Incorrect umbilical vein catheterization is associated with severe periventricular hemorrhages and mortality in extremely premature newborns.

OBJECTIVE: To investigate the relationship between umbilical vein catheter (UVC) placement and death in extremely premature newborns (<29 weeks gestation). STUDY DESIGN: Utilizing a retrospective, case-control study design, results for newborns that received UVC placements and died were compared with those who received UVC placements and survived (n = 719) by univariate and multiple logistic regression analyses. RESULT: Death rate was 30% in infants with low lines versus 16% in those without (p = 0.012). High UVC tip placement significantly and independently increased severe periventricular hemorrhages (p = 0.014). Severe periventricular hemorrhage increased death rates by 3-fold independent of gestational age (p <  0.001). Proper line placement significantly reduced severe periventricular hemorrhage by 2.5-fold independent of gestational age (p = 0.019). CONCLUSION: In extremely premature newborns, incorrect UVC placement is significantly associated with death through its relation to severe periventricular hemorrhage.

Impact of umbilical catheterization on morbidity and mortality in extremely premature newborns.

OBJECTIVE: Investigate the benefit of umbilical catheterization upon survival and selected morbidities in extremely premature newborns (<28 weeks gestation). Outcomes of successfully catheterized extremely premature newborns are compared with others who cannot be successfully catheterized, and we hypothesize that umbilical catheterization promotes survival and reduces morbidities. STUDY DESIGN: Utilizing a retrospective, cohort study design, survival and outcomes of catheterized and non-catheterized newborns (n = 722) were compared by univariate and multiple logistic regression analyses. RESULTS: Of all newborns, 66.8% had both umbilical arterial catheter (UAC) and umbilical venous catheter (UVC) placements, 15.0% had only UAC, 13.7% had only UVC, and 4.6% had neither. Overall survival was 82.5%. Survivals with and without UAC were 82.5% and 82.6% (NS), but survival with UVC was 80.7% versus 90.1% without UVC (p = 0.012). Analysis of risk factors associated with death during umbilical catheterization reaffirmed that death remained significantly dependent upon UVC placement (OR = 35.7; 95% CI: 3.7-347.3, p = 0.002). CONCLUSION: Successful umbilical catheterization of extremely premature newborns does not provide benefit through promotion of survival or reduction of morbidities when compared to others who are not successfully catheterized at the umbilicus.

Multicenter study to determine antibody concentrations and assess the safety of administration of INH-A21, a donor-selected human Staphylococcal immune globulin, in low-birth-weight infants.

Nosocomial or late-onset sepsis is a common complication among premature infants, with a frequency inversely correlated with birth weight. Increased susceptibility to infection is due in part to an immature humoral (antibody-mediated) immune response. This study investigated the pharmacokinetics (PKs) and safety of a donor-selected specific intravenous immune globulin (IVIG) preparation, INH-A21 (Veronate), for prevention of sepsis in premature infants. Thirty-six infants weighing between 500 and 1,250 g during the first postnatal week were eligible to begin a series of up to four intravenous infusions of 500 or 750 mg/kg of body weight INH-A21. Blood samples were analyzed for antibodies against the Ser-Asp dipeptide repeat G (SdrG) and clumping factor A (ClfA) surface proteins of staphylococci. Sparse sampling and population PK analyses were performed to derive PK parameters. Following administration of the 500- and 750-mg/kg doses, the estimated average steady-state levels of anti-ClfA were 6.1 U/ml and 9.2 U/ml, respectively, and those of anti-SdrG were 5.2 U/ml and 7.7 U/ml, respectively. The elimination half-lives for anti-ClfA and anti-SdrG were 719 h and 701 h, respectively, and the clearances were 0.18 ml/h and 0.21 ml/h, respectively. In the final model, the values of the PK parameters were independent of gestational age. Both doses of INH-A21 were well tolerated, and the safety profile was similar to those of other IVIG preparations. These results suggest that a shorter dosing interval should be utilized between the first and second doses to achieve and maintain higher titers of anti-ClfA and anti-SdrG antibodies. Further studies examining INH-A21 for the prevention of late-onset sepsis in infants within the weight range studied are warranted.

Auditory brainstem response detects early bilirubin neurotoxicity at low indirect bilirubin values.

When sedation, prematurity or other disease processes mask symptoms in the clinically ill newborn, serum bilirubin concentration is monitored as the sole indicator of kernicterus risk. This case emphasizes the value of auditory brainstem responses for the management of indirect hyperbilirubinemia complicated by prematurity, hemolytic anemia, asphyxia, and direct hyperbilirubinemia.

