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PubMed1992

Thrombin inhibition is impaired in plasma of sick neonates.

The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

PubMed1999

Increased neonatal platelet deposition on subendothelium under flow conditions: the role of plasma von Willebrand factor.

In vitro platelet function of umbilical cord blood and neonatal peripheral vein blood from full-term newborns was compared with that of adults. Citrated whole blood was subjected to shear stress (1300 s(-1)) on subendothelial extracellular matrix (ECM)-coated wells in a cone and plate(let) analyzer. Adhered platelets on the ECM were quantitated by image analyzer. Both umbilical cord and neonatal peripheral blood platelets demonstrated more extensive adhesion than adult platelets, and similar aggregate formation on ECM. The ability of neonatal platelets to form aggregates on ECM was confirmed by scanning electron microscopy. Similar activation of neonatal and adult platelets after subjection to shear stress, in the suspension phase, was established by flow cytometry, which showed an increase in fibrinogen binding and a decrease in glycoprotein Ib expression on platelet membrane. The difference in adhesion rates between neonatal and adult platelets was preserved even when the hematocrit level of the neonatal blood was adjusted to that of adults. Reconstitution of neonatal or adult platelet-rich plasma with autologous or heterologous red packed cells yielded no change in adhesion and aggregation. When von Willebrand factor-covered plates were used to prevent deposition of plasma von Willebrand factor on the surface, no difference in platelet adhesion was seen between neonatal and adult blood. In conventional aggregometry assay, the response to ristocetin of washed platelets of either neonatal or adult source was higher on addition of plasma from neonates than from adults. Our data suggest that the extensive neonatal platelet deposition on ECM is mediated by plasma von Willebrand factor, which is known to be more multimerized and, therefore, more active in neonates than in adults. This mechanism may provide balanced primary hemostasis in neonates despite the platelet hyporeactivity to agonists without application of shear stress.

Adult↗

PubMed2001

Comparison of androgen receptor and oestrogen receptor beta immunoexpression in the testes of the common marmoset (Callithrix jacchus) from birth to adulthood: low androgen receptor immunoexpression in Sertoli cells during the neonatal increase in testosterone concentrations.

The aims of this study were: (i) to investigate the cellular immunoexpression of androgen receptor and oestrogen receptor beta in the testes of the common marmoset (Callithrix jacchus) during neonatal life compared with their expression at later ages; (ii) to establish whether neonatal marmoset Sertoli cells are targets for androgens or oestrogens or both; and (iii) to investigate the relationship between neonatal plasma testosterone concentrations and androgen receptor immunoexpression by abolishing the neonatal testosterone surge with a potent GnRH antagonist. Androgen receptor and oestrogen receptor beta immunoexpression were evaluated in neonatal animals aged 1-4 days, 4 weeks and 6 weeks, and compared with immunoexpression in animals aged 18-22 weeks (early infancy), 35 weeks (late infancy), 58-62 weeks (late pubertal) and > 100 weeks (adult). Immunoexpression of androgen receptor in the reproductive tract was also evaluated at each age. Sertoli cell immunoexpression of androgen receptor was weak or absent in neonatal animals, but increased substantially in infant animals, reaching adult levels by the end of infancy. In contrast, immunoexpression of androgen receptor during the neonatal period was strong in testicular interstitial cells and very strong in epithelial cell nuclei throughout the reproductive tract, and did not change greatly with age in these cells or tissues. Similarly, immunoexpression of oestrogen receptor beta was prominent in many Sertoli cells and in the germ cells of neonatal animals, and was relatively constant throughout life. Weak immunoexpression of androgen receptor in neonatal Sertoli cells was associated with high plasma testosterone concentrations (2.7-5.5 ng ml(-1)), whereas strong Sertoli cell immunoexpression was associated with baseline (approximately 0.12 ng ml(-1)) testosterone concentrations in infant animals and with > 10 ng ml(-1) in late pubertal and adult animals. Immunoexpression of androgen receptor and oestrogen receptor beta was also evaluated in co-twin males aged 4 and 35 weeks, after treatment from birth to 4 weeks or from week 25 to week 35, respectively, with either vehicle or with GnRH antagonist at a dose known to suppress the neonatal testosterone surge completely. Only GnRH antagonist treatment during weeks 25-35 reduced androgen receptor immunoexpression, whereas immunoexpression of oestrogen receptor beta was unaffected by treatment during either period. On the basis of these findings it is suggested that: (i) neonatal marmoset Sertoli cells may be targets primarily for oestrogens rather than androgens; (ii) androgen receptor expression in the testes of neonatal and infant marmosets is not regulated in a straightforward way by testosterone; and (iii) high neonatal concentrations of plasma testosterone are not absolutely necessary for expression of androgen receptor in marmoset testes at this time.

