Fat trajectory after birth in very preterm infants mimics healthy term infants.

BACKGROUND: Infants born very preterm experience poor postnatal growth relative to intrauterine growth, but at term equivalent age, they have increased percentage body fat compared with infants born at term. OBJECTIVES: The aim of this study was to assess body composition in very preterm infants born before 32 weeks postmenstrual age and to compare this with infants born at 32-36 weeks of gestation. METHODS: Percentage fat, fat mass and fat-free mass were measured in 87 very preterm infants born <32 weeks of gestation and studied at 32-36 weeks and in 88 control infants born at 32-36 weeks of gestation and measured on days 2-5 postnatally. RESULTS: At 32-36 weeks, very preterm infants were lighter and shorter, had significantly greater percentage fat and absolute fat mass and had a significantly lower absolute fat-free mass than the control group. The trajectory in percentage fat over increasing postnatal age in very preterm infants was closely aligned to that in term infants. CONCLUSIONS: Infants born very preterm accumulate fat rapidly after birth and have a deficit in fat-free mass. Fat accumulation may be triggered by birth or associated events. If this rapid fat accretion is not taken into account, assessment of growth based on weight alone will underestimate the deficit in fat-free mass.

Bioelectrical impedance analysis for assessment of fluid status and body composition in neonates--the good, the bad and the unknown.

BACKGROUND/OBJECTIVES: There is a critical need for improved technologies to monitor fluid balance and body composition in neonates, particularly those receiving intensive care. Bioelectrical impedance analysis meets many of the criteria required in this environment and appears to be effective for monitoring physiological trends. SUBJECT/METHODS: The literature regarding the use of bioelectrical impedance in neonates was reviewed. RESULTS: It was found that prediction equations for total body water, extracellular water and fat-free mass have been developed, but many require further testing and validation in larger cohorts. Alternative approaches based on Hanai mixture theory or vector analysis are in the early stages of investigation in neonates. CONCLUSIONS: Further research is required into electrode positioning, bioimpedance spectroscopy and Cole analysis in order to realise the full potential of this technology.

Prediction of body water compartments in preterm infants by bioelectrical impedance spectroscopy.

BACKGROUND/OBJECTIVES: To evaluate nutritional interventions in preterm infants, a simple, accurate assessment of the type of growth, that is, change in body composition through the relative contributions of lean body tissue and fat mass to weight gain, is needed. Bioelectrical impedance may provide such a method. The aim of this study was to develop resistivity coefficients appropriate for use in bioelectrical impedance spectroscopy (BIS) analysis of body water volumes in preterm infants. SUBJECTS/METHODS: A total of 99 preterm infants were enrolled (mean gestational age 32 completed weeks). Total body water (TBW) and extracellular water (ECW) were determined using the reference methods of deuterium and bromide dilution. BIS measurements taken at the same time allowed calculation of resistivity coefficients. Predictions of TBW and ECW obtained using these coefficients were then validated against volumes determined using the reference methods in a separate cohort of infants. RESULTS: Data were available for 91 preterm infants. BIS-predicted TBW and ECW correlated well with the measured volumes (Pearson's r(p)=0.825 and 0.75, respectively). There was a small bias (TBW 10 ml and ECW 40 ml) but large limits of agreement (TBW ± 650 ml and ECW ± 360 ml). CONCLUSIONS: BIS appears to have limited clinical utility; however, the relatively small bias means that it may be useful for measurements within a population or for comparisons between groups in which population means rather than individual values are compared.

Automated criterion-based analysis for Cole parameters assessment from cerebral neonatal electrical bioimpedance spectroscopy measurements.

