BACKGROUND: Highly active antiretroviral therapy(HAART) is used in pregnancy to suppress viral load(pVL) before delivery, reducing risk of vertical HIV-transmission. Nelfinavir(NFV) containing HAART has been highly used in pregnancy, but dosages may be inadequate due to the physiologic changes that occur. Given concerns regarding optimal viral suppression in pregnancy, drug toxicity and resistance development, NFV levels need to be evaluated in this population to guide dosing recommendations. METHODS: As part of a prospective cohort study maternal blood was collected at 18-28wks, 32-37wks and at delivery. Times of last medication dose and blood sampling were recorded and drug levels were measured using HPLC MS-MS. NFV concentration-ratios(NFV-CRs) were calculated by dividing individual levels by a time-adjusted population value. Plasma NFV concentrations and NFV-CRs were compared across gestational age and correlated to variables of interest. Rate and maintenance of viral suppression were analyzed in relation to NFV concentrations and CRs. Statistical tests included ANOVA, χ2, linear regression, and Kaplan Meier estimates. RESULTS: 113 samples were collected from 32 subjects. Samples were eliminated if not in steady state (n=20); 93 samples from 32 subjects were analyzed. Mean NFV-CR at 18-28wks (1.1±0.73) and 32-37wks (0.86±0.73) were not significantly different but were both significantly higher by ANOVA (p=0.049) than the mean NFV-CR at delivery (0.44±0.50). CRs were highly variable. Of 49 antepartum samples, 49%(24) had a CR<0.90 (clinically relevant threshold). Four women reached a pVL <50 copies/mL by 34wks but had a detectable pVL at delivery. One woman never reached an undetectable pVL in pregnancy. Minimum and mean NFV-CRs in these 5 women were not significantly different than those who achieved and maintained virologic suppression. Vertical HIV transmission rate was 0%. CONCLUSIONS: There were no HIV transmissions but 16% (5/32) of women were inadequately suppressed at delivery, which is of concern. Factors associated with inadequate suppression and NFV-CRs need to be explored in conjunction with patient/physician reported adherence and viral resistance profiles. Extreme variability in CRs may limit the potential usefulness of random timed drug levels in all pregnant women.

The partograph, developed over 50 years ago and based on research conducted by Friedman (1954, 1955 & 1956), has been promoted by the World Health Organisation as the “gold” standard for assessing progress in labour. The basic premise of the partograph is that regular vaginal examinations throughout labour that calculate the extent and rate of cervical dilation will be the most reliable indicator of labour progress. A review of the medical and midwifery literature suggested that the progress of labour can also be assessed by observing women’s behavioural responses to labour. This study set out to describe and test the reliability and consistency of these behavioural cues. These cues were derived from published literature and used to construct a “Labour Assessment Tool” (LAT). The LAT was tested and modified using an expert reference group and results of a pilot test. Inter-rater reliability was established during the pilot study and verified with other experienced midwives as data collectors. The LAT recorded partograph observations as well as labour behaviours. The study was undertaken in two Australian hospitals between 1999 and 2002. Women were given information on the study during regular antenatal visits to the hospitals from 30 weeks gestation and invited to participate during one of their antenatal visits between 37 weeks and 42 weeks of pregnancy. There were 21 women of the 225 women approached who declined to participate. The LAT observations were recorded on 203 participants however only 179 participants (94 nulliparous and 85 multiparous women) who generated 47,768 individual observations were suitable for analysis. There were 59 participants (31 nulliparous and 28 multiparous women) who were induced into labour or had their labours augmented. Women excluded from the study included those with complications of pregnancy and labour. Women were also withdrawn from the study at the time an epidural was commenced but their data to that point were retained for analysis. The data were examined from three perspectives. The first was from a ‘phases of labour’ perspective based on the work of Friedman (1954; 1955). Data obtained at the time the women had an internal cervical assessment were allocated to early labour, active labour, transition or full dilation, based on the results of the cervical measurements. The second perspective examined all the descriptors over the course of labour from admission to hospital or the beginning of an induction of labour, to second stage of labour. Frequencies were again generated for each behaviour from admission to hospital until full dilation. They were compared to the mean dilation generated for both parity groups based on the 279 cervical examinations that were performed on the participants. The third perspective examined behavioural patterns observed within each woman’s labour unrelated to the time to full dilation or Friedman’s phases of labour model. Results indicate that specific behavioural descriptors associated with progress were observed before cervical dilation increased. Descriptors indicating cervical dilation was occurring, or had occurred, and descriptors indicating impending second stage as well as second stage itself, were identified. Differences were observed between the labours of multiparous and nulliparous women and induced labours and non induced labours.

