Elevated iron indices in preterm infants: association with male gender.

Elevated iron indices may be underrecognized in preterm infants. Sixty growing, stable preterm infants < 1500 g studied had elevated iron indices, which was especially elevated in male infants. Careful evaluation of iron indices is essential to prevent potential organ injury and unnecessary iron supplementation.

Long-term sequelae of postnatal surfactant and corticosteroid therapies for BPD.

OBJECTIVE: This retrospective analysis assessed the relationship between medical treatment (postnatal steroids, surfactant) received neonatally and outcomes at 3 and 8 years using a longitudinal sample of children with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Four groups were formed retrospectively based on the type of neonatal medical treatment received: no drug intervention (n=37), surfactant only (n=29), postnatal steroids only (n=13) and combined surfactant and postnatal steroids (n=16). Groups were compared on neurological and medical outcomes. RESULT: Combined postnatal steroids and surfactant treatment was associated with more days on supplemental oxygen than no intervention or surfactant only. Surfactant replacement therapy alone was not associated with adverse consequences; however, postnatal steroid exposure appeared to be related. CONCLUSION: Although retrospective analyses make statements about causation impossible, the differential relationships of therapies with cognitive outcomes argues for careful monitoring of therapeutic agents with very low birth weight infants.

Developmental outcomes and environmental correlates of very low birthweight, cocaine-exposed infants.

Fetal cocaine exposure may have differentially adverse effects on developmental outcomes of very low birthweight (VLBW) infants. As part of a longitudinal study, 31 cocaine-positive very low birthweight infants, and age, race and socioeconomic status matched VLBW controls enrolled at birth were followed. Neonatal maternal-child interactions, concurrent maternal psychological characteristics and environmental factors conceptualized as important for child outcome were assessed as well as standard developmental outcomes at 3 years. In the neonatal period, cocaine-exposed VLBW infants who remained in maternal custody tended to be rated as less responsive and their mothers as less nurturing, less emotionally available and with a tendency to use more maladaptive coping mechanisms than nonexposed VLBW infants. At follow-up, cocaine-exposed VLBW children were delayed in cognitive, motor and language development compared to controls. Almost half (45%) of the exposed children scored in the range of mental retardation compared to 16% of the comparison VLBW children. The persistent cognitive, motor and language delays of the cocaine-exposed VLBW children, combined with the poorer behavioral interactions of cocaine-using women with their infants in the neonatal period, indicate a need for increased developmental surveillance of cocaine-exposed VLBW infants with a focus on maternal drug treatment and parenting interventions.

Preschool language outcomes of children with history of bronchopulmonary dysplasia and very low birth weight.

A prospective follow-up of very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD) and term control infants was conducted. The effects of BPD and VLBW on speech-language development and specific language impairment at 3 years of age were investigated, controlling for the effects of sociodemographic and other medical risk factors. Groups were compared on cognitive and speech-language outcomes using the Battelle Language and Bayley Mental Scales of Infant Development. Children with a history of BPD had lower receptive language skills than VLBW children without BPD, who in turn had lower receptive skills than term children. Children with a history of BPD also had lower expressive skills than the two comparison groups, whereas VLBW children without BPD did not differ in expressive language from term children. When IQ score was controlled, children with BPD demonstrated specific language impairment in receptive language. The presence of patent ductus arteriosis (PDA) was the best predictor of language deficits and the combined occurrence of PDA and BPD resulted in differentially lower language scores. Neurologic complications, low socioeconomic status, and minority race were also significant predictors of language delay. The findings emphasize the importance of considering both medical and sociodemographic factors in evaluating the risk of VLBW infants for poorer speech-language outcomes.

Maternal psychological distress and parenting stress after the birth of a very low-birth-weight infant.