Aging↗

PubMed2000

Frequency, natural course, and outcome of neonatal neutropenia.

OBJECTIVE: We studied the frequency, onset, duration, and prognosis of neutropenia in a neonatal hospital population to define subgroups of neonates who might benefit from cytokine therapy. STUDY DESIGN: The study comprised of 2 parts: in a first retrospective study (I), clinical data of neonates with sepsis (n = 168) were analyzed; in a second retrospective and prospective study (II), clinical data of neonates with neutropenia (n = 131) were studied. In study I, the analysis focused on septic neonates with and without neutropenia, and in study II, on neutropenic neonates with and without primary infection. In the prospective part of study II, granulocyte colony-stimulating factor (G-CSF) plasma concentrations were analyzed in neutropenic neonates (n = 32). RESULTS: Thirty-eight percent of septic neonates were neutropenic. Neutropenia lasted <24 hours in 75% of these patients. It was recorded before or on the day of the clinical onset of sepsis in 87% of patients. The overall incidence of neutropenia was 8.1%. Seventy-two percent of these neutropenic episodes occurred in patients without infection at the time of diagnosis of neutropenia. In the latter patients, the risk of infection secondary to neutropenia was 9%, affecting only premature neonates. Neutropenic episodes without infection were of longer duration and were accompanied by lower G-CSF plasma concentrations than were episodes associated with infection. The percentage of neutropenic episodes primarily associated with infection was higher in VLBW neonates than in term neonates. Likewise, the risk of infection secondary to neutropenia (27%) and the mortality attributable to infection and neutropenia (28%) were significantly higher than in term newborns. CONCLUSION: Considering the priming time for induction of neutrophilia, G-CSF therapy in neonates presenting with severe bacterial infection and neutropenia may be too late. In contrast, neutropenic very low birth weight neonates without primary infection might benefit from prophylactic G-CSF treatment.neonatal sepsis, neutropenia, granulocyte colony-stimulating factor.

Birth Weight↗

PubMed1992

Time course of trough serum gentamicin concentrations in preterm and term neonates.

Trough serum concentrations (Cmin) of gentamicin were followed during up to 96h of treatment in 44 neonates (17 preterm and 27 term), treated with intramuscular gentamicin 2.5 +/- 0.3 mg/kg (mean +/- SD) twice daily, a dosage that was not changed during the follow-up period. Relationships with patients' gestational age, postnatal age, postconceptional age and bodyweight were analysed to identify circumstances in which gentamicin should be monitored. Gentamicin Cmin values after 24h correlated better with neonate's postconceptional age (r = -0.42) or gestational age (r = -0.37) than with postnatal age or bodyweight. Correlations with postconceptional age and gestational age improved after 96h (r = -0.71 and r = -0.67, respectively). From 24 to 96h Cmin increased from 1.5 to 2 mg/L (p < 0.001) in the preterm neonates and from 1.5 to 2.5 mg/L (p < 0.01) in those preterm neonates < or = 32 weeks of gestational age, while differences between neonates < or = 3 days and > 3 days of postnatal age were nonsignificant. The Cmin at 24h was potentially toxic (> 2 mg/L) in 9% of the neonates (12% of preterm and 7% of term neonates). At 96h, the percentage of neonates with toxic Cmin values increased to 25% (65% of all preterm neonates and 100% of preterm neonates < or = 32 weeks of gestational age), whereas in term neonates it decreased to 0%. In conclusion, in preterm neonates < or = 32 weeks of gestational age a dosage of 2.5 mg/kg every 24h should be used, and gentamicin concentrations should be monitored. However, in term neonates > 7 days of postnatal age a dosage of 3.5 mg/kg twice daily should be recommended.

