediatricians per 100 000 children, IQR 0.4-2.6 and median of 4, IQR 3-9, respectively) and fewest paediatricians entering the workforce. 82% of countries reported transition to adult care by age 18% and 39% by age 15. Most countries (91%) but only 64% of low-income countries reported provision of paediatric preventative care (p<0.001, Cochran-Armitage trend test). Systems of primary care provision varied widely. A majority of countries (63%) anticipated increases in their paediatric workforce in the next decade., Conclusions: Paediatrician density mirrors known inequities in health provider distribution. Fewer paediatricians are entering the workforce in areas with already low paediatrician density, which may exacerbate disparities in child health outcomes. In some regions, children transition to adult care during adolescence, with implications for healthcare training and delivery. Paediatrician roles are heterogeneous worldwide, and country-specific strategies should be used to address inequity in child health provision., Competing Interests: Competing interests: None declared.

Background: Helping Babies Breathe (HBB), a skills-based program in neonatal resuscitation for birth attendants in resource-limited settings, has been implemented in over 80 countries since 2010. Implementation studies of HBB incorporating low-dose high-frequency practice and quality improvement show substantial reductions in fresh stillbirth and first-day neonatal mortality. Revision of the program aimed to further augment provider and facilitator skills and address gaps in implementation with the goal of improving neonatal survival., Methods: The Utstein Formula for Survival-Medical Science X Educational Efficiency X Local Implementation = Survival-provided a framework for the revisions. The 2015 Neonatal Resuscitation Consensus on Science and Treatment Recommendations by the International Liaison Committee on Resuscitation informed scientific updates, which were harmonized with the 2012 World Health Organization Basic Newborn Resuscitation Guidelines. Published literature and program reports, consensus guidelines on reprocessing equipment, systematic collection of suggestions from frontline users, and responses to a semistructured online questionnaire informed educational/implementation revisions. Links to maternal care were added. Draft materials underwent Delphi review and field testing in India and Sierra Leone. An Utstein-style meeting of stakeholders identified key actions for successful implementation., Results: Scientific revisions included expectant management of infants with meconium-stained amniotic fluid, limitation of suctioning, and initiating and continuing effective ventilation until spontaneous respirations. Frontline users (N=102) suggested augmented simulation methods to build confidence and competence and additional guidance for facilitators on implementation. Users identified a need for sufficient practice during the workshop, systematized ongoing practice, and enough simulators for participants. Field trials refined approaches to self-reflection, feedback and debriefing, and quality improvement. Utstein meeting stakeholders validated the importance of quality improvement and use of data to improve outcomes., Conclusions: The second edition of HBB provides a newer paradigm of learning for providers that incorporates workshop practice, self-reflection, and feedback and debriefing to reinforce learning as well as the promotion of mentorship and development of facilitators, systems for low-dose high-frequency practice in facilities, and quality improvement related to neonatal resuscitation., (© Kamath-Rayne et al.)

Background: Essential Care for Every Baby (ECEB) is an evidence-based educational program designed to increase cognitive knowledge and develop skills of health care professionals in essential newborn care in low-resource areas. The course focuses on the immediate care of the newborn after birth and during the first day or until discharge from the health facility. This study assessed the overall design of the course; the ability of facilitators to teach the course; and the knowledge and skills acquired by the learners., Methods: Testing occurred at 2 global sites. Data from a facilitator evaluation survey, a learner satisfaction survey, a multiple choice question (MCQ) examination, performance on two objective structured clinical evaluations (OSCE), and pre- and post-course confidence assessments were analyzed using descriptive statistics. Pre-post course differences were examined. Comments on the evaluation form and post-course group discussions were analyzed to identify potential program improvements., Results: Using ECEB course material, master trainers taught 12 facilitators in India and 11 in Kenya who subsequently taught 62 providers of newborn care in India and 64 in Kenya. Facilitators and learners were satisfied with their ability to teach and learn from the program. Confidence (3.5 to 5) and MCQ scores (India: pre 19.4, post 24.8; Kenya: pre 20.8, post 25.0) improved (p < 0.001). Most participants demonstrated satisfactory skills on the OSCEs. Qualitative data suggested the course was effective, but also identified areas for course improvement. These included additional time for hands-on practice, including practice in a clinical setting, the addition of video learning aids and the adaptation of content to conform to locally recommended practices., Conclusion: ECEB program was highly acceptable, demonstrated improved confidence, improved knowledge and developed skills. ECEB may improve newborn care in low resource settings if it is part of an overall implementation plan that addresses local needs and serves to further strengthen health systems.

