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Objective: To identify a polyunsaturated fatty acid (PUFA) biomarker able to detect which women with singleton pregnancies are most likely to benefit from omega-3 supplementation to reduce their risk of early preterm birth.Design: Exploratory analysis of a randomised controlled trial.Setting: Six Australian hospitals.Population: Women with a singleton pregnancy enrolled in the ORIP trial.Methods: Using maternal capillary whole blood collected ~14 weeks' gestation, the fatty acids in total blood lipids were quantified using gas chromatography. Interaction tests examined whether baseline PUFA status modified the effect of omega-3 supplementation on birth outcomes.Main Outcome Measure: Early preterm birth (<34 weeks' gestation).Results: A low total omega-3 PUFA status in early pregnancy was associated with a higher risk of early preterm birth. Among women with a total omega-3 status ≤4.1% of total fatty acids, omega-3 supplementation substantially reduced the risk of early preterm birth compared with control (0.73 versus 3.16%; relative risk = 0.23, 95% confidence interval [CI] 0.07-0.79). Conversely, women with higher total omega-3 status in early pregnancy were at lower risk of early preterm birth. Supplementing women with a baseline status above 4.9% increased early preterm birth (2.20 versus 0.97%; relative risk = 2.27, 95% CI 1.13-4.58).Conclusions: Women with singleton pregnancies and low total omega-3 PUFA status early in pregnancy have an increased risk of early preterm birth and are most likely to benefit from omega-3 supplementation to reduce this risk. Women with higher total omega-3 status are at lower risk and additional omega-3 supplementation may increase their risk.Tweetable Abstract: Low total omega-3 fat status helps identify which women benefit from extra omega-3 to reduce early prematurity. [ABSTRACT FROM AUTHOR]

Objective: To estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies.Design: Secondary analysis of data from 12 RCTs.Setting: Obstetric care in multiple countries, 2004-2012.Population or Sample: 4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy.Methods: Intraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models.Main Outcome Measures: Perinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome.Results: ICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies.Conclusions: The correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs.Tweetable Abstract: Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the impact that Academic Detailing (AD) had on General Practitioners' use of diagnostic imaging for shoulder complaints in general practice and their knowledge and confidence to manage shoulder pain.Methods: One-to-one Academic Detailing (AD) for management of shoulder pain was delivered to 87 General Practitioners (GPs) in metropolitan Adelaide, South Australia, together with locally developed clinical guidelines and a video/DVD on how to examine the shoulder. Three months after the initial AD a further small group or an individual follow up session was offered. A 10-item questionnaire to assess knowledge about the shoulders was administered before, immediately after, and 3 months after AD, together with questions to assess confidence to manage shoulder complaints. The number of requests for plain film (X-ray) and ultrasound (US) imaging of the shoulder was obtained for the intervention group as well as a random comparison group of 90 GP's from the same two Divisions. The change in the rate of requests was assessed using a log Poisson GEE with adjustment for clustering at the practice level. A linear mixed effects model was used to analyse changes in knowledge.Results: In an average week 54% of GPs reported seeing fewer than 6 patients with shoulder problems. Mean (SD) GP knowledge score before, immediately after and 3-months after AD, was 6.2/ 10 (1.5); 8.6/10 (0.96) and; 7.2/ 10 (1.5) respectively (p < 0.0001). Three months after AD, GPs reported feeling able to take a more meaningful history, more confident managing shoulder pain, and felt their management of shoulder pain had improved. Requests for ultrasound imaging were approximately 43.8% higher in the period 2 years before detailing compared to six months after detailing (p < 0.0001), but an upward trend toward baseline was observed in the period 6 months to I year after AD. There was no statistically significant change in the rate of requests from before to after AD for plain-radiographs (p = 0.11). No significant changes in the rate of requests over time were observed in the control groups.Conclusion: These results provide evidence that AD together with education materials and guidelines can improve GPs' knowledge and confidence to manage shoulder problems and reduce the use of imaging, at least in the short term. [ABSTRACT FROM AUTHOR]

