Environmental stress and salivary cortisol levels in preterm infants.

BACKGROUND: Preterm infants are exposed to numerous environmental stressors during their Neonatal Intensive Care Unit (NICU) stay, particularly during the first week after birth. The aim of this study is to assess whether salivary cortisol levels are correlated with Neonatal Infant Stressor Scale (NISS) scores in preterm infants during the first week of life. We also quantified the changes in both NISS scores and cortisol levels in the first week, and whether cortisol levels are associated with gestational age. METHODS: Preterm infants (n = 38, birth weight <1250 g and/or gestational age <29 weeks) were included. Saliva samples were collected on day 0-3 (early) and day 4-7 (late), and cortisol concentrations were measured by immunoassay. NISS scores were assessed retrospectively for the six hours preceding each saliva collection. RESULTS: NISS scores were not significantly correlated with salivary cortisol levels at either time point. However, infants born at <28 weeks gestation had higher median cortisol levels than infants born at >28 weeks (p = 0.0068), and there was also a significant inverse relationship between NISS score and gestational age (p = 0.04). There was no significant difference between the early and late time points for either NISS scores or cortisol levels. CONCLUSIONS: Cortisol levels are elevated in infants <28 weeks gestation but do not correlate with NISS scores. NISS scores are inversely related to gestational age, likely reflecting increased exposure to interventions and invasive procedures for the smallest infants.

Optimizing iron supplementation by monitoring serum ferritin levels in premature infants.

BACKGROUND: Iron (Fe) is essential for growth, but optimal intake is controversial. Our NICU practice was to supplement 2 mg/kg/d Fe for all preterm infants receiving human milk when they achieved full feeding volume. Adjusting Fe supplementation based on ferritin levels is thought to better address physiologic requirements. Our objective was to assess the impact of therapeutic monitoring of ferritin levels on the initiation and dosing of iron supplementation, hematocrit, transfusions, and oxygen radical diseases in preterm infants. METHODS: Preterm infants (< 32 weeks gestation, n = 100) were included. Ferritin was measured when full feeds were achieved, and then every 2 weeks. Fe was started at 2 mg/kg/d or continued at current dose for ferritin 40-300µg/L, increased by 1-2 mg/kg/d for < 40µg/L, or discontinued for > 300µg/L. Outcomes were compared with a historical control group. RESULTS: Ferritin levels were not predictable by dietary or transfusion histories. Using the ferritin protocol, 70% of infants received Fe at the time of full feeds, compared to 100% of controls. In contrast, all infants received Fe 4 weeks later, compared to 87% of controls. Mean age at Fe initiation increased (14.8±6.3 to 21.0±11.76 days). Peak doses were higher, with 32% receiving > 2 mg/kg day by 6 weeks, with fewer transfusions. The incidence of bronchopulmonary dysplasia and necrotizing enterocolitis did not change. CONCLUSION: An iron protocol based on ferritin levels results in later initiation, higher doses, and fewer transfusions, without increasing oxygen radical diseases.

Serum ghrelin is associated with early feeding readiness but not growth in premature infants.

BACKGROUND: Feeding tolerance among premature infants is unpredictable using clinical parameters. Ghrelin, a peptide hormone, acts on the hypothalamus to increase hunger and gut motility. It is present in fetal tissues, promotes intestinal maturation, and is secreted in milk. We hypothesized that higher serum ghrelin levels on days 0-7 are associated with improved feeding tolerance and growth in premature infants. METHODS: Infants (< 1500 g birth weight, n = 36) were recruited on day (D) 0-7. Serum ghrelin was measured by ELISA on D 0-7, D 10-14, and D 24-32, and milk ghrelin in a feeding concurrent with each serum sample. Feeding tolerance was assessed as days to first and full enteral feeds. Growth was quantified as both weight and adipose and muscle deposition by ultrasound. RESULTS: Mean serum ghrelin levels decreased from D 0-7 to D 24-32. Higher ghrelin levels on D 0-7 were correlated with shorter time to first enteral feeding, but not with time to full enteral feeds, rate of weight gain, or rate of accretion of muscle or adipose tissue. Milk ghrelin was not related to serum ghrelin or growth. Abdominal and suprascapular muscle and adipose increased during the first month, but weight gain correlated only with the rate of accretion of abdominal adipose. CONCLUSIONS: Elevated serum ghrelin in the first days of life may contribute to gut motility and readiness to feed. Weight gain in premature infants may primarily indicate abdominal fat accumulation, suggesting that ultrasound measurement of muscle accretion is a better marker for lean body growth.