Analysis of Variance↗

PubMed1998

Occult spinal dysraphism in neonates: assessment of high-risk cutaneous stigmata on sonography.

OBJECTIVE: In this study, we evaluated the incidence of dorsal cutaneous stigmata in a healthy neonate population; we also assessed whether specific types of cutaneous stigmata are associated with underlying spinal dysraphism. SUBJECTS AND METHODS: From July 1993 through December 1996, we prospectively examined term neonates with dorsal cutaneous stigmata. Each neonate underwent spinal sonography and clinical assessment of the cutaneous stigmata. Incidence of dorsal cutaneous stigmata in a healthy neonatal population was determined by dividing the number of neonates with cutaneous stigmata by the total number of neonates examined. RESULTS: The incidence of cutaneous stigmata in the healthy neonate study population was 4.8%. We examined 207 neonates with 216 cutaneous stigmata, the most common of which was the simple midline dimple (74%). None of the neonates with only a simple midline dimple had spinal dysraphism. Of the 207 neonates we examined, 16 had spinal dysraphism. Clinical examination revealed 180 dimples and 36 other types of cutaneous stigmata (e.g., hemangiomas, hairy patches, masses, tails, lesions). Fourteen (39%) of 36 other cutaneous stigmata were positive for spinal dysraphism. Eight (40%) of 20 atypical dimples were positive for spinal dysraphism. Three were large clefts (>5 mm); the remaining five cases were seen in combination with other lesions and were all located more than 2.5 cm from the anus. Six (67%) of the nine neonates with multiple cutaneous stigmata had spinal dysraphism. CONCLUSION: Simple midline dimples are the most commonly encountered dorsal cutaneous stigmata in neonates and indicate low risk for spinal dysraphism. Only atypical dimples are associated with a high risk for spinal dysraphism, particularly those that are large (>5 mm), high on the back (>2.5 cm from the anus), or appear in combination with other lesions. High-risk cutaneous stigmata in neonates include hemangiomas, upraised lesions (i.e., masses, tails, and hairy patches), and multiple cutaneous stigmata.

Humans↗

PubMed1992

Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection.

Neonatal neutropenia occurs in approximately 50% of newborns delivered by women with pregnancy-induced hypertension. It is thought to be transient, independent of birth weight and gestational age, and unassociated with significant risks, including infection. It recently was suggested that neonatal neutropenia occurs primarily in smaller, younger neonates, is related to the severity of pregnancy-induced hypertension, and importantly, may be associated with an increased risk for nosocomial infection. We examined these points in a large inborn population in consecutive years, performing retrospective (n = 110, 1989) and prospective (n = 151, 1990) studies in low birth weight (less than or equal to 2200 g) neonates delivered by women with pregnancy-induced hypertension. Overall, 40% to 50% of neonates studied developed neonatal neutropenia, and they were younger and smaller (P less than .01) than non-neutropenic neonates. In the prospective study, neutropenic neonates were more likely to have mothers with severe pregnancy-induced hypertension (P less than .001), and the incidence of neonatal neutropenia was primarily among neonates less than 30 weeks of gestation and less than 1500 g birth weight, approximately 80% vs 35% to 45% in older, larger neonates or infants (P less than .001). Although nosocomial infection occurred more frequently among the group of neutropenic neonates in the prospective study (P less than .02), the incidence was similar to that in matched non-neutropenic controls delivered of normotensive women. Thrombocytopenia (less than 100,000/mm3) was not more frequent in neutropenic neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

PubMedDate not supplied

Cerebellar vermian atrophy after neonatal hypoxic-ischemic encephalopathy.