BACKGROUND: Point-of-care testing is increasingly being used in general practice to assist GPs in their management of patients with chronic disease. However, patient satisfaction and acceptability of point-of-care testing in general practice has not been widely studied. AIM: To determine if patients are more satisfied with point-of-care testing than with pathology laboratory testing for three chronic conditions. DESIGN OF STUDY: As part of a large multicentre, randomised, controlled trial assessing the use of point-of-care testing in Australian general practice, satisfaction was measured for patients having pathology testing performed by point-of-care testing devices or pathology laboratories. Patients in the trial were managed by GPs for diabetes, hyperlipidaemia, and/or anticoagulant therapy. METHOD: Patient satisfaction was measured using level of agreement with a variety of statements at the end of the study with a patient satisfaction questionnaire for both the intervention and control groups. Analysis was performed using a mixed model analysis of variance (ANOVA) with allowance for clustering at the practice level following Box-Cox transformations of the data to achieve normality. RESULTS: Overall, intervention patients reported that they were satisfied with point-of-care testing. In comparison with the control group, the intervention group had a higher level of agreement than control patients with statements relating to their satisfaction with the collection process (P<0.001) and confidence in the process (P<0.001). They also viewed point-of-care testing as strengthening their relationship with their GP (P = 0.010) and motivational in terms of better managing their condition (P<0.001). CONCLUSION: The results from this trial support patient satisfaction and acceptability of point-of-care testing in a general practice setting. [ABSTRACT FROM AUTHOR]

Background: Point of care testing (PoCT) may be a useful adjunct in the management of chronic conditions in general practice (GP). The provision of pathology test results at the time of the consultation could lead to enhanced clinical management, better health outcomes, greater convenience and satisfaction for patients and general practitioners (GPs), and savings in costs and time. It could also result in inappropriate testing, increased consultations and poor health outcomes resulting from inaccurate results. Currently there are very few randomised controlled trials (RCTs) in GP that have investigated these aspects of PoCT.Design/methods: The Point of Care Testing in General Practice Trial (PoCT Trial) was an Australian Government funded multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost effectiveness and satisfaction of PoCT in a GP setting.The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes, hyperlipidaemia and patients on anticoagulant therapy. The primary outcome measure was the proportion of patients within target range, a measure of therapeutic control. In addition, the PoCT Trial investigated the safety of PoCT, impact of PoCT on patient compliance to medication, stakeholder satisfaction, cost effectiveness of PoCT versus laboratory testing, and influence of geographic location.Discussion: The paper provides an overview of the Trial Design, the rationale for the research methodology chosen and how the Trial was implemented in a GP environment. The evaluation protocol and data collection processes took into account the large number of patients, the broad range of practice types distributed over a large geographic area, and the inclusion of pathology test results from multiple pathology laboratories.The evaluation protocol developed reflects the complexity of the Trial setting, the Trial Design and the approach taken within the funding provided. The PoCT Trial is regarded as a pragmatic RCT, evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that, in these circumstances, internal and external validity was maintained.Trial Registration: 12612605000272695. [ABSTRACT FROM AUTHOR]

Numerous randomised controlled trials have explored the effect of docosahexaenoic acid (DHA) supplementation in early life on neurodevelopment, with some suggested positive effects on language. Australian women with a singleton pregnancy <21 weeks' gestation were randomised to receive 800 mg DHA/day or a placebo until birth. A sample of 726 children (all n=96 born preterm, random sample of n=630 born at term) were invited to undergo assessments of language, academic, and language-based cognitive abilities at 1.5, four and seven years of age. No group differences were detected for any group comparison. Exploratory analyses for sex by treatment interactions revealed a possible adverse effect of DHA supplementation on the language of females at 1.5 years but no effects on outcomes at four or seven years. Taken as a whole, evidence of an effect of prenatal DHA supplementation on language abilities across childhood is negligible and could be a chance finding., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Omega-3 long chain polyunsaturated fatty acids (LCPUFA) have been associated with a reduction in risk for preterm birth. However, there is limited understanding of how fatty acids and their bioactive derivatives (oxylipins) change over the course of pregnancy. Here we document the changes in concentration of fatty acids and oxylipins during pregnancy and how fatty acid