Neuroendocrine consequences of childhood traumatic brain injury

OBJECTIVES: 1) To determine the prevalence, aetiology and clinical significance of pituitary dysfunction after moderate or severe childhood traumatic brain injury (TBI); and 2) to examine its impact on quality of life (QoL) and body composition.SUBJECTS: Retrospective observational study of 33 survivors of accidental TBI (27 males) and two of inflicted TBI (both males). Accidental TBI group: mean (SD) age at study was 13.4y (3.7y) and interval since injury, 4.1y (1.6y). King's Outcome Scale for Childhood Head Injury (KOSCHI) rating: 15 good recovery, 16 moderate disability, 2 severe disability. Inflicted TBI group: ages at study were 5.0 and 3.7 years at 4.9 and 3.3 years post-injury with good recovery and moderate disability respectively.METHODS: Early morning urine samples were obtained for osmolality. Basal hormone evaluation (0800-1 OOOh) was followed by the gonadotropin-relasing hormone (GnRH) and insulin tolerance (ITT, n=26) or glucagon tests (ifprevious seizures, n=9). Subjects were not primed. Body composition was evaluated using bioelectrical impedance analysis. Standardised quality of life (QoL) questionnaires were completed. Head injury details were extracted from patient records.RESULTS: There were no abnormal findings in the two survivors of inflicted TBI. Among the accidental TBI group, no subject had clinical evidence of impaired growth: mean height standard deviation score (SDS) was +0.5 (range -1.6 to +3.0 SD). Median peak growth hormone (GH) response to stimulation was 7.9 pg/L. Six peri-pubertal males had suboptimal GH responses (<5 pg/L). Their height SDS at study ranged from -1.5 to +1.4; one had slow growth on follow-up. GH response was borderline low in one post-pubertal male (3.2 pg/L).Median peak Cortisol responses were 538 nmol/L (ITT) and 562 nmol/L (glucagon). 9/25 (ITT) and 2/8 (glucagon) subjects had sub-optimal responses. In two cases (one ITT, one glucagon test), basal Cortisol levels were high (624 and 722 nmol/L). For the rest, in 6/9, further testing or no action was advised; in 3/9, steroid cover was recommended for moderate or severe illness or injury. None required routine glucocorticoid replacement. No subject had diabetes insipidus. Thyroid function, IGF-I, oestradiol/testosterone, and baseline and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. One male was prolactin deficient (<50 mU/L).Abnormal endocrine findings were unrelated to severity of TBI, nature of primary or secondary brain injury, or KOSCHI rating. No significant difference in QoL was observed between those with normal or abnormal pituitary function <16y. QoL was poorer in the post-pubertal male with GH deficiency than in other subjects >16y.CONCLUSIONS: Whilst mild pituitary 'dysfunction' was common (39%), no unequivocal clinically significant endocrinopathies were found, although the GH and hypothalamopituitary-adrenal axes may be vulnerable

Medium-term health and social outcomes in adolescents following sexual assault: a prospective mixed-methods cohort study.

PURPOSE: To describe medium-term physical and mental health and social outcomes following adolescent sexual assault, and examine users' perceived needs and experiences. METHOD: Longitudinal, mixed methods cohort study of adolescents aged 13-17 years recruited within 6 weeks of sexual assault (study entry) and followed to study end, 13-15 months post-assault. RESULTS: 75/141 participants were followed to study end (53% retention; 71 females) and 19 completed an in-depth qualitative interview. Despite many participants accessing support services, 54%, 59% and 72% remained at risk for depressive, anxiety and post-traumatic stress disorders 13-15 months post-assault. Physical symptoms were reported more frequently. Persistent (> 30 days) absence from school doubled between study entry and end, from 22 to 47%. Enduring mental ill-health and disengagement from education/employment were associated with psychosocial risk factors rather than assault characteristics. Qualitative data suggested inter-relationships between mental ill-health, physical health problems and disengagement from school, and poor understanding from schools regarding how to support young people post-assault. Baseline levels of smoking, alcohol and ever drug use were high and increased during the study period (only significantly for alcohol use). CONCLUSION: Adolescents presenting after sexual assault have high levels of vulnerability over a year post-assault. Many remain at risk for mental health disorders, highlighting the need for specialist intervention and ongoing support. A key concern for young people is disruption to their education. Multi-faceted support is needed to prevent social exclusion and further widening of health inequalities in this population, and to support young people in their immediate and long-term recovery

