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PubMed2003

The development of cerebral perfusion in healthy preterm and term neonates.

Quantitative measurement of cerebral blood flow (CBF) volume was performed by sonographic flowmetry of both internal carotid (ICA) and vertebral arteries (VA) in 113 healthy preterm and term infants of 32 - 42 weeks postmenstrual age (PA) in order to delineate the physiological characteristics of brain perfusion in a time period very sensitive to brain injury. Mean CBF volume increased with PA, beginning with 33 +/- 9 ml/min in neonates of 32 - 34 weeks and rising to 45 +/- 10, 58 +/- 13, 69 +/- 14, and 83 +/- 16 ml/min, respectively, in the PA groups of 35 - 36, 37 - 38, 39 - 40 and 41 - 42 weeks. There was no difference in CBF volume between the sexes. The bilateral sum of flow volumes in both ICA and VA rose markedly with PA. The relative contribution of bilateral VA flow volume to total CBF volume was 26 +/- 8 % and remained constant with PA. In addition, we calculated the approximate CBF (ml/100 g brain weight/min) using the brain weights of each child as estimated by means of an equation based on head circumference measurements. Estimated CBF correlated significantly with PA (r = 0.49; p </= 0.0001), reflecting the rising metabolic demand of the growing brain during the time period examined.

Age Factors↗

PubMed2004

Gastroesophageal reflux in infants < 32 weeks gestational age at birth: lack of relationship to chronic lung disease.

The objective of this study was to determine the incidence of gastroesophageal reflux (GER) as documented by extended esophageal pH monitoring in symptomatic premature infants and to identify its relationship with chronic lung disease (CLD). This was a retrospective study of 629 infants born < 32 weeks gestational age and admitted to the neonatal intensive care unit during the study period. Univariate analyses were done on the 137 infants undergoing the test for the association of the following risk factors with acid reflux: birth weight, gestational age, race, sex, length of stay, bronchopulmonary dysplasia (BPD; O2 requirement at 28 days), and severe CLD (O2 requirement at 36 weeks postmenstrual age). Eighty-seven of 137 infants were positive for GER. There was no association of GER with the risk factors studied, nor were there correlations with BPD or severe CLD. GER is common (63%) in premature infants < 32 weeks gestational age but clinical symptoms and CLD are poorly correlated with this diagnosis.

Bronchopulmonary Dysplasia↗

PubMed2004

The effect of positioning on energy expenditure in preterm infants: a feasibility study.

The aim of this study was to determine the feasibility of a study of the effect of positioning on energy expenditure in preterm infants. We performed a prospective, randomized, clinical cross-over pilot study of eight healthy, appropriate weight for gestational age, gavage-fed, clinically stable preterm infants at the postmenstrual age of 30 weeks. Prior to the study and in accord with our feeding protocol, infants uniformly received either their own mother's milk or a preterm formula. Each infant was studied in four different positions after randomization to eight different sequences. Infants were studied asleep, 90 minutes after feeding, after 20 minutes of being nursed in a given position. They were cared for in a servo-controlled convective incubator during the metabolic measurements, which were performed by indirect calorimetry. Energy expenditure was not significantly affected by the body position in which the infant was studied. The difference between the highest and the lowest mean energy expenditure was 3.7% of the highest one. We conclude that attempts to minimize energy expenditure by modifying infant positioning are likely to be insignificant, from a practical standpoint, because of the nonsignificant or minimal differences in energy expenditure.

Calorimetry, Indirect↗

PubMed2006

Are routine cranial ultrasounds necessary in premature infants greater than 30 weeks gestation?

The purpose of this study was to validate the recommendation of the American Academy of Neurology and the Child Neurology Society that screening cranial ultrasonography be performed routinely on all infants of less than 30 weeks gestation at 7 to 14 days of age and again between 36 and 40 weeks postmenstrual age, and, by using this practice parameter, to determine the number of babies with a clinically significant abnormal screening cranial ultrasound (US) who would otherwise have been missed. A retrospective study of 486 infants of 30 to 33 weeks gestation born January 1, 1999 to June 30, 2004 was done. All had screening cranial ultrasounds. Grade III and/or grade IV intraventricular hemorrhage (IVH) occurred in 4 (0.8%) infants of 30 to 31 weeks gestation. Infants with significant IVH had either risk factors for brain injury or symptoms that would eventually warrant US during their hospitalization. Seven (1.4%) infants had periventricular leukomalacia (PVL). All infants with a final diagnosis of PVL had pre- and/or perinatal risk factors associated with PVL. There was a significant trend toward fewer abnormal cranial ultrasounds from 30 to 33 weeks gestation (p=0.04). Our study supports the recommendation by the American Academy of Neurology and the Child Neurology Society that screening US can be limited but suggests that the gestational age cut off should be 30 weeks or less.

