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Frontiers in Endocrinology 2021The gonadotropin-releasing hormone (GnRH) stimulation test is the benchmark for diagnosing precocious puberty (PP). However, it is invasive, time-consuming, costly, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The gonadotropin-releasing hormone (GnRH) stimulation test is the benchmark for diagnosing precocious puberty (PP). However, it is invasive, time-consuming, costly, and may create an unpleasant experience for participants. Moreover, some overlaps may occur between PP and premature thelarche (PT) in the early stage of PP. Female pelvic ultrasonography may provide additional information to help differentiate PP from PT and subsequently initiate early treatment. In this study, we aimed to first directly compare pelvic ultrasonography parameters between PP and PT groups and secondly, investigate their diagnostic accuracy compared with the GnRH stimulation test.
METHODS
A systematic search of the PubMed/MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed up to March 31, 2021. All types of studies, except for case reports and review articles, were included. The GnRH stimulation test was used to confirm PP diagnosis. Those whose organic conditions might cause PP were excluded. The mean, standard deviation, sensitivity, and specificity of each parameter were documented. Forest plots were constructed to display the estimated standardized mean differences (SMDs) from each included study and the overall calculations. A bivariate model was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR).
RESULTS
A total of 13 studies were included for analysis. The SMDs (95% confidence interval - CI) in ovarian volume, fundal-cervical ratio, uterine length, uterine cross-sectional area, and uterine volume between PP and PT groups were 1.12 (0.78-1.45; p < 0.01), 0.90 (0.07-1.73; p = 0.03), 1.38 (0.99-1.78; p < 0.01), 1.06 (0.61-1.50; p < 0.01), and 1.21 (0.84-1.58; p <0.01), respectively. A uterine length of 3.20 cm yielded a pooled sensitivity of 81.8% (95% CI 78.3%-84.9%), specificity of 82.0% (95% CI 61.0%-93.0%), PLR of 4.56 (95% CI 2.15-9.69), NLR of 0.26 (95% CI 0.17-0.39), and DOR of 19.62 (95% CI 6.45-59.68). The area under the summary receiver operating characteristics curve was 0.82.
CONCLUSION
Female pelvic ultrasonography may serve as a complementary tool to the GnRH stimulation test in differentiating PP from PT.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232427, ID: CRD42021232427.
Topics: Child; Diagnosis, Differential; Female; Humans; Puberty, Precocious; Sensitivity and Specificity; Ultrasonography; Uterus
PubMed: 34539579
DOI: 10.3389/fendo.2021.735875 -
PloS One 2021The objective of this systematic review was to evaluate the association between a soy-based infant diet and the onset of puberty. We included studies in which children... (Meta-Analysis)
Meta-Analysis
The objective of this systematic review was to evaluate the association between a soy-based infant diet and the onset of puberty. We included studies in which children were fed a soy-based diet, and we compared them with those who were not. The primary outcomes were the onset of puberty in girls (thelarche, pubarche, and menarche age), boys (pubarche, voice change, testicular and penis enlargement age), and both (risk of delayed and precocious puberty [PP]). Search strategies were performed in PubMed, Embase, LILACS, and CENTRAL databases. Two reviewers selected eligible studies, assessed the risk of bias, and extracted data from the included studies. The odds ratio (OR) and mean difference (MD) were calculated with a 95% confidence interval (CI) as a measure of the association between soy consumption and outcomes. We used a random-effects model to pool results across studies and the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the certainty of evidence. We included eight studies in which 598 children consumed a soy-based diet but 2957 did not. The primary outcomes that could be plotted in the meta-analysis were the risk of PP and age at menarche. There was no statistical difference between groups for PP (OR: 0.51, 95% CI: 0.09 to 2.94, 3 studies, 206 participants, low certainty of evidence). No between-group difference was observed in menarche age (MD 0.14 years, 95% CI -0.16 to 0.45, 3 studies, 605 children, low certainty of evidence). One study presented this outcome in terms of median and interquartile range, and although the onset of menarche was marginally increased in girls who received a soy-based diet, the reported age was within the normal age range for menarche. We did not find any association between a soy-based infant diet and the onset of puberty in boys or girls. Trial Registration: PROSPERO registration: CRD42018088902.