status and oxylipin concentrations are affected by supplementation with omega-3 LCPUFA. We also investigate the degree to which fatty acid and oxylipin changes across pregnancy are influenced by baseline omega-3 status., Materials and Methods: We profiled the fatty acids in all lipids in dried blood spots (total blood fatty acids) by gas chromatography and free (unesterified) fatty acids and their associated oxylipins in separate dried blood spot samples by LC-MS-MS collected from a random sample of 1263 women with a singleton pregnancy who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) trial. ORIP is a double-blind, randomized controlled trial involving 5544 participants and designed to determine the effect of supplementing the diets of pregnant women with omega-3 LCPUFA on the incidence of early preterm birth. Maternal whole blood finger prick samples were collected at baseline (~14 weeks gestation) and at completion of the study intervention period (34 weeks gestation)., Results: The concentration of most total and free polyunsaturated fatty acids and their associated oxylipins declined over the course of pregnancy. Omega-3 LCPUFA supplementation increased total DHA and 7-HDHA and mitigated the decline in free DHA, 4-HDHA and 14-HDHA. The intervention had minimal or no effect on free EPA, LA, AA and their associated oxylipins. Omega-3 LCPUFA supplementation in women with higher omega-3 status at baseline was associated with a significant increase in 7-HDHA and 4-HDHA between the treatment and control whereas there were no differences between groups in 7-HDHA and 4-HDHA in women with intermediate or lower baseline omega-3 status., Conclusion: Our data suggest a differential response with or without omega-3 supplementation for DHA and DHA-derived oxylipins, which may have an important role to play in modulating pregnancy duration. Further work is needed to understand their role, which may allow us to better tailor omega-3 supplementation for preterm birth prevention., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To identify a polyunsaturated fatty acid (PUFA) biomarker able to detect which women with singleton pregnancies are most likely to benefit from omega-3 supplementation to reduce their risk of early preterm birth., Design: Exploratory analysis of a randomised controlled trial., Setting: Six Australian hospitals., Population: Women with a singleton pregnancy enrolled in the ORIP trial., Methods: Using maternal capillary whole blood collected ~14 weeks' gestation, the fatty acids in total blood lipids were quantified using gas chromatography. Interaction tests examined whether baseline PUFA status modified the effect of omega-3 supplementation on birth outcomes., Main Outcome Measure: Early preterm birth (<34 weeks' gestation)., Results: A low total omega-3 PUFA status in early pregnancy was associated with a higher risk of early preterm birth. Among women with a total omega-3 status ≤4.1% of total fatty acids, omega-3 supplementation substantially reduced the risk of early preterm birth compared with control (0.73 versus 3.16%; relative risk = 0.23, 95% confidence interval [CI] 0.07-0.79). Conversely, women with higher total omega-3 status in early pregnancy were at lower risk of early preterm birth. Supplementing women with a baseline status above 4.9% increased early preterm birth (2.20 versus 0.97%; relative risk = 2.27, 95% CI 1.13-4.58)., Conclusions: Women with singleton pregnancies and low total omega-3 PUFA status early in pregnancy have an increased risk of early preterm birth and are most likely to benefit from omega-3 supplementation to reduce this risk. Women with higher total omega-3 status are at lower risk and additional omega-3 supplementation may increase their risk., Tweetable Abstract: Low total omega-3 fat status helps identify which women benefit from extra omega-3 to reduce early prematurity., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Background: Previous studies have suggested that maternal supplementation with n-3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n-3 long-chain polyunsaturated fatty acids in pregnancy., Methods: We performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n-3 long-chain polyunsaturated fatty acids (n-3 group) or vegetable-oil capsules that contained trace n-3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed., Results: A total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n-3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P = 0.50). There were no significant differences between the groups in the incidence of interventions in post-term (>41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n-3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n-3 group than in the control group., Conclusions: Supplementation with n-3 long-chain polyunsaturated fatty acids from early pregnancy (<20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control. (Funded by the Australian National Health and Medical Research Council and the Thyne Reid Foundation; ORIP Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729.)., (Copyright © 2019 Massachusetts Medical Society.)

