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Biomedical subjects

K Costeloe

Publications and source records attributed to K Costeloe.

At least 19 recordsLinked to original sources

EPICure: facts and figures: why preterm labour should be treated.

The principal objective of the EPICure studies was to determine both short- and long-term outcomes of extremely preterm birth. Data were collected for all births before 26 completed weeks of gestation in the UK and Republic of Ireland for 10 months in 1995. Of 811 infants admitted to neonatal units, 314 (39%) survived. Of these, 283 (92%) were assessed at 2.5 years and 241 (78%) at 6 years, together with a comparator group selected from classmates in normal schools. At 6 years, 32 (13%) of those assessed had disabling cerebral palsy and 31 (13%) had severe sensory impairment. Cognitive impairment was a more frequent adverse outcome: the mean intelligence quotient (IQ) was 82 (SD 19). Fifty children (21%) had IQs > 3 SD less than that of the comparator group, and in 48 children (20%), IQ was 2-3 SD less than that of the comparator group. Infants whose mothers had received antenatal steroids had fewer severely abnormal head scan findings. In this population, abnormal head scan findings are independent predictors of reduced, severe motor disability at 2.5 years. Using step-wise logistic regression analysis, postnatal transfer was associated with severe motor disability; prolonged membrane rupture with reduced Mental Development Index (MDI) and antenatal steroid with increased MDI. It is clear that factors around the time of birth are critical in determining outcome, irrespective of later complications during neonatal intensive care. Since 1995, there is good evidence of improved survival, but it is not clear whether or not the number of survivors with severe adverse outcomes has changed. A new cohort of births <27 completed weeks is currently being collected in English maternity units. Data collection around the time of birth is more detailed than in 1995 in order to better explore the relationship between perinatal factors and later outcomes.

Cerebral Palsy↗

The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth.

AIMS: To describe perinatal factors associated with later morbidity among extremely preterm children at 30 months of age corrected for prematurity. POPULATION: Of 308 surviving children born at <or=25 weeks gestation in the United Kingdom and Ireland from March to December 1995, 283 (92%) were evaluated at 30 months of age corrected for prematurity. METHODS: Cerebral palsy, severe motor disability, and Bayley scores were used as dependent variables in sequential multiple regression analyses to identify factors associated with adverse outcomes. RESULTS: Adverse outcomes were consistently more common in boys. Factors related to perinatal illness, ultrasound evidence of brain injury, and treatment (particularly postnatal steroids) were associated with adverse motor outcomes (cerebral palsy, disability or Bayley psychomotor development index). Increasing duration of postnatal steroid treatment was associated with poor motor outcomes. A score was developed for severe motor disability with good negative predictive value. In contrast, mental development was associated with a broader range of factors: ethnic group, maternal educational level, the use of antenatal steroids, and prolonged rupture of membranes in addition to chronic lung disease. CONCLUSION: Male sex is a pervasive risk factor for poor outcome at extremely low gestations. Avoidable or effective treatment factors are identified, which may indicate the potential for improving outcome.

Cerebral Palsy↗

Decision making and modes of death in a tertiary neonatal unit.

AIMS: To study the frequency and reason for withdrawal/withholding of life sustaining treatment (LST) and do not resuscitate (DNR) orders in infants who died in a tertiary neonatal unit. METHODS: Infants who died at Homerton University Hospital between January 1998 and September 2001 were studied by retrospective analysis of patient records. RESULTS: The case notes of 71 (84%) of 85 infants who died were studied. Mode of death was withdrawal of LST in 28 (40%), DNR in 11 (15%), withholding of LST in two (3%), and natural in 30 (42%) infants. Withdrawal of LST was discussed with the parents of 39 seriously ill infants; 28 (72%) parents agreed. There was no difference in birth weight and gestational age of babies whose parents agreed or refused withdrawal of LST. White and Afro-Caribbean parents and those from the Indian subcontinent (20 of 23) were more likely to agree to withdrawal of LST than Black African or Jewish (eight of 16, p = 0.015) parents. The median age at withdrawal of LST was 4 days (range 1-57). The median duration between discussion and the parents agreeing to withdrawal of LST was 165 minutes (range 30-2160), and median duration between withdrawal of LST and death was 22 minutes (range 5-210). The most common reason for withdrawal of LST was complications of extreme prematurity (68%). CONCLUSION: The most common mode of death was withdrawal of LST, and the most common reason was complications of extreme prematurity. The ethnic and cultural background of the parents influenced agreement to withdrawal of LST.

