An international comparison of retinopathy of prematurity grading performance within the Benefits of Oxygen Saturation Targeting II trials.

PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

The incidence, characteristics, management and outcomes of anaphylaxis in pregnancy: a population-based descriptive study.

OBJECTIVE: The aim of this study was to estimate the incidence of anaphylaxis in pregnancy and describe the management and outcomes in the UK. DESIGN: A population-based descriptive study using the UK Obstetric Surveillance System (UKOSS). SETTING: All consultant-led maternity units in the UK. POPULATION: All pregnant women who had anaphylaxis between 1 October 2012 and 30 September 2015. Anaphylaxis was defined as a severe, life-threatening generalised or systemic hypersensitivity reaction. METHODS: Prospective case notification using UKOSS. MAIN OUTCOME MEASURES: Maternal mortality, severe maternal morbidity, neonatal mortality and severe neonatal morbidity. RESULTS: There were 37 confirmed cases of anaphylaxis in pregnancy, giving an estimated incidence of 1.6 (95% CI: 1.1-2.2) per 100 000 maternities. Four cases of anaphylaxis were in women with known penicillin allergies: two received co-amoxiclav and two cephalosporins. Twelve women had anaphylaxis following prophylactic use of antibiotics at the time of a caesarean delivery. Prophylactic use of antibiotics for Group B streptococcal infection accounted for anaphylaxis in one woman. Two women died (5%), 14 (38%) women were admitted to intensive care and seven women (19%) had one or more additional severe maternal morbidities, which included three haemorrhagic events, two cardiac arrests, one thrombotic event and one pneumonia. No infants died; however, in those infants whose mother had anaphylaxis before delivery (n = 18) there were seven (41%) neonatal intensive care unit admissions, three preterm births and one baby was cooled for neonatal encephalopathy. CONCLUSIONS: Anaphylaxis is a rare severe complication of pregnancy and frequently the result of a reaction to antibiotic administration. This study highlights the seriousness of the outcomes of this condition for the mother. The low incidence is reassuring given the large proportion of the pregnant population that receive prophylactic antibiotics during delivery. TWEETABLE ABSTRACT: Anaphylaxis is a rare severe complication of pregnancy and frequently the result of a reaction to antibiotic administration.

The effect of implementing an automated oxygen control on oxygen saturation in preterm infants.

OBJECTIVE: To evaluate the effect of implementing automated oxygen control as routine care in maintaining oxygen saturation (SpO2) within target range in preterm infants. METHODS: Infants <30 weeks gestation in Leiden University Medical Centre before and after the implementation of automated oxygen control were compared. The percentage of time spent with SpO2 within and outside the target range (90-95%) was calculated. SpO2 values were collected every minute and included for analysis when infants received extra oxygen. RESULTS: In a period of 9 months, 42 preterm infants (21 manual, 21 automated) were studied. In the automated period, the median (IQR) time spent with SpO2 within target range increased (manual vs automated: 48.4 (41.5-56.4)% vs 61.9 (48.5-72.3)%; p<0.01) and time SpO2 >95% decreased (41.9 (30.6-49.4)% vs 19.3 (11.5-24.5)%; p<0.001). The time SpO2<90% increased (8.6 (7.2-11.7)% vs 15.1 (14.0-21.1)%; p<0.0001), while SpO2<80% was similar (1.1 (0.4-1.7)% vs 0.9 (0.5-2.1)%; ns). CONCLUSIONS: During oxygen therapy, preterm infants spent more time within the SpO2 target range after implementation of automated oxygen control, with a significant reduction in hyperoxaemia, but not hypoxaemia.

The effect of oxygen saturation targeting on retinal blood vessel growth using retinal image data from the BOOST-II UK Trial.

