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Biomedical subjects

R Hagan

Publications and source records attributed to R Hagan.

At least 19 recordsLinked to original sources

Structure of the neuronal protein calexcitin suggests a mode of interaction in signalling pathways of learning and memory.

The three-dimensional structure of the neuronal calcium-sensor protein calexcitin from Loligo pealei has been determined by X-ray analysis at a resolution of 1.8A. Calexcitin is up-regulated following Pavlovian conditioning and has been shown to regulate potassium channels and the ryanodine receptor. Thus, calexcitin is implicated in neuronal excitation and plasticity. The overall structure is predominantly helical and compact with a pronounced hydrophobic core between the N and C-terminal domains of the molecule. The structure consists of four EF-hand motifs although only the first three EF hands are involved in binding calcium ions; the C-terminal EF-hand lacks the amino acids required for calcium binding. The overall structure is quite similar to that of the sarcoplasmic calcium-binding protein from Amphioxus although the sequence identity is very low at 31%. The structure shows that the two amino acids of calexcitin phosphorylated by protein kinase C are close to the domain interface in three dimensions and thus phosphorylation is likely to regulate the opening of the domains that is probably required for binding to target proteins. There is evidence that calexcitin is a GTPase and the residues, which have been implicated by mutagenesis in its GTPase activity, are in a short but highly conserved region of 3(10) helix close to the C terminus. This helix resides in a large loop that is partly sandwiched between the N and C-terminal domains suggesting that GTP binding may also require or may cause domain opening. The structure possesses a pronounced electropositive crevice in the vicinity of the 3(10) helix, that might provide an initial docking site for the triphosphate group of GTP. These findings elucidate a number of the reported functions of calexcitin with implications for neuronal signalling.

Amino Acid Sequence↗

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

BACKGROUND: Gentamicin is widely used in the treatment of suspected or proven neonatal sepsis. Animal studies and systematic reviews from trials in older children and adults suggest that a one dose per day regimen is superior to a multiple doses per day regimen. Pharmacokinetic studies and retrospective audits in neonatal population also favour once a day administration of gentamicin. However, there is no consensus regarding the dose interval regimen in the neonatal population. OBJECTIVES: To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. SEARCH STRATEGY: Eligible studies were identified by searching MEDLINE (March 2005), EMBASE 1980 - 2004, Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2005) and CINAHL (December 1982 - March 2005). Abstracts of the Society for Pediatric Research were hand searched from 1980 to 2004 inclusive. No language restrictions were applied. SELECTION CRITERIA: All randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life. DATA COLLECTION AND ANALYSIS: Methodological quality of eligible studies was assessed according to allocation concealment, blinding of intervention, blinding of outcome assessment and completeness of follow up. Data were sought regarding effects on clinical efficacy, pharmacokinetic efficacy, ototoxicity and nephrotoxicity of the two regimens. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data, the typical relative risk (RR), typical risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS: Twenty four studies were initially identified. Thirteen were excluded and eleven studies (N = 574) included. All studies compared the effectiveness and safety of 'once a day' versus 'multiple doses a day' regimen of gentamicin in newborn infants. Only one study enrolled infants less than 32 weeks gestation. All except one trial used intravenous infusion. One trial used gentamicin as a bolus dose over one minute. Two trials used intramuscular gentamicin in some of their study infants. For the primary outcome of 'clearance of sepsis', all infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [Typical RD 0.00 (95% CI - 0.19, 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics, 'once a day dosing' of gentamicin was superior. 'Once a day' gentamicin regimen is associated with less failures to attain peak level of at least 5 microg/ml [Typical RR 0.22 (95% CI 0.11, 0.47); Typical RD -0.13 (95% CI -0.19, -0.08); 9 trials; N = 422]; less failures to achieve trough levels of < 2 microg/ml [Typical RR 0.38 (95% CI 0.27, 0.55); Typical RD -0.22 (95% CI -0.29, -0.15); 11 trials N = 503]; higher peak levels [WMD 2.58 (95% CI 2.26, 2.89); 10 trials; N = 440] and lower trough levels [WMD -0.57 (95% CI -0.69, -0.44); 10 trials; N = 440] compared to 'multiple doses a day' regimen. Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens. Significant heterogeneity was noted for some of the outcomes measured. Hence the results need to be interpreted with caution. Possible reasons for heterogeneity are different gestational ages of study infants and the timing of collection of blood samples in relation to a particular dose and the day of therapy on which the samples were collected. AUTHORS' CONCLUSIONS: There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates more than 32 weeks gestation.

