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Introduction: Chorioamnionitis is common in preterm birth and associated with a higher risk of intestinal inflammation and necrotizing enterocolitis. The intestinal inflammation influences the enteric nervous system development. We hypothesized that inflammation and innervation in the fetal ileum may be modified by chorioamnionitis induced by repeated challenge with lipopolysaccharide and/or preexisting Ureaplasma parvum infection at very low gestational age equivalent to 60% of term., Materials and Methods: Time mated ovine fetuses were exposed by intraamniotic injections to chronic Ureaplasma parvum for 24 days and/or lipopolysaccharide for 7 days, 2 days, or 7 & 2 days before delivery at 94 +/-2 days of gestational age (term at approximately 150 days). Intestinal inflammation as well as structural changes of the enteric nervous system were assessed., Results: Lipopolysaccharide exposure increased CD3 and myeloperoxidase-positive cells (p < 0.05). Repetitive exposure to lipopolysaccharide or combined Ureaplasma parvum & lipopolysaccharide exposure increased intestinal inflammation (p < 0.05). The reduction of nuclei of neurons was most significant with repetitive lipopolysaccharide exposures but could be detected in all other intervention groups compared to the control group. Astrocyte-like glial cells increased if exposure to lipopolysaccharide was only 2 days before delivery or chronic exposure to Ureaplasma parvum existed beforehand (p < 0.05)., Discussion: After exposure to chorioamnionitis induced by Ureaplasma parvum and/or lipopolysaccharide, inflammatory responses as well as structural changes of the enteric nervous system were more pronounced the longer and the more frequent the exposure to pro-inflammatory stimuli before birth. These changes may cause functional effects of clinical importance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Heiter, Kemp, Spiller, Singer, Newnham, Kallapur, Jobe and Kramer.)

Background: Vaginal progesterone therapy significantly reduces preterm birth (PTB) rates in those high-risk pregnancies with a sonographic short cervix (≤25 mm) and/or a history of spontaneous PTB. Cervical length (CL) is routinely measured at the midtrimester morphology scan; however, CL surveillance thereafter is not currently recommended. Progesterone's precise mechanism of action remains unknown, though if it indeed influences CL, shortening after treatment initiation could indicate therapeutic failure and risk of PTB., Aims: The aim was to explore the utility of serial transvaginal ultrasound (TVU) measurement of CL at 16, 19 and 22 weeks for predicting PTB in high-risk pregnancies prescribed progesterone therapy., Methods: A retrospective cohort study was conducted involving women who attended the King Edward Memorial Hospital PTB Prevention Clinic from 2015 to 2019 and were prescribed progesterone therapy. CL was measured at 16, 19 and 22 weeks by TVU. CL change across three time points was assessed using linear mixed models; then relationships between CL change between 16-19 and 19-22 weeks and PTB were analysed using logistic regression models., Results: Term birth was most likely when CL did not decrease across both time periods. The addition of 16-19 week decrease in CL to a model, including CL at 19 weeks alone, for predicting PTB increased sensitivity from 43.2 to 56.3%, specificity from 73.2 to 77.4%, and overall accuracy from 61.7 to 70.2%., Conclusion: For high-risk women prescribed vaginal progesterone therapy, serial measurement of the cervix at 16 and 19 weeks improves clinical ability to predict PTB from current recommendations of 19-week measurement alone., (© 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Preterm birth (PTB) is the greatest cause of mortality and morbidity in children up to five years of age globally. The Western Australian (WA) PTB Prevention Initiative, the world's first whole-of-population whole-of-state program aimed at PTB prevention, was implemented across WA in 2014., Methods: We conducted a prospective population-based cohort study using pregnancy data for singleton births in WA from 2009 to 2019. Logistic regression using the last full year before the Initiative (2013) as the reference, and run charts were used to examine changes in PTB rates compared to pre-Initiative levels, by gestational age group, hospital type, low and high risk of PTB in mid-pregnancy, and onset of labour (spontaneous/medically initiated). Analyses were stratified by Aboriginal and non-Aboriginal maternal ethnicity., Results: Amongst non-Aboriginal women, there was initially a reduction in the PTB rate across the state, and in recent years it returned to pre-Initiative levels. Amongst Aboriginal women there was a small, non- significant reduction in the state-wide PTB rate in the first three years of the Initiative, followed by a rise in recent years. For non-Aboriginal women, the reduction in the rate of PTB at the tertiary centre was sustained and improved further for women of all risk levels and onsets of labour. This reduction was not observed for Aboriginal women giving birth at the tertiary centre, amongst whom there was an increase in the PTB rate overall and in all subgroups, with the exception of medically initiated PTB. Amongst Aboriginal women the PTB rate has also increased across the state. At non-tertiary hospitals there was a large increase in PTB amongst both Aboriginal and non-Aboriginal women, largely driven by medically initiated late PTB. Maternal risk factors cannot account for this increase., Conclusions: The reduction in PTB rates amongst non-Aboriginal women at the state's tertiary hospital demonstrates that with the right strategies, PTB can be reduced. A sustained collaborative model is required to realise this success in non-tertiary hospitals. The series of interventions was of limited use in Aboriginal women, and future efforts will need to be directed at strategies more likely to be successful, such as midwifery continuity of care models, with Aboriginal representation in the healthcare workforce., (© 2023. The Author(s).)