Exhaled breath condensate nitrite in premature infants with bronchopulmonary dysplasia.

BACKGROUND: Tracheal aspirate is the conventional method to measure biomarkers of inflammation and oxidation from premature infants on mechanical ventilation at risk for bronchopulmonary dysplasia (BPD), but this method is invasive. Exhaled breath condensate (EBC) is a novel, non-invasive method that has been used in older populations. Nitrite, a stable metabolite of nitric oxide (NO), is elevated in inflammatory conditions. We aim to investigate the feasibility of EBC nitrite collection from ventilated premature infants and to quantify EBC nitrite in infants with and without BPD. We hypothesize that EBC nitrite correlates with TA nitrite, and that EBC nitrite in the first week of life is higher in infants who will develop BPD than those without BPD. METHODS: In a pilot prospective cohort study, TA and EBC were collected in the first week of life from mechanically ventilated premature infants. Nitrite levels were measured using chemiluminescence. RESULTS: EBC nitrite significantly correlated with TA nitrite (r = 0.45, p = 0.025). Of 40 infants, 33 (82.5%) developed BPD. EBC and TA nitrite levels collected in the first week of life had a higher trend in infants with BPD than those without BPD (p = 0.23 and 0.38 respectively). CONCLUSIONS: Higher trend of EBC nitrite in the first week of life was associated with the development of BPD. Correlation of nitrite level in EBC with that in TA (conventional method) highlights the utility of EBC as an alternative, non-invasive method to measure inflammation. Further refinement of conditions and timing may optimize the predictive value of EBC nitrite.

Adult vaccination against tetanus and diphtheria: the European perspective.

Besides immunizations against influenza, Streptococcus pneumoniae and herpes zoster, which are recommended specifically for elderly people, regular booster vaccinations against tetanus, diphtheria and in some cases pertussis and polio are recommended in many European countries for adults, including elderly people. Vaccination recommendations for adults differ greatly between individual countries and coverage data is scarce. Tetanus-specific antibody concentrations are generally higher than diphtheria-specific antibodies, and a substantial proportion of adults, and particularly of elderly people, do not have protective antibody concentrations against diphtheria. Antibody levels increase upon booster vaccination in all age groups, but diphtheria-specific antibody concentrations remain below protective levels in some older individuals, even immediately after vaccination and long-term protection is frequently not achieved. Future vaccination strategies should therefore include regular and well-documented booster shots, e.g. against tetanus and diphtheria, throughout life.

How immunosuppressive therapy affects T cells from kidney transplanted patients of different age: the role of latent cytomegalovirus infection.

The average age of patients receiving renal transplantation is increasing as programmes have been established which support the donation of organs from elderly donors to older recipients. Little is known about the effect of immunosuppressive therapy on the immune system of older patients. In this study, T cell function and the composition of the T cell repertoire were analysed in immunosuppressed renal transplant recipients of different age and cytomegalovirus (CMV) status in comparison to age- and CMV-matched controls. Independent of age and CMV status, the production of interleukin (IL)-2 and interferon (IFN)-γ by T cells was decreased in the patient groups and autologous serum from patients was capable of inhibiting the proliferation of CD3⁺ T cells. CXCR5 expression on T cells was increased in patients versus controls reflecting reduced endogenous IL-2 signalling under immunosuppressive therapy. In CMV-seronegative patients kidney transplantation and immunosuppressive therapy did not induce changes in the CD8⁺ T cell pool, but there was a moderate increase in CD4⁺CD28⁻ effector T cells when compared to age-matched controls. In contrast, latent CMV infection triggered a shift from early to late differentiated CD4⁺ and CD8⁺ T cells in patients and controls. This shift was most pronounced in elderly transplant patients under immunosuppressive therapy. In conclusion, our results demonstrate that immunosuppressive therapy following kidney transplantation is effective in patients older than 65 years. Latent CMV infection, however, accelerates age-related changes in the T cell repertoire in elderly people under immunosuppressive therapy. These patients should therefore be monitored with special care.

