Design and Rationale of Penn Medicine Healthy Heart, a Randomized Trial of Effectiveness of a Centrally Organized Approach to Blood Pressure and Cholesterol Improvement Among Patients at Elevated Risk of Atherosclerotic Cardiovascular Disease.

RATIONALES: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of non-clinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior non-randomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C). PRIMARY HYPOTHESIS: Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention. DESIGN: Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of four modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team. SITES: University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas PRIMARY OUTCOMES: Improvement in systolic blood pressure and LDL-C SECONDARY OUTCOMES: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention. ESTIMATED ENROLLMENT: 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C > 100 despite being on statins and (b) had systolic blood pressure>140 at two recent ambulatory visits. ENROLLMENT DATES: March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist. CURRENT STATUS: Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394.

Association between early postnatal weight loss and death or BPD in small and appropriate for gestational age extremely low-birth-weight infants.

OBJECTIVE: To examine the association between weight loss during the first 10 days of life and the incidence of death or bronchopulmonary dysplasia (BPD) in small for gestational age (SGA) and appropriate for gestational age (AGA) extremely low-birth-weight infants. DESIGN/METHODS: This is a retrospective analysis of a cohort of ELBW (birth weight <1000 g) infants from the NICHD Neonatal Research Network's database. The cohort consisted of 9461 ELBW infants with gestational age of 24-29 weeks, admitted to Network's participating centers during calendar years 1994-2002 and surviving at least 72 h after birth. The cohort was divided into two groups, 1248 SGA (with birth weight below 10th percentile for gestational age) and 8213 AGA (with birth weight between 10th and 90th percentile) infants. We identified infants with or without weight loss during the first 10 days of life, which we termed as 'early postnatal weight loss' (EPWL). Univariate analyses were used to predict whether EPWL was related to the primary outcome, death or BPD, within each birth weight/gestation category (SGA or AGA). BPD and death were also analyzed separately in relation to EPWL. Logistic regression analysis was done to evaluate the risk of death or BPD in SGA and AGA groups, controlling for maternal and neonatal demographic and clinical factors found to be significant by univariate analysis. RESULTS: SGA ELBW infants had a lower prevalence of EPWL as compared with AGA ELBW infants (81.2 vs 93.7%, respectively, P<0.001). In AGA infants, univariate analysis showed that death or BPD rate was lower in the group of infants with EPWL compared with infants without EPWL (53.4 vs 74.3%, respectively, P<0.001). The BPD (47.2 vs 64%, P<0.001) and death (13.8 vs 32.9%, P<0.001) rate were similarly lower in the EPWL group. The risk-adjusted odds ratios (ORs) showed that EPWL was associated with lower rate of death or BPD (OR 0.47, 95% CI: 0.37-0.60). In SGA infants, on univariate analysis, a similar association between EPWL and outcomes was seen as shown in AGA infants: death or BPD (55.9 vs 75.2%, P<0.001), BPD rate (48.3 vs 62.1%, P=0.002) and rate death (19 vs 40.8%, P<0.001) for those with or without EPWL, respectively. Multiple logistic regression showed that as in AGA ELBW infants, EPWL was associated with lower risk for death or BPD (OR 0.60, 95% CI: 0.41-0.89) among SGA infants. CONCLUSIONS: SGA infants experienced less EPWL when compared with their AGA counterparts. EPWL was associated with a lower risk of death or BPD in both ELBW AGA and SGA infants. These data suggest that clinicians who consider the association between EPWL and risk of death or BPD should do so independent of gestation/birth weight status.

Clinical trial of tin mesoporphyrin to prevent neonatal hyperbilirubinemia.

OBJECTIVE: To assess the efficacy of the heme oxygenase inhibitor, tin mesoporphyrin (SnMP), to reduce total bilirubin (TB) levels. STUDY DESIGN: Masked, SnMP (4.5 mg kg(-1)), placebo-controlled, multicenter trial of single intramuscular injection to newborns ⩾35 weeks gestational age whose predischarge screening transcutaneous bilirubin (TcB) was >75th percentile. RESULTS: Two hundred and thirteen newborns (median age 30 h) were randomized to treatment with SnMP (n=87) or 'sham' (n=89). We found that the duration of phototherapy was halved. Within 12 h of SnMP administration, the natural TB trajectory was reversed. At age 3 to 5 days, TB in the SnMP-treated group was +8% but sixfold lower than the 47% increase in the sham-treated group (P<0.001). At age 7 to 10 days, mean TB declined 18% (P<0.001) compared with a 7.1% increase among controls. No short-term adverse events from SnMP treatment were noted other than photoreactivity due to inadvertent exposure to white light phototherapy. CONCLUSION: Early, predischarge SnMP administration decreased the duration of phototherapy, reversed TB trajectory and reduced the severity of subsequent hyperbilirubinemia.

Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era.

OBJECTIVES: To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods. STUDY DESIGN AND PATIENTS: Comparative cohort study of very low birthweight (501-1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991-1994, n=1408; group II, 1995-1998, n=1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated. RESULTS: Mortality was higher for group I (63.1% v 56.7%; p=0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p=0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p=0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94). CONCLUSION: Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.

Estimation of total body water in very-low-birth-weight infants by using anthropometry with and without bioelectrical impedance and H2[(18)O].

The usefulness of bioelectrical impedance (BI) with anthropometry to measure total body water (TBW) was evaluated in very-low-birth-weight (VLBW) infants. A specific regression equation to measure TBW in a VLBW population was developed by simultaneously using the H2[(18)O] dilution method and BI in 12 infants with a gestational age of 24-30 wk and weighing <1200 g at birth. After an oral dose of H2[(18)O], the tracer dilution was measured in expired carbon dioxide. BI measurements were made with a model BIA-101 apparatus (RJL Systems, Detroit). Electrodes were placed in the standard position as well as proximally on the leg and the forearm. The best correlation was observed between body weight and TBW (r = 0.989). For BI, the best correlation was obtained when gestational age was used as a covariable along with body weight and crown-heel length (r = 0.985). The correlation was comparable with proximal electrode placement (r = 0.985). The new correlation was evaluated in 6 infants weighing < 1008 g. A significant correlation between BI and H2[(18)O]-measured TBW was observed (r = 0.988). Published regression equations for infants consistently gave higher estimates of TBW in another group of 14 infants weighing <1200 g than did the new correlations. TBW represented 84-95% of body weight in these VLBW infants. TBW could be computed simply from body weight alone. Use of BI and length as covariables did not add significantly to the estimate of TBW in VLBW infants.

Outcomes of extremely low birth weight infants.

BACKGROUND: Our goal was to determine the effects of recent changes in delivery room and neonatal care, including surfactant and dexamethasone therapy, on survival, neonatal morbidity, and 20-month neurodevelopmental outcome of infants with birth weights of less than 750 g. METHODS: We compared the outcomes of 114 infants of 500 to 750 g birth weight delivered at our perinatal center between January 1990 and December 1992 (period II), when surfactant and postnatal dexamethasone were used, with the outcomes of 166 such infants born between July 1982 and June 1988 (period I). RESULTS: The rate of cesarean section increased from 17% to 27% and delivery room intubation increased from 54% to 72% during periods I and II, respectively. Survival increased from 23% during period I to 43% during period II. The increase in survival was significant at birth weights of 600 to 700 g and at 24 weeks' gestation and greater. During period II fewer infants died at less than 24 hours of age and more died at more than 28 days of life. Neonatal morbidity did not change appreciably; neither did 20-month neurodevelopmental outcomes. Twenty percent of the infants had subnormal cognitive function (Mental Development Indices < 70) and 10% had cerebral palsy during period II. CONCLUSIONS: Despite an increase in survival during 1990 to 1992, the neonatal and early childhood outcomes of the survivors were unchanged. Physicians and parents anticipating the delivery of extremely low birth weight infants must be aware of these outcomes to make informed decisions as to the advisability of aggressive care at birth and thereafter.

Bradycardia in preterm infants: indications and hazards of atropine therapy.

Eight preterm infants are presented to demonstrate the indications and hazards of using atropine for treatment of bradycardia in the high-risk premature nursery. Three infants developed bradycardia following initiation of nipple feedings, one following gavage feedings, three following surgical manipulation of visceral structures, and one associated with presence of chronic pulmonary disease. It is suggested that the first seven cases represent "reflexic bradycardia," probably vagally mediated and thus amenable to atropine therapy, whereas the eighth is an example of "hypoxic bradycardia" where administration of atropine may be detrimental. Polygraphic monitoring, arterial blood gases, and the clinical status are helpful in distinguishing reflexic from hypoxic bradycardia. These parameters should be evaluated prior to institution of atropine therapy.

