Effects of an antenatal dietary intervention in overweight and obese women on 6 month infant outcomes: follow-up from the LIMIT randomised trial.

BACKGROUND: The immediate impact of providing an antenatal dietary intervention during pregnancy has been extensively studied, but little is known of the effects beyond the neonatal period. Our objective was to evaluate the effect of an antenatal dietary intervention in overweight or obese women on infant outcomes 6 months after birth. METHODS: We conducted a follow up study of infants born to women who participated in the LIMIT trial during pregnancy. Live-born infants at 6-months of age, and whose mother provided consent to ongoing follow-up were eligible. The primary follow-up study endpoint was the incidence of infant BMI z-score ≥90th centile for infant sex and age. Secondary study outcomes included a range of infant anthropometric measures, neurodevelopment, general health, and infant feeding. Analyses used intention to treat principles according to the treatment group allocated in pregnancy. Missing data were imputed and analyses adjusted for maternal early pregnancy BMI, parity, study centre, socioeconomic status, age, and smoking status. Outcome assessors were blinded to the allocated treatment group. RESULTS: A total of 1754 infants were assessed at age 6 months (Lifestyle Advice n = 869; Standard Care n = 885), representing 82.1% of the eligible sample (n = 2136). There were no statistically significant differences in the incidence of infant BMI z-score ≥90th centile for infants born to women in the Lifestyle Advice group, compared with the Standard Care group (Lifestyle Advice 233 (21.71%) vs. Standard Care 233 (21.90%); adjusted relative risk (aRR) 0.99; 95% confidence interval 0.82 to 1.18; p = 0.88). There were no other effects on infant growth, adiposity, or neurodevelopment. CONCLUSION: Providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention did not alter 6-month infant growth and adiposity. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS Study): A multicentre, randomised, placebo-controlled trial.

BACKGROUND: Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity. The withdrawal of progesterone, either actual or functional, is thought to be an antecedent to the onset of labour. There remains limited information on clinically relevant health outcomes as to whether vaginal progesterone may be of benefit for pregnant women with a history of a previous preterm birth, who are at high risk of a recurrence. Our primary aim was to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth reduced the risk and severity of respiratory distress syndrome in their infants, with secondary aims of examining the effects on other neonatal morbidities and maternal health and assessing the adverse effects of treatment. METHODS: Women with a live singleton or twin pregnancy between 18 to <24 weeks' gestation and a history of prior preterm birth at less than 37 weeks' gestation in the preceding pregnancy, where labour occurred spontaneously or in association with cervical incompetence or following preterm prelabour rupture of the membranes, were eligible. Women were recruited from 39 Australian, New Zealand, and Canadian maternity hospitals and assigned by randomisation to vaginal progesterone pessaries (equivalent to 100 mg vaginal progesterone) (n = 398) or placebo (n = 389). Participants and investigators were masked to the treatment allocation. The primary outcome was respiratory distress syndrome and severity. Secondary outcomes were other respiratory morbidities; other adverse neonatal outcomes; adverse outcomes for the woman, especially related to preterm birth; and side effects of progesterone treatment. Data were analysed for all the 787 women (100%) randomised and their 799 infants. FINDINGS: Most women used their allocated study treatment (740 women, 94.0%), with median use similar for both study groups (51.0 days, interquartile range [IQR] 28.0-69.0, in the progesterone group versus 52.0 days, IQR 27.0-76.0, in the placebo group). The incidence of respiratory distress syndrome was similar in both study groups-10.5% (42/402) in the progesterone group and 10.6% (41/388) in the placebo group (adjusted relative risk [RR] 0.98, 95% confidence interval [CI] 0.64-1.49, p = 0.912)-as was the severity of any neonatal respiratory disease (adjusted treatment effect 1.02, 95% CI 0.69-1.53, p = 0.905). No differences were seen between study groups for other respiratory morbidities and adverse infant outcomes, including serious infant composite outcome (155/406 [38.2%] in the progesterone group and 152/393 [38.7%] in the placebo group, adjusted RR 0.98, 95% CI 0.82-1.17, p = 0.798). The proportion of infants born before 37 weeks' gestation was similar in both study groups (148/406 [36.5%] in the progesterone group and 146/393 [37.2%] in the placebo group, adjusted RR 0.97, 95% CI 0.81-1.17, p = 0.765). A similar proportion of women in both study groups had maternal morbidities, especially those related to preterm birth, or experienced side effects of treatment. In 9.9% (39/394) of the women in the progesterone group and 7.3% (28/382) of the women in the placebo group, treatment was stopped because of side effects (adjusted RR 1.35, 95% CI 0.85-2.15, p = 0.204). The main limitation of the study was that almost 9% of the women did not start the medication or forgot to use it 3 or more times a week. CONCLUSIONS: Our results do not support the use of vaginal progesterone pessaries in women with a history of a previous spontaneous preterm birth to reduce the risk of neonatal respiratory distress syndrome or other neonatal and maternal morbidities related to preterm birth. Individual participant data meta-analysis of the relevant trials may identify specific women for whom vaginal progesterone might be of benefit. TRIAL REGISTRATION: Current Clinical Trials ISRCTN20269066.