Cerebral Hemorrhage↗

PubMed2006

Serum caffeine concentrations in preterm neonates.

Caffeine therapy reduces apnea of prematurity, promotes successful extubation from invasive positive-pressure ventilation, and decreases the incidence of bronchopulmonary dysplasia. The recommended dosing for caffeine is a loading dose of 20 mg/kg followed by a 5 mg/kg/d maintenance dose. However, controversy exists about the optimal dosing regimen and data on serum caffeine concentrations in extremely immature infants are scant. We determined serum caffeine concentrations approximately 7 days after starting therapy with a 20 or 25 mg/kg loading dose and a 6 mg/kg/d maintenance dose in 154 infants with a mean gestational age of 29 weeks. The 25th to 75th percentile range for the serum caffeine concentrations with the two dosing regimens was equivalent, approximately 18 to 23 mg/L. Within the first 14 postnatal days, the serum caffeine concentrations were not dependent on postmenstrual age, weight, or postnatal age, and were in a range that is safe and therapeutic. This latter observation remained valid over the ranges of clinical and laboratory assessments of renal and hepatic functions that are usually found in practice. Routine measurement of steady-state serum caffeine concentrations in infants 24 to 35 weeks gestational age is not required in the absence of ongoing apnea/hypopnea or signs compatible with toxicity.

Apnea↗

PubMed1999

Asymmetrical myelination of the posterior limb of the internal capsule in infants with periventricular haemorrhagic infarction: an early predictor of hemiplegia.

AIM: To prospectively assess the predictive value of asymmetrical myelination on MRI of the posterior limb of the internal capsule (PLIC) in newborn infants with an intraventricular haemorrhage (IVH) associated with unilateral haemorrhagic parenchymal involvement (PI), for subsequent development of a hemiplegia. METHODS: 12 preterm infants (GA 25-36 wks) and 4 full-term infants were studied. Using cranial ultrasound (US), the pre-term infants were diagnosed to have an IVH with unilateral PI. The term infants presented with a porencephalic cyst (PC) on the first postnatal US, following an antenatal IVH with PI. MRI was performed at 40 wks postmenstrual age in the pre-term infants and during the first 2 weeks of life in the full-term infants, using a 1.5T magnet. Using an inversion recovery sequence, the myelination of the internal capsule was recorded as normal, abnormal or equivocal. Neurological assessment > or = 12 months disclosed the presence of a hemiplegia or asymmetry in tone pattern. RESULTS: All 4 cases with a normal internal capsule had a normal outcome in spite of the development of a PC. All 9 cases with an abnormal PLIC developed a hemiplegia, while 1 of the 3 cases with an equivocal PLIC is normal on neurological assessment, one developed a mild asymmetry in tone and 1 a mild hemiplegia. CONCLUSION: While a symmetrical signal intensity within the internal capsule on MRI, performed at 40 weeks PMA, in infants with an IVH and unilateral PI appears to be strongly related to a normal outcome, an asymmetrical PLIC is an early predictor of future hemiplegia.

Cerebral Infarction↗

PubMedDate not supplied

[Anterior fontanelle as a window to the brain--normal values and timing of closure].

Nowadays an exact examination of the infant's brain is possible through the anterior fontanelle by ultrasonography (US); however for that a certain minimal size of the fontanelle is necessary. In the literature standards for size and timing of closure are scarce. In the Bonn Longitudinal Study of growth and development of preterm infants in comparison with full term infants also the length (anterior-posterior diameter) and width (transversal) of the anterior fontanelle have been measured monthly from birth, and the timing of closure was registered. As a measure of fontanelle size here the width (transversal diameter) is used. For the full term infants the width (50. percentile) at birth is 2.0 cm; it decreases to 0.6 cm until the age of 12 months. The great variability of fontanelle size observed in the Bonn study is also confirmed in the literature. In the appropriate for gestational age (AGA) preterm infants the anterior fontanelle (50. percentile) increases between 32 and 40 postmenstrual weeks from 1.8 to 2.5 cm and is then significantly greater than in the full term infants. At least at the age of 3 months there is no significant difference between the AGA preterm infants and the full term infants, either for the boys or for the girls. For the boys, in spite of their significantly greater head circumference there is a tendency to have a smaller fontanelle than the girls; the difference is at no age significant. For preterm as well as for full term infants timing of closure occurs somewhat earlier in the boys than in the girls.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMed1987

Neurological, electrophysiological and MRI abnormalities in infants with extensive cystic leukomalacia.