Anti-Bacterial Agents↗

Human leucocyte antigen class II polymorphism in Irish patients with multiple sclerosis.

The contribution of human leucocyte antigen (HLA) to the genetic risk for multiple sclerosis (MS) in patients of Northern European Caucasoid ancestry has been known since the 1970s. The northern part of Ireland, including county Donegal, is known to be a high-risk area for the development of MS. Recorded prevalence rates for county Wexford in the south-east Ireland have been markedly lower and suggest the existence of a prevalence gradient within the island. To evaluate the association of HLA-DRB1 and -DQB1 haplotypes with MS in both Wexford and Donegal, we examined a total of 118 patients and 400 regionally matched controls. The aim of this exploratory study was to test the possibility of heterogeneity in HLA class II associations with MS and to identify potential predisposing or protective haplotypes, associated with MS risk in Ireland. We confirmed the association of DRB1*1501-DQB1*0602 haplotype carriage with MS in both Wexford [odds ratio (OR) = 2.95, P= 0.0020, P(cor)= 0.0220] and Donegal (OR = 2.29, P= 0.0030, P(cor)= 0.0420). A higher frequency and a significantly higher homozygosity rate of this haplotype in Donegal are likely contributing factors to the higher prevalence of MS in Donegal compared with Wexford. The distribution of HLA class II alleles among Irish MS patients and controls establishes that there is heterogeneity in HLA class II associations with MS within Ireland.

Adult↗

Development, reliability and validity of a new measure of overall health for pre-school children.

BACKGROUND: Few comprehensive systems are available for assessing and reporting the overall health of preschool children. OBJECTIVES: (i) To develop a multi-dimension health status classification system (HSCS) to describe pre-school (PS) children 2.5-5 years of age; (ii) to report reliability and validity of the newly developed measure. DESIGN: Existing systems (Health Utilities Index, Mark 2 and 3) were adapted for application to a pre-school population. The new system was tested for acceptability, validity and reliability. PARTICIPANTS: Three cohorts of children and their parents from Canada and Australia were utilized: Cohort 1 (MAC)-101 3-years old very low birthweight (VLBW, <1500 g) and 50 same age term children from Canada; Cohort 2 (AUS)-150 VLBW 3-years old from Australia; Cohort 3 (OMG)-222 3-years old with cerebral palsy (CP) from Ontario. METHODS: Parental intra-rater reliability was evaluated by completion of the HSCS-PS Parent questionnaire (MAC) at the clinic visit and again 14 days later. Health professionals (MAC) completed the HSCS-PS Clinician questionnaire. Percent agreement and Kappa values were used to assess parent-clinician agreement. Concurrent validity was tested in two populations of VLBW children (MAC and AUS) and a reference group of term children (MAC) by exploring the relationships between dimensions of the HSCS-PS and well-recognized norm-referenced measures: the Bayley Scales of Infant Development (BSID-II), the Vineland Adaptive Behavior Scales (VABS) and the Stanford-Binet (SB). Construct validity was tested by comparing ratings on both the HSCS-PS and the Gross Motor Function classification system (GMFCS) using a population of pre-school children with CP. Analyses were done using chi2, ANOVA and correlations with tau-b statistic. RESULTS: The HSCS-PS has 12 dimensions and 3-5 levels per dimension. Response rate for parental intra-rater reliability was 95%, with percent agreement ranging between 86 and 100%. Kappa values for various dimensions ranged from 0.38 to 1.00. Inter-rater reliability between parents and clinicians showed agreement ranging from 72 to 100%. Kappa values ranged from 0.30 to 1.00. CONCURRENT VALIDITY: There was a statistically significant gradient between HSCS-PS Mobility levels and motor scale scores of the BSID-II and VABS. A significant gradient also occurred when comparing HSCS-PS cognition levels to psychometric scores on the BSID-II and SB, as well as HSCS-PS self-care levels compared to VABS Daily Living scores. DISCRIMINATIVE AND CONSTRUCT VALIDITY: Birthweight category was shown to be a significant determinant of proportion of children with multiple HSCS-PS dimensions affected. In addition, HSCS-PS dimension levels were congruent with GMFCS levels where expected: mobility had excellent correlation; self-care, dexterity, speech and cognitive dimensions had moderate correlations. CONCLUSIONS: The HSCS-PS is readily accepted, quick to complete, widely applicable and provides a multi-dimensional description of health status. Preliminary assessments of reliability and validity are promising. The HSCS-PS can discriminate across populations by birthweight and shows strong relationships with standardized psychometric measures in comparable domains. It can pro- vide a summary profile of functional limitations in various populations of pre-school children in a consistent manner across programs and in different settings.