The effect of an antenatal lifestyle intervention in overweight and obese women on circulating cardiometabolic and inflammatory biomarkers: secondary analyses from the LIMIT randomised trial.

BACKGROUND: Maternal overweight and obesity during pregnancy is associated with insulin resistance, hyperglycaemia, hyperlipidaemia and a low-grade state of chronic inflammation. The aim of this pre-specified analysis of secondary outcome measures was to evaluate the effect of providing antenatal dietary and lifestyle advice on cardiometabolic and inflammatory biomarkers. METHODS: We conducted a multicentre trial in which pregnant women who were overweight or obese were randomised to receive either Lifestyle Advice or Standard Care. We report a range of pre-specified secondary maternal and newborn cardiometabolic and inflammatory biomarker outcomes. Maternal whole venous blood was collected at trial entry (mean 14 weeks gestation; non-fasting), at 28 weeks gestation (fasting), and at 36 weeks gestation (non-fasting). Cord blood was collected after birth and prior to the delivery of the placenta. A range of cardiometabolic and inflammatory markers were analysed (total cholesterol, triglycerides, non-esterified fatty acids, high-density lipoprotein cholesterol, insulin, glucose, leptin, adiponectin, C-reactive protein, granulocyte macrophage-colony stimulating factor, interferon gamma, TNF-α, and interleukins 1ß, 2, 4, 5, 6, 8, and 10). Participants were analysed in the groups to which they were randomised, and were included in the analyses if they had a measure at any time point. RESULTS: One or more biological specimens were available from 1951 women (989 Lifestyle Advice and 962 Standard Care), with cord blood from 1174 infants (596 Lifestyle Advice and 578 Standard Care). There were no statistically significant differences in mean cardiometabolic and inflammatory marker concentrations across pregnancy and in infant cord blood between treatment groups. Estimated treatment group differences were close to zero, with 95% confidence intervals spanning a range of differences that were short of clinical relevance. There was no evidence to suggest that the intervention effect was modified by maternal BMI category. CONCLUSIONS: Despite our findings, it will be worth considering potential relationships between cardiometabolic and inflammatory markers and clinical outcomes, including longer-term infant health and adiposity. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ; Date Registered 09/03/2007).

The effect of antenatal dietary and lifestyle advice for women who are overweight or obese on emotional well-being: the LIMIT randomized trial.