CONTEXT: Few studies document how parents adapt to the experience of a very low-birth-weight (VLBW; <1500 g) birth despite societal concerns about the ethics and justification of intensive care for these infants. OBJECTIVE: To determine the degree and type of stress experienced over time by mothers whose infants vary in degree of prematurity and medical and developmental risk. DESIGN: Longitudinal prospective follow-up study of a cohort of mothers of high- and low-risk VLBW and term infants from birth to 3 years. SETTING: All level III neonatal intensive care units from a large midwestern metropolitan region. PARTICIPANTS: Mothers and infants prospectively and consecutively enrolled in a longitudinal study between 1989 and 1991. High-risk VLBW infants were diagnosed as having bronchopulmonary dysplasia, and comparison groups were low-risk VLBW infants without bronchopulmonary dysplasia and term infants (>36 weeks, >2500 g). MAIN OUTCOME MEASURES: Standardized, normative self-report measures of maternal psychological distress, parenting stress, family impact, and life stressors. RESULTS: Mothers of VLBW infants (high risk, n = 122; low risk, n = 84) had more psychological distress than mothers of term infants (n=123) at 1 month (13% vs 1%; P = .003). At 2 years, mothers of low-risk VLBW infants did not differ from term mothers, while mothers of high-risk infants continued to report psychological distress. By 3 years, mothers of high-risk VLBW children did not differ from mothers of term children in distress symptoms, while parenting stress remained greater. Severity of maternal depression was related to lower child developmental outcomes in both VLBW groups. CONCLUSIONS: The impact of VLBW birth varies with child medical risk status, age, and developmental outcome. Follow-up programs should incorporate psychological screening and support services for mothers of VLBW infants in the immediate postnatal period, with monitoring of mothers of high-risk VLBW infants.

A longitudinal study of developmental outcome of infants with bronchopulmonary dysplasia and very low birth weight.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is now the leading cause of lung disease in US infants. In a large regional cohort, we tested the hypothesis that despite innovations in neonatal care, very low birth weight (VLBW) infants (<1500 g) with BPD had poorer developmental outcomes than nonaffected infants during the first 3 years of life, and that BPD predicted poorer outcome beyond the effects of other risk factors. METHODS: Three groups of infants (122 with BPD, 84 VLBW without BPD, and 123 full-term) were followed longitudinally to 3 years of age with the Bayley Scales of Mental and Motor Development. Comparison groups of VLBW infants without BPD and full-term infants did not differ in sex, race, or socioeconomic status. Statistical analyses included hierarchical and stepwise multiple regression. RESULTS: Infants with BPD performed more poorly at all ages. By 3 years, cognitive and/or motor development was in the range of retardation (<70 standard score) for 21% to 22% of infants with BPD. In multiple regression analyses controlling for socioeconomic and neonatal risk conditions, BPD had an independent negative effect on motor outcome at 3 years. Neurologic risk, a summary measure of neurologic problems other than intraventricular hemorrhage, and the presence of BPD independently predicted motor delay. By 3 years, social class, race, and neurologic risk predicted mental outcome, suggesting that the specific effects of BPD are primarily on the motor domain. CONCLUSIONS: In VLBW infants, BPD predicts poorer motor outcome at 3 years, after control for other risks. Cohorts of infants with BPD also had higher rates of mental retardation, associated with greater neurologic and social risk. These findings underscore the need for intensive prevention and habilitation efforts for this growing group of VLBW survivors, as well as investigation into the potential role of BPD in the higher rates of learning disabilities in VLBW cohorts at school age.

Feeding interactions in infants with very low birth weight and bronchopulmonary dysplasia.

Infants with very low birth weight (VLBW) are at increased risk for feeding disorders that can affect growth and development. One hundred and forty one mother-infant pairs were compared [55 with infants with high medical risk due to infant VLBW and bronchopulmonary dysplasia (BPD), 34 VLBW without BPD, and 52 term infants] on operationally defined measures of feeding behaviors and maternal self-report of depression and anxiety. Mothers of VLBW infants with and without BPD spent more time prompting their infants to feed when their infants engaged in nonfeeding behavior. Despite increased maternal efforts, infants with BPD took in less formula, spent less time sucking, and spent a greater proportion of time nonfeeding. VLBW infants without BPD were equivalent to term infants in percentage of time sucking and in volume of formula ingested and were more likely to take in higher calories than infants with BPD. Mothers of VLBW infants with and without BPD were also more likely to report clinically significant symptoms of depression and anxiety than mothers of term infants. Because mothers of VLBW infants who were more depressed or anxious were less likely to verbally prompt their infants to eat, maternal psychological symptoms should be considered in assessing interactions of VLBW mother-infant dyads.

Hospitalization as a measure of morbidity among very low birth weight infants with chronic lung disease.

