Biomedical subjects
Publications and source records attributed to Alan R Spitzer.
This article discusses the application of mass spectroscopy, a technology that may have great potential for screening neonatal brain injury. This approach is anticipated to become increasingly important in neonatal and perinatal research and newborn care during the next few years.
Pulmonary alveolar type II cells synthesize and secrete phospholipids and surfactant proteins. In most mammalian species, the synthesis of phospholipids and proteins of lung surfactant increases with fetal lung maturation, which occurs late in gestation. Factors that may promote lung maturation and surfactant production include the placental hormone, leptin, whose expression increases with advancing gestational age. We demonstrate that physiologic concentrations of leptin (1 and 10 ng/mL) increase the levels of surfactant proteins (SP) A, B, and C mRNA as well as SP-A and SP-B protein in d-17 fetal rat lung explants in vitro. To determine whether leptin exerts similar effects in vivo, we administered leptin antenatally to pregnant rats and compared its effects to that of dexamethasone, a known mediator of fetal lung development. Antenatal treatment with leptin for 2 d significantly increased the average weight of the fetal lungs in relation to their body weight. Histologic analysis revealed that the increase in fetal lung weight was accompanied by an increase in the number and maturation of type II alveolar cells and the expression of surfactant proteins B and C in these cells. Collectively, these results suggest that leptin is a cytokine regulator of rat fetal lung maturity.
BACKGROUND: We reported previously that the use of cephalosporin among premature neonates increased the risk of subsequent fungal sepsis. As a result, we recommended that ampicillin and gentamicin be used as empiric coverage for early-onset neonatal sepsis while culture results are awaited. OBJECTIVES: To describe antibiotic use during the first 3 days after birth for neonates admitted to the NICU and to evaluate the outcomes for neonates treated with 2 different antibiotic regimens. METHODS: We assembled a cohort of inborn neonates, from our deidentified administrative database, who had documented exposure to ampicillin during the first 3 days after birth. Infants treated concurrently with cefotaxime or gentamicin were evaluated, to identify the factors that were associated independently with death before discharge, with both univariate and multivariate analyses. RESULTS: There were 128,914 neonates selected as the study cohort; 24,111 were treated concurrently with ampicillin and cefotaxime and 104,803 were treated concurrently with ampicillin and gentamicin. Logistic modeling showed that neonates treated with ampicillin/cefotaxime were more likely to die (adjusted odds ratio: 1.5; 95% confidence interval: 1.4-1.7) and were less likely to be discharged to home or foster care than were neonates treated with ampicillin/gentamicin. This observation was true across all estimated gestational ages. Other factors that were associated independently with death included immature gestational age, need for assisted ventilation on the day of admission to the NICU, indications of perinatal asphyxia or major congenital anomaly, and reported use of ampicillin/cefotaxime. CONCLUSIONS: For patients receiving ampicillin, the concurrent use of cefotaxime during the first 3 days after birth either is a surrogate for an unrecognized factor or is itself associated with an increased risk of death, compared with the concurrent use of gentamicin.