Being born preterm (prior to 37 weeks of completed gestation) is a leading cause of childhood death up to five years of age, and is responsible for the demise of around one million preterm infants each year. Rates of prematurity, which range from approximately 5 to 18% of births, are increasing in most countries. Babies born extremely preterm (less than 28 weeks' gestation) and in particular, in the periviable (20 0/7 -25 6/7 weeks) period, are at the highest risk of death, or the development of long-term disabilities. The perinatal care of extremely preterm infants and their mothers raises a number of clinical, technical, and ethical challenges. Focusing on 'micropremmies', or those born in the periviable period, this paper provides an update regarding the aetiology and impacts of periviable preterm birth, advances in the antenatal, intrapartum, and acute post-natal management of these infants, and a review of counselling/support approaches for engaging with the infant's family. It concludes with an overview of emerging technology that may assist in improving outcomes for this at-risk population., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Preterm birth is the greatest cause of death up to five years of age and an important contributor to lifelong disability. There is increasing evidence that a meaningful proportion of early births may be prevented, but widespread introduction of effective preventive strategies will require financial support., Aims: This study estimated the economic cost to the Australian government of preterm birth, up to 18 years of age., Materials and Methods: A decision-analytic model was developed to estimate the costs of preterm birth in Australia for a hypothetical cohort of 314 814 children, the number of live births in 2016. Costs to Australia's eight jurisdictions included medical expenditures and additional costs to educational services., Results: The total cost of preterm birth to the Australian government associated with the annual cohort was estimated at $1.413 billion (95% CI 1047-1781). Two-thirds of the costs were borne by healthcare services during the newborn period and one-quarter of the costs by educational services providing special assistance. For each child, the costs were highest for those born at the earliest survivable gestational age, but the larger numbers of children born at later gestational ages contributed heavily to the overall economic burden., Conclusion: Preterm birth leaves many people with lifelong disabilities and generates a significant economic burden to society. The costs extend beyond those to the healthcare system and include additional educational needs. Assessments of economic costs should inform economic evaluations of interventions aimed at the prevention or treatment of preterm birth., (© 2021 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Intrauterine infection accounts for a quarter of the cases of spontaneous preterm birth; however, at present, it is not possible to efficiently identify pregnant women at risk to deliver preventative treatments., Objective: This study aimed to establish a vaginal microbial DNA test for Australian women in midpregnancy that will identify those at increased risk of spontaneous preterm birth., Study Design: A total of 1000 women with singleton pregnancies were recruited in Perth, Australia. Midvaginal swabs were collected between 12 and 23 weeks' gestation. DNA was extracted for the detection of 23 risk-related microbial DNA targets by quantitative polymerase chain reaction. Obstetrical history, pregnancy outcome, and demographics were recorded., Results: After excluding 64 women owing to losses to follow-up and insufficient sample for microbial analyses, the final cohort consisted of 936 women of predominantly white race (74.3%). The overall preterm birth rate was 12.6% (118 births); the spontaneous preterm birth rate at <37 weeks' gestation was 6.2% (2.9% at ≤34 weeks' gestation), whereas the preterm premature rupture of the membranes rate was 4.2%. No single individual microbial target predicted increased spontaneous preterm birth risk. Conversely, women who subsequently delivered at term had higher amounts of Lactobacillus crispatus, Lactobacillus gasseri, or Lactobacillus jensenii DNA in their vaginal swabs (13.8% spontaneous preterm birth vs 31.2% term; P=.005). In the remaining women, a specific microbial DNA signature was identified that was strongly predictive of spontaneous preterm birth risk, consisting of DNA from Gardnerella vaginalis (clade 4), Lactobacillus iners, and Ureaplasma parvum (serovars 3 and 6). Risk prediction was improved if Fusobacterium nucleatum detection was included in the test algorithm. The final algorithm, which we called the Gardnerella Lactobacillus Ureaplasma (GLU) test, was able to detect women at risk of spontaneous preterm birth at <37 and ≤34 weeks' gestation, with sensitivities of 37.9% and 44.4%, respectively, and likelihood ratios (plus or minus) of 2.22 per 0.75 and 2.52 per 0.67, respectively. Preterm premature rupture of the membranes was more than twice as common in GLU-positive women. Adjusting for maternal demographics, ethnicity, and clinical history did not improve prediction. Only a history of spontaneous preterm birth was more effective at predicting spontaneous preterm birth than a GLU-positive result (odds ratio, 3.6)., Conclusion: We have identified a vaginal bacterial DNA signature that identifies women with a singleton pregnancy who are at increased risk of spontaneous preterm birth and may benefit from targeted antimicrobial therapy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality worldwide. Being born too early contributes to approximately 70% of neonatal mortality and approximately half of long-term neurodevelopmental disabilities. Various PTB prevention programs have been described going back more than 30 years, and some have described possible success in decreasing the rate of PTB. In addition, there are also PTB prenatal care clinics in many parts of the world, each with the singular goal of reducing the PTB rate in their region. Interventions can be directed at all women for primary prevention and reducing the risk of PTB or used to mitigate risk in women identified to be at increased risk., Methods: A Medline and ClinicalTrials.gov ( www.clinicaltrials.gov ) search was performed (1982-2018), using preterm birth prevention program as the primary medical subject heading, reporting randomized clinical trials, quasi-experimental trials, and analytic studies (including retrospective and prospective cohort studies). We also searched Google for preterm birth prevention programs and prenatal care clinics published on-line., Results: Some prevention programs have reported success in lowering rates of PTB, principally using historical controls although the majority were not followed by improved outcomes., Conclusion: Increasing knowledge and the use of social media to enhance education should now enable greater effectiveness of new programs. Development of regional and national PTB prevention programs should now be considered.

