Academic literature on the topic 'RJ Pediatrics : RG Gynecology and obstetrics'

This thesis consists of a series of studies utilising quantitative ultrasound (Sunlight Omnisense 7000P) to assess bone health of infants. Preterm infants are at risk of osteopenia of prematurity (OP) which can result in fractures in the short term and may have an impact on growth in infancy and childhood. OP has a multifactorial aetiology including factors such as poor mineral intake and immobility. There is an increasing number of ex-preterm survivors therefore morbidity becomes more important. There is also increasing evidence from epidemiological studies that growth in infancy can have an effect on adult diseases such as osteoporosis. The first study was a cross-sectional study of bone quantitative ultrasound measurements in 110 term and preterm infants shortly after birth. Speed of sound (SOS) was measured at the tibial and the radius. This validated the technique showing reproducible measurements with low inter and intra-observer error, and also showed no benefit to measuring multiple sites. Preterm infants were found to have a significantly lower SOS than term infants. There was a positive correlation between tibial SOS and gestation, with birthweight being a less significant factor than gestation. The second study followed 18 preterm infants longitudinally from birth to hospital discharge or term corrected gestational age (CGA). SOS fell significantly with time in all infants. The most preterm infants had the greatest fall in SOS. SOS at the end of the study period was negatively associated with peak serum alkaline phosphatase and severity of illness score. SOS was significantly lower in the infants who required total parenteral nutrition for longer than 3 weeks. These results show that the neonatal course has a significant impact on SOS trajectory. When preterm infants were followed up in the out-patient clinic over the first two years of life the SOS measurements taken as the next part of this study showed a catch up phenomenon. In the majority of infants, but not all infants, SOS moved into the normal range by 6 months CGA. In the subgroup of infants followed longitudinally those with the lowest SOS at hospital discharge/term corrected age had the greatest increase in SOS over time. An interventional study of passive exercise was performed to explore its role in influencing the bone health of preterm infants. Thirty one infants born at less than 33 weeks gestation were randomised to receive range of motion flexion and extension exercises once daily for 5 days each week starting ‘early’(n=15) or ‘late’ (when on 100kcal/kg/day enteral feeds, n=16) and continuing until term corrected gestational age (CGA) or discharge from hospital. Tibial SOS declined significantly from birth to end of physical activity in both ‘early’ and ‘late’ groups, and this was similar to the decrease seen in a group of historical controls from the earlier longitudinal study. Weight gain and head growth did not show a significant difference between groups or between study infants and controls. No infant was reported to have sustained a fracture, and length of hospital stay was not significantly different between groups. There was no significant increase in sepsis rate, retinopathy of prematurity or chronic lung disease in study infants but numbers were small. On longer term follow-up the intervention was not associated with any adverse effects. To investigate the possibility that the maternal environment plays an important role in influencing infants’ bone health we also studied SOS changes in 188 pregnant women and their offspring. Most women had SOS in the normal range antenatally, and there was no significant change in SOS across pregnancy in the group as a whole. There was a significant negative correlation with SOS SDS and BMI in early pregnancy. Women who smoked cigarettes had lower SOS throughout pregnancy and so did their infants. Serum bone biochemistry was measured in the women antenatally and after delivery, and umbilical cord blood was also taken where possible. Vitamin D deficiency was found to be common at the end of pregnancy. Women of Asian origin had significantly lower vitamin D levels at all stages of pregnancy. There was no significant relationship between maternal and infant SOS, or between maternal vitamin D status and infant SOS. The work of this thesis establishes quantitative ultrasound as a useful technique in the assessment of infant bone health. It is a radiation free tool which provides precise and reproducible measurements in both term and preterm infants. In agreement with a small number of other studies we found that preterm infants have a lower speed of sound at birth compared to term infants; speed of sound increases with increasing gestation while in utero. By including infants who were both appropriately grown and small for gestational age we found maturity to be a more important factor in bone strength than birthweight. Despite the apparent self limiting nature of osteopenia of prematurity an intervention to improve neonatal bone health is still desirable, to prevent fractures. Our results do not substantiate conclusions from previous studies that physical activity alone can improve neonatal bone health. .Findings are however limited by the small sample size. Further studies are needed which investigate alternative exercise regimens, taking into account mineral and nutrient supply. Vitamin D deficiency, smoking and obesity may adversely affect bone health of women and their offspring. In the west of Scotland vitamin D deficiency is common in pregnancy: women of south asian origin are at particularly high risk, and should be supplemented with Vitamin D.