OBJECTIVES: The objectives were (1) to identify the drugs reported most commonly during NICU care, (2) to examine how different methods of documenting drug use could influence prioritization of drugs for future research aimed at evaluating safety and efficacy, (3) to describe the demographic differences in the population samples for some specific medications, (4) to identify which reported medications are used for patient populations with >20% mortality rates, and (5) to examine how reports of drug use change over time. METHODS: A retrospective review of a large national data set was performed. RESULTS: The 10 medications reported most commonly for the NICU were ampicillin, gentamicin, ferrous sulfate, multivitamins, cefotaxime, caffeine citrate, furosemide, vancomycin, surfactant, and metoclopramide. Medications used for patient populations with >20% mortality rates included amphotericin, clonazepam, dobutamine, epinephrine, ethacrynic acid, insulin, lidocaine, metolazone, milrinone, inhaled nitric oxide, nitroglycerin, octreotide, pancuronium, phenytoin, sodium nitroprusside, sodium polystyrene sulfonate (Kayexalate), tris-hydroxymethylaminomethane acetate buffer, and tolazoline. Several of these drugs (eg, amphotericin B and bumetanide) were used primarily for extremely premature neonates, and this usage might explain the high mortality rates for the population of neonates treated with these medications. Other medications (clonazepam, milrinone, inhaled nitric oxide, and phenytoin) were used primarily for near-term and term infants. The explanation for the high mortality rates for these neonates is less clear and may be related primarily to the severity of illness for which the medications are used. Utilization rates for several different medications (eg, cisapride, metoclopramide, and dexamethasone) changed by >50% during the past 5 years. CONCLUSIONS: Data reported here are the first from a large national data set on the use of different medications for neonates admitted for intensive care and should be helpful in establishing priority agendas for future drug studies in this population.
Annexin A7 (synexin, annexin VII), a member of the annexin family of proteins, causes aggregation of membranes in a Ca2+-dependent manner and has been suggested to promote membrane fusion during exocytosis of lung surfactant, catecholamines, and insulin. Although annexin A7 (A7) was one of the first annexin proteins described, limited studies of its physical characteristics or of structural domains affecting any of its proposed functions have been conducted. As postulated for other annexin proteins, the unique NH2-domain possibly determines the functional specificity of A7. Therefore, we evaluated the effects of segmental deletions in the NH2-terminus on several characteristics associated with the COOH-terminus of A7. The COOH-terminus contains the only tryptophan residue, and all potential trypsin sites, and the Ca2+ and phospholipid binding sites. Recombinant rat A7 and its deletion mutants were expressed using constructs based on the cDNA sequence obtained by screening a rat lung cDNA library. Ca2+ increased the tryptophan fluorescence of A7 and caused a small red shift in the emission maximum (lambdamax), which was further increased in presence of phospholipid vesicles (PLV). NH2-terminal deletions of 29, 51, and 109 residues affected the peak width of fluorescence and lambdamax, surface-exposure of tryptophan residue, and caused a smaller Ca2+-dependent red shift in lambdamax of membrane-bound protein in comparison to A7. Limited proteolysis with trypsin showed that Ca2+ increased the proteolysis of all proteins, but the deletions also affected the pattern of proteolysis. The presence of PLV protected against Ca2+-dependent increase in proteolysis of all proteins. The deletion of first 29 residues also caused decreased membrane binding, aggregation, and fusion, when compared with A7. Collectively, these results suggest that specific NH2-terminus domains can alter those properties of A7 that are normally associated with the COOH-terminus. We speculate that interactions between the NH2- and COOH-termini are required for membrane binding, and aggregation and fusion properties of annexin A7.
OBJECTIVE: The most common admission to intensive care nurseries is the infant with suspected neonatal sepsis. To determine the clinical practice of neonatologists with respect to this diagnosis, we examined a large neonatal database during a 2-year period of time. The goal of this study was to define whether there were optimal practice strategies that could identify a "benchmark" clinical approach for this diagnosis. DESIGN: The PROACT database of ParadigmHealth was examined for all term infants with an admitting ICD - 9 code for suspected neonatal sepsis between January 1, 2001 and December 31, 2002. Infants had to be asymptomatic by 24 hours of life with no significant respiratory signs and receiving oral feedings. All infants had negative blood cultures. Maternal risk factors were examined to determine if they influenced the duration of therapy. The impact of treatment upon subsequent length of stay was also evaluated. Several areas of the country were individually examined to see if possible regional variations existed with respect to treatment of suspected sepsis. RESULTS: There were no significant differences noted in the management when maternal risk factors for suspected sepsis were assessed. In general, neonates were treated for 3.3+/-1.8 to 3.5+/-2.1 days, regardless of the number of maternal risk factors present at birth (p=NS). Length of stay ranged from 4.2+/-2.1 to 4.4+/-1.9 days in these groups (p=NS). The duration of treatment ranged from 1 to 10 days, even though all infants were clinically well and feeding by 24 hours of life. A total of 170 infants (17.0%) were treated for 4 to 6 days and 116 (11.6%) neonates received antibiotics for 7 to 10 days, even with negative blood cultures. One region of the country appeared to treat infants for a longer period of time than the other four regions examined, increasing the mean length of stay by 1.8 days (p<0.05). CONCLUSIONS: Treatment of neonates with suspected sepsis appears to be influenced by considerations other than maternal risk factors or the infant's clinical condition beyond the first day of life. There appears to be a great deal of practice variation among neonatologists confronted by patients with suspected sepsis. Awareness of this unnecessary variation may be of great value in reducing the duration of antibiotic therapy in the NICU and shortening the length of stay.