Resuscitation at the limit of viability: trapped between a rock and a hard place.

BACKGROUND: Current professional guidelines, such as the Neonatal Resuscitation Program, specify significant roles for parents in decision-making at periviability. However, current federal regulations and some legal precedents indicate that resuscitation decisions should be made by the physician at the time of delivery, based on physical assessment of the infant. The enforcement of such approach would potentially increase the resuscitation of infants with poor prognoses. OBJECTIVE: To characterize the resuscitation practices of neonatologists attending deliveries of premature infants at the borderline of viability, in the context of current federal legislation. STUDY DESIGN: A questionnaire was administered to directors of all level III neonatal intensive care units in the state of New Jersey, eliciting resuscitation decisions for hypothetical birth scenarios as well as knowledge of legal statutes. RESULTS: Resuscitation decisions for infants born at 24 weeks of gestational age were not associated with parental wishes. In contrast, parental requests were significantly associated with decisions whether to treat infants born at 22 and 23 weeks gestation. Most neonatologists believed they were knowledgeable about federal legislation, but that knowledge did not change the way they practiced. CONCLUSIONS: Our findings suggest that resuscitation of premature infants at 24 weeks gestation is the standard of care in New Jersey, a socioeconomically and ethnically diverse state that may represent broader national trends. The high compliance with parental wishes at 22 or 23 weeks is probably related to physicians' expectation of poor outcomes at these gestational ages. This approach is consistent with current recommendations of the Neonatal Resuscitation Program but may not be compatible with existing federal statutes and legal precedent.

Vaccines for the elderly.

Vaccination is the most efficient strategy to prevent infectious disease. The increased vulnerability to infection of the elderly makes them a particularly important target population for vaccination. However, most vaccines are less immunogenic and efficient in the elderly because of age-related changes in the immune system. Vaccination against influenza, Streptococcus pneumoniae and varicella zoster virus is recommended for the elderly in many countries. Various strategies such as the use of adjuvants and novel administration routes are pursued to improve influenza vaccination for the elderly and recent developments in the field of pneumococcal vaccination led to the licensure of protein-conjugated polysaccharide vaccines containing up to 13 serotypes. As antibody titres are generally lower in the elderly and-particularly for inactivated vaccines-decline fast in the elderly, regular booster immunizations, for example against tetanus, diphtheria and, in endemic areas, tick-borne encephalitis, are essential during adulthood to ensure protection of the elderly. With increasing health and travel opportunities in old age the importance of travel vaccines for persons over the age of 60 is growing. However, little is known about immunogenicity and efficacy of travel vaccines in this age group. Despite major advances in the field of vaccinology over the last decades, there are still possibilities for improvement concerning vaccines for the elderly. Novel approaches, such as viral vectors for antigen delivery, DNA-based vaccines and innovative adjuvants, particularly toll-like receptor agonists, will help to achieve optimal protection against infectious diseases in old age.

Performance of carbon arc-discharge nanotubes to hydrogen energy storage.

Adsorption properties of gram-scale samples of different kind of arc discharge nanotubes were studied, namely: (A) raw collaret collected on the cathode, (B) raw soots collected on the lateral reactor wall, (C) thermally treated soot, and (D) thermally then chemically treated soot. The morphology, structure, and composition of these materials were characterized by SEM, TEM, TGA, and BET. In addition, hydrogen adsorption isotherms were recorded experimentally for A, B, and D samples over the pressure range of 0 to 55 bar at ambient temperature. Our experiments indicated a maximum-yet weak-hydrogen storage at room temperature of approximately 0.13 H2 wt% for the purified product (D).

Capillary condensation and adsorption of binary mixtures.

