Intensive care noise and mean arterial blood pressure in ELBW neonates

Objective. Loud noises in neonatal intensive care units (NICUs) may impede growth and development for extremely low birthweight (ELBW, < 1000 grams) newborns. The objective of this study was to measure the association between NICU sound levels and ELBW neonates' arterial blood pressure to determine whether these newborns experience noise-induced stress. ^ Methods. Noise and arterial blood pressure recordings were collected for 9 ELBW neonates during the first week of life. Sound levels were measured inside the incubator, and each subject's arterial blood pressures were simultaneously recorded for 15 minutes (at 1 sec intervals). Time series cross-correlation functions were calculated for NICU noise and mean arterial blood pressure (MABP) recordings for each subject. The grand mean noise-MABP cross-correlation was calculated for all subjects and for lower and higher birthweight groups for comparison. ^ Results. The grand mean noise-MABP cross-correlation for all subjects was mostly negative (through 300 sec lag time) and nearly reached significance at the 95% level at 111 sec lag (mean r = -0.062). Lower birthweight newborns (454-709 g) experienced significant decreases in blood pressure with increasing NICU noise after 145 sec lag (peak r = -0.074). Higher birthweight newborns had an immediate negative correlation with NICU sound levels (at 3 sec lag, r = -0.071), but arterial blood pressures increased to a positive correlation with noise levels at 197 sec lag (r = 0.075). ^ Conclusions. ELBW newborns' arterial blood pressure was influenced by NICU noise levels during the first week of life. Lower birthweight newborns may have experienced an orienting reflex to NICU sounds. Higher birthweight newborns experienced an immediate orienting reflex to increasing sound levels, but arterial blood pressure increased approximately 3 minutes after increases in noise levels. Increases in arterial blood pressure following increased NICU sound levels may result from a stress response to noise. ^

The relationship between premature rupture of the membranes and sepsis in preterm neonates

This investigation was designed as a hospital-based, historical cohort study. The objective of the study was to determine the association between premature rupture of the membranes (PROM) and its duration on neonatal sepsis, infection, and mortality. Neonates born alive with gestational ages between 25 and 35 weeks from singleton pregnancies complicated by PROM were selected. Each of the 507 neonates was matched on gestational age, gender, ethnicity, and month of birth with a neonate without the complication of PROM.^ Data were abstracted from deliveries between January 1979 and December 1985 describing the mother's demographics, labor and delivery treatments and complications, the neonate's demographics, infection status, and medical care. The matched pairs analysis reveals a significant increase in risk of neonatal sepsis (RR = 3.5) and neonatal infection (RR = 2.4) among preterm births complicated by PROM, with a PROM exposure contributing an excess 4 to 5 cases of sepsis per 100 infants (RD = 0.04 for infection and RD = 0.05 for sepsis). Generally PROM remains an important risk factor for sepsis and infection when controlling for various other characteristics, and the risk difference remains constant.^ PROM was not significantly associated with neonatal mortality (RR = 1.02). There is an increase in risk difference for mortality associated with PROM among septic and infected infants, but it is not significant.^ A clear increase in risk of sepsis and infection from PROM occurs when durations of PROM are long (more than 48 hours), e.g., for sepsis the RR is 2.42 for short durations and RR is 6.0 for long durations. No such risk with long duration appears for neonatal mortality.^ This study indicates the importance of close observation of neonates with PROM for sepsis and infection so treatment can be initiated early. However, prematurity is the major risk for sepsis and the practice of early delivery to avoid prolonged durations of PROM does not alter the magnitude of risk. The greatest protection against these infection complications was provided when the neonate weighed over 1500 grams or had more than 33 weeks gestation. ^

DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life

The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-γ (IFN-γ) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens.

