Search PubMed⌕ Search

Biomedical subjects

K Costeloe

Publications and source records attributed to K Costeloe.

At least 37 records · Page 2Linked to original sources

The risk of neonatal death and respiratory distress syndrome in relation to birth weight of preterm infants.

The aim of this study was to determine the risk of respiratory distress syndrome (RDS) and neonatal death (NND) in relation to birth weight in preterm neonates. A group of 255 singleton preterm neonates born at 22-36 weeks were examined. The mean birth weight for each gestational week was estimated from a fitted curve. Each birth weight was recalculated as a multiple of the mean. This approach allowed description of a range of birth weight for the whole population of preterm infants. As expected, the incidence of neonatal death and respiratory distress syndrome was higher among the less mature infants. However, there were no significant differences in outcome (NND, severe RDS) between infants whose birth weight was above or below the mean for gestational age, and no excess of "growth retardation" (birth weight below the 5th centile) in babies with NND or RDS. We conclude that, in our population, the risk of RDS and neonatal death does not appear to be related to the birth weight of preterm neonates but is, of course, related to gestational age.

Birth Weight↗

Are deficits of arachidonic and docosahexaenoic acids responsible for the neural and vascular complications of preterm babies?

We review evidence suggesting that pre- or postnatal deficits of arachidonic acid (AA) and docosahexaenoic acid (DHA) together with underdeveloped antioxidant protection contribute to neurovisual developmental disorders and other complications of premature birth. These two synergistic deficits occur at a time when 70% of energy is focused on brain development and when the brain and blood vessels are growing at high speed. The types of essential fatty acids fed to preterm babies bear no relation to what the infant would have received had it remained a fetus. This failure to meet essential fatty acid requirements exacerbates the AA and DHA deficits seen at birth; furthermore, the immature superoxide defenses remain depressed until the expected date of delivery. Deficits of these systems, which are required for cell membranes, the endothelium, and neural tissue, could provide the biochemical prerequisite for the membrane disorders to which these babies are at high risk: intraventricular hemorrhage, periventricular leucomalacia, retinopathy of prematurity, and bronchopulmonary dysplasia. Although poor vascular development during fetal and neonatal life may be repaired, the structural and antioxidant deficits identified in preterm babies may impair blood vessel development with long-term consequences. The conclusion drawn from this review is that present parenteral and enteral lipid nutrition for preterm babies is flawed and could be pathogenic. Full-term milk composition is the basis for the design of preterm infant foods, but full-term milk is different from the placental product that is rich in AA and DHA. Preterm lipid nutrition should be revised to be more in line with placental lipid transfer to the fetus.

Arachidonic Acid↗

Urinary antimony in infancy.

OBJECTIVE: To determine whether antimony may be detected in the urine during infancy and early childhood and its association with passive exposure to tobacco smoke, as assessed by urinary cotinine. DESIGN: Analysis of spare aliquots of urine collected from infants participating in studies of respiratory function and passive smoking. Urinary antimony was assayed using inductively coupled plasma mass spectroscopy in 201 urine specimens collected at different ages throughout the first two years of life from 122 term and 26 preterm infants. Urinary cotinine was measured using gas liquid chromatography. MAIN OUTCOME MEASURE: Urinary antimony concentrations. RESULTS: Absolute antimony concentrations varied widely between infants, being below the laboratory detection limit of 0.02 microgram/l in 7% of samples, below 0.5 microgram/l in 90.5%, and above the reference value of 1 microgram/l reported for non-occupationally exposed UK populations in 4%. Creatinine standardised antimony values were unrelated to postnatal age or urinary cotinine concentrations and were highest in urine collected from preterm infants within 24 hours of birth (geometric mean (95% confidence interval): 2.3 ng/mg (1.5 to 3.4)). CONCLUSIONS: Although antimony is present at very low concentrations in urine during infancy and early childhood, the relevance to health is uncertain. The higher levels found in preterm infants may reflect prematurity or fetal assimilation of antimony. Tobacco is unlikely to be an important source of environmental exposure to antimony during infancy and early childhood.

Aging↗

Influence of ethnicity and gender on airway function in preterm infants.