PURPOSE: Retinopathy of prematurity (ROP) is a disorder of developing retinal blood vessels in preterm infants. The purpose of this nested study was to investigate the effects of higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting on retinal blood vessel growth in preterm infants. METHODS: Retinal blood vessel growth in the higher (91-95%) and lower (85-89%) oxygen saturation (SpO2) targeting groups was compared. Suitable RetCam (Clarity, Pleasanton, CA, USA) images collected in the BOOST-II UK trial were used. The distances between the centre of the optic disc and the ROP ridge in the temporal and nasal retina were measured in pixel units. RESULTS: Images from 38 infants were studied, 20 from the higher SpO2 target group and 18 from the lower SpO2 target group. On average, temporal blood vessels extended further from the optic disc than nasal blood vessels, mean (standard deviation (SD)) 463.39 (55.05) pixels compared with 360.13 (44.47) pixels, respectively, P<0.0001. Temporal blood vessels extended less far from the optic disc in the higher SpO2 target group than in the lower SpO2 target group: mean (SD) 449.83 (56.16) pixels compared with 480.02 (49.94), respectively, P=0.055. Nasal retinal blood vessel measurements were broadly similar in the higher and lower SpO2 target groups; mean (SD) 353.96 (41.95) compared with 370.00 (48.82) pixels, respectively, P=0.38. CONCLUSIONS: Relatively high oxygen saturation targeting (91-95%) was associated with a trend (P=0.055) towards reduced retinal blood vessel growth in this study of preterm infants.

Influence of pulmonary factors on pulse oximeter saturation in preterm infants.

AIM: To describe how the stability of oxygen saturation measured by pulse oximetry (SpO2%) varies within and between infants with bronchopulmonary dysplasia (BPD). METHODS: Clinically stable infants with BPD had SpO2 measured at different inspired oxygen concentrations (FIO2 expressed as %). A computer model of gas exchange, that is, ventilation/perfusion ratio (VA/Q) and shunt, plotted the curve of SpO2 versus FIO2 best fitting these data. The slope of this curve is the change in SpO2 per % change in FIO2, hence SpO2 stability, calculated at each SpO2 from 85% to 95%. RESULTS: Data from 16 infants with BPD previously described were analysed. The dominant gas exchange impairment was low VA/Q (median 0.35, IQR, 0.16-0.4, normal 0.86). Median shunt was 1% (IQR, 0-10.5; normal <2%). Slope varied markedly between infants, but above 95% SpO2 was always <1.5. In infants with least severe BPD (VA/Q ≈0.4, shunt ≤2%) median slope at 85% SpO2 was 5.1 (IQR, 3.7-5.5). With more severe BPD (VA/Q ≤0.3) slope was flatter throughout the SpO2 range. The highest FIO2 for 90% SpO2 was in infants with the lowest VA/Q values. CONCLUSIONS: In infants with BPD, there was large variation in the slope of the curve relating SpO2% to inspired oxygen fraction in the SpO2 range 85%-95%. Slopes were considerably steeper at lower than higher SpO2, especially in infants with least severe BPD, meaning that higher SpO2 target values are intrinsically much more stable. Steep slopes below 90% SpO2 may explain why some infants appear dependent on remarkably low oxygen flows.

LXR is a negative regulator of glucose uptake in human adipocytes.

AIMS/HYPOTHESIS: Obesity increases the risk of developing type 2 diabetes mellitus, characterised by impaired insulin-mediated glucose uptake in peripheral tissues. Liver X receptor (LXR) is a positive regulator of adipocyte glucose transport in murine models and a possible target for diabetes treatment. However, the levels of LXRα are increased in obese adipose tissue in humans. We aimed to investigate the transcriptome of LXR and the role of LXR in the regulation of glucose uptake in primary human adipocytes. METHODS: The insulin responsiveness of human adipocytes differentiated in vitro was characterised, adipocytes were treated with the LXR agonist GW3965 and global transcriptome profiling was determined by microarray, followed by quantitative RT-PCR (qRT-PCR), western blot and ELISA. Basal and insulin-stimulated glucose uptake was measured and the effect on plasma membrane translocation of glucose transporter 4 (GLUT4) was assayed. RESULTS: LXR activation resulted in transcriptional suppression of several insulin signalling genes, such as AKT2, SORBS1 and CAV1, but caused only minor changes (<15%) in microRNA expression. Activation of LXR impaired the plasma membrane translocation of GLUT4, but not the expression of its gene, SLC2A4. LXR activation also diminished insulin-stimulated glucose transport and lipogenesis in adipocytes obtained from overweight individuals. Furthermore, AKT2 expression was reduced in obese adipose tissue, and AKT2 and SORBS1 expression was inversely correlated with BMI and HOMA index. CONCLUSIONS/INTERPRETATION: In contrast to murine models, LXR downregulates insulin-stimulated glucose uptake in human adipocytes from overweight individuals. This could be due to suppression of Akt2, c-Cbl-associated protein and caveolin-1. These findings challenge the idea of LXR as a drug target in the treatment of diabetes.

