Analysis of risk factors affecting the growth potential of girls with precocious puberty and early puberty：a retrospective case-control study

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Methods Clinical datas of 100 girls we have selected aged 5–9 years presenting with secondary sexual characteristics at the Growth and Development Outpatient of Shanghai Fifth People's Hospital Affiliated to Fudan University from September 2022 to September 2025 were collected. They were divided into two groups: 43 cases aged 5-7.5 years and 57 cases aged 7.6-9 years. Clinical characteristic datas were collected from patients, including anthropometric measurements, vitamin D levels, insulin-like growth factor-1 (IGF-1), thyroid hormones and bone age etc.Statistical analysis showed no significant differences between the two groups of children on above clinical characteristic. Then we stratified the girls into groups with normal growth potential and impaired growth potential, respectively, based on whether their bone age predicted adult height was greater than their genetic target height(PAH-TH), and next analyze the risk factors that affect the growth potential of the two groups of girls. Conclution 1.Compared with the normal growth potential group, girls in the impaired growth potential group exhibited lower vitamin D and Free Triiodothyronine (FT3) levels.2.Compared with the normal vitamin D group, the risk of impaired growth potential increased in the vitamin D deficiency group (OR = 4.619, 95%CI:1.26–16.99). Affecting Growth potencial Precocious Puberty Early Puberty Figures Figure 1 Introduction The prevalence trend and definition of the precocious puberty In recent years, the incidence of precocious puberty has been increasing year by year, especially among obese girls[ 1 ]. Under normal circumstances, about 2.5% of children experience early puberty, and 2.5% of children experience delayed puberty[ 2 , 3 , 4 ]. In a meta-analysis study, the combined prevalence of precocious puberty and early puberty was estimated to be 7.87% in girls and 3.98% in boys, which is significantly higher than historical norms[ 5 ]. The development of central precocious puberty is mediated by complex hormonal interactions within the hypothalamus-pituitary-gonadal (HPG) axis, promoting the maturation of the reproductive system and achieving fertility, a process influenced by multiple factors such as genes, environment, and nutrition. Generally, when girls show breast tissue development before the age of 8 and boys show testicular enlargement before the age of 9, such pubertal development is defined as precocious puberty[ 6 ]. However, more recent evidence indicates that the onset of puberty, especially breast development in girls, has been observed in children at younger ages. The latest guidelines on precocious puberty in China in 2022 have indicated that precocious puberty refers to the development of secondary sexual characteristics in girls before the age of 7.5 and in boys before the age of 9, or the onset of menstruation in girls before the age of 10. Once a child is determined to have precocious puberty, it is further classified into central precocious puberty, peripheral precocious puberty, and incomplete precocious puberty based on whether the HPG axis function has been activated early[ 7 ]. The impact of precocious puberty on children's health The onset of puberty is due to the intermittent secretion of gonadotropin–releasing hormone (GnRH) from the hypothalamus into the pituitary portal circulation, which in turn controls the release of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH) ) from the anterior pituitary, promoting the maturation and function of the gonads (testes and ovaries). These gonadotropins are involved in the maturation and function of the gonads, which synthesize sex hormones[ 8 ], thereby facilitating the development of secondary sexual characteristics and the generation of germ cells. During the early stages of sexual maturation, low levels of estradiol trigger the pubertal growth spurt, but in late puberty, high concentrations of estradiol can cause the fusion of growth plates and cease skeletal growth[ 9 ], resulting in a reduced adult height for children with precocious puberty. However, girls exhibiting early breast development during the initial stages of puberty may experience accelerated bone age progression due to central precocious puberty, and without intervention, their adult height is often less than their genetic potential, leading to a reduction in final adult height. Additionally, young children may find it challenging to adapt to the physical changes of puberty, particularly menarche, which can lead to adverse psychological effects and warrant serious attention. Additionally, early physical maturation within the normal age range in girls is associated with increased risks of anxiety, depression [ 10 ], and harmful behaviors during puberty, such as substance use [ 11 ], behavioral problems [ 12 ], and eating disorders. Early physical development and onset of menarche in girls are related to an increased risk of obesity, diabetes mellitus type 2 [ 13 ], cardiovascular diseases [ 14 ], and breast cancer [ 15 ] in adulthood. Early puberty also has adverse effects on the healthy of girls In clinical practice, it has been found that many girls exhibit secondary sexual characteristics at ages over 7.5 but below the average puberty onset age (9–10 years), not meeting the diagnostic criteria for precocious puberty, and are clinically diagnosed with early puberty [ 16 ]. In early studies, Cassio et al. [ 17 ] demonstrated that girls aged 7.5–8.5 years in puberty, whether treated with gonadotropin–releasing hormone agonist(GnRHa) or not, achieved a final height comparable to their target height; however, untreated girls exhibited faster pubertal progression and an average menarche age of 10.8 years. Recent meta-analyses have shown [ 18 ] that GnRHa treatment can improve the final height of children with early puberty, but the treatment duration needs to exceed 2 years. Therefore, whether the treatment of girls with early puberty can benefit their final height is uncertain, but it is undeniable that precocious puberty and early puberty development can affect children's physiological healthy, such as early menarche, premature epiphyseal closure, impact on final height, and feelings of inferiority. In the long term, it may harm reproductive health in adulthood, and precocious puberty is a high-risk factor for breast cancer and metabolic diseases [ 19 ]. This study focuses on the clinical characteristics of girls with precocious and early puberty, exploring clinical risk factors that lead to impaired growth potential, to enhance parents' awareness of risks and improve treatment outcomes during the clinical practice. Methods Study sample : We retrieved all female patients aged 5 to 9 years who visited the Growth and Development Clinic of Fudan University Affiliated Shanghai Fifth People's Hospital from September 2022 to September 2025. Among them, 43 girls aged 5 to 7.5 years and 57 girls aged 7.6 to 9 years,total 100 cases. Inclusion criteria: (1) Girls aged 5–9 years showing the development of secondary sexual characteristics,including breast development or growth of axillary and pubic hair,at Tanner Stage II; (2) Results from the sex hormone stimulation test indicate the onset of central pubertal development; (3) All patients were newly diagnosed within the past 6 months and had not received any treatment related to precocious puberty, including traditional Chinese medicine. Exclusion criteria for all cases: (1) Presence of chronic diseases (such as liver and kidney-related diseases, or significant organ damage in the digestive system, morbus cardiacus,etc.); 2. Children with other endocrine diseases (such as thyroid diseases, diabetes, growth hormone deficiency,etc.); 3. Exclusion of secondary sexual characteristic development caused by central nervous system lesions, adrenal lesions, or other diseases. Measurements Cases meeting the inclusion and exclusion criteria were screened through the hospital’s growth and development specialty outpatient and inpatient records. Relevant clinical data were then collected, including