The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro-BNP performance.

AIM: Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants. METHODS: Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development. RESULTS: Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28). CONCLUSION: The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.

Feasibility of pulse oximetry screening for critical congenital heart defects in homebirths.

BACKGROUND: Pulse oximetry has been shown to be a valuable additional screening test for detecting critical congenital heart defects in newborns. The feasibility of homebirth screening by the attending midwife has not been reported previously. AIM: Routine pulse oximetry screening of homebirths at 2 h of age was introduced in a UK tertiary maternity service in January 2014. The process and outcomes were evaluated. METHODS: Retrospective review of the clinical record of all babies undergoing pulse oximetry screening performed following homebirths over a 16-month period was undertaken. The acceptability of screening among the home care team (n=11) was also evaluated. RESULTS: Ninety babies underwent routine pulse oximetry screening within 2 h following homebirth; two had a positive result and were admitted to the neonatal unit with significant respiratory illness. Screening was acceptable and reassuring to midwives enabling prompt postnatal decision making and confirming normal transition without significantly increasing workload. CONCLUSIONS: Early pulse oximetry screening for homebirths is both feasible and acceptable.

Pulse oximetry as a screening test for congenital heart defects in newborn infants: a cost-effectiveness analysis.

OBJECTIVE: To undertake a cost-effectiveness analysis that compares pulse oximetry as an adjunct to clinical examination with clinical examination alone in newborn screening for congenital heart defects (CHDs). DESIGN: Model-based economic evaluation using accuracy and cost data from a primary study supplemented from published sources taking an NHS perspective. SETTING: Six large maternity units in the UK. PATIENTS: 20 055 newborn infants prior to discharge from hospital. INTERVENTION: Pulse oximetry as an adjunct to clinical examination. MAIN OUTCOME MEASURE: Cost effectiveness based on incremental cost per timely diagnosis. RESULTS: Pulse oximetry as an adjunct to clinical examination is twice as costly but provides a timely diagnosis to almost 30 additional cases of CHD per 100 000 live births compared with a modelled strategy of clinical examination alone. The incremental cost-effectiveness ratio for this strategy compared with clinical examination alone is approximately £24 000 per case of timely diagnosis in a population in which antenatal screening for CHDs already exists. The probabilistic sensitivity analysis suggests that at a willingness-to-pay (WTP) threshold of £100 000, the probability of 'pulse oximetry as an adjunct to clinical examination' being cost effective is more than 90%. Such a WTP threshold is plausible if a newborn with timely diagnosis of a CHD gained just five quality-adjusted life years, even when treatment costs are taken into consideration. CONCLUSION: Pulse oximetry as an adjunct to current routine practice of clinical examination alone is likely to be considered a cost-effective strategy in the light of currently accepted thresholds.

Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness.