While maximal expiratory flow at functional residual capacity, calculated from partial expiratory flow volume curves (V'maxFRC), is a valuable measure of peripheral airway function in infants, limited data are available in preterm infants despite their high prevalence of respiratory problems. To investigate the influence of gender and ethnic group, V'maxFRC and other indices of respiratory function were measured in 28 black and 28 white preterm infants (50% female in each group) at time of discharge from the neonatal unit (mean [SD] weight 2.36 [0.3] kg, postnatal age 19 [9] d). No infant had any history of cardiorespiratory disease and all were born to non-smoking mothers. V'maxFRC tended to be higher in girls than boys (115 versus 94 ml.s-1 [95% CI: -5; 47]) but there was no significant difference in this parameter between black and white infants (111 versus 98 ml.s-1 [95% CI of difference: -12; 40]). Respiratory resistance (Rrs) was significantly lower in black than white infants (95% CI: -2.9; -0.4 kPa.L-1.s) and tended to be lower in female than male infants (95% CI: -2.3; 0.2 kPa.L-1.s). Similarly, time to peak tidal expiratory flow as a proportion of total expiratory time (tPTEF:tE) was significantly longer in black than white (95% CI: 0.06, 0.20) and in female than male (95% CI: 0.02, 0.15) infants. These findings suggest that certain parameters of airway function may be influenced by both ethnic group and gender in preterm infants, both of which should therefore be taken mw account when investigating the effects of disease and/or therapeutic interventions in this group.

Airway Resistance↗

Thermal entrainment of heart rate in the preterm infant.

Using spectral analysis we have studied changes in the heart rate during periodic thermal stimulation of one foot of infants during quiet sleep. Twenty-two appropriately grown preterm infants were studied in the first 15 d after birth to quantify responses in comparison with previously reported term infants. Babies were stimulated at 0.05, 0.10, and 0.15 Hz. Spectral power was calculated at the stimulus frequency +/-0.01 Hz and +/-0.02 Hz and over the low frequency range 0.03 Hz to 0.17 Hz. The data show that 1) there is an increase in power around the frequency of stimulation for each frequency studied (p < 0.002); and 2) there is an increase in the ratio of local to low frequency power at 0.05 Hz (p = 0.002) and 0.10 Hz (p = 0.001), but not at 0.15 Hz (p = 0.109). These data confirm the concept of entrainment in the appropriately grown preterm infant but demonstrate that it occurs over a wider frequency range than previously reported. The wider range is the same as that of the term infant, although there are differences in the patterns of entrainment between the two groups. Further work is required to map out the maturation of the autonomic nervous system in both the term and the preterm infant with respect to the low frequency components of the heart rate variability power spectrum.

Age Factors↗

The relationship of ponderal index and other measurements to birthweight in preterm neonates.

The objective was to determine the relationship between birthweight and anthropometric indices (PI and MAC/ OFC) in preterm infants. A group of 163 singleton preterm neonates born at 24-36 weeks were examined. Measurements were made of crown-heel length, midarm circumference, and occipito-frontal circumference. Birthweights were calculated as multiples of the mean (MoMs) for a given stage of gestation. There was a highly significant correlation between gestational age and MAC/OFC (p < 0.0001) but none with ponderal index. There was a significant correlation between weight expressed as multiples of the mean and both ponderal index (p < 0.008) and MAC/OFC (p < 0.0001). This relationship between birthweight and anthropometric indices suggests that measurement of the ponderal index does not provide a useful index of intrauterine nutrition.

Anthropometry↗

The deep breath vasoconstriction reflex--a new tool for autonomic assessment in infancy?

We describe the presence of the deep breath vasoconstriction reflex in the neonatal and postneonatal period in a group of 24 infants, of whom 11 were term and 13 were preterm. Our results suggest that the development of this reflex correlates to postnatal rather than postconceptional age. The reflex is suggested for future use in autonomic assessment of babies to define normal and abnormal development and in the assessment of infants thought to be at risk of Sudden Infant Death Syndrome (SIDS).

Autonomic Nervous System↗

A new microtransducer catheter for measuring esophageal pressure in infants.

Measurement of esophageal pressure, as a reflection of pleural pressure, is essential for assessment of dynamic lung mechanics in neonates and infants. Conventionally, an esophageal balloon or a fluid-filled catheter is used, but considerable skill is required to obtain accurate results. Both devices have problems, and failure to achieve valid occlusion tests have been reported, particularly in small infants with lung disease. Recently, a flexible #3 French gauge (FG) microtransducer catheter (MTC, Dräger Netherlands) has become available for medical monitoring. We have assessed the accuracy and feasibility of using this device for measuring lung mechanics in 51 spontaneously breathing infants and small children aged 1 day to 24 months (weight 1.35 to 12.0 kg), 9 of whom were healthy neonates, the remainder suffering from a variety of cardio-respiratory diseases, and in 18 sick ventilated infants (weight 0.6 to 4.0 kg). Positioning of the catheter was well tolerated by all infants. The ratio of esophageal to airway opening pressure changes (delta Pes:delta Pao) ranged from 0.94 to 1.09 [mean (SD) 1.013 (0.03)] for the spontaneously breathing infants and from 0.98 to 1.06 [mean (SD) 1.003 (0.02)] In the ventilated infants with no significant difference in this ratio between the two groups (p = 0.16). This new generation of catheter tip pressure transducers may provide a simpler and more reliable tool for assessing transpulmonary pressure changes in infants than has previously been available.

