The role of Ureaplasma urealyticum in adverse pregnancy outcome

We investigated Ureaplasma urealyticum genital tract colonisation rates in an Australian population to determine whether colonisation was associated with adverse pregnancy outcome. Women attending an antenatal clinic were evaluated for lower genital tract colonisation at their first antenatal visit (162 women) and at 28 weeks gestation (120 women). Placentas from 92 women were cultured. U. urealyticum was the predominant isolate from the lower (57.4%) and upper (17.4%) genital tract in this population of pregnant women. U. urealyticum was a persistent coloniser during mid-trimester of pregnancy (in 88% of women colonised) whereas M. hominis, G. vaginalis, and Group B streptococcus were present as transient flora of the lower genital tract. Lower genital tract colonisation during pregnancy was not directly associated with adverse pregnancy outcome. However preterm delivery in afebrile, asymptomatic women, could possibly be associated with chorioamnionitis (four of 16 preterm births). Screening of women with a history of preterm birth may prevent upper genital tract infections and preterm delivery.

Estimating vulnerable windows of exposure to air pollution during pregnancy

Exposure to air pollution during pregnancy is a potential cause of adverse birth outcomes such as preterm birth and stillbirth. The risk of exposure may be greater during vulnerable windows of the pregnancy which might only be weeks long. We demonstrate a method to find these windows based on smoothing the risk of weekly exposure using conditional autoregression. We use incidence density sampling to match cases with adverse birth outcomes to controls whose gestation lasted at least as long as the case. This matching means that cases and controls are have equal length exposure periods, rather than comparing, for example, cases with short gestations to controls with longer gestations. We demonstrate the ability of the method to find vulnerable windows using two simulation studies. We illustrate the method by examining the association between particulate matter air pollution and stillbirth in Brisbane, Australia.

Triclosan and benzophenone-3 in Australian pooled infant urine

The period of developmental vulnerability begins at conception and extends through gestation, parturition, infanthood and adolescence. The World Health Organisation (WHO) acknowledges that children experience quantitatively and qualitatively different exposures to chemicals than adults, and that children may be more or less sensitive to a chemical than adults [1, 2]. For instance, because of mouthing behaviours, children have higher exposure to chemicals through non-dietary ingestion than adults [3, 4], and the possibility exists for different metabolism and/or toxicity between different groups due to the immaturity of defense mechanisms that are fully developed in adults [1]. Traditional toxicological studies are inappropriate for assessing the results of exposure at very low levels during critical periods of development. Biomonitoring data can be used to identify where policies should be directed in order to reduce exposure.

Ureaplasma speioces are associated with chorioamnionitiis in late preterm placentas

Background: Preterm birth is a major cause of neonatal morbidity and mortality, with 75% of preterm births occurring late preterm. Previous studies have investigated the microbial diversity within placentas delivered early preterm but there has been no investigation of the prevalence of bacteria, particularly Ureaplasma spp. in late preterm placentas. Method: Women giving birth late preterm (320 – 366 weeks of gestation) in Cincinnati were recruited for this study. Samples of chorioamnion were collected aseptically at the time of delivery, shipped to QUT and tested for Ureaplasma spp. and other bacteria by culture and/or PCR assays. The presence of bacteria was correlated with adverse pregnancy outcomes, including histological chorioamnionitis (tissue sections read by US pathologists). Results: To date, Ureaplasma spp. have been detected in 15/270 (5.5%) of placentas by culture and 19/270 (7%) by PCR. Ureaplasma presence correlated with histological chorioamnionitis (12/19%; 63%). However, the presence of other bacteria was not associated with chorioamnionitis (5%). Chorioamnionitis was unevenly distributed in ethnic groups, with a higher incidence in African-Americans’ (6/7; 86%), compared to Caucasians’ (6/12; 50%) who were colonised with ureaplasmas. Conclusion: This study is the first to report the prevalence of ureaplasmas in women (7%) who deliver late preterm. Ureaplasma spp. were associated with a higher incidence of chorioamnionitis (63% compared to 15% for non-infected women). This data strongly suggests that ureaplasmas are a cause of late preterm deliveries and African-American women are at greater risk of chorioamnionitis.

