Zsuzsoka Kecskes

Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants

BACKGROUNDnThe safest ranges of oxygen saturation in preterm infants have been the subject of debate.nnnMETHODSnIn two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial.nnnRESULTSnAfter 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001).nnnCONCLUSIONSnUse of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

Placental Mesenchymal Dysplasia Associated with Hepatic Mesenchymal Hamartoma in the Newborn

Placental mesenchymal dysplasia is an uncommon disorder in which the placenta is enlarged with abnormal, large, and often cystic villi with dilated and/or thick-walled vessels. These placental changes can mimic a partial hydatidiform mole but in contrast to a partial mole can coexist with a fully viable fetus. Fetal anatomical and vascular anomalies frequently coexist with placental mesenchymal dysplasia. In this case, placental mesenchymal dysplasia was associated with preterm labor at 33 weeks gestation, fetal compromise, and a large abdominal mass with a large hepatic cyst that was de-roofed at exploratory laparotomy. The neonate remained critically ill with hypoxic ischaemic encephalopathy and coagulopathy and died despite intensive care. Biopsy and autopsy findings showed a large cystic mesenchymal hamartoma affecting the left lobe of the liver. This appears to be the 3rd histologically confirmed association of placental mesenchymal dysplasia with mesenchymal hamartoma of the liver in the English language literature.

Rapid correction of early metabolic acidaemia in comparison with placebo, no intervention or slow correction in LBW infants

BACKGROUNDnMetabolic or mixed (metabolic and respiratory) acidosis are commonly encountered problems in the low birth weight (LBW) infant after delivery, and they may contribute to mortality and morbidity. Causes for the lactic acidosis are multiple and include maternal, placental and fetal factors. It is unclear whether metabolic acidaemia in the first 24 hours of life in LBW infants should be corrected by rapid infusion of alkali.nnnOBJECTIVESnThe main objective was to assess the short and long-term effects of the rapid correction of early (first 24 hours) metabolic acidaemia in LBW (<2500g birth weight) neonates.nnnSEARCH STRATEGYnSearches were undertaken of MEDLINE from October 2001 back to 1966 and the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2001). The title and abstract of each retrieved study were examined to assess eligibility. If there was uncertainty, the full paper was examined.nnnSELECTION CRITERIAnTypes of studies All randomised controlled trials where short or long term effects of treatment with alkalising agents by rapid infusion were compared with placebo or no treatment, or where rapid infusion of alkalising agents was compared with slow infusion. Types of participants Newborn infants with birth weight <2500g and less than 24 hours of age with proven metabolic acidaemia (on arterial blood gas). Types of interventions Rapid correction of acidaemia with alkalising agents (sodium bicarbonate and/or THAM) given as a bolus over 5 minutes or less compared with either placebo, no intervention or slow infusion (>5 minutes). Types of outcome measures 1) maximal oxygen requirement in first 24 hours 2) duration of oxygen therapy 3) need for and duration of assisted ventilation 4) intraventricular haemorrhage and/or periventricular leucomalacia 5) survival to discharge 6) long term survival (to 24 months of age) 7) neurological and developmental outcome at 24 months of agennnDATA COLLECTION AND ANALYSISnEach reviewer assessed eligibility, trial quality and extracted data separately, then compared and resolved differences. Study authors were contacted for additional information if necessary.nnnMAIN RESULTSnNo studies were found meeting the criteria for inclusion in this review.nnnREVIEWERS CONCLUSIONSnThere is no evidence available from randomised controlled trials to support or refute the rapid correction of metabolic acidaemia, in LBW infants in the first 24 hours of life, as compared with slow or no correction.

NSE and S100 after Hypoxia in the Newborn Pig

Perinatal asphyxia is an important cause of neonatal morbidity and mortality. There is the potential to halt cerebral damage if neural rescue strategies are applied within a short period of time after an insult. It is therefore important to be able to accurately identify neonates who may benefit from neural rescue therapies. Recent studies in asphyxiated neonates have correlated S100B and NSE with outcome; however, interpretation of these studies were difficult, as the timing of the measurements were not consistent. We measured NSE and S100 in 1-d-old piglets after a mild or severe hypoxic insult. Measurements were performed at 6–72 h after the insult and correlated with histologic outcome. There were no differences of the NSE or S100 concentrations between controls and the mild hypoxia group. After 24 h, there was a significant difference of NSE between the control/mild insult group and severe insult group. After 48 h, the S100 concentrations were significantly different between the control/mild insult group and the severe insult group. Both proteins showed good correlation at these time points with outcome as measured by histology score at 72 h. In conclusion, NSE and S100B measured in the serum of piglets after hypoxia increased significantly and correlated with outcome. This increase occurs too late to be used within the first 24 h but might be helpful for the clinician in determining the timing of an insult.

