CARBON MONOXIDE AND PREGNANCY: A SEARCH FOR A POSSIBLE THERAPEUTIC IN THE TREATMENT OF PRE-ECLAMPSIA

Pre-eclampsia (PE) is a pregnancy disorder that affects roughly 5-7% of all pregnancies and is a leading cause of both maternal and fetal/neonatal morbidity and mortality. With no present cure for the disease, researchers are interested in the lower incidence of PE observed among the cigarette smoking pregnant population. However, women who use smokeless tobacco do not experience the same decreased incidence of PE, leading to hypothesis of protection against PE from the largest combustible product of cigarette smoke, carbon monoxide (CO). Studies evaluated levels of CO in PE women and found that they were statistically lower than those of healthy pregnancy. Researchers have found CO to possess many cytoprotective and regulatory properties and specifically within the placenta, it has been found to increase perfusion pressure, decrease oxidative stress, decreases ischemia/reperfusion induced apoptosis and maintain endothelial functioning. The idea for use of CO as a possible therapeutic for PE has thus become a real possibility. This study determined CO levels in pregnant women ± smoking as well as in PE women±smoking, as to discover a possible therapeutic range for future treatments. The best correlated automated CO measurement device with blood CO levels was determined, for use in future clinical studies. This thesis also sought a possible CO delivery concentration, in order to achieve the CO levels observed in the human correlation study. A threshold level of maternal CO exposure in a murine animal model was found, for which fetal and maternal negative toxicities were not observed. The results of this thesis lend a few more pieces to the complicated puzzle involving CO and PE and offer another step toward the possibility of a therapeutic treatment/prevention using this gaseous molecule.

Design, construction and evaluation of systems to predict risk in obstetrics

We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy. We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.

Pré-eclâmpsia : o estado da arte : fisiopatologia, fatores de risco, rastreio, profilaxia : uma revisão da literatura

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

The safety of medications for the treatment of bipolar disorder during pregnancy and the peurperium

Risks associated with pharmacological treatment of bipolar disorder are heightened during reproductive events. Treatments need to be planned with the mutual agreement of both the treating physician and the patient and tailored to the needs of the individual so as to minimise risk while providing adequate treatment. Conventional treatments have all been associated with teratogeny in first trimester exposure, lithium with cardiac malformation and valproate and carbamazepine with neural tube malformations. There have been an insufficient number of first trimester exposures to the newer anticonvulsant mood stabilisers, lamotrigine and oxcarbazepine, to determine whether there is a safety advantage in switching to these agents. Increasingly, atypical antipsychotics are being suggested as useful agents for the treatment of bipolar disorder. While not known to be teratogenic, there are other reproductive safety concerns associated with these agents. Bipolar disorder patients may be prescribed antidepressants, and many of these agents are associated with a low safety risk during reproductive events, however data regarding use of these agents are currently equivocal. Adverse outcomes from inadequate pharmacological prophylaxis have been documented for both the mother and the baby. Risks and benefits need to be carefully balanced based on an accurate review of the evidence.

Pregnancy in inherited hypokalemic salt-losing renal tubular disorder

The management of inherited hypokalemia has improved and the issue of pregnancy has become important.

Pregnancy loss and psychiatric disorders in young women : an Australian birth cohort study

Background Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Aims To examine whether abortion or miscarriage are associated with subsequent psychiatric and substance use disorders. Method A sample (n=1223) of women from a cohort born between 1981 and 1984 in Australia were assessed at 21 years for psychiatric and substance use disorders and lifetime pregnancy histories. Results Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis): abortion odds ratio (OR)=3.6 (95% CI 2.0–6.7) and miscarriage OR=2.6 (95% CI 1.2–5.4). Abortion was associated with alcohol use disorder (OR=2.1, 95% CI 1.3–3.5) and 12-month depression (OR=1.9, 95% CI 1.1–3.1). Conclusions These findings add to the growing body of evidence suggesting that pregnancy loss per se, whether abortion or miscarriage, increases the risk of a range of substance use disorders and affective disorders in young women.

FP01-5 Pregnancy loss and psychiatric disorders in young men and women : results from Australian longitudinal cohort study

Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Little is known about later adverse psychiatric outcomes in young men whose partners have fallen pregnant and either go on to have a child, have an abortion or miscarry. 1223 women and 1159 men, from an Austrailan cohort born between 1981 and 1984, were assessed at 21 years for psychiatric and substance misuse and lifetime pregnancy histories. Young women reporting a pregnancy loss (either miscarriage or abortion) had nearly three times the odds of experiencing a illicit drug disorder (excluding cannabis), and nearly twice the odds of an alcohol misuse compared to never pregnant women. Young men whose partner had an abortion, but not a miscarriage, had nearly twice the odds of cannabis disorder, illicit drug disorder, and mood disorder compared to men that had never fathered a pregnancy. Young women who have lost a pregnancy have an increased risk of developing alcohol or substance abuse in later life. Young men whose partner aborted a pregnancy only had an increased of substance abuse and mood disorder in later life. These findings add to the growing body of evidence suggesting that pregnancy loss per se increases the risk of a range of substance use disorders in young women. The findings for young men are novel and raise the possibility that the associations measured may be due to common unmeasured factors associated with early pregnancy in young people rather than pregnancy loss.