OBJECTIVE: To test the hypothesis that histological chorioamnionitis (CA) is not associated with increased risk of early onset intraventricular hemorrhage (IVH). STUDY DESIGN: Clinical data were prospectively collected for 62 consecutive neonates born before 28 weeks of gestation. Placental histology for CA was performed by a pathologist unaware of the head ultrasound scan (HUS) results. The first HUS was obtained by 30 minutes of life. Follow-up HUS were performed before 24 hours and again at 48 to 72 postnatal hours of life. An IVH (grade I to IV) at less than 72 hours of life was deemed an early hemorrhage. RESULTS: Nine of the 62 (14.5%) infants had early onset IVH. In all, 29 infants were born to women with histological evidence of CA; 33 infants did not have CA. Infants did not differ in birth weight, gestational age, sex, cord blood pH, 5-minute Apgar score of <7, cesarean delivery, prenatal use of steroids, administration of tocolytics, need for resuscitation, presence of pneumothorax, platelet count at birth, or use of surfactant. Early IVH rates (3/29 in CA vs 6/33 in non-CA) were similar (p=0.48). Two infants in each group with early IVH died before 2 weeks of age. Five additional infants from the CA group developed IVH at more than 72 postnatal hours of life (late onset IVH), and two of those infants progressed to develop periventricular leukomalacia (PVL). In contrast, only three non-CA infants had late IVH and none developed PVL. Logistic regression confirmed that no perinatal variables including CA were associated with early onset IVH. CONCLUSION: Chorioamnionitis is not associated with increased risk of early IVH.
OBJECTIVE: To determine the effect of the genetic counselor on the acceptance of genetic amniocentesis. METHODS: We studied women with singleton pregnancies who would be at least 35 years of age at the estimated date of delivery without fetal structural anomalies or family history of chromosomal abnormalities. The acceptance rate of genetic amniocentesis among women evaluated by each counselor was compared with the average acceptance rate for our population. Chi-square test, Fisher exact test and ANOVA were used for analysis. RESULTS: Of the 2,180 women met our inclusion criteria, 1,719 (78.9%) accepted genetic amniocentesis. The maternal age at estimated date of delivery, the proportion of women who conceived by in vitro fertilization, and the proportion with history of miscarriage were similar among women evaluated by each of the six genetic counselors. However, the acceptance rate of genetic amniocentesis was significantly lower in women evaluated by counselor C [115/170 (67.6%), P=0.001] and significantly higher in the group evaluated by counselor D [138/154 (89.6%), P=0.002] compared with the overall study population rate [1719/2180 (78.9%)]. The acceptance rate of 80.4% (210/261, P=0.52), 75.6 % (232/307, P=0.23), 80.9% (443/547, P=0.30] and 78.4% (581/741, P=0.83) for Counselors A, B, E and F respectively did not differ from the overall study population rate. CONCLUSIONS: Considerable variation exists in the acceptance rate of genetic amniocentesis among women based on the genetic counselor.