Monozygotic (MZ) and dizygotic (DZ) twins participate in research that partitions variance in health, disease, and behavior into genetic and environmental components. However, there are other innovative roles for twins in medical research. One such way is involving MZ and/or DZ twins in co-twin control-designed randomized controlled trials (RCTs). To our knowledge, no reviews have been conducted that summarizes the involvement of twins in RCTs. Therefore, we conducted a systematic literature search using the U.S. Clinical Trials Database, NHS electronic databases, MEDLINE, EMBASE, and PsychINFO for RCTs on publications involving MZ and/or DZ twins as RCT participants. Out of the 186,027 clinical trials registered in the U.S. clinical trial register ClinicaTrails.gov, only six RCTs used twins as participants. From 1,598 articles identified in our search, 50 peer-reviewed English language publications met our pre-defined inclusion criteria. Sample sizes for RCTs have ranged from a total number of participants from 2 to 1,162; however, 32 (64%) studies had a sample size of 100 or less, and of those, 12 (24%) had fewer than 10. Both MZ and DZ twins have been recruited to the RCTs. In most instances (33/50) each twin from a pair were assigned to different study arms. Most of those studies included MZ twins only. Despite the methodological advantages, the use of MZ and DZ twins as participants in interventional RCTs appeared limited. The continuous development of innovative twin designs, especially RCTs, indicates that twin research can extend beyond the more widely recognized heritability estimates.

Introduction: Preterm birth accounts for more than 85% of all perinatal complications and deaths. Seventy-five per cent of early preterm births (EPTBs) occur spontaneously and without identifiable risk factors. The need for a broadly applicable, effective strategy for primary prevention is paramount. Secondary outcomes from the docosahexaenoic acid (DHA) to Optimise Mother Infant Outcome trial showed that maternal supplementation until delivery with omega-3 (ω-3) long chain polyunsaturated fatty acid (LCPUFA), predominantly as DHA, resulted in a 50% reduction in the incidence of EPTB and an increase in the incidence of post-term induction or post-term prelabour caesarean section due to extended gestation. We aim to determine the effectiveness of supplementing the maternal diet with ω-3 LCPUFA until 34 weeks' gestation on the incidence of EPTB., Methods and Analysis: This is a multicentre, parallel group, randomised, blinded and controlled trial. Women less than 20 weeks' gestation with a singleton or multiple pregnancy and able to give informed consent are eligible to participate. Women will be randomised to receive high DHA fish oil capsules or control capsules without DHA. Capsules will be taken from enrolment until 34 weeks' gestation. The primary outcome is the incidence of EPTB, defined as delivery before 34 completed weeks' gestation. Key secondary outcomes include length of gestation, incidence of post-term induction or prelabour caesarean section and spontaneous EPTB. The target sample size is 5540 women (2770 per group), which will provide 85% power to detect an absolute reduction in the incidence of preterm birth of 1.16% (from 2.45% to 1.29%) between the DHA and control group (two sided α=0.05). The primary analysis will be based on the intention-to-treat principle., Trial Registration Number: Australia and New Zealand Clinical Trial Registry Number: 2613001142729; Pre-results., Competing Interests: Competing interests: The authors declare: financial support for the submitted work from the National Health and Medical Research Council (NHMRC) Australia (Project Grant 1050468). RG serves on a scientific advisory board for Fonterra; MM serves on scientific advisory boards for Nestle and Fonterra. Associated Honoraria for RG and MM are paid to their institutions to support conference travel and continuing education for postgraduate students and early career researchers. The authors declare that they have no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The DHA to Optimize Mother Infant Outcome (DOMInO) and Kansas DHA Outcomes Study (KUDOS) were randomized controlled trials that supplemented mothers with 800 and 600mg DHA/day, respectively, or a placebo during pregnancy. DOMInO was conducted in Australia and KUDOS in the United States. Both trials found an unanticipated and statistically significant reduction in early preterm birth (ePTB; i.e., birth before 34 weeks gestation). However, in each trial, the number of ePTBs were small. We used a novel Bayesian approach to estimate statistically derived low, moderate or high risk for ePTB, and to test for differences between the DHA and placebo groups. In both trials, the model predicted DHA would significantly reduce the expected proportion of deliveries in the high risk group under the trial conditions of the parent studies. Among the next 300,000 births