Complex post-traumatic stress symptoms in female adolescents:the role of emotion dysregulation in impairment and trauma exposure after an acute sexual assault

Background: Adolescents are at high risk of sexual assault compared to any other age group. The pattern of post-traumatic stress symptoms plus life-impairing disturbances in self-organization (emotion dysregulation, negative self-concept and interpersonal problems) is termed Complex Post-Traumatic Stress Disorder (CPTSD). Research about CPTSD after sexual assault in adolescents is limited owing to the challenges associated with assessing this group. This study aims to determine the frequency and structure of CPTSD, and the relationship of emotion dysregulation with impairment and additional trauma exposure among adolescents who have been sexually assaulted. Method: Prospective cohort study of adolescents attending the Sexual Assault Referral Centres serving London over a 2-year period. We conducted cross-sectional analyses (n = 99) on data collected 4–5 months after sexual assault, and Confirmatory Factor Analyses (CFA) and Latent Class Analyses (LCA) to determine the CPTSD profile. CTPSD was defined according to the ICD-11, selecting symptom indicators from the following measures: Strengths and Difficulties Questionnaire (SDQ), Children’s Revised Impact of Event Scale (CRIES-13), Short version of the Mood and Feelings Questionnaire (S-MFQ), The Development and Well-Being Assessment (DAWBA). We analysed the association of CPTSD symptom domains with impairment (measured with the SDQ, and the Children’s Global Assessment Scale; C-GAS) and with additional trauma exposure. Results: The frequency of ICD-11 PTSD was 59%, and of ICD-11 CPTSD was 40%. CPTSD symptoms showed a strong fit for a correlated 4-factor model, and LCA distinguished a class of participants with high levels of CPTSD symptoms. Emotion dysregulation was associated with impairment in functioning and exposure to trauma beyond other self-organization disturbances and core PTSD symptoms. Conclusions: Disturbances in self-organization are frequent in sexually assaulted adolescents, and emotion dysregulation is associated with impairment and further exposure to trauma. Emotion dysregulation should be considered in preventive and treatment strategies for these vulnerable youth

Early medical treatment of gender dysphoria: Baseline characteristics of a UK cohort beginning early intervention

Aims: To describe characteristics of patients referred early (<16 yrs) medical treatment for gender dysphoria (GD). GD is a rare condition in which individuals experience clinically significant distress due to incongruence between their psychological perception of, and their natally assigned, sex. Methods: We collected data prospectively on all patients referred from May 2010––July 2014 for early pubertal suppression using gonadotropin – releasing hormone analogue (GnRHa) therapy. Results: 61 young people (34 natal males; 55.7%) were referred for early intervention to the national GD service endocrine liaison clinic at mean age of 13.1 years (range 9.8–15.3). All patients had a karyotype consistent with their natal sex. More natal males were in early puberty (32.4% Tanner 1/2; n = 11) than natal females (11.1% Tanner 1/2; n = 3). Baseline endocrinology and physical examination were normal for natal sex in all patients. All females who had standard synacthen tests to exclude adrenal dysfunction (77.8%; n = 21) had normal cortisol and 17OHP. 38.2% (n = 13) males had low bone mineral density compared with 11.1% of females (n = 3). 50 patients (81.9%) elected to receive GnRHa following full explanation and informed consent at Tanner stage 3, following international guidelines. GnRHa could not be commenced immediately if pre-pubertal (10/61), having very low bone mineral density (3/61) or low body mass index (BMI) (2/61). All who began GnRHa achieved full gonadatropin suppression. No young people withdrew from GnRHa treatment in the first 2 years. Many GPs were unwilling to prescribe GnRHa (56.0%; n = 28/50) therefore local hospitals (8.0%; n = 4) or the tertiary centre (36.0%; n = 18) issued prescriptions. Conclusion: Early medical intervention in GD with GnRH suppression of puberty is effective and well–tolerated. Assessment of growth, bone health and psychological outcomes will be important to assess the medium-and long-term safety and effectiveness of early intervention for GD

UK and Irish surveillance study of gender identity disorder (GID) in children and adolescents