PURPOSE OF REVIEW: To examine recent research relevant to sudden infant death syndrome (SIDS) to determine whether there is a place for home monitoring in the care of children believed to be at risk. RECENT FINDINGS: Current SIDS research has focused on the genetics of SIDS, brainstem abnormalities and arousal failures, the effects of tobacco smoke and other environmental agents, the role of infectious diseases, and prenatal factors that may contribute to SIDS. Investigations have suggested that there are infants who appear to respond less effectively when challenged by certain environmental or infectious agents. These infants have blunted responses to stress and diminished arousal to hypoxemia, in part because of failures in genetically determined brainstem function. It is unclear at this time whether home monitoring would offer protection in all circumstances, but it may be helpful in certain patients. SUMMARY: There appears to be progress in understanding the causes of SIDS. As additional studies emerge, the optimal approaches to care will become more apparent, with home monitoring one of the possible interventions.
The birthing process represents a traumatic eviction from the warm, quiet womb with a constant supply of food to the cold, bright world with nothing to eat. Tremendous physiologic strains are suddenly placed on the newborn infant. In a time frame of a few days, the neonate must transition successfully to extrauterine life, and the family must be prepared for the care of their newborn at home. This article reviews the physiologic and social issues that face the newborn and mother, discusses the specific issues created by early discharge, and provides suggested criteria for the timing of discharge of the well term neonate.
The public's increasing use of the Internet as a personal medical consultant poses new problems and special opportunities for the practicing physician. This article outlines how the Internet is already changing medical practice and how physicians can begin to use this resource to an advantage in their daily medical practice.
OBJECTIVES: To determine the effect of in vitro fertilization (IVF), multiple gestation, and history of unkaryotyped miscarriage on the acceptance of genetic amniocentesis. METHODS: We studied women expected to be at least 35 years of age at the estimated date of delivery without family history of chromosomal abnormalities or fetal structural anomalies. The influence of IVF, multiple gestation, and history of miscarriage on the acceptance rate of genetic amniocentesis was evaluated. Chi-square test and logistic regression were used for analysis. RESULTS: In singleton pregnancies, the acceptance rate of genetic amniocentesis was 70.7% (58/82) in the IVF group compared to 77.9% (1837/2356) (P = 0.14) in the women who conceived spontaneously. The corresponding values in multiple gestation pregnancies were 71.1% (37/52) and 62.9% (34/54) respectively (P = 0.41). There was no difference in the acceptance rate of amniocentesis between singletons (70.7%) and multiple gestations (71.1%) after IVF (P = 0.96), while in women who conceived spontaneously, the acceptance rate of 78% in singletons was significantly higher than the acceptance rate of 63% in multiple gestations (P = 0.008). Adjusting for confounding variables, women with multiple gestations were about 40% less likely to accept genetic amniocentesis (OR = 0.63, 95% CI = 0.39-1.00, P = 0.05), while women with a history of miscarriage were about 17% less likely to accept genetic amniocentesis (OR = 0.83, 95% CI = 0.68-1.00, P = 0.05). Adjusting for multiple gestation and previous miscarriage, IVF was not independently associated with acceptance of genetic amniocentesis (OR = 0.84, 95% CI = 0.54-1.29, P = 0.42). CONCLUSIONS: There is no difference in the acceptance rate of genetic amniocentesis among women with IVF pregnancies compared with those who conceive spontaneously, after adjusting for multiple gestation and previous miscarriage. Unlike women who conceive spontaneously, the decision to accept amniocentesis appears not to be influenced by the presence of multiple gestation in women with IVF pregnancies.