in Australia we estimated that 1112 ePTB (95% credible interval 51-2189) could be avoided by providing DHA. And in the USA we estimated that 106,030 ePTB (95% credible interval 6400 to 175,700) could be avoided with DHA., Competing Interests: The other authors declare no conflicts of interest. All authors read and approved the final manuscript., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We explored the degree to which maternal and offspring outcomes resulting from consuming prenatal docosahexaenoic acid (DHA, 800mg/day) in a clinical trial were influenced by maternal characteristics. Among non-smokers, women who received DHA had heavier babies (adjusted mean difference (MD)=99g 95% CI 45-153, p<0.01; interaction p=0.01) and fewer low birth weight babies than control women (adjusted relative risk=0.43 95% CI 0.25-0.74, p<0.01; interaction p=0.01). From women who had not completed further education, children in the DHA group had higher cognitive scores at 18 months compared with control children (adjusted MD=3.15 95% CI 0.93-5.37, p=0.01; interaction p<0.01). Conversely, the children of women who completed further education in the DHA group had lower language scores than control children (adjusted MD -2.82 95% CI -4.90 to -0.73, p=0.01; interaction p=0.04). Our results support the notion that responsiveness to prenatal DHA may depend on the characteristics of specific population subgroups., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effect of providing antenatal dietary and lifestyle advice on neonatal anthropometry, and to determine the inter-observer variability in obtaining anthropometric measurements., Design: Randomised controlled trial., Setting: Public maternity hospitals across metropolitan Adelaide, South Australia., Population: Pregnant women with a singleton gestation between 10(+0) and 20(+0) weeks, and body mass index (BMI) ≥25 kg/m(2)., Methods: Women were randomised to either Lifestyle Advice (comprehensive dietary and lifestyle intervention over the course of pregnancy including dietary, exercise and behavioural strategies, delivered by a research dietician and research assistants) or continued Standard Care. Analyses were conducted using intention-to-treat principles., Main Outcome Measures: Secondary outcome measures for the trial included assessment of infant body composition using body circumference and skinfold thickness measurements (SFTM), percentage body fat, and bio-impedance analysis of fat-free mass., Results: Anthropometric measurements were obtained from 970 neonates (488 Lifestyle Advice Group, and 482 Standard Care Group). In 394 of these neonates (215 Lifestyle Advice Group, and 179 Standard Care Group) bio-impedance analysis was also obtained. There were no statistically significant differences identified between those neonates born to women receiving Lifestyle Advice and those receiving Standard Care, in terms of body circumference measures, SFTM, percentage body fat, fat mass, or fat-free mass. The intra-class correlation coefficient for SFTM was moderate to excellent (0.55-0.88)., Conclusions: Among neonates born to women who are overweight or obese, anthropometric measures of body composition were not modified by an antenatal dietary and lifestyle intervention., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objective: To report the influence of maternal overweight and obesity on fetal growth and adiposity and effects of an antenatal dietary and lifestyle intervention among these women on measures of fetal growth and adiposity as secondary outcomes of the LIMIT Trial., Design: Randomised controlled trial., Setting: Public maternity hospitals in metropolitan Adelaide, South Australia., Population: Pregnant women with a body mass index ≥ 25 kg/m(2), and singleton gestation between 10(+0) and 20(+0) weeks., Methods: Women were randomised to Lifestyle Advice or continued Standard Care and offered two research ultrasound scans at 28 and 36 weeks of gestation., Main Outcome Measures: Ultrasound measures of fetal growth and adiposity., Results: For each fetal body composition parameter, mean Z-scores were substantially higher when compared with population standards. Fetuses of women receiving Lifestyle Advice demonstrated significantly greater mean mid-thigh fat mass, when compared with fetuses of women receiving Standard Care (adjusted difference in means 0.17; 95% CI 0.02-0.32; P = 0.0245). While subscapular fat mass increased between 28 and 36 weeks of gestation in fetuses in both treatment groups, the rate of adipose tissue deposition slowed among fetuses of women receiving Lifestyle Advice, when compared with fetuses of women receiving Standard Care (P = 0.0160). No other significant differences were observed., Conclusions: These findings provide the first evidence of changes to fetal growth following an antenatal dietary and lifestyle intervention among women who are overweight or obese., (© 2015 Royal College of Obstetricians and Gynaecologists.)