Modulation of LPS-induced chorioamnionitis by ureaplasma parvum in sheep chorioamnionitis in sheep

ABSTRACT Objective: Ureaplasma parvum colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that ureaplasma colonization of amniotic fluid will modulate chorioamnionitis induced by E.coli lipopolysaccharide (LPS). Methods: Sheep received intra-amniotic (IA) injections of media (control) or live ureaplasma either 7 or 70d before delivery. Another group received IA LPS 2d before delivery. To test for interactions, U.parvum exposed animals were challenged with IA LPS, and delivered 2d later. All animals were delivered preterm at 125±1 day gestation. Results: Both IA ureaplasmas and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of pro-inflammatory cytokines and myeloperoxidase in leukocytes, while ureaplasmas alone caused modest responses. Interestingly, 7d but not 70d ureaplasma exposure significantly downregulated LPS induced pro-inflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion: U.parvum can suppress LPS induced experimental chorioamnionitis.

Ureaplasma parvum multiple banded antigen (MBA) size variation - association with fetal inflammation in a sheep model (Published abstract)

Background: Ureaplasma species are the most prevalent isolates from women who deliver preterm. The MBA, a surface exposed lipoprotein, is a key virulence factor of ureaplasmas. We investigated MBA variation after chronic and acute intra-amniotic (IA) ureaplasma infections. Method: U. parvum serovar 3 (2x104 colony-forming-units) was injected IA into pregnant ewes at: 55 days gestation (d, term = 145d) (n=8); 117d (n=8) and 121d (n=8). Fetuses were delivered surgically (124d) and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord were tested by western blot and PCR assays to demonstrate MBA and mba gene variation respectively. Tissue sections were sectioned and stained by haemotoxylin and eosin and inflammatory cell counts and pathology were reported (blinded to outcome). Results: Numerous MBA/mba variants were generated in vivo after chronic exposure to ureaplasma infection but after acute infection no variants (3d) or very few variants (7d) were generated. Identical MBA variants were detected within the AF and FL but different ureaplasma variants were detected within chorioamnion specimens. The severity of inflammation within chronically infected tissues varied between animals ranging from no inflammation to severe inflammation with/without fibrosis. Chorioamnion, FL and cord from the same animal demonstrated the same degree of inflammation. Conclusions: MBA/mba variation in vivo occurred after the initiation of the host immune response and we propose that ureaplasmas vary the MBA antigen to evade the host immune response. In some animals there was no inflammation despite colonisation with high numbers of ureaplasmas.

Genetic variability and antimicrobial resistance of Ureaplasma parvum in response to maternal erythromycin treatment : a study in pregnant sheep

Background: Ureaplasmas are the most frequently isolated microorganisms from the amniotic fluid (AF) of pregnant women and can cause chronic infections that are difficult to eradicate with standard macrolide treatment. We tested the effects of erythromycin treatment on phenotypic and genotypic markers of ureaplasmal antimicrobial resistance in sheep. Method: At 50 days of gestation (d, term=145d) 12 pregnant ewes received intra-amniotic injections of U. parvum serovar 3 (erythromycin-sensitive, 2x104 colony-forming-units). At 100d ewes received: erythromycin treatment (500 mg, q3h for 4 days, IM, n=6) or no treatment (n=6). Fetuses were delivered surgically (125d) and AF and chorioamnion were collected for: culture, minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) testing; 23S rRNA sequencing; and detection of macrolide-lincosamide-streptogramin resistance (MLSr) genes. Results: MICs of erythromycin, azithromycin and roxithromycin against AF isolates were low (range = 0.06 mg/L to 1.0 mg/L); however, chorioamnion isolates demonstrated increased resistance to roxithromycin (0.13 – 5.33 mg/L). 62.5% of chorioamnion ureaplasmas formed biofilms in vitro and mutations (125 nucleotides, 29.6%) were found in the 23S rRNA gene (domain V) of chorioamnion (but not AF) ureaplasmas. MLSr genes (ermB, msrC and msrD) were detected in 100% of chorioamnion isolates and only msrD was detected in AF isolates (40%). Conclusions: 23S rRNA mutations and MLSr genes occurred independently of erythromycin treatment, suggesting that the anatomical site of infection and microenvironment may exert selective pressures on ureaplasmas that cause genetic changes and alter antimicrobial sensitivity profiles. These results have serious implications for treatment of in utero infections.

Ureaplasma parvum serovar 3 multiple banded antigen size variation after chronic intra-amniotic infection/colonization