Numerous studies have shown the benefits of breastfeeding, however, the incidence and duration of breastfeeding in the UK is low and static, and breastfeeding rates in Liverpool in the North West of the UK are even lower. Breastfeeding is frequently promoted as being free yet little research has been carried out to substantiate this claim. Further, little is known about breastfeeding practices in Liverpool. Four inter-related studies were conducted to investigate the cost of infant feeding and associated practices. Initially a database was compiled of infant feeding products, this revealed a vast number of products marketed to both breast and formula feeding mothers. Semi-structured interviews were then conducted to identify all the items purchased for feeding infants up to the age of four months. The results of these interviews revealed that breastfeeding was more expensive than formula feeding but high and low cost models suggest that substantial savings could be made. Many mothers purchased items and subsequently did not use or need them. The suggestion that infant feeding and particularly breastfeeding has become unnecessarily commercialised was supported by content analysis of a wide range of UK pregnancy and baby magazines. These were consistent with parenthood being a consumer experience to be 'perfected', in addition to emphasising the need for 'expert' advice. Breastfeeding messages were undermined by formula company advertisements and breastfeeding was frequently presented as being painful and problematic. With these conflicting messages, it may not be surprising that many women initiated breastfeeding but ceased within three months. Those who did initiate breastfeeding frequently gave 'baby-centred' reasons such as breast is best whilst those who initiated formula feeding gave 'mother-centred' reasons such as others could help with feeding. Many women who ceased breastfeeding would have liked to have continued, and cited reasons that could have been overcome with increased support and encouragement. The importance of being supported was further highlighted by the women who attended the infant feeding clinic. This study has demonstrated that the materials needed for breastfeeding are clearly identified and health professionals are trained to support parents. In addition, the media needs to be persuaded to help create and support a breastfeeding culture, with the risks of formula feeding clearly communicated.

The use of antiretroviral therapy (ART) during pregnancy and lactation has significantly reduced the rate of mother-to-child transmission (MTCT) of HIV. However, pregnancy is known to affect the pharmacokinetics of many drugs, including key antiretroviral (ARV) drugs. In addition, ARV use during lactation raises questions about unintended exposure of breastfed infants to maternal drugs through breast milk. For drugs with significant genetic contribution to observed pharmacokinetic variability, we hypothesised that polymorphisms in drug disposition genes may accentuate or attenuate pregnancy-induced changes and/or breastfed infants’ exposure. HIV positive pregnant women and nursing mothers taking efavirenz (EFV)- or nevirapine (NVP)-based ART were recruited from three hospitals in Benue State, Nigeria. A novel strategy involving a preliminary pharmacogenetic association study was used to investigate the magnitude of pregnancy-induced changes in EFV and NVP pharmacokinetics in women stratified by single nucleotide polymorphisms (SNPs) in disposition genes. EFV apparent clearance (CL/F) was higher and AUC0-24, Cmax and Cmin were significantly lower in pregnant compared with postpartum women. When stratified based on the SNP with the highest predictive power, pregnant women with CYP2B6 516GG genotype were especially at risk. In the NVP cohort, exposure was also significantly lower in pregnant compared with postpartum women. When stratified based on composite CYP2B6 516G > T and 983T > C genotypes, Cmin was below target in most patients with combined CYP2B6 516GG and 983TT during pregnancy and postpartum. Cmin was below target in at least 50% of pregnant women with one or two variant alleles, compared with 0% in postpartum women. The intensive pharmacokinetics of EFV and NVP in breast milk and pharmacogenetic predictors were described for the first time. Breast milk pharmacokinetic parameters of EFV in breast milk differed significantly between patient groups stratified by CYP2B6 516G > T. The median time averaged milk-to-plasma concentration (M/P) ratio was 1.10 (range: 0.57-1.71) and the paediatric dose weight-adjusted exposure index was 4.05% (1.08-13.8). The resulting infant plasma concentration was influenced by CYP2B6 516G > T, highest up to 8 days of age at 1590 ng/mL (190-4631) and decreased by about 90% in the age stratum 9 days to 3 months. NVP AUC0-12, Cmax and Cmin in breast milk were significantly lower in patients with composite CYP2B6 516GG/983TT than those with at least one variant allele. The M/P ratio was 0.88 (0.74-1.2) and paediatric dose weight-adjusted exposure index was 3.64% (1.99-9.88). Infant plasma concentration differed significantly based on CYP2B6 516G > T/983T > C and CYP3A4 20230G > A (*1G), highest in those exposed through both breast milk and post-exposure prophylaxis compared with either alone. A breastfeeding physiologically-based pharmacokinetic (PBPK) model to predict infant exposure to maternal drugs through breast milk was developed and validated, with over 90% of all individual observed data points within the predictive interval. This thesis presents details about five different studies where these findings were observed. Their clinical implications in the context of current knowledge and practice were also explored.