Purpose: The incidence of childhood/adolescent Gender Identity Disorder (GID) is unknown. GID is an important condition where gender identity differs from biological sex. It is associated with significant distress, particularly with puberty, with much controversy internationally over the optimal timing of hormonal treatment. We examine the incidence and clinical presentation in UK and Irish children and adolescents. Methods: STUDY POPULATION: Children and adolescents aged 4-15.9 years in the UK and Republic of Ireland. DESIGN: Joint British Paediatric Surveillance Unit (BPSU) and Child and Adolescent Psychiatry Surveillance System (CAPSS) study. New cases of GID reported by clinicians over a 19-month reporting period (01-Nov-2011 to 01-June-2013) are validated against the authoritative DSM-IV-TR (2000). Exclusions include disorders of sexual differentiation and major psychosis. PRIMARY OUTCOME: Incidence of childhood/ adolescent GID, calculated by dividing the number of validated cases by the base population of children and adolescents aged 4-15.9 years. Sources of denominator data: UK Office of National Statistics and the Central Statistics Office in Ireland. STATISTICAL ANALYSIS: Descriptive statistics and comparisons using two-sample t-tests or Mann- Whitney U tests for continuous data and Chi-squared or Fisher’sexact tests for categorical data. Results: Preliminary descriptive data from the first 15 months’sur-veillance (n¼ 138 cases, 69 males) indicate that similar numbers of males and females are affected by this condition. Early estimates suggest UK and Irish incidences of 1:80,000 and < 1:200,000 respectively. There is a lag of several years between median [inter- quartile range] onset of symptoms (7y [4-12y]) and presentation to Paediatricians or Psychiatrists (14.5y [11.9-15.2y]), with most cases presenting at 14 or 15 years. Only a quarter of all cases (n¼35) were less than 12 years old at reporting, but 50% of cases reported by Paediatricians. There are high levels of psychiatric co-morbidity at pre- sentation, with at least one other mental health diagnosis in 45%, and two or more other diagnoses in adolescents aged 12 years and over. Conclusions: We present the first ever population-level data on the incidence, clinical features and presentation of childhood/ adolescent GID. These data will inform clinical management, including the highly controversial debate around early pubertal suppression in this group

A systematic review of short and medium-term mental health outcomes in young people following sexual assault

Objective: Sexual assault peaks in adolescence, yet sequelae at this age are not well understood. This systematic review aimed to describe mental health outcomes following sexual assault in young people.Method: Two reviewers independently searched databases, screening publications from 1990 to 2018. Inclusion criteria included: longitudinal studies, systematic reviews, and meta-analyses with ≥50% participants aged ten to 24 years; baseline mental health assessment prior to/or &lt;8 weeks post-assault with follow-up ≥ 3 months after the initial assessment.Results: 5 124 titles and abstracts were screened, with 583 papers examined in full. Ten studies met inclusion criteria (sample size 31 to 191). Five studies examined rates of post-traumatic stress disorder (PTSD), reporting rates of up to 95% within one month and up to 60% at 12 months post-assault. Studies evaluating post-traumatic (n = 5) and anxiety (n = 3) symptom scores showed symptoms were highest in the immediate aftermath of the trauma, generally reducing over four to 12 months post-assault. Depressive symptomology appeared to vary between studies (n = 5). However, the majority showed symptoms decreasing over the same time period.Conclusions: Psychopathology is common following sexual assault in young people. Most studies observed reduced rates over time, but there is a paucity of longitudinal research. Psychopathology during the first year after sexual assault is an important treatment target to consider

Mental and sexual health outcomes following sexual assault in adolescents:a prospective cohort study