Objective: This study evaluated the effectiveness of Helping Babies Breathe (HBB) newborn care and resuscitation training for birth attendants in reducing stillbirth (SB), and predischarge and neonatal mortality (NMR). India contributes to a large proportion of the worlds annual 3.1 million neonatal deaths and 2.6 million SBs., Methods: This prospective study included 4187 births at >28 weeks' gestation before and 5411 births after HBB training in Karnataka. A total of 599 birth attendants from rural primary health centers and district and urban hospitals received HBB training developed by the American Academy of Pediatrics, using a train-the-trainer cascade. Pre-post written trainee knowledge, posttraining provider performance and skills, SB, predischarge mortality, and NMR before and after HBB training were assessed by using χ(2) and t-tests for categorical and continuous variables, respectively. Backward stepwise logistic regression analysis adjusted for potential confounding., Results: Provider knowledge and performance systematically improved with HBB training. HBB training reduced resuscitation but increased assisted bag and mask ventilation incidence. SB declined from 3.0% to 2.3% (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59-0.98) and fresh SB from 1.7% to 0.9% (OR 0.54, 95% CI 0.37-0.78) after HBB training. Predischarge mortality was 0.1% in both periods. NMR was 1.8% before and 1.9% after HBB training (OR 1.09, 95% CI 0.80-1.47, P = .59) but unknown status at 28 days was 2% greater after HBB training (P = .007)., Conclusions: HBB training reduced SB without increasing NMR, indicating that resuscitated infants survived the neonatal period. Monitoring and community-based assessment are recommended.

There has been increasing awareness over recent years of the persisting burden of worldwide maternal, newborn, and child mortality. The majority of maternal deaths occur during labor, delivery, and the immediate postpartum period, with obstetric hemorrhage as the primary medical cause of death. Other causes of maternal mortality include hypertensive diseases, sepsis/infections, obstructed labor, and abortion-related complications. Recent estimates indicate that in 2009 an estimated 3.3 million babies died in the first month of life and that overall, 7.3 million children under 5 die each year. Recent data also suggest that sufficient evidence- and consensus-based interventions exist to address reproductive, maternal, newborn, and child health globally, and if implemented at scale, these have the potential to reduce morbidity and mortality. There is an urgent need to put elements in place to promote integrated interventions among healthcare professionals and their associations. What is needed is the political will and partnerships to implement evidence-based interventions at scale., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Of 136 million babies born annually, around 10 million require assistance to breathe. Each year 814,000 neonatal deaths result from intrapartum-related events in term babies (previously "birth asphyxia") and 1.03 million from complications of prematurity. No systematic assessment of mortality reduction from tactile stimulation or resuscitation has been published., Objective: To estimate the mortality effect of immediate newborn assessment and stimulation, and basic resuscitation on neonatal deaths due to term intrapartum-related events or preterm birth, for facility and home births., Methods: We conducted systematic reviews for studies reporting relevant mortality or morbidity outcomes. Evidence was assessed using GRADE criteria adapted to provide a systematic approach to mortality effect estimates for the Lives Saved Tool (LiST). Meta-analysis was performed if appropriate. For interventions with low quality evidence but strong recommendation for implementation, a Delphi panel was convened to estimate effect size., Results: We identified 24 studies of neonatal resuscitation reporting mortality outcomes (20 observational, 2 quasi-experimental, 2 cluster randomized controlled trials), but none of immediate newborn assessment and stimulation alone. A meta-analysis of three facility-based studies examined the effect of resuscitation training on intrapartum-related neonatal deaths (RR= 0.70, 95%CI 0.59-0.84); this estimate was used for the effect of facility-based basic neonatal resuscitation (additional to stimulation). The evidence for preterm mortality effect was low quality and thus expert opinion was sought. In community-based studies, resuscitation training was part of packages with multiple concurrent interventions, and/or studies did not distinguish term intrapartum-related from preterm deaths, hence no meta-analysis was conducted. Our Delphi panel of 18 experts estimated that immediate newborn assessment and stimulation would reduce both intrapartum-related and preterm deaths by 10%, facility-based resuscitation would prevent a further 10% of preterm deaths, and community-based resuscitation would prevent further 20% of intrapartum-related and 5% of preterm deaths., Conclusion: Neonatal resuscitation training in facilities reduces term intrapartum-related deaths by 30%. Yet, coverage of this intervention remains low in countries where most neonatal deaths occur and is a missed opportunity to save lives. Expert opinion supports smaller effects of neonatal resuscitation on preterm mortality in facilities and of basic resuscitation and newborn assessment and stimulation at community level. Further evaluation is required for impact, cost and implementation strategies in various contexts., Funding: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to the Saving Newborn Lives program of Save the Children, through Save the Children US.