This paper aimed to identify the dietary and non-dietary determinants of docosahexaenoic acid (DHA) levels in umbilical cord blood at delivery. DHA was measured in cord blood plasma phospholipids of 1571 participants from the DOMInO (DHA to Optimize Mother Infant Outcome) randomized controlled trial. Socioeconomic, lifestyle and clinical data relating to the mother and current pregnancy were obtained from all women and their relationships with cord blood DHA assessed. DHA concentrations in the cord plasma phospholipids at delivery covered a 3-4 fold range in both control and DHA groups. The total number of DHA-rich intervention supplement capsules consumed over the course of pregnancy and gestational age at delivery individually explained 21% and 16% respectively of the variation in DHA abundance in the cord blood plasma phospholipids at delivery, but no other clinical or life-style factors explored in this study could account for >2% of the variation. Indeed, more than 65% of the variation remained unaccounted for even when all factors were included in the analysis. These data suggest that factors other than maternal DHA intake have an important role in determining cord blood DHA concentrations at delivery, and may at least partially explain the variation in the response of infants to maternal DHA supplementation reported in published trials., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To evaluate a slower (compared with a standard) infusion rate of the loading dose of magnesium sulphate for preterm fetal neuroprotection as a strategy to reduce maternal adverse effects., Design: Randomised controlled trial., Setting: South Australian maternity hospital., Population: Fifty-one women at <30 weeks of gestation, where birth was planned or expected within 24 hours., Methods: Women received a loading infusion of 4 g of magnesium sulphate over either 60 or 20 minutes (followed by maintenance of 1 g/hour until birth, or for up to 24 hours)., Main Outcome Measures: Any maternal adverse effects associated with the infusion., Results: Overall, 71% of women experienced adverse effects during the first hour of their infusion; the difference between groups was not significant [15/25 (60%) 60-minute loading; 21/26 (81%) 20-minute loading; risk ratio (RR) 0.74; 95% confidence interval (95% CI) 0.51-1.08]. Although no serious maternal complications occurred, adverse effects led to three women ceasing the loading treatment (1/25 in the 60-minute loading group; 2/26 in the 20-minute loading group; RR 0.52; 95% CI 0.05-5.38). Women in the 60-minute loading group experienced significantly less warmth and flushing at 20 minutes into the infusion (7/25 in the 60-minute loading group; 15/26 in the 20-minute loading group; RR 0.49; 95% CI 0.24-0.99). No other differences between groups for maternally reported and clinical adverse effects were shown., Conclusions: A slower rate of administering the loading dose of magnesium sulphate did not reduce the occurrence of maternal adverse effects overall. Flushing and warmth at 20 minutes into the infusion was reduced with a slower infusion., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Background: It is estimated that between 34% and 50% of Australian women entering pregnancy are overweight and obese, which is associated with an increased risk in complications for both the woman and her infant. Current tools used in clinical and research practice for measuring body composition include body mass index (BMI), waist circumference and bioimpedance analysis. Not all of these measures are applicable for use during pregnancy due to a lack of differentiation between maternal and fetal contributions. While skinfold thickness measurement (SFTM) is increasingly being used in pregnancy, there is limited data and a lack of a standard tool for its use in overweight and obese pregnant women., Methods: We developed a standard tool for evaluating SFTM among women with a BMI≥25 kg/m2. Forty-nine women were measured as part of a prospective cohort study nested within a multicentre randomised controlled trial (The LIMIT Randomised Controlled Trial). Two blinded observers each performed 2 skinfold measurements on the biceps, triceps and subscapular of each woman. Intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were used to analyse SFTM, body fat percentage (BF%) and inter-observer variability., Results: The ICC for inter-observer variability in measurements were considered moderate for biceps SFTM (ICC=0.56) and triceps SFTM (ICC=0.51); good for subscapular SFTM (ICC=0.71) and BF% (ICC=0.74); and excellent for arm circumference (ICC=0.97). The standard error of measurements ranged from 0.53 cm for arm circumference to 3.58 mm for the subscapular SFTM., Conclusion: Our findings indicate that arm circumference and biceps, triceps and subscapular SFTM can be reliably obtained from overweight and obese pregnant women to calculate BF%, using multiple observers, and can be used in a research setting., Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12607000161426.

