Growth patterns in the growth-retarded premature infant.

Approximately 10% of all infants are born prematurely. A large proportion of these infants show evidence of postnatal growth impairment irrespective of whether birth weight was appropriate or small for gestational age. The timing and magnitude of catch-up growth is very variable, with the most immature infants showing markedly delayed catch up which is often incomplete. Long-term studies suggest that final stature may be affected significantly. Growth impairment in itself is of concern and there are suggestions that this group of infants should be eligible for growth hormone treatment. However, in addition, there is increasing evidence to suggest that there should be additional concerns in this group of infants, as abnormal early growth may influence disease susceptibility in adult life. This review assesses the patterns of postnatal growth and the possible later implications of early aberrant growth patterns in later life.

Adult height of preterm infants: a longitudinal cohort study.

BACKGROUND: Many infants born prematurely experience growth failure following delivery, with subsequent catch-up growth. Traditionally catch-up was thought to be complete in the first few years of life. Most studies have focused on groups of infants defined by birth weight, for example <1500 g, resulting in disproportionate numbers of small for gestational age infants. This study aimed to determine whether appropriate weight for gestation (AGA) preterm born children reach their expected adult height when compared with term controls. METHODOLOGY: This UK based prospective longitudinal cohort study recruited 204 preterm children born at a tertiary neonatal unit during 1994 and 50 matched controls. Growth parameters have been assessed annually until the completion of growth. RESULTS: There was no significant difference in the final height SD score (SDS) of children born at term (n=30) and those born prematurely and AGA (n=70) (0.45 term vs 0.22 preterm). Catch-up growth however, continued throughout the whole of childhood. When the difference between final height SDS and mid-parental height SDS were compared, there were again no significant differences (0.13 term vs 0.03 preterm). CONCLUSIONS: Those born prematurely with an AGA achieve a comparable adult height to children born at term, however, catch-up growth continues for much longer than traditionally thought.

Pinching, electrocution, ravens' beaks, and positive pressure ventilation: a brief history of neonatal resuscitation.

Since ancient times many different methods have been used to revive newborns. Although subject to the vagaries of fashion for 2000 years, artificial respiration has been accepted as the mainstay of neonatal resuscitation for about the last 40. Formal teaching programmes have evolved over the last 20 years. The last 10 years have seen international collaboration, which has resulted in careful evaluation of the available evidence and publication of recommendations for clinical practice. There is, however, little evidence to support current recommendations, which are largely based on expert opinion. The challenge for neonatologists today is to gather robust evidence to support or refute these recommendations, thereby refining this common and important intervention.

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

Vitamin C at concentrations observed in premature babies inhibits the ferroxidase activity of caeruloplasmin.

High concentrations of total vitamin C have been measured in the plasma of premature infants. At these concentrations ascorbic acid inhibited the ferroxidase activity of caeruloplasmin measured directly in vitro. The degree of inhibition was dependent on the ratio of ascorbic acid: caeruloplasmin. Values for the ratio of vitamin C: caeruloplasmin measured in premature babies would be predicted to inhibit ferroxidase activity by up to at least 80%. Ferroxidase activity measured in the plasma of premature babies increased from birth but was significantly lower than in plasma collected from adults (< 0.001). Plasma ferroxidase activity was correlated with plasma caeruloplasmin concentration and, in premature babies only, showed a negative correlation with the ratio of vitamin C to caeruloplasmin. High levels of vitamin C in premature babies may compromise antioxidant mechanisms and exacerbate oxidant damage.

High plasma vitamin C concentrations at birth associated with low antioxidant status and poor outcome in premature infants.