Background: Each year approximately 10 million babies do not breathe immediately at birth, of which about 6 million require basic neonatal resuscitation. The major burden is in low-income settings, where health system capacity to provide neonatal resuscitation is inadequate., Objective: To systematically review the evidence for neonatal resuscitation content, training and competency, equipment and supplies, cost, and key program considerations, specifically for resource-constrained settings., Results: Evidence from several observational studies shows that facility-based basic neonatal resuscitation may avert 30% of intrapartum-related neonatal deaths. Very few babies require advanced resuscitation (endotracheal intubation and drugs) and these newborns may not survive without ongoing ventilation; hence, advanced neonatal resuscitation is not a priority in settings without neonatal intensive care. Of the 60 million nonfacility births, most do not have access to resuscitation. Several trials have shown that a range of community health workers can perform neonatal resuscitation with an estimated effect of a 20% reduction in intrapartum-related neonatal deaths, based on expert opinion. Case studies illustrate key considerations for scale up., Conclusion: Basic resuscitation would substantially reduce intrapartum-related neonatal deaths. Where births occur in facilities, it is a priority to ensure that all birth attendants are competent in resuscitation. Strategies to address the gap for home births are urgently required. More data are required to determine the impact of neonatal resuscitation, particularly on long-term outcomes in low-income settings.

Objective: Determine the contemporary incidence of pathogenic tracheal aspirate (TA) cultures when obtained within 12 h of birth, and to associate TA culture results with specific clinical conditions that increase the risk of infection., Study Design: A retrospective study over a 6-month period of admissions to a single outborn neonatal intensive care unit when a TA sample was collected within 12 h of birth (n=139)., Result: In total, 9 of 139 (6.5%) TA cultures were positive for pathogenic bacterial growth. Maternal fever (relative risk (RR)=7.7, P<0.04) and clinical chorioamnionitis (RR=6.4, P<0.02) were significantly associated with pathogenic TA culture results. Infants with a pathogenic TA culture had lower white blood cell counts (7,500 vs 13,900 mm(-3), P<0.05) when compared with infants with a negative culture. In eight of the nine patients with pathogenic cultures, either the mother or the infant received antibiotics before TA sample collection., Conclusion: Early TA culture is a helpful tool in diagnosing pneumonia, especially in certain clinical scenarios, including maternal fever, clinical chorioamnionitis and leukopenia. Administration of antibiotics before sample collection does not seem to preclude culture growth.