A simplified method for deriving shunt and reduced VA/Q in infants.

BACKGROUND: Right to left shunt and regional hypoventilation (reduced ventilation/perfusion ratio (V(A)/Q)) have different effects on the curve relating inspired oxygen (P(I)O(2)) to oxygen saturation measured by pulse oximetry (SpO(2)) and can be derived non-invasively from measurements of SpO(2) and inspired oxygen pressure (P(I)O(2)) using complex models of gas exchange. We developed a simpler computerised "slide-rule" method of making these derivations. AIMS: To describe the slide-rule method and determine agreement between measurements derived with this and a more complex algorithm. METHODS: Series of P(I)O(2) versus SpO(2) data points obtained during 43 studies in 16 preterm infants with bronchopulmonary dysplasia were analysed. Percentage shunt and the degree of right shift (kPa) of the P(I)O(2) versus SpO(2) curve compared with the oxyhaemoglobin dissociation curve (a measure of V(A)/Q) were determined for each dataset with both methods, and the results were compared using the method of Bland and Altman. RESULTS: The computer slide-rule method produced results for all 43 datasets. The more complex model could derive results for 40/43 datasets. The mean differences (95% limits of agreement) between the two methods for measurements of shunt were -1.7% (-6.5 to +3.5%) and for measurements of right shift were 0.3 kPa (-2.9 to +3.6 kPa). CONCLUSION: The slide-rule method was reliable for deriving shunt and right shift (reduced V(A)/Q) of the P(I)O(2) versus SpO(2) curve when compared with the more complex algorithm. The new method should enable wider clinical application of these measurements of oxygen exchange.

Arterial oxygen tension (Pao2) values in infants <29 weeks of gestation at currently targeted saturations.

BACKGROUND: Oxygen saturation (Spo(2)) monitors are commonly used to determine the need for supplemental oxygen. We aimed to describe the range of arterial oxygen tensions (Pao(2)) observed in preterm infants at saturation levels targeted in current trials. METHODS: In a cohort of 98 consecutive infants born at <29 weeks' gestation, the Pao(2) from each arterial blood gas result during the first week of life (n = 2076) was matched to the Spo(2) at time of sampling. The mean (95% CI) Pao(2) was calculated for each saturation. RESULTS: The 95% CI of Pao(2) for the Spo(2) range 85-95% was 3.8 to 8.9 kPa. The mean (95% CI) Pao(2) at a saturation of 85% was 5.3 (3.8 to 6.8) kPa and at a saturation of 95% it was 7.2 (5.5 to 8.9) kPa. CONCLUSION: Saturations within the range 85-95% largely exclude hyperoxia in preterm infants <29 weeks' gestation but permit Pao(2) values far lower than those recommended in traditional guidelines.

Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor.

OBJECTIVE: Levels of the vascular peptide endothelin-1 (ET-1) are significantly elevated in obesity. Adipose tissue-derived ET-1 attenuates insulin-mediated antilipolysis in human visceral adipocytes through the activation of the ET receptor B (ET(B)R), thereby linking ET-1 to insulin resistance. Whether ET-1 has direct effects on lipolysis in human adipocytes is not known. RESEARCH DESIGN AND SUBJECTS: Endothelin-1 receptor (ETR) mRNA expression was determined by quantitative PCR in 130 non-obese and obese subjects. ET-1 mRNA in different adipose tissue regions was also assessed. ETR protein expression was analyzed by western blotting in 37 subjects. The effect of ET-1 on lipolysis was assessed in freshly isolated adipocytes and in vitro differentiated adipocytes from human donors. RESULTS: Freshly isolated human adipocytes incubated with different concentrations of ET-1 showed no acute effect on lipolysis. In contrast, a 24 h incubation in primary cultures of human adipocytes resulted in a significant 50% increase in lipolysis. This effect was concentration dependent and could be mimicked by an agonist of the ET(A) receptor but not with a selective ET(B)R agonist. Adipocyte differentiation was not affected by any of the agonists. In subcutaneous (s.c.) adipose tissue from 19 non-obese and 18 obese subjects, the protein expression of ET(A)R was significantly higher in obese subjects whereas there was no difference in ET(B)R expression. Interestingly, the differences in protein expression were not observed at the mRNA level as ET(A)R expression was similar between lean and obese subjects. CONCLUSION: Long-term but not acute incubation of human adipocytes with ET-1 results in a significant increase in lipolysis. This appears to be mediated through the activation of ET(A)R, demonstrating a yet another receptor-specific effect of ET-1. In addition, the protein expression of ET(A)R is increased in s.c. adipose tissue in obesity, possibly through post-transcriptional mechanisms. An increased effect of ET-1 could be a mechanism that contributes to increased basal lipolysis in human obesity.