Catheterization↗

Delayed maturation of Hering-Breuer inflation reflex activity in preterm infants.

We have previously shown that the strength of the Hering-Breuer inflation reflex (HBIR) diminishes between 2 and 12 mo of age in full-term babies. The purpose of this study was to determine whether the onset of this decline had commenced by 3 to 4 mo of age in healthy full-term infants and whether preterm delivery influences the pattern of maturation. Serial measurements of HBIR activity using the end-inspiratory occlusion technique were made in 25 preterm and 27 full-term infants at matched postnatal and postconceptional ages during the first 6 mo of life. Although similar levels of reflex activity were observed at birth (mean +/- SD of 101.2% +/- 42.4% in preterm, and 101.0% +/- 33.9% in full-term infants), by 40 wk postconceptional age (PCA) (i.e., term equivalent) HBIR activity (mean +/- SD) had increased to 121.7% +/- 51.2% in preterm infants, which was significantly greater than that in full-term infants of similar PCA (95% CI of difference: 0.2; 41.2%). By 15 wk postnatal age (PNA), HBIR activity had decreased to 68.8% +/- 26.6% in full-term infants, but remained significantly higher in those delivered prematurely (87.8% +/- 32.7%). However, when measurements were repeated at approximately 4 mo after the expected rather than actual date of delivery, these differences were no longer evident (95% CI difference preterm-full-term: -21.2; 3.8%). This study suggests that important transitions in respiratory control mechanisms occur between 8 and 15 wk PNA in full-term infants and that these changes are delayed in preterm infants.

Aging↗

Mucosal tumor necrosis factor-alpha production and extensive disruption of sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory distress syndrome.

Many of the clinicopathologic features of neonatal respiratory distress syndrome (RDS) may be related to the inflammatory response mounted by the affected infant, although little is known about the interstitial component of this response. We have thus studied the local inflammatory response in this condition by immunohistochemical analysis of whole lung lobes, obtained at postmortem from 40 infants who died from acute RDS in the first week of life. All had demonstrated classical clinical history and histologic features. An archival subgroup from the early 1970s had never received ventilatory support. Immunohistochemical analysis demonstrated rapid temporal increase from birth in the mucosal density of CD68+ macrophages, MAC-387+ monocytes/macrophages, polymorphonuclear neutrophils, and tumor necrosis factor-alpha-immunoreactive cells, maximal in those dying at or after 72 h. Using a cationic probe specific for sulfated glycosaminoglycans (GAGs), the inflammatory infiltration was seen to be associated with striking loss of endothelial, basement membrane, and interstitial GAGs, which was almost complete by 48-72 h. GAG degradation products were found within hyaline membranes in all infants dying after 48 h. This study confirms that neonatal RDS is characterized by intense interstitial inflammation, significantly underestimated on routine staining. This begins within hours of birth and is maximal by 72 h of age. Breakdown of sulfated GAGs within the extracellular matrix follows the same time course and may explain much of the physiologic derangement characteristic of this condition.

Age of Onset↗

Early production of macrophage inflammatory protein-1 alpha occurs in respiratory distress syndrome and is associated with poor outcome.

Although progression to pulmonary fibrosis in preterm infants with respiratory distress syndrome (RDS) is related to the inflammatory response, the nature of this response remains controversial. We have therefore performed sequential bronchoalveolar lavages in 30 infants with RDS (13 of whom developed bronchopulmonary dysplasia) and 7 ventilated control infants, characterizing the cells obtained by immunohistochemical analysis of lineage-specific markers and assaying macrophage-associated chemokines and cytokines in supernatant fluid. At all ages from birth, lavage supernatants demonstrated highly significant increase over controls of the beta-chemokine macrophage inflammatory protein (MIP)-1 alpha, although not of regulated upon activation, normal T cell expressed and secreted (RANTES), of the cytokines tumor necrosis factor (TNF)-alpha and IL-1 beta, and of elastase/alpha-1 antitrypsin. Significantly higher concentrations of MIP-1 alpha in particular were associated with the later development of fibrosis. Increased numbers of macrophages expressing the activation marker RM/3-1 were found at all ages in bronchopulmonary dysplasic infants, whereas neutrophil numbers were increased from d 3. Dexamethasone administered to 10 infants induced rapid decrease in inflammatory cell numbers and concentrations of MIP-1 alpha, tumor necrosis factor-alpha, IL-1 beta, and elastase/alpha-1 antitrypsin. The inflammatory response in neonatal RDS begins within the first day of life. Long-term outcome is associated with the magnitude of this early response, in particular production of MIP-1 alpha. The early introduction of specific therapy is thus likely to be beneficial.