Hypothermia has been proven as an effective rescue therapy for infants with moderate or severe neonatal hypoxic ischemic encephalopathy. Hypoxia-ischemia alters the electrical impedance characteristics of the brain in neonates; therefore, spectroscopic analysis of the cerebral bioimpedance of the neonate may be useful for the detection of candidate neonates eligible for hypothermia treatment. Currently, in addition to the lack of reference bioimpedance data obtained from healthy neonates, there is no standardized approach established for bioimpedance spectroscopy data analysis. In this work, cerebral bioimpedance measurements (12 h postpartum) in a cross-section of 84 term and near-term healthy neonates were performed at the bedside in the post-natal ward. To characterize the impedance spectra, Cole parameters (R(0), R(∞), f(C) and α) were extracted from the obtained measurements using an analysis process based on a best measurement and highest likelihood selection process. The results obtained in this study complement previously reported work and provide a standardized criterion-based method for data analysis. The availability of electrical bioimpedance spectroscopy reference data and the automatic criterion-based analysis method might support the development of a non-invasive method for prompt selection of neonates eligible for cerebral hypothermic rescue therapy.

Prediction of outcome following hypoxia/ischaemia in the human infant using cerebral impedance.

OBJECTIVE: Changes in cerebral impedance in the newborn piglet are able to discriminate, within 1-2 h of acute hypoxia, between animals which will have a good neurological outcome, and those who have suffered more severe hypoxia resulting in poor outcome. The aim of this study was to determine if cerebral impedance could be used to identify those human infants with an encephalopathy following acute hypoxia who subsequently have a poor neurological outcome. It is these infants who may benefit most from neural rescue treatment. METHODS: Twenty-four newborn term infants with evidence of severe acute intrapartum hypoxia and encephalopathy were studied. Bioimpedance spectroscopy was commenced as soon as possible after birth and repeated every 30 min until the infant was 12 h old. Neurodevelopmental outcome was assessed at 12 months of age. RESULTS: Although cerebral impedance was different to control values, there was no significant difference in cerebral impedance between hypoxic babies with normal and those with abnormal development. CONCLUSION: Cerebral impedance was increased in hypoxic babies, as predicted from animal data, but the method was not suitable for discrimination of outcome. SIGNIFICANCE: Cerebral impedance is not useful for early identification of infants who subsequently have a poor outcome after acute intrapartum hypoxia and who may benefit from neural rescue treatment.

Fate of abstracts published in the proceedings of the first annual Perinatal Society of Australia and New Zealand Congress in 1997.

OBJECTIVES: To examine the fate of research presented at the first annual Perinatal Society of Australia and New Zealand (PSANZ) Congress in 1997, by determining: the rate of publication in peer-reviewed biomedical journals; publication rate by discipline; journals in which work was published; concordance for aims, conclusions, authors and number of study subjects; and time from presentation to publication. METHODS: A MEDLINE search was conducted for any publication in a peer-reviewed journal resulting from a publishable abstract from the proceedings of the first annual PSANZ Congress in 1997. Searching was completed 42 months post-congress. The concordance of aims, conclusions, authors and number of subjects between abstract and published paper was determined. RESULTS: There were 172 publishable abstracts in the proceedings of the PSANZ Congress in 1997, and 78 (45%) were published as 83 articles. Basic sciences had the highest publication rate (67%) and midwifery the lowest (20%). Articles were published in 41 journals, with one-third of the articles in three paediatric journals. There was a match with aims in 75%, and with conclusions in 65%. There were 47/77 with the same number of subjects, 20/77 with more and 10/77 with fewer. There were 22 articles with one author added, 12 had more than one author added, 11 had one author removed and five had more than one author removed. Median time-to-publication was 18 months (interquartile range 9-26 months). CONCLUSIONS: A publication rate of 45% is comparable to other conferences. Basic science and neonatology had the highest publication rates. There were considerable differences between abstract and published article in terms of aims, conclusions, number of subjects and authors.

An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies.

The purpose of this study was to develop a newborn piglet model of hypoxia/ischaemia which would better emulate the clinical situation in the asphyxiated human neonate and produce a consistent degree of histopathological injury following the insult. One-day-old piglets (n=18) were anaesthetised with a mixture of propofol (10 mg/kg/h) and alfentinal (55.5 microg/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were monitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO(2)) to 3-4% and adjusting FiO(2) to maintain the cerebral function monitor peak amplitude at < or =5 microV. The duration of the mild insult was 20 min while the severe insult was 30 min which included 10 min where the blood pressure was allowed to fall below 70% of baseline. Control piglets (n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthesia then euthanased 72 h after the insult. The brains were perfusion-fixed, removed and embedded in paraffin. Coronal sections were stained by haematoxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippocampus, basal ganglia, thalamus and cerebellum for the degree of damage. The total mean histology score for the five areas of the brain for the severe insult was 15.6+/-4.4 (mean +/-S.D., n=7), whereas no damage was seen in either the mild insult (n=4) or control groups. This 'severe damage' model produces a consistent level of damage and will prove useful for examining potential neuroprotective therapies in the neonatal brain.