Background: In 2014, a whole-of-population and multi-faceted preterm birth prevention program was introduced in Western Australia with the single aim of safely lowering the rate of preterm birth. The program included new clinical guidelines, print and social media, and a dedicated new clinic. In the first full calendar year the rate of preterm birth fell by 7.6% and the reduction extended from the 28-31 week gestational age group upwards., Objective: The objective of this study was to evaluate outcomes in greater depth and to also include the first three years of the program., Study Design: This was a prospective population-based cohort study of perinatal outcomes in singleton pregnancies before and after commencement of the program., Results: There was a significant reduction in preterm birth in the tertiary center which extended from 28 weeks gestation onwards and was ongoing. In non-tertiary centers there was an initial reduction, but this was not sustained past the first year. The greatest reduction was observed in pregnancies classified at first attendance as low risk. No benefit was observed in the private sector, but a significant reduction was seen in the remote region of the Kimberley where the program was first launched and vaginal progesterone had been made free-of-charge., Conclusion: Preterm birth rates can be safely reduced by a multi-faceted and whole-of-population program but the effectiveness requires continuing effort and will be greatest where the strategies are most targeted., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To report the prevalence of amblyopia, strabismus, and anisometropia in a young adult population at a single center in Australia and to investigate the underlying prenatal and early-life risk factors., Methods: Participants in the Raine Study have been followed from mid-gestation (n = 2,868 newborns) to young adulthood. At age 20 years, 1,344 participants had a comprehensive eye examination, including visual acuity and a detailed orthoptic assessment. Risk factors were determined from medical records and questionnaires completed by the mothers at 18 weeks' gestation. The main outcome measures were the proportions of participants with amblyopia, esotropia, exotropia, or anisometropia (defined as >1 D difference)., Results: Of the 1,125 white participants, 12 (1.1%) had amblyopia, 39 (3.5%) had strabismus, and 33 (2.9%) had anisometropia. In multivariable logistic regression, amblyopia was associated with a maternal history of pregnancy-induced hypertension (OR = 3.80; 95% CI, 1.19-12.13); esotropia, with lower gestational age (OR = 0.97; 95% CI, 0.95-0.97) and a heavier placenta (OR = 1.02; 95% CI, 1.00-1.04); exotropia, with a maternal history of previously treated hypertension (OR = 4.00; 95% CI, 1.06-15.03) and maternal use of recreational drugs during early pregnancy (OR = 3.61; 95% CI, 1.06-15.03); and anisometropia, with older maternal age (OR = 1.07; 95% CI, 1.01-1.14) and an abnormal umbilical cord (OR = 2.39; 95% CI, 1.04-5.47)., Conclusions: The prevalence of amblyopia, strabismus, and anisometropia in this cohort was similar to that in other studies. Preterm birth and maternal health may have adverse effects on eye development., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Ex vivo uterine environment therapy is an experimental life support platform designed to reduce the risk of morbidity and mortality for extremely preterm infants born at the border of viability (21-24 weeks' gestation). To spare the functionally immature lung, this platform performs gas exchange via a membranous oxygenator connected to the umbilical vessels, and the fetus is submerged in a protective bath of artificial amniotic fluid. We and others have demonstrated the feasibility of extended survival with ex vivo uterine environment therapy therapy in late preterm fetuses; however, there is presently no evidence to show that the use of such a platform can support extremely preterm fetuses, the eventual translational target for therapy of this nature., Objective: The objective of the study was to use our ex vivo uterine environment therapy platform to support the healthy maintenance of 600-700 g/95 days gestational age (equivalent to 24 weeks of human gestation) sheep fetuses. Primary outcome measures were as follows: (1) maintenance of key physiological variables; (2) absence of infection; (3) absence of brain injury; and (4) growth and cardiovascular function patterns matching that of noninstrumented, age-matched in utero controls., Study Design: Singleton fetuses from 8 ewes underwent surgical delivery at 95 days' gestation (term, 150 days). Fetuses were adapted to ex vivo uterine environment therapy and maintained for 120 hours with real-time monitoring of key physiological variables. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, inflammation, and microbial load to exclude infection. Brain injury was evaluated by gross anatomical and histopathological approaches after euthanasia. Nine pregnant control animals were euthanized at 100 days' gestation to allow comparative postmortem analyses. Data were tested for mean differences with an analysis of variance., Results: Seven of 8 ex vivo uterine environment group fetuses (87.5%) completed 120 hours of therapy with key parameters maintained in a normal physiological range. There were no significant intergroup differences (P > .05) in final weight, crown-rump length, and body weight-normalized lung and brain weights at euthanasia compared with controls. There were no biologically significant differences in hematological parameters (total or differential leucocyte counts and plasma concentration of tumor necrosis factor-α and monocyte chemoattractant protein 1) (P > .05). Daily blood cultures were negative for aerobic and anaerobic growth in all ex vivo uterine environment animals. There was no difference in airspace consolidation between control and ex vivo uterine environment animals, and there was no increase in the number of lung cells staining positive for the T-cell marker CD3. There were no increases in interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-α, and monocyte chemoattractant protein 1 mRNA expression in lung tissues compared with the control group. No cases of intraventricular hemorrhage were observed, and white matter injury was identified in only 1 ex vivo uterine environment fetus., Conclusion: For several decades, there has been little improvement in outcomes of extremely preterm infants born at the border of viability. In the present study, we report the use of artificial placenta technology to support, for the first time, extremely preterm ovine fetuses (equivalent to 24 weeks of human gestation) in a stable, growth-normal state for 120 hours. With additional refinement, the data generated by this study may inform a treatment option to improve outcomes for extremely preterm infants., (Copyright © 2019. Published by Elsevier Inc.)

Late preterm and early term birth is associated with adverse short- and long-term consequences, particularly for neurodevelopment. A clear reduction in these births can be achieved by avoidance of non-medically indicated births prior to 39 weeks gestation, as shown following the introduction of prohibitive policies in the USA. However, clinicians and policy-makers must always consider the potential for unintended adverse consequences of such action, such as a potential for an increase in term stillbirth. Finding the balance between optimising long-term neurological outcomes and avoiding rare but devastating term stillbirths is one of the challenges of modern maternity care. In this article we review the current evidence for whether this balance can be found, where early births can be safely prevented, and what remains to be addressed to optimise this balance safely., (© 2018 Published by Elsevier Ltd.)

Antenatal steroids (ANS) are among the most important and widely utilized interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24-34 wk) delivered between 1 and 7 days after the administration of a single course of ANS. Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved, and treatment doses and regimens remain largely unoptimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside the 1- to 7-day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement(s) of this important therapy. Complementary approaches using nonhuman primates, sheep, and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focusing on these three major model groups, this review highlights the role of three key animal models (sheep, nonhuman primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy in an era of personalised medicine.