OBJECTIVE: To assess the effectiveness of an incomplete course of antenatal corticosteroids on perinatal morbidity and mortality. METHOSD: We studied consecutive neonates born at 23-34 weeks' gestation between January 1, 1998, and July 31, 2002. The study population was divided into a group exposed to one 12-mg dose of betamethasone before delivery and a non-corticosteroid-exposed group, which were compared for various perinatal outcome variables. The Student t test, chi(2), Fisher exact tests, and logistic regression were used for analysis. RESULTS: One hundred twenty-five neonates (55.6%) were exposed to one 12-mg dose of betamethasone before delivery, whereas 104 neonates (45.4%) did not receive antenatal corticosteroids. Mean gestational age at delivery (28.4 +/- 3.1 weeks versus 29.7 +/- 3.5 weeks, P =.002) and birth weight (1189 +/- 409 g versus 1289 +/- 441 g, P =.07) were lower among the steroid-exposed group. Adjusting for gestational age, one dose of betamethasone was associated with significant reduction in the need for vasopressors (odds ratio [OR] 0.35; 95% confidence interval [CI] 0.14, 0.85; P =.02), the rate of intraventricular hemorrhage (OR 0.42; 95%CI 0.19, 0.92; P =.03), and neonatal death (OR 0.31; 95% CI 0.11, 0.86; P =.02). There were no differences between groups in the rate of clinical and histological chorioamnionitis, low Apgar scores, postnatal surfactant exposure, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus, retinopathy of prematurity, and neonatal sepsis. CONCLUSION: An incomplete course of antenatal corticosteroids is associated with reduction in the need for vasopressors, the rate of intraventricular hemorrhage, and neonatal death in preterm neonates.
The fusion of lamellar body with plasma membrane, a distal obligatory step in exocytosis of lung surfactant, may be mediated by annexin a7 (anx a7; synexin). To understand the mechanism of anx a7 action, we tested the hypothesis that anx a7 binding to membranes would increase in order to facilitate membrane fusion during stimulation of lung surfactant secretion. Isolated rat alveolar type II cells were treated with established secretagogues of lung surfactant and the membrane and cytosol fractions were analyzed for in vitro binding of anx a7. In cells treated with calcium ionophore (A23187) or phorbol 12-myristate 13-acetate (PMA), anx a7 binding to the membrane fraction was increased by 120%, while that to the cytosol fraction was decreased by 40%, when compared with binding to corresponding fractions from control cells. Protein kinase inhibitors prevented the PMA effects on anx a7 binding. The lamellar body and plasma membrane fractions of A23187-treated cells also showed increased binding of anx a7. The lamellar bodies of A23187-treated cells showed lower K(m) for Ca(2+) and higher maximal binding of anx a7, when compared with those from control cells. Collectively, our findings suggest that these two agents modify membrane proteins to regulate anx a7 binding, which may facilitate increased membrane fusion activity during stimulation of surfactant secretion.
After a prolonged and complicated hospital stay, the NICU graduate enters the world with unique and complex medical problems. A well-coordinated multidisciplinary approach is essential in the follow-up care of these infants. The crucial issues for the pediatrician who cares for these infants are assisting in the catch-up growth and the ongoing healing process with good nutritional supplementation, while preventing further problems by detecting and treating illness early. Timely inclusion of other appropriate health care personnel and facilities in the care may be crucial and rewarding. The role of the pediatrician in helping these infants attain their full physical, neurodevelopmental, emotional, and psychosocial potential by providing optimal care is invaluable. With appropriate support most NICU graduates will become productive and well-adjusted adults. The pediatrician plays a major role in completing this process and contributes to the eventual success of the neonatal intensive care that these infants are subjected to at the very beginning of their lives.