Topics: Child, Preschool; Databases, Factual; Diet; Female; Humans; Infant Food; Infant, Newborn; Male; Menarche; Puberty; Soy Foods
PubMed: 34003856
DOI: 10.1371/journal.pone.0251241 -
Hormone Research in Paediatrics 2020Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. Premature activation of GnRH secretion leads to idiopathic/central gonadotropin-dependent precocious puberty (CPP). We aimed to compare the blood KP concentrations in girls with CPP and healthy controls.
METHODS
A systematic review and meta-analysis was performed. We searched MEDLINE, EMBASE, The Cochrane Library, and SciELO. Random-effects model and standardized mean difference (SMD) were used. Heterogeneity was assessed through I2. Meta-regression considered patient age, KP fraction, and analytical method for KP measurement.
RESULTS
The 11 studies included comprised 316 CPP patients and 251 controls. Higher KP levels in the CPP group were found (SMD 1.53; CI 95% = 0.56-2.51). Subgroup analysis revealed association with patient age (p = 0.048), indicating a positive correlation between elevation in KP concentration and age in CPP group. A group of patients with precocious thelarche (PT) from 5 of the included studies comprising 121 patients showed higher levels of KP (1.10; -0.25-2.45: CI 95%) and high heterogeneity (I2 = 91%). The CPP/PT ratio for KP level indicates KP 36% higher on CPP than PT patients.
CONCLUSIONS
A consistent difference in KP levels between girls with CPP and controls was identified. While there are important limitations in KP assays which argue against its use as a diagnostic tool, the KP levels in CPP versus control and PT children are consistent with the predicted mechanisms and pathophysiology of CPP.
Topics: Case-Control Studies; Child; Female; Humans; Kisspeptins; Puberty, Precocious
PubMed: 33887744
DOI: 10.1159/000515660 -
Clinical Endocrinology May 2021To investigate the long-term efficacy and safety of gonadotropin-releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP). (Meta-Analysis)
Meta-Analysis
Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis.
OBJECTIVE
To investigate the long-term efficacy and safety of gonadotropin-releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP).
METHOD
The protocol was registered with International Prospective Register of Systematic Reviews (CRD42018102792). PubMed, EMBASE and the Cochrane Library were searched for eligible comparative and single-arm studies.
RESULTS
We identified a total of 98 studies that included 5475 individuals. The overall risk of bias of the eligible studies ranged from critical to moderate. The overall quality of evidence for each outcome ranged from very low to moderate. Evidence-based comparative studies showed that GnRHa treatment increase final adult height (FAH, cm; studies = 4, n = 242; mean difference [MD] = 4.83; 95% confidence interval [CI], 2.32 to 7.34; I = 49%) and decrease body mass index (BMI, kg/m ; studies = 3, n = 334; MD = -1.01; 95% CI, -1.64 to -0.37; I = 0%) in girls with idiopathic CPP compared with no treatment. The incidence of polycystic ovary syndrome (PCOS) did not significantly differ with and without GnRHa treatment (studies = 3, n = 179; risk ratio = 1.21; 95% CI, 0.46 to 3.15; I = 48%). The evidence for other long-term outcomes was very weak to deduce the effects of GnRHa treatment. Further, limited evidence is available on its effects in boys.
CONCLUSION
Compared with no treatment, evidence indicates that GnRHa treatment increase FAH and decrease BMI in girls with idiopathic CPP. GnRHa treatment did not evidently increase the risk of PCOS. However, evidence regarding other key long-term outcomes (such as infertility and malignant or metabolic diseases) was considered very weak to suggest the benefits or side effects of GnRHa treatment. Additional high-quality evidence is needed before firm conclusions can be drawn.
Topics: Body Height; Child; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty, Precocious
PubMed: 33387371
DOI: 10.1111/cen.14410 -
JAMA Pediatrics Apr 2020The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first menstruation) to assess secular trends of pubertal timing, no systematic review has been conducted of secular trends of thelarche.