The aim of this study was to assess relationships between the fatty acid contents of plasma and erythrocyte phospholipids and those in liver, heart, brain, kidney and quadriceps muscle in rats. To obtain a wide range of tissue omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFA) we subjected weanling rats to dietary treatment with the n-3 LCPUFA precursor, alpha linolenic acid (ALA, 18:3 n-3) for 3 weeks. With the exception of the brain, we found strong and consistent correlations between the total n-3 LCPUFA fatty acid content of both plasma and erythrocyte phospholipids with fatty acid levels in all tissues. The relationships between eicosapentaenoic acid (EPA, 20:5 n-3) and docosapentaenoic acid (DPA, 22:5 n-3) content in both blood fractions with levels in liver, kidney, heart and quadriceps muscle phospholipids were stronger than those for docosahexaenoic acid (DHA, 22:6 n-3). The strong correlations between the EPA+DHA (the Omega-3 Index), total n-3 LCPUFA and total n-3 PUFA contents in both plasma and erythrocyte phospholipids and tissues investigated in this study suggest that, under a wide range of n-3 LCPUFA values, plasma and erythrocyte n-3 fatty acid content reflect not only dietary PUFA intakes but also accumulation of endogenously synthesised n-3 LCPUFA, and thus can be used as a reliable surrogate for assessing n-3 status in key peripheral tissues., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: There is uncertainty regarding the efficacy of increasing n-3 long-chain PUFA (LCPUFA) intake during pregnancy in reducing the risk of gestational diabetes mellitus (GDM) and preeclampsia., Objectives: The objective was to determine whether n-3 LCPUFA supplementation in pregnancy reduces the incidence of GDM or preeclampsia. A secondary objective was to assess the effect of n-3 LCPUFA supplementation on perinatal complications., Design: This was a double-blind, multicenter randomized control trial-the DHA to Optimize Mother Infant Outcome (DOMInO) trial. Pregnant women (n = 2399) of <21 wk gestation were randomly assigned to receive DHA-enriched fish oil (800 mg/d) or vegetable oil capsules without DHA from trial entry to birth. The presence of GDM or preeclampsia was assessed through a blinded audit of medical records. Birth outcomes and prenatal complications were also assessed., Results: The overall incidences of GDM and preeclampsia were 8% and 5%, respectively, based on clinical diagnosis. The RR of GDM was 0.97 (95% CI: 0.74, 1.27) and of preeclampsia was 0.87 (95% CI: 0.60, 1.25), and they did not differ significantly between the groups. Birth weight, length, and head circumference z scores also did not differ between the groups. There were 12 perinatal deaths and 5 neonatal convulsions in the control group compared with 3 perinatal deaths and no neonatal convulsions in the DHA group (P = 0.03 in both cases)., Conclusion: DHA supplementation of 800 mg/d in the second half of pregnancy does not reduce the risk of GDM or preeclampsia. Whether supplementation reduces the risk of perinatal death and neonatal convulsions requires further investigation. The DOMInO trial was registered with the Australian New Zealand Clinical Trials Registry as TRN12605000569606.

Background: The aim of this individual participant data (IPD) meta-analysis is to assess whether the effects of repeat prenatal corticosteroid treatment given to women at risk of preterm birth to benefit their babies are modified in a clinically meaningful way by factors related to the women or the trial protocol., Methods/design: The Prenatal Repeat Corticosteroid International IPD Study Group: assessing the effects using the best level of Evidence (PRECISE) Group will conduct an IPD meta-analysis. The PRECISE International Collaborative Group was formed in 2010 and data collection commenced in 2011. Eleven trials with up to 5,000 women and 6,000 infants are eligible for the PRECISE IPD meta-analysis. The primary study outcomes for the infants will be serious neonatal outcome (defined by the PRECISE International IPD Study Group as one of death (foetal, neonatal or infant); severe respiratory disease; severe intraventricular haemorrhage (grade 3 and 4); chronic lung disease; necrotising enterocolitis; serious retinopathy of prematurity; and cystic periventricular leukomalacia); use of respiratory support (defined as mechanical ventilation or continuous positive airways pressure or other respiratory support); and birth weight (Z-scores). For the children, the primary study outcomes will be death or any neurological disability (however defined by trialists at childhood follow up and may include developmental delay or intellectual impairment (developmental quotient or intelligence quotient more than one standard deviation below the mean), cerebral palsy (abnormality of tone with motor dysfunction), blindness (for example, corrected visual acuity worse than 6/60 in the better eye) or deafness (for example, hearing loss requiring amplification or worse)). For the women, the primary outcome will be maternal sepsis (defined as chorioamnionitis; pyrexia after trial entry requiring the use of antibiotics; puerperal sepsis; intrapartum fever requiring the use of antibiotics; or postnatal pyrexia)., Discussion: Data analyses are expected to commence in 2011 with results publicly available in 2012.