BACKGROUND AND PURPOSE: Although pathologic evidence of cerebellar injury due to birth asphyxia is well described, neuroimaging evidence is sparse. The primary purpose of this retrospective study was to evaluate the early and late imaging findings in the cerebellum of patients who had neonatal hypoxic-ischemic encephalopathy with thalamic edema shown by neonatal CT. The secondary aims were to validate thalamic edema shown by neonatal CT as a marker of thalamic injury and to assess the late cerebral cortical abnormalities associated with neonatal thalamic edema. METHODS: Fifty-five neonates with thalamic edema shown by CT performed when patients were 3 days old were identified from a cohort of full-term neonates with hypoxic-ischemic encephalopathy. Twenty-six of the 55 underwent follow-up neuroimaging. All sonograms, CT scans, and MR images of the brains of the 55 neonates were retrospectively reviewed by two pediatric neuroradiologists. The examinations were reviewed for evidence of hemorrhage, edema, atrophy, and CT attenuation or MR signal intensity abnormalities in the cerebellum, basal ganglia, and cerebral cortex. The neonatal autopsy findings in four cases were reviewed separately by a pediatric neuropathologist. RESULTS: Of the 55 neonates with thalamic edema shown by neonatal CT, 28 (51%) had thalamic edema with diffuse cerebral cortical edema, and 27 (49%) had thalamic edema without diffuse cortical edema. The cerebellar vermes appeared normal on all neonatal sonograms, CT scans, and MR images. However, atrophy of the cerebellar vermis was found in 12 (46%) of 26 patients by use of follow-up studies (95% CI, 27-65%). One of the 12 patients also had cerebellar hemispheric atrophy. Cerebellar vermian atrophy was shown at follow-up in eight (67%) of 12 patients who had neonatal thalamic edema with cortical sparing, compared with four (29%) of 14 patients who had thalamic edema with diffuse cortical edema. The difference did not reach statistical significance. The thalami appeared abnormal on follow-up neuroimages in 25 of 26 cases. Different patterns of cortical atrophy were observed on the images of patients who had thalamic edema with cortical sparing compared with those obtained in patients who had thalamic edema with cortical involvement. CONCLUSION: Cerebellar vermian atrophy is a frequent finding on follow-up images of patients in whom neonatal CT showed hypoxic-ischemic encephalopathy with abnormal thalami.

Atrophy↗

PubMed1984

Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine.

Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding--behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-beta-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High doses of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1994

Doppler-derived systolic pulmonary artery pressure in acute neonatal respiratory distress syndrome.

OBJECTIVE: To determine the course of systolic pulmonary artery pressure (PAP) in association with ductal shunting and cardiac output (CO) in preterm neonates. DESIGN: During the acute phase of respiratory distress syndrome (RDS) with and without surfactant treatment, serial Doppler ultrasound examinations were performed at the ages of 2, 12, 24, 48, and 72 hours in 51 neonates with RDS and 21 healthy, preterm controls. Twenty-eight of the distressed neonates received two or four doses of synthetic exogenous surfactant at intervals of 12 hours. Measurements of hemodynamic variables in these neonates were performed before and after 8 hours following surfactant treatments. PAP was estimated by the Doppler method from the maximal tricuspid regurgitant flow velocity. Doppler ultrasound was also used to determine simultaneously CO, and the direction and magnitude of the ductal shunting. RESULTS: The PAP was initially at the same level, but remained significantly higher in distressed than in healthy, preterm control neonates between the ages of 12 to 48 hours. The systolic systemic arterial blood pressures did not differ between the distressed and control neonates, but increased gradually during the study period. Consequently, the ratio of systolic pulmonary and systemic pressure was also higher in neonates with RDS than in controls during the first day of life. Bidirectional ductal shunting disappeared in all neonates studied after 2 days of life. Significant left-to-right shunting through the ductus arteriosus persisted more frequently in distressed neonates, especially those with surfactant treatment, than in control neonates during the study period, and more often caused the need for medical or surgical closure. Doppler-derived CO remained stable throughout the study in the distressed neonates, being significantly higher in surfactant-treated neonates than nontreated distressed neonates or healthy controls at 72 hours of life. CONCLUSIONS: The data of the present study confirms that the postnatal decrease in PAP is delayed in acute RDS. Further, significant patent ductus arteriosus shunting persists longer in RDS and may contribute to elevated CO during the resolution of the disease.