Background: The efficacy of antenatal steroids for fetal lung maturation in the periviable period is not fully understood., Objective: We sought to determine the lung maturational effects of antenatal steroids and inflammation in early gestation sheep fetuses, similar to the periviable period in human beings., Study Design: Date-mated ewes with singleton fetuses were randomly assigned to 1 of 4 treatment groups (n = 8/group): (1) maternal intramuscular injection of betamethasone; (2) intraamniotic lipopolysaccharide; (3) betamethasone + lipopolysaccharide; and (4) intraamniotic + intramuscular saline (controls). Fetuses were delivered surgically 48 hours later at 94 days' gestation (63% term gestation) for comprehensive evaluations of lung maturation, and lung and systemic inflammation., Results: Relative to controls, first, betamethasone increased the fetal lung air space to mesenchymal area ratio by 47% but did not increase the messenger RNAs for the surfactant proteins-B and -C that are important for surfactant function or increase the expression of pro-surfactant protein-C in the alveolar type II cells. Second, betamethasone increased expression of 1 of the 4 genes in surfactant lipid synthetic pathways. Third, betamethasone increased genes involved in epithelium sodium channel transport, but not sodium-potassium adenosine triphosphatase or Aquaporin 5. Fourth, lipopolysaccharide increased proinflammatory genes in the lung but did not effectively recruit activated inflammatory cells. Last, betamethasone incompletely suppressed lipopolysaccharide-induced lung inflammation. In the liver, betamethasone when given alone increased the expression of serum amyloid A3 and C-reactive protein messenger RNAs., Conclusion: Compared the more mature 125-day gestation sheep, antenatal steroids do not induce pulmonary surfactants during the periviable period, indicating a different response., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Extremely preterm infants born at the border of viability (22-24 weeks' gestation) have high rates of death and lasting disability. Ex vivo uterine environment therapy is an experimental neonatal intensive care strategy that provides gas exchange using parallel membranous oxygenators connected to the umbilical vessels, sparing the extremely preterm cardiopulmonary system from ventilation-derived injury., Objective: In this study, we aimed to refine our ex vivo uterine environment therapy platform to eliminate fetal infection and inflammation, while simultaneously extending the duration of hemodynamically stable ex vivo uterine environment therapy to 1 week., Study Design: Merino-cross ewes with timed, singleton pregnancies were surgically delivered at 112-115 days of gestation (term is ∼150 days) and adapted to ex vivo uterine environment therapy (treatment group; n = 6). Physiological variables were continuously monitored; humerus and femur length, ductus arteriosus directional flow, and patency were estimated with ultrasound; serial blood samples were collected for hematology and microbiology studies; weight was recorded at the end of the experiment. Control group animals (n = 7) were euthanized at 122 days of gestation and analyzed accordingly. Bacteremia was defined by positive blood culture. Infection and fetal inflammation was assessed with white blood cell counts (including differential leukocyte counts), plasma and lung proinflammatory cytokine measurements, and lung histopathology., Results: Five of 6 fetuses in the treatment group completed the 1-week study period with key physiological parameters, blood counts remaining within normal ranges, and no bacteremia detected. There were no significant differences (P > .05) in arterial blood oxygen content or lactate levels between ex vivo uterine environment therapy and control groups at delivery. There was no significant difference (P > .05) in birthweight between control and ex vivo uterine environment groups. In the ex vivo uterine environment group, we observed growth of fetal humerus (P < .05) and femur (P < .001) over the course of the 7-day experimental period. There was no difference in airway or airspace morphology or consolidation between control and ex vivo uterine environment animals, and there was no increase in the number of lung cells staining positive for T-cell marker CD3 + ., Conclusion: Five preterm lambs were maintained in a physiologically stable condition for 1 week with significant growth and without clinically significant bacteremia or systemic inflammation. Although substantial further refinement is required, a life support platform based around ex vivo uterine environment therapy may provide an avenue to improve outcomes for extremely preterm infants., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ex vivo uterine environment (EVE) therapy is an experimental neonatal intensive care strategy wherein gas exchange is performed by membranous oxygenators attached to the umbilical vessels. Our aim was to assess the ability of a newly refined EVE system to maintain key physiological parameters in preterm lambs within optimal ranges for 48 h. EVE group; n = 6: Preterm lambs were delivered under general anesthesia at 115 ± 2 days of gestational age. Animals were submerged in a bath of artificial amniotic fluid on EVE therapy for 48 h. Physiological parameters were monitored in real-time over the length of the experiment. Control group; n = 11: Ewes carrying a single fetus (115 ± 2 days of gestational age) underwent recovery surgery to allow placement of a fetal carotid artery catheter. Fetuses received an infusion of sterile saline only. After euthanasia, EVE and Control group fetuses underwent necroscopy to perform static pressure-volume curves and for sampling of lung and cord blood plasma for molecular analyses. Five out of six fetuses in the EVE group completed the study period with key physiological variables remaining within their respective reference ranges for the duration of the 48 h study. Bacteremia was identified in four out of five EVE fetuses, and was associated with a systemic inflammatory response. Using our refined EVE therapy platform, preterm lambs were maintained in a stable physiological condition for 48 h. These findings represent a significant advance over earlier work with this system; however, the identification of bacteremia and a fetal inflammatory response suggests that further refinement to the EVE therapy platform is required., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: A comprehensive preterm birth prevention program was introduced in the state of Western Australia encompassing new clinical guidelines, an outreach program for health care practitioners, a public health program for women and their families based on print and social media, and a new clinic at the state's sole tertiary level perinatal center for referral of those pregnant women at highest risk. The initiative had the single aim of safely lowering the rate of preterm birth., Objective: The objective of the study was to evaluate the outcomes of the initiative on the rates of preterm birth both statewide and in the single tertiary level perinatal referral center., Study Design: This was a prospective population-based cohort study of perinatal outcomes before and after 1 full year of implementation of the preterm birth prevention program., Results: In the state overall, the rate of singleton preterm birth was reduced by 7.6% and was lower than in any of the preceding 6 years. This reduction amounted to 196 cases relative to the year before the introduction of the initiative and the effect extended from the 28-31 week gestational age group onward. Within the tertiary level center, the rate of preterm birth in 2015 was also significantly lower than in the preceding years., Conclusion: A comprehensive and multifaceted preterm birth prevention program aimed at both health care practitioners and the general public, operating within the environment of a government-funded universal health care system can significantly lower the rate of early birth. Further research is now required to increase the effect and to determine the relative contributions of each of the interventions., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Problem: Complement is a central defence against sepsis, and increasing complement insufficiency in neonates of greater prematurity may predispose to increased sepsis. Ureaplasma spp. are the most frequently cultured bacteria from preterm blood samples., Method of Study: A sheep model of intrauterine Ureaplasma parvum infection was used to examine in vivo Ureaplasma bacteraemia at early and late gestational ages. Complement function and Ureaplasma killing assays were used to determine the correlation between complement potency and bactericidal activity of sera ex vivo., Results: Ureaplasma was cultured from 50% of 95-day gestation lamb cord blood samples compared to 10% of 125-day gestation lambs. Bactericidal activity increased with increased gestational age, and a direct correlation between functional complement activity and bactericidal activity (R 2 =.86; P<.001) was found for 95-day gestational lambs., Conclusions: Ureaplasma bacteraemia in vivo was confined to early preterm lambs with low complement function, but Ureaplasma infection itself did not diminish complement levels., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intrauterine inflammation, the major cause of early preterm birth, can have microbial and sterile aetiologies. We assessed in a Transwell model the anti-inflammatory efficacies of five drugs on human extraplacental membranes delivered after preterm spontaneous labour (30-34 wk). Drugs [TPCA1 (IKKβ inhibitor), 5 z-7-oxozeaenol (OxZ, TAK1 inhibitor), inhibitor of NF-κB essential modulator binding domain (iNBD), SB239063 (p38 MAPK inhibitor) and N-acetyl cysteine (free radical scavenger free radicals)] were added after 12 h equilibration to the amniotic compartment. Concentrations of IL-6, TNF-α, MCP-1, IL-1β and PGE 2 in the media, and IL6, TNFA and PTGS2 mRNA expression levels in membranes, were determined after 12 h. Data were analysed using mixed models analyses. Thirteen of the 28 membranes had histological chorioamnionitis (HCA + ); five were positive for bacterial culture and six for fetal inflammatory reaction. Baseline PGE 2 and cytokine production was similar between HCA - and HCA + membranes. Anti-inflammatory effects were also similar between HCA - and HCA + membranes. TPCA1 and OxZ were the most effective drugs; each inhibited amniotic secretion of 4/5 pro-inflammatory mediators and mRNA levels of 2/3, regardless of stimulus. We conclude that treatment with TPCA1 or OxZ, in combination with antibiotics, may minimise the adverse effects of intrauterine inflammation in pregnancy.