BACKGROUND: Screening for congenital heart defects (CHDs) relies on antenatal ultrasound and postnatal clinical examination; however, life-threatening defects often go undetected. OBJECTIVE: To determine the accuracy, acceptability and cost-effectiveness of pulse oximetry as a screening test for CHDs in newborn infants. DESIGN: A test accuracy study determined the accuracy of pulse oximetry. Acceptability of testing to parents was evaluated through a questionnaire, and to staff through focus groups. A decision-analytic model was constructed to assess cost-effectiveness. SETTING: Six UK maternity units. PARTICIPANTS: These were 20,055 asymptomatic newborns at ≥ 35 weeks' gestation, their mothers and health-care staff. INTERVENTIONS: Pulse oximetry was performed prior to discharge from hospital and the results of this index test were compared with a composite reference standard (echocardiography, clinical follow-up and follow-up through interrogation of clinical databases). MAIN OUTCOME MEASURES: Detection of major CHDs - defined as causing death or requiring invasive intervention up to 12 months of age (subdivided into critical CHDs causing death or intervention before 28 days, and serious CHDs causing death or intervention between 1 and 12 months of age); acceptability of testing to parents and staff; and the cost-effectiveness in terms of cost per timely diagnosis. RESULTS: Fifty-three of the 20,055 babies screened had a major CHD (24 critical and 29 serious), a prevalence of 2.6 per 1000 live births. Pulse oximetry had a sensitivity of 75.0% [95% confidence interval (CI) 53.3% to 90.2%] for critical cases and 49.1% (95% CI 35.1% to 63.2%) for all major CHDs. When 23 cases were excluded, in which a CHD was already suspected following antenatal ultrasound, pulse oximetry had a sensitivity of 58.3% (95% CI 27.7% to 84.8%) for critical cases (12 babies) and 28.6% (95% CI 14.6% to 46.3%) for all major CHDs (35 babies). False-positive (FP) results occurred in 1 in 119 babies (0.84%) without major CHDs (specificity 99.2%, 95% CI 99.0% to 99.3%). However, of the 169 FPs, there were six cases of significant but not major CHDs and 40 cases of respiratory or infective illness requiring medical intervention. The prevalence of major CHDs in babies with normal pulse oximetry was 1.4 (95% CI 0.9 to 2.0) per 1000 live births, as 27 babies with major CHDs (6 critical and 21 serious) were missed. Parent and staff participants were predominantly satisfied with screening, perceiving it as an important test to detect ill babies. There was no evidence that mothers given FP results were more anxious after participating than those given true-negative results, although they were less satisfied with the test. White British/Irish mothers were more likely to participate in the study, and were less anxious and more satisfied than those of other ethnicities. The incremental cost-effectiveness ratio of pulse oximetry plus clinical examination compared with examination alone is approximately £24,900 per timely diagnosis in a population in which antenatal screening for CHDs already exists. CONCLUSIONS: Pulse oximetry is a simple, safe, feasible test that is acceptable to parents and staff and adds value to existing screening. It is likely to identify cases of critical CHDs that would otherwise go undetected. It is also likely to be cost-effective given current acceptable thresholds. The detection of other pathologies, such as significant CHDs and respiratory and infective illnesses, is an additional advantage. Other pulse oximetry techniques, such as perfusion index, may enhance detection of aortic obstructive lesions. FUNDING: The National Institute for Health Research Health Technology programme.

Assessment of myocardial function in neonates using tissue Doppler imaging.

OBJECTIVE: To measure the left and right ventricular myocardial velocities using tissue Doppler imaging (TDI) in the first 24 h of life in neonates. DESIGN: Left and right ventricular peak systolic (S'), early diastolic (E') and late diastolic (A') myocardial velocities were measured using TDI alongside standard echocardiography (including peak diastolic atrioventricular flow, E). E/E' ratio was calculated for both ventricles. SETTING: UK neonatal intensive care unit. PATIENTS: 43 neonates were prospectively recruited into three groups: term (n=16), preterm (30-36 weeks, n=12) and very preterm (<30 weeks, n=15). RESULTS: Myocardial velocities increased with increasing gestation. Right ventricular velocities were significantly greater than left. E/E' ratio decreased with increasing gestation. Left E/E' ratio was higher than right in each group. CONCLUSIONS: TDI is feasible in preterm neonates and enables the acquisition of myocardial velocities. With increasing gestation, higher myocardial velocities and lower E/E' ratios were found. The addition of TDI to standard neonatal echocardiography may provide additional information about cardiac function.

Prenatal diagnosis, management and outcome of fetal dysrhythmia: a tertiary fetal medicine centre experience over an eight-year period.

OBJECTIVE: To review the prenatal diagnosis, management and outcome of fetal dysrhythmia. SUBJECTS AND METHODS: Prenatal diagnosis, management and outcomes of fetuses with dysrhythmia were reviewed retrospectively (01/01/1997 to 31/12/2004). RESULTS: Over an 8-year period, 318 pregnant mothers were referred for assessment of suspected fetal dysrhythmias. Median gestation was 30 weeks (range 19-41). Fetal dysrhythmia was identified in 182 (57%) and classified as: (i) 126 atrial extrasystoles; (ii) 26 tachyarrhythmia, and (iii) 30 bradyarrhythmia. Of the fetuses with tachyarrhythmia, 23 had supraventricular tachycardia (SVT), 2 atrial flutter and 1 sinus tachycardia. One death associated with severe hydrops occurred in the tachyarrhythmia group. 19 cases of SVT were successfully treated in utero. Both cases of atrial flutter required direct current cardioversion in the neonatal period. In the bradyarrhythmia group, there were 15 isolated cases and 10 cases associated with congenital heart disease, with 73 and 20% survival, respectively. CONCLUSIONS: Benign atrial extrasystoles are the commonest cause for referral and assessment of fetal dysrhythmia. The overall prognosis for SVT is good with the majority responding to transplacental therapy. In cases with congenital atrioventricular block, the outcome was less favourable, especially when the atrioventricular block was associated with congenital heart disease.

