Timing In Girls Research Articles

Prospective associations of mid-childhood plasma per- and polyfluoroalkyl substances and pubertal timing.

Exposure to per- and polyfluoroalkyl substances (PFAS) may disrupt pubertal timing. Higher PFAS plasma concentrations have been associated with later pubertal timing in girls, but cross-sectional findings may be explained by reverse causation. To assess prospective associations between PFAS plasma concentrations in mid-childhood and markers of pubertal timing in male and female adolescents. We studied 640 children in Project Viva, a Boston-area prospective cohort. We examined associations of plasma concentrations of 6 PFAS measured at mean 7.9 (SD 0.8) years (2007-2010) with markers of pubertal timing. Parents reported a 5-item pubertal development score at early adolescence (mean 13.1 (SD 0.8) years) and reported age at menarche annually. We calculated age at peak height velocity using research and clinical measures of height. We used sex-specific linear and Cox proportional hazards regression to estimate associations of single PFAS with outcomes, and we used Bayesian Kernel Machine Regression (BKMR) to estimate associations of the PFAS mixture with outcomes. Plasma concentrations were highest for perfluorooctane sulfonate (PFOS) [median (IQR) 6.4(5.6) ng/mL], followed by perfluorooctanoate (PFOA) [4.4(3.0) ng/mL]. In early adolescence, girls were further along in puberty than boys [pubertal development score mean (SD) 2.9 (0.7) for girls and 2.2(0.7) for boys; age at peak height velocity mean (SD) 11.2y (1.0) for girls and 13.1y (1.0) for boys]. PFAS was associated with later markers of pubertal timing in girls only. For example, each doubling of PFOA was associated with lower pubertal development score (-0.18 units; 95% CI: -0.30, -0.06) and older age at peak height velocity (0.23years; 95% CI: 0.06, 0.40)]. We observed similar associations for PFOS, perfluorodecanoate (PFDA), and the PFAS mixture. PFAS plasma concentrations were not associated with age at menarche or markers of pubertal timing in boys. Higher PFAS plasma concentrations in mid-childhood were associated with later onset of puberty in girls.

Trajectories of participation, mental health, and mental health problems in adolescents with self-reported neurodevelopmental disorders

Purpose Having a neurodevelopmental disorder (NDD) increases the risk of mental health problems and lower participation. We investigated the trajectories of mental health problems and participation in adolescents with NDD and compared these with trajectories for peers without NDD. In addition, the relationship between participation, mental health (well-being), and mental health problems were investigated. Materials and methods Data from a Swedish longitudinal survey study (LoRDIA) was used and adolescents with and without self-reported NDD were followed from 12/13 to 17 years, in three waves. Mental health problems were measured using the Strength and Difficulties Questionnaire, and well-being was measured with the Mental Health Continuum short form. Results Adolescents with NDD experience more mental health problems than adolescents without NDD. Hyperactivity, a key feature of NDD, remains stable, while emotional problems and psychosomatic complaints, increase over time for girls, independent of NDD. Participation is stable over time but is more related to well-being than to NDD or mental health problems. Conclusions Gender is an important factor with girls exhibiting more problems. Mental health explains more of the variation in participation than mental health problems and NDD. Probably participation intervention can enhance mental health which may protect from mental health problems. Implications for rehabilitation Mental health, i.e., emotional-, social-, and psychological well-being is more strongly related to participation and to reduced levels of mental health problems than having an NDD or not, thus assessing mental health separately from measuring NDD is important. Interventions focusing on participation may lead to higher mental health and having high mental health (flourishing) may facilitate participation. Girls with self-reported NDD seem to have a higher burden of mental health problems, especially if they also are languishing, i.e., having low mental health, therefore a strong focus on this group is needed both in research and clinical practice. Half of all adolescents are flourishing, independently of NDD or not, even if they are experiencing some symptoms of mental health problems, adolescents with NDD who are also languishing, have much higher ratings of mental health problems.

Prepubertal Dietary and Plasma Phospholipid Fatty Acids Related to Puberty Timing: Longitudinal Cohort and Mendelian Randomization Analyses.

Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid FAs with several puberty timing traits in boys and girls. In the Avon Longitudinal Study of Parents and Children, prepubertal fat intakes at 3–7.5 years and plasma phospholipid FAs at 7.5 years were measured. Timings of Tanner stage 2 genital or breast development and voice breaking or menarche from repeated reports at 8–17 years, and age at peak height velocity (PHV) from repeated height measurements at 5–20 years were estimated. In linear regression models with adjustment for maternal and infant characteristics, dietary substitution of polyunsaturated FAs for saturated FAs, and higher concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier timing of puberty traits in girls (n = 3872) but not boys (n = 3654). In Mendelian Randomization models, higher genetically predicted circulating dihomo-γ-linolenic acid was associated with earlier menarche in girls. Based on repeated dietary intake data, objectively measured FAs and genetic causal inference, these findings suggest that dietary and endogenous metabolic pathways that increase plasma dihomo-γ-linolenic acid, an intermediate metabolite of n-6 polyunsaturated FAs, may promote earlier puberty timing in girls.

The Relationship of Early Adiposity Rebound With Accelerated Bone Age and Breast Development in Girls: A Prospective Cohort Study

Abstract Introduction: Adiposity rebound (AR) refers to the increase in body mass index (BMI) that follows the BMI nadir in childhood. Earlier AR increases the likelihood of being overweight/obese and may lead to early pubertal advancement, especially in girls. We aimed to evaluate the longitudinal changes in anthropometrics, bone age (BA), and breast development in relation to AR timing in girls. Methods: This study included girls (n = 349) of the Environment and Development of Children (EDC) cohort, a prospective cohort of healthy children started in 2012 with biennial visits to study the effects of environmental exposures on physical and neurobehavioral development. The BMI trajectories of girls with 3 or more measurements between 2 and 8 years of age (n = 242) were visually inspected to determine AR timing. After excluding preterm and multiple births, 204 girls were included and categorized according to the age at AR: group 1 (<3.9 years; n = 34, 17%), group 2 (3.9-5.9 years; n = 55, 27%) and group 3 (≥6 years; n = 115, 56%). AR groups were compared for differences in anthropometric measures, BA progression, and breast development. The relationships between AR and outcomes were analyzed with adjustment for age, gestational age, birthweight, physical activity and diet. Results: At age 2, there were no differences in anthropometric measures. By age 4, group 1 showed higher mean BMI z-scores (0.87) than groups 2 (-0.19) and 3 (-0.45) (P <0.001). The differences in BMI z-scores were significant between all 3 groups at 6 and 8-years (P <0.001, for all). Height differences became significant at 8-years (P = 0.010), with greater mean height z-score in group 1 (0.80) compared to group 3 (0.30). BA progression differed significantly between groups 1, 2 and 3 at 6-years (BA 6.87 vs. 6.44 vs. 6.36 years respectively; P < 0.001) and at 8-years (BA 9.65 vs. 8.82 vs. 8.60 respectively; P < 0.001). The inverse relationship between AR timing and BA remained significant after adjusting for covariates at 6 years (B = -0.222, P = 0.040) and 8 years (B = -0.468, P <0.001). Breast development occurred in 49 girls (24%) by age 8 with increased occurrence in the earlier AR groups: group 1 (n = 16, 47%), group 2 (n = 17, 31%), and group 3 (n = 16, 14%) (P for trend <0.001). When compared to group 3, the earlier AR groups had significantly increased risk of breast development at age 8 (OR 5.1, 95%CI 2.1-12.4 for group 1 and OR 2.4, 95%CI 1.1-5.4 for group 2, P <0.001 for both), after adjusting for covariates (P <0.05, for both). Conclusions: Girls who had earlier AR showed greater BA progression starting at 6 years and continuing at 8 years along with greater height at 8 years. These girls are at risk for early breast development after adjustment for covariates. AR timing may be a predictor for BA progression and onset of breast development in girls.

Family Experiences and Parent Personality as Antecedents of Pubertal Timing in Girls and Boys.

Pubertal timing may be influenced by typical variations in early family environmental events, but questions remain concerning the roles of specific parenting factors, developmental age of exposure to events, moderation by child temperament, and comparability of effects for girls and boys. This study focused on these questions utilizing longitudinal data from 733 same-sex twins (45% girls) in the U.S.; family context was measured at ages 1-3, 4-5, and 6-7 years and pubertal status was assessed annually via self-report at ages 9-15, enabling estimates of pubertal timing. Home environment at ages 4-5 years predicted pubertal timing better than home environment at other ages for both girls and boys, but parent personality was more predictive than home experiences (e.g., divorce, parental harshness, family conflict). Thus, effects of family environment must be considered within the context of parent characteristics, encouraging caution in implicating early environmental experiences as direct influences on early pubertal timing.

