Birth weight discordance of twin pairs and their subsequent growth patterns.

BACKGROUND: Few studies have compared the growth of a twin with its co-twin and particularly in relation to birth weight discordance. AIM: The study investigated how the degree of birth weight discordance affected subsequent growth. METHODS: Birth weight discordance of 762 twin pairs was determined. Subsequent weight, height and occipital-frontal head circumference (OFC) measurements were obtained between the ages of 2-9 years. Corresponding standard deviations scores (SDS) were analysed according to birth weight discordance, sex and zygosity. Weight status was taken into account by assigning twins into sub-groups according to whether they were the heavier twin at birth and remained heavier, became the lighter of the twin pair or had the same weight, for subsequent measurements. RESULTS AND CONCLUSIONS: The degree of birth weight discordance had little effect on subsequent growth except in monozygotic (MZ) twins with >20% discordance. Severe low birth weight ( < 1.95 kg) is more significant in suppressing subsequent growth than the degree of discordance per se. A surprisingly high proportion of twins reversed their weight status when reviewed at an older age.

A comparison of the merits of using birth weight, or appropriateness of birth weight to gestational age, in the assessment of subsequent growth in twin children.

BACKGROUND: Size at birth has an important relationship to subsequent growth. Many reports subgroup subjects according to birth weight or birth weight in relation to the duration of gestation, and it is not clear whether one of these methods is more relevant to subsequent growth or if in fact they are comparable. AIM: The present study compared the outcome of twins in terms of pre-pubertal weight and height when sub-grouped according to birth weight (BW), or the appropriateness of birth weight for the duration of gestation (BW-SDS). SUBJECTS AND METHODS: The birth weights of 1533 twins were graded into four subgroups according to BW or BW-SDS. The relationship of birth weight to subsequent weight and height standard deviation scores, obtained between the ages of 2 and 9 years, were compared on the basis of these two methods. RESULTS: There was a marked difference in identity of the twins who fell into each of the four subgroups by the two methods. Despite this, no difference was found in the subsequent weight and height of the twins. CONCLUSIONS: Analysis of data relating BW-SDS to subsequent growth shows no significant difference to those groups using BW alone.

The growth of twins between the ages of 2 and 9 years.

BACKGROUND: Twin growth studies are mostly based on pooled data without consideration of zygosity, parental heights or birth weight. AIM: The study investigated the effects of gender, zygosity, parental height and birth weight on subsequent twin growth. METHODS: Height and weight measurements of 1533 twins (n = 1077 for occipito-frontal head circumference (OFC)), age range 2-9 years, were converted to standard deviation scores derived from singleton standards. Their growth was evaluated in relation to gender, zygosity, parental heights and birth weight. RESULTS: Mean stature of twins fell only slightly below the reference values of singletons, but they were underweight to a greater extent (boys more than girls). Twins' OFC were low (girls more so than boys). Monozygotic (MZ) twin boys were lighter and shorter than dizygotic twins and MZ twin girls. Deficient growth was most evident in those babies light at birth. Parental heights only partly accounted for the difference in height of twins. CONCLUSIONS: Birth weight and parental height are important in relation to subsequent growth. Boy twins are at a disadvantage compared with girls in terms of their growth in height and weight, particularly in the low birth weight and MZ groups.

A comparison of the early growth of twins and singletons.

BACKGROUND: It is well known that the birth weight of twins is less than that of singletons, but there is less information about how birth lengths compare and how twins grow in the postnatal and early childhood period. The implications of the shorter duration of gestation of twins in comparing their postnatal progress with that of singletons are seldom taken into consideration. AIMS: The study aimed to compare the growth of healthy twins and singletons over the first 4 years of life. SUBJECTS AND METHODS: Birth length data on English twins born between 1990 and 1997 were used to produce reference values for gestational ages from 33 to 40 weeks. Follow-up data of weights and lengths up to the equivalent of 40 weeks' gestation are reported on some of these infants who were born pre-term. On the basis of questionnaires, the growth of twins in terms of weight, length/height and head circumference has been followed up to 4 years of age. RESULTS: Mean birth length of twins showed a fall-off when compared with singletons at comparable gestational ages, which was more marked in boys than girls and evident earlier. Extrauterine growth of twins born pre-term was comparable to that of adequately nourished twins remaining in utero until term. Much of the smallness of twins at birth was because of their shorter gestation. Subsequently singletons gained weight faster. Lengths/heights showed no deficit compared with singletons. Head circumferences of twins were, however, smaller than singletons throughout. CONCLUSIONS: The early growth of normal twins differs markedly from that of singletons. It is important to recognize that singleton reference values do not correctly reflect the growth of twins.

Priming with testosterone enhances stimulated growth hormone secretion in boys with delayed puberty.

BACKGROUND AND OBJECTIVE: Tests for growth hormone (GH) deficiency are not always helpful in the differential diagnosis of physiological delay of growth and puberty and GH deficiency. PATIENTS AND METHODS: To enhance diagnostic specificity, we used a single dose testosterone priming before repeating the arginine stimulation test in 26 boys with short stature and only early signs of puberty who failed to show an adequate response of serum GH in the first test. RESULTS: 77% (20/26 patients) increased their serum GH peak to more than 10 ng/ml, whereas six patients were still below this concentration. CONCLUSION: We propose that testosterone priming is a useful tool to distinguish between physiological delay of growth and puberty and GH deficiency and should be included in the diagnostic procedure.

