Trace elements as predictors of preeclampsia in type 1 diabetic pregnancy

Preeclampsia (PE) affects approximately 5% of all pregnancies, but is increased several-fold in women with pre-gestational type 1 diabetes mellitus (T1DM). Increased oxidative stress and altered maternal plasma trace elements that modulate the antioxidant system have been implicated in PE. In non-diabetic women, increased plasma copper and iron and decreased manganese, selenium, and zinc have been associated with PE in cross-sectional studies. In a longitudinal study, we hypothesized that plasma levels of trace elements differ between T1DM women with vs. without subsequent PE. Samples were collected during the first (gestation 12.2 ± 1.9 weeks, [mean ± SD]), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy, all before the onset of PE. We compared 23 T1DM women who subsequently developed PE with 24 T1DM women who remained normotensive; and we included 19 non-diabetic (non-DM) normotensive pregnant women as reference controls. Trace elements were measured using inductively coupled plasma mass spectroscopy. In T1DM women with subsequent PE vs normotensive, only plasma zinc was significantly higher at the first trimester, while copper:zinc and copper:high-density lipoprotein cholesterol ratios were higher throughout gestation (all P < .05). These findings persisted after adjustment for covariates. Higher copper:zinc ratios may contribute to oxidative stress in T1DM women who develop PE. Ratios of pro- to anti-oxidant factors may predict risk for PE in diabetic pregnancies more effectively than individual trace element levels.

Management of newly diagnosed chronic myeloid leukaemia during a twin pregnancy using leucapheresis: Case report and review of the literature

A case of chronic myeloid leukaemia diagnosed as an incidental finding in a 32-year-old woman, pregnant with twins at 11 weeks gestation, is presented. Management of the patient was with leucapheresis and supportive care until spontaneous delivery of two morphologically normal infants (one male, one female) at 37 weeks gestation. Special considerations while employing leucapheresis in pregnant patients are discussed.

Implications of aligning full registration of doctors with medical school graduation:a qualitative study of stakeholder perspectives

OBJECTIVES: The Shape of Training report recommended that full registration is aligned with medical school graduation. As part of a General Medical Council-funded study about the preparedness for practice of UK medical graduates, we explored UK stakeholders' views about this proposal using qualitative interviews (30 group and 87 individual interviews) and Framework Analysis.

SETTING: Four UK study sites, one in each country.Save

PARTICIPANTS: 185 individuals from eight stakeholder groups: (1) foundation year 1 (F1) doctors (n=34); (2) fully registered trainee doctors (n=33); (3) clinical educators (n=32); (4) undergraduate/postgraduate Deans, and Foundation Programme Directors (n=30); (5) other healthcare professionals (n=13); (6) employers (n=7); (7) policy and government (n=11); (8) patient and public representatives (n=25).

RESULTS: We identified four main themes: (1) The F1 year as a safety net: patients were protected by close trainee supervision and 'sign off' to prevent errors; trainees were provided with a safe environment for learning on the job; (2) Implications for undergraduate medical education: if the proposal was accepted, a 'radical review' of undergraduate curricula would be needed; undergraduate education might need to be longer; (3) Implications for F1 work practice: steps to protect healthcare team integration and ensure that F1 doctors stay within competency limits would be required; (4) Financial, structural and political implications: there would be cost implications for trainees; clarification of responsibilities between undergraduate and postgraduate medical education would be needed. Typically, each theme comprised arguments for and against the proposal.

CONCLUSIONS: A policy change to align the timing of full registration with graduation would require considerable planning and preliminary work. These findings will inform policymakers' decision-making. Regardless of the decision, medical students should take on greater responsibility for patient care as undergraduates, assessment methods in clinical practice and professionalism domains need development, and good practice in postgraduate supervision and support must be shared.

Address inaccuracy in health registration data: determinants and impacts

Access to demographic data that are complete, accurate and up-to-date is fundamental to many aspects of public health, government and academic work and for accurate interpretation of other databases. Health registration data are the prime source of demographic information for health and social care systems; for example, as an indicator of need, as a source of denominators to convert number of events into rates, or in the case of the residential address information as the basis for generating the call-recall invitation letters that are used for most screening programs (e.g. breast, colo-rectal and AAA screening). However, list inflation (ghosts, duplicates or emigrants) and a degree of address inaccuracy are recognised caveats with the health registration data and a recent NILS-related study on breast screening suggests that improved address accuracy might be a fast and efficient means of increasing screening uptake rates in cities and amongst deprived populations. In NI these data are collated by the BSO who uniquely in the UK also have access to data relating to prescribing, dental registrations and use of A&E services. These can be used to supplement the standard demographic and address information by (i) indicating patients who are alive and resident in NI and (ii) providing an independent source of probably improved address information. This study will use the NI Unique Property Reference Number (UPRN), rather than the addresses per se which are difficult to work with, to compare the addresses registered in the BSO with those addresses in the enumerated 2011 census. Assuming that the census is a more accurate source of address information for individuals, a comparison of the health registration addresses with those recorded at the census, the aim of the proposed study will be to (i) characterise the amount and distributions of these differences, (ii) to see what proportion of those who do not attend for screening did not actually receive an invitation letter because the addresses were incorrect, (iii) to determine how much of the social gradient (and urban/rural differences) in screening uptake are due to address inaccuracies, (iv) a comparison of timing of address changes at the BSO will provide information on the delays in updating of addresses.