Acute Disease↗

PubMed2026

Electro-clinical efficacy and safety of midazolam in neonatal seizures: a systematic review with individual level exploratory analysis of gestational age-related treatment response.

UNLABELLED: Neonatal seizures are the most common neurological emergency during the neonatal period and are associated with increased mortality and adverse neurodevelopmental outcomes. Despite current recommendations supporting phenobarbital as first-line therapy, seizure control remains suboptimal in a large proportion of neonates, prompting the use of second-line antiseizure medications. Midazolam is increasingly administered in refractory neonatal seizures but evidence regarding its electro-clinical efficacy and safety remains limited and heterogeneous. To systematically review the available evidence on the electro-clinical efficacy and safety of midazolam in neonatal seizures and to perform an exploratory individual-level analysis investigating the association between gestational age and treatment response. A systematic review was conducted according to PRISMA 2020 guidelines. Studies including neonates with EEG- or aEEG-confirmed seizures treated with midazolam were included. Binary logistic regression was performed to assess the individual-level association between gestational age and treatment response. Eleven studies involving 146 neonates treated with midazolam were included. Electro-clinical response was observed in 101/146 neonates (69.2%), while seizure cessation was achieved in 61/146 neonates (41.8%). In an exploratory complete-case logistic regression analysis, higher gestational age appeared to be associated with a greater probability of electro-clinical response. The predicted probability curve crossed the 50% response probability at approximately 36.5 weeks of gestation. Hypotension was the most frequently reported adverse event, while respiratory depression, sedation-related effects, and transient EEG/aEEG suppression were reported less frequently. CONCLUSIONS: Midazolam may have a role as an add-on antiseizure medication in neonatal seizures, particularly in refractory cases. However, the evidence remains limited by heterogeneity in study design, EEG monitoring strategies, outcome definitions, and incomplete individual-level data. The observed association between gestational age and response is hypothesis-generating and requires prospective validation. WHAT IS KNOWN: • Phenobarbital often provides incomplete seizure control in neonates, making second-line antiseizure therapies necessary in refractory cases. • Evidence supporting midazolam for neonatal seizures remains limited and heterogeneous. WHAT IS NEW: • This systematic review summarizes the electro-clinical efficacy and safety of midazolam and includes an exploratory patient-level analysis suggesting that higher gestational age may be associated with improved treatment response. • These findings support further prospective studies on developmental determinants of response to GABAergic therapy.

Humans↗

PubMed1996

Survey of the definition and screening of neonatal hypoglycaemia in Australia.