onset times of puberty, body height, weight, Body Mass Index(BMI), Vitamin D, Insulin-like growth factor-1(IGF-1), bone age, uterine and ovarian volumes calculated, sex hormones (LH, FSH), and thyroid function (FT3, FT4, TSH). Anthropometric measurements were routinely performed according to standard procedures by two pediatrician at each outpatient visit, with the subjects dressed lightly and barefoot to the nearest 0.1 cm and 0.1 kg. All anthropometric measurements were recorded with the average calculated for each participant. IGF-1 is measured using the Siemens fully automated chemiluminescent immunoassay analyzer IMMLITE 2000 XPi in the hospital laboratory. Vitamin D, sex hormones, and thyroid hormones are measured using the Roche COBAS E602 fully automated electrochemiluminescent immunoassay analyzer in the hospital laboratory. Uterine and ovarian volume (cm³) were calculated as length × thickness × height × π/6, with all dimensions measured in centimeters.Genetic height is commonly estimated using averaging the parents' heights and adjusting the result based on the child's gender (adding 6.5 cm for boys and subtracting 6.5 cm for girls). Statistical Analysis Data processing was performed using SPSS 26.0 statistical software. Continuous data with a normal distribution are described as mean ± standard deviation, while non-normal distributed data are described using the median (P25–P75), and categorical variables are represented as counts. The independent samples T test was used to compare the means between two groups; non-parametric tests were employed to compare distributions between two groups; and the Chi-square test or Fisher's exact test was used for inter-group comparisons of categorical data. All tests were two-sided, with P < 0.05 considered statistically significant. Results The clinical characteristics comparison results of the girls showed that there were no statistically significant differences in IGF-1, Vitamin D, average volume of uterine, average volume of ovarian, FT3, FT4, TSH, and sex hormones between the two groups of children. As shown in Table 1. The clinical characteristics of two groups of girls cases 5 to 7.5 years 7.6 to 9 yeas P value 43 57 onset times of puberty(years) 7.10(6.4–7.40) 8.30(8.00−8.70) BMI(Kg/m 2 ) 16.25 ± 2.03 17.20 ± 2.64 < 0.05 IGF−1(ng/ml) 214.27 ± 73.3 219.00(173.00−251.00) 0.64 Vitamin D(umol/l) 62.47 ± 19.23 55.90(45.84–70.05) 0.42 Bone age - real age(years) 1.10(−3.35−4.40) −1.00(−4.70−2.70) 0.313 Uterine volume(cm 3 ) 0.80(0.65–1.50) 1.20(0.70–1.60) 0.12 Average ovarian volume(cm 3 ) 2.25 ± 0.78 2.05(1.50–2.70) 0.46 FT3(pmol/L) 6.61(6.09–7.15) 6.37 ± 0.73 0.06 FT4(pmol/L) 16.77(15.93–17.80) 16.72 ± 1.65 0.41 TSH(mIU/L) 2.30(1.0−2.77) 2.15(1.59–3.07) 0.43 LH > 0.3 5 20 0.23 FSH(mIU/L) 1.93(1.53–2.72) 2.36(1.79–3.88) 0.05 The two groups of children were divided into a normal growth potential group (PAH ≥ TH) and a growth potential impaired group (PAH < TH). Significant differences in Vitamin D and TSH were observed between the two groups of children (P < 0.05); see Table 2. Clinical characteristics between the impaired growth potential group and the normal growth potential group cases impaired growth potential group normal growth potential group P value 49 51 onset times of puberty(years) 7.90 ± 0.90 7.72 ± 0.95 0.33 BMI(Kg/m 2 ) 16.95(15.34–19.10) 16.11(15.07–18.24) 0.29 IGF−1(ng/ml) 218.49 ± 65.03 220.0(167.00−262.00) 0.82 Vitamin D(umol/l) 50.38(43.71–66.71) 64.70(50.75–73.73) 0.002 Uterine volume(cm 3 ) 1.34 ± 1.12 1.20 ± 0.73 0.48 Average ovarian volume(cm 3 ) 2.23 ± 0.78 2.10(1.50–2.70) 0.61 FT3(pmol/L) 6.35(5.92–6.88) 6.71 ± 1.07 0.08 FT4(pmol/L) 16.90(15.65–18.15) 16.40(15.70–17.70) 0.32 TSH(mIU/L) 2.26 ± 1.28 2.97 ± 2.31 0.06 LH > 0.3 12 15 0.50 FSH(mIU/L) 2.67 ± 1.34 2.52 ± 1.32 0.58 The variables of vitamin D, FT3, and TSH with statistical significance from Table 2 were included in the binary logistic regression analysis. The result is shown in Table 3: The results of the binary logistic regression equation Independent variable B SE Waldx 2 P OR 95%CI Vitamin D −.047 .016 8.514 .004 .954 0.924 ~ 0.985 FT3 −.573 .253 5.126 .024 .564 0.343 ~ 0.926 TSH −.345 .164 4.420 .036 .708 0.513 ~ 0.977 Then, potential confounding factors such as age,BMI,FT4,were controlled for, the result is shown in Table 4: results of the logistic regression equation after controlling for confounding factors Independent variable B SE WaldX 2 P OR 95%CI Vitamin D −0.044 0.016 7.328 0.007 0.957 0.926 ~ 0.998 FT3 −0.630 0.276 5.194 0.023 0.533 0.310 ~ 0.916 The table above shows that FT3 and vitamin D are independent influencing factors on growth potential impairment in these two groups. To further analyze the impact of different vitamin D levels on growth potential impairment in these two groups, the vitamin D levels were divided into vitamin D deficiency group (n = 33, 75 nmol/L). see Fig. 1. This graph includes the means and standard deviations. We further performed binary logistic regression analyses on different levels of vitamin D and FT3; As shown in Table 5. Independent variable B SE WaldX 2 P OR 95%CI Vitamin D nomal 6.758 0.034 Vitamin D deficiency 1.530 0.665 5.229 0.021 4.619 1.255 ~ 16.999 Vitamin D decrease 0.500 0.617 0.656 0.418 1.648 0.492 ~ 5.517 FT3 −0.505 0.246 4.205 0.04 0.604 0.373 ~ 0.978 The results indicate that elevated FT3 is a protective factor for impaired growth potential in both boys and girls, while vitamin D deficiency is an independent risk factor for reduced growth potential in girls with precocious or early puberty. Moreover, the risk of impaired growth potential in girls with precocious or early puberty and vitamin D deficiency is 4.619 times higher than in girls with normal vitamin D levels. Discussion In recent years, the onset of adolescent development in girls in our country has advanced, with the diagnostic age cutoff for precocious puberty in girls being lowered from 8 years to 7.5 years [ 1 ]. Currently, clinical practice primarily focuses on precocious puberty, while the issue of early adolescent development is often overlooked. However, it poses significant risks to children's psychological and physiological health, as well as their adult final height. Therefore, this study aims to explore the clinical characteristics of girls with varying puberty onset times and analyze the clinical factors affecting growth potential. The results of this study indicate that there are no significant differences in clinical characteristics between girls aged 5 to 7.5 years and those aged 7.6 to 9 years who experience early sexual development. This finding is specifically based on comparisons of IGF-1, vitamin D, thyroid hormones (FT3, FT4, TSH), and sex hormones (LH, FSH) in relation to average uterine and ovarian volume. An epidemiological survey found that compared to normally developing girls, those with earlier onset and faster development have an increased risk of depressive disorder[ 20 ]. Therefore, girls with precocious puberty require careful attention and monitoring, similar to the approach taken for early sexual development. The results of this study show that elevated FT3 is a protective factor against impaired growth potential in girls with precocious puberty and early sexual development. This finding is roughly consistent with those of JUNG[ 21 ] et al, who reported that the FT4 level in the precocious puberty group is lower than that in the non-precocious puberty group. While a case-control study found that after treatment for precocious puberty, the levels of TSH, FT3, and FT4 in the patients decreased and tended to normalize with treatment[ 22 ]. Howevr, a clinical controlled trial found that FT4 levels are elevated in central precocious puberty[ 23 ]. Current research results indicate inconsistent data regarding the effects of thyroid hormones on folliculogenesis. For example, Meng[ 24 ] et al. reported that hypothyroidism reduces the number of follicles in rats while accelerating follicular atresia; however, others pointed out that there is no difference in the number of follicles in hypothyroid rats[ 25 ]. Although the specific mechanisms of thyroid and gonadal development have not been fully understood by humans, these all indicate a strong