Surfactant releases internal calcium stores in neutrophils by G protein-activated pathway.

Pulmonary surfactant with surfactant-associated proteins (PS+SAP) decreases pulmonary inflammation by suppressing neutrophil activation. We have observed that PS+SAP inserts channels into artificial membranes, depolarizes neutrophils, and depresses calcium influx and function in stimulated neutrophils. We hypothesize that PS+SAP suppresses neutrophil activation by depletion of internal Ca(++) stores and that PS+SAP induces depletion through release of Ca(++) stores and through inhibition of Ca(++) influx. Our model predicts that PS+SAP releases Ca(++) stores through insertion of channels, depolarization of neutrophils, and activation of a G protein-dependent pathway. If the model of channel insertion and membrane depolarization is accurate, then gramicidin-a channel protein with properties similar to those of PS+SAP-is expected to mimic these effects. Human neutrophils were monitored for [Ca(++)] responses after exposure to one of two different PS+SAP preparations, a PS-SAP preparation, gramicidin alone, and gramicidin reconstituted with phospholipid (PLG). [Ca(++)] responses were reexamined following preexposure to inhibitors of internal Ca(++) release or the G protein pathway. We observed that (i) 1% PS+SAP-but not PS-SAP-causes transient increase of neutrophil [Ca(++)] within seconds of exposure; (ii) 1% PLG-but not gramicidin alone-closely mimics the effect of PS+SAP on Ca(++) response; (iii) PS+SAP and PLG equally depolarize neutrophils; (iv) direct inhibition of internal Ca(++) stores releases or of G protein activation suppresses Ca(++) responses to PS+SAP and PLG; and (v) preexposure to either PS+SAP or PLG inhibits Ca(++) influx following fMLP stimulation. We conclude that PS+SAP independently depolarizes neutrophils, releases Ca(++) from internal stores by a G protein-mediated pathway, and alters subsequent neutrophil response to physiologic stimulants by depleting internal Ca(++) stores and by inhibiting Ca(++) influx during subsequent fMLP activation. The mimicking of these results by PLG supports the hypothesis that PS+SAP initiates depolarization via channel insertion into neutrophil plasma membrane.

Current practice regarding the enteral feeding of high-risk newborns with umbilical catheters in situ.

OBJECTIVE: Textbooks recognize the controversy of concomitant enteral nutrition (EN) during umbilical catheter usage in high-risk newborns, but support for the practice varies. There is only one clinical trial examining these practices in a small but randomized, controlled trial of enterally fed newborns with umbilical arterial catheters (UACs) in situ, and that trial did not demonstrate any adverse consequences. We speculate that concomitant EN with umbilical catheter usage is more common than some textbooks suggest-practiced by at least 20% of all US neonatal intensive care units (NICUs). The objective of this study is to determine the prevalence of NICUs where high-risk newborns with UAC or umbilical venous catheter (UVC) placement receive concomitant EN. METHODS: Medical Directors listed in the American Academy of Pediatrics United States Neonatologist and Perinatologist Directory were surveyed by mail. On return of surveys, responses to multiple choice questions were recorded by electronic scanning and validated by manually conducted quality control checks. NICU identities were recorded by code to maintain anonymity. RESULTS: Following 2 requests for survey participation, 70% (549/785) of surveys were returned. Respectively, 82% and 62% of NICUs with and without training programs were represented. On average, surveyed medical directors had practiced neonatal medicine 18.1 +/- 0.3 years. Of surveyed NICUs, 99% reported placement of UVCs and UACs. Of the 92% believing that it is safe to provide trophic EN to newborns with UVCs in place, 51% practiced this some of the time, and 37% practiced it most of the time. By comparison, it was reported that newborns with UACs in place receive trophic EN most of the time (30%), some of the time (49%), or none of the time (22%). Of the 80% believing that it is safe to provide more complete EN to newborns with UVCs in place, 44% practiced this some of the time, and 24% practiced it most of the time. For newborns with UACs in place, more complete EN was provided most of the time (15%), some of the time (36%), or none of the time (49%). CONCLUSIONS: Concurrent UVC and UAC usage with EN is more commonly practiced than suggested in textbooks or published articles. The relative risk-benefit profiles of these practices remain uncertain secondary to the limited number of controlled clinical observations and to the infrequent occurrence of adverse events. A prospective, multicenter, controlled trial would address the continued advisability of these unexpectedly common practices.