Age Factors↗

Low birth weight for gestation and airway function in infancy: exploring the fetal origins hypothesis.

BACKGROUND: Poor fetal growth has been associated with impaired airway function in adult life, but evidence linking birth weight and airway function in early childhood is sparse. We examined the hypothesis that low birth weight for gestation is associated with impaired airway function shortly after birth and that this is independent of impaired postnatal somatic growth. METHODS: Airway function was measured using the raised volume technique in healthy white infants of low (< or =10th centile) or appropriate (> or =20th centile) birth weight for gestation and was expressed as forced expiratory volume in 0.4 s (FEV0.4), forced vital capacity (FVC), and the maximal expired flow at 25% of forced vital capacity (MEF25). Infant length and weight, maternal height and weight, maternal report of smoking prenatally and postnatally, and parental occupation were recorded. RESULTS: Mothers of low birth weight for gestation infants (n=98) were lighter, shorter, and more likely to smoke and have partners in manual occupations. At 6 weeks their infants remained lighter and shorter than those of appropriate birth weight (n=136). FEV0.4, FVC, and MEF25 were reduced in infants of low birth weight for gestation, in those whose mothers smoked in pregnancy, or who were in manual occupations. After adjusting for relevant maternal and infant characteristics, infants in the low birth weight for gestation group experienced a mean reduction of 11 ml in FEV0.4 (95% CI 4 to 18; p=0.002), of 12 ml in FVC (95% CI 4 to 19; p=0.004), and of 28 ml/s in MEF25 (95% CI 7 to 48; p=0.03). CONCLUSIONS: Airway function is diminished in early postnatal life as a consequence of a complex causal pathway which includes social disadvantage as indicated by maternal social class, smoking and height, birth weight as a proximal and related consequence of these factors, and genetic predisposition to asthma. Further work is needed to establish the relevance of these findings to subsequent airway growth and development in later infancy and early childhood.

Bronchial Diseases↗

Probiotics for preterm infants?

Infants nursed in special care baby units develop an abnormal pattern of microbial colonisation, which may contribute to disease. Enteric feeding of live microbial supplements (probiotics) may provide benefit to such infants and help to prevent diseases such as neonatal necrotising enterocolitis.

Enteral Nutrition↗

The EPICure study: growth and associated problems in children born at 25 weeks of gestational age or less.

AIM: To define growth outcomes of a geographically defined population of extremely preterm babies. POPULATION: The EPICure study identified all surviving children in the United Kingdom and Ireland born at < or = 25 weeks 6 days gestation between March and December 1995. Of 308 survivors, 283 (92%) were evaluated at 30 months of age corrected for prematurity. METHODS: Growth was measured as part of a medical and full neurodevelopmental assessment. Growth parameters were evaluated in relation to other 30 month outcomes and perinatal variables. RESULTS: The children were smaller in each of the five growth measures compared with published population norms: mean (SD) standard deviation scores were -1.19 (1.32) for weight, -1.40 (1.37) for head circumference, -0.70 (1.19) for height, -1.00 (1.38) for body mass index, and -0.75 (0.95) for mid-upper arm circumference. Despite being of average size at birth, children were significantly lighter with smaller head circumferences at the expected date of delivery, compared with population norms, and only weight showed later catch up, by 0.5 SD. Poorer growth was found in children whose parents reported feeding problems and with longer duration of oxygen dependency, as a marker for neonatal respiratory illness. Although severe motor disability was associated with smaller head circumference, overall there was no relation between Bayley scores and head growth. CONCLUSIONS: Poor growth in early childhood is common in extremely preterm children, particularly when prolonged courses of systemic steroids have been given for chronic lung disease. Improving early growth must be a priority for clinical care.