Ureaplasma species are the microorganisms most frequently associated with adverse pregnancy outcomes. The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a key virulence factor of ureaplasmas. The MBA demonstrates size variation, which we have shown previously to be correlated with the severity of chorioamnion inflammation. We aimed to investigate U. parvum serovar 3 pathogenesis in vivo, using a sheep model, by investigating: MBA variation after long term (chronic) and short term (acute) durations of in utero ureaplasma infections, and the severity of chorioamnionitis and inflammation in other fetal tissues. Inocula of 2x107 colony-forming-units (CFU) of U. parvum serovar 3 (Up) or media controls (C) were injected intra-amniotically into pregnant ewes at one of three time points: day 55 (69d Up, n=8; C69, n=4); day 117 (7d Up, n=8; C7, n=2); and day 121 (3d Up, n=8; C3, n=2) of gestation (term=145-150d). At day 124, preterm fetuses were delivered surgically. Samples of chorioamnion, fetal lung, and umbilical cord were: (i) snap frozen for subsequent ureaplasma culture, and (ii) fixed, embedded, sectioned and stained by haematoxylin and eosin stain for histological analysis. Selected fetal lung clinical ureaplasma isolates were cloned and filtered to obtain cultures from a single CFU. Passage 1 and clone 2 ureaplasma cultures were tested by western blot to demonstrate MBA variation. In acute durations of ureaplasma infection no MBA variants (3d Up) or very few MBA variants (7d Up) were present when compared to the original inoculum. However, numerous MBA size variants were generated in vivo (alike within contiguous tissues, amniotic fluid and fetal lung, but different variants were present within chorioamnion), during chronic, 69d exposure to ureaplasma infection. For the first time we have shown that the degree of ureaplasma MBA variation in vivo increased with the duration of gestation.

Business planning, innovation and performance in nascent firms

Debate about the relationships between business planning and performance has been active for decades (Bhidé, 2000; Mintzberg, 1994). While results have been inconclusive, this topic still strongly divides the research community (Brinckmann et al., 2010; Chwolka & Raith, 2011; Delmar & Shane, 2004; Frese, 2009; Gruber, 2007; Honig & Karlsson, 2004). Previous research explored the relationships between innovation and the venture creation process (Amason et al., 2006, Dewar & Dutton, 1986; Jennings et al., 2009). However, the relationships between business planning and innovation have mostly been invoked indirectly in the strategy and entrepreneurship literatures through the notion of uncertainty surrounding the development of innovation. Some posited that planning may be irrelevant due to the iterative process, the numerous changes innovation development entails and the need to be flexible (Brews & Hunt, 1999). Others suggested that planning may facilitate the achievement of goals and overcoming of obstacles (Locke and Latham, 2000), guide the venture in its allocation of resources (Delmar and Shane, 2003) and help to foster the communication about the innovation being developed (Liao & Welsh, 2008). However, the nature and extents of the relationships between business planning, innovation and performance are still largely unknown. Moreover, if the reasons why ventures should engage (Frese, 2009) –or not- (Honig, 2004) in business planning have been investigated quite extensively (Brinckmann et al., 2010), the specific value of business planning for nascent firms developing innovation is still unclear. The objective of this paper is to shed some light on these important aspects by investigating the two following questions on a large sample of random nascent firms: 1) how is business planning use over time by new ventures developing different types and degrees of innovation? 2) how do business planning and innovation impact the performance of the nascent firms? Methods & Key propositions This PSED-type study draws its data from the first three waves of the CAUSEE project where 30,105 Australian households were randomly contacted by phone using a methodology to capture emerging firms (Davidsson, Steffens, Gordon, Reynolds, 2008). This screening led to the identification of 594 nascent ventures (i.e., firms that were not operating yet at the time of the identification) that were willing to participate in the study. Comprehensive phone interviews were conducted with these 594 ventures. Likewise, two comprehensive follow-ups were organised 12 months and 24 months later where 80% of the eligible cases of the previous wave completed the interview. The questionnaire contains specific sections investigating business plans such as: presence or absence, degree of formality and updates of the plan. Four types of innovation are measured along three degrees of intensity to produce a comprehensive continuous measure ranging from 0 to 12 (Dahlqvist & Wiklund, 2011). Other sections informing on the gestation activities, industry and different types of experiences will be used as controls to measure the relationships and the impacts of business planning and innovation on the performance of nascent firms overtime. Results from two rounds of pre-testing informed the design of the instrument included in the main survey. The three waves of data are used to first test and compare the use of planning amongst nascent firms by their degrees of innovation and then to examine their impact on performance overtime through regression analyses. Results and Implications Three waves of data collection have been completed. Preliminary results show that on average, innovative firms are more likely to have a business plans than their low innovative counterpart. They are also most likely to update their plan suggesting a more continuous use of the plan over time than previously thought. Further analyses regarding the relationships between business planning, innovation and performance are undergoing. This paper is expected to contribute to the literature on business planning and innovation by measuring quantitatively their impact on nascent firms activities and performance at different stages of their development. In addition, this study will shed a new light on the business planning-performance relationship by disentangling plans, types of nascent firms regarding their innovation degres and their performance over time. Finally, we expect to increase the understanding of the venture creation process by analysing those questions on nascent firms from a large longitudinal sample of randomly selected ventures. We acknowledge the results from this study will be preliminary and will have to be interpreted with caution as the business planning-performance is not a straightforward relationship (Brinckmann et al., 2010). Meanwhile, we believe that this study is important to the field of entrepreneurship as it provides some much needed insights on the processes used by nascent firms during their creation and early operating stages.

