Academic literature on the topic 'RG Gynecology and obstetrics ; RJ101 Child Health. Child health services'

Disorders of sex development (DSD) are a diverse group of conditions in which there is variation from the typical chromosomal, gonadal, or anatomical developmental pathway. While much has been learnt about the genetic aetiology of many of these disorders, a significant proportion of cases remain without a definitive diagnosis. This thesis consists of a series of studies designed to look at different aspects of DSD in order to identify causes and develop better ways to assess and research these conditions in the future. Chapter 1 is an extensive literature review of normal sex development, models to describe the sex phenotype, steroidogenesis, steroid hormone structure and physiological role, classification of DSD, clinical uses of progestogens and determinants of foetal growth. An understanding of these diverse subjects is essential to consider the topics investigated. Chapter 2 presents the rationale for, and specific aims of, this thesis. Chapter 3 describes a study using the I-DSD registry, the largest international register of cases of DSD, to identify associated conditions co-occurring in DSD. 649 cases with documented consent were identified and analysed from the registry, with further information obtained from the reporting clinician where necessary. Associated conditions were reported in 168 cases (26%), overall, and when considered according to karyotype were reported in 112 cases of 46,XY DSD (24%), 27 cases of 46,XX DSD (22%), 19 cases of 45,X/46,XY (45%), and 6 cases of 45,X (75%). In 46,XY DSD, which represents the largest group of cases in the Registry, small for gestational age (SGA), cardiac and CNS anomalies were the most commonly reported associated conditions. This study strengthens the recognised association between SGA and non-specific 46,XY DSD. Additionally, the data indicate a possible association between genetically confirmed AIS and skeletal and renal anomalies. These results provide new research targets for cases in which the aetiology of DSD remains unclear. They also highlight the need for multi-disciplinary teams for management of these patients. Chapter 4 documents a clinical study investigating the association between hypospadias, one of the mildest conditions on the spectrum of DSD, and the measurement of anogenital distance (AGD). 88 boys had AGD measured under general anaesthetic during hypospadias surgery, alongside assessment of severity of hypospadias. Medical notes were reviewed for further information including birth weight, gestation and the presence of additional genital anomalies, as described by the external masculinisation score (EMS). Median AGD was found to be shorter in boys with severe hypospadias (63mm), than those with mild hypospadias (75mm) (p < 0.001). Additionally these boys were more likely to have lower birth weight SDS (-0.61) than boys with mild hypospadias (-0.42) (p= 0.013). This study is the first to show a link between severity of hypospadias, additional genital anomalies, and degree of AGD shortening. This supports the hypothesis that severe forms of hypospadias may be linked to inadequate androgen exposure in utero. Results also show that boys with more severe hypospadias have a lower birthweight, reinforcing the link between 46,XY DSD and SGA. Chapter 5 describes the use of a rat model to investigate the developmental effects of exposure to the progestogen medroxyprogesterone acetate (MPA) during the male programming window. It has been previously suggested that antenatal exposure to progestogens may be associated with DSD. In this study Sprague Dawley dams were injected with 75mg/kg or 150mg/kg of subcutaneous MPA on gestational days 14.5 to 18.5. Results showed that MPA exposure was associated with a shorter than normal AGD in male rats, and a longer AGD in female rats. Offspring of both sexes had reduced birth weight when exposed to MPA (control weight 5.99g, MPA 75mg/kg 4.58g, MPA 150mg/kg 4.72g). There was no evidence of an effect on internal reproductive structures, including testis weight. Chapter 6 describes studies using small vessel myography to investigate vascular function in the pregnant dams exposed to MPA in the previous studies. Low birth weight can be the result of altered vascular remodelling during pregnancy, leading to impaired placental function. It has previously been suggested that impaired placental function may be responsible for the combination of intra-uterine growth restriction and DSD. Uterine artery segments from animals exposed to MPA 150mg/kg demonstrated greater vessel wall thickness, and a trend towards an increase in internal and external diameter, with increased distensibility at higher pressures when compared to control segments. Wire myography showed that vasoconstriction in response to noradrenaline and NG-nitro-L-arginine methyl ester (L-NAME) was reduced following MPA exposure. These studies do not explain the causes of reduced growth in MPA exposed offspring. The responses seen are the opposite of those seen in animals with pre-eclampsia and hypertension, and may demonstrate the protective effect of progestogens in pregnancies complicated by these conditions. Chapter 7 draws together the findings of all the studies in this thesis, to reach overall conclusions. The common theme of an association between DSD and impaired foetal growth from all three branches of this work in discussed. The potential for further investigations in pursuing this work to strengthen conclusions and inform future practice is considered.