Fetal Alcohol Spectrum Disorder diagnosis and counselling

The Foetal Alcohol Syndrome has long gone unrecognised and undiagnosed in Australia. In the last few years of the 21st Century (2010-14) health practitioners are finally seeking ways of diagnosing the effects of alcohol in pregnancy on the next generation. The author offers a power point presentation which gives guidance on making an accurate diagnosis.

Health communication: A pilot study comparing perceptions of women with and without high functioning autism spectrum disorder

Research indicates significant health disparities for individuals with autism. Insight into characteristic sensory, cognitive, communication, social, emotional, and behavioural challenges that may influence health communication for patients with autism is vital to address potential disparities. Women with high functioning autism spectrum disorder (ASD) may have specific healthcare needs, and are likely to independently represent themselves and others in healthcare. A pilot study compared perceptions of healthcare experiences for women with and without ASD using on-line survey based on characteristics of ASD likely to influence healthcare. Fifty-eight adult female participants (32 with ASD diagnosis, 26 without ASD diagnosis) were recruited on-line from autism support organisations. Perceptions measured included self-reporting of pain and symptoms, healthcare seeking behaviours, the influence of emotional distress, sensory and social anxiety, maternity experiences, and the influence of autistic status disclosure. Results partially support the hypothesis that ASD women experience greater healthcare challenges. Women with ASD reported greater challenges in healthcare anxiety, communication under emotional distress, anxiety relating to waiting rooms, support during pregnancy, and communication during childbirth. Self-disclosure of diagnostic status and lack of ASD awareness by healthcare providers rated as highly problematic. Results offer detailed insight into healthcare communication and disparities for women with ASD.

Clinical characteristics and management of bipolar disorder in women across the life span

Though prevalent in both genders, specific consideration needs to be given when treating a woman suffering from bipolar disorder over her lifetime. Bipolar disorder is a serious and incapacitating illness affecting an estimated 5% of women. The first episode of illness in women is usually a depressive episode. Female gender has been associated with greater axis-one comorbidity, more depressive episodes, rapid cycling and mixed affective states. Special consideration is required for the treatment of bipolar disorder during reproductive events. More studies are required to better understand the course, outcome and gender-specific treatment strategies of this disorder.

Identification and genetic determination of an early life risk disposition for depressive disorder : atypical stress-related behaviour in early childhood

Progress in psychiatric genetics has been slow despite evidence of high heritability for most mental disorders. We argue that greater use of early detectable intermediate traits (endophenotypes) with the highest likely aetiological significance to depression, rather than complex clinical phenotypes, would be advantageous. Longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study were used to identify an early life behavioural endophenotype for atypical hypothalamic-pituitaryadrenocortical function in adolescence, a neurobiological indicator of anxiety and depression. A set of descriptors representing rigid and reactive behaviour at age 1 year discriminated those in the top 20% of the free salivary cortisol exposure at age 17 years. Genetic association analysis revealed a male-sensitive effect to variation in three specific single nucleotide polymorphisms within selected genes underpinning the overall stress response. Furthermore, support for a polygenic effect on stress-related behaviour in childhood is presented.

Effect of pregnancy for females born small on later life metabolic disease risk

There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. 

Psychopharmacology and pregnancy : treatment efficacy, risks, and guidelines

 This book examines the role of psychopharmacological treatment in a range of disorders that may be encountered during pregnancy, including major depressive disorders, anxiety disorders, bipolar affective disorder, schizophrenia, eating disorders, and substance abuse. The natural history of each condition pre- and post-partum is analyzed, and the evidence for the efficacy of drug treatments, evaluated. Special attention is paid to the potential dangers of different treatment options for both mother and fetus, covering risks of malformation, pregnancy and obstetric risks, neonatal risks, and possible long-term consequences. The risks of not treating a particular condition are also analyzed. On the basis of the available evidence, management guidelines are provided that additionally take into account non-pharmacological options. Closing chapters consider the value of complementary and alternative medicine and ECT and explore future research directions.

Observable essential fatty acid deficiency markers and autism spectrum disorder

Autism Spectrum Disorder (ASD) has been associated with essential fatty acid (EFA) deficiencies, with some researchers theorising that dysregulation of phospholipid metabolism may form part of the biological basis for ASD. This pilot study compared observable signs of fatty acid status of 19 children with an ASD diagnosis to 23 of their typically developing siblings. A pregnancy, birth and breastfeeding history was also obtained from their parents, which included a measure of infant intake of fatty acid rich colostrum immediately post-partum. When considered within their family group, those infants not breastfed (with colostrum) within the first hour of life and who had a history of fatty acid deficiency symptoms were more likely to have an ASD diagnosis. Other variables such as formula use, duration of breastfeeding, gestational age and Apgar scores were not associated with group membership. The results of this study are consistent with previous research showing a relationship between fatty acid metabolism, breastfeeding and ASD such that early infant feeding practices and the influence this has on the fatty acid metabolism of the child may be a risk factor for ASD.