Arm↗

The association between birthweight, sex, and airway function in infants of nonsmoking mothers.

The risk of respiratory illness and death is increased in infants of low birthweight for gestational age, but the underlying physiologic mechanisms remain unclear. We examined the hypothesis that airway function is diminished in infants of low birthweight for gestational age, independent of exposure to maternal smoking. Respiratory function was measured using partial and raised volume forced expiratory maneuvers in 103 infants (> 35 wk gestation; 56 boys) not exposed pre- or postnatally to maternal smoking who, according to birthweight, were either small (SGA; n = 38) or appropriate (AGA; n = 65) for gestational age. At testing, SGA infants were of similar postnatal age (mean [SD]: SGA 6.8 [2.4] wk, AGA 5.9 [2.3] wk), but remained shorter and lighter than AGA infants. In univariate analyses, FVC, forced expired volume in 0.4 s (FEV(0.4)), and FEF(75) were significantly diminished in SGA compared with AGA infants (mean [95% CI of difference]: FVC: 127 versus 143 ml [-29, -2]; FEV(0.4): 112 versus 125 ml [-24, -2]; and FEF(75): 173 versus 203 ml s(-1) [-57, -3], respectively), but these differences were no longer significant after allowing for sex and body size. Furthermore, FEF(75) was on average 35 ml s(-1) lower in boys than girls (95% CI: -61, -8). We conclude that diminished airway function in SGA infants shortly after birth appears to be primarily mediated through impaired somatic growth.

Analysis of Variance↗

Neurologic and developmental disability after extremely preterm birth. EPICure Study Group.

BACKGROUND AND METHODS: Small studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria. RESULTS: At a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability. CONCLUSIONS: Severe disability is common among children born as extremely preterm infants.

Cohort Studies↗

Arachidonic and docosahexaenoic acids are strongly associated in maternal and neonatal blood.

BACKGROUND: The red cell membrane fatty acid composition has frequently been used as an index of essential fatty acid (EFA) nutrition. After birth there is a decline in plasma arachidonic acid (AA) and docosahexaenoic (DHA) acids in babies fed on conventional formula which contains only the parent linoleic and alpha-linolenic acids. In human studies, the red cell phosphoglyceride composition appears to be more constant than that of plasma. In infants fed fish oil without AA, the AA proportions fall in the plasma but much less so in the red cells. This result might be considered to mean that there is no need for preformed AA. On the other hand, in a study where the levels of AA fell there was reduction of infant growth. Indeed, where cell membrane composition does change there is often an associated alteration in physiological functions of membranes. We therefore felt it worth investigating the balance between AA and DHA in a physiological situation where plasma levels are known to change, namely in pregnancy. PURPOSE: The aim of the study was to investigate a relationship between blood phosphoglyceride AA and DHA in pregnant women and neonates. SUBJECTS: Health pregnant women from London, England (n=193) and their term babies (n=45); healthy pregnant women from Seoul, South Korea (n=40) and their term babies (n=40); and preterm neonates (n=72) from London. METHOD: Blood samples were taken from British and Korean pregnant women during the third trimester, and from term and preterm babies at birth. These samples were taken for routine monitoring purposes in Korea and were a part of a study on pregnancy outcome for which ethical permission was granted from the East London and The City Health Authority and Lambeth, Southwark and Lewisham Health Authority. Approval was also obtained from the Ethical Committee of the Asan Medical Centre, Seoul, South Korea. RESULTS: AA and DHA correlated in plasma choline phosphoglycerides (CPG) of the British mothers (r=0.52 P<0.0001). The correlation coefficients and significance were much stronger in the red cell CPG and even more so in the term and preterm infant red cell CPGs ( r=0.75, 0.80 and 0.88, respectively). Similarly, AA and DHA correlated in red cell CPGs of the Korean women and their term babies. There was also a significant relationship between the two fatty acids in red cell ethanolamine phosphoglycerides in the mothers and their babies. Both linoleic (LA) and alpha-linolenic acids (ALA) were inversely associated with AA and DHA in some of the phosphoglyceride fractions of the mothers and babies. CONCLUSIONS: Although AA and DHA have different primary dietary origins, there were significant relationships between AA and DHA in the phosphoglycerides of the red cell membrane. This finding seems surprising if the red cell composition is determined by diet. These results suggest a physiological mechanism which attempts to maintain an appropriate balance between AA and DHA. It is plausible that there is an optimum balance between AA and DHA for membrane stability, deformability, enzyme and receptor function. SPONSORSHIP: The British Diabetic Association, March of Dimes Birth Defects Foundation and The Christopher H.R. Reeves Charitable Trust. European Journal of Clinical Nutrition (2000) 54, 50-56

Adult↗

The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability.

