Regulation of biosimilar medicines and current perspectives on interchangeability and policy.

Competition arising from the increasing availability of biosimilar medicines has resulted in healthcare savings and has provided greater patient access to high cost therapeutics in Europe. The biosimilar market in the USA is relatively new so the full impact of biosimilar availability remains to be seen. Educational initiatives relating to the use of biosimilar medicines are currently being undertaken by regulators, policy makers and industry. The debate on biosimilars has moved on from the appropriateness of the regulatory framework which governs their approval, to the practice of interchangeability. Interchangeability is an important issue for healthcare professionals but different definitions and regulatory frameworks exist in the USA and Europe. In the USA, an interchangeable biological product is a biosimilar which may be substituted by a pharmacist, subject to local State policies. The interchangeability of a biosimilar with its reference medicine will be evaluated by the United States Food and Drug Administration (FDA) in cases where approval as an 'interchangeable product' is sought. In contrast, the European Medicines Agency (EMA) does not assess or make recommendations on interchangeability, therefore, in Europe, interchangeability does not mean substitution but is generally physician-led or driven by national policy. This paper provides an overview of the regulation of biosimilar medicines. Challenges associated with the demonstration of interchangeability and practical considerations relating to switching are also discussed. Finally, we present policies that have been adopted to date in several European countries, the USA and Australia, which aim to promote the use of biosimilar medicines.

An economic evaluation of planned immediate versus delayed birth for preterm prelabour rupture of membranes: findings from the PPROMT randomised controlled trial.

OBJECTIVE: This study is an economic evaluation of immediate birth compared with expectant management in women with preterm prelabour rupture of the membranes near term (PPROMT). DESIGN: A cost-effectiveness analysis alongside the PPROMT randomised controlled trial. SETTING: Obstetric departments in 65 hospitals across 11 countries. POPULATION: Women with a singleton pregnancy with ruptured membranes between 34+0 and 36+6 weeks gestation. METHODS: Women were randomly allocated to immediate birth or expectant management. Costs to the health system were identified and valued. National hospital costing data from both the UK and Australia were used. Average cost per recruit in each arm was calculated and 95% confidence intervals were estimated using bootstrap re-sampling. Averages costs during antenatal care, delivery and postnatal care, and by country were estimated. MAIN OUTCOMES MEASURES: Total mean cost difference between immediate birth and expectant management arms of the trial. RESULTS: From 11 countries 923 women were randomised to immediate birth and 912 were randomised to expectant management. Total mean costs per recruit were £8852 for immediate birth and £8740 for expectant delivery resulting in a mean difference in costs of £112 (95% CI: -431 to 662). The expectant management arm had significantly higher antenatal costs, whereas the immediate birth arm had significantly higher delivery and neonatal costs. There was large variation between total mean costs by country. CONCLUSION: This economic evaluation found no evidence that expectant management was more or less costly than immediate birth. Outpatient management may offer opportunities for cost savings for those women with delayed delivery. TWEETABLE ABSTRACT: For women with preterm prelabour rupture of the membranes, the relative benefits and harms of immediate and expectant management should inform counselling as costs are similar.

Association between interpregnancy interval and the risk of recurrent loss after a midtrimester loss.