INTRODUCTION: Our aim was to evaluate the effect of dietary and lifestyle advice given to women who were overweight or obese during pregnancy on maternal quality of life, anxiety and risk of depression, and satisfaction with care. MATERIAL AND METHODS: We conducted a randomized trial, involving pregnant women with body mass index ≥25 kg/m(2) , recruited from maternity units in South Australia. Women were randomized to Lifestyle Advice or Standard Care, and completed questionnaires assessing risk of depression (Edinburgh Postnatal Depression Scale), anxiety (Spielberger State-Trait Anxiety Inventory), and quality of life (SF-36) at trial entry, 28 and 36 weeks' gestation, and 4 months postpartum. Secondary trial outcomes assessed for this analysis were risk of depression, anxiety, maternal quality of life, and satisfaction with care. RESULTS: One or more questionnaires were completed by 976 of 1108 (90.8%) women receiving Lifestyle Advice and 957 of 1104 (89.7%) women receiving Standard Care. The risk of depression [adjusted risk ratio 1.01; 95% confidence interval (CI) 0.82-1.24; p = 0.95], anxiety (adjusted risk ratio 1.09; 95% CI 0.93-1.27; p = 0.31), and health-related quality of life were similar between the two groups. Women receiving Lifestyle Advice reported improved healthy food choice [Lifestyle Advice 404 (68.9%) vs. Standard Care 323 (51.8%); p < 0.0001], and exercise knowledge [Lifestyle Advice 444 (75.8%) vs. Standard Care 367 (58.8%); p < 0.0001], and reassurance about their health [Lifestyle Advice 499 (85.3%) vs. Standard Care 485 (77.9%); p = 0.0112], and health of their baby [Lifestyle Advice 527 (90.2%) vs. Standard Care 545 (87.6%); p = 0.0143]. CONCLUSION: Lifestyle advice in pregnancy improved knowledge and provided reassurance without negatively impacting well-being.

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial.

BACKGROUND: Overweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity. METHODS: We conducted a randomised controlled trial, in which pregnant women with a body mass index≥25 kg/m2, and singleton gestation between 10(+0) to 20(+0) weeks were recruited and randomised to Lifestyle Advice (involving a comprehensive dietary and lifestyle intervention over their pregnancy) or Standard Care. Within the intervention group, we conducted a nested randomised trial in which a subgroup of women were further randomised to receive access to supervised group walking sessions in addition to the standard information presented during the intervention contacts (the Walking group) or standard information only. The outcome measures were maternal dietary intake, (including food groups, macronutrient and micronutrient intake, diet quality (using the Healthy Eating Index; HEI), dietary glycaemic load, and glycaemic index) and maternal physical activity. Women completed the Harvard Semi-Structured Food Frequency Questionnaire, and the Short Questionnaire to Assess Health-enhancing Physical Activity (SQUASH), at trial entry, 28 and 36 weeks' gestational age, and 4 months postpartum. Analyses were performed on an intention-to-treat basis, using linear mixed effects models with adjustment for the stratification variables. RESULTS: Women randomised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day, as well as increased consumption of fibre, and reduced percentage energy intake from saturated fats (P<0.05 for all). Maternal HEI was significantly improved at both 28 (73.35±6.62 versus 71.86±7.01; adjusted difference in means 1.58; 95% CI 0.89 to 2.27; P<0.0001) and 36 (72.95±6.82 versus 71.17±7.69; adjusted difference in means 1.77; 95% CI 1.01 to 2.53; P<0.0001) weeks. There were no differences in dietary glycaemic index or glycaemic load. Women randomised to Lifestyle Advice also demonstrated greater total physical activity (adjusted difference in means 359.76 metabolic equivalent task units (MET) minutes/week; 95% CI 74.87 to 644.65; P=0.01) compared with women receiving Standard Care. The supervised walking group was poorly utilised. CONCLUSIONS: For women who are overweight or obese, antenatal lifestyle advice improves maternal diet and physical activity during pregnancy. Please see related articles: http://www.biomedcentral.com/1741-7015/12/163 and http://www.biomedcentral.com/1741-7015/12/201. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426).

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial.

