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PubMed2005

Automated state analyses: proposed applications to neonatal neurointensive care.

The two principal challenges of neonatal physiologic monitoring device are: (1) the development of computational strategies that consider the rudimentary forms of neonatal sleep state especially for preterm infants and (2) any physiologic monitoring device for clinical applications in a neonatal intensive care setting must be small, portable, and user-friendly. Our multicenter neonatal sleep consortium has acquired more than 1,100 multihour EEG-sleep recordings on over 370 neonates, ranging from 24 to 44 weeks gestation. Each recording was visually-scored for state, arousals, movements, and rapid eye movements, which were used as templates when applying spectral analyses. The authors have defined a brain dysmaturity index to represent functional brain reorganization as the prenate matures to a full-term age; delayed or accelerated physiologic behaviors have been described for the preterm cohort when compared to the full-term group at the same postmenstrual age. Seven EEG-sleep measures comprise this index: quiet sleep percentage, sleep cycle length, rapid eye movements, arousals, spectral beta EEG energies, spectral EEG correlations, and a spectral measure of respiratory regularity. Linear and nonlinear computational algorithms are being developed to automate the computation of the dysmaturity index and to identify new feature types that correlate with dysmaturity. Automated neonatal sleep monitoring system can potentially improve neonatal neurointensive care by facilitating analyses of pervasive neonatal brain disorders expressed primarily as altered sleep state organization, and help predict altered developmental trajectories of children at higher risk for neurologic sequelae.

Brain↗

PubMed2006

Local holder exponent analysis of heart rate variability in preterm infants.

Heart rate variability (HRV) displays scale-invariant fractal properties. Recent studies have revealed multifractal properties in the healthy human HRV, which could be characterized by singularities with various strength of local Hölder exponents embedded in HRV. In this paper, HRV time series from preterm infants, whose autonomic nervous system undergoes dramatic development, were collected longitudinally. Changes in fractality/multifractality of those HRV time series as the postmenstrual age were examined in order to see if they could quantify development of the autonomic nervous system. Temporal structure of the singularities at several representative time scales was also analyzed to show that intersingular event intervals could be well described by "power law distribution," and the singular events appeared with age-dependent long-range correlation in its strength. Detailed analyses suggested that fractality and multifractality of HRV, respectively, could quantify the development of the respiratory center and the parasympathetic nervous system in the preterm infants. The results obtained in this study might be beneficial for detecting occurrences of life threatening singular events such as big apnea in preterm infants.

Algorithms↗

PubMed2005

Litmus tests for verification of feeding tube location in infants: evaluation of their clinical use.

AIMS: To examine the clinical use of litmus paper tests for the assessment of aspirates in infants. BACKGROUND: In connection with establishing a programme for home care of infants with requirement of tube feeding with parents as the infants' carers, the need for a research-based method for verification of feeding tube position was identified by nurses as a complement to other methods. In adult care the litmus paper test is commonly used when visual inspection is not sufficient for assessment of aspirates obtained from feeding tubes. DESIGN: Observational study. METHODS AND MATERIAL: Nurses performed litmus tests for verification of feeding tube location in a convenience sample of 60 infants born at a gestational age (GA) of 24-42 weeks. Presence/absence and volumes of aspirates were recorded as well as positive/negative litmus test reactions. Analyses on the association between test results and the infants' GA and postmenstrual and postnatal age at the time of the tests were conducted. RESULTS: Data were obtained from 2970 tube feeds. Aspirates were present on 1840 occasions (62%). A higher proportion of infants with absence of aspirates were born at a GA below 32 weeks. A positive reaction occurred in 97% of the tests in volumes between 0.01 and 22 ml. Birth at a GA below 32 weeks and respiratory problems were associated with negative tests. CONCLUSION: The high ratio of positive litmus reactions at all maturational levels supports the bedside use of analysis of pH in gastric aspirates for verification of feeding tube location. RELEVANCE TO CLINICAL PRACTICE: Application of pH indicator paper is recommended as a complementary method for assessment of aspirates from feeding tubes.

Age Factors↗

PubMed2005

Dose-finding study of ibuprofen in patent ductus arteriosus using the continual reassessment method.

