Infant mortality in the United States.

The infant mortality rate (IMR) of 6.0 per 1000 live births in the United States in 2013 is nearly the highest among developed countries. Moreover, the IMR among blacks is >twice that among whites-11.11 versus 5.06 deaths per 1000 live births.This higher IMR and racial disparity in IMR is due to a higher preterm birth rate (11.4% of live births in 2013) and higher IMR among term infants. The United States also ranks near the bottom for maternal mortality and life expectancy among the developed nations-despite ranking highest in the proportion of gross national product spent on health care. This suggests that factors other than health care contribute to the higher IMR and racial disparity in IMR. One factor is disadvantaged socioeconomic status. All of the actionable determinates that negatively impact health-personal behavior, social factors, heath-care access and quality and the environment-disproportionately affect the poor. Addressing disadvantaged socioeconomic status by improving access to quality health care and increasing social expenditures would have the greatest impact on the USA's IMR and racial disparity in IMR.

Early radiologic evidence of severe respiratory distress syndrome as a predictor of nasal continuous positive airway pressure failure in extremely low birth weight newborns.

OBJECTIVE: To determine whether early radiologic evidence of severe respiratory distress syndrome (RDS) is predictive of nasal continuous positive airway pressure (CPAP) failure in extremely low birth weight (ELBW) infants during the first 72 h of age. STUDY DESIGN: Retrospective analysis of 235 consecutively inborn ELBW infants who received initial support with CPAP. CPAP success (n=151) and CPAP failure (n=84) groups were designated according to outcome within the first 72 h of age. We assessed the ability of radiologic evidence of severe RDS in the initial chest radiograph, alone and in combination with other variables available in the first hours of life, to predict CPAP failure. RESULT: Severe RDS had a positive predictive value (PPV) of 0.81 (95% confidence interval (CI) 0.64, 0.92) for CPAP failure. The combination of severe RDS and gestational age (GA) ⩽ 26 weeks had a PPV of 0.92 (95% CI 0.68, 0.96). CONCLUSION: Early radiologic evidence of severe RDS is predictive of CPAP failure, especially in infants with GA ⩽ 26 weeks.

Neonatal bacterial meningitis.

Despite major improvements in infant intensive care, neonatal meningitis remains a devastating disease. Survivors of bacterial meningitis are at high-risk for life-long neurological handicaps, and despite a reduction in mortality, the morbidity of neonatal meningitis has not changed substantially over the last thirty years. A substantial improvement in outcome is unlikely to result from further refinements in ICU technology or new antibiotics. However, recent advancements in our understanding of the pathogenesis of meningitis and the pathophysiology of brain injury in meningitis may provide the opportunity to interrupt the mechanisms that allow bacteria to enter the central nervous system and initiate the inflammatory response. Strategies aimed at modulating the inflammatory response must be chosen carefully, so as not to disrupt normal host responses needed for the infant to recover from the infectious episode.

Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia.

OBJECTIVE: In recent years, the increased prevalence of breastfeeding in conjunction with early discharge practices has increased the risk for marked hyperbilirubinemia in neonates. This has resulted in the potential for bilirubin brain injury in affected infants. The purpose of this study was to identify all infants >/=36 weeks' gestational age with bilirubin levels >25 mg/dL and evaluate them for early and late evidence of bilirubin brain injury. METHODS: We reviewed the charts of all infants (from 1993-1996) >/=36 weeks' gestational age who were readmitted to the hospital during the first week of life with bilirubin levels >25 mg/dL. Readmission records were reviewed for early signs of bilirubin encephalopathy. Magnetic resonance imaging (MRIs) and Brainstem auditory-evoked responses (BAERs) were reviewed for evidence of bilirubin toxicity. At follow-up, study infants had a complete neurodevelopmental examination, repeat MRIs, and behavioral hearing evaluations. RESULTS: From 1993 to 1996, we identified 6 term and near-term infants readmitted to the hospital within the first week of life with peak bilirubin values ranging from 26.4 mg/dL (451 micromol/L) to 36.9 mg/dL (631 micromol/L). Five of 6 infants had bilirubin values >30 mg/dL (513 micromol/L). All were exclusively breastfed or fed a combination of breast and bottle feedings. Five of 6 infants presented with abnormal neurologic signs. Four infants had initial MRIs, 3 of whom had increased signal intensity in the basal ganglia consistent with kernicterus. Two infants had abnormal BAERs; both also had abnormal MRIs. Five of 6 infants received exchange transfusions and all were treated with phototherapy and intravenous fluids. Follow-up examinations between 3 months and 2 years showed resolution of clinical signs in all but 1 infant. Four infants had a subsequent normal MRI and 1 had residual hearing impairment. One infant demonstrated severely abnormal developmental evaluations, as well as both an abnormal initial MRI and BAERs. Follow-up MRI showed evidence of encephalomalacia with changes not characteristic of kernicterus. CONCLUSIONS: We observed transient neurologic abnormalities in 5 of 6 infants readmitted to the hospital during the first week of life with marked hyperbilirubinemia. The abnormalities resolved following aggressive management using hydration, phototherapy, and exchange transfusion and may not correlate with long-term prognosis. Less aggressive therapy may be associated with residual neurologic abnormalities. We speculate that inadequate establishment of breastfeeding coupled with early discharge practices may play a role in the development of marked hyperbilirubinemia in these infants.