association between thyroid hormones and sexual development. Subsequently, we will continue to explore this mysterious field. The results of this study indicate that vitamin D deficiency is an independent risk factor for impaired growth potential in girls with precocious puberty and early pubertal development. The risk of impaired growth potential in girls with vitamin D deficiency is 4.619 times that of those with normal vitamin D levels. These findings are consistent with the results of a clinical study [ 26 ], which indicated that low levels of vitamin D are an independent risk factor for the conversion of simple breast development to idiopathic central precocious puberty. It is also consistent with the clinical research results of Sun Yan et al. [ 27 ], which showed that GnRHa combined with vitamin D treatment in children with idiopathic precocious puberty can reduce the bone formation index, modulate bone metabolism, delay the progression of bone age development, and improve final height. It is well known that the main physiological role of vitamin D is to enhance the absorption of calcium and phosphorus in the small intestine. By acting on osteoblasts, it promotes the formation, development, and mineralization of bones. When blood calcium levels decrease, it mobilizes calcium from bone stores into the bloodstream to maintain the calcium concentration required for key functions such as muscle and nerve activity[ 28 ]. The mechanism linking vitamin D deficiency to impaired skeletal growth potential is not yet clear, but many studies show that may involve three main mechanisms: (1) Vitamin D deficiency leads to impaired bone matrix mineralization: Normal mineralization of the bone matrix highly depends on the concentrations of calcium ions (Ca²⁺) and phosphate ions (PO₄³⁻) in the extracellular fluid, and their product must reach a saturated state to form hydroxyapatite crystals and deposit on osteoid[ 29 , 30 ]. Calcium ion (Ca²⁺) signaling regulates gene expression, and Ca²⁺ transport affects the formation of calcium phosphate as well as the deposition and mineralization of collagen fibers. Therefore, fluctuations in calcium ion flux are considered key factors in the biological mineralization mechanism[ 31 ]. Vitamin D (its active form − 1,25-dihydroxyvitamin D₃ (Calcitriol)) is the key hormone that maintains this homeostasis. Calcitriol can stimulate the transient receptor potential vanilloid subtype 6 channel (TRPV6) - a highly selective calcium channel located in the intestinal epithelium, thus facilitating calcium entry into intestinal cells [ 32 ]. Therefore, vitamin D deficiency affects bone matrix mineralization, leading to bone softening and decreased strength, which cannot support the mechanical stress associated with normal growth, thereby limiting skeletal growth potential.(2) Structural and functional disorders of the growth plate: Accumulation of hypertrophic chondrocytes and abnormal vascular invasion in the growth plate disrupt the normal endochondral ossification process, leading to structural deformities. Long bones elongate through endochondral ossification of chondrocytes, which occurs via an increase in chondrocyte volume during their proliferation and differentiation[ 33 ]. Vitamin D deficiency can cause hypertrophic chondrocytes to fail to undergo normal apoptosis and clearance, resulting in thickening and irregularity of the temporary calcification zone in the growth plate, thus affecting normal longitudinal growth of bones. Additionally, vascular invasion of mineralized cartilage is a key step in the endochondral ossification process, aimed at degrading chondrocytes and forming osteocytes. An animal-based experimental study has shown[ 34 ] that active vitamin D3 signaling can stimulate the expression of vascular endothelial growth factor (VEGF). This is accompanied by enhanced vascular invasion of mineralized cartilage, promoting the formation of new blood vessels in the growth plate in vivo, thereby facilitating longitudinal bone growth. Therefore, vitamin D deficiency impairs this process, affecting the differentiation of chondrocytes into osteocytes.(3) Negative effects of secondary hyperparathyroidism due to hypocalcemia: In response to low blood calcium, the body compensatorily secretes excessive parathyroid hormone (PTH). Although PTH aims to elevate blood calcium, its side effects further damage the bones. First, it exacerbates bone resorption: High levels of PTH excessively stimulate osteoclasts, accelerating the breakdown and resorption of bones. Although calcium is released, it leads to a net loss of bone mass, weakening the macrostructure and microstructure of the bones[ 35 ]. Second, phosphorus depletion: PTH inhibits the reabsorption of phosphates by renal tubules, leading to increased phosphorus excretion in urine[ 36 – 38 ], further exacerbating hypophosphatemia and thereby perpetuating mineralization disorders in a vicious cycle. Strengths and limitations One advantage of this study lies in its focused attention on girls in the pre-adolescent stage (aged 5–9) who have early puberty and precocious puberty. Girls in this age group have the highest risk of their final height being affected due to early puberty, but current treatments mainly focus on using GnRHa drugs for intervention. Based on clinical practice, our research results can help identify risk factors and be applied in clinical settings. Our study has several limitations.Firstly, this study was conducted in a single center and the sample was sourced from a single medical institution, therefore findings may not be generalisable to other settings.Secondly,The population in this study has specific characteristics in terms of race and economic status, which limits its application in other regional medical institutions.Thirdly,This study relied on the secondary extraction of case data. Some confounding factors that could not be traced back (such as dietary and nutritional status, exercise habits, emotional factors, over-the-counter drug use, etc.) were not included in the analysis,.This study was mainly based on the secondary extraction of economic data from relevant cases. Some untraceable interfering factors (such as dietary and nutritional status, exercise habits, emotional factors, use of over-the-counter drugs, etc.) were not included in the analysis scope. These factors may have a positive impact on the results, thus potentially amplifying the effect of the results.Lastly, Currently, there is no completely unified and authoritative definition of growth potential internationally. However, different academic organizations have formed some consensus statements based on research and practice. In the field of children and adolescents' development, Growth potential refers to the maximum height that an individual can reach by fully leveraging their genetic factors before the epiphysis closes. This figure is calculated based on factors such as the current growth stage, bone age, and sexual maturity. This value can be estimated through methods like bone age prediction.We acknowledge that this approach may overestimate the probability of impaired growth potential and the inconsistencies in the definitions, thereby limiting its direct comparability with studies that strictly follow international guidelines.Therefore, in the future, larger-scale multi-center studies need to be conducted to establish standards based on clinical evidence, which can more accurately identify the risk factors for impaired growth potential. Conclusion This study was conducted in a single center, and its data were mainly derived from the secondary extraction of cases. Some untraceable confounding factors (such as diet and nutritional status, genetic factors, and the use of over-the-counter drugs, etc.) were not included in the analysis scope. As a result, there was bias in the data, and the application of the research results should be done with. Abbreviations IGF-1 Insulin-like growth factor-1 PAH Predicted adult height TH Genetic target height FT3 Free Triiodothyronine FT4 Free thyroxine TSH Thyroid stimulating hormone HPG Hypothalamus-pituitary-gonadal GnRH Gonadotropin--releasing hormone LH Luteinizing hormone FSH Follicle-stimulating hormone BMI Body Mass Index