Measurement of extracellular fluid volume in the neonate using multiple frequency bio-impedance analysis.

Bioelectrical impedance analysis may be useful for cot-side monitoring of fluid balance in the neonatal intensive care unit (NICU). However the presence of cardio-respiratory monitoring equipment, non-ideal electrode placement and inability to obtain accurate crown-heel measurements may interfere with the ability to obtain reliable impedance data in this setting. This study aimed to investigate the effects of these factors on impedance analysis and to develop a prediction equation for extracellular fluid volume in the neonate. The study found that cardio respiratory monitoring had no significant effect on multi-frequency impedance measurements. Placement of current delivering electrodes on the ventral rather than dorsal surfaces improved separation of current and voltage electrodes but did not alter impedance results. Contralateral measurements were not significantly different to ipsilateral measurements. In 24 infants, extracellular fluid volume was measured using corrected bromide space (CBS) and simultaneous impedance analysis was performed. There was good correlation between CBS and the impedance quotient FF2/Ro where F is foot length and R0 is resistance at zero frequency. The study concludes that despite many potential difficulties associated with impedance analysis in the NICU, reliable measurements of impedance can be obtained and further work to validate prediction equations for ECF is warranted.

Prediction of aminoglycoside distribution space in neonates by multiple frequency bioelectrical impedance analysis.

OBJECTIVE: Aminoglycoside antibiotics have a narrow margin of safety between therapeutic and toxic levels. The current study used multiple frequency bioelectrical impedance analysis to develop prediction equations for gentamicin distribution space in neonates. METHODS: Gentamicin pharmacokinetic parameters and bioimpedance were measured in 14 infants in the neonatal intensive care unit. Stepwise regression analysis was used to develop predictive models, using impedance quotients (F2/R), weight and gestational age as variables, whose predictive performance was then tested in a second group of ten infants. RESULTS: The prediction model with the smallest bias and highest concordance correlation was that which included F2/R0 and weight. This bias of 50 ml or 6.7% was less than half of that found using a model including weight alone. CONCLUSION: A bioelectrical impedance-based prediction equation for prediction of gentamicin distribution space in neonates was produced. Although this prediction equation represents only a small improvement over that using weight alone, this is of clinical significance due to the narrow margin between therapeutic and toxic levels for gentamicin. A clinical trial to confirm the value of this methodology is now warranted.

Passive permeability of ovine amnion and allantois to chloride--gestational changes.

The passive permeability to 36Cl of isolated pieces of amnion (112), amniochorion (41) and allantois (54) from 55 pregnant ewes was studied in vitro. There was a significant decrease in the permeability coefficient (K) with increasing age in both amnion and allantois when samples from two age groups (72 to 109; 110 to 147 days of gestation) were analysed. There was a highly significant correlation (P less than 0.001) between amnion permeability and amniotic fluid [Cl-], but none between allantoic permeability and allantoic fluid [Cl-]. Amniotic fluid osmolality decreased significantly over the last third of gestation and was significantly correlated with amniotic fluid [Cl-]. Allantoic fluid osmolality increased with age and did not correlate with allantoic fluid [Cl-]. The anion exchange blocker, SITS, significantly decreased K in the amnion in the younger age group, suggesting that anion exchange through cell membranes may be one route of Cl- movement through the young amnion. The results suggest that the permeability of the amnion may play a role in the regulation of the composition of amniotic but not allantoic fluid in sheep.

Anatomy, physiology and pathology of the amniotic and allantoic compartments in the sheep and cow.