Periextubation caffeine in preterm neonates: A randomized dose response trial

Objective: To compare the effectiveness of three dosing regimens of caffeine for preterm infants in the periextubation period. Methods: A randomized double-blind clinical trial of three dosing regimens of caffeine citrate ( 3, 15 and 30 mg/kg) for periextubation management of ventilated preterm infants was undertaken. Infants born < 32 weeks gestation who were ventilated for > 48 h were eligible for the study. Caffeine citrate was given as a once daily dose for a period of 6 days commencing 24 h prior to a planned extubation, or within 6 h of an unplanned extubation. The primary outcome measure was extubation failure, defined as neonates who were unable to be extubated within 48 h of caffeine loading or who required reventilation or doxapram dose within 7 days of caffeine loading. Continuous recordings of oxygen saturation and heart rate were undertaken in a subgroup of enrolled infants. Results: A total of 127 babies were enrolled into the study ( 42, 40, 45, in the 3, 15, and 30 mg/kg groups, respectively). No statistically significant difference was demonstrated in the incidence of extubation failure between dosing groups ( 19, 10, and 11 infants in the 3, 15, and 30 mg/kg groups, respectively), however, infants in the two higher dose groups had statistically significantly less documented apnoea than the lowest dose group. Of the 37 neonates with continuous pulse oximetry recordings, those on higher doses of caffeine recorded a statistically significantly higher mean heart rate, oxygen saturations and less time with oxygen saturations < 85%. Conclusions: This trial indicated there were short-term benefits of decreased apnoea in the immediate periextubation period for ventilated infants born < 32 weeks gestation receiving higher doses of caffeine. Further studies with larger numbers of infants assessing longer-term outcomes are necessary to determine the optimal dosing regimen of caffeine in preterm infants.

Pontosubicular apoptosis ("necrosis") in human neonates with intrauterine growth retardation and placental infarction

In a previous study of 37 autopsied stillbirths with non-dysmorphic intrauterine growth retardation ( IUGR), 26 cases were associated with placental infarction, a morphologic marker of uteroplacental insufficiency. Nine of the 26 cases with both IUGR and placental infarction, where archival tissue was available, had grey matter ischaemic lesions that were subsequently identified as pontosubicular necrosis. This lesion is now regarded as a localized form of apoptosis. A further eight third trimester stillbirth cases with both IUGR and placental infarction were ascertained prospectively. Sixteen of these 17 cases showed pontosubicular apoptosis, identified morphologically and verified using activated caspase-3 and TUNEL. Five of the 17 cases showed apoptosis in the frontal or temporal cortex as well. In this current study, pontosubicular apoptosis was strongly associated with IUGR and placental infarction in third trimester stillborns, suggesting that uteroplacental insufficiency leading to chronic fetal hypoxaemia may cause cerebral apoptosis.

A rapid and sensitive microscale HPLC method for the determination of indomethacin in plasma of premature neonates with patent ductus arteriousus

Indomethacin (IND) is the drug of choice for the closure of a patent ductus arteriosus (PDA) in neonates. This paper describes a simple, sensitive, accurate and precise microscale HPLC method suitable for the analysis of IND in plasma of premature neonates. Samples were prepared by plasma protein precipitation with acetonitrile containing the methyl ester of IND as the internal standard (IS). Chromatography was performed on a Hypersil C-18 column. The mobile phase of methanol, water and orthophosphoric acid (70:29.5:0.5, v/v, respectively), was delivered at 1.5 mL/min and monitored at 270 nm. IND and the IS were eluted at 2.9 and 4.3 min, respectively. Calibrations were linear (r > 0.999) from 25 to 2500 mu g/L. The inter- and intra-day assay imprecision was less than 4.3% at 400-2000 mu g/L, and less than 22.1% at 35 mu g/L. Inaccuracy ranged from -6.0% to +1.0% from 35 to 2000 mu g/L. The absolute recovery of IND over this range was 93.0-113.3%. The IS was stable for at least 36 h when added to plasma at ambient temperature. This method is suitable for pharmacokinetic studies of IND and has potential for monitoring therapy in infants with PDA when a target therapeutic range for IND has been validated. (c) 2005 Elsevier B.V. All rights reserved.