VEGF Vascular endothelial growth factor TRPV6 Transient receptor potential vanilloid subtype 6 channel PTH Parathyroid hormone Declarations Ethics approval and consent to participate : This study was performed with ethics approval and waiver of informed consent (Medical Ethics Committee of Shanghai Fifth People's Hospital Affiliated to Fudan University,Approval Number: 2023(081)).This study utilized secondary data that were anonymized. Consent for publication : Not applicable. Availability of data and materials :The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests :The authors declare that they have no competing interests. Funding :The authors received no financial support for the research. Authors' contributions :F.L. and F.W. conceptualised and designed the study.F.L. and Z.L. were responsible for the collection and verification of data and ultimately wrote the article. F.L. and F.W. were responsible for the interpretation and analysis of the data. L.Z. provided resources and supervision for the paper. All authors reviewed and approved the final version of the paper. Acknowledgements :We ackownledge Xing Shen from the Information Statistics Department of Shanghai Fifth People's Hospital for providing the clinical case retrieval service for this research. References Shi L, Jiang Z, Zhang L. Childhood obesity and central precocious puberty[J]. Front Endocrinol. 2022;13:1056871. Soriano-Guillén L, Argente J. Central precocious puberty, functional and tumor-related[J]. Best practice & research. 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How to build an inducible cartilage-specific transgenic mouse[J]. Volume 16. ARTHRITIS RESEARCH & THERAPY; 2014. p. 210. 3. Lin R, Amizuka N, Sasaki T, et al. 1Alpha,25-dihydroxyvitamin D3 promotes vascularization of the chondro-osseous junction by stimulating expression of vascular endothelial growth factor and matrix metalloproteinase 9[J]. J bone mineral research: official J Am Soc Bone Mineral Res. 2002;17(9):1604–12. Lewiecki EM, Miller PD. Skeletal effects of primary hyperparathyroidism: bone mineral density and fracture risk[J]. J Clin densitometry: official J Int Soc Clin Densitometry. 2013;16(1):28–32. Goltzman D, Mannstadt M, Marcocci C. Physiology of the Calcium-Parathyroid Hormone-Vitamin D Axis[J]. Front Horm Res. 2018;50:1–13. Arnold A, Dennison E, Kovacs CS, et al. Hormonal regulation of biomineralization[J]. Nat Rev Endocrinol. 2021;17(5):261–75. Rizzoli R, Fleisch H, Bonjour JP. Role of 1,25-dihydroxyvitamin D3 on intestinal phosphate absorption in rats with a normal vitamin D supply[J]. J Clin Investig. 1977;60(3):639–47. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 06 May, 2026 Editor invited by journal 14 Apr, 2026 Editor assigned by journal 13 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 First submitted to journal 08 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9357369","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":640317474,"identity":"3be0895d-fd28-4244-b6b4-4b78516d6195","order_by":0,"name":"Fengfeng Liu","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Fengfeng","middleName":"","lastName":"Liu","suffix":""},{"id":640317477,"identity":"5bc9a6d2-c4ed-483b-96e4-8a8f7a971a9e","order_by":1,"name":"Zhen Liu","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Liu","suffix":""},{"id":640317481,"identity":"ea469ead-d61c-44b8-8687-e6ff8f8ac5ed","order_by":2,"name":"Fei Wang","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Wang","suffix":""},{"id":640317484,"identity":"b50e3611-5170-4053-aa19-7a0253c23334","order_by":3,"name":"Lan Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIie3QsQrCMBCA4SsH0eEkm0Qq9BUqLgqCr6J7Bx/ALaCLOlfUd/ARIgedFFdBB0FwcugkTmI7K6ZuDvmHm/KRSwBcrn+s5J2BAEhKbUz6KEIQw5zUa3HS38wnP5BOaKIml0UBEWgU6jY8EZhtyhkOZNV8J15GasvkSp6ernnQgsZ80bPtJROfBBPCbs0xQS88WohAFD49mQRE53zaCeWkMmIiiKAYUYjYXs2YlErC7JOV/S3BWHuH25273b2+pOmjE0jfQt5u/e24y+VyuT73AjTLPuuKGmV7AAAAAElFTkSuQmCC","orcid":"","institution":"Fudan University","correspondingAuthor":true,"prefix":"","firstName":"Lan","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-04-08 13:08:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9357369/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9357369/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109332100,"identity":"5cf81df4-e218-4c45-85b4-a1ba285f1e80","added_by":"auto","created_at":"2026-05-15 16:13:12","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47042,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9357369/v1/e8c5ab0ed65051487861f077.jpeg"},{"id":109332102,"identity":"c5ba8f56-31ce-47b1-a8b9-5a2f9f89d917","added_by":"auto","created_at":"2026-05-15 16:13:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":291473,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9357369/v1/6913f0fe-478d-4b42-a494-28b12cbc6777.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of risk factors affecting the growth potential of girls with precocious puberty and early puberty：a retrospective case-control study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe prevalence trend and definition of the precocious puberty\u003c/p\u003e \u003cp\u003eIn recent years, the incidence of precocious puberty has been increasing year by year, especially among obese girls[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Under normal circumstances, about 2.5% of children experience early puberty, and 2.5% of children experience delayed puberty[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In a meta-analysis study, the combined prevalence of precocious puberty and early puberty was estimated to be 7.87% in girls and 3.98% in boys, which is significantly higher than historical norms[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The development of central precocious puberty is mediated by complex hormonal interactions within the hypothalamus-pituitary-gonadal (HPG) axis, promoting the maturation of the reproductive system and achieving fertility, a process influenced by multiple factors such as genes, environment, and nutrition. Generally, when girls show breast tissue development before the age of 8 and boys show testicular enlargement before the age of 9, such pubertal development is defined as precocious puberty[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, more recent evidence indicates that the onset of puberty, especially breast development in girls, has been observed in children at younger ages. The latest guidelines on precocious puberty in China in 2022 have indicated that precocious puberty refers to the development of secondary sexual characteristics in girls before the age of 7.5 and in boys before the age of 9, or the onset of menstruation in girls before the age of 10. Once a child is determined to have precocious puberty, it is further classified into central precocious puberty, peripheral precocious puberty, and incomplete precocious puberty based on whether the HPG axis function has been activated early[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe impact of precocious puberty on children's health\u003c/p\u003e \u003cp\u003eThe onset of puberty is due to the intermittent secretion of gonadotropin\u0026ndash;releasing hormone (GnRH) from the hypothalamus into the pituitary portal circulation, which in turn controls the release of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH) ) from the anterior pituitary, promoting the maturation and function of the gonads (testes and ovaries). These gonadotropins are involved in the maturation and function of the gonads, which synthesize sex hormones[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], thereby facilitating the development of secondary sexual characteristics and the generation of germ cells. During the early stages of sexual maturation, low levels of estradiol trigger the pubertal growth spurt, but in late puberty, high concentrations of estradiol can cause the fusion of growth plates and cease skeletal growth[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], resulting in a reduced adult height for children with precocious puberty. However, girls exhibiting early breast development during the initial stages of puberty may experience accelerated bone age progression due to central precocious puberty, and without intervention, their adult height is often less than their genetic potential, leading to a reduction in final adult height. Additionally, young children may find it challenging to adapt to the physical changes of puberty, particularly menarche, which can lead to adverse psychological effects and warrant serious attention. Additionally, early physical maturation within the normal age range in girls is associated with increased risks of anxiety, depression [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and harmful behaviors during puberty, such as substance use [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], behavioral problems [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and eating disorders. Early physical development and onset of menarche in girls are related to an increased risk of obesity, diabetes mellitus type 2 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], cardiovascular diseases [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and breast cancer [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] in adulthood.