Pulmonary hypertension in children following extracorporeal membrane oxygenation therapy and repair of congenital diaphragmatic hernia.

OBJECTIVE: Pulmonary hypertension (PHT) is present in all children at birth, but its degree and rate of resolution in infants diagnosed with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) need to be established. STUDY DESIGN: Twenty-one ECMO/CDH survivors (aged 3.2 +/- 1.4 years) were prospectively evaluated by Doppler echocardiography (ECHO) to determine the presence of PHT. Twenty children without structural heart disease were used as controls. Study patients received a physical examination and an electrocardiograph examination, and their charts were reviewed for neonatal course data. Patients found to have PHT by ECHO received a complete history and exercise treadmill/oxygen desaturation study. RESULTS: Eight of the 21 patients (38%) met echocardiographic criteria for PHT. No neonatal course data were found to be predictive of eventual PHT status. There was no correlation between physical examination or electrocardiographic findings and PHT. Complete histories showed five of the eight patients with PHT had some degree of exercise intolerance and seven had wheezing. Two of the seven patients studied on the treadmill desaturated 5% or greater from baseline. CONCLUSION: There is evidence that PHT either persists or recurs in a significant portion of the ECMO/CDH population and may remain symptomatic well beyond the neonatal period.

Enteric defensin expression in necrotizing enterocolitis.

Immaturity of local innate defenses has been suggested as a factor involved in the pathophysiology of necrotizing enterocolitis (NEC). The mRNA of enteric human defensins 5 (HD5) and 6 (HD6), antibiotic peptides expressed in Paneth cells of the small intestine, have significantly lower levels of expression in fetal life compared with the term newborn and adult. In the current study, intracellular HD5 was demonstrated by immunohistochemistry at 24 wk of gestation, but at low levels, consistent with findings at the mRNA level. These data suggest that the low level enteric defensin expression, characteristic of normal intestinal development, may contribute to the immaturity of local defense, which predisposes the premature infant to NEC. To test if levels of defensin expression are altered in NEC, specimens from six cases of patients with NEC and five control subjects (four patients with atresia and one with meconium ileus) were analyzed to determine HD5 and HD6 mRNA levels by in situ hybridization. Compared with the control group, the level of enteric defensin expression per Paneth cell assessed by image analysis was increased 3-fold in cases of NEC (p = 0.02, analysis of variance and covariance). In addition, the number of Paneth cells was increased 2-fold in the small intestinal crypts of NEC specimens compared with those of control subjects (p < 0.01, covariance analysis). In healthy tissue, peptide levels within Paneth cells paralleled mRNA levels through development. In tissue from infants with NEC, the steady state level of intracellular peptide was not increased in conjunction with the observed rise in defensin mRNA. A straightforward interpretation of this finding is that HD5 is actively secreted in this setting and the Paneth cells maintain a constant steady state level of intracellular peptide, but the possibility of translational regulation of peptide expression is also consistent with these data. The associations between NEC and enteric defensin expression reported here offer support for future studies to address the role of these endogenous host defense factors in the pathophysiology of this disease.

Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.