Biomarkers↗

Erythrocyte cupric/zinc superoxide dismutase exhibits reduced activity in preterm and low-birthweight infants at birth.

In a comparative study in term, preterm and low-birthweight infants, the mean activity and standard error of the mean for copper/zinc superoxide dismutase (Cu/Zn SOD) in cord erythrocytes from five term small for gestational age infants was 0.94 +/- 0.10 SOD units (mg protein)-1. This value was significantly lower than the activity (2.34 +/- 0.24) in nine term, appropriate for gestational age (AGA) babies (p < 0.005). In 15 preterm (AGA) infants, the activity at birth (1.05 +/- 0.07 SOD units (mg protein)-1) was also significantly lower (p < 0.001) relative to term AGA babies. An increased level of activity (1.59 +/- 0.09) was detected in the red cells of eight preterm AGA infants on their expected date of delivery compared with (0.87 +/- 0.06) at birth (p < 0.001). However, the activity (1.59 +/- 0.09) was still lower than that detected in term AGA babies (2.34 +/- 0.24; p < 0.02). Similar findings were obtained when enzymatic activity was expressed in units per millilitre of packed erythrocytes. The low activity of Cu/Zn SOD in preterm and low-birthweight babies may render them susceptible to diseases associated with membrane lipid peroxidation.

Erythrocytes↗

Effect of periodic thermal stimulus on heart rate in term newborn infant.

We studied heart rate changes in 25 term infants aged 1-7 days in quiet sleep during periodic thermal stimulation of one foot to widen the range of frequencies previously studied by others and to develop spectral analysis methods to quantify responses to thermal and other periodic sensory stimuli. The stimulation frequency was 0.10 Hz in all babies and ranged from 0.05 to 0.15 Hz in some. At 0.10 Hz, there was 1) an increase in spectral power at the frequency of stimulation (P < 0.001), 2) a tendency for overall low-frequency power to increase, 3) a reduction in respiratory sinus arrhythmia (P < 0.025), and 4) attenuation in the response between the first and second minute of stimulation (P < 0.01). At other frequencies of stimulation, essentially similar results were obtained. Respiration and other types of periodic sensory stimulation may also entrain the heart rate; we raise the question of whether low-frequency oscillations in heart rate are in fact related to thermoregulation or are a nonspecific feature of integrative processes in the brain stem.

Autonomic Nervous System↗

Risk factors for HIV infection overlooked in routine antenatal care.

We have ascertained the extent to which risk factors for HIV infection may escape detection by standard history-taking procedures in an antenatal clinic. This study was based on 1264 women from a multi-ethnic population in an inner London health district (City and Hackney). All had agreed to undergo attributable HIV testing and a detailed personal interview. Thirty-nine per cent (494 of 1264 women) reported risk factors contributed personally or by a partner. Most of these risk factors had not been earlier disclosed by routine history taking. In most cases the risk was residence and risk activity in a World Health Organization (WHO) Pattern 2 country. [HIV spread WHO categories: Pattern 1--principally homosexual/bisexual males and i.v. drug use (areas = North America, Western Europe, Australasia, parts of South America) with male to female ratio 10/1; Pattern 2--Heterosexual (areas = Sub Saharan Africa, Caribbean and part South America) with male to female 1/1.] Thirty-one subjects (2.4%) were aware that their partners had participated in bisexual activity. Only six subjects perceived themselves at risk through their own or partner's drug injecting activity. The frequency of risk factors was substantially greater than that ascertained by the routine history. The findings highlight the potential risk of heterosexual spread resulting from travel to or residence in high prevalence territories. The contribution by male partners is significant and is particularly difficult to detect during a routine interview. These data support the recommendation that voluntary HIV serum testing should be universal rather than a selective offer based on risk factors determined at a routine history.

