Alan Gibson

Growth and the Premature Baby

There is considerable evidence to show that babies born prematurely have poor postnatal growth, and the more premature the baby, the greater the impairment is likely to be and the longer it will persist. Nutrition has been shown to play an important part in this, but adequate nutrition is difficult, if not impossible, to achieve in these infants. In the most immature infants, growth retardation may continue for many months and catch-up may be delayed and incomplete. Evidence from long-term studies suggests that preterm infants will be shorter and lighter than term controls and that reduced stature and head size may be linked with lower intelligence. Although there is evidence linking better growth to better neurodevelopmental outcome, with reports suggesting that this can be achieved with dietary manipulation, there are also data that suggest that there could be a link between increased postnatal growth and increased morbidity and mortality in later childhood and adult life. Here, we provide an overview of current understanding of growth impairment in infants born prematurely and the effects in later life.

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.

Measurement and the Newborn Infant

Measurement of newborn babies is widely regarded as being too inaccurate to justify its regular practice. It is common for infants to be weighed at birth and for no other measurements to be made. Although such assumptions are superficially correct, it is possible to train people to perform accurate measurements and for improved performance to be sustained. Accurate sequential measurements are possible and provide more information than single measurements. Detailed measurements show that postnatal growth may change rapidly and dramatically, particularly in preterm infants. Postnatal growth impairment is common in such infants and may be sustained. Limited evidence suggests that there may be a significant reduction in final stature. Preliminary data also suggest that many preterm infants may also show evidence of alterations in biochemical and physiological variables consistent with early programming and the potential for altered disease susceptibility in adult life.

The contributions of plasma IGF-I, IGFBP-3 and leptin to growth in extremely premature infants during the first two years.

We determined the contributions of IGF-I, IGFBP-3 and leptin to growth in -extremely premature infants over the first two years. Weight (Wt), crown-to heel length (CHL), plasma IGF-I, IGFBP-3 and leptin were measured in infants (gestation 24–33 wk) at birth (n = 54), expected date of delivery (EDD) and 6, 12 and 24 mo post-EDD (n = 29). Area under the curve (AUC) for hormone levels was calculated over 4 periods: birth–EDD, EDD–200 d, EDD–350 d and EDD–700 d. IGFBP-3, but not IGF-I or leptin, on day 1 correlated with birth Wt SD scores (SDS) (r = 0.46, p = 0.002) and CHL SDS (r = 0.41, p = 0.01). Wt SDS at EDD correlated with AUC IGF-I, IGFBP-3 and leptin (birth–EDD), but leptin was the best predictor in multiple regression(r = 0.65, p < 0.0001). Wt at EDD + 700 d correlated with AUC leptin (EDD–700 d) (r = 0.62, p = 0.002). CHL SDS at EDD correlated with AUC IGFBP-3 and leptin (birth–EDD), but IGFBP-3 was the best predictor (r = 0.55, p < 0.0001). CHL at EDD + 700 d correlated with AUC IGF-I and IGFBP-3 (EDD–700 d), but IGFBP-3 was the best predictor (r = 0.47, p = 0.01). Wt and CHL at birth were associated with IGFBP-3 levels in these infants. Wt at EDD and EDD + 700 d was predicted by concurrent leptin output while linear growth at EDD and EDD + 700 d was predicted by IGFBP-3 output.

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.

CASE REPORTS: Unusual Case of Tracheal Agenesis

ABSTRACT 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.

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.

EARLY GROWTH AND SUBSEQUENT STATURE

To evaluate the effect of disturbance in early growth on subsequent stature we have made detailed measurements of weight, length and lower leg length in the early postnatal period and at 8 months corrected age in 33 babies who received intensive care.Mean leg length SD score decreased by 1.22 (p = 0.0001, paired t test) between birth and 36 weeks postconceptual age. Both length and weight at 8 months most closely correlated with length or mean leg length at 36 weeks (r = 0.762 & 0.703, p = 0.0001 for length; r = 0.556 & 0.511, p = 0.0017 & 0.003 for weight). Correlation with any measure of early weight was less strong.Using stepwise linear regression leg length velocity in the first eight weeks of life was most strongly associated with length at eight months (adjusted r squared = 0.3, F = 10.4, p = <0.001). Duration of ventilation was found to have the strongest correlation with early leg length velocity (adjusted r squared = 0.299, P = 20.9, p = <0.005). Calorie intake was found to be significantly lower during ventilation (85.5 v 142 kcal/kg/day) but inclusion of it in the stepwise regression model did not alter the importance of duration of ventilation.Length and weight at 8 months are largely determined by early postnatal length changes. There is a strong association with the duration of ventilation which requires further evaluation.

GROWTH IMPAIRMENT IN BRONCHOPULMONARY DYSPLASIA (BPD)

Impairment of growth in BPD is well described but the amount by which growth is disturbed and the stage at which impairment occurs is unclear. We have compared lower leg growth, measured by knemometry, and weight gain, in 16 babies who needed home oxygen, 22 babies who needed oxygen for more than 28 days but were discharged in air and 24 babies who needed supplementary oxygen for less than 28 daysAll groups exhibited an initial weight loss followed by steady weight gain, with no apparent difference in weight gain for the two oxygen dependent groups. Changes in leg length are shown in the figure. Comparison of leg length velocities demonstrated differences in the three groups between 0-13 days (p=0,12); 14-27 days (p=0.0001) and 28-41 davs (p=0.006).A significant impairment of growth in the early postnatal period is seen in those babies who will develop moderate and severe BPD. This may occur despite apparently similar weight gains

STEROID INDUCED SUPPRESSION OF BONE GROWTH IN THE PREMATURE NEONATE - SILVERMAN REVISITED

In 1951 Silverman reported significant growth disturbance in premature infants who received ACTH for the treatment of retinopathy. Despite the dramatic response that was demonstrated the effects of steroids on growth in this age group remain poorly understood. We have used the neonatal knemometer to assess bone growth in 26 babies who received a total of 32 nine day courses of dexamethasone for the treatment of chronic lung disease. Growth of the lower leg and weight gain were assessed for 10 days before, during and 30 days after the course. There was a decrease in leg length velocity in all subjects during steroid administration and actual limb shrinkage occurred in 15. There was then catch-up growth to the estimated pre-steroid length by 30 days. Oxygen requirements fell and calorific intake rose during steroid treatment Dexamethasone has a profound effect on cartilage and bone growth even in the preterm neonate. The long term consequences of this effect are no clearer today than they were for Silverman more than 40 years ago.