OBJECTIVE: To determine the approach to identifying neonatal hypoglycaemia and the definition of neonatal hypoglycaemia used by neonatal paediatricians in Australian Level 3 neonatal intensive care units (NICU). METHODOLOGY: A questionnaire was sent to the 101 neonatal paediatricians in the 22 Level 3 NICU in Australia asking their method of screening for, and definition of, neonatal hypoglycaemia. RESULTS: Responses were received from 70 neonatal paediatricians, including all 22 directors. A bedside glucose meter is used in 19 of 22 NICU to screen for hypoglycaemia, whilst one NICU uses a glucose analyzer and another NICU uses a visual colour comparison method. One NICU does not screen, but has blood glucose measured in a satellite laboratory. If the screening method suggests hypoglycaemia, 62 of 63 neonatal paediatricians proceed to blood glucose determination in a laboratory, mostly using plasma samples. Based on the laboratory measurement, the definition of neonatal hypoglycaemia ranged from < 1.1 to 3.0 mmol/L. CONCLUSIONS: The majority of neonatal paediatricians in Australian NICU screen for neonatal hypoglycaemia using a bedside glucose meter. There is a wide range in the definition of neonatal hypoglycaemia from < 1.1 to 3.0 mmol/L.

Australia↗

PubMed2006

Intravenous morphine and topical tetracaine for treatment of pain in [corrected] neonates undergoing central line placement.

CONTEXT: There is limited evidence of the analgesic effectiveness of opioid analgesia or topical anesthesia during central line placement in neonates, and there are no previous studies of their relative effectiveness. OBJECTIVE: To determine the effectiveness and safety of topical tetracaine, intravenous morphine, or tetracaine plus morphine for alleviating pain in ventilated neonates during central line placement. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, controlled trial enrolling 132 ventilated neonates (mean gestational age, 30.6 [SD, 4.6] weeks at study entry) and conducted between October 2000 and July 2005 in 2 neonatal intensive care units in Toronto, Ontario. INTERVENTIONS: Prior to central line insertion, neonates were randomly assigned to receive tetracaine (n = 42), morphine (n = 38), or both (n = 31); a separate nonrandomized group of 21 neonates receiving neither tetracaine nor morphine was used as a control group. MAIN OUTCOME MEASURES: The primary outcome measure was a pain score for the proportion of time neonates displayed facial grimacing (brow bulge) during different phases of the procedure (skin preparation, needle puncture, and recovery). In randomized neonates, safety assessments included blood pressure, ventilatory support, and local skin reactions. RESULTS: Compared with no treatment, pain scores were lower in the morphine and tetracaine-morphine groups during skin preparation (mean difference, -0.22; 95% confidence interval [CI], -0.4 to -0.04; P = .02 and -0.29; 95% CI, -0.49 to -0.09; P = .01, respectively), and needle puncture (mean difference, -0.35; 95% CI, -0.57 to -0.13; P = .003 and -0.47; 95% CI, -0.71 to -0.24; P<.001, respectively), but pain scores did not differ statistically for tetracaine alone vs no treatment. Pain scores were lower for morphine and tetracaine-morphine vs tetracaine during the skin preparation phase and for tetracaine-morphine vs tetracaine during needle puncture. Compared with neonates without morphine, morphine-treated neonates required larger increases in ventilation rate in the first 12 hours (mean difference, 3.9/min; 95% CI, 1.3-6.5/min; P = .003). Local skin reactions occurred in 30% of neonates given tetracaine vs 0% for morphine (risk difference, 0.30; 95% CI, 0.19-0.41; P<.001). CONCLUSION: In this study of ventilated neonates undergoing central line placement, morphine and tetracaine plus morphine provided superior analgesia to tetracaine; however, morphine caused respiratory depression and tetracaine caused erythema.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00213200.

Administration, Topical↗

PubMed2004

Lipopolysaccharide-binding protein in critically ill neonates and children with suspected infection: comparison with procalcitonin, interleukin-6, and C-reactive protein.