The aim of this study is to develop a pain assessment scale for use during neonatal transport. Underpinned by the rights of the child to have appropriate assessment and management of pain and the important deleterious effects pain can have on the physiological stability of the neonate, this study utilises a qualitative consensus paradigm of enquiry to inform the content and structure a pain assessment scale specific to the transport setting. The study was conducted in three Phases, the first Phase consisted of a nominal group meeting with transport clinicians to ascertain their views on items to include in a pain assessment scale for transport. Phase Two utilised the Delphi technique to gain consensus from a large cohort of clinicians experienced in the field of neonatal transport on the content, structure and design of a transport pain assessment scale. Results of the first two Phases of the study were then applied to the adaptation of an existing pain assessment scale. Face validity of the newly developed Neonatal Transport Pain Assessment Scale (NTPAS) was then tested in Phase Three by semi-structured interviews with transport clinicians. Results of initial face validity testing suggested positive results in relation to feasibility and clinical utility of the scale, however further testing is strongly recommended. Currently there are no pain assessment scales developed for use in the transport setting, and little evidence on the effects of transport on pain and pain assessment. This study offers a unique approach in adding to the body of knowledge on neonatal pain assessment and facilitated the development of a scale adapted to transport. Further research is suggested to undertake psychometric testing of the scale and establish validity and reliability in the clinical setting.

Breast milk is acknowledged and recommended as the best food for babies by the World Health Organization. However, globally the proportion of mothers who breastfeed is still low and this is particularly the case in Thailand. The aim of this study is to improve women’s ability to breastfeed. A two phase study was designed. Phase I was to better understand women’s experiences and breastfeeding support needs, which formed the development of the ‘Breastfeeding Support Package’. The package, which consisted of the tool and leaflets, was to be administered by the nurses with the postpartum women. Phase II aimed to explore mother’s and nurses’ experiences following the use of the package. A pragmatic qualitative approach was used throughout. A government hospital in Bangkok, Thailand, was the setting for this research. Purposive sampling was used to recruit the participants for both phases of the study. In Phase I, semi-structured interviews of 17 mothers who visited the Family Planning Clinical, post-delivery, were undertaken. Thematic analysis was used to examine the data. For phase II, three groups of participants were involved: five participants from phase 1, five postpartum women and five nurses working on the postpartum ward. Telephone interviews were used to assess face validity to the tool while semi-structured interviews were used to investigate mothers’ and nurses’ experiences regarding the use of the package. Three themes that contributed to women’s experience of breastfeeding were ‘knowledge and attitude towards breastfeeding’, ‘practicality’ and ‘support’. Three themes that contributed to ‘women’s needs of breastfeeding support’ were ‘knowledge’, ‘attitude’, and ‘practice’. The use of the package could open a ‘platform to communication’ regarding women’s needs and act as a ‘platform to support’ for nurses. The postpartum women were able to better communicate their needs regarding breastfeeding support with the nurses, as well as receiving the support they required. The packaged worked well with present conditions and environment at the postpartum ward of the hospital.

I investigated the role of genetic, environmental and intrauterine factors in child development using data from two large twin studies; the East Flanders Prospective Twin Survey (EFPTS) and the Twins and Multiple Births Association Heritability Study (TAMBAHS). An association between birth weight and child development has already been established. Potential associations between other factors of the intrauterine environment and child development were investigated in this thesis. Heritabilities of the umbilical cord, IQ, temperament and behaviour problems were estimated. Fetal characteristics, such as birth weight, placental weight and morphology, umbilical cord knots, length and insertions were investigated in relation to cognitive development in the EFPTS study. The impact of maternal pre-pregnancy weight on temperament and behaviour problems was examined in the TAMBAHS study. High heritability estimates were observed for certain dimensions of the umbilical cord, temperament and IQ; for behaviour problems, genetic, shared and non-shared environment were important. Low birth weight and cord knotting was associated with lower IQ; an association was observed between maternal overweight and children aggressive behaviour. The results are discussed in the context of the Developmental Origins of Health and Disease (DOHaD) hypothesis, highlighting the role of the intrauterine environment in child development.

Earlier studies have shown that individuals whose mothers were diabetic when they were in utero, have an increased risk of early obesity, and impaired glucose tolerance (lGT) and type 2 diabetes in adult life. This study was designed to test whether adiposity, glucose tolerance and insulin concentrations are altered in Indian children born to mothers with gestational diabetes (GDM), and are related to maternal glucose and insulin concentrations in pregnancy even in the absence of GDM. 830 pregnant women attending the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India underwent an Oral Glucose Tolerance Test (OGTT) at 30+/-2 weeks. 674 of these women delivered at HMH. Detailed anthropometry was performed on the offspring at birth, and annually thereafter. 585 mothers returned with their offspring at 5 years of age for detailed investigations including OGTT for glucose and insulin concentrations, bio-impedance for fat estimation and blood pressure measurement. OGTT was administered to mothers and fasting plasma glucose and insulin concentrations were measured in fathers. The Mysore babies were small compared to UK neonates, but the deficit varied for different body measurements. While birthweight (-1.1 SD) was considerably lower, crown-heel length (-0.3 SD) and subscapular skinfold thickness (-0.2 SD) were relatively spared. At five years, subscapular skinfold thickness was larger than the UK standards (+0.23 SD, p