OBJECTIVE: Intravenous ibuprofen (IBU) has been found to be as effective as indomethacin for the treatment of patent ductus arteriosus (PDA) in preterm infants and has been associated with fewer adverse effects in comparative phase III studies. The dose regimen used (10-5-5 mg/kg/day) was based on limited pharmacokinetic data and no phase II study was available to determine the optimal dose of IBU for this indication. The present study was designed to determine the minimum effective dose regimen (MEDR) of IBU (one course) required to close ductus arteriosus in preterm infants. METHOD: A double-blind dose-finding study was conducted using the continual reassessment method, a Bayesian sequential design. Two distinct target closure rates were initially chosen according to postmenstrual age (PMA) at birth: 80% in infants with a PMA of 27-29 weeks, and 50% in infants with a PMA < 27 weeks. Forty neonates (20 in each PMA group) with PDA were treated between days 3 and 5 of life. Four different dose regimens were tested: loading doses of 5, 10, 15 or 20 mg/kg, followed by two doses (1/2 loading dose) at 24-h intervals. Efficacy was evaluated by echocardiography 24 h after the third infusion. RESULTS: In infants with a PMA of 27-29 weeks, the estimated MEDR was 10-5-5 mg/kg with a final estimated probability of success of 77% (95% credibility interval: 56-92%). The 15-7.5-7.5 mg/kg dose regimen had a better estimated probability of success (88%, 95% credibility interval: 68-97%), but resulted in more minor renal adverse effects. In contrast, in infants with a PMA < 27 weeks, the estimated MEDR was 20-10-10 mg/kg with an estimated probability of success of 54.8% (95% credibility interval: 22-84%), whereas the conventional dose regimen resulted in a low estimated probability of success (30.6%, 95% credibility interval: 13-56%). In these infants, compared with those with a PMA of 27-29 weeks, minor renal adverse effects were more frequent from the 10-5-5 mg/kg/day dose regimen and did not appear to be clearly dose related. CONCLUSION: This study confirms that the currently recommended dose regimen (10-5-5 mg/kg) of IBU is associated with a high closure rate (80%) and few adverse effects in premature infants with a PMA of 27-29 weeks. The failure rate was much higher below 27 weeks. A higher dose regimen (20-10-10 mg/kg) might achieve a higher closure rate. However, tolerability and safety of this dose regimen should be assessed in a larger population before considering the use of these doses for ductus arteriosus closure.

Bayes Theorem↗

PubMed2005

Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults.

We evaluated the upper oesophageal sphincter (UOS) relationship with oesophageal body during primary peristalsis (PP) sequences in healthy human neonates during maturation and compared with that of healthy adult volunteers. Forty-nine studies were performed using a water perfusion manometry system and a specially designed oesophageal catheter with a UOS sleeve concurrent with submental electromyogram in 31 subjects in supine position (18 preterm neonates, 29.9 +/- 2.5 weeks gestation; four full-term neonates, 39.3 +/- 1.0 weeks gestation; and nine adults, 18-65 years). The preterm neonates were studied longitudinally at 33 and 36 weeks postmenstrual age (PMA) and full-term born at 40 weeks PMA. Data were compared between the groups to recognize the effects of gestation, postnatal age and ageing. We evaluated 403 consecutive spontaneous solitary swallows during maturation (preterm at time-1 vs time-2) and growth (preterm and full-term vs adults) and observed significant (P < 0.05) differences in the basal UOS resting pressure, UOS relaxation characteristics, proximal and distal oesophageal body amplitude, duration, propagation and peristaltic velocity. Characteristics of UOS and PP are well-developed by 33 weeks PMA and undergo further maturation during the postnatal period, and are significantly different from that of adult.

Adult↗

PubMed1992

Audiological evaluation of very low birthweight infants.