OBJECTIVE: To evaluate markers of infection in critically ill neonates and children, comparing lipopolysaccharide-binding protein (LBP) with procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP). DESIGN AND SETTING: Prospective, observational study in the level III multidisciplinary neonatal and pediatric intensive care unit. PATIENTS: Sixty patients with systemic inflammatory response syndrome (SIRS) and suspected infection classified into two groups: SIRS/sepsis ( n=33) and SIRS/no sepsis ( n=27). We included 29 neonates aged less than 48 h (neonates <48 h), 12 neonates older than 48 h (neonates >48 h), and 19 children. Median disease severity was high in neonates aged under 48 h and moderate in neonates aged over 48 h and children. INTERVENTIONS: Serum LBP, PCT, IL-6, and CRP were measured on two consecutive days. Area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and predictive values were evaluated. RESULTS: Serum LBP was higher in patients with SIRS/sepsis than in patients with SIRS/no sepsis. AUC for LBP on the first day of suspected infection was 0.89 in the younger neonates, 0.93 in the older neonates, and 0.91 in children. CONCLUSIONS: In critically ill neonates aged under 48 h LBP on the first day of suspected infection is a better marker of sepsis than IL-6 and PCT, and is similar to CRP. In critically ill neonates aged over 48 h and children LBP is a better marker than IL-6 and CRP, and is similar to PCT.

Acute-Phase Proteins↗

PubMed2003

[Multicentric study on neonatal medical pain management in the Nord-Pas-de-Calais].

UNLABELLED: The aim of this study was to describe pain management for newborn infants in neonatal intensive care units and neonatal units in the Nord-Pas-de-Calais. PATIENTS AND METHODS: A questionnaire was distributed to the 52 physicians practising in the six neonatal intensive care units and six neonatal units. The questions were in reference to pain assessment, treatment and prevention. RESULTS: Forty questionnaires were completed (77%). Eleven units proclaimed an interest in neonatal pain management. The tool for assessing pain was the EDIN scale (Echelle Douleur Inconfort Nouveau-né, neonatal pain and discomfort scale). Analgesic treatment was administered in 100% of cases for the insertion of chest tube, in 92% of cases for the insertion of percutaneous central catheter in a ventilated newborn infant and in 91% of cases for necrotizing enterocolitis requiring a mechanical ventilation. Prescribed analgesic drugs were propacetamol, nalbuphin or fentanyl; a sedation by midazolam or diazepam was occasionally associated. Emla cream was used before lumbar puncture in 80% of cases in the neonatal intensive care units and in 92% of cases in the neonatal units. Three neonatal intensive care units and four neonatal units administered a sucrose solution for blood samples. CONCLUSION: At the time of study, the interest in the pain of the physicians working in neonatal intensive care units and neonatal units was inadequate to guarantee an optimum management of pain in newborn infants. Physicians' approach remained heterogeneous.

Analgesics↗

PubMed2003

[Utility of congenital hypothyroidism screening in neonates for monitoring iodine deficit disorders in the Canary Islands (Spain)].

BACKGROUND: Newborns in European cities where iodine intake is low have been demonstrated to present high frequencies of transitory hypothyroidism. Because the neonatal period is critical for cerebral development, this is a cause for concern. Published studies (WHO/UNICEF/ICCIDD) indicate that neonates with a thyroid-stimulating hormone (TSH) concentration of more than 5 mU/ml revealed by screening for congenital hypothyroidism present mild iodine deficiency. OBJECTIVE: To analyze the utility of TSH values as an indicator of the prevalence of iodine deficiency in the general population. MATERIAL AND METHODS: We prospectively evaluated 19 809 neonates, corresponding to all the neonates screened from May 2001 to April 2002 in the Canary Islands.TSH determination in whole blood dried on filter paper was performed using immunofluorescence (Delphia) in the Center for the Detection of Metabolic Disorders in the Canary Islands. The percentage of neonates in each island with TSH values of > 5 mU/l was calculated. Samples of cord blood were not used. RESULTS: A total of 19 809 infants were analyzed. Of these 1800 had values of TSH > 5 mU/L, representing 9.08 % of neonates. The mean age at blood extraction was 4.31 6 3.78 days (range: 0.5-40). The percentage of neonates with values of THS > 5 mU/L in each island was 13.1 % in Gran Canaria, 5.1 % in Lanzarote, 7.3 % in Fuerteventura, 6.0 % in Tenerife, 6.2 % in La Palma, 6.6 % in Gomera and 10.1 % in Hierro. In 77.5 % of neonates in Gran Canaria blood was extracted for screening within the first 72 hours of life and 15.2 % of these neonates had TSH concentrations of > 5 mU/L. In 22.5 % of neonates blood was extracted on the third day of life or later and 7.9 % of these neonates had TSH values of > 5 mU/L. CONCLUSIONS: In the Canary Islands, the percentage of neonates with iodine deficiency, according to elevated TSH levels detected screening for congenital hyperthyroidism, was small. The validity of TSH level as an indicator of the prevalence of iodine deficiency in the general population is influenced by the days of life at which the blood sample is taken.