\u003c/p\u003e \u003cp\u003eEarly puberty also has adverse effects on the healthy of girls\u003c/p\u003e \u003cp\u003eIn clinical practice, it has been found that many girls exhibit secondary sexual characteristics at ages over 7.5 but below the average puberty onset age (9\u0026ndash;10 years), not meeting the diagnostic criteria for precocious puberty, and are clinically diagnosed with early puberty [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In early studies, Cassio et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] demonstrated that girls aged 7.5\u0026ndash;8.5 years in puberty, whether treated with gonadotropin\u0026ndash;releasing hormone agonist(GnRHa) or not, achieved a final height comparable to their target height; however, untreated girls exhibited faster pubertal progression and an average menarche age of 10.8 years. Recent meta-analyses have shown [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] that GnRHa treatment can improve the final height of children with early puberty, but the treatment duration needs to exceed 2 years. Therefore, whether the treatment of girls with early puberty can benefit their final height is uncertain, but it is undeniable that precocious puberty and early puberty development can affect children's physiological healthy, such as early menarche, premature epiphyseal closure, impact on final height, and feelings of inferiority. In the long term, it may harm reproductive health in adulthood, and precocious puberty is a high-risk factor for breast cancer and metabolic diseases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This study focuses on the clinical characteristics of girls with precocious and early puberty, exploring clinical risk factors that lead to impaired growth potential, to enhance parents' awareness of risks and improve treatment outcomes during the clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e \u003cb\u003eStudy sample\u003c/b\u003e: We retrieved all female patients aged 5 to 9 years who visited the Growth and Development Clinic of Fudan University Affiliated Shanghai Fifth People's Hospital from September 2022 to September 2025. Among them, 43 girls aged 5 to 7.5 years and 57 girls aged 7.6 to 9 years,total 100 cases. Inclusion criteria: (1) Girls aged 5\u0026ndash;9 years showing the development of secondary sexual characteristics,including breast development or growth of axillary and pubic hair,at Tanner Stage II; (2) Results from the sex hormone stimulation test indicate the onset of central pubertal development; (3) All patients were newly diagnosed within the past 6 months and had not received any treatment related to precocious puberty, including traditional Chinese medicine. Exclusion criteria for all cases: (1) Presence of chronic diseases (such as liver and kidney-related diseases, or significant organ damage in the digestive system, morbus cardiacus,etc.); 2. Children with other endocrine diseases (such as thyroid diseases, diabetes, growth hormone deficiency,etc.); 3. Exclusion of secondary sexual characteristic development caused by central nervous system lesions, adrenal lesions, or other diseases.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eMeasurements\u003c/strong\u003e \u003cp\u003eCases meeting the inclusion and exclusion criteria were screened through the hospital\u0026rsquo;s growth and development specialty outpatient and inpatient records. Relevant clinical data were then collected, including onset times of puberty, body height, weight, Body Mass Index(BMI), Vitamin D, Insulin-like growth factor-1(IGF-1), bone age, uterine and ovarian volumes calculated, sex hormones (LH, FSH), and thyroid function (FT3, FT4, TSH). Anthropometric measurements were routinely performed according to standard procedures by two pediatrician at each outpatient visit, with the subjects dressed lightly and barefoot to the nearest 0.1 cm and 0.1 kg. All anthropometric measurements were recorded with the average calculated for each participant. IGF-1 is measured using the Siemens fully automated chemiluminescent immunoassay analyzer IMMLITE 2000 XPi in the hospital laboratory. Vitamin D, sex hormones, and thyroid hormones are measured using the Roche COBAS E602 fully automated electrochemiluminescent immunoassay analyzer in the hospital laboratory. Uterine and ovarian volume (cm\u0026sup3;) were calculated as length \u0026times; thickness \u0026times; height\u0026thinsp;\u0026times;\u0026thinsp;π/6, with all dimensions measured in centimeters.Genetic height is commonly estimated using averaging the parents' heights and adjusting the result based on the child's gender (adding 6.5 cm for boys and subtracting 6.5 cm for girls).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical Analysis\u003c/strong\u003e \u003cp\u003eData processing was performed using SPSS 26.0 statistical software. Continuous data with a normal distribution are described as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while non-normal distributed data are described using the median (P25\u0026ndash;P75), and categorical variables are represented as counts. The independent samples T test was used to compare the means between two groups; non-parametric tests were employed to compare distributions between two groups; and the Chi-square test or Fisher's exact test was used for inter-group comparisons of categorical data. All tests were two-sided, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe clinical characteristics comparison results of the girls showed that there were no statistically significant differences in IGF-1, Vitamin D, average volume of uterine, average volume of ovarian, FT3, FT4, TSH, and sex hormones between the two groups of children. As shown in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eThe clinical characteristics of two groups of girls\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ecases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 to 7.5 years\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.6 to 9 yeas\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eonset times of puberty(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.10(6.4\u0026ndash;7.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.30(8.00\u0026minus;8.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI(Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIGF\u0026minus;1(ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e214.27\u0026thinsp;\u0026plusmn;\u0026thinsp;73.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e219.00(173.00\u0026minus;251.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D(umol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.47\u0026thinsp;\u0026plusmn;\u0026thinsp;19.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.90(45.84\u0026ndash;70.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone age - real age(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.10(\u0026minus;3.35\u0026minus;4.