A Longitudinal Cohort Study of Precocious Puberty and Autism Spectrum Disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is defined by persistent deficits in communication, socialization, and stereotypic behaviors. It was previously hypothesized that hormone dysfunction is a frequent occurrence among children diagnosed with an ASD. OBJECTIVES: A hypothesis-testing epidemiological study examined the relationship between precocious puberty (PP) (a known disorder of childhood sex hormone dysfunction) and ASD diagnoses. METHODS: The Independent Healthcare Research Database is composed of de-identified linked eligibility and claims health-care records prospectively generated from the Florida Medicaid system. A cohort of 101,736 children eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth were examined using SAS and StatsDirect software. There were 1,593 children (15,738 person-years) in the ASD diagnosed cohort utilizing the Diagnostic and Statistical Manual of Mental Disorders, 4th revision criteria (the International Code for Disease, 9th revision [ICD-9] codes: 299.00 or 299.80) and 100,143 children (996,835 person-years) in the undiagnosed cohort. RESULTS: The incidence rate of PP (ICD-9 code: 259.1) was examined using Cox proportional hazards ratio (HR) and frequency models. PP per 10,000 person-years in the ASD cohort (43.2) relative to the undiagnosed cohort (13.7) was significantly increased in frequency modeling (risk ratio = 3.15, p < 0.0001) and Cox proportional HR modeling (adjusted HR = 4.64, p < 0.0001). Further analyses revealed the incidence rate of PP diagnosed after 3 years of age was significantly increased (adjusted HR = 5.16, p < 0.0001) in the ASD cohort relative to the undiagnosed cohort but not for the incidence rate of PP diagnosed before 3 years (adjusted HR = 1.57, p = 0.44). CONCLUSION: This hypothesis-testing study provides strong evidence of an increased incidence rate of PP among children diagnosed with an ASD.

Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

Sexual maturity assessment in Indian children-a study from western India.

OBJECTIVES: Pubertal assessment is crucial as puberty is the transition from childhood to adulthood. Pubertal assessment, growth, and secular trend in puberty need to be explored further in India. The objectives were to assess Sexual Maturity Rating (SMR) among children and establish normative data of puberty from western India. We also compared age of attainment of various stages of puberty with BMI and secular trend in menarche. METHODS: A cross-sectional observational study was undertaken at a tertiary care pediatric center. The study population were healthy girls and boys between 6 and 18 years. Demographic data was noted. Anthropometry and SMR assessment (Tanner staging) were performed. The age of menarche was noted among the girls and their mothers. Data were analyzed using SPSS 21. RESULTS: In girls, median age of thelarche, pubarche, and menarche was 9.37 (8.5-10.2), 10.18 (9.87-10.49), and 12.55 years (12.41-12.75) respectively. There was an early appearance of thelarche but menarche was delayed in overweight-obese girls (statistically not significant). Age of menarche showed a shift to left in girls as compared to their mothers (p=0.036). In boys, median age of testicular stage 2 and pubarche was 10.7 (9.9-11.8) and 11.6 years (11.1-12.1) respectively. In overweight-obese boys the pubertal milestones were achieved earlier (statistically not significant). CONCLUSIONS: Normative data on pubertal assessment from western India is presented. Age of menarche shows a shift to left in girls as compared to their mothers. Pubertal milestones were observed at a younger age in overweight obese children which was not significant.

Is menarche occuring earlier among Lebanese girls?

BACKGROUND: Early menarche is associated with increased risks for several diseases such as cardiovascular diseases and breast cancer. This analysis aimed at generating evidence on a historical trend towards younger age at menarche among Lebanese girls. METHODS: A secondary analysis was conducted on data consolidated from three serial cross-sectional national surveys of women in Lebanon (2007, 2009 and 2012). A total of 6150 women were included in order to study the association between date of birth intervals and age at menarche. RESULTS: The mean age at menarche was 13.06 years, with a peak of the distribution at age 12. Women born before 1950 had a significantly higher mean age at menarche (13.21) compared to those born in 1970 and thereafter (12.95). A stratified analysis showed that women living outside the metropolitan Greater Beirut (GB) area were characterized by an older mean age at menarche (13.11) in all date of birth intervals compared to those in GB (12.89). However, age at menarche declined more significantly over the last two decades among women outside GB, compared to those living in GB. CONCLUSIONS: Epidemiological figures emerging from this study confirm that trends in Lebanon are in line with a global pattern of decreasing age at menarche. Urban-rural differences suggest that higher caloric content of diet and consequent early overweight, more evident in urban areas, are likely determinants of younger menarche. Evidence from this study calls for an urgent implementation of comprehensive multisectoral obesity prevention in children in Lebanon.