BACKGROUND: Persistent pulmonary hypertension of the newborn causes systemic arterial hypoxemia because of increased pulmonary vascular resistance and right-to-left shunting of deoxygenated blood. Inhaled nitric oxide decreases pulmonary vascular resistance in newborns. We studied whether inhaled nitric oxide decreases severe hypoxemia in infants with persistent pulmonary hypertension. METHODS: In a prospective, multicenter study, 58 full-term infants with severe hypoxemia and persistent pulmonary hypertension were randomly assigned to breathe either a control gas (nitrogen) or nitric oxide (80 parts per million), mixed with oxygen from a ventilator. If oxygenation increased after 20 minutes and systemic blood pressure did not decrease, the treatment was considered successful and was continued at lower concentrations. Otherwise, it was discontinued and alternative therapies, including extracorporeal membrane oxygenation, were used. RESULTS: Inhaled nitric oxide successfully doubled systemic oxygenation in 16 of 30 infants (53 percent), whereas conventional therapy without inhaled nitric oxide increased oxygenation in only 2 of 28 infants (7 percent). Long-term therapy with inhaled nitric oxide sustained systemic oxygenation in 75 percent of the infants who had initial improvement. Extracorporeal membrane oxygenation was required in 71 percent of the control group and 40 percent of the nitric oxide group (P=0.02). The number of deaths was similar in the two groups. Inhaled nitric oxide did not cause systemic hypotension or increase methemoglobin levels. CONCLUSIONS: Inhaled nitric oxide improves systemic oxygenation in infants with persistent pulmonary hypertension and may reduce the need for more invasive treatments.

Effect of gamma interferon on expression of Fc gamma receptors in monocytes of newborn infants and adults.

Fc gamma receptors provide an essential link between cellular and humoral immunity, and little is known about their expression in monocytes of newborn infants. We compared baseline and gamma interferon (IFN-gamma)-induced expression of Fc gamma RI and Fc gamma RII protein and Fc gamma RI mRNA in monocytes from healthy, term infants and adults. Fluorescence-activated cell sorter analysis demonstrated that baseline expression of monocyte Fc gamma RI in newborn infants was not significantly different from that in adults, while Fc gamma RII protein expression in monocytes derived from newborns was significantly higher than that for adults (mean channel fluorescence [MCF] for newborns and adults, 5.53 and 4.50, respectively [P = 0.039]). In vitro treatment with recombinant IFN-gamma increased the expression of Fc gamma RI in monocytes of newborns and adults to the same extent (2.4- and 2.2-fold increase in MCF in newborns and adults, respectively, at 42 h). We developed a semiquantitative fluorescence reverse transcriptase PCR which demonstrated a significant increase in mRNA for Fc gamma RI in monocytes of newborns and adults with in vitro IFN-gamma exposure, indicating that IFN-gamma acts by increasing the transcription or transcript stability of Fc gamma RI mRNA. While there was no significant effect of IFN-gamma treatment on Fc gamma RII expression in monocytes from adults, there was a 20% increase in Fc gamma RII in monocytes from newborns (P = 0.009). Monocytes from healthy, term newborns and adults exhibit comparable baseline and IFN-gamma-induced levels of expression of Fc gamma RI and higher baseline and IFN-gamma-induced levels of expression of Fc gamma RII.

Survivors of extracorporeal membrane oxygenation at 1 year of age: the relationship of primary diagnosis with health and neurodevelopmental sequelae.