Effect of COVID-19-Related Home Confinement on Sleep Quality, Screen Time and Physical Activity in Tunisian Boys and Girls: A Survey.

COVID-19 home confinement has led to a stressful situation for children around the world and affected their lifestyle. The present study aimed to investigate the effect of these restrictions on sleep quality, screen time (ST) and physical activity (PA) in Tunisian children with a special focus on gender differences. An online survey was launched in April 2020. Questions were presented in a differential format, with expected responses related to “before” and “during” confinement. Participants (52 boys and 48 girls, age: 8.66 ± 3.3 years) responded to the Pittsburgh Sleep Quality Index (PSQI), the digital media use, and the Ricci and Gagnon sedentary behavior questionnaires. Findings revealed that COVID19 home confinement had a negative effect on all the considered parameters (p < 0.05). Significant effects of gender were found on sleep disturbances (p = 0.016, np2 = 0.05), subjective sleep quality (p < 0.01, np2 = 0.07), global score of PSQI (p = 0.01, np2 = 0.01) and nocturnal and global screen time (p < 0.001, np2 = 0.09) with poorer sleep and higher screen time in girls compared to boys during home confinement. A significant correlation was shown between Global ST and PSQI score (r = 0.39, p < 0.001). Programs of PA for children and sensitization campaigns against the use of screens have been deemed urgent with special focus oriented to girls.

Exposure to non-persistent pesticides and puberty timing: a systematic review of the epidemiological evidence

Numerous modern non-persistent pesticides have demonstrated estrogenic/anti-androgenic activity and have been classified as endocrine-disrupting chemicals (EDCs). Processes involved in puberty development are vulnerable to EDCs, such as compounds that interfere with the metabolism or activity of sex steroids. To conduct a systematic review of epidemiological studies on the relationship between early-life exposure to non-persistent pesticides and puberty timing and/or sexual maturation in girls and boys. A systematic search was carried out using MEDLINE and SCOPUS databases, including original articles published up to November 2020. Thirteen studies were selected after excluding non-original and non-human studies. Exposure to different types of pesticides has been associated with altered puberty timing in girls and/or boys in eight studies. In utero exposure to atrazine has been related to earlier age of menarche in girls; exposure to organophosphate (OP) pesticides has been related to delayed sexual development in boys and girls; childhood pyrethroid exposure has been associated with pubertal delay in girls and pubertal advancement in boys; and prenatal/childhood exposure to multiple pesticides has been linked to earlier puberty onset in girls and pubertal delay in boys. Most of the reviewed studies describe a relationship between pesticide exposure and changes in the age of puberty onset or sex hormone levels, although the quality of the evidence is generally low. Further well-designed longitudinal studies are warranted on specific classes of pesticides and on possible interactions between different types of compounds.

Prospective links between acculturative stress and academic well-being among Latinx adolescents

Two salient domains of acculturative stress, bicultural stress and English competency pressures, were examined as predictors of academic well-being, including grades, educational expectations, and academic identity over a one-year period using a heterogeneous sample of 329 Latinx youth (MTime1age = 13.67, SD = 0.57; 51% boys). The buffering effects of coping and school belonging were tested along with an exploration of the moderating roles of adolescent gender and nativity. Higher levels of bicultural stress were associated with lower levels of academic well-being over time for girls, whereas English competency pressures had nuanced relations to changes in academic well-being over time that were qualified by gender and nativity. Active coping was a protective factor in links between bicultural stressors and GPA; but, its effect on relations between English competency pressures and academic well-being was more nuanced, only present for foreign-born youth. School belonging did not emerge as a significant protective factor for Latinx youth.

Revisiting the critical weight hypothesis for regulation of pubertal timing in boys

ABSTRACTBackgroundRecent findings indicate that there is a body weight–sensing homeostatic regulation of body weight in postpubertal rodents and humans. It is possible that body weight sensing also might be involved in the regulation of pubertal timing. Although an early small study suggested that there is a critical body weight for pubertal timing in girls, most studies have focused on BMI and reported an inverse association between BMI and pubertal timing.ObjectivesIn the present longitudinal well-powered cohort study, we revisited the critical weight hypothesis and tested if prepubertal body weight is a more robust inverse predictor of pubertal timing than prepubertal BMI in boys.MethodWe included men born during 1945–1961 (old cohort; n = 31,971) and men born during 1981–1996 (recent cohort; n = 1465) in the large BMI Epidemiology Study (BEST) Gothenburg (combined BEST cohort n = 33,436). Men with information on prepubertal body weight and BMI at 8 y of age and age at peak height velocity (PHV; an objective measure of pubertal timing) were included.ResultsBody weight explained more of the variance in age at PHV than BMI in both the old cohort and the recent cohort (combined cohort, body weight 6.3%, BMI 3.6%). Both body weight (β: −0.24 SD/SD increase in weight; 95% CI: −0.25, −0.23) and BMI (β: −0.18 SD/SD increase in BMI, 95% CI: −0.19, −0.17) were inversely associated with age at PHV but the association for body weight was significantly more pronounced than the association for BMI (P < 0.001).ConclusionsIn conclusion, prepubertal body weight is a more robust inverse predictor of pubertal timing than prepubertal BMI in boys. We propose that body weight sensing constitutes a feedback mechanism to regulate pubertal timing.