Incidence and Prevalence of Central Precocious Puberty in Korea: An Epidemiologic Study Based on a National Database.

OBJECTIVES: To investigate the prevalence and incidence of central precocious puberty in Korea using claims data provided by the Health Insurance Review and Assessment Service in Korea as the population-based epidemiologic study. STUDY DESIGN: In this national registry-based, longitudinal, epidemiologic study, patients who were registered with an International Classifications of Diseases, Tenth Revision diagnosis of central precocious puberty (E22.8 according to International Classifications of Diseases, Tenth Revision) and treated with gonadotropin-releasing hormone agonist were included. We assessed the age- and sex-specific prevalence and incidence rates of central precocious puberty in Korea from 2008 to 2014. RESULTS: A total of 37 890 girls and 1220 boys were newly registered with a diagnosis of central precocious puberty from 2008 to 2014. The overall incidence of central precocious puberty during the study period was 122.8 per 100 000 persons (girls, 262.8; boys, 7.0). The overall prevalence of central precocious puberty during the study period was 193.2 per 100 000 persons (girls, 410.6; boys, 10.9). The incidence and prevalence of central precocious puberty steeply increased during the study period in both girls and boys. CONCLUSIONS: This epidemiologic study, based on a national registry that included Korean children, demonstrated that the incidence and prevalence rates of central precocious puberty were high and increased steeply during the study period. Further investigations to determine the underlying causes for this rapid increase in central precocious puberty are needed.

[Risk assessment in young people living in Bobo Dioulasso: analysis of factors associated with sexual precocity and multiple partners]. / Prises de risques chez les jeunes de Bobo Dioulasso: une analyse des facteurs associés à la précocité et au multipartenariat sexuel.

INTRODUCTION: Despite health education efforts, young people continue to adopt risky sexual behaviors which may have a significant impact on their health. This study aims to analyze the factors associated with sexual precocity and multiple partners among young people aged 19-24 years living in Bobo-Dioulasso. METHODS: We conducted a quantitative, cross-sectional study. Survey data were collected from 573 young people aged 15-24 years in Bobo-Dioulasso (Burkina Faso) in December 2014. The respondents were selected using two stages cluster sampling. Risk factors for sexual precocity and multiple partners were analyzed using Stata 13 IC software. We used P<0.05 as the significance level. RESULTS: More than half of respondents (54%) were sexually active, of whom 14% before the age of 16. Having multiple sex partners was reported by 24% of sexually active youth. Determinants of sexual precocity and multiple partners were age, sex, level of education and economic status of parents. Our data have also shown that early sexual debut was associated with multiple sexual partners (p<0.005). CONCLUSION: Actions aimed to convince young people to delay sexual debut and to better assess risks are of utmost importance. Enhancing parents, teachers and carers capabilities is essential to improve the quality of their relationships with young people.

Medical resource use and costs related to central precocious puberty: a retrospective cohort study.

OBJECTIVE: To evaluate the economic burden of central precocious puberty (CPP) by examining direct health care resource utilization and costs. METHODS: Administrative claims from the Medstat MarketScan Commercial Claims database were analyzed, and 2 cohorts of children ≤ 12 years of age were identified. The CPP cohort included patients newly diagnosed with precocious sexual development and puberty (International Classification of Diseases, Ninth Revision, Clinical Modification code 259.1x) between January 1, 2004, and June 30, 2006 (date of the initial diagnosis of CPP was designated as the "index date") who used gonadotropin-releasing hormone agonists during the 12 months after diagnosis. Each patient with CPP was matched with 4 control patients without CPP on the basis of age, sex, geographic region, and type of health insurance plan. Resource utilization and costs during the 12 months before and the 12 months after the index date were examined. RESULTS: A total of 172 patients with CPP and 688 control patients were identified after matching. Approximately 62% of patients were 7 to 9 years of age, and 87% were female. The patients with CPP had higher annual health care costs than did the control patients during the 12-month pre-index ($10,968 versus $783; P<.001) and the 12-month post-index ($21,071 versus $849; P<.001) periods, primarily attributable to outpatient and pharmacy costs. For the patients with CPP, annual health care costs increased by $10,103 after diagnosis. On average, annual CPP-related costs were $10,605. Monthly total health care costs for the patients with CPP increased sharply during the first month after diagnosis and remained high throughout the post-index period. CONCLUSION: In this study, health care resource use and costs among patients with CPP were substantial before and after the initial diagnosis of CPP.