Pain relief for neonates in Australian hospitals: A need to improve evidence-based practice

Objective: To ascertain the extent to which neonatal analgesia was used in Australia for minor invasive procedures as an indicator of evidence-based practice in neonatology. Methods: A cross-sectional telephone survey of hospitals in all Australian states and territories with more than 200 deliveries per year was carried out. Questions were asked regarding awareness of the benefits and the use of analgesia for minor invasive procedures in term and near term neonates. Analysis was undertaken according to state and territory, annual birth numbers and the level of neonatal nursery care available. Results: Data were available from 212 of 214 eligible hospitals. Of the total respondents, 51% and 70% respectively were aware of the benefits of sucrose and breast-feeding for neonatal analgesia. Eleven per cent of units administered sucrose before venepuncture and 25% of units used breast-feeding. Ten per cent of units used sucrose before heel prick with 49% utilizing breast-feeding. Expressed breast milk was used in 10% of units. Analgesia was given less frequently before intravenous cannulation compared to venepuncture and heel prick. Awareness and implementation of neonatal analgesia varied widely in the states and territories. There was a trend for hospitals providing a higher level of neonatal care to have a greater awareness of sucrose as an analgesic (P < 0.0001) and the use of sucrose for venepuncture (P = 0.029), heel prick (P = 0.025) and intravenous catheter insertion (P = 0.013). Similar trends were found on analysis according to birth number of the maternity units. Smaller units had a greater usage of breast-feeding as an analgesic for heel prick (P = 0.017). Conclusion: Despite good evidence for the administration of sucrose and breast milk in providing effective analgesia for newborn infants, it is not widely used in Australia. It is imperative that the gap between research findings and clinical practice with regard to neonatal analgesia be addressed.

Reference values for whole body and cerebral multi-frequency bio-impedance data in neonates less than 12 h postpartum

Multiple frequency bio-electrical impedance analysis (MFBIA) may be useful for monitoring fluid balance in newborn infants or to provide early prediction of the outcome following perinatal asphyxia. A reference range of data is needed for identification of babies with abnormal impedance values. This was a cross-sectional observational study in 84 term and near-term healthy neonates less than 12 h postpartum. Whole body and cerebral MFBIA measurements were performed at the bedside in the post-natal ward. Gestational age, post-natal age, gender, birthweight, head circumference and foot length measures were recorded. Reference values for impedance at the characteristic frequency (Z(C)) and resistance at zero frequency (R-0) are reported for whole body and cerebral impedance. Significant correlations (p < 0.05) were observed between whole body impedance and birthweight, footlength and head circumference. Females had a significantly higher whole body R0 than males. Cerebral impedance did not correlate significantly with any of the demographic measures and therewere no gender differences observed for cerebral impedance. The reference range for whole body multi-frequency bio-impedance values in term and near-term infants within the first 12 h postpartum can be calculated from the footlength (FL) using the following equations: Z(C) = (942.9 - 4.818* FL) +/- 124.6 Omega; R-0 = (1042 - 4.520(*)FL) +/- 135.5 Omega. For cerebral impedance the reference range is 29.5-48.7 Omega for Z(C) and 33.7-58.0 Omega for R-0.

Seizure detection algorithm for neonates based on wave-sequence analysis

Objective: The description and evaluation of the performance of a new real-time seizure detection algorithm in the newborn infant. Methods: The algorithm includes parallel fragmentation of EEG signal into waves; wave-feature extraction and averaging; elementary, preliminary and final detection. The algorithm detects EEG waves with heightened regularity, using wave intervals, amplitudes and shapes. The performance of the algorithm was assessed with the use of event-based and liberal and conservative time-based approaches and compared with the performance of Gotman's and Liu's algorithms. Results: The algorithm was assessed on multi-channel EEG records of 55 neonates including 17 with seizures. The algorithm showed sensitivities ranging 83-95% with positive predictive values (PPV) 48-77%. There were 2.0 false positive detections per hour. In comparison, Gotman's algorithm (with 30 s gap-closing procedure) displayed sensitivities of 45-88% and PPV 29-56%; with 7.4 false positives per hour and Liu's algorithm displayed sensitivities of 96-99%, and PPV 10-25%; with 15.7 false positives per hour. Conclusions: The wave-sequence analysis based algorithm displayed higher sensitivity, higher PPV and a substantially lower level of false positives than two previously published algorithms. Significance: The proposed algorithm provides a basis for major improvements in neonatal seizure detection and monitoring. Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology.