The mediating effects of gestational diabetes on fetal growth and adiposity in women who are overweight and obese: secondary analysis of the LIMIT randomised trial.

OBJECTIVE: To describe the mediating effect of maternal gestational diabetes on fetal biometry and adiposity measures among overweight or obese pregnant women. DESIGN: Secondary analysis of the LIMIT randomised trial. SETTING: Public hospitals, metropolitan Adelaide, South Australia. POPULATION: Pregnant women with body mass index (BMI) ≥25 kg/m2 and singleton gestation. METHODS: Fetal ultrasound measures at 36 weeks of gestation and baseline BMI from women randomised to the LIMIT trial Standard Care group (n = 912 women) were used to conduct causal mediation analyses using regression-based methods. MAIN OUTCOMES MEASURES: Ultrasound measures of fetal biometry and adiposity at 36 weeks of gestation. RESULTS: Increased maternal BMI was associated with increased measures of fetal head circumference [direct (unmediated) effect 0.18 (95% CI: 0.05-0.31), P = 0.005; total effect 0.17 (95% CI: 0.02-0.31), P = 0.018], abdominal circumference [direct effect 0.26 (95% CI: 0.11-0.41), P = 0.001; total effect 0.26 (95% CI: 0.11-0.42), P = 0.001] and estimated fetal weight [direct effect 0.22 (95% CI: 0.08-0.35), P = 0.002; total effect 0.22 (95% CI: 0.08-0.35), P = 0.002], with no evidence of mediation by treated gestational diabetes. There was no apparent association between maternal BMI and fetal adiposity measures, or mediation by treated gestational diabetes. CONCLUSIONS: We show an important association between increased maternal BMI and fetal growth, not mediated by treated gestational diabetes. There was no association between increased maternal BMI and fetal adiposity measures, or mediation by treated gestational diabetes. Whether these findings represent 'saturation' in the effect of maternal BMI on fetal growth or the effect of treatment of GDM is unclear. FUNDING: This project was funded by a 4-year project grant from the National Health and Medical Research Council (NHMRC), Australia (ID 519240); The Channel 7 Children's Research Foundation, South Australia; and the US National Institutes of Health (R01 HL094235-01). TWEETABLE ABSTRACT: Increased fetal growth associated with maternal obesity is not mediated by gestational diabetes.

Fetal middle cerebral artery Doppler to time intrauterine transfusion in red-cell alloimmunization: a randomized trial.

OBJECTIVES: To evaluate whether Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) for timing subsequent intrauterine transfusions (IUTs) in fetuses that had undergone one IUT for anemia secondary to red-cell alloimmunization is non-inferior to timing based on expected decrease in fetal hematocrit (Hct) or fetal hemoglobin level, without compromising infant hemoglobin at birth. METHODS: This was an international, pragmatic multicenter randomized controlled trial. Women with a pregnancy complicated by fetal anemia secondary to red-cell alloimmunization (due to any antibody alone or in combination), as indicated by the need to undergo a single IUT, were eligible for inclusion. Women were randomized to the determination of timing of further transfusion(s) by Doppler measurement of MCA-PSV (MCA-PSV Group), with a serial upward trend of values >1.5 multiples of the median considered indicative of the need for another IUT, or timing of transfusion by a decrease in fetal Hct (fetal Hct Group), with subsequent IUTs timed according to an estimated fall in fetal Hct of 1% per day or fetal hemoglobin of 0.3 g/dL per day, to maintain fetal hemoglobin level between 7 and 10 g/dL. The primary outcome was infant hemoglobin level measured at birth. RESULTS: A total of 71 women were randomized, 36 to the MCA-PSV Group and 35 to the fetal Hct Group. Median gestational age at randomization was 30.3 weeks, the majority of women were Caucasian and non-smokers, 9.9% of women had Kell alloimmunization, and 14% of fetuses were hydropic at their first IUT. No statistically significant differences between the two treatment groups were observed with regard to mean hemoglobin levels at birth (MCA-PSV Group, 10.36 ± 3.82 g/dL vs fetal Hct Group, 12.03 ± 3.14 g/dL; adjusted mean difference -1.56 g/dL (95% CI, -3.24 to 0.13 g/dL); P = 0.070), or the number of IUTs performed after randomization (MCA-PSV Group, 1.75 ± 1.79 vs fetal Hct Group 1.80 ± 1.32; adjusted relative risk 0.88 (95% CI, 0.61-1.26); P = 0.474). There was no statistically significant difference between the two groups with respect to the risk of adverse infant outcomes related to alloimmunization or procedure-related complications. CONCLUSION: Both Doppler measurement of MCA-PSV and estimation of the decrease in fetal Hct or hemoglobin can be used to determine the timing of second and subsequent IUTs in fetuses with red-cell alloimmunization. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The characterisation of overweight and obese women who are under reporting energy intake during pregnancy.

BACKGROUND: Misreporting of energy intake is common and can contribute to biased estimates of the relationship between diet and disease. Energy intake misreporting is poorly understood in pregnancy and there is limited research assessing characteristics of women who misreport energy intake or changes in misreporting of energy intake across pregnancy. METHODS: An observational study in n = 945 overweight or obese pregnant women receiving standard antenatal care who participated in the LIMIT randomised trial. Diet, physical activity, psychological factors, body image satisfaction and dieting behaviour were assessed at trial entry (10-20 weeks gestation) and 36 weeks gestation. Energy misreporting status was assessed through the ratio of daily energy intake over basal metabolic rate. Logistic regression analyses were conducted with the dependent variable of under reporting of energy intake at study entry or 36 weeks in separate analysis. RESULTS: At study entry and 36 weeks, women were classified as under reporters (38 vs 49.4%), adequate reporters (59.7 vs 49.8%) or over reporters of energy intake (2.3 vs 0.8%) respectively. The prevalence of under reporting energy intake at 36 weeks was higher than at study entry (early pregnancy). Body mass index (BMI) at study entry and 36 weeks and socioeconomic status, dieting behaviour and risk of depression at 36 weeks were independent predictors of under reporting of energy intake. CONCLUSIONS: Under reporting of energy intake was present in over a third of overweight and obese pregnant women and was higher in late compared to early pregnancy. Characteristics such as BMI, socioeconomic status, past dieting behaviour and risk of depression may aid in identifying women who either require support in accurate recording of food intake or attention for improving diet quality. Results were unable to distinguish whether under reporting reflects misreporting or a true restriction of dietary intake. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12607000161426 , registered 9/3/2007.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

Antenatal dietary and lifestyle advice for women who are overweight or obese and the effect on fetal growth and adiposity: the LIMIT randomised trial.

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.

The effect of antenatal lifestyle advice for women who are overweight or obese on secondary measures of neonatal body composition: the LIMIT randomised trial.

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.

Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey.

OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.

A decrease in diet quality occurs during pregnancy in overweight and obese women which is maintained post-partum.

BACKGROUND: Ensuring adequate dietary intake during pregnancy has important implications for optimising maternal and fetal health. It is not known whether diet quality is altered over pregnancy and the post-partum period. OBJECTIVE: The aim of this study was to perform a comprehensive assessment of diet quality in overweight and obese women during pregnancy and early post-partum. DESIGN: In a prospective cohort study, n=301 overweight or obese pregnant women completed a food frequency questionnaire at study entry (10-20 weeks gestation), 28 weeks gestation, 36 weeks gestation and 4 months post-partum for assessment of macronutrient and micronutrient intake and diet quality by the Healthy Eating Index (HEI). RESULTS: Energy, macronutrient and dietary sources of micronutrients did not alter across pregnancy or post-partum. The HEI was of below average quality in 31.0% of women at baseline. This decreased from week 28 (P<0.001) and was maintained at a lower level post-partum such that HEI levels were lower compared with study entry (53.3±12.7 versus 56.7±10.1, P<0.001). The HEI decrease occurred in association with decreases in the milk, meat and unsaturated oil components, and increases in the proportion of energy from solid fats, alcohol and added sugars (P<0.001), and was independently predicted by the socioeconomic index for areas score (ß=-0.011, s.e.=0.011, P=0.031). CONCLUSION: We report for the first time that dietary quality decreases across pregnancy and is maintained at this reduced level in the early post-partum period in overweight and obese women. Dietary interventions aimed at improving diet quality should be targeted to early pregnancy and post-partum.

Overweight and obese women's perceptions about making healthy change during pregnancy: a mixed method study.

Overweight and obesity during pregnancy is associated with risk of a range of adverse health outcomes. While intervention studies aim to promote behavioral change, little is known about the underlying psychological mechanisms facilitating and hindering change. The aim of this study was to evaluate overweight and obese women's perceptions of making behavior change during pregnancy. We explored beliefs through self-administrated questionnaires (n = 464) and semi-structured face-to-face interviews (n = 26). Questions were designed according to the Health Belief Model. A triangulation protocol was followed to combine quantitative and qualitative data. A total of 269 women (58 %) indicated that high gestational weight gain is a concern, with 348 (75 %) indicating excessive weight gain is associated with complications during pregnancy or child birth. Women were aware of maternal complications associated with high gestational weight gain, but had more limited awareness of neonatal complications. While most women indicated in questionnaires that healthy eating and physical activity were associated with improved health during pregnancy, they were unable to identify specific benefits at interview. Barriers to making healthy behavior changes were highly individualized, the main barrier being lack of time. While the majority (91 %) of women indicated that they would make behavior changes if the change made them feel better, only half felt confident in their ability to do so. Interventions for overweight and obese pregnant women should incorporate education about neonatal health consequences and benefits of healthy behavior change in addition to incorporating strategies to enhance self-efficacy.

Elective birth at 37 weeks of gestation versus standard care for women with an uncomplicated twin pregnancy at term: the Twins Timing of Birth Randomised Trial.

OBJECTIVE: To evaluate whether for women with an uncomplicated twin pregnancy, elective birth at 37 weeks of gestation was associated with reduced risk of death or serious outcomes for babies, without increasing harm. DESIGN: Randomised controlled trial. SETTING: Maternity hospitals across Australia, New Zealand and Italy. POPULATION: A total of 235 women with an uncomplicated twin pregnancy at 36(+6) weeks of gestation, with no contraindication to continuing their pregnancy. METHODS: Using a computer-generated, central telephone randomisation service, 235 women were randomised to Elective Birth (birth at 37 weeks; n=116) or Standard Care (continued expectant management, with birth planned from 38 weeks; n=119). Outcome assessors were masked to treatment allocation. MAIN OUTCOME MEASURE: A composite of serious adverse outcome for the infant. RESULTS: For women with an uncomplicated twin pregnancy, elective birth at 37 weeks of gestation was associated with a significant reduction in risk of serious adverse outcome for the infant (Elective Birth 11/232 [4.7%] versus Standard Care 29/238 [12.2%]; risk ratio [RR] 0.39; 95% CI 0.20-0.75; P=0.005), reflecting a reduction in birthweight less than the third centile using singleton gestational age-specific charts (Elective Birth 7/232 [3.0%] versus Standard Care 24/238 [10.1%]; RR 0.30; 95% CI 0.13-0.67; P=0.004). In a post hoc analysis using twin gestational age-specific charts, there was evidence of a trend towards a reduction in the primary composite of serious adverse infant outcome (Elective Birth Group 4/232 [1.7%] versus Standard Care Group 12/238 [5.0%]; RR 0.34; 95% CI 0.11 to 1.05; P=0.06). CONCLUSION: The findings of our study support recommendations for women with an uncomplicated twin pregnancy to birth at 37 weeks of gestation.

Antenatal interventions for overweight or obese pregnant women: a systematic review of randomised trials.

BACKGROUND: Overweight and obesity during pregnancy is an increasing health problem. OBJECTIVE: A systematic review to assess the benefits and harms of antenatal dietary or lifestyle interventions for pregnant women who are overweight or obese. SEARCH STRATEGY: The Cochrane Controlled Trials Register(CENTRAL) was searched (last search January 2010). Reference lists of retrieved studies were searched by hand. No date or language restrictions were used. SELECTION CRITERIA: Randomised controlled trials comparing antenatal dietary and/or lifestyle or other interventions with no treatment for overweight or obese women were considered.Studies were evaluated independently for appropriateness for inclusion and methodological quality. The primary outcome was large-for-gestational-age infants. DATA COLLECTION AND ANALYSIS: Nine randomised controlled trials were included involving 743 women who were overweight or obese during pregnancy. Seven trials compared a dietary intervention with standard antenatal care. MAIN RESULTS: There were no statistically significant differences identified between women who received an antenatal intervention and those who did not for the large-for-gestational-age infant outcome (three studies; 366 women; risk ratio 2.02; 95% CI 0.84,4.86) or mean gestational weight gain [four studies; 416 women;weighted mean difference )3.10 kg; 95% CI )8.32, 2.13 (random effects model)]. There were no statistically significant differences identified for other reported outcomes. AUTHOR'S CONCLUSIONS: The effect of providing an antenatal dietary intervention for overweight or obese pregnant women on maternal and infant health outcomes remains unclear.

Screening for placental insufficiency in high-risk pregnancies: is earlier better?

OBJECTIVE: To compare a profile of placental function between the first and second trimesters in pregnancies at high risk of adverse perinatal outcomes attributable to placental insufficiency. STUDY DESIGN: Prospective cohort study in 61 singleton pregnancies. Uterine artery Doppler and placental morphology (shape and texture) were determined at 11-13(+6) weeks and at 18-23(+6) weeks. First trimester (pregnancy-associated placental protein-A [PAPP-A]) and second trimester (total hCG and alpha fetoprotein [AFP]) serum biochemistry were determined. The two screening periods were compared for the prediction of a range of severe adverse perinatal outcomes (intrauterine growth restriction [IUGR], abruption, severe pre-eclampsia/HELLP syndrome, delivery<32 weeks, or stillbirth). RESULTS: Adverse perinatal outcomes occurred in 14 (23%) women; 3 (4.9%) losses<20 weeks, 2 (3.3%) stillbirths>20 weeks, 4 (6.6%) IUGR, 7 (11.5%) severe pre-eclampsia/HELLP syndrome, and 10 (16.4%) deliveries<32 weeks. Abnormal second trimester placental morphology was significantly associated with adverse outcome [+LR: 3.6, 95% CI: 1.3-8.5; -LR: 0.63, 95% CI: 0.36-0.93; p=0.025], as was > or = 1 abnormal second trimester tests [+LR: 5.9, 95% CI: 1.6-24; -LR: 0.68, 95% CI: 0.59-0.89; p=0.005] or > or = 2 abnormal second trimester tests [+LR: 3.6, 95% CI: 1.3-7.7; -LR: 0.58, 95% CI: 0.27-0.94; p=0.035]. No combination of first trimester tests significantly predicted severe adverse perinatal outcomes. A study sample size of 822 women with similar high-risk characteristics would be needed in order to refute the conclusion that present methods of first trimester screening are not inferior to second trimester screening for severe placental insufficiency (p=0.05, power 80%, z-test). CONCLUSIONS: In clinically high-risk pregnancies, prediction of adverse perinatal outcomes using placental function testing is more effective in the second compared with the first trimester.

Specialised antenatal clinics for women with a multiple pregnancy to improve maternal and infant outcomes.

BACKGROUND: Regular antenatal care for women with a multiple pregnancy is accepted practice, and while most women have an increase in the number of antenatal visits, there is no consensus as to what constitutes optimal care. 'Specialised' antenatal clinics have been advocated as a way of improving outcomes for women and their infants. OBJECTIVES: To assess, using the best available evidence, the benefits and harms of 'specialised' antenatal clinics compared with 'standard' antenatal care for women with a multiple pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2006), the Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library 2005, Issue 4), and PubMed (January 1966 to January 2006). SELECTION CRITERIA: Randomised controlled trials with reported data that compared outcomes in mothers and babies who received 'specialised' antenatal care with outcomes in mothers and babies who received 'standard' antenatal care. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed trial quality and extracted data. MAIN RESULTS: There are no included studies. AUTHORS' CONCLUSIONS: There is no information available from randomised controlled trials to support the role of 'specialised' antenatal clinics for women with a multiple pregnancy compared with 'standard' antenatal care in improving maternal and infant health outcomes. The value of 'specialised' multiple pregnancy clinics in improving health outcomes for women and their infants requires evaluation in appropriately powered and designed randomised controlled trials.

Elective repeat caesarean section versus induction of labour for women with a previous caesarean birth.

BACKGROUND: When a woman has had a previous caesarean birth and requires induction of labour in a subsequent pregnancy, there are two options for her care: elective repeat caesarean or planned induction of labour. While there are risks and benefits for both elective repeat caesarean birth and planned induction of labour, current sources of information are limited to non-randomised cohort studies. Studies designed in this way have significant potential for bias and consequently conclusions based on these results are limited in their reliability and should be interpreted with caution. OBJECTIVES: To assess, using the best available evidence, the benefits and harms of elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1) and PubMed (1966 to January 2006). SELECTION CRITERIA: Randomised controlled trials with reported data that compared outcomes in mothers and babies who planned a repeat elective caesarean section with outcomes in women who planned induction of labour, where a previous birth had been by caesarean. DATA COLLECTION AND ANALYSIS: There was no data extraction performed. MAIN RESULTS: There were no randomised controlled trials identified. AUTHORS' CONCLUSIONS: Planned elective repeat caesarean section and planned induction of labour for women with a prior caesarean birth are both associated with benefits and harms. Evidence for these care practices is drawn from non-randomised studies, associated with potential bias. Any results and conclusions must therefore be interpreted with caution. Randomised controlled trials are required to provide the most reliable evidence regarding the benefits and harms of both planned elective repeat caesarean section and planned induction of labour for women with a previous caesarean birth.

Tocolysis for assisting delivery at caesarean section.

BACKGROUND: Caesarean section involves making an incision in the woman's abdomen and cutting through the uterine muscle. The baby is then delivered through that incision. Difficult caesarean birth may result in injury for the infant. Medication that relaxes the uterus (tocolytic medication) may facilitate the birth of the baby at caesarean section. OBJECTIVES: To compare the use of tocolysis (routine or selective use) with no use of tocolysis or placebo at the time of caesarean section for outcomes of infant birth trauma, maternal complications (particularly postpartum haemorrhage requiring blood transfusion), and long-term measures of infant and childhood morbidity. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1) and PubMed (1966 to January 2006). SELECTION CRITERIA: Use of tocolytic agents (routine or selective) at caesarean section versus no use of tocolytic or placebo at caesarean section to facilitate the birth of the baby. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: A single randomised trial involving 97 women was identified and included in the review. Maternal and infant health outcomes were not reported. AUTHORS' CONCLUSIONS: There is currently insufficient information available from randomised trials to support or refute the routine or selective use of tocolytic agents to facilitate infant birth at the time of caesarean section.

Oral betamimetics for maintenance therapy after threatened preterm labour.