Maternal methadone therapy increases QTc interval in newborn infants.

INTRODUCTION: Prolongation of the QT interval is a risk factor for sudden death. Methadone treatment is a well-recognised cause of QT interval lengthening in adults. The effect of maternal methadone treatment on the QT interval of the newborn infant is not known. This is the first prospective study of corrected QT (QTc) interval in infants born to mothers receiving methadone. AIM: To compare QTc interval in infants born to mothers receiving methadone therapy with healthy controls. METHOD: Twenty-six term infants (median gestation 38 weeks, range 37-40) born to mothers on methadone therapy had ECG recordings on days 1, 2, 4 and 7. The QTc interval was calculated using the Bazzett formula. Results for days 1 and 2 were compared with healthy matched control infants born to mothers who were not receiving methadone. Results for days 4 and 7 were compared with published normal values. RESULTS: In the methadone group, the QTc interval was significantly prolonged on days 1 and 2 of life. On days 4 and 7, this increase was no longer present. None of the infants in either group had any evidence of significant cardiac rhythm disturbance. CONCLUSION: Maternal methadone therapy can cause transient prolongation of the QTc interval in newborn infants in the first 2 days of life. Newborns exposed to methadone are at risk of cardiac rhythm disturbances. Bradycardia, tachycardia or an irregular heart rate in an infant born to a mother on methadone treatment should prompt investigation with a 12-lead ECG.

Prognosis in isolated gastroschisis with bowel dilatation: a systematic review.

OBJECTIVES: To investigate prognosis of the fetus with isolated gastroschisis and bowel dilatation from a systematic review of the literature. We aimed to compare the incidence of (a) intrauterine death, (b) death within 4 weeks of delivery, (c) bowel resection, (d) length of time to oral feeds and (e) time as inpatient in fetuses with gastroschisis with and without evidence of bowel dilatation. METHODS: Literature was identified by searching two bibliographical databases between 1980 and 2007. Studies were assessed for quality and stratified according to the definition of bowel dilatation. The data extracted were inspected for clinical and methodological heterogeneity. RESULTS: The search strategy yielded 1335 potentially relevant citations. Full manuscripts were retrieved for 92 citations. 10 studies (273 patients) were finally included in the systematic review. No difference was found between groups for death within 4 weeks of delivery (OR = 0.62 (95% CI 0.11 to 3.32); heterogeneity p = 0.39) or bowel resection (OR = 3.35 (95% CI 0.82 to 13.74); heterogeneity p = 0.39). There were insufficient data to compare the risk of intrauterine death and length of time to oral feeds. The mean inpatient stay was not significantly different between groups (OR = 16.63 (95% CI 0.98 to 32.28); heterogeneity p = 0.23). CONCLUSION: Current available evidence suggests that fetuses with isolated gastroschisis and bowel dilatation are not at increased risk of adverse perinatal outcome compared to those without bowel dilatation. However, there is a paucity of studies, and a randomised controlled trial is urgently needed.

Outcome following prenatal diagnosis of complete atrioventricular septal defect.

OBJECTIVE: To identify in a case cohort study, overall outcome following prenatal diagnosis of complete AVSD (cAVSD) in a tertiary referral fetal cardiology center. METHOD: We retrospectively reviewed all pregnancies from 1997 to 2004 in which the fetus was identified on ultrasound examination as having a cAVSD. RESULTS: A prenatal diagnosis of cAVSD was made using fetal echocardiography in 99 fetuses. The median (range) gestational age at diagnosis was 23 weeks (17-37). In 41 cases, cAVSD was the sole cardiac lesion. The remaining 58 fetuses had associated additional intracardiac malformations. Prenatal karyotype was obtained in 43 fetuses and was abnormal in 23. Extracardiac anomalies were also identified in 25 fetuses. Following prenatal counseling, 35 couples chose termination. Of the 64 continuing pregnancies, 12 were stillbirths and 4 were lost to follow-up. Of the 48 live births, 16 were neonatal deaths without surgery while 32 babies underwent surgery and 19 have survived to date (follow-up between 2 years 10 months to 9 years 10 months). CONCLUSION: At the time of prenatal diagnosis at a regional fetal medicine center, the overall survival rate for fetuses with cAVSD is 32% (excluding termination and those lost to follow-up). This information has important implication for parents of fetuses with cAVSD and when undergoing prenatal counseling.