Context: Uncertainty about the benefits of dietary docosahexaenoic acid (DHA) for pregnant women and their children exists, despite international recommendations that pregnant women increase their DHA intakes., Objective: To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children., Design, Setting, and Participants: A double-blind, multicenter, randomized controlled trial (DHA to Optimize Mother Infant Outcome [DOMInO] trial) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks' gestation with singleton pregnancies and who were recruited between October 31, 2005, and January 11, 2008. Follow-up of children (n = 726) was completed December 16, 2009., Intervention: Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth., Main Outcome Measures: High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum. Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition, at 18 months., Results: Of 2399 women enrolled, 96.7% completed the trial. The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19%; adjusted relative risk, 0.85; 95% confidence interval [CI], 0.70-1.02; P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01; 95% CI, -1.36 to 1.37; P = .99) and mean language composite scores (adjusted mean difference, -1.42; 95% CI, -3.07 to 0.22; P = .09) of children in the DHA group did not differ from children in the control group., Conclusion: The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood., Trial Registration: anzctr.org.au Identifier: ACTRN12605000569606.

Objective: To investigate whether responses to a previously validated four-item medication adherence questionnaire were associated with adverse cardiovascular events., Design: Survey conducted among a cohort of participants in the Second Australian National Blood Pressure Study., Setting: Australian general practice., Participants: 4039 older people with hypertension., Main Outcome Measures: All major cardiovascular events or death; first specific cardiovascular event., Results: Subjects who adhered to their medication regimen (compared with non-adherent subjects) were significantly less likely to experience a first cardiovascular event or a first non-fatal cardiovascular event (hazard ratio [HR] for both, 0.81; 95% CI, 0.67-0.98; P = 0.03); a fatal other cardiovascular event (HR, 0.68; 95% CI, 0.48-0.99; P = 0.04); or a first occurrence of heart failure (HR, 0.58; 95% CI, 0.37-0.90; P = 0.02). Those who answered yes to "Did you ever forget to take your medication?" were significantly more likely to experience a cardiovascular event or death (HR, 1.28; 95% CI, 1.04-1.57; P = 0.02); a first cardiovascular event or death (HR, 1.31; 95% CI, 1.07-1.60; P = 0.01); a first cardiovascular event (HR, 1.34; 95% CI, 1.09-1.65; P = 0.01); or a first non-fatal cardiovascular event (HR, 1.35; 95% CI, 1.09-1.66; P = 0.01). Those who answered yes to "Sometimes, if you felt worse when you took your medicine, did you stop taking it?" were significantly more likely to experience a first occurrence of heart failure (HR, 2.06; 95% CI, 1.16-3.64; P = 0.01)., Conclusions: Subjects who adhered to their medication regimen were less likely to experience major cardiovascular events or death. The question relating to forgetting to take medication identified non-adherent subjects likely to experience a cardiovascular event or death. Clinicians could use this question to identify patients with hypertension who are likely to benefit from medication adherence strategies.

Background: Recent single photon emission computed tomography (SPECT) studies have reported age related increases in regional brain perfusion (called preservation here) as well as losses., Aim: To apply optimized SPECT processing to better define and understand both age related preservation and loss in brain SPECT., Methods: Brain SPECT was performed on 85 healthy subjects using Tc hexamethylpropylene amine oxime (HMPAO), processed using findings from recent optimization work, and subjected to voxel based statistical analysis., Results: SPECT preservation was seen in white matter. This distribution differs from other SPECT reports, but is similar to that for preservation observed with structural magnetic resonance imaging (MRI). This suggests that SPECT preservation may arise from age related changes in brain anatomy, not regional cerebral blood flow (rCBF), and we demonstrate that it can arise from the partial-volume effect in areas where white matter contracts with age. Age related losses extended over the whole pre-frontal midline area and an extended pattern of focal losses was seen in the peripheral cortex that was consistent with major sulci. There were also focal losses in the cerebellum. The most significant SPECT loss was in the anterior cingulate, although no structural changes were observed there in the MRI study. A model of sulcal widening at the junction of the inter-hemispheric fissure and cingulate sulcus, when degraded by the partial-volume effect, could explain this anterior cingulate loss., Conclusion: Optimized processing has revealed spatial patterns for age related preservation and losses in brain SPECT that indicate their origin is primarily structural. Correction for structural effects in optimized SPECT is needed to confirm whether any regional ageing effects derive from changes in rCBF.