Atlantic Islands↗

PubMed1994

Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years' experience.

OBJECTIVE: To assess the performance and impact of a two tier neonatal screening programme for cystic fibrosis based on an initial estimation of immunoreactive trypsinogen followed by direct gene analysis. DESIGN: Four year prospective study of two tier screening strategy. First tier: immunoreactive trypsinogen measured in dried blood spot samples from neonates aged 3-5 days. Second tier: direct gene analysis of cystic fibrosis mutations (delta F508, delta I506, G551D, G542X, and R553X) in samples with immunoreactive trypsinogen concentrations in highest 1% and in all neonates with meconium ileus or family history of cystic fibrosis. SETTING: South Australian Neonatal Screening Programme, Adelaide. SUBJECTS: All 88,752 neonates born in South Australia between December 1989 and December 1993. INTERVENTIONS: Neonates with two identifiable mutations were referred directly for clinical assessment and confirmatory sweat test; infants with only one identifiable mutation were recalled for sweat test at age 3-4 weeks. Parents of neonates identified as carriers of cystic fibrosis mutation were counselled and offered genetic testing. MAIN OUTCOME MEASURES: Identification of all children with cystic fibrosis in the screened population. RESULTS: Of 1004 (1.13%) neonates with immunoreactive trypsinogen > or = 99th centile, 912 (90.8%) had no identifiable mutation. 23 neonates were homozygotes or compound heterozygotes; 69 carried one identifiable mutation, of whom six had positive sweat tests. Median age at clinical assessment for the 29 neonates with cystic fibrosis was 3 weeks; six had meconium ileus and two had affected siblings. 63 neonates were identified as carriers of a cystic fibrosis mutation. Extra laboratory costs for measuring immunoreactive trypsinogen and direct gene analysis were $A1.50 per neonate screened. CONCLUSION: This strategy results in early and accurate diagnosis of cystic fibrosis and performs better than screening strategies based on immunoreactive trypsinogen measurement alone.

Cystic Fibrosis↗

PubMed1993

Failed extubation in the neonatal intensive care unit.

One of the roles of the pediatric otolaryngologist in the neonatal intensive care unit (NICU) is the assessment and management of the neonate who fails a trial of extubation. This paper reviews the recent 5-year institutional experience at The Hospital for Sick Children, Toronto, with neonates who failed extubation and who subsequently underwent diagnostic endoscopy. One hundred twenty-eight neonates from the NICU underwent diagnostic endoscopy. Of these, 58 neonates underwent diagnostic endoscopy for failure to extubate. Nine neonates were extubated after diagnostic endoscopy and retrial (16% of the series). Eleven neonates were extubated after additional endoscopic procedures (19% of the series). Twenty-four neonates underwent anterior cricoid split, of whom 20 or 83% (34% of the series) were eventually successfully extubated with no further airway intervention required during the study period (minimum 6 months' follow-up). Eleven neonates underwent tracheotomy (19% of the series). Four neonates underwent another external procedure to allow extubation (7% of the series). Three neonates died while still intubated (5% of the series). Our management of the neonate who fails a trial of extubation is discussed.

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