OBJECTIVE: Although extracorporeal membrane oxygenation (ECMO) has been responsible for the improved survival of infants with cardiorespiratory failure, its use over the last decade has raised concern as to the health of the survivors and the severity of neurodevelopmental sequelae. Though infants meeting ECMO criteria have a variety of reasons prompting the use of this therapy, most studies to date have simply reported outcome on the entire population that has survived without regard to the original nature of the child's illness. The purpose of this study was to determine the type and extent of health-related problems and neurodevelopmental sequelae in infants requiring ECMO therapy and the association of these findings with the infants' primary diagnosis. METHODS: Eighty-two neonates required ECMO therapy between May 1990 and December 1993. The most common diagnosis prompting ECMO therapy included 26% with meconium aspiration syndrome, 34% with congenital diaphragmatic hernia (CDH), 16% with persistence of the fetal circulation, and 9% with sepsis. Information concerning the hospital course was obtained through chart review, and the infants were seen at 6 and 12 months of age for medical and neurodevelopmental follow-up. Data were analyzed using descriptive statistics and Fisher's exact test, t-tests, and analysis of variance where appropriate. Assessment of hospital course and discharge data focused on the four main diagnostic groups, whereas follow-up data were further limited to the two most frequently encountered groups (meconium aspiration syndrome and CDH). RESULTS: Overall survival was 79%. Significant differences in survival were noted based on primary diagnostic category. Those with CDH fared the worst, with an overall survival rate of 68% and a more complicated hospital course with a longer duration of ECMO. At discharge, the CDH group demonstrated a greater incidence of bronchopulmonary dysplasia, gastroesophageal reflux, feeding dysfunction, and hypotonia. No significant differences were noted in the incidence of intraventricular hemorrhage, cerebral infarction, extra-axial fluid collection, or seizures. Hearing loss was uncommon. During the first year of life, although no differences were noted in growth rate, infants in the CDH group continued to experience a higher incidence of gastroesophageal reflux (43%) and feeding dysfunction, with 36% of this group requiring tube feedings for nourishment. Although 40% of the entire ECMO population was diagnosed with bronchopulmonary dysplasia before initial discharge, by 1 year of age, 50% of those with CDH versus 17% of those with meconium aspiration syndrome continued to be clinically symptomatic. Although the ECMO population as a whole scored in the normal range developmentally, CDH infants had significantly lower motor and slightly lower cognitive scores at 1 year of age. Despite finding abnormal muscle tone in a high percentage of the entire ECMO population at discharge, most demonstrated resolution by 1 year of age. Of the CDH infants, however, 75% continued to evidence some degree of hypotonicity, which affected acquisition and quality of gross motor skills. CONCLUSION: Despite the impact that ECMO has had on the survival of infants with severe respiratory failure, the efficacy of ECMO cannot be assessed accurately without an analysis of the extent and morbidity in the surviving population. Most centers are reporting relatively low morbidity for the entire ECMO population. However, upon separating this population into primary diagnostic categories, we found that the CDH population encountered a greater number of neurodevelopmental, respiratory, and feeding abnormalities during the first year of life. The reasons for these differences are unclear but may be related to the severity of the primary illness itself or the variables associated with prolonged ECMO therapy. Stratifying outcome by primary diagnosis gives the health care provider more information to improve

Endotoxin, tumor necrosis factor, and dexamethasone effects on human endothelial cell fibronectin dynamics: synthesis, matrix assembly, and receptor expression.

The three inflammatory modulators endotoxin, tumor necrosis factor (TNF) alpha, and dexamethasone (DEX) were studied for their effects on fibronectin (FN) dynamics in human umbilical vein endothelial cells. Cell culture supernatants were analyzed for new soluble pool FN synthesis. Endotoxin (LPS) (10 micrograms/mL) decreased the newly synthesized soluble pool of FN (p < 0.05). An increase in soluble FN was demonstrated with 1 and 10 ng/mL TNF alpha (p < 0.05). DEX decreased newly synthesized endothelial cell (EC) FN in the soluble pool at 4, 40, and 400 micrograms/mL (p < 0.05). Extracellular matrix FN content was examined using immunofluorescence. The thick FN mesh seen in control cells contrasted with a decreased FN matrix after treatment with each of the three study agents. Immunoprecipitation of the FN receptor alpha 5 beta 1 integrin from [35S]methionine-labelled cell extracts demonstrated down regulation of receptor expression by both TNF alpha and DEX as compared with control samples. These data indicate that LPS, TNF alpha, and DEX may weaken EC-substratum adhesion by differential effects on FN synthesis and secretion, FN incorporation into the extracellular matrix, and down regulation of FN receptor expression.

Outcome for infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: the first year.

Congenital diaphragmatic hernia (CDH) has been associated with a high mortality rate. The purposes of this study were to determine the impact of extracorporeal membrane oxygenation (ECMO) on the survival of infants with CDH and to document the sequelae and 1-year neurodevelopmental outcome for CDH infants who required ECMO. Thirty neonates with CDH were admitted between May 7, 1990 and October 1, 1992. Twenty required ECMO and were enrolled in our neonatal follow-up program. Information about the infants' neonatal course was obtained from chart review, and the infants were seen at 3, 6, and 12 months of age for medical and neurodevelopmental follow-up. Primary diaphragmatic repair was performed in 13 infants. Five required Goretex graft reconstruction (GGR), and two did not have repair. Sixteen (80%) of the 20 infants who required ECMO survived. The overall survival rate increased from 31% (10 of 32) in the 5 years previous to the start of the ECMO program to 63% (19 of 30) since then (P = .01). The most common sequelae noted by the time of discharge included gastroesophageal reflux (GER; 81%), the need for tube feeding (69%), and chronic lung disease (CLD; 62%). At 1 year of age, mean cognitive skills were average (87 +/- 23) and motor skills were borderline (75 +/- 24) according to the Bayley Scales of Infant Development. Hypotonia was present in 10 of 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants.