BACKGROUND: Overweight and obesity during pregnancy represents a considerable health burden. While research has focused on interventions to limit gestational weight gain, there is little information describing their impact on neonatal health. Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese. METHODS: We report a range of pre-specified secondary neonatal outcomes from a large randomised trial in which antenatal dietary and lifestyle advice was provided to women who were overweight or obese. Pregnant women were eligible for participation with a body mass index of 25 kg/m(2) or over, and singleton gestation between 10(+0) and 20(+0) weeks. Outcome measures included gestational age at birth; Apgar score below 7 at 5 minutes of age; need for resuscitation at birth; birth weight above 4.5 kg or below 2.5 kg; birth weight, length and head circumference (and Z-scores); admission to the nursery; respiratory distress syndrome; and postnatal length of stay. Data relating to the primary outcome (large for gestational age infants defined as birth weight above the 90th centile) and birth weight above 4 kg have been reported previously. Analyses used intention-to-treat principles. RESULTS: In total, 2,142 infants were included in the analyses. Infants born to women following lifestyle advice were significantly less likely to have birth weight above 4.5 kg (2.15% versus 3.69%; adjusted risk ratio (aRR)=0.59; 95% confidence interval (CI) 0.36 to 0.98; P=0.04), or respiratory distress syndrome (1.22% versus 2.57%; aRR=0.47; 95% CI 0.24 to 0.90; P=0.02), particularly moderate or severe disease, and had a shorter length of postnatal hospital stay (3.94±7.26 days versus 4.41±9.87 days; adjusted ratio of means 0.89; 95% CI 0.82 to 0.97; P=0.006) compared with infants born to women who received Standard Care. CONCLUSIONS: For women who are overweight or obese, antenatal dietary and lifestyle advice has health benefits for infants, without an increase in the risk of harm. Continued follow-up into childhood will be important to assess the longer-term effects of a reduction in high infant birth weight on risk of child obesity. Please see related articles: http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/201 . CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ).

Australasian randomised trial to evaluate the role of maternal intramuscular dexamethasone versus betamethasone prior to preterm birth to increase survival free of childhood neurosensory disability (A*STEROID): study protocol.

BACKGROUND: Both dexamethasone and betamethasone, given to women at risk of preterm birth, substantially improve short-term neonatal health, increase the chance of the baby being discharged home alive, and reduce childhood neurosensory disability, remaining safe into adulthood. However, it is unclear which corticosteroid is of greater benefit to mother and child.This study aims to determine whether giving dexamethasone to women at risk of preterm birth at less than 34 weeks' gestation increases the chance of their children surviving free of neurosensory disability at two years' corrected age, compared with betamethasone. METHODS/DESIGN: Design randomised, multicentre, placebo controlled trial.Inclusion criteria women at risk of preterm birth at less than 34 weeks' gestation with a singleton or twin pregnancy and no contraindications to the use of antenatal corticosteroids and who give informed consent.Trial entry & randomisation at telephone randomisation eligible women will be randomly allocated to either the dexamethasone group or the betamethasone group, allocated a study number and corresponding treatment pack.Study groups women in the dexamethasone group will be administered two syringes of 12 mg dexamethasone (dexamethasone sodium phosphate) and women in the betamethasone group will be administered two syringes of 11.4 mg betamethasone (Celestone Chronodose). Both study groups consist of intramuscular treatments 24 hours apart.Primary study outcome death or any neurosensory disability measured in children at two years' corrected age.Sample size a sample size of 1449 children is required to detect either a decrease in death or any neurosensory disability from 27.0% to 20.1% with dexamethasone compared with betamethasone, or an increase from 27.0% to 34.5% (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). DISCUSSION: This study will provide high-level evidence of direct relevance for clinical practice. If one drug clearly results in significantly fewer deaths and fewer disabled children then it should be used consistently in women at risk of preterm birth and would be of great importance to women at risk of preterm birth, their children, health services and communities. TRIAL REGISTRATION NUMBER: ACTRN12608000631303.

Reduced corticomotor excitability and motor skills development in children born preterm.

The mechanisms underlying the altered neurodevelopment commonly experienced by children born preterm, but without brain lesions, remain unknown. While individuals born the earliest are at most risk, late preterm children also experience significant motor, cognitive and behavioural dysfunction from school age, and reduced income and educational attainment in adulthood. We used transcranial magnetic stimulation and functional assessments to examine corticomotor development in 151 children without cerebral palsy, aged 10-13 years and born after gestations of 25-41 completed weeks. We hypothesized that motor cortex and corticospinal development are altered in preterm children, which underpins at least some of their motor dysfunction. We report for the first time that every week of reduced gestation is associated with a reduction in corticomotor excitability that remains evident in late childhood. This reduced excitability was associated with poorer motor skill development, particularly manual dexterity. However, child adiposity, sex and socio-economic factors regarding the child's home environment soon after birth were also powerful influences on development of motor skills. Preterm birth was also associated with reduced left hemisphere lateralization, but without increasing the likelihood of being left handed per se. These corticomotor findings have implications for normal motor development, but also raise questions regarding possible longer term consequences of preterm birth on motor function.