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;1.00(\u0026minus;4.70\u0026minus;2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine volume(cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.80(0.65\u0026ndash;1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20(0.70\u0026ndash;1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage ovarian volume(cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.05(1.50\u0026ndash;2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT3(pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.61(6.09\u0026ndash;7.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT4(pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.77(15.93\u0026ndash;17.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH(mIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.30(1.0\u0026minus;2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.15(1.59\u0026ndash;3.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH\u0026thinsp;\u0026gt;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH(mIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.93(1.53\u0026ndash;2.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.36(1.79\u0026ndash;3.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe two groups of children were divided into a normal growth potential group (PAH\u0026thinsp;\u0026ge;\u0026thinsp;TH) and a growth potential impaired group (PAH\u0026thinsp;\u0026lt;\u0026thinsp;TH). Significant differences in Vitamin D and TSH were observed between the two groups of children (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); see Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eClinical characteristics between the impaired growth potential group and the normal growth potential group\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ecases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eimpaired growth potential group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003enormal growth\u003c/p\u003e \u003cp\u003epotential group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eonset times of puberty(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI(Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.95(15.34\u0026ndash;19.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.11(15.07\u0026ndash;18.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIGF\u0026minus;1(ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218.49\u0026thinsp;\u0026plusmn;\u0026thinsp;65.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220.0(167.00\u0026minus;262.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D(umol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.38(43.71\u0026ndash;66.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.70(50.75\u0026ndash;73.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine volume(cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage ovarian volume(cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.10(1.50\u0026ndash;2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT3(pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.35(5.92\u0026ndash;6.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT4(pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.90(15.65\u0026ndash;18.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.40(15.70\u0026ndash;17.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH(mIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH\u0026thinsp;\u0026gt;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH(mIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eThe variables of vitamin D, FT3, and TSH with statistical significance from Table\u0026nbsp;2 were included in the binary logistic regression analysis. The result is shown in Table\u0026nbsp;3:\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe results of the binary logistic regression equation\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndependent variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWaldx\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.954\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.924\u0026thinsp;~\u0026thinsp;0.985\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.343\u0026thinsp;~\u0026thinsp;0.926\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;.345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.708\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.513\u0026thinsp;~\u0026thinsp;0.977\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eThen, potential confounding factors such as age,BMI,FT4,were controlled for, the result is shown in Table\u0026nbsp;4:\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eresults of the logistic regression equation after controlling for confounding factors\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndependent variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWaldX\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.957\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.926\u0026thinsp;~\u0026thinsp;0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.310\u0026thinsp;~\u0026thinsp;0.916\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe table above shows that FT3 and vitamin D are independent influencing factors on growth potential impairment in these two groups. To further analyze the impact of different vitamin D levels on growth potential impairment in these two groups, the vitamin D levels were divided into vitamin D deficiency group (n\u0026thinsp;=\u0026thinsp;33, \u0026lt; 50 nmol/L), vitamin D insufficiency group (n\u0026thinsp;=\u0026thinsp;50, 50\u0026ndash;75 nmol/L), and vitamin D normal group (n\u0026thinsp;=\u0026thinsp;17, \u0026gt;\u0026thinsp;75 nmol/L). see Fig.\u0026nbsp;1. This graph includes the means and standard deviations.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe further performed binary logistic regression analyses on different levels of vitamin D and FT3; As shown in Table\u0026nbsp;5.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabe\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndependent variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWaldX\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D nomal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.758\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.665\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.229\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.255\u0026thinsp;~\u0026thinsp;16.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D decrease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.656\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.492\u0026thinsp;~\u0026thinsp;5.517\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;0.505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.373\u0026thinsp;~\u0026thinsp;0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe results indicate that elevated FT3 is a protective factor for impaired growth potential in both boys and girls, while vitamin D deficiency is an independent risk factor for reduced growth potential in girls with precocious or early puberty. Moreover, the risk of impaired growth potential in girls with precocious or early puberty and vitamin D deficiency is 4.619 times higher than in girls with normal vitamin D levels.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn recent years, the onset of adolescent development in girls in our country has advanced, with the diagnostic age cutoff for precocious puberty in girls being lowered from 8 years to 7.5 years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Currently, clinical practice primarily focuses on precocious puberty, while the issue of early adolescent development is often overlooked. However, it poses significant risks to children's psychological and physiological health, as well as their adult final height. Therefore, this study aims to explore the clinical characteristics of girls with varying puberty onset times and analyze the clinical factors affecting growth potential.