Antenatal perspective of hypoplastic left heart syndrome: 5 years on.

BACKGROUND: Palliative staged reconstructive surgery has radically altered the outcome of babies with hypoplastic left heart syndrome (HLHS). AIM: To compare the current outcome of antenatally diagnosed HLHS with a series 5 years previously now that paediatric cardiothoracic and postnatal paediatric intensive care techniques have been further refined. METHOD: Comparison of all cases of HLHS diagnosed antenatally at Birmingham Women's Hospital between 1 January 2000 and 31 December 2004 with results of the previous series. RESULTS: 79 fetuses were identified with HLHS. The median gestational age at diagnosis was 22 weeks. After counselling, 20 (25.3%) couples terminated the pregnancy compared with 43.7% in the previous cohort (p = 0.01). Of the 59 couples who continued with the pregnancy, four had stillbirths and two were lost to follow-up. Subsequently, there were 53 live births, of which six babies had an alternative major congenital heart disease diagnosed postnatally; 10 babies were not considered for surgery (parents' wishes) and died after compassionate care; 31 babies underwent surgery. The early (30 days) surgical mortality after stage 1 Norwood procedure was 19.4% and 20 patients are still alive. In the cohort of intention-to-treat cases, the overall survival was 46.9% (23/49). CONCLUSION: The number of parents choosing termination after an antenatal diagnosis of HLHS has almost halved since 5 years ago. Despite the significant increase in surgical survival following stage 1 Norwood in this period, in the intention-to-treat cohort the survival was 46.9%. These data again highlight the poorer outcome for babies with congenital malformations diagnosed in utero in comparison with those identified postnatally.

An analysis of volatiles in the headspace of the faeces of neonates.

A gas chromatography/mass spectrometry (GCMS) analysis of the headspace from the faeces of neonates was undertaken to record the volatiles associated with preterm babies on a neonatal unit. The compounds ethanol, acetone, 2-ethyl-1-hexanol, 3-methylbutanal, hexanal and 2,3-butanedione occurred with the highest frequency. The volatiles analysed were then compared to a previously published study of the volatiles from asymptomatic adult faeces. Fewer compounds were found in the neonatal faeces and virtually no sulfides were detected, in contrast to the adult samples where carbon disulfide, dimethyl disulfide and dimethyl sulfide were ubiquitous. In addition, 7 of the most abundant 15 volatile compounds were found to be aldehydes, while in contrast only 2, acetaldehyde and benzaldehyde, were present in the most abundant 15 compounds found in the headspace of adult faeces. 2-Ethyl-1-hexanol was considerably more abundant in the neonate stool compared to adult stool, and probably reflects high exposure to plastic materials containing plasticizers. The potential of disease diagnoses from the analysis of volatiles emitted from neonate faeces is discussed.

Laser ablation of foetal microcystic lung lesion: successful outcome and rationale for its use.

OBJECTIVE: A foetus with an echodense, microcystic lung lesion complicated by non-immune hydrops has a high mortality rate. Because of the limited treatment options available, laser ablation was offered in an attempt to reduce the size of the lesion and reduce hydrops fetalis. METHODS AND RESULTS: A 25-year-old nulliparous woman presented at 21 weeks gestation. Ultrasound revealed a male foetus with a large microcystic right sided lung lesion that completely occupied the right hemithorax causing marked mediastinal deviation. The foetus was hydropic with polyhydramnios. Percutaneous laser ablation of the large microcystic lung lesion was performed under direct ultrasound control. At a power setting of 45 W, and using a 400 microm Nd:YAG laser fibre, the core of the lesion was photocoagulated in pulses lasting 5 s at 5 s intervals. The total target dose was 1683 J. This led to a marked but temporary reduction in amniotic fluid volume. The patient was commenced on sulindac and amniodrainage was performed at 27 weeks as reaccumulation of the polyhydramnios occurred. Pre-eclampsia complicated the pregnancy at 38 weeks gestation and an emergency caesarean section was performed. The baby underwent a thoracotomy and lobectomy at 48 h of age, made a good recovery, and is currently well 8 weeks post-delivery. CONCLUSIONS: In cases of cystic lung lesion complicated by hydrops, laser ablation should be considered as a treatment option.

A systematic review of the accuracy of first-trimester ultrasound examination for detecting major congenital heart disease.

