Hypoplastic left heart syndrome: factors influencing therapeutic choice.

Parent's choices among therapeutic options for their infants born with hypoplastic left heart syndrome are difficult and controversial. Currently, management options include surgical reconstruction, cardiac transplantation, and comfort measures only. We retrospectively reviewed medical records of 47 patients (1989-1999) to create a database of clinical features of infants who received either an operation or comfort care only. Eleven families were interviewed by means of a structured questionnaire pertaining to their experience and reasons for their choice. Of the 47, 20 were prenatally diagnosed and nine of these (45%) aborted. The remaining 38 of the 47 were liveborns. Of the 38, 20/38 (53%) chose comfort care only. The other 18 chose operation. Although 17 were able to survive until first stage repair, only 8/17 (47%) survived beyond five months. At the time of last contact (ages one to 4.5 years), 5/17 (29%) remained alive. Over the nine years an increasing proportion of parents chose operative reconstruction; 8/11 (73%) for 1996-99 vs 10/27 (37%) for 1989-1995. Interviewed families who chose comfort care were more likely to believe the rate of survival following operation was poor, quality of life was diminished, and seemed concerned that their infant would suffer. Influence by optimistic physicians at surgical centers seemed important for an operative choice. Most suggested that provision of written materials, professional family counseling, and support groups of hypoplastic left heart syndrome families are or would be helpful.

The design and development of a biosensor to measure the concentration of meconium in amniotic fluid.

Meconium aspiration syndrome occurs in 0.2% to 1% of all deliveries and has a mortality rate as high as 18%. The disease is responsible for 2% of all perinatal deaths. Meconium may be classified as being thick or thin, but this assessment is normally performed visually by clinicians. A "meconiumcrit" analysis has been developed to objectively define the concentration of meconium. However, this analysis does not provide real-time continuous readings. This study focused on the design and development of a sensor to provide an objective, continuous, real-time assessment of meconium thickness. Meconium has an absorption spectrum centered at 410 nm and observes Beer's law. Blue light centered at 430 nm was delivered through meconium solutions, and a photodiode translated the strength of the incoming light into a voltage. This voltage was analyzed by a microcontroller to determine the concentration of meconium.

Placental blood sampling: an aid to the diagnosis of neonatal sepsis.

OBJECTIVE: To determine the usefulness of placental blood cultures in establishment of the diagnosis of early onset sepsis. STUDY DESIGN: Babies born to mothers with suspected intraamniotic fluid infection had blood cultures obtained from a branch of the umbilical vein on the fetal surface of the placenta immediately after delivery. The babies at highest risk (n = 35) had subsequent neonatal blood cultured from a peripheral vein (group 1), whereas 26 newborns at a lower risk did not (group 2). A group of 20 term babies born after uncomplicated labor and vaginal delivery or by elective cesarean delivery served as control subjects. RESULTS: Placental blood cultures were more often positive for pathogens in group 1 (7 of 35; 20%; 0.09 to 0.36) than in group 2 (0 of 26; 0 to 0.11) or control subjects (0 of 20; 0 to 0.14; p < 0.02). Within group 1, placental blood cultures were more often positive (7 of 35; 20%; 0.09 to 0.36) than subsequent neonatal blood cultures (1 of 35; 3%; 0 to 0.15; p < 0.05). Contaminants were cultured in 3 of 81 (4%; 01 to 0.11) placental samples (all from group 1) compared with 1 of 35 (3%; 0 to 0.11) neonatal samples (difference not significant). CONCLUSIONS: A carefully obtained culture of placental blood may be a useful addition or substitute for neonatal blood culturing in newborns at risk for early-onset sepsis by virtue of maternal risk factors.

Nosocomial sepsis in neonates with single lumen vascular catheters.

Catheter-related sepsis is commonly encountered in the neonatal intensive care unit. We retrospectively studied infants with vascular catheters at 2 NICUs. Data were obtained from the computerised admission records available at both the hospitals. Our aims were to describe the clinical and microbial profile of nosocomial sepsis in infants with vascular catheters [umbilical artery (UA), umbilical venous (UV), central venous Broviac (CV), percutaneously placed central venous (PC), peripheral artery (PA)], and to determine the association between catheter type, duration and sepsis in a subset of the population. Nosocomial sepsis (positive blood culture after the 3rd postnatal day) occurred in 217 of 2091 (10.4%) infants. Infected infants, in contrast to non-infected, had a significantly (P < 0.001) greater number of multiple catheters (2.3 vs 1.4) had lower birth weights (1.2 vs 2.1 kg), were younger (28 vs 33 weeks) and had lower 1 and 5 minute Apgar scores (4.3 and 6.7 vs 5.5 and 7.4). The most common organism was coagulase negative Staphylococcus. In a subset population as analyses revealed, longer duration of UA use was associated with higher infection rates [13.6% with UA use for > or = 8 days vs 1.3% for < or = 7 days (P < 0.0001)]. PC use had a lower rate of sepsis than CV use (5.1% vs 15.2%; P < 0.05). Use of intravascular catheters should be balanced between the need for vascular access and the risk of sepsis.