Concentrations of circulating antioxidants may be important in the aetiology of disease in premature infants. Blood samples were taken from 49 premature infants within two hours of birth. Plasma ascorbic acid, caeruloplasmin, and the ability of plasma to prevent lipid peroxidation in vitro were measured. Plasma ascorbic acid concentrations at birth ranged from 26.3 to 185.4 mumol/l. Plasma antioxidant activity at birth (microliter plasma required to inhibit lipid peroxidation) showed a strong negative correlation with plasma ascorbic acid and the plasma ascorbic acid to caeruloplasmin ratio. After correcting for gestational age and birth weight, plasma antioxidant activity at birth remained a significant predictor of mortality. Such plasma antioxidant activity is partly determined by the ferroxidase activity of caeruloplasmin. This may be modulated by high concentrations of ascorbic acid which may inhibit the antioxidant activity of plasma and thereby influence outcome.

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.

Antioxidant activity, packed cell transfusions, and outcome in premature infants.

AIM: To evaluate the relative importance of biochemical markers of antioxidant status, gestational age, and parameters of neonatal care in the clinical outcome of premature infants. METHOD: A prospective, observational, longitudinal study of the association between these factors was conducted. Blood was collected from an in situ arterial line within two hours of birth and at intervals thereafter, when blood was drawn for routine clinical purposes. Outcome was assessed as death, or survival with or without bronchopulmonary dysplasia (BPD). One hundred and forty four babies of 22 to 39 weeks of gestation, who required intensive care at the Jessop Hospital for Women, between January 1993 and April 1994, were recruited. RESULTS: Low gestational age at birth was the most important predictor of mortality and the development of BPD. Having corrected for gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Plasma vitamin C at birth was significantly higher in the babies who died compared with those with a good outcome, but this effect was not sustained after correcting for gestational age. Repeated measures of Analysis of Variance revealed a postnatal increase in antioxidant activity, caeruloplasmin, retinol, cholesterol corrected alpha tocopherol, and red blood cell superoxide dismutase (SOD) activity. Vitamin C, on the other hand, declined in all groups after birth. Logistic regression analysis revealed that the greater the number of packed cell transfusions received during intensive care, and the higher the concentration of vitamin C on the second day of life, the greater the risk of developing BPD. CONCLUSIONS: After correcting for the effect of gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Frequent blood cell transfusions over the first week of life are associated with an increased risk of developing BPD. This association may be causal.

Parenting the premature infant: balancing vulnerability and quality of life.

BACKGROUND: Relationships between child quality of life (QOL), maternal well-being and parenting were explored in a questionnaire study. METHOD: Mothers of 126 full-term (FT) and 91 pre-term (PT) infants during the child's second year of life completed measures of their own and the child's quality of life and behavioural difficulties. We developed a measure of parenting style derived from Regulatory Focus Theory (RFT), to distinguish greater reported use of promotion as opposed to prevention strategies (emphasising gains rather than losses, and encouraging pursuit of goals rather than prevention of harm). RESULTS: The two groups of mothers showed no differences on the parenting measure, but those in the PT compared with the FT group described their infant as having lower QOL and more behavioural and mood problems, and rated their own well-being as less satisfactory. Greater use of promotion was associated with reports of fewer difficulties (better QOL) for the child and better mothers' well-being. Differences in mothers' well-being as a function of group (FT vs. PT) and promotion were strongly mediated by mothers' perceptions of their child's difficulties. At the same time, associations with child difficulties were partly mediated by mothers' well-being, suggesting that maternal distress may have partly contributed to higher perceptions of such difficulties. Among PT infants, the degree of prematurity predicted child difficulties, but was not consistently related to mothers' well-being. DISCUSSION: Mothers of PT infants report more physical health and behavioural difficulties than mothers of FT infants, but specific parenting styles can contribute to child difficulties and QOL in both infants and their mothers. CONCLUSION: We conclude that RFT has potential for understanding the conflicts experienced by parents caring for vulnerable children.

Surfactant and the neonatal lung.

Deficiency of pulmonary surfactant is responsible for a substantial proportion of the mortality and morbidity in infants born prematurely. Surfactant replacement therapy has been extensively investigated and has become a central part of neonatal intensive care in the UK over the last 3 years. Evidence for the efficacy of this treatment is provided as is a discussion of the different surfactant preparations available and different protocols for administration.