Twenty infants, diagnosed by cranial ultrasound as having extensive cystic leukomalacia, had visual evoked responses (VER) and electroencephalograms (EEG) in the neonatal period and MRI scans later in infancy. The early ultrasound findings and results from the electrophysiological tests were correlated with later MRI findings and functional abilities. In infants with periventricular leukomalacia (PVL), the cysts were usually no longer visible by ultrasonography, beyond 40 weeks postmenstrual age (PMA), but later MRI scans showed a consistent pattern of delayed myelination around the irregularly dilated occipital horns of the lateral ventricles. VER's were present in the neonatal period and vision was maintained, although all infants developed a marked squint. EEG's were either normal or abnormal initially, but improvement was noted within several weeks. In those with subcortical or mixed lesions, cysts were noted to persist beyond 40 weeks PMA. Later MRI scans showed very poor myelination, with poor progress on subsequent scans and cortical atrophy. VER's were absent and all infants later became cortically blind. EEG's were severely abnormal and recovery was very poor. The infants with PVL developed spastic diplegia with moderate developmental delay, while those with mixed or subcortical lesions developed quadriplegia with severe mental retardation. An integrated approach, consisting of ultrasound imaging and electrophysiological recordings in the neonatal period and MRI imaging later in infancy, may provide a more reliable prediction of the pattern of later deficits.

Brain↗

PubMed1986

Normal cerebrospinal fluid pressure in the newborn.

Lumbar CSF pressure (CSFP) was measured on 61 occasions, in 49 babies undergoing lumbar puncture as part of a septic screen, by means of Gaeltec pressure transducers. In normal circumstances, intracranial pressure (ICP) has the same value. Measurements were made when the baby was horizontal and quiet, with the head deflexed. For acceptance of the measurement, it was essential for the CSF to be clear and to show pressure pulses with respiration, heartbeat and jugular occlusion. The mean CSFP and standard deviation were 2.8 +/- 1.4 mm Hg (3.8 +/- 1.9 cm water), with a normal range of 0 to 5.7 mm Hg (0 to 7.6 cm water). This value is similar to previous reports of CSFP measured invasively in infants, but is much lower than the "ICP" established noninvasively. No relationship was found between birthweight, gestational age, current weight, postmenstrual age, or postnatal age and CSFP.

Birth Weight↗

PubMed1982

Neurological and neurobehavioural differences between preterm infants at term and full-term newborn infants.

A detailed neurological and neurobehavioural examination was done in 80 preterm infants of 27 to 35 weeks gestation in the first week of life and again at 40 weeks postmenstrual age, and in 40 appropriately-sized full-term infants on the first and fifth days of life. There were several consistent differences between the preterm infants reaching term and the newborn full-term infants. The preterm infants reaching 40 weeks showed less flexion in their posture, and less arm traction, arm recoil and leg recoil than the full-term infants on day 1, although this difference was less apparent by day 5. The preterm infants appeared not to develop the flexor tone of the full-term newborn. The preterm infants demonstrated better visual and auditory orientation and alertness than the full-term infants. The significance of these findings, both for initial neonatal examinations and for subsequent assessments, is evaluated.

Arousal↗

PubMed1990

Does very preterm birth impair myelination of the central nervous system?

Myelination of the central nervous system (CNS) can be demonstrated with magnetic resonance (MR) imaging. Myelin formation may be reduced in conditions of neonatal "undernutrition". Very preterm infants have a reduced postnatal growth rate when compared with intrauterine fetuses of the same gestational age. Using MR imaging, we studied qualitative myelination patterns in healthy preterm infants of less than 30 weeks gestation with an optimal nutritional intake and in term infants at 44 weeks postmenstrual age (PMA). At that age, preterm infants had a significantly lower mean body weight than term infants, but mean head circumference did not differ significantly. All preterm and term infants had reached myelination stage M3 (myelin in brainstem, internal capsule, and corona radiata) and M4 (myelin in brainstem, internal capsule, corona radiata, and centrum semiovale). There was no significant difference in myelination stage between the preterm and term infants. We conclude that adequate nutrition in the neonatal period leads to qualitatively adequate myelination of the CNS in very preterm infants.