New syndrome of hydrocephalus, endocardial fibroelastosis, and cataracts (HEC syndrome).

We report on two unrelated male infants with similar findings of communicating hydrocephalus, endocardial fibroelastosis (EFE) and congenital cataracts, who died at 4 months of age. Both mothers reported an upper respiratory infection during the first trimester of pregnancy which was further complicated by polyhydramnios in the third trimester. The infants were diagnosed with bilateral congenital nuclear cataracts at birth. Serologic tests for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and galactosemia screens were negative. Chromosome analyses were normal. Both children developed communicating hydrocephalus between one and three months after birth. Patient 1 died suddenly at 4 months following an upper respiratory infection. Patient 2 developed congestive heart failure and also died at 4 months. At autopsy, both infants had enlarged hearts with endocardial fibroelastosis. No identifiable organism could be isolated. We discuss the association of birth defects in widely separated organ systems in these patients and suggest that this may represent a genetic syndrome; however, a viral etiology cannot entirely be excluded. We believe this is a distinct disorder and propose the acronym HEC for hydrocephalus, EFE and cataracts.

Lack of compliance with influenza immunization for caretakers of neonatal intensive care unit patients.

BACKGROUND: Both the Centers for Disease Control and Prevention and the American Academy of Pediatrics have recommended influenza immunizations for neonatal intensive care unit staff. Compliance rates for influenza immunization among neonatal intensive care unit staff have not yet been reported. METHODS: To determine both the rates and the associated factors for compliance between 1990 and 1993 among neonatal intensive care unit nursing staff, interviews were conducted at three Hartford area hospitals by means of a structured questionnaire. RESULTS: Compliance rates at the three hospitals were 15% in 1990 to 1991, 20% in 1991 to 1992, and 17% in 1992 to 1993 (89% sampling of all nurses with direct patient care). Sixty-three percent were not immunized between 1991 and 1993, 26% were vaccinated once, 9% were vaccinated twice, and 2% were vaccinated three times within the 3-year period. Convictions regarding vaccine safety and effectiveness, concern about getting influenza, and awareness of national recommendations for annual influenza immunization were shown to be associated with vaccination compliance. Concern over exposing neonates, peer influence, pain from injection, and previous adverse reaction were not statistically significant factors differentiating compliers from noncompliers. CONCLUSIONS: There is a poor acceptance of the influenza vaccine among our neonatal intensive care unit nursing staff. Educational and research efforts directed toward influenza risks among neonates and vaccine safety and effectiveness, along with incentives to comply, may improve compliance rates.

Surveillance for influenza in a newborn intensive care unit.

Although influenza may cause fatal neonatal infections, the current prevalence of disease in newborn intensive care units (NICU) is unknown. Furthermore, because compliance of NICU staff with annual influenza immunization is poor, absence of antibody may provide an indication of influenza susceptibility for neonatal patients and staff. We studied our NICU staff and patients during the winter of 1992-93 to determine seroprevalence of influenza antibody and attempted to document infection serologically or by culture in symptomatic staff and by culture in neonatal patients. Before the influenza season commenced or at birth (using cord blood), antibody to influenza A was absent in 9% (4/43) of the staff and 11% (9/83) of the neonatal patients. Antibody to influenza B was absent in 26% (11/43) of the staff and in 37% (31/83) of the neonates. We were able to document influenza serologically in only one nurse during the study. None of our staff or patients had positive cultures; however, we demonstrated a susceptible population of both staff and particularly neonates who need protection. There were study limitations of sampling and a low incidence of influenza in Connecticut for 1993. Nevertheless, continuing surveillance for influenza in NICUs could provide a more rational basis for immunization and prevention practices.

Effect of corticosteroids on the maturation of neutrophil motility in very low birthweight neonates.