STUDY QUESTION: After an initial midtrimester loss, is the interval to the next conception associated with the risk of a recurrent loss? SUMMARY ANSWER: Among women who had a pregnancy loss at 14-19 weeks gestation, conception at least 3 months after this initial loss was associated with a reduced risk of a recurrent loss. WHAT IS KNOWN ALREADY: A short interpregnancy interval (IPI) has been thought to increase risk but recent studies of pregnancy after a loss have found no effect; however, these studies have been based almost entirely on an initial first trimester (<14 weeks) loss. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study drawing on over 997 000 linked birth and hospital records from New South Wales, Australia for 2003-2011. Index pregnancies were those of women who had a first recorded pregnancy loss of 14-23 weeks gestation (miscarriage, termination and perinatal death). The study population was 4290 women who conceived again within 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: The index loss was categorized by subgroups: 14-19 weeks gestation versus 20-23 weeks, and by whether spontaneous or a termination. The primary outcome was any loss or perinatal death before 24 weeks in the subsequent pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: After a 14-19 weeks index loss, an IPI of ≤3 months had an increased rate of recurrent loss compared with an IPI of >9-12 months: 21.9% versus 11.3% (adjusted relative risk (aRR) = 2.02, 95% CI 1.44-2.83). For women who had a spontaneous index loss of 20-23 weeks, there was no evidence that a short IPI increased or decreased the risk of recurrent loss. For any gestational age group of index losses, an IPI of >18-24 months increased the risk of a recurrent loss; the risk was highest after a 20-23 weeks index loss (aRR = 2.15, 95% CI 1.18-3.91). LIMITATIONS, REASONS FOR CAUTION: We do not know how many cycles were required to achieve conception. Pregnancies resulting in early first trimester losses are unlikely to have resulted in hospitalization so would not have been identified. WIDER IMPLICATIONS OF THE FINDINGS: The risk of recurrent loss after an initial midtrimester loss may differ from the risk after an initial first trimester loss. STUDY FUNDING/COMPETING INTERESTS: This work was supported by an Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant (1001066). C.L.R. is supported by an NHMRC Senior Research Fellowship (#APP1021025). J.B.F. is supported by an ARC Future Fellowship (#120100069). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review.

AIM: High iron measured using dietary intake and biomarkers is associated with Type 2 diabetes. It is uncertain whether a similar association exists for gestational diabetes mellitus. The aim of this systematic review was to conduct a cohort study examining first trimester body iron stores and subsequent risk of gestational diabetes, and to include these findings in a systematic review of all studies examining the association between maternal iron status, iron intake (dietary and supplemental) and the risk of gestational diabetes. METHODS: Serum samples from women with first trimester screening were linked to birth and hospital records for data on maternal characteristics and gestational diabetes diagnosis. Blood was analysed for ferritin, soluble transferrin receptor and C-reactive protein. Associations between iron biomarkers and gestational diabetes were assessed using multivariate logistic regression. A systematic review and meta-analysis, registered with PROSPERO (CRD42014013663) included studies of all designs published in English from January 1995 to July 2015 that examined the association between iron and gestational diabetes and included an appropriate comparison group. RESULTS: Of 3776 women, 3.4% subsequently developed gestational diabetes. Adjusted analyses found increased odds of gestational diabetes for ferritin (OR 1.41; 95% CI 1.11, 1.78), but not for soluble transferrin receptor (OR 1.00; 95% CI 0.97, 1.03) per unit increase of the biomarker. Two trials of iron supplementation found no association with gestational diabetes. Increased risk of gestational diabetes was associated with higher levels of ferritin and serum iron and dietary haem iron intakes. CONCLUSIONS: Increased risk of gestational diabetes among women with high serum ferritin and iron levels and dietary haem iron intakes warrants further investigation.

Fluoroscopically guided transforaminal epidural steroid injections at a quaternary-care teaching institution: effect of trainee involvement and patient body mass index on fluoroscopy time and patient dose.

AIM: To investigate whether there are differences in fluoroscopy time and patient dose for fluoroscopically guided lumbar transforaminal epidural steroid injections (TFESIs) performed by staff radiologists versus with trainees and to evaluate the effect of patient body mass index (BMI) on fluoroscopy time and patient dose, including their interactions with other variables. MATERIALS AND METHODS: Single-level lumbar TFESIs (n=1844) between 1 January 2011 and 31 December 2013 were reviewed. Fluoroscopy time, reference point air kerma (Ka,r), and kerma area product (KAP) were recorded. BMI and trainee involvement were examined as predictors of fluoroscopy time, Ka,r, and KAP in models adjusted for age and gender in multivariable linear models. Stratified models of BMI groups by trainee presence were performed. RESULTS: Increased age was the only significant predictor of increased fluoroscopy time (p<0.0001). Ka,r and KAP were significantly higher in patients with a higher BMI (p<0.0001 and p=0.0009). When stratified by BMI, longer fluoroscopy time predicted increased Ka,r and KAP in all groups (p<0.0001). Trainee involvement was not a statistically significant predictor of fluoroscopy time or Ka,r in any BMI category. KAP was lower with trainees in the overweight group (p=0.0009) and higher in male patients for all BMI categories (p<0.02). CONCLUSION: Trainee involvement did not result in increased fluoroscopy time or patient dose. BMI did not affect fluoroscopy time; however, overweight and obese patients received significantly higher Ka,r and KAP. Male patients received a higher KAP in all BMI categories. Limiting fluoroscopy time and good collimation practices should be reinforced in these patients.