The adsorption of equimolar binary mixtures of hydrogen-carbon dioxide, hydrogen-methane, and methane-carbon dioxide in porous material models is determined by grand canonical Monte Carlo simulations. The material models have an adsorbent surface similar to that of nanofibers with a herringbone structure. Our main result, which is relevant for hydrogen purification and carbon dioxide capture, is that the adsorption selectivities calculated for the mixtures can differ significantly from those deduced from simulations of the adsorption of pure gases, in particular, when one of the adsorbed gases presents a capillary condensation induced by confinement within the pore network. A comparison of our data is also made with theoretical models used in the literature for predicting the properties of the mixture adsorption.

Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants.

Potential mechanisms underlying impaired chemotactic responsiveness of neonatal neutrophils were investigated. Two distinct chemoattractants were compared: bacterially derived N-formyl-methionyl-leucyl-phenylalanine (fMLP) and a unique chemotactic monoclonal antibody, designated DL1.2, which binds to a neutrophil antigen with an apparent molecular mass of 120 kDa. Chemotaxis of neutrophils toward fMLP, as well as DL1.2, was reduced in neonates when compared with adult cells. This did not appear to be a result of decreased fMLP receptor or DL1.2 antigen expression by neonatal neutrophils. fMLP, but not DL1.2, induced a rapid increase in intracellular calcium in adult and neonatal cells, which reached a maximum within 30 s. The calcium response of cells from neonates to fMLP was reduced when compared with adult cells, and an unresponsive subpopulation of neonatal neutrophils was identified. NF-kappaB nuclear binding activity induced by fMLP and DL1.2, as well as expression of the p65 NF-kappaB subunit and IkappaB-alpha, was also significantly reduced in neonatal cells, when compared with adult cells. In contrast, although fMLP, but not DL1.2, activated p42/44 and p38 mitogen-activated protein (MAP) kinases in neutrophils, no differences were observed between adults and neonates. Chemotaxis of adult and neonatal neutrophils toward fMLP and DL1.2 was also blocked to a similar extent by inhibitors of phosphatidylinositol 3-kinase, as well as an inhibitor of NF-kappaB. These findings indicate that reduced chemotactic responsiveness in neonatal neutrophils is a result of, at least in part, aberrations in chemoattractant-induced signaling. However, the biochemical pathways mediating this defect appear to be related to the specific chemoattractant.

Functional heterogeneity in liver and lung macrophages.

Although initially considered merely "scavenger cells" that participate in immunologic responses only after B and T lymphocytes have performed their biological tasks, more recent evidence suggests that macrophages play a key role in host defense as well as in the maintenance of normal tissue structure and function. For macrophages to perform their biological functions, they must be activated. This involves up-regulation of an array of signaling pathways resulting in altered gene expression and increased biochemical and functional activity. Macrophages have been identified in almost all tissues of the body. However, the basal activity of these cells, as well as their ability to respond to inflammatory mediators, varies considerably with their location. In addition, even within a particular tissue, there is evidence of macrophage heterogeneity. The largest populations of macrophages in the body are located in the liver and lung. Because of the unique attributes of these tissues, hepatic and pulmonary macrophages play essential roles not only in nonspecific host defense but also in the homeostatic responses of these tissues. In this review, the functional and biochemical activities of macrophages localized in the liver and lungs are compared. Evidence suggests that these represent distinct cell populations with unique functions and responsiveness to inflammatory agents.

Urinary thiobarbituric acid-reacting substances as potential biomarkers of intrauterine hypoxia.