We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I-IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells.

Enhancement in vitro of the low interferon-gamma production of leukocytes from human newborn infants.

Interferon-gamma (IFN-gamma), a lymphokine produced by lymphocytes with the help of monocytes, is essential for host resistance to intracellular pathogens. Leukocytes from normal term newborn infants cannot produce IFN-gamma in vitro in response to stimulation by antigen or mitogens in vitro or in vivo. We investigated the production of IFN-gamma in vitro using endotoxin from Salmonella typhimurium as a stimulus. In contrast to those from adults, mononuclear cells derived from the cord blood of newborn infants did not produce IFN-gamma in response to this endotoxin. We investigated the contribution of the functional immaturity of cord blood monocytes to this relative inability to produce IFN-gamma. Aging of the monocytes for 2 weeks in vitro or treatment of freshly isolated cord blood monocytes with conditioned medium (from cultures of mononuclear cells from healthy adults) greatly enhanced IFN-gamma production stimulated by endotoxin. Furthermore, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), or IFN-gamma was able to substitute in part for the conditioned medium from adult cells. Thus correction of the functional immaturity of monocytes derived from newborn infants can result in enhanced production of IFN-gamma in vitro.

Thiol suppression of human immunodeficiency virus type 1 replication in primary cord blood monocyte-derived macrophages in vitro.

We investigated the effects of glutathione (GSH), the major naturally occurring thiol, and a pharmacologic thiol precursor of GSH, N-acetyl cysteine (NAC), on the expression of human immunodeficiency type 1 (HIV-1) in primary cord blood and adult donor monocyte-derived macrophages (MDM). HIV-1 infection of cord blood and adult MDM was accomplished after incubating 10-15-d-old cultures for 4 h with a monocyte-tropic strain of HIV-1 (Bal). After 1 wk in culture cell supernatants were tested for reverse transcriptase (RT) activity. MDM were exposed to 5, 10 and 20 mM concentrations of both GSH and NAC before infection, during infection, and after infection was established. GSH and NAC suppressed the replication of HIV-1 in both primary cord blood and adult donor MDM in a concentration dependent fashion. These suppressive effects were more pronounced in cord-derived cells than in adult-derived cells. In cells treated with GSH or NAC before infection, there was no significant rise in RT activity as compared with controls. Similarly, when cells were treated with GSH and NAC and simultaneously infected, there was also no significant rise in RT activity after 1 wk in culture. In cells treated after infection was established, RT values were suppressed 80-90% that of untreated controls. This effect persisted for 1-2 wk after exposure to GSH and NAC. Untreated controls demonstrated syncytium formation and lost characteristics of spreading and elongation 2 wk after HIV-1 infection, whereas most of the treated cells remained free of syncytium and retained cytoplasmic spreading, adherence, and elongation. These data are consistent with other studies of thiol suppression of HIV-1 replication and demonstrate a similar observation for primary cultured cord MDM. These results may offer new approaches toward cellular protection after infection with HIV-1.

Adherence of human newborn infants' monocytes to matrix-bound fibronectin.

The localization of monocytes to sites of inflammation is mediated by interactions with extracellular matrix components including fibronectin, a nonimmune opsonin with binding sites for collagen, fibrin, heparin, and cell surfaces. This study demonstrates that newborn infants' monocytes bind to both gelatin (i.e., denatured collagen) and matrix-bound fibronectin to a degree comparable to that of adult-derived cells.

Effects of a night-float system on resident activities and parent satisfaction.

Night-float systems have recently been proposed as a way to reduce resident stress resulting from irregular sleep patterns. We prospectively evaluated the effects of a night-float system in which designated residents relieved on-call senior residents and interns of routine admissions of patients in medically stable condition during the late-night period (11 PM to 7 AM). Senior residents (3.7 vs 2.4 hours) and interns (3.7 vs 3.2 hours) reported sleeping more under the night-float system than under the traditional system. The night-float system did not affect residents' overall ratings of call nights. Educators who reviewed medical records agreed with residents' decisions about patients' appropriateness for admission using the night-float system in 95 (81%) of 117 cases. When educators disagreed with residents, the most common reasons were the patient's potential educational value or medical instability. The night-float system did not affect interns' ratings of the educational value of late-night admissions or parents' ratings of satisfaction with medical care. We conclude that the night-float system can increase resident sleep with little cost to parent satisfaction, but standards for selective use may be needed to avoid compromising patient care and resident education.

