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Biomedical subjects

J Newnham

Publications and source records attributed to J Newnham.

At least 19 recordsLinked to original sources
PubMed2000

Antenatal retinoic acid does not alter alveolization or postnatal lung function in preterm sheep.

Retinoic acid exposure has been shown to promote surfactant production in foetal rats and to promote alveolization in neonatal rats. It was hypothesized that antenatal retinoic acid treatment would promote alveolization and accelerate functional maturation in the lungs of late gestation preterm sheep. Foetuses received a single i.m. injection of all-trans retinoic acid (RA, 20 mg x kg(-1)) or vehicle control at 115 days gestation (term=150 days) and were delivered at 125 days gestation. To examine the longer term effects of RA on alveolization a second group of animals received RA or vehicle at 121 days gestation and were delivered at 146 days gestation. Liver retinol levels at time of delivery were 2-3-fold higher in both preterm and near-term RA treated animals, indicating a significant impact of RA treatment on retinol metabolism. Dynamic compliance, gas exchange, lung gas volume and saturated phosphatidylcholine pool size at 125 days were unaffected by antenatal RA treatment. Alveolar volume, wall thickness and number at 125 or 146 days were also unaffected by RA treatment. Retinoic acid, as administered in this study, does not appear to accelerate structural or functional maturation of the foetal sheep lung. Response to retinoic acid may be species dependent, highlighting a need for caution when interpreting results from animal based studies.

Animals↗
PubMed2000

Pulmonary interstitial emphysema 24 hours after antenatal betamethasone treatment in preterm sheep.

During a series of studies investigating the maturational response to antenatal glucocorticoids, we observed that 70% of lambs delivered at 128 d gestation (term = 150 d), 24 h after a single injection of 0.5 mg/kg betamethasone or betamethasone + L-thyroxine (15 microgram/kg), developed pulmonary interstitial emphysema (PIE), compared with less than 5% of control animals or animals delivered 48 h or 7 d after hormone treatment. This study examined whether the lungs of animals that developed PIE were functionally or structurally different from those that did not. Lambs were mechanically ventilated for 40 min after cesarean section delivery. Hormone-treated animals with PIE were ventilated at similar peak inspiratory pressure (PIP) to control animals, whereas those without PIE were able to be ventilated at significantly lower PIP. Volume-dependent elastance (E2V), which provides an index of overdistension during mechanical ventilation, was lowest in PIE animals. Alveolar architecture was distorted in almost all ventilated animals, the most severe distortion occurring in PIE animals. There was no evidence of excessive alveolar wall thinning in PIE animals, although parenchymal collagen was 30% lower, and elastin 120% higher than in control animals. PIE was associated with structural differences, but not with overventilation.

Animals↗
PubMed2000

Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs.

In utero inflammation may accelerate fetal lung maturation but may also play a role in the pathogenesis of chronic lung disease. We examined the impact of endotoxin, a potent proinflammatory stimulus, on structural and functional maturation of preterm sheep lungs. Date bred ewes received 20 mg Escherichia coli endotoxin or saline by ultrasound guided intra-amniotic injection at 119 d gestation. A comparison group of animals received 0.5 mg/kg betamethasone, a known maturational agent, at 118 d gestation. Lambs were delivered by cesarean section at 125 d (term = 150 d) and ventilated for 40 min. Lung function data are reported elsewhere. Total and differential white cell counts were performed on amniotic fluid and fetal lung fluid samples. Morphometric analyses were performed on inflation fixed right upper lobes. Total cell count increased slightly but not significantly in both amniotic fluid and fetal lung fluid. Both endotoxin and betamethasone had similar effects on alveolarization: average alveolar volume increased by approximately 20% and total alveolar number decreased by almost 30%. Both treatments led to thinning of alveolar walls, although this was statistically significant in the betamethasone-treated group only. Although antenatal endotoxin leads to striking improvements in postnatal lung function, this may be at the expense of normal alveolar development.