Australia↗

Neonatal congenital microvillus atrophy.

Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6-8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently approximately 50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately.

Atrophy↗

Two sets of HLA Class II DRB and DQB1 alleles co-segregate among family members in a single maternal haplotype.

HLA class II typing by sequence specific oligonucleotide probes (SSOP) on the family of a Burkit's Lymphoma patient produced hybridization patterns indicating the presence of two DRB1, and two linked DQB1 genes on the same maternal chromosome. DRB and DQB1 exon 2 amplification products associated with the novel maternal haplotype were identified by DNA typing techniques: These products corresponded to DRB1*0101, DRB1*1501, DRB5*01, DQB1*0501 and DQB1*0602 alleles. These alleles were seen to co-segregate among siblings sharing the same maternal haplotype. The patient, his mother and two of his siblings each appeared to possess elements of three DRB1, DQA1 and DQB1 genes. HLA DNA typing results indicated that a DNA sequence of approximately 100 Kb, spanning the region between, and including, DRB1 and DQB1 genes was inserted into the maternal haplotype. Serological typing on EBV transformed B lymphocytes obtained from the patient's mother showed three expressed DRB1 antigens. Serology on EBV transformed patient's cells also indicated multiple DRB1 antigen expression. The expression of three DRB1 and DQB1 genes on the cells of this patient would make it virtually impossible to obtain a suitably matched unrelated stem cell donor.

Alleles↗

Identification and nucleotide sequence of a new null allele, HLA B*3540N.

We report the definition of an HLA class I null allele that has been identified within the B35 group by a combination of serological and molecular typing. This allele, which has been named B*3540N, was detected in a French, potential unrelated hematopoietic stem cell donor of unknown ethnic origin, selected as a probable match for an Irish patient. The presence of the null allele was initially determined by the absence of B35 reactivity by serological typing, in contrast to positive reactions by PCR-SSP and PCR-SSO typing. Subsequent sequencing of clones containing the full genomic sequence of the B*35 allele identified a single nucleotide deletion within exon 4 which resulted in the introduction of a stop codon downstream within exon 4.

Alleles↗

CD4 T-cell count, viral load, and squamous intraepithelial lesions in women infected with the human immunodeficiency virus.

BACKGROUND: Recent studies have reported an increased incidence of squamous intraepithelial lesions in women infected with the human immunodeficiency virus (HIV). However, to the authors' knowledge there are scarce data regarding the relation between the CD4 T-lymphocyte count (CD4+), HIV viral load, and the development of cervical dysplasia as evidenced by cervicovaginal cytology. The objective of the current study was to examine the association between cervicovaginal smears (with and without squamous lesions) from HIV-infected women and their CD4+ counts and HIV viral load. METHODS: Two hundred ninety-six cervicovaginal smears from 108 HIV-infected women were reviewed and classified according to the Bethesda system. Abnormal cytologies (n = 74) were followed by colposcopy and/or biopsy. CD4+ counts and HIV viral loads were available at the time of the cytologic evaluation. Statistical analysis was performed using the Student t test and the Mann-Whitney U test. RESULTS: The control group (n = 222) had significantly higher CD4+ counts (378 vs. 246 cells/microL; P < 0.001) compared with the group with cervical lesions. There was no apparent difference between the CD4+ counts from women with low grade lesions and those from women with high grade lesions. The HIV viral load was significantly higher in patients with cytologic abnormalities than in those with negative Papanicolaou smears (P = 0.006). CONCLUSIONS: The degree of immunosuppression may contribute to the development of intraepithelial lesions in HIV-positive women, but once the lesion is established disease progression may not be affected by the CD4+ counts.