OBJECTIVE: To examine the spectrum of hospitalization and rehospitalization among very low birth weight (VLBW, <1500 gm) infants with severe chronic lung disease during the first 2 years of life. POPULATION: All 124 VLBW infants admitted to our center from October 1988 to September 1990 who were oxygen and ventilator dependent at 21 days of age. One hundred infants survived to discharge, of whom two subsequently died. The 98 surviving infants are the subject of this report. METHODS: The duration of the neonatal stay, the use of a long-term care facility, and rehospitalizations were recorded to a postnatal age of 24 months. The duration of these hospitalizations and the total duration of hospitalization during the first year of life were correlated with demographic and perinatal risk factors and 20-month outcome. RESULTS: The 98 infants spent a median of 125 days (range, 44 to 365) of their first year hospitalized; the neonatal stay accounted for 85% of this time. Forty-nine of the infants (50%) were rehospitalized in their first year (median stay, 14 days), and 36 (37%) were rehospitalized in their second year (median stay, 7 days). Long-term care facility stay and rehospitalizations accounted for 6% and 9% of the first-year hospitalizations, respectively. A median of 9 days (range, 1 to 365) of the second year of life were spent in hospital. The infants rehospitalized during their first year of life did not differ significantly from those not requiring rehospitalization with regard to maternal demographic descriptors, birth data, severity of chronic lung disease, or measures of 20-month outcome. Both duration of neonatal stay and total hospital stay during the first year were significantly associated with all measures of chronic lung disease severity and with 20-month neurodevelopmental outcome measures, whereas the duration of rehospitalization was associated only with duration of oxygen dependence. CONCLUSION: Among infants with severe chronic lung disease, the total duration of hospitalization during the first year of life provides a better index of morbidity than the number or duration of rehospitalizations alone.

Twenty-month outcome in ventilator-dependent, very low birth weight infants born during the early years of dexamethasone therapy.

We sought to examine the effect of the introduction of dexamethasone therapy on health, growth, and neurodevelopmental outcome in very low birth weight (VLBW) infants at 20 months of age. We compared outcomes in all 86 VLBW infants (mean birth weight 871 gm, mean gestational age 26.4 weeks) who were ventilator dependent on day 21 of life during the 2 years preceding October 1988 (period 1), when dexamethasone therapy became accepted clinical practice in our unit, with outcomes in all 124 infants (mean birth weight 891 gm, mean gestational age 26.9 weeks) with similar ventilator status during the subsequent 2 years (period 2). In addition, we compared outcomes in infants who received dexamethasone during period 2 with those in a concurrent cohort of less ill infants who were not given dexamethasone. There were no significant differences between periods 1 and 2 in mortality rates after 21 days (17% vs 21%), need for home oxygen (23% vs 25%), oxygen dependence at 20 months of corrected age (11% vs 10%), rate of neurosensory impairment (24% vs 25%), and mean Bayley Mental scores (81.5 vs 77.2) or Psychomotor Development Index (81.6 vs 71.1). Infants who received dexamethasone during period 2 had significantly more severe lung disease and poorer respiratory, growth, and developmental outcomes. We conclude that VLBW infants with ventilator-dependent chronic lung disease have very poor outcomes, even when treated with dexamethasone. More information is needed from prospective, randomized trials before dexamethasone can be accepted as routine therapy for chronic lung disease.

Frequency and significance of isolation of Ureaplasma urealyticum and Mycoplasma hominis from cerebrospinal fluid and tracheal aspirate specimens from low birth weight infants.

To investigate the pathogenicity of Ureaplasma urealyticum and Mycoplasma hominis in preterm infants, we conducted a study to determine (1) frequency of isolation from cerebrospinal fluid and tracheal aspirate specimens and (2) clinical outcomes and effect of erythromycin treatment in ureaplasma-colonized infants. From the cerebrospinal fluid of 920 infants, U. urealyticum was isolated from 2 (0.2%) and M. hominis from none. From tracheal aspirate specimens from 224 infants, U. urealyticum was recovered from 37 (17%) and M. hominis from 4 (2%). Demographic characteristics and clinical outcomes were compared in very low birth weight infants (< 1500 gm) who were culture-positive or -negative for U. urealyticum. Although infants with positive results were less mature than their cohorts with negative results, there were no substantive differences in clinical outcomes between the two groups. Initiation of erythromycin treatment of infants with positive ureaplasma culture results at a mean age of 16.4 days did not appear to alter the clinical outcome. We conclude that in preterm infants (1) infection of the cerebrospinal fluid by U. urealyticum is infrequent, (2) ureaplasma organisms are frequently present in tracheal aspirate specimens but do not appear to be related to the presence or the subsequent development of respiratory disease, and (3) initiation of erythromycin treatment at 1 to 3 weeks of age does not alter the clinical course.

Increased incidence of intraventricular hemorrhage and developmental delay in cocaine-exposed, very low birth weight infants.