\u003c/p\u003e \u003cp\u003eThe results of this study indicate that there are no significant differences in clinical characteristics between girls aged 5 to 7.5 years and those aged 7.6 to 9 years who experience early sexual development. This finding is specifically based on comparisons of IGF-1, vitamin D, thyroid hormones (FT3, FT4, TSH), and sex hormones (LH, FSH) in relation to average uterine and ovarian volume. An epidemiological survey found that compared to normally developing girls, those with earlier onset and faster development have an increased risk of depressive disorder[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Therefore, girls with precocious puberty require careful attention and monitoring, similar to the approach taken for early sexual development. The results of this study show that elevated FT3 is a protective factor against impaired growth potential in girls with precocious puberty and early sexual development. This finding is roughly consistent with those of JUNG[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] et al, who reported that the FT4 level in the precocious puberty group is lower than that in the non-precocious puberty group. While a case-control study found that after treatment for precocious puberty, the levels of TSH, FT3, and FT4 in the patients decreased and tended to normalize with treatment[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Howevr, a clinical controlled trial found that FT4 levels are elevated in central precocious puberty[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Current research results indicate inconsistent data regarding the effects of thyroid hormones on folliculogenesis. For example, Meng[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] et al. reported that hypothyroidism reduces the number of follicles in rats while accelerating follicular atresia; however, others pointed out that there is no difference in the number of follicles in hypothyroid rats[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Although the specific mechanisms of thyroid and gonadal development have not been fully understood by humans, these all indicate a strong association between thyroid hormones and sexual development. Subsequently, we will continue to explore this mysterious field.\u003c/p\u003e \u003cp\u003eThe results of this study indicate that vitamin D deficiency is an independent risk factor for impaired growth potential in girls with precocious puberty and early pubertal development. The risk of impaired growth potential in girls with vitamin D deficiency is 4.619 times that of those with normal vitamin D levels. These findings are consistent with the results of a clinical study [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], which indicated that low levels of vitamin D are an independent risk factor for the conversion of simple breast development to idiopathic central precocious puberty. It is also consistent with the clinical research results of Sun Yan et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], which showed that GnRHa combined with vitamin D treatment in children with idiopathic precocious puberty can reduce the bone formation index, modulate bone metabolism, delay the progression of bone age development, and improve final height.\u003c/p\u003e \u003cp\u003eIt is well known that the main physiological role of vitamin D is to enhance the absorption of calcium and phosphorus in the small intestine. By acting on osteoblasts, it promotes the formation, development, and mineralization of bones. When blood calcium levels decrease, it mobilizes calcium from bone stores into the bloodstream to maintain the calcium concentration required for key functions such as muscle and nerve activity[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe mechanism linking vitamin D deficiency to impaired skeletal growth potential is not yet clear, but many studies show that may involve three main mechanisms: (1) Vitamin D deficiency leads to impaired bone matrix mineralization: Normal mineralization of the bone matrix highly depends on the concentrations of calcium ions (Ca\u0026sup2;⁺) and phosphate ions (PO₄\u0026sup3;⁻) in the extracellular fluid, and their product must reach a saturated state to form hydroxyapatite crystals and deposit on osteoid[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Calcium ion (Ca\u0026sup2;⁺) signaling regulates gene expression, and Ca\u0026sup2;⁺ transport affects the formation of calcium phosphate as well as the deposition and mineralization of collagen fibers. Therefore, fluctuations in calcium ion flux are considered key factors in the biological mineralization mechanism[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Vitamin D (its active form\u0026thinsp;\u0026minus;\u0026thinsp;1,25-dihydroxyvitamin D₃ (Calcitriol)) is the key hormone that maintains this homeostasis. Calcitriol can stimulate the transient receptor potential vanilloid subtype 6 channel (TRPV6) - a highly selective calcium channel located in the intestinal epithelium, thus facilitating calcium entry into intestinal cells [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Therefore, vitamin D deficiency affects bone matrix mineralization, leading to bone softening and decreased strength, which cannot support the mechanical stress associated with normal growth, thereby limiting skeletal growth potential.(2) Structural and functional disorders of the growth plate: Accumulation of hypertrophic chondrocytes and abnormal vascular invasion in the growth plate disrupt the normal endochondral ossification process, leading to structural deformities. Long bones elongate through endochondral ossification of chondrocytes, which occurs via an increase in chondrocyte volume during their proliferation and differentiation[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Vitamin D deficiency can cause hypertrophic chondrocytes to fail to undergo normal apoptosis and clearance, resulting in thickening and irregularity of the temporary calcification zone in the growth plate, thus affecting normal longitudinal growth of bones. Additionally, vascular invasion of mineralized cartilage is a key step in the endochondral ossification process, aimed at degrading chondrocytes and forming osteocytes. An animal-based experimental study has shown[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] that active vitamin D3 signaling can stimulate the expression of vascular endothelial growth factor (VEGF). This is accompanied by enhanced vascular invasion of mineralized cartilage, promoting the formation of new blood vessels in the growth plate in vivo, thereby facilitating longitudinal bone growth. Therefore, vitamin D deficiency impairs this process, affecting the differentiation of chondrocytes into osteocytes.(3) Negative effects of secondary hyperparathyroidism due to hypocalcemia: In response to low blood calcium, the body compensatorily secretes excessive parathyroid hormone (PTH). Although PTH aims to elevate blood calcium, its side effects further damage the bones. First, it exacerbates bone resorption: High levels of PTH excessively stimulate osteoclasts, accelerating the breakdown and resorption of bones. Although calcium is released, it leads to a net loss of bone mass, weakening the macrostructure and microstructure of the bones[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Second, phosphorus depletion: PTH inhibits the reabsorption of phosphates by renal tubules, leading to increased phosphorus excretion in urine[\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], further exacerbating hypophosphatemia and thereby perpetuating mineralization disorders in a vicious cycle.\u003c/p\u003e\n\u003ch3\u003eStrengths and limitations\u003c/h3\u003e\n\u003cp\u003eOne advantage of this study lies in its focused attention on girls in the pre-adolescent stage (aged 5\u0026ndash;9) who have early puberty and precocious puberty. Girls in this age group have the highest risk of their final height being affected due to early puberty, but current treatments mainly focus on using GnRHa drugs for intervention. Based on clinical practice, our research results can help identify risk factors and be applied in clinical settings.