Female↗

Fatty acid composition of plasma and red cell phospholipids of preterm babies fed on breast milk and formulae.

UNLABELLED: Fatty acids of plasma and red cells of preterm babies, gestational age 28-33 weeks, weighing less than 2200 g were studied between birth and the expected date of delivery (EDD). Babies were fed either mothers' breast milk, or if they were unable, or chose not to breast-feed, randomly assigned to milk formula A or B. Milk B had 26% oleic acid, 0.5% docosahexaenoic acid (DHA) and 0.12% arachidonic (AA); A had 13% oleic acid, less than 0.05% AA and no DHA. The proportions of gamma linoleic and the other fatty acids, and the ratio of linoleic acid (LA)/alpha linolenic acid (ALA) were comparable in the two formulae. Diet and/or physiological adaptation seemed to be responsible for the significant changes in the proportions of certain fatty acids between birth and EDD. Incorporation of DHA in formula B increased its concentration in plasma and red cells, and reduced the conversion of LA to AA. With respect to maintenance of DHA status, milk B was superior to milk A but did not match breast milk. CONCLUSION: Fortification of formula with DHA without concomitant incorporation of AA may precipitate AA insufficiency and may have developmental implications.

Arachidonic Acids↗

Vitamin A and related essential nutrients in cord blood: relationships with anthropometric measurements at birth.

Following the advice given by the Department of Health to women who are, or may become pregnant, not to eat liver and liver products because of the risk of vitamin A toxicity, the concentrations of vitamins A and E, and copper, magnesium and zinc in cord blood were investigated. The study was conducted in Hackney, an inner city area of London. Esters of vitamin A were not detected in any of the samples, indicating that there was no biochemical evidence of a risk of toxicity. Indeed, vitamin A correlated significantly with birthweight, head circumference, length, and gestation period. There was also a significant positive relationship between zinc and birthweight. In contrast, copper showed a negative correlation with birthweight and head circumference. Vitamin E and magnesium were not associated with any of the anthropometric measurements, although magnesium showed an increasing trend with birthweight. The data suggest that most of the mothers of the subjects studied may have been marginal with respect to vitamins A and E and zinc. In those with low birthweight babies. a higher intake would have improved their nutritional status and possibly the outcome of their pregnancy. For these low-income mothers, liver and liver products are the cheapest and the best source of vitamins A and E, haem iron, B vitamins and several other essential nutrients; hence the advice of the Department of Health may have been misplaced.

Adult↗

Risk identification for HIV infection in an inner London antenatal population.

This study was carried out to ascertain whether routine antenatal history taking is an effective means of identifying risk factors for HIV infection. Information about risk obtained at routine booking was compared with answers to selected questions obtained at a research interview. The study was conducted at St. Bartholomew's Hospital Homerton, and ran from February 1991 to March 1992. Of the 3729 women interviewed, 1671 had been hand booked (unstructured questionnaire) and 2058 had been computer booked (structured questionnaire). Hand booking failed to identify 77% of risk factors compared with 7% for computer booking. The findings highlight the underdetection of risk activity and confirm the need for intermittent, anonymous sampling to obtain background information against which a decision to implement universal testing may be made.

Female↗

Evaluation of an antenatal HIV testing programme in an inner London health district.

OBJECTIVE: To study an antenatal human immunodeficiency virus (HIV) testing programme in an inner London health district. DESIGN: A standardised research interview was given to women in the first half of pregnancy and the findings were compared with those of the routine clinical interview. The observations were analysed in relation to the results of HIV antibody testing, either attributable by consent or anonymously, in these women. SETTING: The Homerton Hospital, London. SUBJECTS: Three thousand seven hundred and twenty-nine women, of whom 1696 (45.5%) consented to testing. RESULTS: Four women who had consented to testing had a positive result. Amongst the 2,033 women (54.5%) who declined the test, four (or five) had a positive result. The number of risk factors ascertained by the research study interview was substantially greater than that elicited by the preceding routine interview. In addition, more information was obtained by a routine computer interview than by its unstructured equivalent. There was no obvious association between the presence of a risk factor and whether or not the women had consented to the test. CONCLUSIONS: Our formal voluntary testing programme detected nearly 44% of HIV seropositive individuals. Thus, there were four known positives during the study period against a total of nine detected by anonymous testing. Since all the known positive results in the study were associated with recognised risk factors, there is some doubt as to the value of a universal testing programme. However, if testing is to be based upon the existence of a risk factor elicited at the booking history, then the deficiencies in this history revealed by the present study need to be corrected.

Female↗