Despite an era of marked success with universal screening, Group B Streptococcus (GBS) continues to be an important cause of early-onset sepsis, and thus remains a significant public health issue. Improved eradication of GBS colonization and disease may involve universal screening in conjunction with rapid diagnostic technologies or other novel approaches. Given the complications and potential limitations associated with maternal intrapartum prophylaxis, however, vaccines may be the most effective means of preventing neonatal GBS disease. The global utility of conjugated GBS vaccines may be hampered by the variability of serotypes in diverse populations and geographic locations. Modern technologies, such as those involving proteomics and genomic sequencing, are likely to hasten the development of a universal vaccine against GBS.

Thoracostomy tubes are commonly required to treat pnuemothoraces in premature infants. Evidence of impalement of the lungs by tube thoracostomy has been seen in autopsy studies. In neonates, there has been described a surprisingly high incidence of lung perforation. The premature lung is thought to be at greater risk for this complication owing to the pliant, thin chest wall, the proximity of vital tissues and the fragility of the lung tissue itself. The modified Fuhrman catheter, or polyurethane pigtail catheter, has been developed for the drainage of pneumothorax in premature infants. In a study of complications of the placement of pigtail catheters, no instance of penetration of the lungs was reported. We report the case of a premature infant with pigtail catheter placement that, at autopsy, was found to have impaled the lung and discuss the incidence of lung injury associated with invasive management of pnuemothoraces.

Objective: Describe the incidence of catheter-related blood stream infection (CRBSI), following removal of peripherally inserted central venous catheters (PICC) in preterm infants., Study Design: A retrospective cohort study of infants <29 weeks gestational age with a PICC revealed 101 PICCs placed (2159 PICC days). Patients were hospitalized in a level III Neonatal Intensive Care Unit (NICU) between January 2002 and December 2003. Chi(2) analysis was performed., Results: One infection was detected after the removal of a PICC (1 per 202 days). Ten infants had a CRBSI attributed to a PICC (1 per 216 PICC days). CRBSI during indwelling PICC was associated with increased risk for sepsis evaluation after PICC removal (P<0.05)., Conclusions: The incidence of CRBSI in the 48 h following PICC removal was not different than the incidence of CRBSI while a PICC was in-dwelling. There was no evidence from this study to support antibacterial prophylaxis before PICC removal.

Objective: The purpose of this study was to identify the risk of respiratory disease for developing inguinal hernia (IH)., Study Design: A retrospective case-control study reviewed medical records of 100 outborn infant males, gestational age (GA) less than 35 weeks, admitted between July 1999 and November 2002 to our level III neonatal intensive care unit. Prospectively selected variables were reviewed from 50 cases of IH and 50 controls., Results: Premature infants expressing IH were more likely to have had lower GA and birth weight, longer duration of mechanical ventilation, use of high-frequency oscillating ventilator (HFOV), higher peak mean airway pressures during mechanical ventilation, and postnatal dexamethasone exposure. Adjusted results showed dexamethasone, HFOV in infants less than 28 weeks GA, and length of mechanical ventilation remained significant. Multivariate analysis revealed dexamethasone as an independent risk for the expression of IH., Conclusions: The association of IH expression with mechanical support and dexamethasone administration was substantial. These data provide further caution when using either HFOV or dexamethasone in preterm infants with respiratory insufficiency.

Objective: To evaluate the efficacy of inhaled albuterol for treatment of hyperkalemia in premature neonates by conducting a prospective, randomized placebo-controlled and double-blinded clinical trial., Study Design: Neonates <2000 g receiving mechanical ventilation with central serum potassium > or =6.0 mmol/L (6.0 mEq/L), were randomly assigned to treatment or placebo groups. Albuterol (400 microg) or saline was given by nebulization. The dose was repeated every 2 hours until the potassium level fell below 5 mmol/L (maximum 12 doses) or there were signs of toxicity., Results: Nineteen patients completed the study (8 in the albuterol and 11 in the saline group). Serum potassium levels declined rapidly in the first 4 hours in the albuterol group, from 7.06 +/- 0.23 mmol/L to 6.34 +/- 0.24 mmol/L (P =.003) versus no significant change in the saline group (6.88 +/- 0.18 mmol/L to 6.85 +/- 0.24 mmol/L; P =.87). At 8 hours, the fall continued to be greater in the albuterol group versus the saline group (5.93 +/- 0.3 mmol/L and 6.35 +/- 0.22 mmol/L, respectively; P =.04)., Conclusion: Albuterol inhalation may be useful in rapidly lowering serum potassium levels in premature neonates.