\u003c/p\u003e \u003cp\u003eOur study has several limitations.Firstly, this study was conducted in a single center and the sample was sourced from a single medical institution, therefore findings may not be generalisable to other settings.Secondly,The population in this study has specific characteristics in terms of race and economic status, which limits its application in other regional medical institutions.Thirdly,This study relied on the secondary extraction of case data. Some confounding factors that could not be traced back (such as dietary and nutritional status, exercise habits, emotional factors, over-the-counter drug use, etc.) were not included in the analysis,.This study was mainly based on the secondary extraction of economic data from relevant cases. Some untraceable interfering factors (such as dietary and nutritional status, exercise habits, emotional factors, use of over-the-counter drugs, etc.) were not included in the analysis scope. These factors may have a positive impact on the results, thus potentially amplifying the effect of the results.Lastly, Currently, there is no completely unified and authoritative definition of growth potential internationally. However, different academic organizations have formed some consensus statements based on research and practice. In the field of children and adolescents' development, Growth potential refers to the maximum height that an individual can reach by fully leveraging their genetic factors before the epiphysis closes. This figure is calculated based on factors such as the current growth stage, bone age, and sexual maturity. This value can be estimated through methods like bone age prediction.We acknowledge that this approach may overestimate the probability of impaired growth potential and the inconsistencies in the definitions, thereby limiting its direct comparability with studies that strictly follow international guidelines.Therefore, in the future, larger-scale multi-center studies need to be conducted to establish standards based on clinical evidence, which can more accurately identify the risk factors for impaired growth potential.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study was conducted in a single center, and its data were mainly derived from the secondary extraction of cases. Some untraceable confounding factors (such as diet and nutritional status, genetic factors, and the use of over-the-counter drugs, etc.) were not included in the analysis scope. As a result, there was bias in the data, and the application of the research results should be done with.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIGF-1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Insulin-like growth factor-1\u003c/p\u003e\n\u003cp\u003ePAH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Predicted adult height\u003c/p\u003e\n\u003cp\u003eTH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Genetic target height\u003c/p\u003e\n\u003cp\u003eFT3 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Free Triiodothyronine\u003c/p\u003e\n\u003cp\u003eFT4 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Free thyroxine\u003c/p\u003e\n\u003cp\u003eTSH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Thyroid stimulating hormone\u003c/p\u003e\n\u003cp\u003eHPG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hypothalamus-pituitary-gonadal\u003c/p\u003e\n\u003cp\u003eGnRH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gonadotropin--releasing hormone\u003c/p\u003e\n\u003cp\u003eLH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Luteinizing hormone\u003c/p\u003e\n\u003cp\u003eFSH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Follicle-stimulating hormone\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Body Mass Index\u003c/p\u003e\n\u003cp\u003eVEGF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Vascular endothelial growth factor\u003c/p\u003e\n\u003cp\u003eTRPV6 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Transient receptor potential vanilloid subtype 6 channel\u003c/p\u003e\n\u003cp\u003ePTH \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Parathyroid hormone\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e:\u0026nbsp;This study was performed with ethics approval and waiver of informed consent (Medical Ethics Committee of Shanghai Fifth People\u0026apos;s Hospital Affiliated to Fudan University,Approval Number: 2023(081)).This study utilized secondary data that were anonymized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e:\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e:The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e:The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:The authors received no financial support for the research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e:F.L. and F.W. conceptualised and designed the study.F.L. and Z.L. were responsible for the collection and verification of data and ultimately wrote the article. F.L. and F.W. were responsible for the interpretation and analysis of the data. L.Z. provided resources and supervision for the paper. All authors reviewed and approved the final version of the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e:We ackownledge Xing Shen from the Information Statistics Department of Shanghai Fifth People\u0026apos;s Hospital for providing the clinical case retrieval service for this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShi L, Jiang Z, Zhang L. Childhood obesity and central precocious puberty[J]. Front Endocrinol. 2022;13:1056871.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoriano-Guill\u0026eacute;n L, Argente J. Central precocious puberty, functional and tumor-related[J]. Best practice \u0026amp; research. 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J Clin Investig. 1977;60(3):639\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Affecting, Growth potencial, Precocious Puberty, Early Puberty","lastPublishedDoi":"10.21203/rs.3.rs-9357369/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9357369/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo analysis clinical characteristics and clinical factors affecting growth potential in girs with precocious and early puberty.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical datas of 100 girls we have selected aged 5–9 years presenting with secondary sexual characteristics at the Growth and Development Outpatient of Shanghai Fifth People's Hospital Affiliated to Fudan University from September 2022 to September 2025 were collected. They were divided into two groups: 43 cases aged 5-7.5 years and 57 cases aged 7.6-9 years. Clinical characteristic datas were collected from patients, including anthropometric measurements, vitamin D levels, insulin-like growth factor-1 (IGF-1), thyroid hormones and bone age etc.Statistical analysis showed no significant differences between the two groups of children on above clinical characteristic. Then we stratified the girls into groups with normal growth potential and impaired growth potential, respectively, based on whether their bone age predicted adult height was greater than their genetic target height(PAH-TH), and next analyze the risk factors that affect the growth potential of the two groups of girls.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.Compared with the normal growth potential group, girls in the impaired growth potential group exhibited lower vitamin D and Free Triiodothyronine (FT3) levels.2.Compared with the normal vitamin D group, the risk of impaired growth potential increased in the vitamin D deficiency group (OR = 4.619, 95%CI:1.26–16.99).\u003c/p\u003e","manuscriptTitle":"Analysis of risk factors affecting the growth potential of girls with precocious puberty and early puberty：a retrospective case-control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 16:13:08","doi":"10.21203/rs.3.rs-9357369/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-05-06T14:55:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-14T07:54:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-13T14:32:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-13T14:31:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-04-08T12:51:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3fbb447e-9ae4-48d9-948e-3ec84194bd5d","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewersInvited","content":"30","date":"2026-05-06T14:55:59+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T16:13:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 16:13:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9357369","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9357369","identity":"rs-9357369","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}