What factors contribute to hospital variation in obstetric transfusion rates?

BACKGROUND AND OBJECTIVES: To explore variation in red blood cell transfusion rates between hospitals, and the extent to which this can be explained. A secondary objective was to assess whether hospital transfusion rates are associated with maternal morbidity. MATERIALS AND METHODS: Linked hospital discharge and birth data were used to identify births (n = 279 145) in hospitals with at least 10 deliveries per annum between 2008 and 2010 in New South Wales, Australia. To investigate transfusion rates, a series of random-effects multilevel logistic regression models were fitted, progressively adjusting for maternal, obstetric and hospital factors. Correlations between hospital transfusion and maternal, neonatal morbidity and readmission rates were assessed. RESULTS: Overall, the transfusion rate was 1.4% (hospital range 0.6-2.9) across 89 hospitals. Adjusting for maternal casemix reduced the variation between hospitals by 26%. Adjustment for obstetric interventions further reduced variation by 8% and a further 39% after adjustment for hospital type (range 1.1-2.0%). At a hospital level, high transfusion rates were moderately correlated with maternal morbidity (0.59, P = 0.01), but not with low Apgar scores (0.39, P = 0.08), or readmission rates (0.18, P = 0.29). CONCLUSION: Both casemix and practice differences contributed to the variation in transfusion rates between hospitals. The relationship between outcomes and transfusion rates was variable; however, low transfusion rates were not associated with worse outcomes.

Reinfection after successful eradication of Helicobacter pylori in three different populations in Alaska.

We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14·5%, 22·1%, and 12·0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0·02), low education level (P = 0·04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0·03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.

Methods of classification for women undergoing induction of labour: a systematic review and novel classification system.

BACKGROUND: A lack of reproducible methods for classifying women having an induction of labour (IOL) has led to controversies regarding IOL and related maternal and perinatal health outcomes. OBJECTIVES: To evaluate articles that classify IOL and to develop a novel IOL classification system. SEARCH STRATEGY: Electronic searches using CINAHL, EMBASE, WEB of KNOWLEDGE, and reference lists. SELECTION CRITERIA: Two reviewers independently assessed studies that classified women having an IOL. DATA COLLECTION AND ANALYSIS: For the systematic review, data were extracted on study characteristics, quality, and results. Pre-specified criteria were used for evaluation. A multidisciplinary collaboration developed a new classification system using a clinically logical model and stakeholder feedback, demonstrating applicability in a population cohort of 909 702 maternities in New South Wales, Australia, over the period 2002-2011. MAIN RESULTS: All seven studies included in the systematic review categorised women according to the presence or absence of varying medical indications for IOL. Evaluation identified uncertainties or deficiencies across all studies, related to the criteria of total inclusivity, reproducibility, clinical utility, implementability, and data availability. A classification system of ten groups was developed based on parity, previous caesarean, gestational age, number, and presentation of the fetus. Nulliparous and parous women at full term were the largest groups (21.2 and 24.5%, respectively), and accounted for the highest proportion of all IOL (20.7 and 21.5%, respectively). AUTHOR'S CONCLUSIONS: Current methods of classifying women undertaking IOL based on medical indications are inadequate. We propose a classification system that has the attributes of simplicity and clarity, uses information that is readily and reliably collected, and enables the standard characterisation of populations of women having an IOL across and within jurisdictions.

Variation in hospital caesarean section rates and obstetric outcomes among nulliparae at term: a population-based cohort study.