OBJECTIVE: To evaluate the accuracy of first-trimester ultrasound examination in detecting major congenital heart disease (CHD) using a systematic review of the literature. METHODS: General bibliographic and specialist computerized databases along with manual searching of reference lists of primary and review articles were used to search for relevant citations. Studies were included if a first-trimester ultrasound scan was carried out to detect CHD that was subsequently verified by a reference standard. Data were extracted on study characteristics and quality, and 2 x 2 tables were constructed to calculate sensitivity and specificity. RESULTS: Ten studies (involving 1243 patients) were suitable for inclusion. Of these, four used transabdominal ultrasonography, four used transvaginal and two used a combination. Pooled sensitivity and specificity were 85% (95% CI, 78-90%) and 99% (95% CI, 98-100%), respectively. CONCLUSION: Ultrasound examination of the fetus in the first trimester is feasible for accurately detecting major CHD. It may be offered to women at high risk of having children with CHD.

Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units.

AIM: There is relatively little published information regarding gastro-oesophageal reflux (GOR) in preterm infants, therefore the aim of this study was to elucidate the incidence of GOR and management regimes employed for this condition in major neonatal intensive care units (NICUs). METHODS: A standard questionnaire was sent to consultants in 77 level II (or secondary) and III (or tertiary) NICUs. RESULTS: Seventy-eight percent of consultants responded. Of babies born in these units, 40% were less than 34 wk gestational age and the estimated incidence of GOR in this group was 22%. GOR was diagnosed on a clinical basis alone in 42% of units, 8% used clinical features and/or investigations, and 50% used clinical features plus investigations and/or therapeutic trials. Intra-oesophageal pH monitoring was available in 93% of units but used regularly in only 32% of suspected cases. Common treatment strategies for diagnosed GOR included non-drug options--body positioning (98%) and placement on a slope (96%); and drugs--H2-receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetic agents (79%), proton-pump inhibitors (65%) and dopamine-receptor antagonists (53%). However, the frequency with which all of these treatments were used varied widely between units. Surgery was required in only 1% of cases. CONCLUSIONS: GOR is perceived to be a common condition in preterm infants but the lack of published evidence relating to the management of GOR in preterm infants is reflected in the wide variation in diagnostic and treatment strategies used in major NICUs. It is clear that randomized, controlled trials to evaluate appropriate and effective treatments are needed.

The use of volume expansion in preterm infants.

There is no consensus of opinion regarding the appropriate use of volume expansion in the sick preterm infant. Recent evidence suggests that excessive volume expansion may increase mortality in this group. We determined the use of volume expansion in non-surgical preterm infants (<30 weeks gestation) among neonatal consultants in the West Midlands. A questionnaire was sent to 40 consultants working in all 16 neonatal units in the West Midlands region and re-sent one year later after presentation of interim regional mortality data. Responses were received from 15 units in 2000 and all 16 in 2001. Written guidelines for volume expansion were available in only 6 units (38%) in 2000 compared with 15 (94%) in 2001. The maximum volume expansion considered appropriate in the first 36 h of life reduced from a mean 37 mL/kg (range 15-150 mL/kg) in 2000 to 24 mL/kg (range 10-60 mL/kg) in 2001. In 2000 64% limited volume expansion to < or = 30 mL/kg (compared with 94% in 2001). Following regional discussion of interim mortality data and the subsequent development of unit guidelines, the prescription of volume expansion in the West Midlands region changed, with a reduction in the mean volume considered appropriate and greater consistency between units. The impact on neonatal outcome needs to be determined.

The role of platelet activating factor in a neonatal piglet model of necrotising enterocolitis.

BACKGROUND AND AIMS: Necrotising enterocolitis (NEC) is a potentially devastating disorder of preterm infants but its aetiology remains unclear. The aim of these studies was to develop a neonatal piglet model for NEC and to then use the model to investigate the role of platelet activating factor (PAF) in its pathogenesis. METHODS: Anaesthetised newborn piglets were divided into six groups: (i) controls, and groups subjected to (ii) hypoxia, (iii) lipopolysaccharide (LPS), (iv) hypoxia+LPS, (v) hypoxia+LPS and the PAF antagonist WEB 2170, and (vi) PAF. Arterial blood pressure (ABP), superior mesenteric artery blood flow (MBF), mesenteric vascular conductance (MVC), and arterial blood gases were recorded, and intestinal histology was evaluated. RESULTS: Exposure to LPS, hypoxia+LPS, or PAF all caused haemorrhagic intestinal lesions associated with varying degrees of intestinal injury. PAF caused a significant initial decrease in both MVC and MBF whereas hypoxia+LPS caused a significant late reduction in ABP and MBF with a trend towards a decrease in MVC. The effects of hypoxia+LPS on both haemodynamic changes and intestinal injury were ameliorated by WEB 2170. CONCLUSIONS: Administration of hypoxia and LPS or of PAF in the neonatal piglet induces haemodynamic changes and intestinal lesions that are consistent with NEC. These effects are ameliorated by prior administration of WEB 2170, indicating an important role for PAF in the pathogenesis of NEC.