Drawing on responses to a small-scale sensitizing sociological probe of 'technological stratification' in academic sociology, this article considers the role of academic staff delegated to oversee the distribution of information and communications technology resources within their departments between the years 1987-1996. From their recollections as local 'gatekeepers' of the new knowledge technologies, these 'subalterns of Technopoly' perceived themselves as relatively powerless 'techno-power brokers' unable to make a significant difference to the 'technological stratification' they encountered in their working environments in that period.

Objective: To examine the hypothesis that fat intolerance in newborns who receive intravenous lipid is related to both infection and liver dysfunction., Design: Prospective survey., Setting: Tertiary intensive care nursery., Patients: All newborns who were admitted to the neonatal intensive care unit during a 20-month period and received parenteral lipid for 2 or more weeks were eligible for the study. Of 279 newborns who received parenteral nutrition, 162 met eligibility criteria and form the basis of this report., Interventions: None., Main Outcome Measure: Fat intolerance as defined by a serum triglyceride level of 1.69 mmol/L or greater (> or = 150 mg/dL)., Results: Triglyceride levels were similar in infected and noninfected patients. Newborns with hypertriglyceridemia were more likely to have liver dysfunction (P < .001) or growth retardation (P < .01), but not infections. Hypertriglyceridemia was approximately twice as likely (P < .05) in newborns with either growth retardation or liver dysfunction., Conclusions: Liver dysfunction and fetal growth retardation were associated with lipid intolerance in newborns who received intravenous fat. Infection does not appear to be independently associated with hypertriglyceridemia. In the absence of liver dysfunction or growth retardation, there is no a priori reason to limit intravenous lipid use in the presence of infection. Close monitoring of triglyceride levels with adjustments in lipid dose is warranted, especially in small, sick newborns who are at highest risk for hypertriglyceridemia.

Recently, we encountered four neonates who developed severe reversible partial lower airway obstruction. This communication describes their clinical course and the pathogenesis and treatment of acute bronchospasm resembling status asthmaticus and leading to life-threatening respiratory acidosis.

Periodic breathing (PB) during sleep was investigated in two groups of full-term infants with histories of apnea that were terminated by resuscitation. One group of infants had been reported to be asleep whereas the other group had been reported to be awake when apnea was noted. Electrophysiologic sleep recordings were made after the apneic incident. The infants with histories of prolonged apnea while asleep exhibited more PB during recorded sleep than infants with histories of apnea while awake. Increased PB during sleep in full-term infants, therefore, may not be associated with all prolonged apneic episodes in infants but may be specifically associated with those episodes that occur during sleep.

Desquamative interstitial pneumonitis (DIP) is rare in children. Its cause is unknown. In general, it is of sporadic occurrence. We report 4 infants: 2 sibs in each of 2 separate families, who had DIP. All 4 infants died despite intensive care and immunosuppressive therapy. Our cases, plus one other similar kindred in the literature, confirm the occurrence of familial DIP in infancy. Further, our experience suggests that DIP in these familial cases carries a worse prognosis than that reported in sporadic cases.

Many major medical centers are presently utilizing a shortened method (Keller) for determining serum aspirin levels which does not remove interfering compounds. This report documents that the presence of even 1 mg of bilirubin/dl of serum is sufficient to cause a falsely high aspirin level. It is suggested that any method for determining serum bilirubin which does not remove interfering substances constitutes a danger to many groups of patients and should be discontinued.