In both cows and sheep the allantoic fluid is confined to 2 sacs connected by a flattened isthmus, one in the non-pregnant horn and one in the upper part of the pregnant horn. The chorion encloses the amniotic and allantoic compartments, forming the amniochorion and chorioallantois, respectively. In the last third of gestation the compositions of both amniotic and allantoic fluids differ substantially from each other and from those of foetal urine, and maternal and foetal plasma. There is less variation in composition than in volume for a given gestational age. Abnormalities of volume are more common in cows than sheep, and hydrallantois is more common than hydramnois. Data obtained from both physiological experiments and pathological cases suggest that the foetal membranes play an important role in the regulation of composition and volume of foetal fluids. Evidence is presented that the permeability of the membranes to various solutes, as well as their capacity to produce and respond to a number of hormones, can affect the foetal fluid composition and/or volume. Progesterone, oestrogens and prolactin are some of the hormones known to affect foetal fluids. Foetal adrenal insufficiency has been associated with hydramnios implying a lack of hormones from this gland in this disease. The changes in allantoic fluid composition from normal to that closely resembling maternal/foetal extracellular fluid, in hydrallantois, suggests an alteration of membrane function as an aetiology and the continued production of fluid, after removal of the foetus in some cases, favours this hypothesis.

Amniotic fluid volume and in vivo permeability of ovine fetal membranes.

Serial measurements of amniotic fluid volume were made using a tracer dilution technique in sheep during the last half of gestation. No consistent trends were observed in amniotic fluid volume changes over this period. Disappearance of tracer-labeled urea and water from the amniotic fluid was observed at various gestational ages during the last half of pregnancy. The rate of disappearance of urea from the amniotic fluid decreased with gestational age. The disappearance rate of water did not change. Relationships between disappearance rates and amniotic fluid volume suggest that the permeability of the fetal membranes may be important in determining amniotic fluid volume.

Permeability of ovine amnion and amniochorion to urea and water.

Permeability of ovine amnion and amniochorion to urea and water was measured in vitro at various gestational ages. Permeability of amniochorion was between 30 and 100% of that of amnion. Permeability of the membranes to water did not change with fetal age, whereas permeability of amnion to urea decreased from 1.548 +/- 0.541 (49) 10(-4) cm . sec-1 to 0.277 +/- 0.339 (102) 10(-4) cm . sec-1 as fetal age increased. There was a significant relationship between the permeability of the amnion to urea and the concentration of urea in the amniotic fluid. It was concluded that the decrease in membrane permeability to urea may be responsible in part for the increase in amniotic fluid urea concentration observed as gestation progresses.

Amniotic fluid volume and composition following experimental manipulations in sheep.

Twenty to thirty percent of amniotic fluid volume was replaced by isotonic solutions of saline, mannitol, or dextrose in chronically cannulated ovine fetuses. In all cases the sodium, potassium, and chloride concentrations returned to control values in 3 to 6 hours. Urea and creatinine behaved similarly in the saline and mannitol experiments, but rose above control values within 1 hour of dextrose replacement. Amniotic fluid volume increased with return of solute. Fetal urine drainage to the exterior abolished the rapid return of urea and creatinine concentrations in the dextrose experiments, although no changes in renal function occurred in any experiments. It was concluded that dextrose inhibited the exit of urea and creatinine from the amniotic compartment.

Placental transfer of aldosterone in the sheep.

To determine the percentage of the maternal secretion of aldosterone which crosses the placenta the blood clearance rate (BCR) of aldosterone was measured in pregnant sheep and in chronically cannulated fetuses by the constant infusion of [3H]aldosterone alternately into the maternal and fetal compartments. When equilibrium had been reached the concentration of [3H]aldosterone was measured in both maternal and fetal compartments. Aldosterone BCR in eight pregnant ewes was 98 +/- 5 (S.E.M.) litres/h which was not significantly different from that of ten non-pregnant ewes at 95 +/- litres/h. The BCR of aldoterone in seven fetuses was 24 +/- litres/h. A small percentage (4.4 +/- 0.3; n = 7) of the maternal production rate was transferred to the fetus, whilst 29 +/- 4% (n = 8) of the fetal production rate was transferred to the maternal compartment. Whjen aldosterone was measured in maternal and fetal blood samples collected simultaneously from sodium-replete sheep more than 80% of the aldosterone in fetal blood was of fetal origin if the actual fetal concentration of aldosterone was greater than 1.5 ng/dl.