BACKGROUND: Some women who have threatened to give birth prematurely, subsequently settle. They may then take oral tocolytic maintenance therapy to prevent preterm birth and to prolong gestation. OBJECTIVES: To assess the effects of oral betamimetic maintenance therapy after threatened preterm labour for preventing preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Trials Register (June 2005) and MEDLINE (from 1966 to August 2003). SELECTION CRITERIA: Randomised controlled trials comparing oral betamimetic with alternative tocolytic therapy, placebo or no therapy, for maintenance following treatment of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the selection criteria and carried out data extraction and quality assessment of studies. MAIN RESULTS: Eleven randomised controlled trials (RCTs) were included. No differences were seen for admission to the neonatal intensive care unit when betamimetics were compared with placebo (relative risk (RR) 1.29, 95% confidence interval (CI) 0.64 to 2.60; one RCT of terbutaline with 140 women) or with magnesium (RR 0.80, 95% CI 0.43 to 1.46; one RCT of 137 women). The rate of preterm birth (less than 37 weeks) showed no significant difference in four RCTs, two comparing ritodrine with placebo/no treatment and two comparing terbutaline with placebo/no treatment (RR 1.08, 95% CI 0.88 to 1.32, 384 women). No differences between betamimetics and placebo, no treatment or other tocolytics were seen for perinatal mortality and morbidity outcomes. Some adverse effects such as tachycardia were more frequent in the betamimetics groups than the groups allocated to placebo, no treatment or another type of tocolytic. AUTHORS' CONCLUSIONS: Available evidence does not support the use of oral betamimetics for maintenance therapy after threatened preterm labour.

Prenatal administration of progesterone for preventing preterm birth.

BACKGROUND: Preterm birth is the major complication of pregnancy associated with perinatal mortality and morbidity and occurs in up to 6% to 10% of all births. Administration of progesterone for the prevention of preterm labour has been advocated. OBJECTIVES: To assess the benefits and harms of progesterone administration during pregnancy in the prevention of preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Specialised Register of Controlled Trials (March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to January 2005), EMBASE (1988 to August 2004), and Current Contents (1997 to August 2004). SELECTION CRITERIA: All published and unpublished randomised controlled trials, in which progesterone was given by any route for preventing preterm birth. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by two authors. Results are presented using relative risk with 95% confidence intervals. MAIN RESULTS: For all women administered progesterone, there was a reduction in the risk of preterm birth less than 37 weeks (six studies, 988 participants, relative risk (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.79) and preterm birth less than 34 weeks (one study, 142 participants, RR 0.15, 95% CI 0.04 to 0.64). Infants born to mothers administered progesterone were less likely to have birthweight less than 2500 grams (four studies, 763 infants, RR 0.63, 95% CI 0.49 to 0.81) or intraventricular haemorrhage (one study, 458 infants, RR 0.25, 95% CI 0.08 to 0.82). There was no difference in perinatal death between women administered progesterone and those administered placebo (five studies, 921 participants, RR 0.66, 95% CI 0.37 to 1.19). There were no other differences reported for maternal or neonatal outcomes. AUTHORS' CONCLUSIONS: Intramuscular progesterone is associated with a reduction in the risk of preterm birth less than 37 weeks' gestation, and infant birthweight less than 2500 grams. However, other important maternal and infant outcomes have been poorly reported to date, with most outcomes reported from a single trial only (Meis 2003). It is unclear if the prolongation of gestation translates into improved maternal and longer-term infant health outcomes. Similarly, information regarding the potential harms of progesterone therapy to prevent preterm birth is limited. Further information is required about the use of vaginal progesterone in the prevention of preterm birth.

Effects of synthetic mammalian gonadotrophin releasing hormone and dogfish hypothalamic extracts on levels of androgens and oestradiol in the circulation of the dogfish (Scyliorhinus canicula L.).

Intravenous injection of synthetic mammalian gonadotrophin releasing hormone (GnRH; 5 microgram per fish) induced a significant increase in androgen levels in the circulation of male dogfish within 4 h. Female dogfish injected with 10 microgram GnRN in November showed significantly raised plasma levels of androgens and oestradiol-17 beta after 90 min as well as an increase in the rat of oviposition. Twice this dose of GnRH failed to produce significant increases in plasma levels of oestradiol in female dogfish in February and the androgen response in these animals was less than that seen after injection of GnRH in November. Injection of an acid extract of dogfish hypothalamus significantly increased plasma levels of androgen and oestradiol in female fish when they were compared with control fish injected with extracts of dogfish cerebellum and the latency of response was similar to that encountered when GnRH was injected. It was concluded that the dogfish hypothalamus contains a factor capable of increasing plasma sex steroid levels in the same species and which is similar in its effects to mammalian GnRH.