Amniotic Fluid↗
PubMed1998

Consequences of fetal growth restriction.

An increasing number of diseases in child and adult life are now thought to have their origins in the fetal period. Central to this predisposition is restriction of fetal growth. During the period reviewed in this article, the associations between adult hypertension and low birthweight were confirmed, and numerous studies have investigated possible mechanisms by which the metabolism of an individual may be programmed by an adverse intrauterine environment. The consequences in adult life of intrauterine undernutrition now highlight prenatal care as one of the most crucial issues in medicine and challenge many aspects of current obstetric decision-making. Research targeting fetal growth and development can be expected to result in improved health at all ages.

Adrenal Cortex↗
PubMed1998

Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids.

BACKGROUND: Although single courses of antenatal glucocorticoids decrease respiratory distress syndrome and mortality, repetitive courses of antenatal glucocorticoids are being given to women at risk of preterm delivery without evidence of benefit or appreciation of potential risks. OBJECTIVES: To evaluate the effects of single and repetitive antenatal glucocorticoid exposures on fetal growth and postnatal lung function in sheep. METHODS: Pregnant ewes were randomized to three protocols that included one or three doses (at 7-day intervals) of 0.5 mg/kg of betamethasone (beta) given to the ewe or fetus beginning at gestations ranging from 104 to 128 days' gestation with delivery at 125, 135, and 146 days' gestation. Postnatal assessments included measurements of gas exchange, compliance, ventilation efficiency, static lung volume, and lung tissue and alveolar wash saturated phosphatidylcholine. RESULTS: Single or repetitive maternal beta but not fetal beta caused fetal growth retardation at delivery at 125, 135, and 146 days' gestation. Single-dose fetal beta had no effect on postnatal lung function whereas single-dose maternal beta significantly increased compliance, lung volume, and tissue and alveolar surfactant after preterm delivery. Although three-dose fetal beta improved all indicators of postnatal lung function, three-dose maternal beta resulted in larger responses. The added benefits of repetitive beta relative to a single-dose beta on postnatal lung function after preterm delivery were not as great when therapy was begun later in gestation. Postnatal lung function after delivery at 146 days' gestation (term is 150 days) was improved after repetitive maternal beta at early gestational age. CONCLUSIONS: In sheep, single or repetitive maternal beta causes growth retardation from 104 to 121 days' gestation and the growth retardation persists to term. In contrast, single or repetitive fetal beta does not cause fetal growth retardation and is less potent at improving postnatal lung function and increasing surfactant pools. There are potential benefits as well as risks for the use of repetitive antenatal glucocorticoids. Randomized, controlled trials in humans are essential given the widespread use of repetitive courses of antenatal glucocorticoids in women at risk of preterm delivery. respiratory distress syndrome, maturation, prematurity, growth retardation, surfactant.

Animals↗
PubMed1997

Preterm lung function after retreatment with antenatal betamethasone in preterm lambs.

OBJECTIVE: We hypothesized that two doses of betamethasone administered 1 week apart would further enhance postnatal pulmonary function in preterm lambs (compared with a single dose). STUDY DESIGN: Fetal sheep (121 days' gestation) randomly received saline solution or betamethasone (0.5 mg/kg) as a single injection. Six days later fetal sheep were retreated with either saline solution or corticosteroid, and postnatal lung function was evaluated 1 day later. RESULTS: Betamethasone improved compliance and ventilation efficiency index nearly 50%, and total lung volume increased twofold. No effects of treatment-to-delivery interval (1 vs 7 days) or corticosteroid retreatment on pulmonary function were apparent. Although surfactant pool sizes increased as a function of duration of exposure, no additional effect of corticosteroid retreatment was noted. Antenatal betamethasone increased messenger ribonucleic acid levels for the surfactant proteins A and C, and retreatment augmented surfactant protein B messenger ribonucleic acid levels but suppressed surfactant protein A and C messenger ribonucleic acid. CONCLUSION: Improved postnatal lung function resulting from antenatal betamethasone was not augmented by retreatment.