Adolescent↗

The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C.

BACKGROUND & AIMS: In hepatitis C infection, several studies have examined the role of the major histocompatibility complex (MHC) in determining outcome, with variable results. To clarify the importance of MHC, we examined class II DR and DQ antigens in a homogenous cohort of women exposed to hepatitis C genotype 1b from a single inoculum. METHODS: Of 243 participants, 95 had spontaneous viral clearance and 148 are chronically infected. The frequencies of HLA class II DR and DQ antigens were compared between the 2 groups and between liver biopsy findings of 145 chronically infected subjects. RESULTS: DRB1*0101 and DQB1*0501 alleles were more frequent in subjects who sustained viral clearance than in chronically infected subjects (32.3% and 36.8% vs. 8.8% and 14.2%, respectively; P = 0.002). DRB1*03011 and DQB1*0201 occurred more frequently in chronically infected subjects than in those who cleared the virus (41.5% and 42.6% vs. 16.7% and 15.8%, respectively; P = 0.001). Both DRB1*03011 and DQB1*0201 were significantly less frequent in those with higher inflammatory scores on liver biopsy. CONCLUSIONS: We show that in a homogenous cohort of women infected with the same hepatitis C virus, several HLA antigens are associated with either viral clearance or persistence. This suggests a strong role for host immunogenetic factors in determining outcome in hepatitis C infection.

Adult↗

Cuttlefish use polarization sensitivity in predation on silvery fish.

Cephalopods are sensitive to the linear polarization characteristics of light. To examine if this polarization sensitivity plays a role in the predatory behavior of cuttlefish, we examined the preference of Sepia officinalis when presented with fish whose polarization reflection was greatly reduced versus fish whose polarization reflection was not affected. Cuttlefish preyed preferably on fish with normal polarization reflection over fish that did not reflect linearly polarized light (n = 24, chi 2 = 17.3, P < 0.0001), implying that polarization sensitivity is used during predation. We suggest that polarization vision is used to break the countershading camouflage of light-reflecting silvery fish.

Animals↗

Repeated antenatal corticosteroids: size at birth and subsequent development.

OBJECTIVE: The objective was to study the effects of repeated antenatal corticosteroids on birth size, growth, and development in preterm infants. STUDY DESIGN: This observational study followed up for 3 years a prospective geographic cohort in the state of Western Australia of 477 singleton infants born at <33 weeks' gestation. RESULTS: Birth weight ratio decreased with increasing number of corticosteroid courses (P =.001), and multivariate analyses confirmed a reduction in birth weight of as much as 9% (P =.014) and a reduction in head circumference of as much as 4% (P =.0024). There were no additional benefits in mortality or respiratory outcomes, and there was a trend toward more severe chronic lung disease. At age 3 years growth and severe disability outcomes did not appear to be related to increasing number of corticosteroid courses. CONCLUSIONS: In this cohort study repeated corticosteroid courses were associated with adverse effects on size at birth without apparent benefits. These changes have the potential to affect later development.

Adrenal Cortex Hormones↗

Hospital admissions in the first year of life in very preterm infants.

OBJECTIVE: To analyse hospital readmissions to 1 year in infants < 33 weeks' gestation. STUDY DESIGN: Cohort of very preterm infants born in Western Australia. METHODS: Parental social class, history of asthma, race, gestational age, birthweight, sex, severity of respiratory disease and oxygen requirement at 28 days chronic lung disease (CLD), 36 weeks and term, maternal smoking, cohabitation with siblings, breast-feeding duration and hospital readmissions were recorded prospectively. RESULTS: Data were available for 538 of 560 (96%) infants discharged. Eight died in the first year. Two hundred and twenty-five infants (42%) had 443 readmissions, of which 370 were medical and 73 surgical. Risk factors for medical readmission were Aboriginal race, male sex and CLD. Breast-feeding was protective. Risk factors for surgical admission were male sex, lower gestation, severe hyaline membrane disease, severe CLD and birthweight < 10th centile. CONCLUSIONS: Readmission is common after very preterm birth. Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission.