Very severe maternal obesity (BMI > 40kg/m2) increases significantly the risks of poor pregnancy outcomes for both mothers and babies. In light of the limited success of behavioural interventions to date in improving outcomes in very severely obese women, this study sought to gain an understanding of women's beliefs and experiences regarding weight, health and pregnancy, within the context of their everyday lives. Qualitative serial interviews were conducted with eleven very severely obese women during pregnancy and the postnatal period. Seven partners of the women took part in one semi-structured interview during the woman's pregnancy. Analysis took place in several stages using a thematic approach. Themes were identified within and between individual women's accounts, as well as within and between the accounts of members of couples. Participants' narratives demonstrated the ways in which they navigated the experience of high-risk pregnancy, and stigma emerged as a key theme. This research contributes new knowledge about the complex ways in which women experience ‘very severe obese' pregnant embodiment, relating to both formal and informal discourses around weight and health in pregnancy. Most undertook ‘moral accounting' in response to stigma, and several accounts resonated with Monaghan's (2006) categorisations of excuses, justifications, contrition and repudiation, in both accounting for their weight and in demonstrating their ‘fitness' for pregnancy and motherhood. Following birth, high levels of motivation to enact behaviour change were expressed, in some cases alongside repudiatory accounting regarding the associated risks and the medicalisation of very severe obesity. Participants experienced a lack of formal healthcare support in the postnatal period. Future approaches to policy and practice should consider ways in which to engage women and partners during pregnancy, exploring ways which in which stigma can be acknowledged and neutralised, in order to provide support and advice during and after pregnancy and birth, and into parenthood.

Background: The relationship between interpersonal trauma (IPT) and substance misuse is complex and multi-factorial, but has not been examined fully in the existing few studies involving pregnant women who misuse substances. UK based midwifery education and practice is unique, but there is limited evidence regarding midwives experiences and perceptions of supporting this client group. Aims: The aim of this study was to chronologically map out pregnant women's past experiences of abuse and substance use, explore their experiences and perceptions of their journey to motherhood and explore midwives' experiences and perceptions of supporting this client group. Methods: A qualitative study was conducted. Five eligible pregnant women supported by specialist midwifery services in Central Scotland were recruited. Data were collected using a life history calendar (LHC), followed by an in-depth, semi-structured interview. Six eligible midwives were recruited from one NHS board in Central Scotland. In depth, semi-structured interviews were carried out. Findings: Individual LHCs were converted into chronological timelines. Transcribed interviews were analysed using Interpretative Phenomenological Analysis. The life history calendars revealed the pregnant participants' experiences of IPT and substance misuse as complex, interconnected and ongoing, including during pregnancy and motherhood. Three major overarching themes emerged from the pregnant participants' interview transcripts: “psychological trauma”, “dabbling to addiction” and “addiction and the identity of pregnancy and motherhood”. Three major overarching themes emerged from the midwifery participants' interview transcripts: “psychological trauma”, “stigma” and “managing unmanageable situations”. Conclusions: This study sheds new light on the lived experiences and perceptions of a previously under-researched and largely misunderstood group of vulnerable women. It highlights some of the challenges faced by midwives in clinical practice. Important areas for future research are highlighted, along with implications for multi-disciplinary education, policy and practice.