Neonatal circulatory changes: an echocardiographic study.

Serial echocardiograms were performed in the first three days of life on 38 normal full-term infants. Right ventricular systolic time intervals were measured from the pulmonic valve echogram and left ventricular systolic time intervals were determined from the aortic valve echogram. The heart rate, left ventricular pre-ejection period (LPEP), left ventricular ejection time (LVET), and LPEP/LVET ratio showed insignificant variation with increasing postnatal age. The right ventricular pre-ejection period (RPEP) shortened, the right ventricular ejection time (RVET) lengthened, and the RPEP/RVET ratio decreased with increasing age. The findings suggested that alterations in the RPEP/RVET ratio reflected the decreasing pulmonary artery diastolic pressure and pulmonary vascular resistance of the early neonatal period and may be valuable in the noninvasive evaluation of the newborn's pulmonary vascular bed.

Echographic ventricular systolic time intervals in normal term and preterm neonates.

Right ventricular and left ventricular systolic time intervals (RVSTIs and LVSTIs) were measured in normal term and preterm infants from 1 hour to 90 days of life. LVSTIs in both term and preterm infants were similar in the first five days of life. The ratio of left pre-ejection period (LPEP) to left ventricular ejection time (LVET) was lower in preterm infants older than age 5 days. Estimated gestational age had no influence on LVSTI. The ratio of right pre-ejection period (RPEP) to right ventricular ejection time (RVET) was lower in preterm infants (0.32) than in term newborns (0.37). The preterm RPEP/RVET ratio decreased with age, but at a slower rate than in term babies. This was consistent with the lower pulmonary vascular resistance present in preterm infants.

Neonatal morbidity after elective repeat cesarean section and trial of labor.

OBJECTIVE: To evaluate neonatal outcomes after an elective repeat cesarean section (ERCS) compared with a trial of labor (TOL). POPULATION AND METHOD: All mothers who underwent previous cesarean section and delivered singleton infants at term gestation were identified during a 1-year period. Neonatal outcomes were compared between infants delivered by ERCS (n = 497) and those delivered by TOL (n = 492), and between infants delivered by a successful (n = 336) and a failed (n = 156) TOL. A cohort of mothers and their term infants delivered by routine vaginal delivery were also identified. RESULTS: Infants delivered by ERCS had an increased rate of transient tachypnea compared with infants born by TOL (6% vs 3%). Compared with routine vaginal deliveries, the adjusted odds ratio of developing any respiratory problem after an ERCS was 2.3 (95% confidence interval [CI]: 1.4, 3.8), and for developing transient tachypnea was 2.6 (CI: 1.5, 4.5). In addition, two infants delivered by ERCS developed respiratory distress syndrome. Infants delivered after a TOL had increased rates of suspected and proven sepsis (5% vs 2% and 1% vs 0.1%, respectively). Compared with a successful TOL, the infants delivered by cesarean section after a failed TOL had more neonatal morbidity and had a longer hospital stay (4.8 +/- 2 vs 3.1 +/- 2 days). The odds ratio for developing any respiratory illness after a failed TOL was 2.1 (95% CI: 1.1, 4.1), for suspected sepsis was 4.8 (95% CI: 2.6, 9.0), and for proven sepsis was 19.3 (95% CI: 2.0, 187). Neonatal outcomes after a successful TOL were similar to routine vaginal births. CONCLUSION: Infants born by ERCS are at increased risk for developing respiratory problems compared with those born by TOL. However, TOL is associated with increased rates of suspected and proven sepsis. This appears to be limited to infants delivered by cesarean section after a failed TOL.

Fungal colonization in the very low birth weight infant.