Background: Detection of Ureaplasma, Mycoplasma and Candida spp. in the vagina during pregnancy has previously been associated with preterm birth (PTB). However, the prevalence of these microorganisms and the associated obstetric risks (likely to be population-specific) have not been determined in Australian women; furthermore, in the case of Ureaplasma spp., very few studies have attempted characterisation at the species level and none have examined genotype/serovar status to further refine risk assessment., Methods: In order to address these issues we sampled the vaginal fluid of 191 pregnant Australian women at three time points in pregnancy. Culture methods were used for detection of Ureaplasma spp. and Candida spp., and real-time PCR was used for speciation of U. parvum and U. urealyticum, non-albicans Candida spp., Mycoplasma hominis and Mycoplasma genitalium. High-resolution melt PCR was used to genotype U. parvum. Data on various lifestyle factors (including sex during pregnancy and smoking), antimicrobial use and pregnancy outcome were collected on all participants. Chi-square tests were used to assess the association of vaginal microorganisms with PTB., Results: Detection of Ureaplasma spp. was higher among spontaneous PTB cases, specifically in the presence of U. parvum [77 % preterm (95 % confidence interval (CI) 50-100 %) vs. 36 % term (CI: 29-43 %), p = 0.004], but not U. urealyticum. The association with PTB strengthened when U. parvum genotype SV6 was detected (54 % preterm (CI: 22-85 %) vs. 15 % term (CI: 10-20 %), p = 0.002); this genotype was also present in 80 % (4/5) of cases of PTB <34 weeks gestation. When present with Candida albicans in the same sample, the association with PTB remained strong for both U. parvum [46 % preterm (CI: 15-78 %) vs. 13 % term (CI: 8-18 %), p = 0.005] and U. parvum genotype SV6 [39 % preterm (CI: 8-69 %) vs. 7 % term (CI: 3-11 %), p = 0.003]. With the exception of Candida glabrata, vaginal colonisation status for all organisms was stable throughout pregnancy. Smoking significantly increased the likelihood of detection of all target organisms., Conclusions: These data suggest that the presence of different species and serovars of Ureaplasma spp. in the vagina confers an increased risk of spontaneous PTB, findings which may be useful in risk assessment for identifying women who would benefit from antimicrobial treatment.

Introduction: Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume., Methods: Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups., Results: Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups., Conclusion: In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.