Induction of monocytic cell adherence to matrix-bound fibronectin by phorbol ester.

The inflammatory response requires the localization of monocytic cells to sites of tissue injury through adherence to extracellular matrix molecules such as fibronectin (Fn), a nonimmune opsonin, which binds to collagen, fibrin, heparin and cell surfaces. Adherence to this molecule of two myeloid cell lines differing in their stage of differentiation, was studied. In the baseline state, U937 monocytic cells bound specifically to matrix-bound Fn, while HL-60 promyelocytic cells bound minimally. Exposure to Phorbol myristate acetate (PMA) dramatically increased binding of both U937 and HL-60 cells to Fn with plateau effects at 10 ng/ml for both cell lines and at 30 and 60 minutes for U937 and HL-60, respectively. Treatment with metabolic inhibitors suggests that PMA stimulation depends at least in part on intact energy metabolism, protein synthesis and cytoskeletal components. This system should help elucidate the early molecular and biochemical events involved in monocyte adherence to the extracellular matrix.

Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial.

To test the hypothesis that restriction of sodium intake during the first 3 to 5 days of life will prevent the occurrence of hypernatremia and the need for administration of large fluid volumes, we prospectively and randomly assigned 17 babies (mean +/- SD: 850 +/- 120 gm; 27 +/- 1 weeks of gestation) to receive in blind fashion either daily maintenance sodium or salt restriction with physician-prescribed parenteral fluid intake. Maintenance-group infants received 3 to 4 mEq of sodium per kilogram per day; restricted infants received no sodium supplement other than with such treatments as transfusion. Sodium balance studies conducted for 5 days demonstrated that maintenance salt intake resulted in a daily sodium balance near zero, whereas sodium-restricted infants continued to excrete urinary sodium at a high rate, which promoted a more negative balance (average daily sodium balance -0.30 +/- 1.78 SD in maintenance group vs -3.71 +/- 1.47 mEq/kg per day in restriction group; p less than 0.001). Care givers tended to prescribe daily increases in parenteral fluids for the salt-supplemented infants, perhaps because serum sodium concentrations were elevated in these infants after the first day of the study (p less than 0.001). Hypernatremia developed in two sodium-supplemented infants (greater than 150 mEq/L), and hyponatremia developed in two sodium-restricted infants (less than 130 mEq/L); however, the restricted infants were more likely to have normal serum osmolality (p less than 0.05). Both groups of infants produced urine that was neither concentrated nor dilute, with a high fractional excretion of sodium; renal failure was not observed. The mortality rate was not affected, but the incidence of bronchopulmonary dysplasia was significantly less in the sodium-restricted babies (p less than 0.02). We conclude that in tiny premature infants, a fluid regimen that restricts sodium may simplify parenteral fluid therapy targeted to prevent hypernatremia and excessive administration of parenteral fluids.

Infection of cord blood monocyte-derived macrophages with human immunodeficiency virus type 1.

We have investigated the susceptibility of cord blood monocyte-derived macrophages to human immunodeficiency virus type 1 (HIV-1) infection in vitro. Cord blood monocytes were maintained in vitro for 10 to 15 days and then infected with HIV-1. Syncytia were observed 14 days after infection by light microscopy. Viral proteins were detected by immunofluorescence assay. Electron microscopic examination demonstrated typical lentivirus particles within cytoplasmic vacuoles. The supernatants from the HIV-1-infected cultures also contained significant reverse transcriptase activity and p24 antigen. Like adult monocyte/macrophages, cord-derived monocyte/macrophages expressed the CD4 receptor molecule. Pretreatment with blocking antibody prior to infection with HIV-1 Bal significantly reduced or blocked infection of cord monocyte/macrophages. When cord and adult monocyte/macrophages were infected with HIV-1 Bal or Ada-M and directly compared, higher reverse transcriptase activities and p24 antigen expression were obtained with cord monocyte/macrophages. However, no significant difference was found between adult and cord monocyte/macrophages infected with HIV-1 IIIB. These observations suggest that cord monocyte-derived macrophages may be important in the pathogenesis of pediatric AIDS and that the increased susceptibility of cord monocyte/macrophages to HIV-1 infection in vitro may be relevant to the enhanced susceptibility of neonates to HIV-1 diseases in vivo.