Twenty vancomycin pharmacokinetic studies were performed on 17 small infants who were receiving the antibiotic for treatment of documented infections. Fourteen patients were less than or equal to 41 weeks' postconception. In this group there was no statistical difference in mean elimination rate, volume of distribution, or clearance between neonates and infants 4 to 8 weeks of age. However, they had significantly lower clearance and prolonged mean beta-half-life than infants who were 3 to 6 months old (greater than 43 weeks' postconception). Vancomycin clearance was directly related to postconceptional age by linear regression analysis. beta-Half-life was influenced by the weight of the patient, volume of distribution, and gestational age. In view of the interpatient variability observed in the prematurely born infants, pharmacokinetic studies should be performed to determine the appropriate dose and intervals in vancomycin therapy.

Nutritional benefits and feeding-related complications were prospectively compared in 53 preterm very-low-birth-weight infants receiving isoenergetic feeding by either the continuous nasogastric (n = 30) or intermittent nasogastric (n = 23) route. Stepwise regression techniques were used to develop models relating feeding-associated factors. Feeding method significantly affected weight gain in infants 1000 to 1249 g birth weight with continuous nasogastric feeding associated with an additional weight gain of 3.6 to 6.1 g/kg/d. No effects of feeding method on changes in occipitofrontal circumference, triceps skin-fold thickness, bilirubin values, or total protein values were demonstrable. There were few major differences between feeding groups on measures of feeding complications. Continuous nasogastric feeding was fairly well tolerated and resulted in improved weight gain when compared with intermittent nasogastric feeding in preterm infants 1000 to 1249 g birth weight.

The energy expenditure (VO2) was measured during the first 36 hours of life in 10 infants of diabetic mothers (IDM) and in 16 normal newborns (NB). The mean VO2 was 5,72 ml/kg/min +/- 0,4 for the NB and 4,94 ml/kg/min. +/- 0,3 for the IDM. The respiratory quotients were similar for both groups. Blood glucose determination from all IDM were greater than 44 mg%. Although the low VO2 for IDM is unexplained, several hypothesis might be anticipated: either lack of utilization of abundant endogenous glycogen stores or increased metabolism of glucose by the cells.

The temporal relationship between apnea and gastroesophageal reflux was examined in 14 infants with abnormal GER scores and histories of prolonged apnea. Simultaneous polysomnographic and intraesophageal pH recordings were performed for each infant. GER episodes were compared to control segments of the recording (without GER) for frequency and type of apnea. Apnea was equally likely to occur during the control segments as during the GER episodes. Brief obstructive apneic episodes were more common during the onset of GER episodes than the onset of control segments. GER duration appeared prolonged during sleep. GER and apnea were not temporally related in the majority of instances, and may be two manifestations of a more general developmental delay.

57 newborn infants delivered by planned, repeat cesarian section were studied to determine the role of surfactant in transient neonatal respiratory distress. 22.8% of the newborn infants studied had transient tachypnea of the newborn. The mean amniotic fluid lecithin-sphingomyelin ratio (L/S) was 2.8 in normal infants and 2.6 in infants with transient tachypnea. The mean gastric aspirate L/S at the time of delivery was 3.0 in the normal infants and 2.7 in infants with transient tachypnea. There were no statistically significant differences in either amniotic fluid L/S or gastric aspirate L/S. Based on these results we speculate that, despite altered lung mechanics in neonates with transient tachypnea, lung maturity as determined by L/S ratio does not differ from that of normal neonates.

Fifty-two Broviac catheters were inserted in 40 preterm and eight term infants for 1733 days of catheter use. Thirty-six (69%) catheters were associated with complications of infection and/or thrombosis, a complication rate of 1/48 catheter days. The patients who developed complications were of a significantly lower gestational age and had a lower mean birth weight when compared with those who developed no complications. The incidence of catheter-related sepsis was 69% in the very low birth weight infants and only 20% in the infants with birth weights over 1500 g. Eighteen of the 26 catheter-associated infections were treated with antibiotics without catheter removal. Successful resolution of the infections with retention of the catheter occurred in 14 of the 18 episodes. Infections with Staphylococcus aureus constituted three of four treatment failures. Urokinase infusion was successful in causing thrombolysis in eight of the nine cases. Broviac catheters in neonates, and especially in preterm infants under 1500 g, are associated with a high incidence of complications. Our experience indicates that some complications can be selectively managed without sacrificing the venous access.

Of the twenty-three employees at a pharmaceutical plant manufacturing a new product containing papain, twelve had respiratory symptoms of cough, wheezing, dyspnoea, or chest paint. Most were studied with in-depth interviews by a doctor, extensive pulmonary function tests, and immunoserological tests for IgE and precipitating antibodies specific for papain, as well as total IgE antibodies to common natural allergens. There were significant correlates (all P values < 0.05) between the presence of specific IgE antibodies to papain and decreases of FEV1, FEF75--85, TLC, RV, and response to bronchodilators as percentage change from baseline for all spirographic flow rates. Atopic workers developed pulmonary symptoms and antipapain antibodies significantly sooner after papain exposure than did the others. Duration of exposure had no effect on symptomatology, pulmonary function, or immunological response. However, those judged to have the greatest amount of dust exposure per work-day had significantly more pulmonary symptoms (P < 0.005). Papain produced lung diseases by acting as an inhalant allergen rather than a proteolytic enzyme. Papain is a potent sensitizer in humans for the production of respiratory disease. The pulmonary reactions, based on physiological data, seem to involve small airways, alveolar, and interstitial lung tissue in an inflammatory rather than destructive manner, and thus resemble bronchitis and interstitial lung disease rather than pulmonary emphysema or typical bronchial asthma.

An anterior pneumothorax in a supine neonate is difficult to diagnose. A correlation was sought between radiographic signs of an anterior pneumothorax and clinical data to facilitate the radiographic diagnosis. A total of 817 consecutive admissions to two regional nurseries were reviewed, and infants with pneumothoraces were identified. Nineteen percent of these neonates had anterior pneumothoraces with Medial Stripe and Large Hyperlucent Hemithorax signs observed on the chest radiographs. The Medial Stripe sign was not associated with any distinguishing clinical features that would assist the physician in the interpretation of the radiograph. The Large Hyperlucent Hemithorax sign was noted predominantly on the left side in near-term infants who were breathing spontaneously. It was concluded that there are specific clinical variables associated with a Large Hyperlucent Hemithorax sign of an anterior pneumothorax in a supine neonate.

The effect of middle-ear dysfunction and disease on hearing and language development at one year of age was evaluated for 143 high-risk infants. These infants were categorized as normal or abnormal based on otologic history, otoscopic examinations, and on tympanometric examinations. Language was significantly related to gestational age, being delayed by approximately the amount of prematurity. Language scores were therefore adjusted for gestational age. Speech-detection threshold was not related to gestational age, and was used as the measure of hearing. Hearing levels were negatively correlated with adjusted language quotients. Infants with abnormal otologic histories reported were not different from infants with normal histories in either hearing or language development. Infants with bilateral otoscopic abnormalities had significantly higher speech-detection thresholds, but did not differ in language development from those with bilaterally normal otoscopy. Infants who were abnormal bilaterally by tympanometric examination had significantly higher speech-detection thresholds as well as significantly delayed language development. A significant effect on both hearing and language was found among those infants bilaterally abnormal by tympanometry for whom evidence of middle-ear disease was not visualized by otoscopic examination. Implications of these findings are discussed.

The usefulness of the microscopic examination of the placenta, associated membranes, and umbilical cord was tested in a retrospective clinical review. Fifty-nine patients with inflammation were matched by sex, race, and gestation with 59 patients without inflammation. Blind review of the clinical course of these infants revealed five cases of culture-positive septicemia, 28 cases of probable sepsis, 39 cases of possible sepsis, and 46 normal infants. The clinical categorization was significantly correlated with the microscopic appearance of the placenta, membranes, and cord. Triple vessel vasculitis in the umbilical cord vessels and chorionic microabscesses were significantly related to the incidence of proven, probable, and possible clinical sepsis. The microscopic examination of the umbilical cord and placenta provides a useful, but not infallible, tool in the evaluation of sepsis in the newly born infant.