Objective: To study the influence of polycystic ovary syndrome (PCOS) on obstetric and perinatal outcomes and on offspring in childhood., Methods: Using statewide data linkage systems within Western Australia, 2,566 hospitalized women with a PCOS diagnosis and at least one pregnancy at 20 weeks of gestation or greater, between 1997 and 2011, were compared with 25,660 randomly selected age-matched women not hospitalized with a PCOS diagnosis with regard to perinatal outcomes, congenital anomalies, and general health of offspring. Hospitalizations were categorized by International Classification of Diseases, 10th Revision diagnoses and rates by 10 years by Kaplan-Meier estimates. Polycystic ovary syndrome effects were summarized using adjusted odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) after controlling for maternal and perinatal characteristics, including maternal diabetes and obesity., Results: Of women with PCOS (n=1,789), 69.7% and 62.9% (n=16,139) of women without PCOS had one or more births. Hospitalizations up to 31 years were examined for 38,361 offspring. Offspring of women with PCOS were at higher risk of preterm birth (15.5% compared with 7.6% OR 1.74, 95% CI 1.53-1.98), perinatal mortality (2.3% compared with 0.7%, OR 1.49, 95% CI 1.02-2.18), more postnatal hospitalizations (14.1% compared with 7.9%, OR 1.21, 95% CI 1.05-1.40), more congenital anomalies (6.3% compared with 4.9%, OR 1.20, 95% CI 1.03-1.40), cardiovascular (1.5% compared with 1.0%, OR 1.37, 95% CI 1.01-1.87), and urogenital defects (2.0% compared with 1.4% OR 1.36, 95% CI 1.03-1.81). Maternal PCOS was associated with increased hospitalizations for their offspring, including metabolic disorder (7.9% compared with 5.3%, HR 1.43, 95% CI 1.26-1.65), disease of the nervous system (9.4% compared with 6.9%, HR 1.17, 95% CI 1.03-1.33), and asthma (6.9% compared with 4.9%, HR 1.32, 95% CI 1.13-1.54)., Conclusion: Controlling for increased perinatal risk, maternal PCOS was associated with a predisposition to adverse health outcomes for their offspring., Level of Evidence: II.

Background: This study tested if second trimester amniotic fluid cytokine levels, Ureaplasma sp. colonisation and sexual activity predict preterm birth and explain the differential preterm birth rates in Chinese compared to Australian women., Methods: Amniotic fluid was collected by amniocentesis (Chinese 480, Australian 492). Cytokines were measured by multiplex assay and Ureaplasma sp. DNA was detected by PCR analysis. Lifestyle factors, including history of smoking and sexual activity during pregnancy, were obtained through completion of questionnaires upon recruitment to the study., Results: Inflammatory cytokine concentrations were poorly predictive of preterm birth. Ureaplasma sp. was detected in two of the Chinese pregnancies and none from Australia. Sexual activity was less frequent in Chinese, and was not associated with preterm birth or amniotic fluid findings in either population., Discussion: Second trimester amniocentesis for measurement of inflammatory markers and Ureaplasma sp. DNA was not indicative of risk of preterm birth, at least in these populations. The lower rate of preterm birth in China was not explained by differences in amniotic fluid inflammatory markers, Ureaplasma sp. colonisation, or sexual activity.

Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30  min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.

Objective: For more than three decades, women at imminent risk of preterm birth (PTB) in Western Australia have been transferred by small aircraft over long distances to the single tertiary level perinatal centre in Perth, with no known case of birth during the flight. We aimed to review recent experience to understand how aircraft travel may delay PTB., Design and Setting: Retrospective observational study of 500 consecutive Royal Flying Doctor Service (RFDS) transfers of women at risk of preterm labour to the tertiary referral centre, from September 2007 to December 31, 2009., Main Outcome Measures: In-flight delivery, complications associated with transfer and factors associated with delay in preterm delivery., Results: There were no in-flight deliveries or serious complications associated with the aeromedical transfer of these patients. In a multivariable Cox proportional hazards regression analysis, clinical factors in the presentation that were associated with a shorter time from landing to subsequent delivery included cervical dilatation ≥ 4 cm, ruptured membranes, gestational age > 32 weeks and nulliparity. The aircraft reaching an ambient altitude > 14,000 feet, or cabin altitude above zero (sea level), was associated with a delay in time from landing to delivery for women who were not in spontaneous preterm labour., Conclusions: Our findings add to a 30-year experience that women at risk of preterm labour do not deliver during aeromedical transfer. Ambient and cabin altitude of the aircraft were associated with an extension in the time to delivery after arrival. The mechanisms underpinning this effect warrant further investigation., (© 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: To (1) investigate the current distribution of PTB phenotypes; (2) identify factors associated with spontaneous preterm labour (SPTL), PPROM, and indicated PTB; (3) investigate the relationship of gestational age (ga) with each PTB phenotype., Methods: Retrospective review of all live, singleton births 23(+0) to 36(+6) weeks ga at an obstetric referral centre 2004-2008., Results: A total of 4,522 PTBs were included (SPTL 31.7%, PPROM 27.4%, indicated 40.8%). PTB phenotype distribution differed between ga groups (<27 weeks: SPTL 45%, PPROM 32%, indicated 23%; 27-33 weeks: SPTL 30%, PPROM 32%, indicated 39%; 34-36 weeks: SPTL 32%, PPROM 24%, indicated 44%, p < 0.001). Between 34-36 weeks', demographic factors were significantly different between PTB phenotypes (age ≥35: SPTL 13.8%, PPROM 15.4%, indicated 21.6%; Caucasian ethnicity: SPTL 61.6%, PPROM 69.0%, indicated 70.2%; Assisted Reproductive Technology (ART): SPTL 2.8%, PPROM 1.9%, indicated 9.3%; all p < 0.001). Between 27-33 weeks' PTB phenotype was associated with smoking (SPTL 24.9%, PPROM 29.3%, indicated 20.2%; p = 0.002) and ART (SPTL 2.3%, PPROM 1.6%, indicated 5.0%; p = 0.002). Demographic factors were not associated with PTB phenotype at 23-26 weeks., Conclusions: The increase in PTB rates may be explained by medical indications at late preterm gestations, primarily in older, Caucasian women requiring fertility assistance. Interventions to reduce the rate of PTB need to be targeted to this high-risk population.