A population of consecutively surviving very low birthweight (VLBW) infants comprising 41 infants (24 female) birthweight less than 1000 g and 108 infants (63 female) birthweight 1000-1500 g received detailed audiological evaluation. The audiological test battery comprised auditory brainstem evoked response (ABR) prior to hospital discharge, behavioural audiometry and tympanometry at 8-12 months and monitoring as necessary. The ABR results were interpreted with reference to a normative group of 36 full-term infants (birthweight 2.4-4.5 kg). Of the 142 VLBW infants completing audiological evaluation, one (0.7%) had evidence of moderate-severe high frequency sensorineural hearing loss, 83 (58.5%) evidence of conductive dysfunction (18 severe, 42 moderate and 23 mild) and only 58 (40.8%) normal hearing. The 19 infants with severe auditory impairment were more likely to have suffered moderate-severe apnoea, greater than or equal to two courses of mechanical ventilation, prolonged oxygen therapy and recurrent upper respiratory tract infections in the first year of life than infants without severe impairment (P less than 0.05). Because of the incidence of conductive pathology, difficulties occurred when attempting to compare ABR status at 36-42 weeks postmenstrual age with peripheral hearing status at 8-12 months as assessed by visual reinforcement orientation audiometry (VROA) and impedance audiometry. The most useful ABR test parameters as screening measures of peripheral auditory status were Wave I-III-V morphology, wave V threshold levels and wave V absolute latency values when used in combination as a test battery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Impedance Tests↗

PubMed2004

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia.

OBJECTIVE: To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use. METHODS: Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age. RESULTS: Two hundred and forty-one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty-one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia. CONCLUSION: The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.

Betamethasone↗

PubMed2004

No correlation of depression and anxiety to plasma estrogen and progesterone levels in patients with premenstrual dysphoric disorder.

A number of studies have demonstrated the correlation of depression and anxiety to estrogen and progesterone in premenstrual dysphoric disorder (PMDD), but the findings are still controversial. The purpose of this study was to determine the correlation of depression and anxiety to estrogen and progesterone concentrations in blood plasma in Taiwanese women with PMDD. A total of 43 women who met the 4th edition of the Diagnostic and Statistical Manual diagnostic criteria for PMDD were enrolled in this study. Blood samples were obtained for determination of estrogen and progesterone levels, and depression and anxiety ratings were summed for each subject during one menstrual cycle to obtain a premenstrual result (2-6 days before menses) and a postmenstrual result (menstrual cycle days 7-11). Anxiety was assessed using the 14-item Hamilton Anxiety Scale-A and was also assessed by the patients themselves using the Trait Anxiety Inventory. Depression was rated using the 21-item Hamilton Anxiety Scale-D. Calculations were made to determine the relationships between hormonal changes and mood changes. There were no statistically significant correlations between depression or anxiety ratings and estrogen or progesterone concentrations.

Adult↗

PubMed1978

Cystic fibrosis of the pancreas in a human fetus.

Postmortem examination of a 26 week old (postmenstrual) human fetus delivered by Cesarean section revealed meconium ileus and many swollen mucus-secreting cells in the gastro-intestinal mucosa. The pancreas showed extensive fibrosis, acinar destruction and dilatation of ducts containing eosinophilic casts. Mucous glands of the lungs also revealed mucous cells swollen and distended with their secretory products. The patient is believed to have cystic fibrosis of the pancreas, suggesting that the pathologic manifestations of the disease may begin early in fetal life.

Cystic Fibrosis↗

PubMed2005

Clinical characteristics of chronic lung disease without preceding respiratory distress syndrome in preterm infants.

BACKGROUND: Recently, the incidence of atypical presentation of chronic lung disease (CLD) that develops in infants without a history of preceding respiratory distress syndrome (RDS) is increasing. Therefore, the clinical characteristics of CLD without RDS in comparison with CLD with RDS were assessed. METHODS: Prospective cohort analysis was done from 117 very low-birthweight infants who were born in Seoul National University Hospital and survived more than 36 weeks postmenstrual age (PMA). RESULTS: Of the 117 infants analyzed, CLD developed in 44 infants (38%). Among these 44 infants, CLD with RDS developed in 27 infants (23%) and CLD without RDS developed in 17 infants (15%). Each type of CLD was subgrouped according to the presence of chorioamnionitis (CA): RDS(+)CA(+) CLD (n = 8) and RDS(+)CA(-) CLD (n = 19); and RDS(-)CA(+) CLD (n = 12) and RDS(-)CA(-) CLD (n = 5). There were no significant differences in the demographic characteristics between CLD with RDS and CLD without RDS. Chorioamnionitis was significantly more common in CLD without RDS, while patent ductus arteriosus was more common in CLD with RDS. Although the severity of initial respiratory failure was not greater than that of CLD with RDS, CLD without RDS showed a gradually increasing chronic oxygen requirement pattern. Chronic oxygen requirement pattern showed that infants with RDS(+)CA(+)CLD required the highest concentrations of oxygen not only initially but also thereafter until the 28th day of life and 36 weeks PMA. CONCLUSIONS: Although CLD without RDS was still less common than CLD with RDS, it comprised over a third of all cases of CLD in our study. Clinical characteristics and chronic oxygen requirement pattern of CLD without RDS seems to be less severe than those of CLD with RDS. Our data suggest that CLD without RDS may be developed by causes other than initial acute lung injury. Chorioamnionitis may be one of antecedents of CLD without RDS.