Characterization of the human CIDEA promoter in fat cells.

BACKGROUND: Cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) is a protein that regulates lipolysis in human adipocytes through cross-talk involving tumor necrosis factor-alpha (TNF-alpha). TNF-alpha downregulates CIDEA mRNA although it is unclear whether this is mediated through transcriptional or post-transcriptional mechanisms. CIDEA has important metabolic effects in human fat cells and genetic variations in the human CIDEA gene have been correlated to the development of obesity. However, little is known about the factors regulating CIDEA expression in human adipocytes. We set out to describe the transcriptional control of human CIDEA. METHODS: A 1.1-kb genomic fragment upstream of the transcriptional start site (TSS) of human CIDEA was cloned and deletion fragments were generated. Transcriptional activity of the promoter was analyzed by luciferase reporter assays in in vitro-differentiated human adipocytes. The effect of TNF-alpha was assessed in human adipocytes and murine 3T3-L1 cells transfected with deletion fragments of the CIDEA promoter. Protein-DNA interactions were analyzed by electrophoretic mobility shift assays (EMSA). RESULTS: Basal transcriptional activity was found in a 97-bp region upstream of the TSS. We studied the effect of three common haplotypes in the promoter region but found no significant difference in transcriptional activity among them. Incubation of in vitro-differentiated human adipocytes as well as 3T3-L1 cells with TNF-alpha reduced the transcriptional activity of the human CIDEA promoter, demonstrating a direct effect on CIDEA transcription. EMSAs and mutational analysis indicated that this was mediated by a nuclear factor-kappaB (NF-kappaB) site at position -163/-151. CONCLUSION: We demonstrate that basal transcription of the human CIDEA gene is confined to the 97 first bases upstream of TSS and that TNF-alpha negatively regulates transcription of this gene, which at least in part involves NF-kappaB activation.

Does the monitoring method influence stability of oxygenation in preterm infants? A randomised crossover study of saturation versus transcutaneous monitoring.

INTRODUCTION: Hyperoxia and variable oxygenation are associated with morbidity in preterm infants. The optimal range of oxygen tensions is not known. This study aimed to determine whether care based on transcutaneous oxygen tension (TcPO2) or saturation (SpO2) monitoring is associated with less time spent with high oxygen tension and less variability of oxygenation. METHODS: SpO2 and TcPO2 were measured simultaneously during two 3-h study periods allocated in random order. During one period supplemental oxygen was adjusted according to TcPO2 (target range 6.0-9.0 kPa) and during the other according to SpO2 (target range 86-94%). During each period, readings from the second monitor were not displayed. Both TcPO2 and SpO2 were downloaded every second. For each period the mean level and the variability (standard deviation) of SpO2 and TcPO2 and the percentage of time spent above and below target range were calculated and compared. RESULTS: 19 infants, 13 ventilated and 6 on continuous positive airway pressure, were studied at mean corrected gestational age of 27.2 weeks and mean postnatal age of 6.8 days. Their mean fraction of inspired oxygen at the start of the study was 0.34. Care based on SpO2 monitoring was associated with more time spent with high oxygen tension (median increase 2.62%, p = 0.01), more time with low oxygen tension (median increase 17.41%, p = 0.01), more variability in oxygen tension (median increase 0.28 kPa, p = 0.02) and more variability in oxygen saturation (median increase 0.82%, p = 0.01) than care based on TcPO2 monitoring. CONCLUSION: Within the target ranges studied SpO2 monitoring was associated with significantly more variable oxygenation than TcPO2 monitoring.

Is intrapartum asphyxia preventable?