Animals↗
PubMed1997

A scoring system for the prediction of successful delivery in low-risk birthing units.

OBJECTIVE: To establish and test the effectiveness of a low-risk scoring system to predict obstetric outcome for the selection of women suitable for confinement in low-intervention units. METHODS: Retrospective analyses were performed on data from 2900 women enrolled in the Western Australian Pregnancy Cohort Study and 1353 women managed at a midwifery-based birth center. A combination of the principal predictors of obstetric outcome, incorporating a previously published scoring system and various clinical features, was used to exclude high-risk cases at 18 weeks' and 36 weeks' gestation. Stepwise multivariate logistic regression analyses of the remaining pregnancies then produced a low-risk scoring system. RESULTS: This system predicted a 55% chance of an uncomplicated delivery in a midwifery-based setting after allocating 54% of women to the low-risk category. It predicted an 82% chance of an uncomplicated delivery in a primary medical care setting with the allocation of 84% of women as low risk. CONCLUSION: The results of this study suggest that adding induction and augmentation of labor, together with low pelvic instrumental delivery, to the treatment options in a low-intervention unit would raise the rate of successful confinement within the unit from 55% to 82%. Our scoring system now requires prospective evaluation to further assess its clinical value.

Adult↗
PubMed1997

Intermittent auscultation for the intrapartum assessment of fetal well-being in Western Australia.

In May 1995, in response to a decision of the Perinatal and Infant Mortality Committee of Western Australia, a survey of Western Australian hospitals was performed to ascertain what policies were in use for the monitoring of the fetal heart rate in labour and what proportion of these hospitals had access to electronic monitoring by cardiotocography. A response was received from 96% of the surveyed hospitals. More than half the births in this State (13,950 of 25,238) were monitored in labour using intermittent auscultation as the primary test; 7.5% of Western Australian births each year occurred in hospitals in which electronic monitoring was not available. Fewer than 50% of hospitals had written protocols describing the method of auscultation of the fetal heart during labour, the indications to contact a doctor or the management of fetal distress. The protocols which did exist displayed considerable variation in the recommended frequency of intermittent auscultation. The lack of standard practice in this field probably results from uncertainties in the literature. Intermittent auscultation has not been subjected to rigorous scientific evaluation as a screening tool and guidelines documenting ideal auscultatory practices need to balance the precision of electronic monitoring and freedom from intervention. Based on this compromise and existing evidence, a protocol for intermittent auscultation in normal labour is proposed.

Cardiotocography↗
PubMed1997

Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs.

We evaluated the effects of multiple fetal exposures to glucocorticoids on postnatal lung function and growth. Ewes were randomized to receive 1 to 4 doses of 0.5 mg/kg betamethasone or saline placebo at 7 d intervals from 104 d to 118 d and at 124 d gestation. All lambs were delivered preterm at 125 d gestation, and postnatal lung function was evaluated. There were sequential improvements in compliance, ventilation efficiency, and lung volumes for two, three, and four doses of betamethasone. The maximal effect was a 150% increase in compliance and a 4-fold increase in lung volume after fetal exposure to four doses of betamethasone. However, birth weights decreased (15% after one dose, 19% after two doses, and 27% after three and four doses). There were no changes in lung to body weight ratios, lung dry to wet weight ratios, lung protein to body weight ratios, or lung hyaluronan content. Prenatal glucocorticoid exposure also altered postnatal cortisol, thyroid, and catecholamine plasma levels. Repetitive 7-d interval exposures of fetal lambs to glucocorticoids progressively enhanced postnatal lung function and resulted in growth and endocrine abnormalities.

Animals↗
PubMed1997

Postnatal lung function after prenatal steroid treatment in sheep: effect of gender.