Case-Control Studies↗

PubMed2005

Risk factors for the different types of chronic lung diseases of prematurity according to the preceding respiratory distress syndrome.

BACKGROUND: Recently, atypical chronic lung disease (CLD) of prematurity that develops in the absence of preceding respiratory distress syndrome (RDS) have been observed frequently. The specific risk factors for atypical CLD that are presumed to be different from those for classical CLD that develops following RDS were assessed. METHODS: Prospective cohort analysis was done from 115 very low-birthweight infants who were born in Seoul National University Hospital, Seoul, Korea, and survived more than 36 weeks postmenstrual age or 28 days of life. All subjects were classified into either a preceding RDS group (n = 35) or a non-RDS group (n = 80). Logistic regression analysis was done for the multivariate assessment of specific risk factors for CLD in both groups. RESULTS: The analysis showed that short gestational age (GA; relative risk [RR], 3.1 per 1 week decrement; 95% confidence intervals [CI], 2.7-3.4), of the male gender (RR, 9.8; CI, 0.9-112), and poor response to surfactant (RR, 14; CI, 1.2-156) were significant risk factors for CLD in the preceding RDS group. In the non-RDS group, chorioamnionitis was one of the significant risk factors for CLD (RR, 4.8; CI, 1.1-21) along with short GA and high mean airway pressure (MAP) during the first 3 days of life. CONCLUSION: Chorioamnionitis was a risk factor for atypical CLD in addition to short GA and high MAP during the early postnatal period, and poor response to surfactant was a risk factor for classical CLD in addition to short GA and being male. Therefore, CLD is considered to have type-specific risk factors.

Chorioamnionitis↗

PubMed1991

Endometrial shedding and regeneration: an electron microscopic study in the human being.

Whether the stroma of the endometrium, the spongy layer or the deeper parts of the endometrial glands is the origin of the postmenstrual surface epithelium is a matter of different opinions. The endometrium was examined during the second day of the menstrual bleeding in 20 fertile females using the scanning electron microscope (SEM). Proliferative and secretory endometrium were present denoting the onset of regeneration by that time. The superficial parts of the endometrial glands in some areas were projecting on the surface of the remaining spongy layer like worms having nipple like heads and an opening like a mouth. Endometrial regeneration began in the deeper parts of the endometrial glands as columns of rounded cells with central cavities which had everted thick edges on reaching the surface. These everted edges were growing in all directions to cover the remaining spongy layer with surface epithelium containing ciliated and non-ciliated cells. Exposure of the deeper parts of the glands is essential for regeneration. The delay in shedding the superficial parts of the glands may play an important role in dysfunctional uterine bleeding.

Endometrium↗

PubMedDate not supplied

High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds.

Associations between antenatal maternal anxiety, measured with the State Trait Anxiety Inventory, and disorders in 8- and 9-year-olds were studied prospectively in 71 normal mothers and their 72 firstborns. Clinical scales were completed by the mother, the child, the teacher, and an external observer. Hierarchical multiple regression analyses showed that maternal state anxiety during pregnancy explained 22%, 15%, and 9% of the variance in cross-situational attention deficit hyperactivity disorder symptoms, externalizing problems, and self-report anxiety, respectively, even after controlling for child's gender, parents' educational level, smoking during pregnancy, birth weight, and postnatal maternal anxiety. Anxiety at 12 to 22 weeks postmenstrual age turned out to be a significant independent predictor whereas anxiety at 32 to 40 weeks was not. Results are consistent with a fetal programming hypothesis.