In the neonate, fungal infections result in significant morbidity and mortality. For very low birth weight (less than 1,500 g) infants, we prospectively determined the fungal colonization rate to be 26.7%. In one third of infants with fungal colonies, mucocutaneous candidiasis developed, and in 7.7%, systemic disease developed. Two thirds of the infants had colonies in the first week of life. This colonization was probably acquired during labor and delivery, because those infants who had colonization were more often delivered vaginally than by cesarean section. Early colonization, commonly from the gastrointestinal or respiratory tract, featured Candida albicans and Candida tropicalis. Late colonization, occurring after 2 weeks of life (15.0% of patients), was more likely to be cutaneous and was associated with either Candida parapsilosis or such poor growth that the organism could not be identified. Infants with colonization only rarely had budding yeasts (6.1%), whereas more than half of the infants with either a urinalysis showing budding yeasts or a urine culture growing fungi had invasive disease. Fungal contamination was not found on either thoracotomy tubes or catheter tips. In the low birth weight infant, fungal colonization represents a significant risk factor for cutaneous or systemic candidiasis in these infants.

Efficacy of computer-assisted management of respiratory failure in neonates.

We modified an algorithm for mechanical ventilation of infants with respiratory distress syndrome to create an interactive user-friendly computer program. To determine the effectiveness of this computer program, we evaluated the correction of deranged arterial blood gases in three groups of neonates: group I, treated before the introduction of the computer into the nursery; group II, managed by pediatric residents with the guidance of the computer program; group III, treated after the introduction of the computer into the nursery but managed without consideration of the computer output. Arterial blood gas values improved more frequently in the neonates managed with computer consultation (group II, 65/75, 87%) than in both control groups (group I, 37/57, 65%, P less than .005; and group III, 46/63, 73%, P less than .05). Furthermore, increases in ventilatory support in the presence of normal arterial blood gas values occurred only in patients managed without computer guidance. In a teaching institution, more effective care of neonates with respiratory failure may be facilitated by computer-assisted management of mechanical ventilators.

Preschool performance of children with normal intelligence who were very low-birth-weight infants.

Children who were very low-birth-weight infants (less than 1,500 g), beneficiaries of modern neonatal intensive care, are now of school age. To evaluate their school performance 80 children born in 1976 who had very low-birth-weight (mean birth weight 1.2 kg, mean gestational age 30 weeks) were examined at age 5 years. Sixty-five children were neurologically intact and had normal IQ (greater than or equal to 85) on the Stanford-Binet; five children were neurologically abnormal and ten had IQ below 85. Of the 65 children with normal intelligence and no neurologic impairments, 46 were single births and enrolled in preschool. These 46 children were matched by race, sex, and family background with classmate control children who had been born at full term. Outcome measurements included the Slosson Intelligence Test, the Woodcock-Johnson Psycho-Educational Battery (including subscales of Picture Vocabulary, Spatial Relations, Memory for Sentences, Visual Auditory Learning, Quantitative Concepts, and Blending) and the Beery Developmental Test of Visual-Motor Integration. No significant differences in IQ were found between children who were very low-birth-weight infants and control children; however, children who were very low-birth-weight infants performed significantly less well on the Spatial Relations subtest of the Woodcock-Johnson and on the Visual-Motor Integration test. Similar results were found for nine sets of twins and their control children. Recognition of these perceptual and visual-motor problems may permit appropriate early remedial intervention and prevent the compounding of these difficulties.

Effect of supine and prone positions on arterial oxygen tension in the preterm infant.

To determine the optimal position for the preterm infant, arterial oxygen tension (Pao2) was monitored in 16 preterm infants by the transcutaneous method with the infants in both supine and prone positions. When the infants were prone, Pao2 rose by a mean of 7.4 mm Hg (P less than .001), an increase of 15%. In those infants with residual cardiopulmonary disease a 25% increase was noted. The higher Pao2 in the prone position was accompanied by a significant decrease in the amount of time the chest wall moved asynchronously. This improved oxygenation in the prone position appears to be the result of enhanced ventilation/perfusion ratios and not merely secondary to an alteration in sleep state with positioning of the infant. These findings may have important implications in the management of preterm infants, requiring neonatal intensive care.

Disseminated fungal infections in very low-birth-weight infants: therapeutic toxicity.