Growth reference charts for use in the United Kingdom.

Since the introduction of new growth charts in the mid 1990s, there has been confusion about which charts should be used, with many districts using more than one version. Because of this uncertainty, an expert working party, the Growth Reference Review Group, was convened by the Royal College of Paediatrics and Child Health to provide guidance on the validity and comparability of the different charts currently in use. This paper describes the technical background to the construction and evaluation of growth charts and outlines the group's findings on the validity of each growth reference in relation to contemporary British children. The group concluded that for most clinical purposes the UK90 reference is superior and for many measures is the only usable reference that can be recommended, while the original Tanner-Whitehouse and the Gairdner-Pearson charts are no longer reliable for use at any age. After the age of 2 the revised Buckler-Tanner references are still suitable for assessing height. There are presently no reliable head circumference reference charts for use beyond infancy. The group propose that apart from refinements of chart design and layout, the new UK90 reference should now be "frozen", with any future revisions only undertaken after careful planning and widespread consultation.

A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis.

BACKGROUND: Turner syndrome accounts for 15-20% of childhood usage of growth hormone (GH) in the UK but final height benefit remains uncertain. The most effective strategy for oestrogen replacement is also unclear. METHODS: Fifty eight girls who, at start of treatment, were of mean age 9.1 years and projected final height 142.2 cm were randomised to receive in year 1, either low dose ethinyloestradiol 50-75 ng/kg/day, GH 28 IU/m(2) surface area/week as a daily injection, or a combination of ethinyloestradiol and GH. After the first year, the ethinyloestradiol treated girls received combination treatment. After two years, girls aged over 12 years were given escalating ethinyloestradiol to promote pubertal development. RESULTS: Near final height was available for 49 girls at age 16.5 years, 146.8 cm, representing a gain of 4.6 cm, range -7.9 to +11.7 cm. Twelve of the 49 girls gaining 7.5 cm or more were less than 13 years at the start and had received GH for at least four years. Height gain was correlated with greater initial height deficit. Fifteen girls (31%) reached 150 cm or more compared to a predicted 10%. Early supplementation with ethinyloestradiol provided no final height advantage. CONCLUSIONS: Final height gain was modest at 4.6 cm. Younger, shorter girls gained greatest height advantage from GH. Low dosage ethinyloestradiol before planned induction of puberty was not beneficial.

A limited repertoire of mutations of the luteinizing hormone (LH) receptor gene in familial and sporadic patients with male LH-independent precocious puberty.

Herein, we report mutation analysis of the LH receptor gene in 17 males with LH-independent precocious puberty, of which 8 were familial and 9 had a negative family history. A total of 7 different mutations (all previously reported) were detected in 12 patients. Among 10 European familial male-limited precocious puberty (FMPP) patients who had a LH receptor gene mutation, none had the Asp578Gly mutation, which is responsible for the vast majority of cases in the U.S. The restricted number of activating mutations of the LH receptor observed in this and other studies of FMPP strongly suggests that an activating phenotype is associated with very specific sites in the receptor protein. Clinical follow-up of the 5 patients who did not have LH receptor mutations shows that such cases most likely do not have true FMPP. LH receptor mutation analysis provides a sensitive tool for distinguishing true FMPP from other causes of early-onset LH-independent puberty in males.

Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators.

OBJECTIVE: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). DESIGN: Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. RESULTS: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. CONCLUSIONS: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.

Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone.

UNLABELLED: In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth. OBJECTIVE: We have aimed to determine the efficacy and safety of growth hormone-releasing hormone (GHRH) (1-29)-NH2 given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation-induced GH deficiency. DESIGN: A multicentre study comparing growth before and after 1 year of treatment with GHRH (1-29)-NH2, 15 micrograms/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On completion of the study year all children were treated with GH (0.5 U/kg/week) and growth parameters were documented over the next year. PATIENTS: Nine children (six boys) with radiation-induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic-pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy. MEASUREMENTS: Anthropometry and pubertal staging were carried out at 3-monthly intervals and bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, a change in leg-length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin-fold thickness and bone age during the GHRH study year were documented. Adverse events and 3-monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded. RESULTS: There was a significant increase in height velocity from 3.3 (SD 1.1) cm/year before treatment, to 6.0 (SDS 1.5) cm/year after 1 year of GHRH treatment (P = 0.004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 1.1 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 7.5 (SD 1.5)cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy. CONCLUSION: In cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.

Biochemical tests in the diagnosis of childhood growth hormone deficiency.

