Introduction

The diagnostic criterion for small for gestational age (SGA)/intrauterine growth restriction (IUGR) is a birth weight and/or length below –2 standard deviations (SD) according to population standards for the given gestational age and sex [1]. It should be emphasised that patients born SGA are typically of short stature and usually do not exhibit spontaneous “catch-up growth”. In Poland, children with this diagnosis are eligible for recombinant human growth hormone (rhGH) therapy under a reimbursed program financed by the National Health Fund. This therapy is intended for short-statured children with SGA/IUGR who present with impaired growth velocity and in whom other causes of short stature have been excluded.

Aim of the study

The aim of this study was to retrospectively analyse the efficacy of rhGH therapy in patients born SGA in relation to age and sex, based on clinical data from 39 patients followed between 2016 and 2025, as well as a review of the current literature.

Material and methods

The analysis included patients diagnosed with SGA who received rhGH therapy. All patients included in the study were treated at a single clinical centre, and the data were collected in a consistent and standardised manner. The inclusion criteria comprised patients born SGA who were treated with rhGH within a drug reimbursement program. The exclusion criteria included incomplete data regarding treatment completion and patients who had not yet completed therapy at the time of analysis. The study group consisted of 39 patients: 25 boys and 14 girls. The mean age at initiation of therapy was 11 years and 10 months (range: 6 years 5 months – 15 years 8 months). Data were obtained from medical records and included perinatal information, age, height, and body weight at the start of treatment. Final parameters after therapy, as well as treatment outcomes expressed as increases in height and weight over time and changes in SD score (SDS), were also considered. Duration of therapy and reasons for its discontinuation were analysed. Statistical analysis was performed using descriptive methods. To assess the significance of differences between groups, Student’s t-test for independent samples was applied, with a significance level of p < 0.05. The literature review concerned studies on the effects of rhGH therapy in children with SGA and was conducted based on the medical databases PubMed and Medline.

Results

Analysing the study group, the mean duration of rhGH therapy was 3 years and 9 months (range: 1 year to 7 years 11 months). According to birth data, the mean gestational age at delivery was 37.6 weeks (range: 28–41 weeks, n = 38; birth data missing for one patient). The majority of patients (73%, n = 29) were born at term (> 37 weeks), while 27% (n = 9) were born preterm. The mean birth weight SDS was –2.67, and the mean birth length SDS was –0.41.

The efficacy of rhGH therapy was analysed according to sex. The mean annual height gain in girls was 5.87 cm (range: 3.88–6.83 cm), while in boys it was 7.22 cm (range: 2.85–12.5 cm). The mean annual weight gain in girls was 4.48 kg (range: 3.7–6.47 kg), and in boys 5.74 kg (range: 1.37–9.6 kg). Comparison of mean annual gains in height and weight between sexes showed that boys had a significantly greater mean annual height gain compared with girls (p = 0.013), indicating a stronger treatment effect on growth in boys. For weight gain, the difference between sexes was not statistically significant (p = 0.08).

In the analysed group of 39 patients diagnosed with SGA and treated with rhGH, the efficacy of therapy was also assessed according to the age at treatment initiation. Patients were divided into three subgroups: initiation before age 10 years (n = 13), between 10 and 13 years (n = 14), and after age 13 years (n = 12). All groups presented with a similar degree of growth and weight deficit at baseline, expressed in SDS units, which allowed for a reliable comparison of treatment response.

Patients were thus divided into three groups according to the age at which rhGH therapy was started. The collected data are presented in Table I.

The mean annual height gain during rhGH treatment was similar across all three analysed age groups: 6.4 cm/year (< 10 years), 6.86 cm/year (10–13 years), and 6.84 cm/year (> 13 years). The analysis revealed no statistically significant differences between groups (p = 0.49). Growth velocity, expressed as annual height gain in cm/year, was comparable in all age groups, suggesting that the efficacy of rhGH therapy does not depend on the age at which treatment is initiated.