Planned vaginal birth or elective repeat caesarean: patient preference restricted cohort with nested randomised trial.

BACKGROUND: Uncertainty exists about benefits and harms of a planned vaginal birth after caesarean (VBAC) compared with elective repeat caesarean (ERC). We conducted a prospective restricted cohort study consisting of a patient preference cohort study, and a small nested randomised trial to compare benefits and risks of a planned ERC with planned VBAC. METHODS AND FINDINGS: 2,345 women with one prior caesarean, eligible for VBAC at term, were recruited from 14 Australian maternity hospitals. Women were assigned by patient preference (n = 2,323) or randomisation (n = 22) to planned VBAC (1,225 patient preference, 12 randomised) or planned ERC (1,098 patient preference, ten randomised). The primary outcome was risk of fetal death or death of liveborn infant before discharge or serious infant outcome. Data were analysed for the 2,345 women (100%) and infants enrolled. The risk of fetal death or liveborn infant death prior to discharge or serious infant outcome was significantly lower for infants born in the planned ERC group compared with infants in the planned VBAC group (0.9% versus 2.4%; relative risk [RR] 0.39; 95% CI 0.19-0.80; number needed to treat to benefit 66; 95% CI 40-200). Fewer women in the planned ERC group compared with women in the planned VBAC had a major haemorrhage (blood loss ≥ 1,500 ml and/or blood transfusion), (0.8% [9/1,108] versus 2.3% [29/1,237]; RR 0.37; 95% CI 0.17-0.80). CONCLUSIONS: Among women with one prior caesarean, planned ERC compared with planned VBAC was associated with a lower risk of fetal and infant death or serious infant outcome. The risk of major maternal haemorrhage was reduced with no increase in maternal or perinatal complications to time of hospital discharge. Women, clinicians, and policy makers can use this information to develop health advice and make decisions about care for women who have had a previous caesarean. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53974531

The IDEAL study: investigation of dietary advice and lifestyle for women with borderline gestational diabetes: a randomised controlled trial - study protocol.

BACKGROUND: The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) showed that treatment of pregnant women with mild gestational diabetes mellitus is beneficial for both women and their infants. It is still uncertain whether there are benefits of similar treatment for women with borderline gestational diabetes.This trial aims to assess whether dietary and lifestyle advice and treatment given to pregnant women who screen for borderline gestational diabetes reduces neonatal complications and maternal morbidities. DESIGN: Multicentre, randomised controlled trial. INCLUSION CRITERIA: Women between 240 and 346 weeks gestation with a singleton pregnancy, a positive oral glucose challenge test (venous plasma glucose ≥7.8 mmol/L) and a normal oral 75 gram glucose tolerance test (fasting venous plasma glucose <5.5 mmol/L and a 2 hour glucose <7.8 mmol/L) with written, informed consent.Trial entry and randomisation: Women with an abnormal oral glucose tolerance test (fasting venous plasma glucose ≥5.5 mmol/L or 2 hour glucose ≥7.8 mmol/L) will not be eligible and will be offered treatment for gestational diabetes, consistent with recommendations based on results of the ACHOIS trial. Eligible women will be randomised into either the 'Routine Care Group' or the 'Intervention Group'.Study groups: Women in the 'Routine Care Group' will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the 'Intervention Group' will receive obstetric care, which will include dietary and lifestyle advice, monitoring of blood glucose and further medical treatment for hyperglycaemia as appropriate.Primary study outcome: Incidence of large for gestational age infants. SAMPLE SIZE: A sample size of 682 women will be sufficient to show a 50% reduction in the risk of large for gestational age infants (alpha 0.05 two-tailed, 80% power, 4% loss to follow up) from 14% to 7% with dietary and lifestyle advice and treatment. DISCUSSION: A conclusive trial outcome will provide reliable evidence of relevance for the care of women with borderline glucose intolerance in pregnancy and their infants. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry - ACTRN12607000174482.