OBJECTIVE: Cerebral function monitoring (CFM), using compressed single-channel amplitude-integrated electroencephalogram recorded from 2 biparietal electrodes, has been shown previously to be a simple bedside tool for monitoring neonatal central nervous system (CNS) status. As the pattern of the CFM changes with gestational age, the technique can be used to assess brain maturation in premature infants. We have developed a new scoring system for the interpretation of neonatal CFM recordings. The objective of this study was to evaluate CFM tracings at increasing gestational and postnatal ages to develop a scoring system to quantify CFM pattern changes. METHODS: Term and preterm neonates were studied with CFM at 12 to 24 hours of life, 48 to 72 hours of life, and then weekly or biweekly until hospital discharge. Each study comprised 8 to 24 hours of continuous CFM recording. CFM recordings were evaluated using the scoring system for record continuity, presence of cyclic changes in electrical activity, degree of voltage amplitude depression, and bandwidth. Each variable was scored for each recording. All variables were summed to yield a total score (minimum 0, maximum 13). Total scores were correlated with gestational and postconceptional ages. RESULTS: Thirty infants were studied with gestational ages at birth that ranged from 24 to 39 weeks and birth weights that varied between 450 and 3850 g. A total of 146 CFM tracings were analyzed. With advancing gestational and postconceptional age, scores for each variable as well as total scores progressively increased with CNS maturation. The highest scores were attained at 35 to 36 weeks' postconceptional age, which corresponded to previously reported subjective observations performed by visual description of CFM patterns. Of the 4 component variables that we analyzed, the most sensitive indicators of CNS maturity were 1) the presence of a cycling pattern, 2) the continuity of the record pattern, and 3) the CFM recording bandwidth. CONCLUSIONS: Our proposed scoring system may be a valuable tool to quantify changes during CFM more objectively, reflecting variations in CNS activity in newborn infants and allowing for better statistical comparisons between amplitude-integrated electroencephalogram tracings from different patients as well as from the same patient at different points of time.
The use of ultrasound imaging in the neonatal intensive care unit (NICU) has become an essential part of the evaluation and delivery of care for most neonates. Until recently, ultrasound machines were large, expensive, and often not immediately available, particularly at night and during weekends. Additionally, serial studies to define the evolution of an acute clinical situation were often not practical because of the dedicated time required and the expense involved. The recent introduction into our NICU of a high-quality, reasonably priced, and completely portable neonatal ultrasound unit (Sonosite, Bothell, WA) has now made it possible for neonatologists to rapidly obtain the hour-by-hour information that can be extremely helpful in the evaluation of a critically ill neonate. This paper illustrates some of the capabilities of this simplified device, and the value of having continuous on-site ultrasound availability in the NICU.
The objective of this study was to evaluate the patterns of hospitalization of term infants in 3 major metropolitan areas. We hypothesized that regional practice variation occurred in the care of term infants and that these differences would be reflected in the hospitalization patterns of infants. All infants cared for in an Intensive Care Nursery (ICN) after maternal discharge in 1 of 3 major metropolitan areas followed up by the same neonatal management company were compared (n=4,487). Term infants were grouped into 1 of 2 categories based on illness severity: Group 1 (G1) infants-those who required supplemental oxygen or ventilation for 24 hours or more (n=611); and Group 2 (G2) infants-those infants without an oxygen or ventilation requirement (n=1,549). Excluded were infants in the following categories: birth weight <2,500 grams, major congenital anomalies, surgical patients, extracorporeal membrane oxygenation (ECMO) support, or babies who died before discharge. The number of infants in each of these categories was compared as a percentage of the total number of infants cared for in that region. The average length of stay (ALOS) and percentage of patient days attributed to infants in each category were compared across regions using multiple comparison tests (Tukey). The total ALOS was greatest in City A, as was the ALOS for sick term infants. Patient days for sick term infants were lowest in City C, and healthier term infants comprised the lowest percentage of patient days in City A. This difference resulted in the lowest percentage of patient days for all term admissions in City A. These data demonstrated that significant variation existed in the delivery of care to term neonates among major metropolitan regions. Cities that admitted fewer term infants for observation periods (G2) tended to have sicker term neonates with higher acuity hospitalizations (GI) and longer lengths of stay (LOS). These findings suggested that a conservative admission policy for this population can decrease overall LOS.