Background Unexplained stillbirth is the largest contributor to perinatal death, accounting for one third of stillbirths. Although prognostic information is limited, there is no increase in perinatal death rates in subsequent pregnancies after an unexplained stillbirth. However, those pregnancies have increased rates of preterm birth, low birthweight, induced labour, instrumental and caesarean delivery, 'fetal distress,' and postpartum haemorrhage. These outcomes might be iatrogenic, caused by obstetric intervention. Aims 1. To examine obstetricians' and womens' wishes for management in pregnancies subsequent to an unexplained stillbirth, and whether these might contribute to an increase in rates of intervention. 2. To examine whether socio-demographic factors, or how women perceive that an unexplained stillbirth was managed, influence how women want their next pregnancy managed. 3. To assess whether management of unexplained stillbirth differs according to model of care, or country where the event occurred. Methods 1. An anonymous postal survey of all Australian obstetricians to determine recommended management of the next pregnancy after an unexplained stillbirth. 2. An Internet-based survey of women after an unexplained stillbirth, seeking details about their wishes for subsequent pregnancy management. Results 1. Obstetricians' survey Early pregnancy managements were little different from standard care of low-risk pregnancy. Increased 'fetal surveillance' (by ultrasound, cardiotocography, and formal fetal movement charting) in late pregnancy was recommended by most respondents. Induction of labour would be offered by 93% of respondents, as early as 37 weeks by one third. More than one third of obstetricians would offer elective caesarean delivery, with 13% offering this before 38 weeks. 2. Womens'survey 93% of respondents wanted 'testing' over and above normal pregnancy care in their next pregnancy. 81% of respondents wanted early delivery, and 26% wanted a caesarean delivery, irrespective of obstetric indications. These wishes were not influenced by socio-demographic factors, management of the index stillbirth (with the exception of having had a caesarean delivery), or advice received about management of the next pregnancy (with the exception of being advised to have an early or caesarean delivery). Conclusions Both obstetricians and the women they care for wanted increased fetal surveillance and early delivery, but not necessarily elective caesarean section. These practices have the potential to increase the rate of intervention, with consequent adverse maternal and neonatal outcomes.

This study examined the effects of prenatal exposure to methadone on clinical and neurobehavioural outcomes of infants between 40 and 42 weeks gestation. The aims of this study were: (a) to describe clinical and neurobehavioural outcomes of infants exposed to methadone during pregnancy, (b) to examine the effects of maternal methadone dose during pregnancy on infant clinical and neurobehavioural measures, and (c) to examine the extent to which associations between exposure to methadone during pregnancy and infant outcomes persisted after statistical control for a range of confounding variables. Two groups of study infants were recruited. These consisted of 51 consecutively recruited infants born to mothers maintained on methadone during their pregnancy and 42 randomly identified non-methadone exposed comparison infants. Prior to her child's birth, each pregnant woman completed a comprehensive maternal interview. At birth and during the infant's hospital stay a broad perinatal data-base was collected. At 42 weeks gestation infants underwent a neurobehavioural assessment including the NICU Network Neurobehavioural Scale (NNNS; Lester & Tronick, 2004) and infant cry analysis. Study results showed significant differences across several clinical and neurobehavioural measures. Infants exposed to methadone in utero were found to be significantly lighter, have smaller head circumferences, and spend longer in hospital. Neurobehaviourally, they were significantly less well regulated, less attentive, more easily aroused, more excitable, and more hypertonic. In addition, they exhibited less motor maturity, displayed more stress abstinence symptomatology, and required more support from the assessor in order to remain in an appropriate state. Concurrent analysis of infant cry characteristics revealed no significant differences between the fundamental frequencies or the melody contours of the two groups. However, infants prenatally exposed to methadone did display higher levels of frequency perturbation in their cries, as evidenced by analysis of their jitter factor and percentage of directional jitter. Analysis of the effects of maternal dose during pregnancy suggested that maternal dose levels above 60mg/day were general indicative of poorer infant outcomes than those below 60mg/day, with significant linear trends occurring across a number of measures. The extent to which associations between methadone exposure during pregnancy and infant outcomes reflected either a) the direct effects of methadone exposure and/or b) the effects of confounding factors correlated with maternal methadone use was examined using regression analysis. The results of this analysis for infant clinical outcomes showed confounding variables attenuated the effects of methadone exposure on infant birth length and, to some degree, infant head circumference. In contrast, associations between methadone exposure during pregnancy and most neurobehavioural outcomes remained significant, suggesting that maternal methadone use during pregnancy is an important, independent predictor of infant neurobehavioural functioning. These findings support the view that prenatal exposure to methadone has at least short term impacts on the infant's central nervous system (CNS) development. Important implications of possible vulnerabilities faced by these infants and their families are discussed.

