Andrew K Ewer

Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis

BACKGROUND Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. We assessed the performance of pulse oximetry as a screening method for the detection of critical congenital heart defects in asymptomatic newborn babies. METHODS In this systematic review, we searched Medline (1951-2011), Embase (1974-2011), Cochrane Library (2011), and Scisearch (1974-2011) for relevant citations with no language restriction. We selected studies that assessed the accuracy of pulse oximetry for the detection of critical congenital heart defects in asymptomatic newborn babies. Two reviewers selected studies that met the predefined criteria for population, tests, and outcomes. We calculated sensitivity, specificity, and corresponding 95% CIs for individual studies. A hierarchical receiver operating characteristic curve was fitted to generate summary estimates of sensitivity and specificity with a random effects model. FINDINGS We screened 552 studies and identified 13 eligible studies with data for 229,421 newborn babies. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76·5% (95% CI 67·7-83·5). The specificity was 99·9% (99·7-99·9), with a false-positive rate of 0·14% (0·06-0·33). The false-positive rate for detection of critical congenital heart defects was particularly low when newborn pulse oximetry was done after 24 h from birth than when it was done before 24 h (0·05% [0·02-0·12] vs 0·50 [0·29-0·86]; p=0·0017). INTERPRETATION Pulse oximetry is highly specific for detection of critical congenital heart defects with moderate sensitivity, that meets criteria for universal screening. FUNDING None.

Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study

BACKGROUND Screening for congenital heart defects relies on antenatal ultrasonography and postnatal clinical examination; however, life-threatening defects often are not detected. We prospectively assessed the accuracy of pulse oximetry as a screening test for congenital heart defects. METHODS In six maternity units in the UK, asymptomatic newborn babies (gestation >34 weeks) were screened with pulse oximetry before discharge. Infants who did not achieve predetermined oxygen saturation thresholds underwent echocardiography. All other infants were followed up to 12 months of age by use of regional and national registries and clinical follow-up. The main outcome was the sensitivity and specificity of pulse oximetry for detection of critical congenital heart defects (causing death or requiring invasive intervention before 28 days) or major congenital heart disease (causing death or requiring invasive intervention within 12 months of age). FINDINGS 20,055 newborn babies were screened and 53 had major congenital heart disease (24 critical), a prevalence of 2·6 per 1000 livebirths. Analyses were done on all babies for whom a pulse oximetry reading was obtained. Sensitivity of pulse oximetry was 75·00% (95% CI 53·29-90·23) for critical cases and 49·06% (35·06-63·16) for all major congenital heart defects. In 35 cases, congenital heart defects were already suspected after antenatal ultrasonography, and exclusion of these reduced the sensitivity to 58·33% (27·67-84·83) for critical cases and 28·57% (14·64-46·30) for all cases of major congenital heart defects. False-positive results were noted for 169 (0·8%) babies (specificity 99·16%, 99·02-99·28), of which six cases were significant, but not major, congenital heart defects, and 40 were other illnesses that required urgent medical intervention. INTERPRETATION Pulse oximetry is a safe, feasible test that adds value to existing screening. It identifies cases of critical congenital heart defects that go undetected with antenatal ultrasonography. The early detection of other diseases is an additional advantage. FUNDING National Institute for Health Research Health Technology Assessment programme.

Accuracy of pulse oximetry in screening for congenital heart disease in asymptomatic newborns: a systematic review.

Objective: To evaluate the accuracy of pulse oximetry as a screening tool for congenital heart disease in asymptomatic newborns. Design, data sources and methods: Systematic review of relevant studies identified through MEDLINE, EMBASE, Cochrane Library, MEDION, and bibliographies of retrieved primary and review articles. Two reviewers independently extracted data on study characteristics, quality and results to construct 2×2 tables with congenital heart disease as the reference standard. A random-effects bivariate model was used to meta-analyse estimates of sensitivity and specificity. Logit pairs of sensitivity and specificity of each study were analysed in a single model, accounting for their correlation due to differences in threshold between studies. Results: Eight studies were included with a total of 35 960 newborns. Pulse oximetry was performed on asymptomatic newborns in all studies; three studies excluding newborns with an antenatal diagnosis of congenital heart disease. Either functional or fractional oxygen saturation was measured by pulse oximetry with oxygen saturation below 95% as the cut-off level in most studies. On the basis of the eight studies, the summary estimates of sensitivity and specificity were 63% (95% CI 39% to 83%) and 99.8% (95% CI 99% to 100%), respectively, yielding a false positive rate of 0.2% (95% CI 0% to 1%). Conclusion: Pulse oximetry was found to be highly specific tool with very low false positive rates to detect congenital heart disease. Large, well-conducted prospective studies are needed to assess its sensitivity with higher precision.

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

To evaluate the accuracy of first‐trimester ultrasound examination in detecting major congenital heart disease (CHD) using a systematic review of the literature.

Gastric emptying in preterm infants.