Australia↗

Cytologic detection of Trichomonas esophagitis in a patient with acquired immunodeficiency syndrome.

Trichomonads are pathogens of the female genital tract and colonizers of the oropharynx. Gastrointestinal and pulmonary diseases have been reported in association with Trichomonas species, but a direct pathogenic effect of this organism in these organ systems remains controversial. Esophageal disease due to trichomonads has not been previously reported. A 43-yr-old man with acquired immunodeficiency syndrome (AIDS) with odynophagia and esophageal erosions was evaluated by endoscopy. Cytologic brushings from three of four sites in the esophagus were positive for trichomonads. Treatment with metronidazole resulted in clearance of the organism from the esophagus and improvement in clinical symptoms. We report esophageal trichomoniasis diagnosed on esophageal brush cytology in a man with AIDS. Clinical response was confirmed by cytologic studies and odynophagia improved with metronidazole treatment. Study of cytologic preparations was superior to biopsy for identification of this organism and was particularly useful in following the post-treatment course of disease.

Acquired Immunodeficiency Syndrome↗

Prostate cancer screening--a physician survey in Missouri.

This study investigated prostate cancer screening practices using prostate specific antigen testing (PSA), digital rectal examination (DRE), and transrectal ultrasonography (TRUS) by primary care physicians in Missouri. In 1993, a mail survey was sent to a stratified random sample of 750 physicians whose primary specialty was general practice, family practice, or internal medicine. Three separate mailings resulted in an overall adjusted response rate of 60 percent. Ninety-five percent of physicians were more inclined to use PSA compared with three years previously, with only 45 percent of physicians more inclined to use DRE. An increase in the use of PSA following a negative DRE was reported by 85 percent and a greater inclination to use TRUS following a positive PSA was reported by 90 percent Eighty-six percent agreed with the American Cancer Society (ACS) guidelines on prostate cancer screening. Using logistic regression adjusted across levels of demographic and practice factors, prevalence odds ratios were derived with results indicating that agreement with ACS guidelines and being in private practice are strong predictors of a physician's inclination to routinely screen asymptomatic patients for prostate cancer. Our findings have provided baseline information on prostate cancer screening in Missouri and suggest that primary care physicians view PSA testing as a useful procedure and appear to be using it in a manner similar to the general pattern seen across the country.

Adult↗

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants.

AIMS: To investigate (1) perinatal factors affecting condition at birth in very preterm infants (23-32 weeks) and (2) the relationship between poor condition at birth and neonatal respiratory morbidity and mortality. METHODOLOGY: Convenience sample (n = 479) drawn from a geographic population inception cohort. RESULTS: Antenatal steroid use reduced the risk of pH < or = 7.20 [Adjusted Odds Ratio 0.29 (95% CI 0.17, 0.50)], one minute Apgar < 4 [0.54 (0.33, 0.88)], and 5 min Apgar < 7 [0.44 (0.23, 0.84)]. Gestational age was significantly related to Apgar score but not cord arterial acid-base status. No other perinatal factor was significant. Poor condition at birth was associated with an increase in the incidence and severity of hyaline membrane disease and death. These effects were lessened in those exposed to steroids. CONCLUSION: Antenatal steroid use is associated with improved condition at birth and reduces the deleterious effects of poor condition at birth on early respiratory morbidity and mortality.

Acid-Base Equilibrium↗

Very preterm birth--a regional study. Part 1: Maternal and obstetric factors.