Comparison of normalised values (SDS) of height and weight relative to population reference standards in the individual age groups clearly shows the beneficial effect of rhGH therapy in each of them. In patients who began therapy before the age of 10 years, the mean height SDS improved from –2.63 to –1.33. Improvement was also noted in weight SDS, from –1.38 at treatment initiation to –1.18 at treatment completion. Among children who started therapy between the ages of 10 and 13 years, mean height SDS changed from –2.47 to –1.32, and weight SDS from –1.56 to –1.05. In the oldest group, comprising patients who began therapy after the age of 13 years, height SDS improved from –2.36 to –1.44, while weight SDS improved from –1.46 to –1.0. These results indicate that after several years of treatment, patients significantly reduced their height deficit compared with population norms. However, the greatest benefits were observed in patients who started therapy in early childhood. This suggests that although therapy is effective at any age, early initiation allows for the most optimal clinical outcomes.

By contrast, mean annual weight gain differed between the three groups: in the youngest patients (< 10 years) it was 4.0 kg/year, in the 10–13-year age group 5.43 kg/year, and in the oldest group (> 13 years) as much as 6.41 kg/year. Statistically significant differences were found between groups (p = 0.0018). These findings indicate greater weight gain in patients who began therapy at an older age. It should be emphasised that this effect may be partly influenced by physiological factors associated with puberty, which are particularly relevant in the oldest age group.

The most common reason for discontinuing treatment in the analysed cohort was slowed growth velocity below 2 cm/year (59.1%, n = 23). The second most frequent reason (28%, n = 11) was lack of parental consent to continue therapy. In one patient (2.6%), treatment was stopped due to advanced bone age. Less common reasons were complications associated with rhGH therapy. In 3 patients (7.7%), therapy was discontinued due to persistently elevated levels of insulin-like growth factor 1 (IGF-1), and in one patient (2.6%) due to abnormal glucose tolerance in an oral glucose tolerance test.

Discussion

In this retrospective analysis of 39 patients diagnosed with SGA and treated with rhGH, significant improvements in growth and weight parameters during therapy were observed. Height SDS improved in all three age groups. These findings are consistent with existing literature confirming the efficacy of rhGH therapy in children born SGA, reporting marked acceleration of growth and improvements in height SDS during rhGH treatment, and in the long term, a reduction in height deficit relative to the reference population [2, 3].

This analysis highlights that the therapeutic effect depends on the age at treatment initiation. A review of studies shows that the age at which rhGH therapy is started is one of the most important predictors of response. Younger age at initiation correlates with greater height gain in the first years of therapy and better final outcomes [3, 4, 5].

Results regarding sex-related differences in response to rhGH are inconsistent in the literature. Some studies suggest differences arise from variations in referral practices and timing of treatment initiation [6]. Furthermore, research on the influence of sex on short-term rhGH response indicates that sex may affect pharmacokinetics and IGF-1 response, which could indirectly lead to observed clinical differences [7].

The safety of rhGH therapy is consistent with review data showing that, with proper monitoring, treatment is safe but requires observation of metabolic parameters and IGF-1 [8, 9]. Regular monitoring of IGF-1, glucose tolerance, and blood pressure is particularly important in patients with additional metabolic risk factors.

The relatively small sample size is a limitation of this study. Future research should consider prospective, multicentre studies with larger patient cohorts and control of variables such as pubertal stage, rhGH dosing, and compliance.

Summary

In conclusion, rhGH therapy in SGA patients improved both height and weight SDS values in all analysed age groups, confirming its high efficacy. The greatest benefits were observed in patients who started treatment in early childhood, highlighting the importance of early therapeutic intervention. The findings confirm both the efficacy and safety of rhGH therapy in this patient group. However, treatment response depends on individual clinical factors and requires ongoing monitoring of clinical outcomes and regular biochemical control.