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial.

BACKGROUND: Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes.The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes. DESIGN: Multicentred randomised, controlled trial. INCLUSION CRITERIA: Women with a singleton, live gestation between 10(+0)-20(+0) weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10(+0) and 20(+0) weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies. Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice. Outcome assessors will be blinded to the allocated treatment group. Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age). SAMPLE SIZE: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed). DISCUSSION: This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12607000161426.

Stressful life events, social health issues and low birthweight in an Australian population-based birth cohort: challenges and opportunities in antenatal care.

BACKGROUND: Investment in strategies to promote 'a healthy start to life' has been identified as having the greatest potential to reduce health inequalities across the life course. The aim of this study was to examine social determinants of low birthweight in an Australian population-based birth cohort and consider implications for health policy and health care systems. METHODS: Population-based survey distributed by hospitals and home birth practitioners to >8000 women six months after childbirth in two states of Australia. Participants were women who gave birth to a liveborn infant in Victoria and South Australia in September/October 2007. Main outcome measures included stressful life events and social health issues, perceived discrimination in health care settings, infant birthweight. RESULTS: 4,366/8468 (52%) of eligible women returned completed surveys. Two-thirds (2912/4352) reported one or more stressful life events or social health issues during pregnancy. Women reporting three or more social health issues (18%, 768/4352) were significantly more likely to have a low birthweight infant (< 2500 grams) after controlling for smoking and other socio-demographic covariates (Adj OR = 1.77, 95% CI 1.1-2.8). Mothers born overseas in non-English speaking countries also had a higher risk of having a low birthweight infant (Adj OR = 1.85, 95% CI 1.2-2.9). Women reporting three or more stressful life events/social health issues were more likely to attend antenatal care later in pregnancy (OR = 2.06, 95% CI 1.3-3.1), to have fewer antenatal visits (OR = 2.17, 95% CI 1.4-3.4) and to experience discrimination in health care settings (OR = 2.69, 95% CI 2.2-3.3). CONCLUSIONS: There is a window of opportunity in antenatal care to implement targeted preventive interventions addressing potentially modifiable risk factors for poor maternal and infant outcomes. Developing the evidence base and infrastructure necessary in order for antenatal services to respond effectively to the social circumstances of women's lives is long overdue.

Maternal and perinatal health outcomes by body mass index category.

AIMS: To determine the effect of increasing maternal body mass index (BMI) during pregnancy on maternal and infant health outcomes. METHODS: The South Australian Pregnancy Outcome Unit's population database, 2008 was accessed to determine pregnancy outcomes according to maternal BMI. Women with a normal BMI (18.5-24.9 kg/m(2) ) formed a reference population, to which women in other BMI categories were compared utilising risk ratios and 95% confidence intervals. RESULTS: Overweight and obese women had an increased risk of gestational diabetes, hypertension and iatrogenic preterm birth. Labour was more likely to be induced, and the risk of caesarean birth was increased. Infants were more likely to require resuscitation at birth and to have birth weight in excess of 4 kg. The risk increased with increasing maternal BMI. CONCLUSIONS: There is a well-documented increased risk of maternal and perinatal health complications for women who are overweight or obese during pregnancy.

Using conflict negativity to index psychological tension between impartiality and status-upholding principles.

People often endorse the moral principle that all human lives are equally valuable. At the same time, people often privilege high-status individuals over low-status individuals. These two inclinations come into conflict in a scenario involving the potential killing of a high-status person to save the lives of multiple low-status people. In the present study, participants viewed a series of sacrificial dilemmas in which the social status of the victims and beneficiaries was varied. We measured participants' choice (sacrifice vs. don't sacrifice), response time, and electroencephalographic activity, with an emphasis on conflict negativity (CN). Overall, we found no effects of victim/beneficiaries status on choice and response time. However, participants displayed a more pronounced CN effect when contemplating a high-status victim/low-status beneficiaries tradeoff than a low-status-victim/high-status beneficiaries tradeoff. Further analyses revealed that this effect was primarily driven by participants who endorsed deontological principles (e.g., "Some rules must never be broken, no matter the consequences"). In contrast, those who endorsed utilitarian principles displayed equivalent levels of conflict negativity, regardless of the social status of victims and beneficiaries. These findings shed light on the role of conflict in the phenomenology of moral decision making.