Neutrophil (PMN) chemotaxis and chemokinesis were longitudinally studied in a group of 17 neonates with birthweights between 750 and 1250 g. Five of the 17 neonates were treated with prenatal betamethasone to attempt to prevent hyaline membrane disease, six received postnatal dexamethasone in an effort to reduce bronchopulmonary dysplasia, three received both, and three were not treated with corticosteroids. The group of 17 neonates were tested on four separate occasions: (1-2, 3-4, 7-8, and 10-14 postnatal days). PMN chemotaxis and chemokinesis were determined using a standard micropore filter assay. A group of 36 adults was used as additional controls. There were no significant differences noted in PMN chemotaxis or chemokinesis for the corticosteroid vs the noncorticosteroid-treated groups. In the total group of 17 neonates, there was depression in PMN chemotaxis compared with adult values, which lasted at least through postnatal day 8. By day 13 to 14, PMN chemotactic values were similar to those of adults. In contrast, chemokinesis, was depressed during the initial 14 days (except for the first 2 postnatal days). These data suggest that perinatal corticosteroid administration does not affect PMN motility in newborn infants.

Variable clinical expression of mosaic trisomy 16 in the newborn infant.

Trisomy 16 is common in embryos and fetuses aborted early during development. Mosaicism for trisomy 16 is sometimes encountered during prenatal diagnosis, particularly with chorionic villi biopsy specimens, and, until recently, was thought to be confined to the placenta. However, recently, several liveborn infants with trisomy 16 mosaicism have been described. We report on an additional liveborn infant with trisomy 16 mosaicism and compare the clinical findings with those of the previously reported cases in an attempt to delineate a mosaic trisomy 16 syndrome. Cytogenetic analysis from our patient showed that there was a different proportion of abnormal cells in different tissues and that the anomaly was undetectable in blood lymphocyte cultures. This observation was consistent with some of the previous reports. DNA analysis of parents and child was carried out using a polymorphic dinucleotide marker that maps to the long arm of chromosome 16. This analysis showed that the extra chromosome 16 in the infant was maternal in origin and suggested that the nondisjunction was probably a first meiotic division error. Our results suggest that an investigation of multiple tissues is required before concluding that mosaicism is confined to the placenta. We conclude that a finding of trisomy 16 mosaicism at prenatal diagnosis should be regarded with extreme caution. This diagnosis may be associated with a highly variable phenotype that may occasionally be compatible with extrauterine life.

Effect of labor and delivery on neonatal polymorphonuclear leukocyte number and function.

The ability of the neonate to mount an adequate polymorphonuclear leukocyte (PMN) response, either quantitatively or functionally, is impaired. To assess whether neonatal PMN number and function are altered by labor and delivery, three groups of infants were studied: cesarean section without labor (10), cesarean section after labor (10), and vaginal delivery (11). PMN counts were higher in the groups undergoing labor (p less than 0.01) compared with the cesarean section without labor group. Similarly, the labor groups had evidence of complement activation (increased C3a desarg) compared with the cesarean section without labor group. No differences were noted between the groups in measures of PMN motility (chemokinesis or chemotaxis) or PMN degranulation (plasma lysozyme), suggesting that normal labor and delivery does not contribute to the general PMN dysfunction of the neonate.

Prevention of transfusion-associated cytomegalovirus infection in neonatal patients by the removal of white cells from blood.

The usual methods employed to reduce the risk of transfusion-associated cytomegalovirus (TA CMV) disease have been to transfuse blood or cellular blood components that are CMV antibody-negative or to administer deglycerolized frozen red cells. To determine if the reduction of white cells (WBCs) in blood by filtration will also eliminate TA CMV disease in a high-risk population, 48 surviving very low birth weight (less than 1250 g) neonatal infants born to CMV-seronegative mothers at three participating institutions in the Hartford, Connecticut area and receiving at least one CMV-seropositive blood transfusion were studied. The incidence of TA CMV disease in 26 neonatal patients who received blood prepared by a modified spin-cool-filter technique and in 22 neonatal patients who received blood filtered through a WBC-reduction filter was compared with the incidence of transfusion-associated disease in similar populations reported in other studies. The CMV antibody prevalence of the blood donor population was found to be 37 percent. At the time of discharge of the individual neonatal infants in the population studied, and/or 2 to 6 months later, 47 of the 48 who had undergone transfusion had CMV antibody-negative serologic tests and/or urine culture. The other infant transiently seroconverted because of passive transfer of the antibody. None of the 48 neonatal infants had clinical evidence of CMV infection. This study indicates that WBC reduction of donor blood can reduce and perhaps prevent TA CMV disease in high-risk neonatal patients.

Cytomegalovirus antibody detection in blood donors and mothers of very low birth weight neonates by using three serologic methods.