Pregnancy and newborns disorders followed by urine metabolomics

Chapter 1 introduces the scope of the work by identifying the clinically relevant prenatal disorders and presently available diagnostic methods. The methodology followed in this work is presented, along with a brief account of the principles of the analytical and statistical tools employed. A thorough description of the state of the art of metabolomics in prenatal research concludes the chapter, highlighting the merit of this novel strategy to identify robust disease biomarkers. The scarce use of maternal and newborn urine in previous reports enlightens the relevance of this work. Chapter 2 presents a description of all the experimental details involved in the work performed, comprising sampling, sample collection and preparation issues, data acquisition protocols and data analysis procedures. The proton Nuclear Magnetic Resonance (NMR) characterization of maternal urine composition in healthy pregnancies is presented in Chapter 3. The urinary metabolic profile characteristic of each pregnancy trimester was defined and a 21-metabolite signature found descriptive of the metabolic adaptations occurring throughout pregnancy. 8 metabolites were found, for the first time to our knowledge, to vary in connection to pregnancy, while known metabolic effects were confirmed. This chapter includes a study of the effects of non-fasting (used in this work) as a possible confounder. Chapter 4 describes the metabolomic study of 2nd trimester maternal urine for the diagnosis of fetal disorders and prediction of later-developing complications. This was achieved by applying a novel variable selection method developed in the context of this work. It was found that fetal malformations (FM) (and, specifically those of the central nervous system, CNS) and chromosomal disorders (CD) (and, specifically, trisomy 21, T21) are accompanied by changes in energy, amino acids, lipids and nucleotides metabolic pathways, with CD causing a further deregulation in sugars metabolism, urea cycle and/or creatinine biosynthesis. Multivariate analysis models´ validation revealed classification rates (CR) of 84% for FM (87%, CNS) and 85% for CD (94%, T21). For later-diagnosed preterm delivery (PTD), preeclampsia (PE) and intrauterine growth restriction (IUGR), it is found that urinary NMR profiles have early predictive value, with CRs ranging from 84% for PTD (11-20 gestational weeks, g.w., prior to diagnosis), 94% for PE (18-24 g.w. pre-diagnosis) and 94% for IUGR (2-22 g.w. pre-diagnosis). This chapter includes results obtained for an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) study of pre-PTD samples and correlation with NMR data. One possible marker was detected, although its identification was not possible. Chapter 5 relates to the NMR metabolomic study of gestational diabetes mellitus (GDM), establishing a potentially predictive urinary metabolic profile for GDM, 2-21 g.w. prior to diagnosis (CR 83%). Furthermore, the NMR spectrum was shown to carry information on individual phenotypes, able to predict future insulin treatment requirement (CR 94%). Chapter 6 describes results that demonstrate the impact of delivery mode (CR 88%) and gender (CR 76%) on newborn urinary profile. It was also found that newborn prematurity, respiratory depression, large for gestational age growth and malformations induce relevant metabolic perturbations (CR 82-92%), as well as maternal conditions, namely GDM (CR 82%) and maternal psychiatric disorders (CR 91%). Finally, the main conclusions of this thesis are presented in Chapter 7, highlighting the value of maternal or newborn urine metabolomics for pregnancy monitoring and disease prediction, towards the development of new early and non-invasive diagnostic methods.

During pregnancy, recreational drug-using women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce alcohol consumption but continue to smoke tobacco and cannabis

While recreational drug use in UK women is prevalent, to date there is little prospective data on patterns of drug use in recreational drug-using women immediately before and during pregnancy. A total of 121 participants from a wide range of backgrounds were recruited to take part in the longitudinal Development and Infancy Study (DAISY) study of prenatal drug use and outcomes. Eighty-six of the women were interviewed prospectively while pregnant and/or soon after their infant was born. Participants reported on use immediately before and during pregnancy and on use over their lifetime. Levels of lifetime drug use of the women recruited were high, with women reporting having used at least four different illegal drugs over their lifetime. Most users of cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and other stimulants stopped using these by the second trimester and levels of use were low. However, in pregnancy, 64% of the sample continued to use alcohol, 46% tobacco and 48% cannabis. While the level of alcohol use reduced substantially, average tobacco and cannabis levels tended to be sustained at pre-pregnancy levels even into the third trimester (50 cigarettes and/or 11 joints per week). In sum, while the use of ‘party drugs’ and alcohol seems to reduce, levels of tobacco and cannabis use are likely to be sustained throughout pregnancy. The data provide polydrug profiles that can form the basis for the development of more realistic animal models.

Betel Use in Pregnancy

Thesis (Master's)--University of Washington, 2015

PREGNANCY-RELATED CHURN AND ACCESS TO CARE IN THE CONTEXT OF NARROW NETWORKS IN WASHINGTON STATE

Thesis (Master's)--University of Washington, 2016-03