The effect of fetal gender on postnatal lung function and response to prenatal steroid exposure were examined retrospectively in a group of 115 preterm lambs. Fetuses received a single intramuscular injection of 0.5 mg/kg betamethasone alone or in conjunction with L-thyroxine 48 h before delivery at 128-d gestational age. Control animals received an equivalent volume of saline. After delivery, respiratory mechanics and blood gas parameters were recorded for 40 min. Deflation pressure volume curves were constructed in excised lungs. Right upper lobes from a randomly selected subgroup of control animals were examined morphometrically. Control (saline-treated) females were able to be ventilated at lower ventilatory pressures with equivalent tidal volumes and more efficient gas exchange. There were no gender differences in compliance, conductance, or excised lung volumes for saline-treated animals. More efficient gas exchange in females could not be explained by thinner alveolar septa or greater alveolar surface area. After hormone treatment, both males and females exhibited significant improvements in respiratory mechanics, gas exchange, and an increase in alveolar surfactant concentration. However, female exhibited a significantly greater improvement than males for compliance, conductance, excised lung volume, and arterial oxygen partial pressure. These data provide a comprehensive description of gender differences in postnatal lung function and response to steroid treatment in preterm animals, and support clinical findings of sexual dimorphism.

Animals↗
PubMed1996

Characterisation of the possible effect on birthweight following frequent prenatal ultrasound examinations.

The objective of this study was to evaluate and characterise by study of newborn biometry a possible effect on birthweight which we observed previously in a randomised controlled trial of multiple prenatal ultrasound examinations. A total of 2743 women with single pregnancies had been allocated at random to either a protocol of ultrasound imaging and continuous wave Doppler studies at 18, 24, 28, 34 and 38 weeks gestation (intensive group), or to a protocol of a single imaging examination at 18 weeks and further imaging scans only as clinically indicated (regular group). When compared with those in the regular group, and adjusted for other confounding variables, normally formed babies of term gestational age in the intensive group tended to be shorter when measured at birth (P = 0.123) and on day 2-3 of age (P = 0.068). There were statistically insignificant reductions in the circumferences of the chest, abdomen and mid-arm; and in the skinfold thicknesses of the triceps, parascapular and subscapular regions. Principal component analysis showed a trend for a reduction for the skeletal component (P = 0.085) but not for the soft tissue component (P = 0.332). Comparison of the neonatal biometry in the two groups is not conclusive, but the differential effects on the various growth parameters suggest that if multiple scans do indeed restrict fetal growth, the mechanism is more likely to be an effect on bone growth rather than a reduction in nutrient supply from the placenta.

Biometry↗
PubMed1996

Differing patterns of mechanical response to direct fetal hormone treatment.

A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age; however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Airway Resistance↗
PubMed1996

Effect of interval from fetal corticosteriod treatment to delivery on postnatal lung function of preterm lambs.

The effect of altering the interval from treatment to delivery on postnatal lung function of the preterm lamb is unknown. We treated groups of 8-10 singleton fetal sheep with 0.5 mg/kg betamethasone by fetal injection and evaluated postnatal lung function 40 min after preterm delivery at 123 days gestation 2 days after treatment or at 128 days gestation 2, 4, and 7 days after treatment relative to groups of 4-8 saline-injected control animals. At 123 days, betamethasone significantly improved arterial PCO2, dynamic thoracic compliance, and ventilatory efficiency index and doubled lung gas volume relative to a control group. Fetal treatment with betamethasone 2, 4, or 7 days before delivery at 128 days also improved these same indicators of lung function relative to controls, and the magnitude of the improvements was the same for all indicators and independent of treatment-to-delivery interval. Betamethasone suppressed the normal postnatal increase in plasma cortisol after 2 and 4 days of exposure but not after 7 days of exposure. Betamethasone also increased fetal and postnatal triiodothyronine concentrations after 2 days of exposure but not at 4 or 7 days of exposure. Although the hormone effects were transient, postnatal lung functional responses to betamethasone persisted over the 2- to 7-day interval from treatment to delivery.