OBJECTIVE: To explore the variation in hospital caesarean section (CS) rates for nulliparous women, to determine whether different case-mix, labour and delivery, and hospital factors can explain this variation and to examine the association between hospital CS rates and outcomes. DESIGN: Population-based cohort study. SETTING: New South Wales, 2009-2010. POPULATION: Nulliparous women with singleton cephalic live births at term. METHODS: Random effect multilevel logistic regression models using linked hospital discharge and birth data. MAIN OUTCOME MEASURES: Prelabour and intrapartum CS rates following spontaneous labour or labour induction; maternal and neonatal severe morbidity rates. RESULTS: Of 67 239 nulliparous women, 4902 (7.3%) had a prelabour CS, 39 049 (58.1%) laboured spontaneously, and 23 288 (34.6%) had labour induced. Overall, there were 18 875 (28.1%) CSs, with labour inductions twice as likely to result in an intrapartum CS compared with women with a spontaneous onset of labour (34.0% versus 15.5%). After adjusting for differences in case-mix, labour and delivery, and hospital factors, the overall variation in CS rates decreased by 78% for prelabour CSs, 52% for intrapartum CSs following spontaneous labour and 9% following labour induction. Adjusting for labour and delivery practices increased the unexplained variation in intrapartum CSs. The adjusted rates of severe maternal and neonatal morbidity were not significantly different across CS rate quintile groups, except for women in spontaneous labour, where the hospitals in the lowest CS quintile had the lowest neonatal morbidity rate. CONCLUSIONS: Differences in clinical practice were substantial contributors to variation in intrapartum CS rates. Our findings suggest that CS rates in some hospitals could be lowered without adversely affect pregnancy outcomes.

Mandatory reporting of impaired medical practitioners: protecting patients, supporting practitioners.

Taking action to protect patients from impaired colleagues is a long-standing ethical and professional obligation. In 2010, this responsibility was codified in law with the introduction, across Australia, of a new mandatory reporting regimen. While several concerns remain to be addressed, mandatory reporting has the potential not only to reinforce the primacy of patient safety, but also to open internal dialogue about the profession's response to concerns about practitioner health and well-being. Four years after the introduction of the scheme, key challenges include ensuring the reporting threshold is appropriately defined and clearly understood, improving access to evidence-based health programmes for practitioners, and strengthening upstream protections to prevent and minimise impairment at its roots.

To B or not to B cells-mediate a healthy start to life.

Maternal immune responses during pregnancy are critical in programming the future health of a newborn. The maternal immune system is required to accommodate fetal immune tolerance as well as to provide a protective defence against infections for the immunocompromised mother and her baby during gestation and lactation. Natural immunity and antibody production by maternal B cells play a significant role in providing such immunoprotection. However, aberrations in the B cell compartment as a consequence of maternal autoimmunity can pose serious risks to both the mother and her baby. Despite their potential implication in shaping pregnancy outcomes, the role of B cells in human pregnancy has been poorly studied. This review focuses on the role of B cells and the implications of B cell depletion therapy in pregnancy. It highlights the evidence of an association between aberrant B cell compartment and obstetric conditions. It also alludes to the potential mechanisms that amplify these B cell aberrances and thereby contribute to exacerbation of some maternal autoimmune conditions and poor neonatal outcomes. Clinical and experimental evidence suggests strongly that maternal autoantibodies contribute directly to the pathologies of obstetric and neonatal conditions that have significant implications for the lifelong health of a newborn. The evidence for clinical benefit and safety of B cell depletion therapies in pregnancy is reviewed, and an argument is mounted for further clinical evaluation of B cell-targeted therapies in high-risk pregnancy, with an emphasis on improving neonatal outcomes and prevention of neonatal conditions such as congenital heart block and fetal/neonatal alloimmune thrombocytopenia.

Decision aids to improve informed decision-making in pregnancy care: a systematic review.

