Kerstin Albertsson Wikland

Final height in short children born small for gestational age treated with growth hormone.

The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below −2) prepubertal children born SGA (below −2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 μg/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for >2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun <2 y before puberty. Better catch-up growth was observed in the younger (r = −0.56, p < 0.0001), shorter (r = −0.49, p < 0.0001), and lighter (r = −0.46, p < 0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height.

Validated Multivariate Models Predicting the Growth Response to GH Treatment in Individual Short Children with a Broad Range in GH Secretion Capacities

The aim of the study was to develop and validate models that could predict the growth responses to GH therapy of individual children. Models for prediction of the initial one and 2-y growth response were constructed from a cohort of 269 prepubertal children (Model group) with isolated GH deficiency or idiopathic short stature, using a nonlinear multivariate data fitting technique. Five sets of clinical information were used. The “Basic model” was created using auxological data from the year before the start of GH treatment and parental heights. In addition to Basic model data, the other four models included growth data from the first 2 y of life, or IGF-I, or GH secretion estimated during a provocation test (AITT) or a spontaneous GH secretion profile.The performance of the models was validated by calculating the differences between predicted and observed growth responses in 149 new GH treated children (Validation group) who fulfilled the inclusion criteria used in the original cohort. The SD of these differences (SDres) in the validation group was compared with the SDres for the model group. For the 1st y, the SDres for the Basic model was 0.28 SDscores. The lowest SDres (0.19 SDscores), giving the most narrow prediction interval, was achieved adding the 24h GH profile and data on growth from the first 2 y of life to the Basic model. The models presented permit estimation of GH responsiveness in children over a broad range in GH secretion, and with an accuracy of the models substantially better than when using maximal GH response during an provocation test. The predicted individual growth response, calculated using a computer program, can serve as a guide for evidence-based decisions when selecting children to GH treatment.

Growth in Very Preterm Children: A Longitudinal Study

The knowledge about the long-term growth of very preterm children in relation to gestational age at birth is incomplete. Therefore, a retrospective study of longitudinal growth from birth to 7 y of age in 52 of 56 surviving children who were born at a gestational age of <29 wk between 1988 and 1991 to mothers resident in the city of Göteborg, Sweden, was performed. A majority of the children had an initial decrease in weight during the first months of life, followed by an increase, with a maximum weight gain occurring at 36–40 wk postmenstrual age. After a period of decreased weight and length velocity, a second increase in weight velocity was demonstrated from 6 mo to 2 y of corrected age. A corresponding increase in length velocity was found from 2 to 12 mo of corrected age. A later catch-up growth period was found at 4-5 y of age. At 7 y of age, all but two had reached the normal height range of the population. This long-term catch-up in height was established later in those who were born at an earlier gestational age. We conclude that all preterm infants had an initial period of poor growth, which rendered them growth retarded during the first years of life. It took approximately 4-7 y to overcome what the very preterm child lost in growth during the first months of life. However, as a group, they did reach normal height, weight, and weight for height before puberty.

The role of maternal factors, postnatal nutrition, weight gain, and gender in regulation of serum IGF-I among preterm infants

IGF-I is important for somatic growth and development of the human fetus and neonate. IGF-I also plays an important role in normal vascularization of human retina, as it has been suggested that insufficient IGF-I may be a factor in the development of retinopathy of prematurity. The principal regulator of the bioavailability of IGF-I in the circulation is IGF binding protein 3 (IGFBP-3). The aim of this study was to study factors associated with postnatal serum concentrations of IGF-I and of IGFBP-3 in preterm infants from birth to an age corresponding to 40 wk postmenstruation. We conducted a prospective, longitudinal study in which we measured serum IGF-I and IGFBP-3 concentrations in 76 preterm infants from birth (postmenstrual ages 23–32 wk) until discharge from hospital around 40 wk. Information regarding nutrition, weight gain, maternal factors, and treatment with corticosteroids were collected weekly. Variables found to be associated with postnatal change over time of serum IGF-I and IGFBP-3 were postmenstrual age (p < 0.001), weight gain (standard deviation score) (p < 0.001), and enteral intake of protein (p < 0.001). Male gender was associated with lower IGF-I levels (p < 0.001). The relationship between protein intake and IGF-I (and also between protein intake and IGFBP-3) was positive, as was the relationship between weight gain and IGF-I (and between weight gain and IGFBP-3). These results indicate that the degree of prematurity, low enteral protein intake, male gender, and slow weight gain are associated with a slower postnatal increase of IGF-I in preterm infants.

Growth hormone treatment and adverse events in Prader–Willi syndrome: data from KIGS (the Pfizer International Growth Database)

Objective  To evaluate the response to recombinant GH treatment and adverse events in children with Prader–Willi syndrome (PWS) from KIGS, the Pfizer International Growth Database.

