Environmental Impacts on Male Reproductive Development: Lessons from Experimental Models.

Background: Male reproductive development in mammals can be divided into a gonadal formation phase followed by a hormone-driven differentiation phase. Failure of these processes may result in Differences in Sex Development (DSD), which may include abnormalities of the male reproductive tract, including cryptorchidism, hypospadias, infertility, and testicular germ cell cancer (TGCC). These disorders are also considered to be part of a testicular dysgenesis syndrome (TDS) in males.

Idiopathic short stature and growth hormone sensitivity in prepubertal children.

Objective: We compared growth hormone sensitivity to an insulin-like growth factor I (IGF-I) generation test in children with idiopathic short stature (ISS) and of normal stature (NS) across the birthweight range.

Methods: Forty-six prepubertal children (~7.1 years) born at term were studied: ISS (n = 23; 74% boys) and NS (n = 23; 57% boys).

Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices.

Background: PAIS exhibits a complex spectrum of phenotypes and pubertal outcomes. The paucity of reliable prognostic indicators can confound management decisions including sex-of-rearing. We assessed whether external masculinisation score (EMS) at birth or functional assays correlates with pubertal outcome in PAIS patients and whether the EMS is helpful in sex assignment.

Response to IGF-1 Generation Test in Short Prepubertal Children Born Very Preterm or at Term.

Aims: To investigate whether short children born very preterm (<32 weeks of gestation) exhibit features of growth hormone (GH) resistance compared to term peers.

Methods: We studied 26 prepubertal children (aged 7.0 ± 2.

Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015).

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional DSD team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional team acts commonly as the first point of contact.

Anthropometry, glucose homeostasis, and lipid profile in prepubertal children born early, full, or late term.

To examine differences in growth and metabolism in prepubertal children born early term, full term, and late term. We retrospectively studied 294 prepubertal children aged 7.3 years (range 3.

Low frequency of androgen receptor gene mutations in 46 XY DSD, and fetal growth restriction.

Objective: The diagnosis of partial androgen insensitivity syndrome (PAIS) should be reserved for infants with a pathogenic androgen receptor gene (AR) mutation. However, only about 20% of infants with a clinical phenotype akin to PAIS have an AR mutation. We aimed to identify clinical features associated with the presence of an AR mutation.

Increasing paternal age at childbirth is associated with taller stature and less favourable lipid profiles in their children.

Background: Paternal age at childbirth has been increasing worldwide, and we assessed whether this increase affects growth, body composition and metabolism in their children.

Methods: We studied 277 children (aged 3-12 years) born to fathers aged 19·8-51·8 years. Clinical assessments were height and weight adjusted for parental measurements, DEXA-derived body composition, fasting lipids, glucose homoeostasis and hormonal profiles.

Increasing maternal age is associated with taller stature and reduced abdominal fat in their children.

Background: Maternal age at childbirth continues to increase worldwide. We aimed to assess whether increasing maternal age is associated with changes in childhood height, body composition, and metabolism.

Methods: 277 healthy pre-pubertal children, born 37-41 weeks gestation were studied.

Phenotypic differences in children conceived from fresh and thawed embryos in in vitro fertilization compared with naturally conceived children.

Objective: To determine whether anthropometric and biochemical features differ in in vitro fertilization (IVF) children conceived via fresh (IVFF) or thawed (IVFT) embryo transfer compared with naturally conceived controls.

Design: A cross-sectional controlled study.

Setting: University clinical research unit.

Birth order progressively affects childhood height.

Background: There is evidence suggesting that first-born children and adults are anthropometrically different to later-borns. Thus, we aimed to assess whether birth order was associated with changes in growth and metabolism in childhood.

Methods: We studied 312 healthy prepubertal children: 157 first-borns and 155 later-borns.

Ovarian stimulation leads to shorter stature in childhood.

Background: We aimed to determine whether children conceived with ovarian stimulation alone (OS(A)) would differ phenotypically and biochemically from naturally conceived children of fertile and subfertile parents.

Methods: Healthy pre-pubertal children aged 3-10 years, born at term, after singleton pregnancies were recruited in Auckland (New Zealand) and were allocated into three groups: (i) children conceived following OS(A) and naturally conceived children of (ii) subfertile and (iii) fertile parents. Anthropometric, endocrine and metabolic parameters were recorded.

Defects in imprinting and genome-wide DNA methylation are not common in the in vitro fertilization population.

Objective: To examine an IVF cohort for imprinted and genome-wide DNA methylation abnormalities.

Design: Retrospective study.

Setting: Research laboratory.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development.

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact.

The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.

Objective: To examine the role of androgens on birth weight in genetic models of altered androgen signalling.

Setting: Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH).

Patients: (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH.

Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

Objective: To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty.

Study Design: Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation.

Results: Children in the CDGD group were shorter and leaner than control subjects.

Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir).

In vitro fertilization improves childhood growth and metabolism.

Background: There is limited information regarding the long-term outcome of children born after in vitro fertilization (IVF), although an increase in rare imprinted gene disorders such as Beckwith-Wiedemann syndrome has been reported.

Methods: We recruited healthy, prepubertal children born at term after singleton pregnancy. The children in the study group were conceived using IVF with fresh embryo transfer, whereas controls were naturally conceived.

Fetal origins of adult disease: a paediatric perspective.

Prepubertal children born SGA or VLBW premature exhibit marked insulin resistance. There are similarities between SGA and VLBW children in that both are exposed to sub-optimal environments that encompass undernutrition and/or malnutrition during the equivalent of the last trimester of pregnancy. Although both SGA and VLBW groups fail to reach genetic height potential and are recognized causes of short stature in childhood, there are differences between the groups with respect to the growth hormone and IGF-I axis.