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. We have examined, therefore, the performance of other tests of the GH axis [urinary GH excretion, serum insulin-like growth factor I(IGF-I), and IGF-binding protein-3 (IGFBP-3) levels] compared with GH stimulation tests in identifying children defined clinically as GH deficient. Group I comprised 60 children (mean age, 10.3 +/- 4.8 yr) whose diagnosis of GHD was based on a medical history indicative of pituitary dysfunction (n = 43) or on the typical phenotypic features and appropriate auxological characteristics of isolated GHD (n = 17). Group II comprised 110 short children (mean age, 9.8 +/- 4 yr) in whom GHD was not suspected, but needed exclusion. The best sensitivity for a single GH test was 85% at a peak GH cut-off level of 10 ng/mL, whereas the best specificity was 92% at 5 ng/mL. The sensitivities of IGF-I, IGFBP-3, and urinary GH, using a cut-off of -2 SD score were poor at 34%, 22%, and 25%, respectively, with specificities of 72%, 92%, and 76% respectively. Only 2 of 21 pubertal children in group I and none of the 27 subjects with radiation-induced GHD had an IGFBP-3 SD score less than -1.5. We devised a scoring system based on the positive predictive value of each test, incorporating data from the GH test and the IGF-I and IGFBP-3 levels. A specificity of 94% could be achieved with a score of 10 or more (maximum 17) (sensitivity 34%). The latter could not be improved above 81% with a score of 5 points or more (specificity, 69%). A high score was, therefore, highly indicative of GHD, but was achieved by few patients. A normal IGFBP-3 level, however, did not exclude GHD, particularly in patients with radiation-induced GHD and those in puberty. A GH test with a peak level more than 10 ng/mL was the most useful single investigation to exclude a diagnosis of GHD.

Spontaneous growth in idiopathic short stature. European Study Group.

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.

Birth weight and head circumference standards for English twins.

This study was undertaken to provide reliable up to date information on birth weights and occipitofrontal head circumference measurements in relation to gestational age for English newborn twins. Records from 36 maternity units in England, mainly from 1988-92, have provided data on birth weights for over 19,000 newborn twins with gestational ages ranging from 23 to 41 weeks, and on head circumference measurements for over 5300 twins ranging from 28 weeks to 40 weeks' gestation. Centile charts have been produced for boy and girl twins showing the distribution of these values against gestational age. The findings confirm the greater weights of boys compared with girls throughout, increasing from a mean of about 50 g at early stages to 100 g later, in a similar way to that reported for singletons. Twins were lighter than comparable singletons by about 100 g at 24 weeks, increasing progressively to 4-500 g at 38 weeks' gestation. In contrast, differences in occipitofrontal head circumferences between singletons and twins were only evident with gestations longer than 35 weeks--and from 37 weeks' gestation onwards the mean head circumference of singletons exceeded that of twins by about 5 mm. It is recommended that in evaluating the significance of the birth weight of a twin in relation to gestation, twin standards such as the ones presented here should be used rather than those relating to singletons.

Growth hormone treatment in non-growth hormone-deficient children: effects of stopping treatment.

Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved GH levels greater than 15 mU/l following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase, demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period, all children received GH according to the same dose regimen; they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating 'catch-down' growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.

Adrenal response in very low birthweight babies after dexamethasone treatment for bronchopulmonary dysplasia.

The tetracosactrin stimulation test was used to assess the adrenal responsiveness of 22 very low birthweight babies who had received a three week course of dexamethasone for the treatment of bronchopulmonary dysplasia. Five babies were studied in detail with blood samples taken for cortisol concentrations at 30 minute intervals for four hours. The tests were performed before, during, and after treatment with dexamethasone. A distinctive pattern of cortisol response to tetracosactrin was found among these babies, which was quite unlike that found in older children and adults. Using our pretreatment results as control data we conclude that there is undoubtedly evidence of modest suppression of the adrenal axis during dexamethasone treatment, although there is considerable recovery one month after stopping steroids. Basal cortisol concentrations, however, remained low in some cases, which may indicate the need for temporary corticosteroid replacement during severe illness.

Which bone age in chronic renal insufficiency and end-stage renal disease?

One hundred radiographs of the left hand and wrist from 40 children with chronic renal insufficiency or end-stage renal disease were examined to determine which method of bone age estimation provided the most useful information in these children. The Tanner and Whitehouse method showed better repeatability than the Greulich and Pyle atlas or the Buckler handbook when a sample of the radiographs were assessed twice by the same observer. The Tanner and Whitehouse 20 (TW20) bone age showed less inter-observer bias than the radius, ulna and short bone age or the carpal bone age when three observers independently assessed the same sample of radiographs. TW20 was the most useful method of bone age assessment in this study of British children. An unexpected finding was that the carpal bones were significantly more retarded than the radius, ulna and short bones. Separate assessment of the carpal bone age may provide extra information of clinical relevance.

Longitudinal study of height and weight at adolescence.

A longitudinal study through puberty of the height and weight of 96 boys and 102 girls in schools in and around the city of Leeds was conducted. Data for height and weight and height and weight velocities are presented, which are based on chronological age and on age relative to the age of peak height velocity. Comparison was made with the Tanner standards: male puberty developed a little later but growth continued longer, so that the adult men were taller and heavier. Girls showed a similar timing of puberty to the Tanner standards but were lighter at all ages and ultimately slightly taller as growth was not completed until later. It is important to know the pubertal state when interpreting growth changes in children.