Adolescent↗

PubMed1985

Maturation of the visual evoked response and its correlation with visual acuity in preterm infants.

Visual evoked responses (VERs) were elicited in 70 infants with postmenstrual ages between 30 and 39 weeks. On the basis of neurological and ultrasound examinations, 30 of the infants were classed as neurologically normal and 40 as abnormal: 26 of the latter had periventricular haemorrhage. Initially the VER consisted of a negative deflection only, and the appearance of a positive wave immediately preceding the negative deflection was taken to indicate maturation of the VER. Maturation was significantly delayed in the neurologically abnormal infants, and the delay was related to the degree of neurological insult. The visual acuity of 32 infants was estimated within seven days of the VER recording. There was a correlation of 79 per cent between the VER and the data for visual acuity.

Birth Weight↗

PubMed1988

Maturation of the neonatal somatosensory evoked response in preterm infants.

A group of 102 neurologically normal neonates with gestations between 26 and 40 weeks, without abnormality on cranial ultrasound, underwent evoked response testing. Satisfactory results were obtained for 90 per cent of the infants. Normal ranges with 95 per cent tolerance limits for the short-latency N1 component of the response were obtained at postmenstrual ages between 29 weeks and term. Somatosensory evoked responses are a practical tool for evaluating sensorimotor pathways in the newborn infant's brain.

Afferent Pathways↗

PubMed1990

A longitudinal study of early leg postures of preterm infants.

The prone and supine resting postures of the pelvis and legs of 106 preterm infants (25 to 34 weeks gestation) were studied longitudinally between 30 and 38 weeks post-menstrual age. All the infants subsequently had normal motor development. Posture was graded in relation to three items: the angle of elevation of the pelvis and the weight-bearing surface of the knee in prone, and the angle of rotation of the leg in supine. Although no grade was found to be exclusive to a particular postmenstrual age, all three items showed a statistically significant progressive trend. Only less than 6 per cent of the infants regressed in grade during the study. Infants dependent on oxygen for more than 28 days had significantly lower grades for leg posture in both prone and supine. Posture was not significantly altered by time ex utero or by intra-uterine growth retardation. The results show that these observation items are suitable measures of the progressive development of antigravity postures of preterm infants.

Gestational Age↗

PubMed1993

Prognostic value of early somatosensory evoked potentials in neonates with cystic leukomalacia.

Somatosensory evoked potentials (SEPs) were performed between 31 and 49 weeks postmenstrual age on 33 neonates with extensive cystic leukomalacia. 27 had periventricular leukomalacia (PVL), while six had deep white matter lesions. All but two of the 27 infants with PVL had a reproducible potential at discharge, being delayed in 11 and within the normal range in 14. No potentials could be obtained in any of the infants with cysts in the deep white matter. All surviving infants developed severe neurological sequelae, irrespective of the N1 being delayed or within normal range. These data suggest that in infants with an ultrasound diagnosis of cystic leukomalacia, little additional information with regard to neurodevelopmental outcome is provided by performing median nerve SEPs, especially for those infants in whom the cystic lesions are restricted to the occipital periventricular white matter.

Brain↗

PubMed1994

Relation between neonatal cranial ultrasound abnormalities and cerebral visual impairment in infancy.

A prospective follow-up study was conducted of a cohort of 65 at-risk neonates to assess the predictive value of neonatal cranial ultrasound abnormalities for cerebral visual impairment in infancy. Visual function was assessed using the acuity card procedure and behavioural visual responses were tested. Normal visual function was found in controls as well as in infants with small haemorrhages or mild leukomalacia. Infants with large haemorrhages performed poorly at 40 weeks postmenstrual age, but recovered to within the normal range in the first half year. In contrast, of the infants with extensive cystic leukomalacia, four of nine preterm infants and three of four term infants were severely visually impaired at 18 months. In the more mature infants, the cystic lesions extended deeper into the subcortical white matter, and this appeared to be associated with a worse visual outcome. Cystic leukomalacia proved to be highly predictive of cerebral visual impairment in infancy.

Cerebral Hemorrhage↗