This study sought to determine whether very low birth weight (VLBW) infants (< 1500 gm) with fetal cocaine exposure differed from non-cocaine-exposed VLBW infants in incidence of neonatal medical complications and in later developmental outcome. Forty-one cocaine-exposed, VLBW infants, followed in a longitudinal study, were compared with 41 non-cocaine-exposed, VLBW infants of comparable race, social class, age, and incidence of bronchopulmonary dysplasia. Cocaine-exposed infants were identified on the basis of combined findings of maternal and/or infant urine immunoassay and on the basis of maternal self-report. At birth, groups did not differ on medical risk factors except that cocaine-exposed infants had a higher incidence of mild (grades I to II) intraventricular hemorrhage. Cocaine-using women were also more likely to use other drugs, especially alcohol, marijuana, and tobacco. At follow-up, at mean corrected ages of 16.5 +/- 8 months for 30 cocaine-exposed infants and 18.5 +/- 7 months for 37 non-cocaine-exposed infants, standardized assessments of cognitive (Mental Development Index) and motor (Psychomotor Development Index) development were administered. Cocaine-exposed infants had lower mean cognitive (83 +/- 27 vs 91 +/- 19), and motor (85 +/- 25 vs 96 +/- 18) scores; the incidence of developmental delay was significantly higher even after control for the effects of intraventricular hemorrhage and chronologic age. Cocaine-exposed VLBW infants were also more likely to be living with relatives or in foster homes. We conclude that these VLBW, cocaine-exposed infants were at increased risk of intraventricular hemorrhage, were more likely to be placed outside maternal care, and had higher incidences of cognitive and motor delays at follow-up.

Comparative study of the immunogenicity and safety of two dosing schedules of Engerix-B hepatitis B vaccine in neonates.

A randomized multicenter study compared the routine hepatitis B vaccine schedule of 0, 1, 6 months with an accelerated schedule of 0, 1, 2 months in newborns. Two hundred ninety-nine infants whose mothers were seronegative for hepatitis B were enrolled in the study and randomized to either the routine or accelerated schedule. All infants had blood drawn for antibody titers to hepatitis B at 2, 3, 6 and 7 months of age. For 222 infants data were evaluable, at least for safety; 193 of these 22 had antibody titers that were evaluable. The infants vaccinated on the accelerated schedule developed seroprotective concentrations of antibody more quickly than the infants vaccinated on the routine schedule; 92.6% vs. 66.1% had seroprotective concentrations (> or = 10 mIU/ml) at 3 months of age (P < 0.001). However, infants in the accelerated schedule had lower geometric mean antibody titers at 7 months, 420.0 vs. 3141.8. We conclude that the accelerated vaccination schedule resulted in the more rapid development of seroprotective concentrations of antibody, but levels of antibodies were not as high as in the routinely vaccinated infants at 7 months. These data suggest that an accelerated vaccine schedule can be used in the newborn period. The effectiveness of the accelerated schedule in preventing perinatal infections compared to the standard schedule and the necessity for booster doses of vaccine remain to be studied.

Neonatal candidiasis: the current challenge.

The current challenge of neonatal candidiasis arises from the increased survival of very low birthweight infants. It is important to understand those factors affecting normal colonization of the neonate, concomitant with those factors that predispose to fungal invasiveness. Disseminated candidiasis may present with subtle signs and symptoms, but has the potential for a wide variety of organ system involvement. Early initiation of aggressive therapy, with careful monitoring, can lead to a successful outcome.

Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates.

To determine the pharmacokinetics of amphotericin B and 5-fluorocytosine in neonates, we measured serum concentrations at first dose and after 5 days of therapy by high-performance liquid chromatography in 13 neonates (mean birth weight 1.2 +/- 0.8 kg). The dose of amphotericin B was serially increased from 0.1 to 0.5 mg/kg/day in 10 infants but was decreased from 0.8 to 1.0 to 0.5 mg/kg/day in three infants. Amphotericin B concentrations were not detectable in infants receiving 0.1 mg/kg/day. Amphotericin B cerebrospinal fluid concentrations were 40% to 90% of serum values obtained simultaneously. Serum concentrations after oral administration of 5-fluorocytosine (dose 25 to 100 mg/kg/day) were detectable in all infants. We found extreme interindividual variability for the half-life, volume of distribution, and clearance for both drugs. Four infants had minimal elimination for both drugs between doses, a finding that correlates with rises in serum creatinine (greater than 0.4 mg/dl, 40 mumol/L) and blood urea nitrogen (greater than 10 mg/dl, 3.6 mmol/L). We recommend that the dose of amphotericin B given on the first day of treatment be greater than the usual testing dose of 0.1 mg/kg/day. We also recommend an initial 24-hour dosing interval for amphotericin B and 5-fluorocytosine. Serum drug concentrations may need to be monitored in high-risk, low birth weight infants.