Does height and IGF-I determine pubertal timing in girls?

Pubertal timing is closely linked to growth regulated by the growth hormone/insulin-like factor (GH/IGF) axis that includes IGF-regulating factors such as pregnancy-associated plasma protein-A/A2 (PAPP-A/PAPP-A2) and stanniocalcin 2 (STC2). We investigated the association between height, IGF-I concentration, and PAPPA, PAPPA2, and STC2 genotypes on the timing of female pubertal milestones. Height, IGF-I, and genotypes were analyzed in 1382 Danish girls from the general population, 67 patients with tall stature (height ≥2 SD), and 124 patients with short stature (height ≤-2 SD). The main outcomes were breast stage and menarche. Thelarche occurred significantly earlier in patients with tall stature (mean age 9.37 years [95% confidence interval (CI) 8.87-9.87]) and later in patients with short stature (11.07 years [95% CI 10.7-11.43]) compared with girls within the normal range (9.96 years [95% CI 9.85-10.07]) (p = 0.02 and p < 0.01, respectively). Girls with higher IGF-I levels experienced thelarche and menarche earlier compared with the rest of the cohort (p < 0.01). Genotypes were not associated with age at thelarche nor menarche, but the PAPPA2 minor allele carriers were shorter compared with major allele carriers, p = 0.03. Height and IGF-I, but not PAPP-A, PAPP-A2, and STC2 genotypes, were negatively associated with age at thelarche and menarche. Girls with tall and short stature enter puberty earlier and later compared with girls with normal height. Girls with higher insulin-growth factor-I in childhood enter puberty earlier. Pubertal timing is influenced by longitudinal growth and IGF-I levels earlier in childhood. Childhood growth and the levels of IGF-I in childhood may be biomarkers of pubertal timing.

Plasma concentrations of per- and polyfluoroalkyl substances and pubertal timing: A prospective analysis in Project Viva

Background/Aim Exposure to per- and polyfluoroalkyl substances (PFAS) may disrupt pubertal and adrenarchal timing. Animal and human studies have shown associations of prenatal PFAS exposure with delayed puberty in females; fewer studies have investigated childhood exposure. Methods We studied 636 children in Project Viva, a Boston-area prospective pre-birth cohort. We examined associations of plasma concentrations of 6 PFAS measured at mean 7.9 (SD 0.8) years (2006-2010) with markers of pubertal timing. At early adolescence (mean 13.1 (SD 0.8) years), parents reported pubertal signs (a 5-item pubertal development score) and children reported adrenarchal stage (pubic hair Tanner staging pictograph) on questionnaires. We calculated age at peak height velocity using research and clinical measures of height. We used sex-specific linear regression (for pubertal development score and age at peak height velocity) and ordinal logistic regression (for pubic hair staging) models, adjusted for demographic and socioeconomic factors. Results Plasma concentrations were highest for perfluorooctanesulfonic acid (PFOS) [median (IQR) 6.4(5.6) ng/mL], followed by perfluorooctanoate (PFOA) [4.4(3.0) ng/mL] and perfluorodecanoate (PFDA) [0.3(0.3) ng/mL]. Girls had earlier pubertal development than boys [pubertal development score mean (SD) 2.9(0.7) for girls and 2.2(0.7) for boys and age at peak height velocity mean(SD) 11.2(1.0) for girls and 13.1(1.0) for boys]. Girls with greater PFAS concentrations had delayed pubertal timing [e.g., each doubling of PFOA was associated with lower pubertal development score (-0.15 units; 95% CI: -0.29, -0.02) and older age at peak height velocity (0.29 years; 95% CI: 0.06, 0.51)], with strongest associations for PFOA, PFOS, and PFDA. Plasma PFAS concentrations were not associated with pubertal timing in boys or with adrenarchal timing in girls or boys.Conclusions In a large, prospective US cohort, higher plasma PFAS concentrations in mid-childhood were associated with later onset of puberty in girls, which may be a risk factor for infertility and osteoporosis.