Central Nervous System↗

PubMed1998

Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group.

BACKGROUND: Pulmonary disease is common in preterm infants, despite antenatal glucocorticoid therapy. The addition of antenatal thyrotropin-releasing hormone therapy has been reported to decrease pulmonary morbidity in these infants. METHODS: We enrolled 996 women at 13 North American centers who were in preterm labor at <30 weeks' gestation in a double-blind, placebo-controlled, randomized trial of antenatal thyrotropin-releasing hormone, given intravenously in four doses of 400 microg each at eight-hour intervals. The primary outcome was chronic lung disease or death of the infant on or before the 28th day after delivery, and secondary outcomes were respiratory distress syndrome and chronic lung disease or death at 36 weeks' postmenstrual age. Complete data were available for 981 women and their 1134 live-born infants. The 769 infants born at < or = 32 weeks' gestation were defined as the group at risk. RESULTS: There were no significant differences between the at-risk treatment and placebo groups in mean (+/-SD) birth weight (1109+/-354 vs. 1097+/-355 g), gestational age (27.9+/-2.1 vs. 27.9+/-2.1 weeks), sex, or race. The frequencies of respiratory distress syndrome (66 percent vs. 65 percent), death at 28 days (11 percent vs. 11 percent), chronic lung disease or death at 28 days (45 percent vs. 42 percent) and at 36 weeks (32 percent vs. 34 percent), and other neonatal complications as well as the severity of lung disease were not significantly different in the at-risk treatment and placebo groups. Similarly, there were no differences in outcome between the treatment and placebo groups for the infants born at >32 weeks' gestation. CONCLUSIONS: In preterm infants at risk for lung disease, antenatal administration of thyrotropin-releasing hormone and glucocorticoid is no more beneficial than glucocorticoid alone.

Adult↗

PubMed2002

High-frequency oscillatory ventilation for the prevention of chronic lung disease of prematurity.

BACKGROUND: There remains uncertainty concerning the safety and efficacy of high-frequency oscillatory ventilation as compared with those of conventional ventilation for the respiratory support of very preterm infants. We conducted a multicenter trial to determine whether early intervention with high-frequency oscillatory ventilation reduced mortality and the incidence of chronic lung disease among newborns with a gestational age of 28 weeks or less. METHODS: We randomly assigned preterm infants with a gestational age of 23 to 28 weeks to either conventional ventilation or high-frequency oscillatory ventilation within one hour after birth. Randomization was stratified according to center and gestational age (23 to 25 weeks or 26 to 28 weeks). RESULTS: A total of 400 infants were assigned to high-frequency oscillatory ventilation, and 397 were assigned to conventional ventilation. The composite primary outcome (death or chronic lung disease, diagnosed at 36 weeks of postmenstrual age) occurred in 66 percent of the infants assigned to receive high-frequency oscillatory ventilation and 68 percent of those in the conventional-ventilation group (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.98; 95 percent confidence interval, 0.89 to 1.08). Similar proportions of infants died or had chronic lung disease in each gestational-age group. In both treatment groups treatment failure occurred in 10 percent of infants (relative risk in the group assigned to high-frequency oscillatory ventilation, 0.99; 95 percent confidence interval, 0.66 to 1.50). There were no significant differences between the groups in a range of other secondary outcome measures, including serious brain injury and air leak. CONCLUSIONS: The results obtained with high-frequency oscillatory ventilation and conventional ventilation do not differ significantly in the early treatment of respiratory disease in very preterm infants. Assessment of long-term effects will require additional follow-up.

Bronchopulmonary Dysplasia↗

PubMed2006

Early inhaled nitric oxide therapy in premature newborns with respiratory failure.

BACKGROUND: The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain. METHODS: We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation. Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g). The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly. RESULTS: Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (71.6 percent vs. 75.3 percent, P=0.24). However, for infants with a birth weight between 1000 and 1250 g, as compared with placebo, inhaled nitric oxide therapy reduced the incidence of bronchopulmonary dysplasia (29.8 percent vs. 59.6 percent); for the cohort overall, such treatment reduced the combined end point of intracranial hemorrhage, periventricular leukomalacia, or ventriculomegaly (17.5 percent vs. 23.9 percent, P=0.03) and of periventricular leukomalacia alone (5.2 percent vs. 9.0 percent, P=0.048). Inhaled nitric oxide therapy did not increase the incidence of pulmonary hemorrhage or other adverse events. CONCLUSIONS: Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury. (ClinicalTrials.gov number, NCT00006401 [ClinicalTrials.gov].).