Granulocyte transfusions in septic adult and newborn rats: distribution of granulocytes and effect on peripheral blood and bone marrow.

Granulocyte transfusions are increasingly being used as therapy for newborns with sepsis and neutropenia. We injected either group B Streptococcus or phosphate-buffered saline solution intraperitoneally into adult and newborn rats. Human granulocytes, labeled with chromium 51, were transfused seven hours later. When the newborn rats were killed 13 to 19 hours after injection, they had 10(2) to 10(6) cfu/gm Streptococcus organisms in both lung and brain. Only one third of the adult rats had 10(2) to 10(4) cfu/gm Streptococcus organisms in either lung or brain. A greater proportion of the transfused granulocytes was present in lung and brain tissue of newborn rats, compared with adult rats (p less than 0.05), irrespective of infection. Granulocyte transfusion did not change the peripheral blood leukocyte count in adult rats but increased the count in newborn rats (p less than 0.05). The immature myeloid pool in the bone marrow of adult rats increased significantly with either infection or transfusion (p less than 0.01). The immature pool in newborn rats increased significantly only with infection (p greater than 0.001), although the combination of infection and transfusion also had a significant effect on the pool (p less than 0.01). Infection and both infection and transfusion, but not transfusion alone, significantly affected the mature myeloid bone marrow pool in adult and newborn rats (p less than 0.001). The depletion of the mature myeloid elements of the bone marrow in response to infection was dramatic in neonatal rats, compared with that in adult rats. Both transfused granulocytes and hematogenously spread streptococci lodge in the brains and lungs of neonatal rats more effectively than in those of adult rats.

Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study.

To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum "target level" of 700 mg/dl. The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization. Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups. The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately. In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued. No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group. There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study. No infant who received IVIG acquired nosocomial sepsis (p less than 0.01). All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed. Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG. These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants.

Gestational age-dependent changes in circulating hematopoietic stem cells in newborn infants.

In the fetus, hematopoietic stem cells originate in the yolk sac and are believed to be transferred to all other hematopoietic organs via the circulation. In humans, the time course of this transfer has not been systematically evaluated in viable premature infants. We examined the cord blood of 13 preterm (25 to 36 weeks of gestation) and 10 term (38 to 42 weeks of gestation) infants for pluripotent (mixed colony-forming unit-granulocyte, erythrocyte, macrophage, megakaryocyte), erythroid (burst-forming unit-erythroid, colony-forming unit-erythroid) and myeloid (colony-forming unit-granulocyte, macrophage) stem cells. A gestational age-dependent decrease in all lineages of circulating hematopoietic stem cells was noted (p less than 0.001). By 34 weeks of gestation, preterm infant cord blood had a similar concentration of circulating stem cells compared with that of term infants. This gestational age-dependent decrease in hematopoietic stem cells of all lineages supports the hypothesis of a blood-borne transfer of hematopoiesis that appears largely complete by 34 weeks of gestation. Infants born after less than 32 weeks of gestation have high levels of circulating hematopoietic stem cells that may reflect the active transfer of hematopoiesis from liver to bone marrow.

Neonatal sepsis: the potential for immunotherapy.

There is tremendous potential for immunotherapy of neonatal sepsis, considering the continued high mortality of the disease. Current studies, particularly of intravenous immunoglobulin, have had encouraging outcomes. However, much more data need to be accumulated before clinical application.

Neonatal neutropenia. Clinical manifestations, cause, and outcome.

Neutropenia, defined as an absolute neutrophil count that falls below 2.0 x 10(9)/L, is being identified more frequently in the newborn intensive care unit and significantly influences clinical decisions regarding therapy. We prospectively identified 119 episodes of neutropenia in 87 infants (6% of admissions). Less than half of the episodes could be attributed to infections. The majority of noninfectious neutropenia episodes were related to specific perinatal events or were of unknown cause. Infants weighing less than 2500 g were more likely to have neutropenia than term infants (13% vs 3%, respectively) and less likely to have neutropenia related to bacterial infections. Short-term survival (89% vs 95%) and long-term survival (74% vs 77%) were not different in infants with infectious diseases compared with those with noninfectious diseases. Mortality was highly correlated with the need for assisted ventilation (20%) or with an absolute neutrophil count of 0.5 x 10(9)/L (24%). We conclude that the cause of neutropenia and the clinical condition must be carefully evaluated before instituting aggressive therapy for infection.