BACKGROUND: Rapid development in health care has resulted in an increasing number of screening and treatment options. Consequently, there is an urgency to provide people with relevant information about benefits and risks of healthcare options in an unbiased way. Decision aids help people to make decisions by providing unbiased non-directive research evidence about all treatment options. OBJECTIVE: To determine the effectiveness of decision aids to improve informed decision making in pregnancy care. SEARCH STRATEGY: We searched MEDLINE (1953-2011), EMBASE (1980-2011), CENTRAL (CENTRAL, the Cochrane Library; 2011, Issue 4), Psycinfo (1806-2011) and Research Registers of ongoing trials (www.clinicaltrials.gov, www.controlled-trials.com). SELECTION CRITERIA: We included randomised controlled trials comparing decision aids in addition to standard care. The study population needed to be pregnant women making actual decisions concerning their pregnancy. DATA COLLECTION AND ANALYSIS: Two independent researchers extracted data on quality of the randomised controlled trial (GRADE criteria), quality of the decision aid (IPDAS criteria), and outcome measures. Data analysis was undertaken by assessing group differences at first follow up after the interventions. MAIN RESULTS: Ten randomised controlled trials could be included. Pooled analyses showed that decision aids significantly increased knowledge, (weighted mean difference 11.06, 95% confidence interval 4.85-17.27), decreased decisional conflict scores (weighted mean difference -3.66, 95% confidence interval -6.65 to -0.68) and decreased anxiety (weighted mean difference -1.56, 95% confidence interval -2.75 to -0.43). CONCLUSIONS: Our systematic review showed the positive effect of decision aids on informed decision making in pregnancy care. Future studies should focus on increasing the uptake of decision aids in clinical practice by identifying barriers and facilitators to implementation.

Fluoroscopy- and CT-Guided Gold Fiducial Marker Placement for Intraoperative Localization during Spinal Surgery: Review of 179 Cases at a Single Institution-Technique and Safety Profile.

BACKGROUND AND PURPOSE: Wrong-level spinal surgery, especially in the thoracic spine, remains a challenge for a variety of reasons related to visualization, such as osteopenia, large body habitus, severe kyphosis, radiographic misinterpretation, or anatomic variation. Preoperative fiducial marker placement performed in a dedicated imaging suite has been proposed to facilitate identification of thoracic spine vertebral levels. In this current study, we report our experience using image-guided percutaneous gold fiducial marker placement to enhance the accuracy and safety of thoracic spinal surgical procedures. MATERIALS AND METHODS: A retrospective review was performed of all fluoroscopy- or CT-guided gold fiducial markers placed at our institution between January 3, 2019, and March 16, 2022. A chart review of 179 patients was performed detailing the procedural approach and clinical information. In addition, the method of gold fiducial marker placement (fluoroscopy/CT), procedure duration, spinal level of the gold fiducial marker, radiation dose, fluoroscopy time, surgery date, and complications (including whether wrong-level surgery occurred) were recorded. RESULTS: A total of 179 patients (104 female) underwent gold fiducial marker placement. The mean age was 57 years (range, 12-96 years). Fiducial marker placement was performed by 13 different neuroradiologists. All placements were technically successful without complications. All 179 (100%) operations were performed at the correct level. Most fiducial markers (143) were placed with fluoroscopy with the most common location at T6-T8. The most common location for placement in CT was at T3 and T4. CONCLUSIONS: All operations guided with gold fiducial markers were performed at the correct level. There were no complications of fiducial marker placement.

Source of angiopoietin-2 in the sera of women during pregnancy.

Placental development requires coordinated angiogenesis regulated by multiple factors including angiopoietins. Previously we demonstrated that the concentration of angiopoietin-2 (Ang-2) in the sera of women rises markedly in pregnancy in early gestation. This increase is reduced in pregnancies subsequently complicated by intrauterine growth restriction (IUGR). We now show that the concentration of Ang-2, but not Ang-1, in maternal serum is increased during normal pregnancy, peaking at the end of the first trimester. We also demonstrate that a key source of the elevated Ang-2 levels during pregnancy is decidual endothelial cells (DECs) but not cytotrophoblasts. Secretion of Ang-2 by DECs relies on the release from intracellular stores and the synthesis of new Ang-2 protein and is regulated by serum factors at a translational level. Further studies on the role of Ang-2 during pregnancy are warranted as well as the evaluation of Ang-2 as a marker to predict adverse pregnancy outcomes.

Percutaneous CT-Guided Core Needle Biopsies of Head and Neck Masses: Review of 184 Cases at a Single Academic Institution, Common and Special Techniques, Diagnostic Yield, and Safety.