OBJECTIVE: To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Ireland. This report is of survival and complications up until discharge from hospital. METHODOLOGY: A prospective observational study of all births between March 1, 1995 and December 31, 1995 from 20 to 25 weeks of gestation. RESULTS: A total of 4004 births were recorded, and 811 infants were admitted for intensive care. Overall survival was 39% (n = 314). Male sex, no reported chorioamnionitis, no antenatal steroids, persistent bradycardia at 5 minutes, hypothermia, and high Clinical Risk Index for Babies (CRIB) score were all independently associated with death. Of the survivors, 17% had parenchymal cysts and/or hydrocephalus, 14% received treatment for retinopathy of prematurity (ROP), and 51% needed supplementary oxygen at the expected date of delivery. Failure to administer antenatal steroids and postnatal transfer for intensive care within 24 hours of birth were predictive of major scan abnormality; lower gestation was predictive of severe ROP, while being born to a black mother was protective. Being of lower gestation, male sex, tocolysis, low maternal age, neonatal hypothermia, a high CRIB score, and surfactant therapy were all predictive of oxygen dependency. Intensive care was provided in 137 units, only 8 of which had >5 survivors. There was no difference in survival between institutions when divided into quintiles based on their numbers of extremely preterm births or admissions. CONCLUSIONS: This study provides outcome data for this geographically defined cohort; survival and neonatal morbidity are consistent with previous data from the United Kingdom and facilitate comparison with other geographically based data.

Analysis of Variance↗

The effect of early inhaled budesonide on pulmonary inflammation in infants with respiratory distress syndrome.

UNLABELLED: The aim of this pilot study was to determine the effect of early inhaled budesonide on clinical and inflammatory parameters in preterm infants ventilated for respiratory distress syndrome. CONCLUSION: Neither the inflammatory process associated with respiratory distress syndrome nor the progression to bronchopulmonary dysplasia appeared to be altered by treatment with inhaled budesonide.

Bronchodilator Agents↗

Plasma vitamin A and E in preterm babies fed on breast milk or formula milk with or without long-chain polyunsaturated fatty acids.

Plasma vitamin A and E, the antioxidant nutrients copper and zinc, and magnesium were investigated in preterm babies. They were fed on their own mother's breast milk, or a formula with, or without, AA and DHA. Vitamin A (2.4 mg/d) and E (15 mg/d) supplements were also given. Vitamin A and E levels of most of the babies were sub-optimal at birth. The mean concentrations of vitamin E increased in all the groups by the expected date of delivery (EDD) (p < 0.001). Those fed on their mother's breast milk had the highest value compared with the other groups (p < 0.001). There was an increase in the mean level of vitamin A (p > 0.05) and copper (p < 0.05) and a decrease in zinc (p < 0.05) between birth and EDD. Concentrations of the two vitamins were not different (p > 0.05) between the babies fed on the formula with, and without, AA and DHA. It is concluded that the amount of AA and DHA incorporated in the formula milk did not adversely influence the plasma vitamin A and E of the babies.

Anthropometry↗

The inadequacy of the essential fatty acid content of present preterm feeds.