BACKGROUND: Young people are disproportionately affected by sexual assault, yet longitudinal data are sparse. This paper examines the characteristics of adolescents presenting to sexual assault services and mental and sexual health outcomes after an assault. METHODS: This was a prospective cohort study in adolescents aged 13-17 years attending the Sexual Assault Referral Centres serving Greater London, UK, over 2 years. Baseline interviews (T0) were done less than 6 weeks after an assault to collect data on sociodemographic and assault characteristics and psychological symptoms, with follow-up interviews (T1) at 4-5 months after the assault. Four psychological symptom questionnaires were used at T0 and T1: The Child Revised Impact of Events Scale, the Short Mood and Feelings Questionnaire, the Screen for Child Anxiety Related Disorders, and the Strengths and Difficulties Questionnaire. The primary outcome was prevalence of any psychiatric disorder at T1, assessed using the Development and Wellbeing Assessment. Secondary outcomes at T1 were pregnancy, sexually transmitted infections, and sexual health screening since the assault. FINDINGS: Between April 15, 2013, and April 20, 2015, 141 (29%) of 491 eligible young people were recruited to the study (134 females; mean age 15·6 years [SD 1·27]), and 106 (75%) of 141 participants had T1 interviews (99 female). At T0, psychological symptom scores showed that 115 (88%) of 130 females were at risk for depressive disorder, 90 (71%) of 126 were at risk for anxiety disorders, and 116 (91%) of 128 were at risk for post-traumatic stress disorder, with symptoms largely persisting at T1. 68 (80%) of 85 females who had a diagnostic assessment at T1 had a psychiatric disorder, with multiple disorders in 47 (55%) of 85. Anxiety, post-traumatic stress, and major depressive disorders were the commonest diagnoses. Presence of a psychiatric disorder was associated with baseline psychosocial vulnerability (previous social services involvement, mental health service use, self-harm, or sexual abuse), but not assault characteristics. At T1, four (4%) of 105 females had been pregnant since the assault, 14 (12%) of 119 had a sexually transmitted infection diagnosed between T0 and T1, and nine (8%) of 107 reported re-victimisation since the assault. INTERPRETATION: Vulnerable adolescents have the double disadvantage of being at risk for both sexual assault and associated psychiatric disorders, highlighting the need for comprehensive support after an assault. Feasibility and effectiveness of prevention programmes should be investigated. FUNDING: National Institute for Health Research Policy Research Programme grant (115/0001)

Randomized controlled trial : impact of glycerin suppositories on time to full feeds in preterm infants

Feed intolerance delays achievement of enteral feeding in preterm infants. Parenteral nutrition is associated with cholestasis and increased risk of sepsis. Glycerin suppositories have been used to promote gastrointestinal motility and feed tolerance. Objectives: To investigate whether daily glycerin suppositories (a) reduce the time to full enteral feeding in infants born at <32 weeks’ gestation, and (b) influence feed tolerance, incidence of sepsis or necrotizing enterocolitis, duration of oxygen requirement, growth or age at discharge. Design – prospective open randomized controlled trial; study population – preterm infants stratified into 2 subgroups, 24–27+6 weeks (24–27 weeks + 6 days) and 28–31+6 weeks; intervention – daily glycerin suppository for 10 days from 24 h of age, 250 mg (24–27+6 weeks subgroup) or 500 mg (two 250-mg suppositories; 28–31+6 weeks subgroup); controls – no intervention. The same feeding protocol and departmental guidelines for other aspects of neonatal intensive care were used in all subjects. Analysis was by intention to treat. 54 babies were recruited (31 males), 29 randomized to receive suppositories; 48 achieved full enteral feeds. The median (range) time to full feeds was 1.6 days shorter in intervention group babies than controls, but not statistically significant: 7.4 (4.6–30.9) days versus 9.0 (4.4–13.3) days (p = 0.780; 9

Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK.

BackgroundIn adolescents with severe and persistent gender dysphoria (GD), gonadotropin releasing hormone analogues (GnRHa) are used from early/middle puberty with the aim of delaying irreversible and unwanted pubertal body changes. Evidence of outcomes of pubertal suppression in GD is limited.MethodsWe undertook an uncontrolled prospective observational study of GnRHa as monotherapy in 44 12-15 year olds with persistent and severe GD. Prespecified analyses were limited to key outcomes: bone mineral content (BMC) and bone mineral density (BMD); Child Behaviour CheckList (CBCL) total t-score; Youth Self-Report (YSR) total t-score; CBCL and YSR self-harm indices; at 12, 24 and 36 months. Semistructured interviews were conducted on GnRHa.Results44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones. There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common.ConclusionsOverall patient experience of changes on GnRHa treatment was positive. We identified no changes in psychological function. Changes in BMD were consistent with suppression of growth. Larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and harms of pubertal suppression in GD