Outcomes at 2 years of age after repeat doses of antenatal corticosteroids.

BACKGROUND: We previously reported the results of a randomized, controlled trial showing that repeat doses of antenatal corticosteroids reduced the risk of respiratory distress syndrome and serious neonatal morbidity. However, data have not been available regarding longer-term effects of this treatment. METHODS: Women who had received an initial course of corticosteroid treatment 7 or more days previously were randomly assigned to receive an intramuscular injection of corticosteroid (11.4 mg of betamethasone) or saline placebo; the dose was repeated weekly if the mother was still considered to be at risk for preterm delivery and the duration of gestation was less than 32 weeks. We assessed survival free of major neurosensory disability and body size of the children at 2 years of corrected age. RESULTS: Of the 1085 children who were alive at 2 years of age, 1047 (96.5%) were seen for assessment (521 exposed to repeat-corticosteroid treatment and 526 exposed to placebo). The rate of survival free of major disability was similar in the repeat-corticosteroid and placebo groups (84.4% and 81.0%, respectively; adjusted relative risk, 1.04, 95% confidence interval, 0.98 to 1.10; adjusted P=0.20). There were no significant differences between the groups in body size, blood pressure, use of health services, respiratory morbidity, or child behavior scores, although children exposed to repeat doses of corticosteroids were more likely than those exposed to placebo to warrant assessment for attention problems (P=0.04). CONCLUSIONS: Administration of repeat doses of antenatal corticosteroids reduces neonatal morbidity without changing either survival free of major neurosensory disability or body size at 2 years of age. (Current Controlled Trials number, ISRCTN48656428 [controlled-trials.com].).

Placental restriction increases adipose leptin gene expression and plasma leptin and alters their relationship to feeding activity in the young lamb.

Low birth weight and catch-up growth predict increased adiposity in children and adults. This may be due in part to leptin resistance, as adults who were born small exhibit increased plasma leptin concentration relative to adiposity. Placental restriction (PR), a major cause of intrauterine growth restriction, reduces size at birth and increases feeding activity and adiposity by 6 wk in sheep. We hypothesized that PR would increase plasma leptin concentration and alter its relationship with feeding activity and adiposity in young lambs. Body size, plasma leptin, feeding activity, adiposity, leptin, and leptin receptor gene expression in adipose tissue were measured (12 control, 12 PR). PR reduced size at birth and increased adiposity. Plasma leptin concentration decreased with age, but to a lesser extent after PR and correlated positively with adiposity similarly in control and PR. PR increased plasma leptin concentration and perirenal adipose tissue leptin expression. Feeding activity correlated negatively with plasma leptin concentration in controls, but positively after PR. PR increases adipose tissue leptin expression and plasma leptin concentration, however, this increased abundance of peripheral leptin does not inhibit feeding activity (suckling event frequency), suggesting PR programs resistance to appetite and energy balance regulation by leptin, leading to early onset obesity.

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial.

BACKGROUND: There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time. The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications. DESIGN: Multicentred randomised trial. INCLUSION CRITERIA: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy. Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care. Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible). Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity. SAMPLE SIZE: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power). DISCUSSION: This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.

Vitamins C and E and the risks of preeclampsia and perinatal complications.

BACKGROUND: Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain. METHODS: We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age. RESULTS: Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16). CONCLUSIONS: Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).

Progesterone after previous preterm birth for prevention of neonatal respiratory distress syndrome (PROGRESS): a randomised controlled trial.