When Can Oral Health Education Begin? Relative effectiveness of three oral health education strategies starting pre-partum

Objective: To test the impact of oral health education provided to pregnant mothers on subsequent practices within the infant’s family. Research design: A quasi-experimental intervention trial comparing the effectiveness of ‘usual care’ to one, or both, of two oral health education resources: a ‘sample bag’ of information and oral health care products; and/or a nine-minute “Healthy Teeth for Life” video on postnatal oral health issues. Participants: Women attending the midwife clinic at approximately 30 weeks gestation were recruited (n=611) in a public hospital providing free maternity services. Results and Conclusions: Four months after the birth of their infant, relative to the usual care condition, each of the oral health education interventions had independent or combined positive impacts on mother’s knowledge of oral health practices. However young, single, health care card-holder or unemployed mothers were less likely to apply healthy behaviours or to improve knowledge of healthy choices, as a result of these interventions. The video intervention provided the strongest and most consistent positive impact on mothers’ general and infant oral health knowledge. While mothers indicated that the later stage of pregnancy was a good time to receive oral health education, many suggested that this should also be provided after birth at a time when teeth were a priority issue, such as when “baby teeth” start to erupt.

Are we missing opportunities? Understanding health behaviours associated with overweight in pregnancy

While maternal obesity, excess pregnancy weight gain and lifestyle behaviours are associated with future overweight for both mothers and babies, there is limited research on how best to intervene. An evidence base that identifies behavioural influences is crucial to the development of effective interventions. This thesis aims to gain an understanding of maternal behavioural outcomes of healthy eating, physical activity and gestational weight gain (GWG), the psychosocial influences on these and to examine differences according to pre-pregnancy weight status. The New Beginnings Healthy Mothers and Babies Study was a prospective observational study using the PRECEDE-PROCEED model of health promotion planning as a framework. A consecutive sample of 715 women was recruited. Height and weight were measured and women completed questionnaires at approximately 16 and 36 weeks gestation. This thesis presents three chapters of original research across four study domains. While healthy eating was widely regarded as important during pregnancy and had become more so, there was more variability in attitudes towards physical activity. Ninety-two percent of participants achieved the maximum knowledge score relating to the influence of nutrition on pregnancy. However, 8% and 36% respectively knew how many serves of fruit and vegetables should be consumed daily. Six percent of participants met the recommendations for fruit consumption, 4% achieved the recommended vegetable intake and 44% achieved sufficient physical activity. There were few differences between healthy and overweight women for measures of physical activity and healthy eating. Many predisposing, reinforcing and enabling factors with a positive influence on health behaviours were lower in women commencing pregnancy overweight and those factors with a negative influence on health behaviours were higher when compared to healthy weight women. Some of these antecedents to health behaviours that were different according to prepregnancy weight status were associated with diet quality and physical activity. While self efficacy was consistently associated with diet quality and physical activity for both weight groups, other associations between specific predisposing, reinforcing and enabling factors differed with behaviour and weight status group. These results highlight the complexity of supporting behaviour change in a one-size-fits-all approach. Sixty-four percent of participants gained weight outside of recommendations. Compared to healthy weight women, those women who were already overweight at the beginning of pregnancy were more likely to gain too much weight (30% vs 56%, p<0.001). Only 35% of participants reported their correct recommended weight gain. Excess GWG was associated with few predisposing factors, however, these were not consistent between prepregnancy weight status groups. Less than 50% of women reported sometimes/usually/always receiving advice from health professionals relating to healthy eating, physical activity or GWG. These results indicate that there are opportunities to improve the advice and support provided by health care professionals in the antenatal period. Evidence from this PhD research suggests that there is a need for effective prevention and management of excess weight in pregnancy. Effective management of this problem is likely to require a multidisciplinary approach with multi-level strategies. Importantly, the strategies may need to be tailored according to pre-pregnancy weight status. Collectively, the evidence derived from this thesis suggests that opportunities to support healthy lifestyles and prevent future overweight are being missed during pregnancy.