OBJECTIVE: To ascertain the demographic, pregnancy and obstetric factors associated with the delivery of a liveborn very preterm infant ( < 33 weeks of gestation) and to investigate any differences in these factors between identifiable aetiological groups. DESIGN: Cohort analytical study. SETTING: King Edward Memorial Hospital for Women (KEMH), Western Australia. MAIN VARIABLES EXAMINED: Maternal demographic and obstetric history, primary complication associated with delivery, obstetric management and mode of delivery. RESULTS: Six hundred and eight women who were delivered of 693 liveborn very preterm infants in Western Australia between 1.1.90 and 31.12.91, representing 1.22% of all women who were delivered of a liveborn infant in those years. Singleton pregnancy occurred in 517 (85%) and 541 (89%) were delivered in KEMH. Mean maternal age was 28 years with an excess of mothers less than 20 years of age and older than 34 years compared with the statewide perinatal data. Pre-eclampsia (n = 128, 21.1%), preterm prelabour rupture of membranes (n = 148, 24.3%), idiopathic preterm labour (n = 195, 30.4%) and antepartum haemorrhage (n = 111, 18.3%) were associated with 94.1% of deliveries. These proportions varied with plurality and period of gestation. Demographic details, use of antenatal steroids, exposure to labour and caesarean section delivery differed between mothers depending on the primary complication. Overall 322 (53.0%) received antenatal steroids and 297 (48.8%) were delivered by caesarean section. Factors associated with decreased use of steroids were gestational age of less than 27 weeks (odds ratio (OR) 0.54; 95% CI 0.36-0.83), preterm prelabour rupture of the membranes (OR 0.48; 95% CI 0.29-0.78) and idiopathic preterm labour (OR 0.56; 95% CI 0.35-0.91). Factors associated with increased use of steroids were multiple pregnancy (OR 1.70; 95% CI 1.02-2.81) and pre-eclampsia (OR 1.87; 95% CI 1.09-3.19). CONCLUSIONS: These very preterm deliveries account for only a small proportion of all deliveries. There are differences in the mother's demographic history, obstetric management and delivery depending on the primary aetiological factor.

Adult↗

Very preterm birth--a regional study. Part 2: The very preterm infant.

OBJECTIVE: To ascertain the growth characteristics, delivery room management and hospital mortality of very preterm liveborn infants (< 33 weeks of gestation) and to identify differences between infants associated with the aetiological factor related to their very preterm delivery. DESIGN: Cohort analytical study. SETTING: King Edward Memorial Hospital for Women, Western Australia. MAIN VARIABLES EXAMINED: Gestational age, birthweight, birthweight ratio, condition at birth and mortality. RESULTS: Six hundred and ninety-three liveborn very preterm infants were born to 608 mothers between 1.1.90 and 31.12.91. This was 1.37% of all liveborns in Western Australia. Three hundred and eighty-five (55.6%) were male. Growth characteristics (birthweight, birthweight ratio and proportion small for gestational age) differed between infants depending on the primary obstetric complication associated with the very preterm delivery. Overall 217 (31%) infants were small for gestational age, 34(4.9%) had a congenital anomaly, and 102 (14.7%) died. Corrected mortality, excluding major fatal congenital anomaly, was 86 (12.7%). The majority of infants died on the first day (n = 59 (57.8%)). The only factors associated with an increased or decreased mortality were decreasing gestation (adjusted odds ratio (AOR) 1.7, 95% CI 1.50-1.93), decreasing birthweight ratio (small for gestational age) (AOR 1.3, 95% CI 1.08-1.53), antepartum haemorrhage as primary complication (AOR 3.1, 95% CI 1.25-7.69) and any antenatal steroids (AOR 0.26, 95% CI 0.14-0.51). In comparison with other studies, survival in the extremely preterm group, defined as a gestational age of less than 28 weeks, is improving. CONCLUSIONS: Very preterm infants account for a large proportion of perinatal mortality. Further studies are required to explore the differences between infants on the basis of the primary obstetric complication and to ensure that increased survival is not associated with an increase in disabilities.

Abortion, Induced↗

Recurrent wheezing in very preterm infants.

AIMS: To document the prevalence of, and identify risk factors for, recurrent wheezing treated with bronchodilators in the first year of life. METHODS: Parental history and neonatal data were collected prospectively in a regional cohort of very preterm infants (< 33 weeks). Data on maternal smoking, siblings at home, breast feeding, respiratory symptoms, and hospital re-admissions were documented at 12 months. RESULTS: Outcome data were available for 525/560 (95%) of survivors. The incidence of recurrent wheeze was 76/525 (14.5%) in very preterm infants and 20/657 (3%) in a cohort of term newborns. Significant risk factors for recurrent wheeze in very preterm infants were parental history of asthma, maternal smoking, siblings at home, neonatal oxygen supplementation at 28 days, 36, and 40 weeks of gestation. CONCLUSIONS: Wheezing respiratory illnesses are common in very preterm infants. The factors involved are similar to those in more mature infants, with the addition of immaturity and neonatal lung injury.

Bronchial Hyperreactivity↗