Placental weight Z-score and pubertal timing: A population-based cohort study.

The placenta provides nutrients, oxygen, and hormonal support for adequate fetal growth and development of the hormonal axes, which are important for pubertal timing later in life. We investigated if an indicator of poor placental function, low gestational age-specific Z-score for placental weight at birth, was associated with earlier pubertal timing. The study is based on a population-based cohort of 15195 singleton boys and girls (68% of 22439 invited) born 20 to 43weeks of gestation (2000-2003) nested within the Danish National Birth Cohort. Placental Z-score was estimated from data collected at birth. Between 2012 and 2018, the children returned half-yearly web-based questionnaires from age of 11years on status of the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne, and axillary hair. We estimated adjusted monthly differences in mean age at attaining the pubertal milestones and pubertal timing overall with placental Z-score continuously and as restricted cubic splines. Further, we explored whether growth by birthweight Z-score and body mass index Z-score around 7years mediated the associations. Placental Z-score was positively associated with age at attaining most of the pubertal milestones in girls, particularly for age at menarche, but not in boys. Effect sizes were modest, and when combining all pubertal milestones, one standard deviation increase in placental Z-score was associated with 0.5months (95% confidence interval [CI] 0.2, 0.9) later pubertal timing overall in girls. The associations in girls were largely mediated through fetal growth. Assuming that placental Z-score correlates with placental function, these findings suggest that placental dysfunction (low placental Z-score) advances pubertal timing in girls slightly by reducing fetal growth. Future studies need to evaluate whether placental weight sufficiently captures intrauterine growth of importance for pubertal development and search for other potential candidates reflecting placental function.

Intra-grade variability in educational and psychosocial competencies of school going adolescent girls, in the coastal region of Kenya: implications for school based interventions

BackgroundThe onset of puberty and menarche is a potentially vulnerable time for girls. Educational and psychosocial competencies are regarded as essential tools that empower them to successfully navigate the adolescent years. The aim of this study is to evaluate to what extent school going girls are equipped with these key competencies, and how they vary across a given grade cohort.MethodsData was collected in Kilifi County, Kenya, from 140 public primary schools from grade 7, across three sub-counties. Bivariate and multivariate analyses were carried out to compare competency outcomes by age groups comprising 10–14 years and 15 year and above. Generalized estimating equations with robust standard errors was used where outcomes were measured as binary outcomes, and linear regression for continuous outcomes. Clustering was factored in at the school level and stratification at the subcounty level. Wilcoxon Rank sum test incorporating clustering effects was used where continuous outcomes were not normally distributed.ResultsA total of 3489 adolescent girls were interviewed with a mean age of 14 years (SD:1.5; min:10, max:21). Compared to the lower age group, girls in the higher age group were less likely to have ambitions of furthering their education beyond secondary school (odds ratio (OR):0.63 (95%CI:0.53, 0.74)), more likely to report not feeling confident enough to answer questions in class (OR:1.18 (95%CI:1.02, 1.36) and scored lower on their cognitive, math and literacy tests. They also displayed less positive gender norms (coefficient (coeff):-0.091 (95%CI:-0.16, − 0.022)) and were more likely to agree with intimate-partner violence in marriage (coeff:1.17 (95%CI:1.00, 1.37)). They however scored higher on the decision-making scale (coeff:0.36 (95%CI:0.13, 0.60)) and were more likely to be able to spontaneously name a method of modern contraception (OR:1.56 (95%CI:1.36, 1.80)).ConclusionLarge variability in age exits within a grade. Compared to older girls, younger girls were more likely to perform better on their educational and social competencies. In countries with large age ranges per grade, identifying the presence of educational and psychosocial competency variabilities will allow informed decisions to be made on how school-based interventions should be adapted to address the varying needs within a grade.Trial registrationISRCTN10894523, date of registration: 22/08/2017. Retrospectively registered.