BACKGROUND AND PURPOSE: Percutaneous CT-guided core needle biopsies of head and neck lesions can be safely performed with vigilant planning. This largest-to-date single-center retrospective study evaluates multiple approaches with consideration of special techniques and examines the histopathologic yield. MATERIALS AND METHODS: Retrospective review of CT-guided core biopsies of head and neck lesions from January 1, 2010, to October 30, 2020, was performed. We recorded the following: patient demographics, sedation details, biopsy needle type and size, lesion location and size, approach, patient positioning, preprocedural intravenous contrast, proceduralists' years of experience, complications, and pathology results. RESULTS: One hundred eighty-four CT-guided core biopsies were evaluated. The initial diagnostic yield was 93% (171/184). However, of 43/184 (23%) originally "negative for malignancy" biopsies, 4 were eventually positive for malignancy via rebiopsy/excision, resulting in a 2% false-negative rate and an adjusted total diagnostic yield of 167/184 (91%). Biopsies were performed by 16 neuroradiologists with variable experience. The diagnostic yield was essentially the same: 91% (64/70) for proceduralists with ≤3 years' experience, and 90% (103/114) with >3 years' experience. The diagnostic yield was 93% (155/166) for lesions of >10 mm. The diagnostic yield per biopsy needle gauge was the following: 20 ga, 81% (13/16); 18 ga, 93% (70/75); 16 ga, 90% (64/71); and 14 ga, 91% (20/22). There were 4 asymptomatic hematomas, with none requiring intervention. CONCLUSIONS: Percutaneous CT-guided core needle biopsies are safe procedures for superficial and deep head and neck lesions with a high diagnostic yield. Careful planning and special techniques may increase the number of lesions accessible percutaneously while minimizing the risk of complications.

A balancing act: mechanisms by which the fetus avoids rejection by the maternal immune system.

Successful pregnancy requires strict temporal regulation of maternal immune function to accommodate the growing fetus. Early implantation is facilitated by inflammatory processes that ensure adequate vascular remodeling and placental invasion. To prevent rejection of the fetus, this inflammation must be curtailed; reproductive immunologists are discovering that this process is orchestrated by the fetal unit and, in particular, the extravillous trophoblast. Soluble and particulate factors produced by the trophoblast regulate maternal immune cells within the decidua, as well as in the periphery. The aim of this review is to discuss the action of recently discovered immunomodulatory factors and mechanisms, and the potential effects of dysregulation of such mechanisms on the maternal immune response that may result in pregnancy loss or preeclampsia.

Trends in obstetric practices and meconium aspiration syndrome: a population-based study.

OBJECTIVE: To determine trends in the incidence of meconium aspiration syndrome (MAS), and maternal factors and obstetric practices associated with any decline. DESIGN: Population-based cohort study. SETTING: New South Wales (NSW), Australia. POPULATION: All 877 037 liveborn, singleton, term infants (≥ 37 weeks of gestation) in the period 1997-2007. METHODS: Data were obtained from birth records linked to the neonatal hospital discharge records. The birth data provided information on maternal and obstetric factors, whereas the outcome of interest, MAS, was obtained from hospital data on the neonates. Multivariable logistic regression was used to estimate the risk of MAS while simultaneously adjusting for the explanatory variables. MAIN OUTCOME MEASURES: The incidence of MAS per 1000 births, and odds ratios and 95% confidence intervals for maternal and obstetric factors for the development of MAS. RESULTS: The incidence of MAS declined significantly by 11.3% per annum (95% CI 10.1-12.6; P < 0.001) from 4.1 per 1000 births in 1997 to 1.3 per 1000 births in 2007. This was associated with a statistically significant decline in risk factors: maternal smoking (from 20 to 12%), gestational age (from 57 to 47% ≥ 40 weeks of gestation), delivery at small hospitals (from 15 to 9%) and infants with birthweight below the third percentile (from 3.3 to 2.4%). There were simultaneous statistically significant increases in practices that reduce the risk of MAS: labour inductions (from 22 to 27%) and birth by caesarean section, both elective, prior to 40 weeks of gestation (from 7.3 to 13.8%), and emergency (from 3.0 to 5.3% prior to 40 weeks of gestation, and from 5.1 to 6.7% at 40 weeks of gestation or later). CONCLUSIONS: The rate of MAS is declining, and this decline is associated with a reduction in maternal and pregnancy risk factors, and an increase in protective obstetric practices.

Amniotic fluid embolism in an Australian population-based cohort.