The improved survival of very low-birth-weight infants, who require prolonged hospitalization and many invasive procedures, increases the risks for nosocomial illnesses, such as disseminated fungal infections. In a 2-year period, systemic fungal infections were clinically diagnosed in ten infants. This necessitated the institution of antifungal therapy in extremely premature infants (mean birth weight 788 g, mean gestational age 28 weeks) despite the paucity of knowledge about the pharmacokinetics and toxicity of these drugs in the very immature patient. Despite the absence of reported toxicity in infants and older children, severe nephrotoxicity was commonly observed with oliguria/anuria, temporally related to the administration of amphotericin B in seven of these infants. Additional evidence of nephrotoxicity included either a rise in creatinine levels (greater than or equal to 1.3 mg/dL), an increase in BUN (greater than or equal to 30 mg/dL), hypokalemia (less than or equal to 2.9 mEq/L), or hyperkalemia (greater than or equal to 6.0 mEq/L). Six of these seven drug-toxic infants died. Interruption of amphotericin B therapy, with reinstitution at a lower dose, was the most successful factor in alleviating the anuria. There is an urgent need for detailed pharmacokinetic and toxicity studies of antifungal agents in immature infants.

Disseminated fungal infections in very low-birth-weight infants: clinical manifestations and epidemiology.

In 1979 and 1980, an apparent increase in the occurrence of disseminated fungal infections was observed. The clinical features of such infections in very low-birth weight infants are poorly described, and diagnosis is often delayed. Over a 24-month period, a discrete group of ten clinically diagnosed and four autopsy-diagnosed cases of systemic fungal infections in very low-birth-weight infants was observed. Prior to developing systemic fungal illness, these infants required prolonged total parenteral nutrition, central arterial or venous catheters, and multiple courses of broad-spectrum antibiotics for documented or suspected bacterial sepsis. The clinically diagnosed disseminated fungal infection (ten infants) was noted at a mean age of 33 days with one or more of the following: respiratory deterioration, abdominal distension, guaiac positive stools, carbohydrate intolerance, candiduria, endophthalmitis, meningitis, abscesses, erythematous rash, temperature instability, and hypotension. These signs and symptoms were seen as chronic or were intermittent in clinical course. In contrast, the autopsy-diagnosed disseminated fungal infection (four infants) was present at an earlier age with fewer recognizable predisposing factors and a more acute onset of infection. Nevertheless, in both groups the diagnosis of systemic candidal infection was delayed, due to an inability to consistently recover the organism from blood, CSF, or urine. The neonatologist caring for the very low-birth-weight infant needs to become more aware of these clinical entities. A high index of suspicion and ancillary diagnostic evaluation, such as retinoscopy or tissue biopsy, may be indicated in the critically ill, culture-negative patient.

Perinatal correlates of cerebral palsy and other neurologic impairment among very low birth weight children.

BACKGROUND AND OBJECTIVE: The etiology of neurologic impairments among very low birth weight (VLBW, <1.5 kg) children is poorly understood. We sought to investigate the perinatal predictors of major neurologic impairment, including cerebral palsy, among VLBW children. METHODS: Antenatal, intrapartum, and neonatal events and therapies were compared between 72 singleton inborn VLBW children born between 1983 to 1991 who had neurologic impairment at 20 months corrected age (including 50 with cerebral palsy and 22 with other neurologic impairments) and 72 neurologically normal VLBW children matched by birth weight, gestational age, race, and sex via a retrospective case-control method. Multiple logistic regression was conducted, entering only those variables found to be significant at the bivariate level. RESULTS: There were no significant differences in the rates of pregnancy-induced hypertension, maternal tocolytic use including magnesium, or antenatal steroid therapy. Higher rates of clinical chorioamnionitis were found among the mothers of the neurologically impaired children as compared with controls (31% vs 11%), but not among the subgroup of mothers of children with cerebral palsy (22% vs 12%). Significant differences in neonatal factors among the total neurologically-impaired group (n = 72) versus controls included oxygen dependence at 36 weeks (31% vs 15%), septicemia (53% vs 31%), severe cranial ultrasound abnormality (50% vs 17%), and hypothyroxinemia (43% vs 25%). In the subgroup with cerebral palsy (n = 50), significant differences included days on the ventilator (23 vs 14 days), septicemia (54% vs 33%), and severe cranial ultrasound abnormality (52% vs 12%). Multivariate analysis controlling for birth weight, gestational age, race, sex, and the birth period (before 1990 versus 1990 and after) revealed direct and independent effects of clinical chorioamnionitis [odds ratio (OR), 3. 79; confidence interval (CI), 1.34-10.78], severe cranial ultrasound abnormality (OR, 9.97; CI, 3.84-25.87), and septicemia (OR, 2.46; CI, 1.10-5.52) on total neurologic impairment. Consideration of the 50 cases with cerebral palsy revealed direct and independent effects of severe cranial ultrasound abnormality only (OR, 15.01; CI, 4.34-51. 93). CONCLUSIONS: Both antenatal and neonatal risk factors contribute to the development of severe neurologic impairment, including cerebral palsy among VLBW children. Because prevention of chorioamnionitis may not be feasible in the near future, attempts to decrease neonatal risk factors such as severe cranial ultrasound abnormalities and sepsis may be most feasible at this time.