Effects of growth environments and two environmental endocrine disruptors on children with idiopathic precocious puberty.

OBJECTIVE: The incidence of idiopathic precocious puberty (IPP) might have an increasing trend. But the causes and risk factors of IPP are unknown. The objective of our study is to evaluate the effects of growth environments and two environmental endocrine disruptors (EDCs), zearalenone (ZEA), and 1,1-dichloro-2,2,bisethylene (p,p'-DDE), on patients with IPP. DESIGN: Case-control study. METHODS: The study consisted of 78 IPP patients at diagnosis and 100 control children matched for age and sex. A questionnaire was designed to collect data on growth environments, and serum ZEA and p,p'-DDE were tested in all subjects. We analyzed data on growth environments, two EDCs, and biological interaction between growth environments and EDCs. RESULTS: In growth environments, small for gestational age, maternal physical disease during pregnancy, early maternal menarche, early puberty of same-degree relatives, and father's absence in 4- to 6-year olds were risk factors for children with IPP (P<0.05). Serum ZEA concentration, ZEA, and p,p'-DDE-positive rates in the IPP group were significantly higher than those in the control group (P<0.05). There was a biological interaction between growth environments and ZEA (relative excess risk due to interaction =34.562, attributable proportion due to interaction =0.745, synergy index =4.193). CONCLUSIONS: Results suggest possible effects of growth environments and two EDCs on the development of IPP. In addition, growth environments and ZEA have biological interaction that might increase the risk of developing IPP.

Assessment of pubertal development in Egyptian girls.

Puberty is a significant event of human growth and maturation associated with marked physiological and psychological changes. The aim of this study was to assess normal pubertal development in Egyptian girls to define normal, precocious and delayed puberty. The present study included a cross-sectional sample of 1,550 normal Egyptian girls of high and middle socioeconomic class living in Cairo. Their ages ranged from 6.5 to 18.5 years. Pubertal assessment was made according to Tanner staging. The mean menarcheal age (MMA) was estimated using probit analysis. Weight and height were measured and body mass index (BMI) was calculated. The mean age at breast bud stage (B2) was 10.71+/-1.6, pubic hair stage (PH2) was 10.46+/-1.36, while axillary hair stage (A2) was 11.65+/-1.62 and MMA was 12.44 years. The mean age at attainment of puberty was compared with those of other Egyptian studies and other populations. Girls of the present study started pubertal development and achieved menarche earlier than those of previous Egyptian studies confirming a secular trend. Differences between the present study and other worldwide studies can be attributed to various genetic, racial, geographical, nutritional, and secular trend factors.

Environmental factors influencing growth and pubertal development.

Postnatal growth is based on hereditary signals and environmental factors in a complex regulatory network. Each factor must be in an optimal state for normal growth of the child. Fetal conditions may also have consequences on postnatal height. Intrauterine growth retardation can be recovered postnatally, although postnatal growth remains depressed in about one-third of cases. After birth, the environment may exert either a positive or negative effect on growth. In underdeveloped countries, malnutrition plays a major role in inhibiting the growth process. Children from families of higher socioeconomic classes are taller than their coevals in the lower socioeconomic groups. Urbanization also has a positive effect on growth. Better child care is supported by sufficient food supply, appropriate health and sanitation services, and a higher level of education. Over the last century, these factors have induced a taller stature and a more rapid maturity in Europe, North America, and Australia; a phenomenon which has been referred to as "the secular trend" in growth. Recently, a secular trend has also been reported in some developing countries. Although urbanization in general appears to be associated with better conditions of living, this is not the case in the slums of South America or in Africa where rural children are better off than children living in the poor cities. This paper describes in more detail the different hereditary and environmental factors that act during the fetal period and postnatally, and which play a role in human growth and pubertal development.