The effect of mode of delivery and anaesthesia on neonatal blood pressure

Background:u2003 Many factors may effect blood pressure (BP) in the early neonatal period, including mode of delivery and anaesthesia, on which there is little reported.

Determining the ventilatory volumes required to ventilate low birth weight infants with respiratory distress syndrome. Prediction of arterial carbon dioxide using minute volumes.

There are limited data on the volumes used to ventilate infants with respiratory distress syndrome (RDS). There are no data on the volumes to aim for to avoid hypocapnia or unacceptable levels of hypercapnia. In this pilot study we measured minute volumes (MV) in ventilated infants to determine whether MV can predict arterial carbon dioxide (PaCO2) within acceptable parameters. Low birth weight infants (n = 14) mechanically ventilated for RDS had lung function recorded (n = 53) as an arterial blood gas was taken. MVs were plotted against PaCO2 giving the regression equation for prediction of PaCO2 (mm Hg) with MV (ml/kg/min): PaCO2 = 58.3 – 0.075 × MV, r = 0.62, r2 = 0.38, p < 0.001, residual variance (s2) of 52.7 (s = 7.26). 95% CI give a predicted PaCO2 ± 15 mm Hg for a given MV. A MV of 200 ml/kg/min predicts a PaCO2 of 43 mm Hg (95% Cl 29–58). PaCO2 correlates reasonably well with MV. Setting appropriate MVs may allow closer targeting of PaCO2, and prevent over- or under-ventilation.

Treatment of pulmonary hypertension with sildenafil in a neonate with spondyloepiphyseal dysplasia congenita

Persistent pulmonary hypertension of the newborn (PPHN) remains an important cause of mortality and morbidity in the term neonate. Preliminary but limited data suggest that there may be a role for sildenafil in the treatment of PPHN. We report the successful treatment of PPHN caused by pulmonary hypoplasia in a patient with spondyloepiphyseal dysplasia congenita.

Cerebral impedance following hypoxia/ischaemia in the human infant

Changes in cerebral impedance are able to discriminate, within 1-2 hours of acute hypoxia in the newborn piglet, between animals which will have a good neurological outcome, and those who have suffered a more severe insult resulting in a poor outcome. The aim of this study was to determine if cerebral impedance is useful in the human infant for early identification of those who will have a poor neurological outcome following acute hypoxia, and thus may benefit from neural rescue treatment. Forty newborn term infants with a history consistent with severe acute intrapartum hypoxia and encephalopathy were studied. Bio-impedance spectroscopy was commenced as soon as possible after birth and repeated every 30 minutes until the infant was 12 hours old. Neurodevelopmental outcome was determined at 12 months of age by medical examination and Bayley score. Infants were retrospectively divided into Group A with both evidence of acute intrapartum hypoxia and a poor neurological outcome (cerebral palsy, mental impairment or cortical blindness); and Group B with all other infants. There were no significant differences in cerebral or whole body impedance between groups.This issue of Physiological Measurement follows the successful 13th ICEBI conference held at the Graz University of Technology, Austria, from 29 August to 2 September 2007. It was organized jointly with the 8th Conference on Electrical Impedance Tomography. The conference was co-organized by the Impedance Imaging Research Centre (IIRC) in Seoul and the Austrian Society for Biomedical Engineering (OGBMT), and it was kindly endorsed by the IFMBE. The combined conferences created a platform for investigators from both research communities of bio-impedance and EIT to engage in common areas of interest whilst also allowing an opportunity for the community to broaden its outlook in the areas of bio-sensors, clinical applications and new technologies. This upholds the tradition of successful conferences on biomedical applications of electrical impedance tomography and bio-impedance. It follows the 7th Conference on Biomedical Applications of Electrical Impedance Tomography combined with the World Congress 2006, which took place in Seoul from 27 August to 1 September 2006. The next EIT conference is scheduled to take place in Dartmouth College, USA, in June 2008. n nThis issue contains papers produced from discussion and feedback during the conference in both bio-impedance and EIT research areas. It was also an opportunity for new researchers to join the community and propose recent innovations. Of the 259 papers presented at the conference, Springer Verlag published 207 in the IFMBE proceedings. All authors were invited to prepare new papers for inclusion in this issue of Physiological Measurement. The manuscripts were put through a process of careful review before selection. A total of 43 were accepted, covering an important range of topics from bio-impedance, hardware, algorithms, new technologies and clinical applications. n nFrom the scientific point of view, bio-impedance has a very long tradition that dates back to the days of Maxwell. Nevertheless, until the end of the 20th century, research was focused on the development of methods and basic experimental work while clinical or other practical applications remained limited. Consequently, there were not so many companies interested enough to produce professional equipment for easy and reliable data collection and interpretation. This may appear surprising as bio-impedance reflects so many (patho-) physiological processes, but on the other hand, a number of proposed applications, though sensitive, still exhibit low specificity, especially when aimed at processes far from the body surface. The 2007 conference may have shown a slight change of tendency. From 2000 to 2006, the number of papers cited in Medline and containing the keywords bio-impedance or impedance tomography increased by 56%. At the same time, we face an increasing number of applications related to micro- and nano-technologies that have emerged along with the tremendous growth of biochemical and cellular engineering. In recent years both the number of newly founded companies for bio-impedance devices and the involvement of established companies in bio-impedance research have increased. n nThe papers included in this years issue clearly reflect this. New developments and trends are visible, such as non-contact methods using magnetic fields; MREIT, bringing together EIT and magnetic resonance imaging; and magnetic induction tomography (MIT), clinical applications, bio-impedance spectroscopy, new hardware and algorithms. The presentations of these new technologies continue to grow and it will be interesting to see how these contribute to future clinical applications. n nAt this conference, clinical applications were strongly represented; they included brain function, breast imaging, and thorax and gastric applications. It is important that researchers do not neglect the challenges of clinical applications of bio-impedance and EIT as there are still many technical difficulties that the technology needs to overcome in order to provide valuable clinical tools; however, there are promising signs that these tools are close to realization. n nThe future of both EIT and bio-impedance continues to provide researchers with new challenges. The high quality of research papers in this special issue shows clear evidence of significant advances in this research field.