Administration, Inhalation↗

PubMed2001

Antenatal glucocorticoid treatment does not reduce chronic lung disease among surviving preterm infants.

BACKGROUND: Antenatal glucocorticoid treatment (AGT) is associated with a number of postnatal benefits to the preterm infant, including reduced risk of respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. OBJECTIVE: To evaluate the hypothesis that maternal AGT not only reduces the risk of surfactant deficiency but also reduces the occurrence of chronic lung disease (CLD) among surviving preterm infants. STUDY DESIGN: Case-referent study of 1454 very low birth weight infants born between January 1991 and December 1993 at 4 university medical centers. RESULTS: Rates of AGT varied among the 4 centers (11%-69%), as did rates of CLD (4%-21%), defined as a requirement for supplemental oxygen at 36 weeks' postmenstrual age. CLD rates at each center, however, did not vary with the rate of AGT exposure. In multivariate logistic regression analyses, AGT did not contribute significantly to CLD risk. CONCLUSION: AGT may play a less prominent role in modifying CLD risk than other factors such as biologic immaturity, infection, or neonatal intensive care unit practices, such as mechanical ventilation, continuous positive airway pressure, and surfactant replacement therapy.

Chronic Disease↗

PubMed2001

Reduced lighting does not improve medical outcomes in very low birth weight infants.

OBJECTIVE: To objectively assess the effect of light reduction as an isolated environmental intervention on neonatal morbidity. STUDY DESIGN: Randomized multicenter trial. Neonates < 1251 g birth weight and < 31 weeks gestational age were randomly assigned to receive goggles or to a control group. Goggles that reduced visible light by 97% were placed within 24 hours of birth and remained in use until 31 weeks postmenstrual age or for a minimum of 4 weeks. RESULTS: Four hundred nine infants were enrolled, and outcome data are reported for 359 surviving infants. There were no significant differences between the groups in weight gain, duration of oxygen therapy, mechanical ventilation, or hospital stay either in the unadjusted analyses or in the analyses adjusted for birth weight, gestational age, race, sex, and inborn (born in study hospital) status. There was no difference between the groups in the incidence of intracranial hemorrhage. CONCLUSIONS: This randomized trial of continuous light reduction in the first few weeks of life for very low birth weight infants showed no effect on medical outcomes.

Child Development↗

PubMed2002

Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula.

OBJECTIVE: To determine if docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation influences growth or visual acuity of formula-fed premature infants. STUDY DESIGN: Double-blind, multi-center study of 194 premature infants given preterm formula with no DHA or ARA (control), 0.15% energy DHA, or 0.14% DHA + 0.27% ARA from single-cell triglycerides for at least 28 days and then fed term formula (no DHA or ARA) to 57 weeks postmenstrual age (PMA), with 90 breast-fed term infants as reference. RESULTS: Infants fed DHA+ARA formula gained weight significantly faster (post-hoc analysis) during preterm formula feeding than control infants (34.7 vs. 30.7 g/d) and had weights and weight:length ratios not different from term breast-fed infants at 48 and 57 weeks PMA. Infants fed control or DHA formula had lower body weights than term infants. Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40, 48, and 57 weeks PMA (r = 0.19 to 0.24, P =.004-.02). Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events. CONCLUSIONS: Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects.

Analysis of Variance↗

PubMed2002

Sleep organization is unaffected by caffeine in premature infants.

We performed 10-hour polysomnographic recordings in 15 neurologically normal and clinically stable 33- to 34-week postmenstrual age (PMA) neonates, 10 of whom had been treated >3 days with once-per-day oral caffeine citrate (5 mg/kg) given at approximately 2 PM. We analyzed (a) the usual sleep-wake variables, including wakefulness, active sleep, quiet sleep, and indeterminate sleep expressed as the number of episodes, duration, and percentage of total sleep time; (b) the duration and order of variable modifications during transitions between the main active sleep and quiet sleep states; and (c) the characteristics of morning data (before caffeine) compared with evening data (after caffeine). We found no significant differences between the controls and the infants receiving maintenance caffeine.

Caffeine↗