BACKGROUND: Currently available clinical tools cannot accurately identify the extent of perinatal hypoxic injuries. During hypoxia, reactive oxygen species cause lipid peroxidation of cell membranes, yielding oxidation products that constitute thiobarbituric acid-reacting substances (TBARS). OBJECTIVE: To see if the concentrations of TBARS excreted in urine would be elevated during the first day of life in term and preterm infants following chronic hypoxia or acute asphyxia. DESIGN: Thiobarbituric acid-reacting substances levels were measured by a spectrophotometric assay in urine samples collected from term and near-term (>/= 34 weeks gestation, n = 22), and preterm (<34 weeks gestation, n = 52) infants on the first day of life. PATIENTS: Infants were admitted to the St Peter's University Hospital (New Brunswick, NJ) neonatal intensive care unit from July 1997 to January 1999. Acute asphyxia was defined as umbilical cord blood pH values less than 7.05, or Apgar scores of less than 5 at 5 minutes. Chronic hypoxia was defined as intrauterine growth retardation or low birth weight (small for gestational age) associated with pregnancy-induced hypertension or reversal of umbilical arterial blood flow. RESULTS: Among term infants, urinary TBARS levels were significantly increased following acute asphyxia (P =.02). Levels of TBARS also tended to be elevated following chronic hypoxia. Urinary TBARS levels in term infants tended to be increased in those requiring mechanical ventilation (P =.05) or delivery room resuscitation (P =.15), as well as in those passing intrauterine meconium (P =.13) or having clinical evidence of hypoxic-ischemic encephalopathy (P =.24). CONCLUSIONS: The results show a correlation between elevated urinary TBARS levels in term and near-term infants, and perinatal hypoxia (as determined by low Apgar scores or umbilical cord blood acidosis). We speculate that TBARS concentrations may be useful as a biomarker for perinatal hypoxic injury in newborns. Further studies are needed to determine whether elevations in TBARS levels are better predictors of the extent of hypoxic injury than existing markers.

Pharmacologic therapy of persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/m2/d [corrected]. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P =.016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

The toxicology of inhaled nitric oxide.

Inhaled nitric oxide is a targeted pulmonary vasodilator that improves clinical outcomes for newborn patients with persistent pulmonary hypertension of the newborn, and may be effective in treating some premature patients with acute respiratory distress syndrome or lung disease of prematurity. Nitric oxide is now recognized as playing an important role in the regulation of diverse physiological processes. However, the pharmacological properties of inhaled nitric oxide are not easy to separate from its toxicological effects. For example, the intended effect of inhaled nitric oxide, vasodilation in the lung, is mediated, in part, by increased cellular cyclic GMP (cGMP). However, increased cGMP can also interfere with normal cellular proliferation. Nitric oxide has also been shown to cause DNA strand breaks and/or base alterations that are potentially mutagenic. Inhaled nitric oxide can rapidly react with oxygen in the lung to form nitrogen dioxide, which is a potent pulmonary irritant. Nitric oxide also reacts with superoxide anion to form peroxynitrite, a cytotoxic oxidant that can interfere with surfactant functioning. The overall effect of inhaled nitric oxide in potentiating or attenuating inflammation and oxidative damage in diseased lung is dependent on the dose administered. Furthermore, despite rapid inactivation by circulating hemoglobin, inhaled nitric oxide exerts effects outside the lung, including blocking platelet aggregation, causing methemoglobinemia, and possibly inducing extrapulmonary vasodilation. The toxicology of inhaled nitric oxide is not completely understood and must be considered in the design of protocols for its safe and effective clinical use.

Effects of perinatal hypoxia on serum unbound free fatty acids and lung inflammatory mediators.

Cellular injury during tissue hypoxia is due, in part, to reactive intermediates released by activated leukocytes. We found that the inflammatory mediators tumor necrosis factor (TNF)-alpha, IL-6, and IL-1beta are elevated in situ in lung macrophages on day 14 following exposure of rats to intermittent or chronic hypoxia from birth. Because inflammatory mediators can increase lipolysis in adipocytes, we also measured serum unbound free fatty acids (FFAu)--the biologically active compartment of FFA--in rat pups exposed to intermittent or chronic hypoxia. FFAu values were markedly elevated during the first 2 days of life in all rats, displaying an approximately 3-fold decrease from day 2 to day 3. Exposure to chronic hypoxia significantly increased FFAu levels measured on day 13. Since elevated serum FFAu are known to suppress leukocyte activation, we speculate that increased FFAu levels represent a mechanism for attenuating inflammation and tissue injury following sublethal hypoxia in the perinatal period, either physiologically in the immediate newborn period, or as a late response to ongoing hypoxic insult.

Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation.

OBJECTIVE: To determine the effect of glutamine suspension on mucositis associated with the administration of high-dose preparative regimens for bone marrow transplantation. METHODS: We performed a retrospective analysis of 21 consecutive patients receiving high-dose paclitaxel and melphalan as the preparative regimen for autologous peripheral blood stem-cell transplantation for metastatic breast cancer between January 1997 and December 1997. Glutamine suspension was given as swish-and-swallow administration every four hours around the clock starting day-7, for a total dose of 24 g/d. RESULTS: The group given oral glutamine suspension demonstrated significantly fewer days of mucositis and a lower maximum grade of mucositis. The treatment group also had fewer days of parenteral morphine for pain relief. The group that did not receive glutamine required an average of 5.22 days of patient-controlled analgesia (PCA) morphine; the glutamine group did not require PCA morphine. The total days of narcotic pain relief were decreased in the glutamine group; however, this did not reach statistical significance. Qualitatively, the patients in the glutamine group had less oral ulceration and bleeding, and were able to tolerate liquids sooner than those in the nonglutamine group. Patients tolerated the glutamine suspension well. CONCLUSIONS: This study showed that around-the-clock administration of oral glutamine may decrease both the severity and duration of mucositis associated with high-dose bone marrow transplant preparative regimens. The decrease in severity and duration of mucositis translated into reduced parenteral narcotic use. A prospective, randomized, controlled trial is needed to determine future applications of glutamine in the support of patients undergoing high-dose chemotherapy.

Antecedents and neonatal consequences of low Apgar scores in preterm newborns: a population study.

BACKGROUND: To examine the antenatal and early neonatal correlates of low Apgar scores (<3 and <6 at 1 and 5 minutes) in preterm newborns (23-34 weeks' gestation). OBJECTIVE: The use of Apgar scoring for premature newborns remains widespread, despite controversy regarding its reliability as a measure of morbidity and mortality in the neonatal period. DESIGN: A cohort of 852 preterm newborns born during a 34-month period between 1984 and 1987 was studied. Newborns were stratified into 2 groups by gestational age (23-28 weeks and 29-34 weeks), and data were analyzed, controlling for gestational age in single weeks. SETTING: Two academic and 1 community hospital, which together accounted for 83% of all preterm births in a tri-county area of central New Jersey during the study period. PATIENTS: All premature newborns (birth weight <2000 g and gestational age <35 weeks) born in the participating hospitals during the study period were evaluated. MAIN OUTCOME MEASURES: Antecedents included maternal illness during pregnancy, maternal complications of labor and delivery, and fetal heart rate abnormalities during labor and delivery. Consequences included delivery room resuscitation, abnormal physical findings, diagnoses, and therapeutic interventions in the first 6 to 8 hours of life. RESULTS: Premature newborns with low Apgar scores received more cardiopulmonary resuscitation in the delivery room and in the first 6 to 8 hours of neonatal intensive care. Mortality was significantly increased among newborns with low Apgar scores (54% vs. 26% in the 23- to 28-week stratum, 30% vs 6% in the 29- to 34-week stratum). Newborns with low Apgar scores in the 29- to 34-week stratum more often required intubation, positive pressure ventilation, and umbilical vessel catheterization. Newborns with low Apgar scores had higher rates of bradycardia, pneumothoraces, acidosis, and increased oxygen requirement during the first 6 to 8 hours of life. Maternal illness, complications of labor and delivery;, and fetal heart rate decelerations did not correlate with subsequent Apgar scores of newborns. The presence of severe bradycardia (<90/min) and fetal heart rate accelerations correlated with low Apgar scores in the 29- to 34-week group. CONCLUSION: Low Apgar scores are associated with increased neonatal morbidity and mortality in preterm newborns. Antenatal maternal history, and pregnancy complications are not clearly associated with low Apgar scores. Therefore, the Apgar score is a useful tool in assessing neonatal short-term prognosis and the need for intensive care among preterm newborns.