The contribution of intrapartum events to asphyxia-related mortality and morbidity and the degree to which it may be prevented are controversial. We examined trends in asphyxia-related mortality and morbidity in a single large regional perinatal centre. Between 1994 and 2005, the rate of asphyxia fell from 2.86/1000 births in 1994 to 0.91/1000 births in 2005 (P < 0.001). Hypoxic-ischaemic encephalopathy of all grades fell from 2.41 to 0.77/1000 live births (P < 0.001). This substantial and steady fall in the rate of asphyxia-related mortality and morbidity over a 12-year period suggests that a significant proportion of cases of intrapartum asphyxia may be preventable.

Non-invasive measurement of reduced ventilation:perfusion ratio and shunt in infants with bronchopulmonary dysplasia: a physiological definition of the disease.

BACKGROUND: An objective definition of bronchopulmonary dysplasia (BPD) is required to interpret trial outcomes and provide a baseline for prognostic studies. Current definitions do not quantify disease severity. The cardinal measures of impaired gas exchange are a reduced ventilation:perfusion ratio (V(A):Q) and increased right to left shunt. These can be determined non-invasively by plotting arterial oxygen saturation (Spo(2)) against inspired oxygen pressure (PIo(2)). AIMS: To describe the reduced V(A):Q and shunt in infants with BPD and evaluate these as graded measures of pulmonary dysfunction. METHODS: 21 preterm infants with BPD were studied. PIo(2) was changed stepwise to vary Spo(2) between 86% and 94%. Pairs of PIo(2) and Spo(2) data points for each infant were plotted and analysed to derive reduced V(A):Q ratio and shunt. RESULTS: In every infant, the Spo(2) versus PIo(2) curve was shifted to the right of the normal because of a reduced V(A):Q. The mean (SD) shift was 16.5 (4.7) kPa (normal 6 kPa). Varying degrees of shunt were also present, but these were less important in determining Spo(2) within the studied range. The degree of shift was strongly predictive of the PIo(2) required to achieve any Spo(2) within the range 86-94% (R(2)>0.9), permitting shift and V(A):Q to be determined from a single pair of PIo(2) and SpO(2) values in this range. CONCLUSIONS: The predominant gas exchange impairment in BPD is a reduced V(A):Q, described by the right shift of the Spo(2) versus PIo(2) relationship. This provides a simpler method for defining BPD, which can grade disease severity.

Effect of delayed sampling on umbilical cord arterial and venous lactate and blood gases in clamped and unclamped vessels.

BACKGROUND: Cord blood lactate at birth is a marker of antenatal hypoxia, and is comparable to pH as a prognostic tool. OBJECTIVE: To determine, by a prospective observational study, the effect of delayed sampling from arteries and veins that were double clamped to isolate the blood from the placenta (clamped), and from vessels that were not isolated from the placenta (unclamped). METHODS: Paired samples taken from clamped and unclamped vessels at 0, 20, 40, and 60 minutes were analysed for lactate, base excess, pH, and Pco(2). Data were analysed as the change from time 0 at 20, 40, and 60 minutes. RESULTS: Thirty eight placentas of infants delivered by elective caesarean section were studied. Arterial samples were taken from 20 placentas, and venous samples from 18 placentas. Arterial and venous lactate was significantly higher than at time 0 by 20 minutes in both clamped and unclamped vessels. Changes in unclamped vessels were greater than in clamped vessels. The pH remained unchanged over 60 minutes in clamped vessels, but changed significantly in unclamped vessels. Base excess changed significantly in both clamped and unclamped vessels. CONCLUSIONS: Cord blood samples taken after 20 minutes delay are unreliable for lactate measurement, even if the vessel has been doubly clamped to isolate the blood from the placenta. Current guidelines that state that blood can be sampled from a clamped cord for up to one hour after delivery should not apply to the interpretation of lactate or base excess. Delayed sampling from unclamped cords is very unreliable.

Effect of partial liquid ventilation and nebulized perfluorocarbon on CT lung density distribution: randomized controlled study of experimental lung injury.