Alae nasi activation (nasal flaring) decreases nasal resistance in preterm infants.

The effect of alae nasi activation on nasal resistance in a group of healthy preterm infants was measured. Alae nasi activity was determined via the alae nasi electromyogram obtained from skin surface electrodes during both active and quiet sleep. Nasal resistance was calculated from airflow measured with a mask pneumotachograph and transnasal pressure drop obtained by simultaneous measurement of nasal pressure via a catheter inserted in one nostril and mask pressure. The percentage of breaths accompanied by phasic alae nasi activity was higher during active sleep than during quiet sleep (43% +/- 10% v 14% +/- 6%; P less than .005), and hypercapnic stimulation (4% CO2 inhalation) significantly increased the incidence of phasic alae nasi activity to comparable levels in both sleep states (82% +/- 8% in active sleep and 82% +/- 9% in quiet sleep). Elevation of tonic alae nasi activity also occurred more frequently during active sleep (P less than .05). The presence of either phasic or elevated tonic alae nasi activity decreased nasal resistance by 23% +/- 4% during active sleep and 21% +/- 3% during quiet sleep. This reduction in nasal resistance resulted in either a lower transnasal pressure during inspiration, a higher peak inspiratory airflow, or a combination of the two. Alae nasi activity may be an important mechanism that facilitates ventilation by reducing nasal resistance, and it may help stabilize the upper airway by preventing the development of large negative pharyngeal pressure during inspiration.

Respiratory distress syndrome: echocardiographic assessment of cardiovascular function and pulmonary vascular resistance.

Echocardiograms were performed for 82 preterm infants comprising 22 normal infants, 29 with mild respiratory distress syndrome (RDS), and 31 with severe RDS. Left ventricular systolic time intervals were measured from aortic valve echograms and right ventricular systolic time intervals from pulmonic valve echograms. Left ventricular performance seemed to be altered early in postnatal adaptation of preterm infants, but played no demonstrable role in the outcome of RDS. The right ventricular preejection period/right ventricular ejection time (RPEP/RVET) ratio was prolonged in 17 out of 31 patients with severe RDS, consistent with increased pulmonary vascular resistance or right ventricular dysfunction. Prolonged RPEP/RVET identified a subgroup with increased mortality and morbidity.

Optimal position for a spinal tap in preterm infants.

Inasmuch as spinal taps in preterm infants are frequently accompanied by clinical deterioration, the optimal position for this procedure was investigated. Three positions were each randomly assigned for five minutes to 17 healthy preterm infants without a spinal tap actually being performed: (1) lateral recumbent with full flexion (flexed position), (2) lateral recumbent with partial neck extension (extended position), and (3) sitting with head support and spine flexion (upright position). Transcutaneous PO2 and PCO2 were monitored in all infants, minute ventilation (VI) in seven, and heart rate and blood pressure in ten infants. Mean transcutaneous PO2 decreased in each of the three positions. This decrease was significantly greater in the flexed (28 +/- 8 mm Hg) as compared with the extended (18 +/- 8 mm Hg, P less than .001) and upright (15 +/- 11 mm Hg, P less than .001) positions. Mean transcutaneous PCO2 increased only in the flexed position (3 +/- 4 mm Hg, P less than .005) and levels were still elevated five minutes after that position had been discontinued. The consistent decrease in transcutaneous PO2 was accompanied by a variable effect of positioning on VI and there were no episodes of airway obstruction or apnea greater than 10 seconds. Heart rate increased in each position whereas blood pressure remained unchanged. These data suggest that although hypoventilation may contribute to the observed decrease in transcutaneous PO2, ventilation/perfusion imbalance appears to be the major mechanism. As spinal taps performed in the widely accepted flexed position carry the greatest risk of potential morbidity, it is recommended that this position be modified with neck extension or that spinal taps be performed in the upright position.