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.

Systemic candidiasis: cutaneous manifestations in low birth weight infants.

The cutaneous manifestations of 18 infants treated for systemic candidiasis during a 3 3/4-year period were examined. Eight infants, with a mean birth weight of 712 +/- 161 g, had a diffuse burn-like dermatitis, usually within the first three days of life. Candida pseudohyphae were identifiable on skin scrapings. A history of a maternal cerclage or intrauterine device complicated by chorioamnionitis was common. A delay in diagnosis or therapy resulted in mortality, whereas promptly treated infants survived. Nine additional infants had monilial diaper rashes, which spread to the trunk and extremities in four infants. These infants were older at the onset of the dermatitis, and all survived the systemic infection. Systemic candidiasis without any cutaneous involvement developed in only one infant. Candidiasis should be more frequently considered, and prompt systemic therapy should be instituted when cutaneous candidiasis occurs within the first few days of life in infants who weigh less than 1,500 g.

Fungal colonization in the very low birth weight infant.

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

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

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

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

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

Buffy coat transfusions in neutropenic neonates with presumed sepsis: a prospective, randomized trial.

Neonatal sepsis, accompanied by neutropenia, is associated with a high mortality. To determine whether granulocyte transfusions improve the survival of critically ill neutropenic infants, we prospectively randomized 25 infants to transfusion and nontransfusion groups, matching for birth weight (less than or equal to 1,500 g or greater than 1,500 g). Infants with necrotizing enterocolitis were randomized separately. Neutropenia was established by two successive absolute neutrophil counts less than or equal to 1,500 cells prior to randomization. The transfusion (n = 12) and nontransfusion (n = 13) groups did not differ with respect to clinical or hematologic characteristics. In 23 of 25, bone marrow aspirations were performed to determine the percentage of neutrophil storage pool. Granulocyte transfusions of buffy coats from single units of whole blood (0.1 to 0.9 X 10(9) polymorphonuclear leukocytes per kilogram) were given daily until the absolute neutrophil count increased to more than 1,500/microL. Only five infants, mostly those with necrotizing enterocolitis, required more than one transfusion. A circulating immature to total neutrophil ratio (I:T) greater than or equal to 0.80 was not predictive of an infant with a neutrophil storage pool less than or equal to 7%, and neither an I:T less than 0.80 nor a neutrophil storage pool greater than 7% were predictive of survival. Granulocyte transfusions did not improve survival when either comparing the whole group, those 17 infants with cultures positive for bacteria or viruses, the 19 infants with a circulating I:T greater than or equal to 0.80, or the nine infants with a neutrophil storage pool less than or equal to 7%.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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 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.

Observations of a support group for parents of children with severe bronchopulmonary dysplasia.

Parents of children with bronchopulmonary dysplasia (BPD) suffer severe stress and anxiety. In order to provide a group of peers and ready access to caregivers, a support group was developed for the families of children with severe BPD. Fifty percent of invited families attended 1 to 11 monthly meetings. Those attending were primarily upper middle social class, white, married parents with a good visiting record. Members initially focused on specific topics (medical and developmental problems), but later discussions were oriented to psychosocial problems. Many parental anxieties had never previously been discussed with staff members. Commonly, parents complained about not understanding the medical care system. The parents were usually aware of the death of a child with BPD prior to the meeting and dealt with their feelings in the group discussion. Continuing interactions outside the hospital were common. The development of similar groups in other hospitals should be encouraged.

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.

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.

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.

Mechanisms of diminished natural killer cell activity in pregnant women and neonates.

Because alterations in natural killer (NK) activity in the perinatal period may be important in the maintenance of a healthy pregnancy, we examined the mechanisms by which these alterations are mediated in neonates and in pregnant and postpartum women. NK activity, as measured in a 4-hr 51Cr-release assay and compared with adult controls, is significantly diminished in all three trimesters of pregnancy and in immediately postpartum women. In postpartum women, NK activity appears to be higher than in pregnant women, although this does not reach statistical significance. Pregnant and postpartum women have normal numbers of large granular lymphocytes and normal target cell binding in an agarose single cell assay but decreased lysis of the bound target cells. NK activity of mononuclear cells from postpartum women, in addition, demonstrate a shift in distribution to higher levels of resistance to gamma-irradiation. Further, sera from postpartum women cause a similar shift to increased radioresistance in mononuclear cells from adult controls. Because radioresistance is a property of interleukin 2-stimulated NK, the shift to radioresistance may represent lymphokine-mediated stimulation occurring during parturition. In contrast, cord blood cells have a more profound decrease in NK activity as determined by 51Cr-release assay and decreases in both binding and lysis of bound target cells in the single cell assay. The resistance of NK activity in cord cells to gamma-irradiation is also increased, as seen in postpartum women. Cord blood serum, however, did not alter radioresistance or inhibit NK activity. The results suggest that the observed diminished NK activity in pregnant women and neonates arise by different mechanisms: an absence of mature NK cells in the neonate and an alteration of the NK cell in pregnancy leading to decreased killing.

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.

Candida endophthalmitis in the premature infant.

An attempt was made to determine the incidence and natural history of Candida endophthalmitis in the premature infant with systemic candidiasis. Each of eight premature infants were examined by indirect ophthalmoscopy within one week of their diagnosis. At this stage, four infants had multiple fluffy white lesions on both the retina and the vitreous, together with a diffuse vitreous haze. Three of the infants had interlesional and lesional-retinal vitreous strands. Three infants treated with amphotericin B and 5-fluorocytosine showed gradual disappearance of the lesions. The fourth infant died early in the course of antifungal therapy, when the eye lesions were progressing. Candida sepsis was particularly prevalent in the very low-birth-weight infant with a prolonged hospital course and treated with multiple broad-spectrum antibiotics. The course of the eye lesions indicates a good prognosis for Candida endophthalmitis, although further follow-up is necessary.