Abstract A14: Infancy and childhood infections and pubertal timing in the LEGACY Girls’ Study

Abstract An earlier age at pubertal development is associated with increased breast cancer risk, and Westernized countries are observing earlier ages of pubertal timing in girls. While increased rates of childhood obesity are associated with earlier ages of pubertal development, earlier ages of puberty are also observed in countries that are not experiencing high rates of childhood obesity. Prior evidence from a birth cohort in Hong Kong suggests that early life infections, as measured by hospitalizations, is associated with pubertal onset. Emerging evidence suggests that early life and childhood exposures to infection may impact pubertal development. Therefore, we aimed to assess whether indirect measures of infections in infancy (birth-12 months) and early childhood (1-5 years) are associated with the age of onset of puberty (menarche and breast and pubic hair development). We used data from the Infection Questionnaire from the multisite prospective LEGACY Girls Study where mothers/guardians reported on daughters’ indirect exposure to infection (daycare attendance, antibiotic use, physician visit due to fever, hospitalization due to infection) and specific exposure to infections (e.g., tonsillitis, cold sores). Mothers/guardians reported on daughters’ age at first menses and the onset of breast and pubic hair development using Tanner Staging (as defined as Tanner Stage 2 or higher). We used Cox Proportional Hazard Ratio (HR) models to examine the prospective association between infection history and pubertal timing. We considered site, race/ethnicity, and maternal education as possible confounders. In 615 girls (average age (SD) 9.5 (2.4) years) whose mother/guardians completed the Infection Questionnaire, 65% were white non-Hispanic, 18% were Hispanic, 5% were Black non-Hispanic, and 9% were Asian. Sixty-nine percent of mothers/guardians had a college degree or higher. We assessed frequency of infectious exposures across infancy and early childhood where 73% of girls ever used antibiotics, 59% of girls ever had an ear infection, 59% of girls ever attended daycare over 10 hours per week, 29% of girls visited a physician due to fever (measured in childhood only), 36% of mothers reported girls having 2 or more infections, and 6% of girls were ever hospitalized due to infection. In multivariable models controlled for socioeconomic and maternal factors, earlier age of pubic hair development was associated with hospitalization due to infection compared to never hospitalized (HR=1.53, 95% CI=1.07-2.21) and ever antibiotic use compared to never antibiotic use (HR=1.31, 95% CI=1.03-1.68). Compared to never, multivariable models suggested that earlier age at menarche was associated with physician visit due to fever (HR=1.30, 95% CI=1.04-1.63). We observed no association between infectious exposures and earlier breast development. These results suggest that infancy and childhood infectious exposures may be related to earlier pubertal development, but more studies are needed to confirm these findings. Citation Format: Yun Huang, Irene L. Andrulis, Angela R. Bradbury, Saundra S. Buys, Mary B. Daly, Esther M. John, Lisa A. Schwartz, Mary Beth Terry, Jasmine A. McDonald. Infancy and childhood infections and pubertal timing in the LEGACY Girls’ Study [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A14.

Association of phthalate exposure with precocious and delayed pubertal timing in girls and boys: a systematic review and meta-analysis.

Exposure to phthalate derivatives has adverse effects on the health and development of humans, especially for children. A growing body of evidence supports the idea that exposure to phthalates can change an individual's physiological set point and the time of puberty in both genders. In this systematic review and meta-analysis, recent studies were evaluated to obtain systematic and regulation results in relation to puberty status and phthalate exposure in girls and boys. We searched English-language papers using Scopus, ISI, and PubMed databases as search engines, with no restriction of time, until the end of July 2019. A comprehensive literature search for an association between phthalate exposure and signs of puberty as well as levels of different types of hormones was carefully performed. Of the 67 studies retained for full-text screening, 39 studies were eligible for data management and extraction. For conducting a meta-analysis, four studies had appropriate effect size and metrics for pooling in the meta-analysis. Our findings revealed that low and high exposure to phthalates could alter pubertal development in both genders; the effects were either early or delayed puberty such as changes in the pubarche, thelarche, and menarche time, as well as in testicular volume. We statistically analyzed the association of pubic-hair development, breast development, and menarche time with exposure to phthalates in girls. For example, the pooled odds ratios of mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) in relation to breast development were (OR: 1.48, 95% CI: 1.11-1.85) and (OR: 1.52, 95% CI: 1.15-1.58) (P-value < 0.001), respectively. In addition, we analyzed the correlation between pubic-hair development and testicular volume with exposure to phthalates in boys. To the best of our knowledge, this is the first systematic review and meta-analysis of its kind for girls and boys. In conclusion, we found that a positive association exists between phthalate exposure and pubertal timing in the pediatric age group. Therefore, prevention of exposure to phthalates and reduction of their use should be underscored in the strategies for primordial prevention of pubertal timing and related consequences.

Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty.

Introduction Studies evaluating effects of gonadotropin-releasing hormone agonist (GnRHa) on weight and body-mass-index (BMI) in girls with idiopathic central precocious puberty (iCPP) include short-term effects. The aim of this study is to investigate changes in BMI during and 2 years after completion of GnRHa to determine the factors that may impact BMI in girls with iCPP. Methods Medical files of 138 girls who completed GnRHa were evaluated. All patients had weight and height measurements at the beginning and end of treatment, and 111 patients had anthropometric measurements 2 years after the completion of treatment. Results In the beginning, 82 (59.4%) had normal weight (NW), 42 (30.4%) were overweight (OW), and 14 (10.2%) were obese (OB). Analysis of BMI-standard deviation score (SDS) in the whole group showed an overall increase during GnRHa treatment (0.92 ± 0.74 vs. 1.20 ± 0.51, p < 0.001). Changes in BMI-SDS (ΔBMI-SDS) during GnRHa differed between NW and OW/OB (0.45 ± 0.31 vs. 0.03 ± 0.20, p < 0.001). BMI-SDSs of both groups returned to baseline scores (or initial levels) 2 years after the completion of treatment. Two factors affecting ΔBMI-SDS in multiple linear regression analyses were baseline BMI and Δheight-SDS, both correlated negatively with ΔBMI-SDS. Conclusions The present study is one of the studies evaluating BMI change over a long period of time in girls with CPP. Although BMI-SDS increased during GnRHa in NW girls, it was reversible in follow-up after treatment. However, BMI-SDS did not change during and in follow-up in OW/OB girls. Conserving BMI-SDS in OW/OB girls may be related to the fact that weight management programs were recommended for these patients. Dietary recommendations should be provided for children with NW who undergo GnRHa, as is the case for OW patients.

Brain Development in School-Age and Adolescent Girls: Effects of Turner Syndrome, Estrogen Therapy, and Genomic Imprinting

BackgroundThe study of Turner syndrome (TS) offers a unique window of opportunity for advancing scientific knowledge of how X chromosome gene imprinting, epigenetic factors, hormonal milieu, and chronologic age affect brain development in females. MethodsWe described brain growth trajectories in 55 girls with TS and 53 typically developing girls (258 magnetic resonance imaging datasets) spanning 5 years. Using novel nonparametric and mixed effects analytic approaches, we evaluated influences of X chromosome genomic imprinting and hormone replacement therapy on brain development. ResultsParieto-occipital gray and white matter regions showed slower growth during typical pubertal timing in girls with TS relative to typically developing girls. In contrast, some basal ganglia, cerebellar, and limited cortical areas showed enhanced volume growth with peaks around 10 years of age. ConclusionsThe parieto-occipital finding suggests that girls with TS may be particularly vulnerable to altered brain development during adolescence. Basal ganglia regions may be relatively preserved in TS owing to their maturational growth before or early in typical pubertal years. Taken together, our findings indicate that particular brain regions are more vulnerable to TS genetic and hormonal effects during puberty. These specific alterations in neurodevelopment may be more likely to affect long-term cognitive behavioral outcomes in young girls with this common genetic condition.

Sex-related features of walking with cognitive tasks

The organization of walking and its disorders remain one of the most difficult sections of the physiology of the nervous system and neurology. The purpose of the work is to analyze the sexual features of the spatio-temporal parameters of the person walking and the directions of their changes in the conditions of performing additional cognitive tasks. Sex-related features of human walking with cognitive tasks are investigated. 608 individuals of both sexes aged 12-43 years were examined by GAITRite®. Consistent naming of animals and consistent subtraction of 7 starting at 100 were used as cognitive tasks. Statistical processing of the obtained results was performed in the license package “STATISTICA 5.5” using parametric estimation methods. At performing the first (simpler) cognitive task in all age groups of men step length, stride length, step extremity ratio, support base, toe-in-out were increased. Temporal parameters in adolescents of both genders did not differ. Girls have longer step time, cycle time, single support, swing time and a slower velocity. The integral index of walking quality (FAP) tended to decrease in all examined groups: in adolescent males by 13.3±3.9 %; in young men by 14.6±2.2 %; in adolescent women by 15.3±1.8 %; in young women by 14.4±1.1 %; in middle-aged women 7.3±4.8 %. Boys and girls performed more complex cognitive tasks with reduced spatial and temporal parameters (primarily by increasing the double support and swing time), the support base and toe-in-out were stable. The step cycle was rebuilt. The support base and toe-in-out remained unchanged both in boys and girls. The boys were moving at a faster velocity, taking more steps per minute. The step time right, cycle time for each leg, single support time and double support time in girls lasted much longer. FAP declined sharply by 30.4 % in boys and by 33.4 % in girls, indicating a major reorganization of basic mechanisms for regulating walking stability. Such a decrease in FAP leads to a decrease in the level of the balance maintaining and a decrease in body stability during movement, which means that it increases the risk of falls. A complex cognitive task led to a decrease in walking performance and a more critical decrease in the quality of walking in favor of moving forward and maintaining the balance. Thus, walking is not an automated process, but requires the use of a variety of additional CNS resources, primarily attention and cognitive resources.