OBJECTIVES
To systematically evaluate published data on pubertal timing based on age at thelarche and evaluate the change in pubertal onset in healthy girls around the world.
DATA SOURCES
A systematic literature search was performed in PubMed and Embase of all original peer-reviewed articles published in English before June 20, 2019.
STUDY SELECTION
Included studies used clinical assessment of breast development in healthy girls and used adequate statistical methods, including the reporting of SEs or CIs. The quality of the articles was evaluated by assessing study design, potential sources of bias, main characteristics of the study population, and methods of statistical analysis.
DATA EXTRACTION AND SYNTHESIS
In accordance with PRISMA guidelines, all articles were assessed for eligibility independently by 2 authors. Weighted regression analysis was performed using a random-effects model.
MAIN OUTCOMES AND MEASURES
Studies examining age at thelarche (development of Tanner breast stage 2) in healthy girls.
RESULTS
The literature search resulted in a total of 3602 studies, of which 30 studies fulfilled the eligibility criteria. There was a secular trend in ages at thelarche according to race/ethnicity and geography. Overall, the age at thelarche decreased 0.24 years (95% CI, -0.44 to -0.04) (almost 3 months) per decade from 1977 to 2013 (P = .02).
CONCLUSIONS AND RELEVANCE
The age at thelarche has decreased a mean of almost 3 months per decade from 1977 to 2013. A younger age at pubertal onset may change current diagnostic decision-making. The medical community needs current and relevant data to redefine "precocious puberty," because the traditional definition may be outdated, at least in some regions of the world.
Topics: Adolescent; Age Factors; Breast; Child; Female; Humans; Puberty
PubMed: 32040143
DOI: 10.1001/jamapediatrics.2019.5881 -
Developmental Medicine and Child... Dec 2019To evaluate neuropsychiatric comorbidities in children and adolescents with hypothalamic hamartoma.
AIM
To evaluate neuropsychiatric comorbidities in children and adolescents with hypothalamic hamartoma.
METHOD
We retrospectively analysed case notes for all individuals with hypothalamic hamartoma referred to Great Ormond Street Hospital, London, between 2000 and 2016. In addition, a systematic review aiming to identify all previous paediatric case series was performed. Psychiatric symptoms, demographics, physical comorbidities, and cognitive functioning were recorded for all cases where possible. Analyses were performed to determine which factors were associated with psychopathology and potential mechanisms investigated.
RESULTS
Forty-six cases were included in the case series (28 males, 18 females; mean age at assessment 11y 8mo [1y 11mo-16y 11mo, SD 4y 0mo]). Twenty-nine papers representing data from 264 cases met inclusion criteria for the systematic review. Overall, at least 50% of cases presented with psychopathology. Epilepsy, intellectual disability, and male sex were associated with externalizing disorders (attention-deficit/hyperactivity disorder, conduct and oppositional defiance disorders, and rage attacks). Intellectual disability mediated the effects of epilepsy on externalizing psychopathology. No factors were associated with internalizing disorders (anxiety and depressive disorders), although these were not well reported.
INTERPRETATION
Psychiatric comorbidities are highly prevalent in the presentation of paediatric hypothalamic hamartoma. The aetiology of psychopathology comprises a range of interacting biological and psychosocial factors with particular influence from epilepsy. Further research is required to achieve an evidence base for treatment.
WHAT THIS PAPER ADDS
Over half of children with hypothalamic hamartoma present with psychiatric comorbidity. Externalizing and internalizing disorders are present in approximately 60% and 30% of children with hypothalamic hamartomas respectively. Epilepsy and male sex are associated with externalizing psychopathology. Intellectual disability mediates the association between epilepsy and externalizing symptoms. No clear associations are evident for internalizing disorders or precocious puberty.
Topics: Adolescent; Child; Child, Preschool; Comorbidity; Epilepsy; Female; Hamartoma; Humans; Hypothalamic Diseases; Infant; Male; Mental Disorders; Sex Factors
PubMed: 30977116
DOI: 10.1111/dmcn.14241