Background: The rates of preterm birth in Chinese women and the potential effects of differing environments are poorly understood., Aim: To determine the rate of preterm birth in Chinese women in China, Hong Kong and Western Australia., Methods: The rates of preterm birth were obtained from records of 26,611 pregnancies in Jiangsu Province in mainland China, 48,976 pregnancies in Hong Kong and 185,798 pregnancies in Western Australia., Results: Preterm birth rates increased from 2.6 and 2.9% in urban and rural Jiangsu Province, respectively, and 2.5% in China-born women in Western Australia who required an interpreter; to 4.9% in China-born women in Western Australia who did not require an interpreter; to 5.6% in non-resident Chinese women in Hong Kong; and 7.6% for women resident in Hong Kong. Within Western Australia, the rate of preterm birth was significantly less in women who were born in China and declared themselves to be Chinese (4.4%) than Caucasians (7.8%), other women who declared themselves to be 'Asian' (8.7%) and women of Aboriginal heritage (14.5%)., Conclusions: The rate of preterm birth in China is relatively low but appears to differ in Chinese women in other environments. Differences between traditional Chinese and contemporary Western lifestyles, possibly including smoking and sexual practices, may contribute to the different rates of preterm birth. Further research in this area may provide avenues for the prevention of preterm birth and also help to prevent a possible rise in this complication of pregnancy as Chinese society continues on the path of economic and social reform., (© 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Ureaplasma species, the most commonly isolated microorganisms in women with chorioamnionitis, are associated with preterm delivery. Chorioamnionitis increases the risk and severity of bronchopulmonary dysplasia and persistent pulmonary hypertension in newborns. It is not known whether the timing of exposure to inflammation in utero is an important contributor to the pathogenesis of bronchopulmonary dysplasia. We hypothesized that chronic inflammation would alter the pulmonary air space and vascular development after 70 days of exposure to infection. Pregnant ewes were given intra-amniotic injection of Ureaplasma parvum serovars 3 or 6 at low (2 x 10(4) cfu) or high doses (2 x 10(7) cfu) or media (controls) at 55 days gestational age. Fetuses were delivered at 125 days (term = 150 days). U. parvum was grown from the lungs of all exposed fetuses, and neutrophils and monocytes were increased in the air spaces. Lung mRNA expression of IL-1beta and IL-8, but not IL-6, was modestly increased in U. parvum-exposed fetuses. U. parvum exposure increased surfactant and improved lung gas volumes. The changes in lung inflammation and maturation were independent of serovar or dose. Exposure to U. parvum did not change multiple indices of air space or vascular development. Parenchymal elastin and collagen content were similar between groups. Expression of several endothelial proteins and pulmonary resistance arteriolar media thickness were also not different between groups. We conclude that chronic exposure to U. parvum does not cause sustained effects on air space or vascular development in premature lambs.

Inflammation is a protective response mediated by both innate and adaptive arms of the immune system following exposure to a range of harmful stimuli. Although inflammation is an essential mechanism in response to challenges including tissue injury and microbiological insult, inappropriate or excessive induction of the inflammatory response is itself a well-characterized cause of morbidity and mortality in adult populations. There is currently a growing appreciation of the potential for inflammation to play an adverse role in fetal health. The expression of cytokines (notably interleukin 1beta [IL-1beta], IL-6, IL-8, and tumor necrosis factor alpha [TNF-alpha]) by either the fetal or maternal tissues has been demonstrated to upregulate the activity of a number of uterine and cervical factors (eg, prostaglandin hormones and their receptors, matrix metalloproteinases, vascular endothelial growth factor [VEGF]), leading to premature initiation of the parturition process. Herein, we review important developments in our understanding of the link between preterm birth and fetal inflammation subsequent to infection, gained from studies undertaken in animal models.

Ureaplasma species are the microorganisms most frequently isolated from women with preterm birth and are associated with an increased risk of bronchopulmonary dysplasia. Initiation of ventilation with high tidal volumes (VT) causes lung injury and inflammation. We investigated whether antenatal colonization with Ureaplasma parvum serovar 3 (UP) would alter the inflammatory response to mechanical ventilation of preterm lambs. Merino ewes were given intraamniotic injections of UP at 55-d gestation, and the lambs were surgically delivered at 128+/-1 d gestation and assigned to three groups: 1) gentle ventilation (GV), 2) high VT ventilation, or 3) unventilated control. Lambs delivered from noncolonized ewes were assigned to parallel groups. GV lambs received surfactant before ventilation with a VT of 7 mL/kg, positive end expiratory pressure (PEEP) 5 cm H2O. High VT lambs received no PEEP and escalating VT to 15 mL/kg by 15 min. At 15 min, surfactant was given, VT was reduced to 7 mL/kg, and PEEP was increased to 5 cm H2O. Monocytes in bronchoalveolar lavage were increased by UP, but colonization did not affect lung function. High VT ventilation increased Egr-1 signaling, proinflammatory cytokine expression, and injury scores compared with GV. Antenatal colonization with UP did not change lung function or modulate the lung injury and inflammation caused by high VT ventilation.

Objective: To investigate whether treating periodontal disease prevents preterm birth and other major complications of pregnancy., Methods: This single-center trial was conducted across six obstetric sites in metropolitan Perth, Western Australia. Pregnant women identified by history to be at risk (n=3,737) were examined for periodontal disease. Approximately 1,000 women with periodontal disease were allocated at random to receive periodontal treatment commencing around 20 weeks of gestation (n=542) or 6 weeks after the pregnancy was completed (controls; n=540). The treatment included mechanical removal of oral biofilms together with oral hygiene instruction and motivation at a minimum of three weekly visits, with further visits if required., Results: There were no differences between the control and treatment groups in preterm birth (9.3% compared with 9.7%, odds ratio [OR] 1.05, 95% confidence interval [CI 0.7-1.58], P=.81), birth weight (3,450 compared with 3,410 g, P=.12), preeclampsia (4.1% compared with 3.4%, OR 0.82, 95% CI 0.44-1.56, P=.55), or other obstetric endpoints. There were four unexplained stillbirths in the control group and no pregnancy losses in the treated group (P=.12). Measures of fetal and neonatal well-being were similar in the two groups, including abnormalities in fetal heart rate recordings (P=.26), umbilical artery flow studies (P=.96), and umbilical artery blood gas values (P=.37). The periodontal treatment was highly successful in improving health of the gums (P<.01)., Conclusion: The evidence provided by the present study does not support the hypothesis that treatment of periodontal disease during pregnancy in this population prevents preterm birth, fetal growth restriction, or preeclampsia. Periodontal treatment was not hazardous to the women or their pregnancies., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00133926., Level of Evidence: I.