A study of the routes by which protein passes from the pericardial cavity to the blood in rabbits.

The routes by which radioiodinated serum albumin placed in the pericardial cavity gains access to the circulation have been investigated in rabbits. 1. Eighty per cent of pericardial cavity protein passes through the parietal pericardium and into the circulation through the thoracic duct. 2. A small amount of protein is drained through the right lymph duct; this is probably derived from protein passing from the pericardial cavity into the pleural cavity. 3. There is no apparent movement of protein directly into blood vessels of the parietal pericardium. For theoretical reasons movement of protein across the visceral pericardium and into the blood vessels of the myocardium is also unlikely. 4. A small amount of protein enters the circulation when both major lymphatics are ligated. It is proposed that lymphatic uptake may continue and secondary lymphovenous junctions will open as a result of raised intralymphatic pressure.

Early changes in lung function and response to surfactant replacement therapy.

Dynamic respiratory system compliance (Cdyn) was measured in 44 preterm babies before, immediately after, and for 96 h following administration of artificial surfactant (Exosurf). There was no significant change in Cdyn for the whole group over the entire study period. Subdivision into three groups on the basis of Cdyn prior to surfactant revealed a significant and sustained deterioration in lung function in those babies with the highest starting compliance and a significant and sustained improvement in those with the lowest compliance. Inspired oxygen and alveolar/arterial oxygen gradient also exhibited significant differences with least improvement in the babies with the best initial lung function and most improvement in the babies with worst initial lung function and most improvement in the babies with worst initial lung function. Despite clear initial differences in clinical status, neither long-term oxygen requirements nor the incidence of chronic lung disease differed significantly between the three groups. We conclude that the response of an individual baby to the administration of surfactant is, in part, determined by the lung function before surfactant is administered. Babies with higher initial lung compliance are more likely to deteriorate after administration and caution should be used before selection of such babies for surfactant treatment.

A study of the composition of pericardial fluid, with special reference to the probable mechanism of fluid formation.

The composition of pericardial fluid and simultaneously withdrawn plasma have been measured in rabbits and greyhounds. 1. Sodium and chloride distributions were found to be not markedly different from the ratio predicted for a passive distribution. The small deviation found in greyhounds could be largely corrected by the in vitro dialysis of plasma against pericardial fluid. 2. Calcium and magnesium were distributed in a manner expected from a passive ultrafiltrate of plasma. 3. Pericardial fluid was found to contain between one quarter and one third of the protein of plasma. 4. Separation of the protein constituents demonstrated a far higher proportion of albumin to other proteins in the pericardial fluid. 5. The osmolality of plasma was slightly higher than that of pericardial fluid, as would be expected from a plasma ultrafiltrate. 6. The potassium concentration of pericardial fluid was higher than the plasma concentration in all animals studied. This difference could be abolished, and an expected distribution obtained in the samples from greyhounds, by the in vitro dialysis of plasma against pericardial fluid. This observation for potassium cannot be attributed to haemolysis of blood in pericardial fluid samples or to the use of any inappropriate references. It is suggested that the elevated potassium concentration of pericardial fluid may reflect the lability of the cardiac intracellular potassium during cardiac contraction. 7. The results obtained in this study do not support the concept of an active secretion of pericardial fluid as has been claimed by others. The distribution of ions would appear to be passive and to follow the values predicted by the Gibbs-Donnan relationship.

Knemometry and the assessment of growth in premature babies.