Children with Septo-Optic Dysplasia – How to Improve and Sharpen the Diagnosis

The data in this article are based on investigations performed in 25 children with suspected septo-optic dysplasia (SOD). There are many signs and methods that help in the diagnosis of SOD. In particular, the ocular fundus, abnormalities of the hypothalamo-pituitary axis and other midline brain structures should be described. In order to achieve a more holistic and functional diagnosis, the degree of neurological, neuropsychiatric and psychological involvement should also be stated. It has been suggested that SOD is associated with autosomal recessive inheritance, and it can be speculated that it is the result of genetic and environmental influences early in gestation. An early diagnosis can favourably influence the outcome of the affected child.

Growth Prediction Models, Concept and Use

There is a principal and qualitative difference between using regression results on data from groups of children, and using validated prediction models for individual children. Using accurate models, it is now possible to predict the growth response to growth hormone (GH) treatment in a slowly growing child with GH deficiency (GHD) or in a child with idiopathic short stature (ISS). The growth response to the standard dose of GH can be regarded as a bioassay for GH (i.e. the tissue GH responsiveness) and the information on this growth response can be used for different purposes: to decide about treatment or not, for monitoring, and for adjusting the GH dose in order to reach a defined goal for height. This last concept is now used in an ongoing prospective randomized GH dose-finding trial.

Puberty in children born small for gestational age.

Small for gestational age (SGA) children are more prone to have precocious pubarche and exaggerated precocious adrenarche, an earlier onset of pubertal development and menarche, and faster progression of puberty than children born of appropriate for gestational age (AGA) size. The majority of studies investigating the onset of puberty in children born SGA and AGA established that, although puberty begins at an appropriate time (based on chronological age and actual height) in SGA children, onset is earlier relative to AGA children. Evaluating pubertal growth in SGA children, a more modest bone age delay from chronological age at the onset of puberty and more rapid bone maturation during puberty compared to AGA children were reported. Peak height velocity in adolescence is reached at an earlier pubertal stage and lasts for a shorter period in children born SGA than in those born AGA. These differences lead to an earlier fusion of the growth plates and a shorter adult height. The pathophysiological mechanism underlying the unique pubertal growth pattern of children born SGA remains unclear. However, it seems that this is not only related to birth weight, gestational age, adiposity or obesity, but that there may also be an influence of rapid weight gain in early childhood on pubertal onset: excess weight gain in childhood may be related to central adiposity, decreased insulin sensitivity, and increased IGF-I levels and might thus predispose to precocious pubarche.

Psychological Importance to the Child of Growth Hormone Replacement

Publisher Summary This chapter reviews the psychological importance of growth hormone (GH) treatment in the child. The measurement of cognitive and intellectual effects is put into the perspective of cognitive theory and is categorized in terms of intelligence quotient, school achievement, and specific cognitive skills, including attention, visual motor skills, and memory. There are three possible modes of action of GH namely, neurological, endocrinological, and psychological. This chapter also examines evidence for the psychological well-being of the GH-deficient child together with quality of life issues. Moreover, the effect of GH replacement therapy can only occur if the receptor sites are sensitive to the GH. When the patient does not respond to treatment in terms of growth, one can speculate whether the problem lies in the sensitivity of the organs to GH. Diminished responsiveness is known to be a reason for nongrowth following GH treatment. Furthermore, an examination of the methodological difficulties of examining the long-term psychological benefits of GH in children is discussed. Finally, the chapter looks at directions for future research in the area and the need for methodological standardization.

Improved final height with long-term growth hormone treatment in Noonan syndrome: Final height and GH treatment in Noonan syndrome

Aim: To assess whether children with Noonan syndrome on long‐term growth hormone (GH) therapy improve their final height to near mid‐parental height. Methods: Twenty‐five prepubertal children (13 girls) with Noonan syndrome (NS) were studied. A single clinician made the diagnosis based on clinical criteria. GH treatment started at an age ranging from 3.1 to 13.8 y and was continued for at least 2 y. Improvement or “gain” in final height (FH) was defined as either the difference between adult height SD scores (SDS) and pre‐treatment height SDS (the childhood component of the Swedish reference) or height SDS compared to the Noonan reference. Results: Ten children received a GH dose of 33 μg/kg/d (mean age at start 7.7±2.1 y, mean age at stop 17.6±1.7 y) and 15 received a dose of 66 μg/kg/d (mean age at start 8.6±3.3 y, mean age at stop 18.4±2.1 y). Eighteen out of 25 patients reached FH. A substantial improvement in FH of 1.7 SDS, equivalent to 10.4 cm compared to pre‐treatment height, was observed. No significant difference was seen between the two GH doses. Females gained a mean height of 9.8 cm and males 1–13 cm (FH 174.5±7.8 cm vs mean adult height of 162.5±5.4 cm for males with NS) at final height. Moreover, 60% reached a mid‐parental height of±1 SD.