UNLABELLED: Arachidonic (AA) and docosahexaenoic (DHA) acids are major components of endothelial, pulmonary and neuro-visual cell membranes. Preterm babies may be born with deficits of both AA and DHA. There is evidence that their endogenous anti-oxidant enzymes defence systems have only reached half the activity expected at term. Yet they are exposed to an oxygen tension greater than physiologically anticipated at this time, and the superoxide dismutase shows no evidence of significant catch-up. After birth, present enteral and parenteral feeds for the preterm baby result in a further drop of AA and DHA plasma proportions to a quarter or third of the intra-uterine expectation. At the same time, the proportion of linoleic acid (LA), the precursor for AA, rises in the plasma phosphoglycerides four-fold, thus denying the preterm infant the provision with which the placenta would have perfused the fetus to meet the very rapid demand for endothelial and neural growth. From the biochemistry it is predictable that this situation could lead to fragile cell membranes, leakage, rupture with peroxidation resulting in the formation of inflammatory and vasoconstrictive agents. CONCLUSION: The essential fatty acid content of current enteral and parenteral feeds for preterm infants is incorrectly formulated.

Arachidonic Acids↗

Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality.

OBJECTIVE: To evaluate gestation-specific risks of stillbirth, neonatal and post-neonatal mortality. DESIGN: Retrospective analysis of 171,527 notified births (1989-1991) and subsequent infant survival at one year, from community child health records. SETTING: Notifications from maternity units in the North East Thames Region, London. MAIN OUTCOME MEASURES: The incidence of births, stillbirths, neonatal and post-neonatal deaths at each gestation after 28 completed weeks. Mortality rates per 1000 total or live births and per 1000 ongoing pregnancies at each gestation were calculated. RESULTS: The rates of stillbirth at term (2.3 per 1000 total births) and post-term (1.9 per 1000 total births) were similar. When calculated per 1000 ongoing pregnancies, the rate of stillbirth increased six-fold from 0.35 per 1000 ongoing pregnancies at 37 weeks to 2.12 per 1000 ongoing pregnancies at 43 weeks of gestation. Neonatal and post-neonatal mortality rates fell significantly with advancing gestation, from 151.4 and 31.7 per 1000 live births at 28 weeks, to reach a nadir at 41 weeks of gestation (0.7 and 1.3 per 1000 live births, respectively), increasing thereafter in prolonged gestation to 1.6 and 2.1 per 1000 live births at 43 weeks of gestation. When calculated per 1000 ongoing pregnancies, the overall risk of pregnancy loss (stillbirth + infant mortality) increased eight-fold from 0.7 per 1000 ongoing pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at 43 weeks of gestation. CONCLUSION: The risks of prolonged gestation on pregnancy are better reflected by calculating fetal and infant losses per 1000 ongoing pregnancies. There is a significant increase in the risk of stillbirth, neonatal and post-neonatal mortality in prolonged pregnancy. This study provides accurate data on gestation-specific risks of pregnancy loss, enabling pregnant women and their carers to judge the appropriateness of obstetric intervention.

England↗

Respiratory function among preterm infants whose mothers smoked during pregnancy.

We examined whether the adverse effects of prenatal exposure to tobacco on lung development are limited to the last weeks of gestation by comparing respiratory function in preterm infants whose mothers had and had not smoked during pregnancy. Maximal forced expiratory flow (Vmax FRC) and time to peak tidal expiratory flow as a proportion of total expiratory time (TPTEF:TE) were measured prior to discharge from hospital in 108 preterm infants (mean [SD] gestational age, 33.5 [1.8] wk), 40 of whose mothers had smoked during pregnancy. Infant urinary cotinine was less than 4 ng/ml in those born to nonsmokers, but it was as high as 458 ng/ml in exposed infants (p < 0.0001). TPTEF:TE was significantly lower in infants exposed to tobacco in utero (mean [SD], 0.369 [0.109]) when compared with those who were not (0.426 [0.135]) (p <= 0.02). Vmax FRC was also reduced in exposed infants (mean [SD], 85.2 [41.7] ml/s versus 103.8 [49.7] ml/s) (p = 0.07). After allowing for sex, ethnic group, body size, postnatal age, and socioeconomic status, TPTEF:TE remained significantly diminished in infants exposed prenatally to tobacco (p < 0.05). Thus, impaired respiratory function is evident in infants born on average 7 wk prior to the expected delivery date, suggesting that the adverse effects of prenatal exposure to tobacco are not limited to the last weeks of pregnancy.

Age Factors↗