The characteristics of a knemometer designed for accurate lower leg measurement in babies were assessed. Repeated measurement of a 100 mm Perspex rod gave a mean length of 99.993 mm and a mean SD of 0.058. When used to measure leg length, technical error of the measurement technique was 0.31 with a mean leg length of 98.49 mm (coefficient of variation 0.31%). Leg lengths measured at birth in 324 babies from 23 to 42 weeks' gestation gave an estimated in utero leg length velocity of 0.43 mm/day (95% confidence interval 0.41 to 0.45). Assessment of interobserver variation showed poor agreement in absolute values of leg length, although similar estimates of leg length velocity could be obtained. The neonatal knemometer allows measurements to be made in situations where conventional growth measurements are not possible. It is believed that knemometry has an important role in accurate evaluation of factors that can influence short term bone growth.

Growth retardation after dexamethasone administration: assessment by knemometry.

Knemometry has been used to measure lower leg growth during 32 nine day courses of dexamethasone in 26 babies ranging from 24 to 32 weeks' gestation at birth. Mean leg length velocity was 0.37 mm/day in the 10 days before steroids. Administration of dexamethasone was associated with a decrease in velocity in all babies, and in 15 leg shortening was documented. Mean leg length velocity during steroid treatment was -0.003 mm/day. After the course of dexamethasone was completed there was an immediate increase in leg length velocity to a mean of 0.52 mm/day over the first 10 days then falling to a value similar to the growth velocity observed before treatment. Leg length had reached the value predicted by growth before steroids about 30 days after dexamethasone. The reduction in leg length velocity occurred despite a significant increase in energy intake and decrease in oxygen requirements.

The measurement of neonates.

Accurate measurements of both healthy and premature neonates are possible but rarely performed. Routine anthropometry is often not performed at all or with large measurement errors due to inadequate training of personnel or inappropriate equipment. Sick neonates are often considered unsuitable for anthropometry and growth is wrongly equated with weight gain. Gain in length may be disturbed by poor health and permanent extrauterine growth retardation and changes in body proportions induced in some survivors of neonatal intensive care. Drug treatments may have profound effects on length gain and the relationship of length to weight.

Does vitamin C intake influence the rate of tyrosine catabolism in premature babies?

A study was conducted to investigate the relationship between vitamin C intake and the rate of tyrosine catabolism in premature babies. A 13C tyrosine breath test was developed for the measurement of tyrosine catabolism. Premature babies were randomly allocated to receive a daily intake of vitamin C which ranged from 8 to 100 mg/kg body weight, for 5 days. Tyrosine catabolism was measured at the beginning and the end of this period. Daily intakes of vitamin C of 20 mg/kg or more elicited a greater increase in tyrosine catabolism over 5 days than 8 mg/kg/day. The magnitude of the difference, in terms of percentage of tyrosine metabolised, was, however, small and of doubtful biological significance. Vitamin C intakes above 20 mg/kg/day had no further measurable effect on the catabolism of tyrosine.

Neonatal respiratory distress in near-term infants--consider surfactant protein B deficiency.

Two infants presenting with respiratory distress in the first 24 h of life are described. Both patients underwent extensive investigation before the diagnosis of surfactant protein B-deficiency was reached. Both children died within 2 months of birth. Parental consanguinity was known to be a feature in the first case, who proved to have a previously unrecognized mutation of the surfactant protein B gene. In the second case, a history of parental consanguinity was not sought from the Caucasian family, but was later volunteered by the parents themselves. Case 2 proved to have the "common" surfactant protein B-deficient genotype. The key to diagnosis is having a high index of suspicion in any term or near-term newborn with severe respiratory distress; parental consanguinity must be excluded. Surfactant protein B-deficiency can be readily diagnosed from bronchoalveolar lavage specimens; a simple, inexpensive procedure which is well tolerated in newborns.

Unusual case of tracheal agenesis.

We describe the clinical presentation and pathological features of an unusual case of tracheal agenesis. The axial derivatives of the primitive foregut between the larynx and stomach were represented by a single structure featuring sequential segmentation into regions showing exclusively tracheal or esophageal differentiation in a pattern that is not easily classified by existing nosologic systems nor explained by the conventional hypothesis of dysontogenesis.