Doctor of Philosophy / Multiple sclerosis (MS) is the most common neurological disease affecting young adults. MS affects approximately 1 in 1000 people and, like other autoimmune diseases, women are more likely to be affected than men. The illness typically onsets between the ages of 20 and 40, and hence usually affects women of child-bearing age. The course of the MS is often unclear for years after diagnosis and since most women are diagnosed in their child-bearing years, they often have to make reproductive choices before their prognosis is clear and while the future remains uncertain. For women with MS, starting a family is an individual choice that needs to balance the importance of motherhood for the woman and her partner against the risks that she will be unable to care for the infant or child as a result of increasing disability. In other areas of medicine where finely balanced decisions are required, there has been a recent proliferation of decision aids that aim to inform people of the benefits and risks of opposing courses of action. In addition, decision aids help patients to weigh their values against the risks and benefits to make an informed decision. Despite the existence of over 200 decision aids to help patients consider decisions related to their medical conditions, not one exists that deals with the decision of whether or not to have a family for women with a chronic disability, such as MS. This thesis developed and evaluated a decision aid for women with MS to help them decide whether to start, forego or enlarge their families. The study utilised the criteria set out for the development of decision aids, according to the Cochrane Systematic Review of Patient Decision Aids (O'Connor et al., 2003). The first aim was to determine the proportion of women who are undecided about the motherhood choice and for whom a decision aid may be relevant. Results found that the motherhood choice was relevant to 46% of the women who responded to an initial mail-out. The second study aimed to establish women’s current concerns and thoughts regarding pregnancy and motherhood, and their response to the pilot decision aid. Twenty women participated in qualitative interviews and results supported previous findings that the mother’s health concerns, coping with parenting and societal attitudes are significant concerns when considering this decision. This study further identified concerns from different groups that had a direct impact on the decision to have children, including the experience of parenting, the child’s well-being and the timing and pressure of the decision. The main study was a randomised controlled trial of the decision aid aiming to determine whether the decision aid facilitated decision-making in women with MS. The study confirmed that the decision aid presented a balanced view to women, increased knowledge, reduced decisional conflict, increased decisional self-efficacy and certainty of the decision, and was free from adverse effects on psychopathology. The final component of the study was a 12 month follow-up which aimed to explore the long-term effectiveness of the decision aid and what aspects were valued by the women who received it. It was found that over time, women in the intervention group did maintain their certainty, but women in the control group also became more certain of their choice. At follow-up, the difference in certainty was no longer significant between the two groups. However, women did report that the intervention was useful in (a) providing access to information previously unavailable or difficult to obtain, (b) facilitating communication between women, their partners and health care professionals, (c) aiding them in considering and utilising their networks of support, and (d) preparing them for potential difficulties. In summary, this thesis developed and evaluated a decision aid for women with MS who are considering motherhood. The results showed that many women were undecided and, in the absence of good information on the topic, many women had concerns about pregnancy and parenthood. The decision aid was shown to be effective across a range of measures and free from adverse psychological effects. Hence, this is evidence-based resource can now be recommended for those women with MS who are currently contemplating motherhood.

Thesis (M.S.) in Human Development--University of Maine, 2004. / Includes vita. Includes bibliographical references (leaves 51-55).

Thesis (Ph. D.)--University of Wyoming, 2005. / Title from PDF title page (viewed on Nov. 14, 2007). Includes bibliographical references (p. 167-211).

Thesis (Ph.D.)--McMaster University, 2003. / Advisor: B. G. Galef, Jr. Includes bibliographical references (leaves 106-115). Also available via World Wide Web.

Thesis (M.S.)--University of Nevada, Reno, 2006. / "December 2006." Includes bibliographical references (leaves 31-34). Online version available on the World Wide Web.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2008. / Härtill 4 uppsatser.