Nonalcoholic fatty liver disease in obese adolescent females is associated with multi-tissue insulin resistance and visceral adiposity markers

ObjectiveNonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and visceral adiposity in adults and boys, but girls with NAFLD are understudied. We sought to evaluate adipose, liver, and skeletal muscle insulin sensitivity in obese adolescent females with or without hepatic steatosis (HS) (intrahepatic triglyceride (IHTG) content >5.5%) along with cardiometabolic components typically associated with IR. Study design73 obese adolescent girls at high risk for NAFLD were enrolled. Participants underwent fasting labs, an MRI to measure IHTG and visceral fat, 31phosphorous MR spectroscopy for muscle mitochondrial function, 1H MR spectroscopy for intramyocellular lipid (IMCL), bicycle ergometry to assess VO2peak and a 4-phase hyperinsulinemic euglycemic clamp with isotope tracers to measure hepatic and peripheral IR. 29 participants had HS [age 15 yrs(13,16), BMI%ile 98.7(97.4,99.0), IHTG 10.4%(8.0,13.5)] and 44 did not [age 15 yrs(13,17), BMI%ile 98.5(96.2,99.0), IHTG 2.0%(1.1,3.0)]. ResultsDuring hyperinsulinemia, participants with HS vs. non-HS had failure to suppress free fatty acids (p = 0.008), endogenous glucose release (p = 0.002), and a lower glucose metabolic rate of disappearance (Rd) (p = 0.012). Girls with NALFD also had higher visceral fat (p < 0.001), systolic blood pressure (p = 0.026), triglycerides (p = 0.02), ALT (p < 0.01) and white blood cell count (p < 0.01), and lower adiponectin (p = 0.02). There was no difference between girls with and without HS in systemic glycerol turnover measured with glycerol release, or in IMCL, mitochondrial function or VO2peak. ConclusionsObese adolescent girls with HS have evidence of multi-tissue IR, visceral adiposity, inflammation and multiple components of the metabolic syndrome, arguing for close cardiometabolic surveillance over time of girls with HS.

Earlier age at menarche as a transdiagnostic mechanism linking childhood trauma with multiple forms of psychopathology in adolescent girls.

Although early life adversity (ELA) increases risk for psychopathology, mechanisms linking ELA with the onset of psychopathology remain poorly understood. Conceptual models have argued that ELA accelerates development. It is unknown whether all forms of ELA are associated with accelerated development or whether early maturation is a potential mechanism linking ELA with psychopathology. We examine whether two distinct dimensions of ELA - threat and deprivation - have differential associations with pubertal timing in girls, and evaluate whether accelerated pubertal timing is a mechanism linking ELA with the onset of adolescent psychopathology. Data were drawn from a large, nationally representative sample of 4937 adolescent girls. Multiple forms of ELA characterized by threat and deprivation were assessed along with age at menarche (AAM) and the onset of DSM-IV fear, distress, externalizing, and eating disorders. Greater exposure to threat was associated with earlier AAM (B = -0.1, p = 0.001). Each 1-year increase in AAM was associated with reduced odds of fear, distress, and externalizing disorders post-menarche (ORs = 0.74-0.85). Earlier AAM significantly mediated the association between exposure to threat and post-menarche onset of distress (proportion mediated = 6.2%), fear (proportion mediated = 16.3%), and externalizing disorders (proportion mediated = 2.9%). Accelerated pubertal development in girls may be one transdiagnostic pathway through which threat-related experiences confer risk for the adolescent onset of mental disorders. Early pubertal maturation is a marker that could be used in both medical and mental health settings to identify trauma-exposed youth that are at risk for developing a mental disorder during adolescence in order to better target early interventions.