Adrenal Cortex Hormones↗
PubMed1995

Postnatal lung function in preterm lambs: effects of a single exposure to betamethasone and thyroid hormones.

OBJECTIVE: We determined the effect of a single direct fetal injection of corticosteroid and thyroid hormones on postnatal pulmonary function in preterm lambs. STUDY DESIGN: Initially fetal sheep (126 days' gestation) randomly received saline solution, betamethasone (Celestone Soluspan, 0.5 mg/kg), betamethasone plus triiodothyronine (5 micrograms/kg), or betamethasone plus thyroxine (15 micrograms/kg) as a single injection. Forty-eight hours later (128 days' gestation) the fetuses were delivered and ventilated for 50 minutes. In a second protocol fetuses were delivered at 128 days' gestation, after only 24 hours of hormone exposure. RESULTS: Betamethasone treatment improved compliance nearly twofold after 24 or 48 hours of exposure. Efficiency of ventilation also improved after steroid therapy; this effect was augmented 48 hours after thyroxine exposure (but not triiodothyronine). No thyroxine effect was noted after 24 hours of exposure. Maximal lung volume increased by 80% after steroid treatment and doubled in response to combination betamethasone and thyroxine therapy. Alveolar pool sizes of saturated phosphatidylcholine and surfactant protein A were comparable for all groups exposed for 48 hours. CONCLUSIONS: A single fetal exposure to betamethasone improves postnatal pulmonary function after 24 or 48 hours. Addition of thyroxine (but not triiodothyronine) augments this effect at 48 hours.

Animals↗
PubMed1995

Screening for the small fetus: a study of the relative efficacies of ultrasound biometry and symphysiofundal height.

In this study 3 different methods of screening for birth-weight < 10th percentile in pregnancy were evaluated both individually and in combination; 1,135 women with singleton pregnancies were studied. Measurements of symphysiofundal height by tape measure, and amniotic fluid index and fetal abdominal circumference by ultrasound imaging, were made at 18, 24, 28, 34 and 38 weeks. At none of these gestational ages did amniotic fluid index perform well as a screening test for birth-weight < 10th percentile. Combining the tests, using symphysiofundal height to select a group at high risk who then had a fetal abdominal circumference measurement, reduced the false positive rate but significantly decreased the percentage of infants diagnosed. The results of this study confirm that the most appropriate antenatal diagnostic test for birth-weight <10th percentile is ultrasound measurement of fetal abdominal circumference. Selecting pregnancies at risk by clinical measurement of symphysiofundal height will provide a lower false positive rate than a policy of performing ultrasound on all pregnancies during the third trimester, but will also reduce the sensitivity.

Adult↗
PubMed1995

Postnatal lung function in lambs after fetal hormone treatment. Effects of gestational age.

We previously found that a single dose of betamethasone in combination with thyroxine given by intramuscular injection to fetal sheep 48 h before preterm delivery at 128 d gestation improved postnatal lung function. We have now asked how the combination of 0.5 mg/kg betamethasone and 15 micrograms/kg T4 given by a single fetal intramuscular injection changes lung response 48 h after treatment at 121 and 135 d gestation. At 121 d gestation the fetal hormone treatment significantly improved postnatal lung function. Compliance increased by 55%, arterial PO2 increased from 39 to 215 mm Hg, PCO2 decreased from 109 to 79 mm Hg, and maximal lung volumes increased by 112%. The hormone treatment decreased the severity of the respiratory failure, although these very preterm lambs still had severe respiratory failure. At 135 d gestation, the fetal hormone treatment decreased the ventilatory pressure requirements that were needed to normalize PCO2 values from 30 to 21 cm H2O. Compliance increased by 40%, and maximal lung volumes increased by 33%. Alveolar or lung tissue, saturated phosphatidylcholine, or alveolar SP-A pool sizes did not change with hormone treatment at 135 d gestation. We conclude that fetal hormone treatment significantly improved postnatal lung function at both gestational ages, although the characteristics of the responses were different.

Animals↗