Short-term neonatal outcomes of growth restricted infants by their mode of delivery

1 Dietz HP, Clarke B. Is the irritable bladder associated with anterior compartment relaxation? A critical look at the ‘integral theory of pelvic floor dysfunction’. Aust N Z J Obstet Gynaecol. 2001 Aug; 41 (3): 317–319. 2 Petros PE, Ulmsten UI. An integal theory of female urinary incontinence. Experimental and clinical considerations. Acta Obstet Gynecol Scand. 1990; S153, 69: 7–31. 3 Petros PE. New ambulatory surgical methods using an anatomical classification of urinary dysfunction improve stress, urge, and abnormal emptying. Int Urogyn J Pelvic Floor Dysfunct. 1997; 8 (5): 270–278.

196 Successful Treatment of Pulmonary Hypertension with Sildenafil in a Neonate with Spondyloepiphyseal Dysplasia Congenita

INTRODUCTION Persistent pulmonary hypertension of the newborn (PPHN) remains an important cause of mortality and morbidity in the term neonate. The severity of the illness and the outcome are related to the underlying cause. Therapies include inhaled nitric oxide (iNO), intravenous prostacyclin and sildenafil. We report the successful treatment of a neonate suffering from PPHN secondary to pulmonary hypertension caused by a skeletal dysplasia.CASE REPORT the female infant was delivered at 37 weeks gestation with antenatal ultrasound findings a skeletal dysplasia. The diagnosis of spondyloepiphyseal dysplasia congenita was made based on the skeletal survey and clinical picture. She required significant ventilatory support and up to 100% oxygen because of PPHN. iNO resulted in a decrease in oxygen requirement to 80%. On day 36 oral sildenafil was commenced at a dose of 0.5mg/kg every 6 hours and increased over the next week to 2mg/kg every 6 hours. iNO was successfully weaned and ceased 4 days after commencing sildenafil. Within a week of commencing sildenafil the infant required less ventilation with a decrease in the oxygen requirement from 80% to 40%. She was successfully extubated to CPAP 4 weeks later. She has subsequently been discharged home on nasopharyngeal CPAP facilitated by home carers.DISCUSSION PPHN occurs in 1–2/1000 live births PPHN is associated with significant mortality of up to 20%. Sildenafil is a specific PDE-5 inhibitor and is mostly known for its use in the treatment of erectile dysfunction. Preliminary findings suggest that sildenafil is effective in the long-term therapy of pulmonary hypertension and is particularly effective in reducing rebound hypertension after discontinuation of NO in patients with arterial pulmonary hypertension. Preliminary but limited data suggests that there might be a role for sildenafil in the treatment of PPHN. Randomised-controlled trials are required to determine its efficacy and safety.