Kate Costeloe

Long chain polyunsaturated fatty acids and fetal growth

Long chain polyunsaturated fatty acid composition of plasma choline phosphoglycerides has been measured at birth in 22 preterm infants. Positive correlations were found between both n-6 and n-3 fatty acids and measurements of growth and maturation. 20:4(n-6) and the sum of 20:3(n-6) + 20:4(n-6) correlated most strongly with weight and head circumference, while 22:6(n-3) showed strongest correlation with length of gestation. These findings are of relevance to understanding the role of nutrition in fetal growth and in establishing the group of infants most at risk of postnatal deficiency of essential fatty acids.

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 β-chemokine macrophage inflammatory protein (MIP)-1α, although not of regulated upon activation, normal T cell expressed and secreted (RANTES), of the cytokines tumor necrosis factor (TNF)-α and IL-1β, and of elastase/α-1 antitrypsin. Significantly higher concentrations of MIP-1α 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-1α, tumor necrosis factor-α, IL-1β, and elastase/α-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-1α. The early introduction of specific therapy is thus likely to be beneficial.

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.

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±0.07SOD units (mg protein)−) 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.

Mucosal Tumor Necrosis Factor-α 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-α-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.

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 α-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 α-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

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

Abstract 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.

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 (ΔPes:ΔPao) 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. Pediatr Pulmonol. 1996; 22:117–124.

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.

Improvement in neonatal intensive care unit care: a cluster randomised controlled trial of active dissemination of information.

Background Research findings are not rapidly or fully implemented into policies and practice in care. Objectives To assess whether an ‘active’ strategy was more likely to lead to changes in policy and practice in preterm baby care than traditional information dissemination. Design Cluster randomised trial. Participants 180 neonatal units (87 active, 93 control) in England; clinicians from active arm units; babies born <27 weeks gestation. Control arm Dissemination of research report; slides; information about newborn care position statement. Active arm As above plus offer to become ‘regional ‘champion’ (attend two workshops, support clinicians to implement research evidence regionally), or attend one workshop, promote implementation of research evidence locally. Main outcome measures timing of surfactant administration; admission temperature; staffing of resuscitation team present at birth. Results 48/87 Lead clinicians in the active arm attended one or both workshops. There was no evidence of difference in post-intervention policies between trial arms. Practice outcomes based on babies in the active (169) and control arms (186), in 45 and 49 neonatal units respectively, showed active arm babies were more likely to have been given surfactant on labour ward (RR=1.30; 95% CI 0.99 to1.70); p=0.06); to have a higher temperature on admission to neonatal intensive care unit (mean difference=0.29oC; 95% CI 0.22 to 0.55; p=0.03); and to have had the babys trunk delivered into a plastic bag (RR=1.27; 95% CI 1.01 to 1.60; p=0.04) than the control group. The effect on having an ‘ideal’ resuscitation team at birth was in the same direction of benefit for the active arm (RR=1.18; 95% CI 0.97 to 1.43; p=0.09). The costs of the intervention were modest. Conclusions This is the first trial to evaluate methods for transferring information from neonatal research into local policies and practice in England. An active approach to research dissemination is both feasible and cost-effective. Trial registration Current controlled trials ISRCTN89683698