Role of platelet-activating factor in the pathophysiology of necrotizing enterocolitis.

UNLABELLED: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal illness that affects predominantly preterm infants. Treatment options are limited and NEC remains a significant cause of morbidity and mortality. The precise aetiology of NEC remains unclear but evidence strongly suggests that the cause is multifactorial and there are four main aetiological factors: prematurity, hypoxia, enteral feeding and bacterial colonization. The presence of similar intestinal lesions, regardless of aetiological trigger, strongly implicates a final common pathway in the pathogenesis. There is now a substantial body of evidence to indicate that endogenous inflammatory mediators, particularly platelet-activating factor (PAF), play a vital role in this final pathway. CONCLUSION: The use of agents that antagonize PAF may provide therapeutic options in the management of NEC.

Prone and left lateral positioning reduce gastro-oesophageal reflux in preterm infants.

AIM: To examine the effect of body position on clinically significant gastro-oesophageal reflux (GOR) in preterm infants. METHODS: Eighteen preterm infants with clinically significant GOR were studied prospectively using 24 hour lower oesophageal pH monitoring. Infants were nursed in three positions (prone, left, and right lateral) for 8 hours in each position, with the order randomly assigned. Data were analysed using analysis of covariance. RESULTS: The median (range) reflux index (RI) for the group was 13.8% (5.8-40. 4). There was no significant difference in the mean time spent in each position. RI (mean % (SEM)) was significantly less in prone (6. 3 (1.7)) and left lateral positions (11.0 (2.2)), when compared with the right lateral position (29.4 (3.2)); p<0.001. The mean (SEM) longest episodes (mins) of GOR were reduced by prone and left positions (8.6 (2.2) and 10.0 (2.4), respectively) compared with the right position (26.0 (3.9)); p<0.001. The mean (SE) number of episodes was reduced by prone (15.4 (2.8)) and left (24.6 (3.5)) positions when compared with right (41.6 (4.6)) (p<0.001). CONCLUSIONS: Prone and left lateral positions significantly reduce the severity of GOR, by reducing the number of episodes and the duration of the longest episodes. Such positioning offers a useful adjunct to the treatment in hospital of preterm infants with gastro-oesophageal reflux.

Acid oro-pharyngeal secretions can predict gastro-oesophageal reflux in preterm infants.

UNLABELLED: Acid gastro-oesophageal reflux (GOR) is common in preterm infants but there is a lack of a non-invasive technique to establish the diagnosis. The aim of this study was to identify whether the presence of acid in oro-pharyngeal secretions (OPS) was a valid indicator of clinically significant acid GOR in preterm infants. A total of 23 infants with suspected GOR were studied with 24 h lower-oesophageal pH monitoring and during this period the OPS were tested for acid with litmus paper at 6 hourly intervals. Median (range) gestation was 28 weeks (24-31), birth weight 1023 g (480-1750) and age at study 34 days (11-76). Significant GOR was defined as a reflux index >5%. Of the investigated infants, 18 subjects (78%) had significant GOR. Of this group, 16 infants had acid in the OPS on at least one occasion. Five infants did not demonstrate significant GOR and in four of these acid was not detected in the OPS. Our data indicate that as a predictor for significant GOR, litmus-testing OPS for acid has a sensitivity of 89%, specificity of 80%, positive predictive value of 94% and a negative predictive value of 67%. The difference in the incidence of acid OPS between the GOR and the No GOR group was significant (P<0.03). CONCLUSION: The presence of acid in the oropharyngeal secretions may help in the prediction of acid gastro-oesophageal reflux in preterm infants. The method is simple, inexpensive cheap and involves minimal disturbance. We suggest that it could aid clinical diagnosis and indicate a need for further investigation of gastro-oesophageal reflux.