Preterm infants exposed to chorioamnionitis and preterm sheep fetuses exposed to intra-amniotic (IA) LPS have lung inflammation, increased IL-8 levels, and lung maturation. We tested the hypothesis that IL-8 signaling mediates IA LPS-induced lung inflammation and lung maturation. Two strategies were used: 1) we tested if IA injection of recombinant sheep IL-8 (rsIL-8) induced fetal inflammation and 2) if IL-8 signaling was blocked by a novel CXCR2 receptor blocker, nicotinanilide thioglycolate methyl ester (NTME). To test effects of IL-8 in the fetus, rsIL-8 was given intravascularly (50 microg) at 124 +/- 1 day of gestation (term = 150 days). A separate group of sheep was given IA rsIL-8 (100 microg) and delivered 5 h to 7 days later at 124 +/- 1 day of gestation. After confirming efficacy of the CXCR2 inhibitor, effects of IL-8 blockade were tested by injecting fetal sheep intramuscularly with NTME (10 mg) before IA injection of Escherichia coli LPS (10 mg). Sheep fetuses were delivered 1 or 7 days after injections at 124 +/- 1 day of gestation. IA rsIL-8 induced a modest fivefold increase in bronchoalveolar lavage (BAL) monocytes and neutrophils and increased lung monocyte hydrogen peroxide generation. However, rsIL-8 did not induce lung maturation. Intravascular rsIL-8 did not change fetal cardiovascular variables, blood pH, or blood leukocyte counts. Inhibition of CXCR2 decreased IA LPS-induced increases in BAL proteins at 1 day but not at 7 days. NTME did not significantly decrease IA LPS-induced BAL leukocyte influx and lung cytokine mRNA expression. Inhibition of CXCR2 did not change IA LPS-induced lung maturation. IL-8 signaling does not mediate LPS-induced lung inflammation and lung maturation.

Objective: The onset of copious milk secretion after birth is known as lactogenesis II. The objective of this study was to investigate the effect of preterm birth and antenatal corticosteroids on the timing of lactogenesis II after birth., Methods: Women who had received antenatal betamethasone treatment and were expressing for a preterm infant whose gestational age was <34 weeks (N = 50) were included. On days 1 to 10 postpartum, participants measured the volume of milk expressed in 24-hour periods and collected milk samples. Lactose and citrate levels were analyzed in the milk., Results: The gestational age at delivery was 31 weeks (range: 24.2-33.7). Milk volume was recorded by 46 women on 320 expression days and was positively associated with gestational age. Gestational age modified the effect of interval between betamethasone administration and delivery on milk volume. At gestational age 28 to 34 weeks, women who delivered 0 to 2 days after betamethasone treatment obtained significantly greater volumes than women who delivered 3 to 9 days after treatment. Milk samples (N = 324) were collected by 42 mothers. Mean +/- SD lactose and citrate levels were 156.800 +/- 36.217 and 3.458 +/- 1.442 mM, respectively. There was a significant positive effect of gestational age on milk lactose levels but not citrate levels. Betamethasone treatment did not alter lactose or citrate levels in milk., Conclusions: Delivery at extremely preterm gestational ages caused a significant delay in the onset of lactogenesis II. The volume of milk was reduced further when antenatal corticosteroids were administered between 28 and 34 weeks' gestation and delivery occurred 3 to 9 days later. In view of the advantages of mothers' own milk, additional support with lactation is recommended for mothers of preterm infants, particularly those who have been treated with corticosteroids before the delivery.

Periodontal disease is a common infectious disease in women of reproductive age. The disease is often not diagnosed and in studies of over 10 000 women has been associated with preterm birth, small for gestational age newborns, and preeclampsia. It has been shown in a smaller number of women that treatment of periodontal disease may reduce the rate of preterm birth. The pregnancy complications of periodontal disease may be due to lipopolysaccharide from the periodontal pockets inciting prostaglandin pathways controlling parturition. Three large randomized controlled trials of treatment of periodontal disease are underway and may provide confirmation of the importance of periodontal disease in causing complications of pregnancy.

Objective: Prenatal Ureaplasma spp exposure is associated with preterm birth and modulates the neonates' susceptibility to respiratory distress syndrome and bronchopulmonary dysplasia. We hypothesized that intra-amniotic ureaplasmas would cause lung inflammation and alter fetal lung development., Study Design: Pregnant ewes bearing singleton fetuses were given an intra-amniotic injection of 20 x 10 6 CFUs of U parvum (serovar 3) or vehicle, either 1, 3, 6, or 10 weeks before the delivery of preterm lambs at 124 days of gestation (n = 4-10 per group) for evaluation of inflammation and fetal lung maturation., Results: Ureaplasmas were recovered from amniotic and fetal lung fluids after intra-amniotic injection. Body weight and umbilical arterial pH were reduced by Ureaplasma exposure for 10 weeks ( P < .05). Ureaplasmas caused progressive lung inflammation and improvements in lung function that were associated with increased surfactant lipids (control, 0.13 +/- 0.02 micromol/kg; 10 weeks of Ureaplasma exposure, 7.43 +/- 3.0 micromol/kg; P < .001) and surfactant protein messenger RNA expression., Conclusion: Long-term exposure to ureaplasmas in amniotic fluid alters ovine fetal development.