We compared three serologic methods for cytomegalovirus (CMV) antibody detection and determined the CMV antibody seroprevalence of blood donors and mothers of very low birth weight (less than 1250 g) neonates in the Greater Hartford region. CMV serology was determined for 577 healthy blood donors as well as for 147 mothers of premature infants. Plasma from blood donors and sera from mothers were tested by either latex agglutination (LA) or by an immunofluorescent antibody assay (IFA), and results were compared with those from an enzyme-linked immunosorbent assay (ELISA). Sensitivity and specificity for LA to ELISA were significantly better than for IFA to ELISA [sensitivity 79/81 (97%) vs 171/202 (85%), and specificity 90/94 (96%) vs 257/347 (74%), p less than 0.01]. These differences remained whether plasma or sera were tested. Borderline values explained only two (33%) of six LA-ELISA as well as only 70 (58%) of 121 IFA-ELISA discordance. CMV seroprevalence rate for the donor blood population was 38%, and for the mothers was 53%. The LA assay is superior to the IFA assay for CMV screening of blood donors and maternal populations.

Enhancement of neonatal neutrophil motility (chemotaxis) with adult fresh frozen plasma.

We examined the effect of adult fresh frozen plasma (FFP) on neonatal neutrophil (PMN) motility (chemotaxis) using a micropore filter assay. Adult FFP was transfused into 13 neonates receiving FFP transfusion for suspected life-threatening sepsis. Blood was obtained from neonates before and after FFP transfusion for assessment of PMN chemotaxis. An increase in PMN chemotaxis was noted in 12 of the 13 neonates following FFP transfusion, with a mean percentage increase of 12 +/- 3% (p less than 0.01). PMN chemotaxis increased 13 +/- 2% (p less than 0.01) in four bacteremic infants and 11 +/- 5% (p = 0.06) in nine infants without bacteremia. Adult FFP transfusion may enhance impaired neonatal PMN motility and improve outcome from infection in newborn infants.

Modulation of neonatal neutrophil function by pentoxifylline.

Immunomodulating agents are being investigated for treatment of infection in newborn infants where morbidity and mortality remain high despite the continued development of new antibiotics. We studied the effect of the methylxanthine pentoxifylline on polymorphonuclear leukocyte (PMN) chemotaxis, F-actin content, and phagocytic activity as measured by nitroblue tetrazolium reduction and H2O2 production in neonates and adults to determine whether pentoxifylline might be useful in augmenting PMN function. The drug was found to have a dose-dependent effect on both neonatal and adult PMN function with enhancement at lower concentrations and suppression at higher concentrations. PMN chemotaxis increased 42% (p less than 0.01) in neonates and 16% (p less than 0.05) in adults at 100 micrograms/mL of pentoxifylline and it decreased 4 and 25%, respectively, at 4000 micrograms/mL. PMN nitroblue tetrazolium reduction increased by 34% in neonates and 23% (p less than 0.05) in adults at 100 micrograms/mL of pentoxifylline and decreased by 52 (p less than 0.01) and 74% (p less than 0.01), respectively, at 2000 micrograms/mL. Similar dose-dependent responses were noted with F-actin content and H2O2 production. These and other observations support the hypothesis that pentoxifylline has a broad range of effects on PMN but that a primary effect is alteration of PMN deformability. Pentoxifylline has potential clinical use as an immunomodulator in augmenting impaired PMN function in neonates and other immunocompromised hosts or in suppressing excessive PMN activity in certain disease processes.

Effects of intravenous fat infusion on neonatal neutrophil and platelet function.

Intravenous fat (Intralipid) is used extensively as a major component of parenteral nutrition for patients in the neonatal intensive care unit. Abnormalities of polymorphonuclear leukocyte (PMN) and platelet number or function related to Intralipid infusion have been reported although conflicting results exist. In order to examine potential adverse hematologic effects of Intralipid, 10 ill neonates were studied before and after a 16-hr infusion of 1 g/kilo of Intralipid. PMN count, chemokinesis, chemotaxis, and aggregation were unchanged pre- and post intralipid infusion. Platelet count, bleeding time, and platelet aggregation were also unchanged. Similar results were obtained in vitro when neonatal and adult PMNs and platelets were incubated in Intralipid and their function analyzed. These findings suggest that short-term, low-dose Intralipid has no measurable impact on neonatal PMN or platelet activity and support its use in neonates even in the presence of infection or thrombocytopenia.

Enhancement of neutrophil function for treatment of neonatal infections.

Newborn infants are at increased risk of morbidity and mortality from infection despite the continued development of new antibiotics. Because impairment of such host defense mechanisms as PMN function is thought to be largely responsible for this problem, correction of these defects in neonates offers a new and potentially important therapy against infection. Further studies are necessary to determine whether transfusion of either adult PMNs, antibody or fresh frozen plasma; administration of immunomodulating drugs; or some combination of these will provide maximum therapeutic benefit for the newborn infant with infection.