BACKGROUND: Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity during infancy and childhood. Survivors of preterm birth continue to remain at considerable risk of both chronic lung disease and long-term neurological handicap. Progesterone is involved in the maintenance of uterine quiescence through modulation of the calcium-calmodulin-myosin-light-chain-kinase system in smooth muscle cells. The withdrawal of progesterone, either actual or functional is thought to be an antecedent to the onset of labour. While there have been recent reports of progesterone supplementation for women at risk of preterm birth which show promise in this intervention, there is currently insufficient data on clinically important outcomes for both women and infants to enable informed clinical decision-making. The aims of this randomised, double blind, placebo controlled trial are to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth will reduce the risk and severity of respiratory distress syndrome, so improving their infant's health, without increasing maternal risks. DESIGN: Multicentered randomised, double blind, placebo-controlled trial. INCLUSION CRITERIA: pregnant women with a live fetus, and a history of prior preterm birth at less than 37 weeks gestation and greater than 20 weeks gestation in the immediately preceding pregnancy, where onset of labour occurred spontaneously, or in association with cervical incompetence, or following preterm prelabour ruptured membranes. Trial Entry & Randomisation: After obtaining written informed consent, eligible women will be randomised between 18 and 23+6 weeks gestation using a central telephone randomisation service. The randomisation schedule prepared by non clinical research staff will use balanced variable blocks, with stratification according to plurality of the pregnancy and centre where planned to give birth. Eligible women will be randomised to either vaginal progesterone or vaginal placebo. Study Medication & Treatment Schedules: Treatment packs will appear identical. Woman, caregivers and research staff will be blinded to treatment allocation. Primary Study Outcome: Neonatal Respiratory Distress Syndrome (defined by incidence and severity). SAMPLE SIZE: of 984 women to show a 40% reduction in respiratory distress syndrome from 15% to 9% (p = 0.05, 80% power). DISCUSSION: This is a protocol for a randomised trial.

Maternal intramuscular dexamethasone versus betamethasone before preterm birth (ASTEROID): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, whether dexamethasone or betamethasone have better maternal, neonatal, and childhood health outcomes remains unclear. We therefore aimed to assess whether administration of antenatal dexamethasone to women at risk of preterm birth reduced the risk of death or neurosensory disability in their children at age 2 years compared with betamethasone. We also aimed to assess whether dexamethasone reduced neonatal morbidity, had benefits for the mother, or affected childhood body size, blood pressure, behaviour, or general health compared with betamethasone. METHODS: In this multicentre, double-blind, randomised controlled trial, we recruited pregnant women from 14 maternity hospitals in Australia and New Zealand that could provide care to preterm babies. Women were eligible for study inclusion if they were at risk of preterm birth before 34 weeks of gestation, had a singleton or twin pregnancy, and had no contraindications to antenatal corticosteroids. We randomly assigned women (1:1) to receive two intramuscular injections of either 12 mg dexamethasone (dexamethasone sodium phosphate) or 11·4 mg betamethasone (Celestone Chronodose), 24 h apart. The randomisation schedule used balanced, variable blocks that were stratified by hospital, gestational age, and number of fetuses (singleton or twins). We masked all participants, staff, and assessors to treatment groups. Analyses were by intention to treat. The primary outcome was death or neurosensory disability at age 2 years (corrected for prematurity). This study is registered with ANZCTR, ACTRN12608000631303. FINDINGS: Between Jan 28, 2009, and Feb 1, 2013, we randomly assigned 1346 (78%) women who were pregnant with 1509 fetuses to groups: 679 (50%) women were assigned to receive dexamethasone and 667 (50%) women were assigned to receive betamethasone. 27 (4%) fetuses, infants, or children in the dexamethasone group and 28 (4%) fetuses, infants, or children in the betamethasone group died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was determined for 603 (79%) of 763 fetuses whose mothers received dexamethasone and 591 (79%) of 746 fetuses whose mothers received betamethasone. We found a similar incidence of death or neurosensory disability in the dexamethasone (198 [33%] of 603 infants) and betamethasone groups (192 [32%] of 591 infants; adjusted relative risk [adjRR] 0·97, 95% CI 0·83 to 1·13; p=0·66). 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group reported side-effects. Discomfort at the injection site, the most frequent side-effect, was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02). INTERPRETATION: The incidence of survival without neurosensory disability at age 2 years did not differ between dexamethasone and betamethasone treatment. Our findings indicate that either antenatal corticosteroid can be given to women before preterm birth to improve infant and child health. FUNDING: National Health and Medical Research Council (Australia).