Unpacking the venture creation process

This paper investigates the dimensions of time and effort and how these factors impact on the venture creation process in Australia. Findings of interest in this paper include: • First and foremost business planning is used as a thinking tool within the boundaries of the firm. • Business planning is more strongly associated with firms that are more ambitious, being built by teams, draw on more experience or education. • Industry characteristics in part drive the duration required for venture creation. Manufacturing and Agriculture based firms seemingly take longer timeframes than other industries. Extended venture creation times frames are also associated with firms that aim to bring more novel concepts to market.

An observational study of nutrition and physical activity behaviours, knowledge, and advice in pregnancy

Maternal obesity, excess weight gain and lifestyle behaviours during pregnancy have been associated with future overweight and other adverse health outcomes for mothers and babies. This study compared the nutrition and physical activity behaviours of Australian healthy (BMI ≤ 25 k/m2) and overweight (BMI ≥ 25 kg/m2) pregnant women and described their knowledge and receipt of health professional advice early in pregnancy. Methods Pregnant women (n=58) aged 29±5 (mean±s.d.) years were recruited at 16±2 weeks gestation from an Australian metropolitan hospital. Height and weight were measured using standard procedures and women completed a self administered semi-quantitative survey. Results Healthy and overweight women had very similar levels of knowledge, behaviour and levels of advice provided except where specifically mentioned. Only 8% and 36% of participants knew the correct recommended daily number of fruit and vegetable serves respectively. Four percent of participants ate the recommended 5 serves/day of vegetables. Overweight women were less likely than healthy weight women to achieve the recommended fruit intake (4% vs. 8%, p=0.05), and more likely to consume soft drinks or cordial (55% vs 43%, p=0.005) and take away foods (37% vs. 25%, p=0.002) once a week or more. Less than half of all women achieved sufficient physical activity. Despite 80% of women saying they would have liked education about nutrition, physical activity and weight gain, particularly at the beginning of pregnancy, less than 50% were given appropriate advice regarding healthy eating and physical activity. Conclusion Healthy pregnancy behaviour recommendations were not being met, with overweight women less likely to meet some of the recommendations. Knowledge of dietary recommendations was poor and health care professional advice was limited. There are opportunities to improve the health care practices and education pregnant women received to improve knowledge and behaviours. Pregnant women appear to want this.

Environments For Healthy Living (EFHL) Griffith birth cohort study : characteristics of sample and profile of antenatal exposures

Background The Environments for Healthy Living (EFHL) study is a repeated sample, longitudinal birth cohort in South East Queensland, Australia. We describe the sample characteristics and profile of maternal, household, and antenatal exposures. Variation and data stability over recruitment years were examined. Methods Four months each year from 2006, pregnant women were recruited to EFHL at routine antenatal visits on or after 24 weeks gestation, from three public maternity hospitals. Participating mothers completed a baseline questionnaire on individual, familial, social and community exposure factors. Perinatal data were extracted from hospital birth records. Descriptive statistics and measures of association were calculated comparing the EFHL birth sample with regional and national reference populations. Data stability of antenatal exposure factors was assessed across five recruitment years (2006–2010 inclusive) using the Gamma statistic for ordinal data and chi-squared for nominal data. Results Across five recruitment years 2,879 pregnant women were recruited which resulted in 2904 live births with 29 sets of twins. EFHL has a lower representation of early gestational babies, fewer still births and a lower percentage of low birth weight babies, when compared to regional data. The majority of women (65%) took a multivitamin supplement during pregnancy, 47% consumed alcohol, and 26% reported having smoked cigarettes. There were no differences in rates of a range of antenatal exposures across five years of recruitment, with the exception of increasing maternal pre-pregnancy weight (p=0.0349), decreasing rates of high maternal distress (p=0.0191) and decreasing alcohol consumption (p<0.0001). Conclusions The study sample is broadly representative of births in the region and almost all factors showed data stability over time. This study, with repeated sampling of birth cohorts over multiple years, has the potential to make important contributions to population health through evaluating longitudinal follow-up and within cohort temporal effects.

Assessing exposures to emerging environmental contaminants in children

The period of developmental vulnerability to toxicants begins at conception and extends through gestation, parturition, infanthood and childhood to adolescence. The concern is that children: (1) may experience quantitatively and qualitatively different exposures, and (2) may have different sensitivity to chemical pollutants. Traditional toxicological studies are inappropriate for assessing the results of chronic exposure at very low levels during critical periods of development. This paper will discuss (1) the health effects associated with exposure to selected emerging organic pollutants, including brominated flame retardants, perfluorinated compounds, organophosphate pesticides and bisphenol A; (2) difficulties in monitoring these substances in children, and (3) suggest techniques and strategies for overcoming these difficulties. Such biomonitoring data can be used to identify where policies should be directed in order to reduce exposure, and to document policies that have successfully reduced exposure.