BACKGROUND: Perfluorocarbon (PFC) liquid can improve gas exchange in acute lung injury. How PFC aerosol is distributed in the lung is unknown. METHODS: We induced lung injury in rabbits with saline lavage, followed by mechanical ventilation in the supine position. The animals were divided into three groups: a control group, a group treated with partial liquid ventilation and a group given nebulized perfluorocarbon (PF 5080). We made CT image slices of the excised lungs. In the apical, middle and caudal slices we defined three regions of interest, from anterior to posterior, and noted the mean attenuation of each area. We also studied two rabbits which had not received lung injury or mechanical ventilation. RESULTS: Group means were different between the normal rabbits and all three study groups. There was a difference between the control and partial liquid ventilation groups, and between the partial liquid ventilation and nebulized groups, but no difference between the nebulized and control groups. Within each treatment group, there was no regional difference in the distribution of density. CONCLUSIONS: PF 5080 is not deposited in large amounts by aerosol. Less PFC was found in the lungs after partial liquid ventilation than expected. Within treatment groups, lung densities indicate less gravitational and regional differences than found in other studies.

Neonatal research: the parental perspective.

OBJECTIVES: To investigate the recollections of parents consenting for their infants to be research subjects and determine their views about the need for consent. SUBJECTS: Parents of 154 sick newborn infants enrolled in a randomised trial in the early neonatal period. All parents had given written consent and received printed information. METHODS: A questionnaire and accompanying letter was sent to the parental home 18 months later. Non-responders were sent a further questionnaire and letter. RESULTS: Response rate was 64% (99/154). Some respondents (12%) did not remember being asked to consent to their baby joining a study, and a further 6% were unsure. Most of the respondents (79%) were happy, 13% neutral, and 8% unhappy with their decision to give consent. None felt heavy pressure to agree. Entering the trial caused 24% of respondents to feel more anxious, 56% neutral, and 20% less anxious about their baby. Most of the respondents (83%) would be unhappy to forgo the consent process for trials passed by the institutional ethics committee. CONCLUSIONS: A significant proportion of parents who give written consent for a trial in the early neonatal period do not later remember having done so. Parents who have had experience of neonatal research would be unhappy for their baby to be enrolled in a study that had ethics committee approval without their consent being obtained.

Preterm meconium staining of the amniotic fluid: associated findings and risk of adverse clinical outcome.

BACKGROUND: The incidence of preterm meconium staining of the amniotic fluid (MSAF) is uncertain. It may be an indicator of possible listeriosis. It is unclear how great this risk is or whether preterm MSAF is a risk factor for adverse neonatal outcome. OBJECTIVE: To investigate the incidence of preterm MSAF, the incidence of associated maternal and neonatal infection, and the outcomes of the infants at discharge. DESIGN: Retrospective case-control study. METHODS: Infants < 33 weeks gestation with preterm MSAF born in the Simpson Memorial Maternity Pavilion, Edinburgh between 1 January 1994 and 2 January 2001 were matched with the next infant of the same sex and gestation with clear liquor. Maternal and infant characteristics, culture results, placental histology, and clinical outcomes were compared. RESULTS: Preterm MSAF was observed in 45/1054 (4.3%) infants below 33 weeks gestation. No maternal or infant listeriosis was identified in cases or controls. There was no significant difference in birth weight, Apgar score, or first pH between cases and controls. Preterm MSAF was associated with prolonged rupture of the membranes (odds ratio (OR) 3.34, 95% confidence interval (CI) 1.07 to 10.49), but not maternal hypertension, sepsis, or chorioamnionitis. Severe (grade 3/4) intraventricular haemorrhage was significantly more common in infants with preterm MSAF (OR 2.03, 95% CI 1.62 to 2.53). There was no significant difference in mortality. Early onset sepsis was observed in two cases and three controls. CONCLUSIONS: Preterm meconium staining of the amniotic fluid may be associated with increased risk of intraventricular haemorrhage. It does not appear to be a useful indicator of listeriosis.

Can polyclonal intravenous immunoglobulin limit cytokine mediated cerebral damage and chronic lung disease in preterm infants?

Recent evidence suggests that inflammatory cytokines may play an important role in cerebral and pulmonary injury, especially in preterm infants. Immunomodulatory agents may help to limit such injury by reducing inflammation. Immunoglobulin has multiple anti-inflammatory properties and can modulate the inflammatory cytokine response. New evidence is required to test the hypotheses that prophylaxis or treatment with intravenous immunoglobulin may limit such inflammatory damage.