We utilised linked birth, hospital and death data for the entire population to determine the incidence of amniotic fluid embolism (AFE) and its mortality and morbidity. AFE diagnoses were identified from International Classification of Diseases, 10th Revision (ICD10)-coded hospital and/or death records with additional case definition criteria imposed. The AFE incidence was 3.3 per 100,000 (95% CI, 1.9-4.7), maternal fatality rate 35% (95% CI, 15-59) and perinatal mortality rate 32% (95% CI, 12-56). Newly identified risk factors included induction with vaginal prostaglandin and manual removal of the placenta, and survivors were at increased risk of cerebral infarction. Although two-thirds of women and infants survived, AFE also caused severe morbidity.

Recurrence of breech presentation in consecutive pregnancies.

OBJECTIVE: To investigate the recurrence risk of breech presentation at term, and to assess the risk factors that contribute to its recurrence. DESIGN: Cohort study. SETTING: New South Wales, Australia. POPULATION: Women with their first two (n = 113 854) and first three (n = 21 690) consecutive singleton term pregnancies, in the period 1994-2002. METHODS: Descriptive statistics including rates, relative risks and adjusted relative risks, as determined from logistic regression and Poisson analyses. MAIN OUTCOME MEASURES: Rates and risks of occurrence and recurrence of breech presentation at birth in each pregnancy, and maternal and infant risk factors associated with breech recurrence. RESULTS: First-time breech presentation at term occurred in 4.2% of first pregnancy deliveries, 2.2% of second pregnancies and 1.9% of third pregnancies. The rate of breech recurrence in a second consecutive pregnancy was 9.9%, and in a third consecutive pregnancy (after two prior breech deliveries) was 27.5%. The relative risk of breech recurrence in a second pregnancy was 3.2 (95% CI 2.8-3.6), and in a third consecutive breech pregnancy was 13.9 (95% CI 8.8-22.1). First pregnancy factors associated with recurrence included placenta praevia [adjusted relative risk (aRR) 2.2; 95% CI 1.3-3.7], maternal diabetes (aRR 1.4; 95% CI 1.0-2.1) and a maternal age of > or =35 years (aRR 1.2; 95% CI 0.9-1.6). Second pregnancy factors included birth defects (aRR 2.5; 95% CI 1.4-4.2), placenta praevia (aRR 2.5; 95% CI 1.5-4.1) and a female infant (aRR 1.2; 95% CI 1.0-1.5). CONCLUSIONS: The increased recurrence risk of breech presentations suggests that women with a history of breech delivery should be closely monitored in the latter stages of pregnancy.

Defining a study population using enhanced reporting of Aboriginality and the effects on study outcomes.

INTRODUCTION: The under-reporting of Aboriginal and Torres Strait Islander people on routinely collected health datasets has important implications for understanding the health of this population. By pooling available information on individuals' Aboriginal or Torres Strait Islander status from probabilistically linked datasets, methods have been developed to adjust for this under-reporting. OBJECTIVES: To explore different algorithms that enhance reporting of Aboriginal status in birth data to define a cohort of Aboriginal women, examine any differences between women recorded as Aboriginal and those assigned enhanced Aboriginal status, and assess the effects of using different reported populations to estimate within-group comparisons for Aboriginal people. METHODS: Three algorithms, with different levels of inclusiveness, were used to establish different study populations all of which aimed to include all singleton babies born to Aboriginal or Torres Strait Islander women residing in New South Wales, Australia between 2010 and 2014 and their mothers. The demographics of the four study populations were described and compared using frequencies and percentages. In order to assess the impact on research outcomes and conclusions of using study populations derived from different algorithms, estimates of the associations between smoking during pregnancy and selected perinatal outcomes were compared using rates and relative risks. RESULTS: Women included in the study population through enhanced reporting were older, less disadvantaged and more commonly resided in urban areas than those recorded as Aboriginal in the birth data. Although rates of smoking and some perinatal outcomes differed between the different study populations, the relative risks of each outcome comparing smoking and non-smoking Aboriginal mothers were very similar when estimated from each of the study populations. CONCLUSIONS: This work provides evidence that estimates of within-group relative risks are reliable regardless of the assumptions made for establishing the study population through the enhanced reporting of indigenous peoples.