An ultrasonic technique was used to compare gastric emptying after a feed of expressed breast milk and formula milk in a blind, cross over study of preterm infants. Fourteen infants (median gestational age 33 weeks) were studied on 46 occasions. Each infant received a nasogastric feed of either expressed breast milk or formula milk, and the alternative at the next feed. Real time ultrasound images of the gastric antrum were obtained and measurements of antral cross sectional area (ACSA) were made before the feed and then sequentially after its completion until the ACSA returned to its prefeed value. The half emptying time (50% delta ACSA) was calculated as the time taken for the ACSA to decrease to half the maximum increment. On average, expressed breast milk emptied twice as fast as formula milk: mean 50% delta ACSA expressed breast milk 36 minutes; formula milk 72 minutes. The technique was reproducible and there was no significant difference between the emptying rates of feeds of the same type for an individual infant. These data show that breast milk has a major effect on gastric emptying, which may have important implications for preterm infants who have a feed intolerance due to delayed gastric emptying.

The impact of routine predischarge pulse oximetry screening in a regional neonatal unit.

Objectives (i) To evaluate the impact of routine early pulse oximetry screening on the rate of unexpected neonatal unit (NNU) admissions and the need for echocardiography. (ii) To review the outcomes of babies admitted as a result of a positive pulse oximetry screening test. Design Retrospective review over a 40-month period. Setting Level 3 NNU. Patients All babies admitted as a result of positive pulse oximetry screening. Main outcome measures Indication for admission, clinical diagnosis and management were collated. Results 3552 babies were admitted during the study period. Of these, 1651 were unexpected admissions and 208/1651 (12.6%) were as a result of positive pulse oximetry screening. 165/208 babies (79%) had a significant clinical condition which required further intervention including 17 with congenital heart defect (CHD) (nine critical), 55 with pneumonia, 30 with sepsis and 12 with pulmonary hypertension. No baby died or collapsed on the postnatal ward during the study period. 61/208 babies (29%) had echocardiography and CHD was detected in 28%. Conclusions Routine use of pulse oximetry screening identifies babies with CHD and other illnesses, which, if not identified early could potentially lead to postnatal collapse. It does not appear to overload clinical services, resulting in appropriate admission in the majority and a modest increase in the number of echocardiograms performed.

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.

Gastric emptying and gastro-oesophageal reflux in preterm infants.

Gastro-oesophageal reflux is common in preterm infants, but the role of gastric emptying as a causal factor has not been studied before. Gastric emptying was therefore measured in 19 healthy preterm infants (median gestational age 32 weeks) while concurrently measuring 24 hour lower oesophageal pH, using an antimony pH electrode, positioned manometrically. Real time ultrasonic images of the gastric antrum were obtained, and measurements of antral cross-sectional area (ACSA) were made immediately before a nasogastric feed and then during subsequent gastric emptying until ACSA returned to its pre-feed value. Half emptying time (50% delta ACSA) was calculated as the time taken for the ACSA to fall to half the maximal postprandial increment. Mean (SEM) reflux index for the group was 11.9 (2.0)%; number of reflux episodes per 24 hours: 15.4 (1.7); and number of reflux episodes longer than five minutes 5.5 (0.8). Average half emptying times for an individual infant were: median (range) 46 (18-105) minutes. There was no association between gastric emptying rates and any of the indices of gastro-oesophageal reflux, either during the entire 24 hour period for which the lower oesophageal pH was recorded, or in the postprandial periods after the feeds which were studied ultrasonically. Gastro-oesophageal reflux was also unrelated to feed volume and feed type. Asymptomatic gastro-oesophageal reflux is common in preterm infants, but gastric emptying time is not a determinant of it. Inappropriate relaxation of the lower oesophageal sphincter or abnormal oesophageal motility offer more plausible explanations.

Analysis of faecal volatile organic compounds in preterm infants who develop necrotising enterocolitis: a pilot study.

Objective: To determine differences in the profiles of volatile organic compounds (VOCs) in faecal samples from preterm infants who develop necrotising enterocolitis (NEC) compared with non-NEC controls. Materials and Methods: Daily faecal samples from preterm infants were collected prospectively during an 8-month period from a level 3 regional neonatal intensive care unit. Six infants subsequently developed NEC and were matched with 7 non-NEC infants. Solid-phase microextraction and gas chromatography and mass spectrometry were used to extract and identify the VOCs from the headspace above the faecal samples taken before the onset of NEC and after the disease was diagnosed. Faecal samples at similar ages were also studied from the control infants. Results: Two hundred twenty-four different VOCs were extracted from 65 samples. Volatile organic compounds increased in number with age for non-NEC infants. In the days before and after the diagnosis of NEC a reduction in the number of VOCs extracted was observed. In addition, 4 specific esters present in controls—2-ethylhexyl acetic ester, decanoic acid ethyl ester, dodecanoic acid ethyl ester, and hexadecanoic acid ethyl ester—were consistently absent from all faecal samples in those infants who developed NEC in the 4 days before the onset of the disease. Conclusion: This pilot study shows that VOC extraction from faeces may be used to identify infants that are at risk of developing NEC.

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.