Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption.
To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 July 2010).
We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism.
Data collection and analysis
Two review authors would have assessed trial eligibility and risk of bias, and extracted data.
No trials were located.
As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.
Hyperthyroidism [prevention & control *therapy]; Pregnancy Complications [prevention & control *therapy]; Randomized Controlled Trials as Topic; Female; Humans; Pregnancy
It has been unclear whether repeat dose(s) of prenatal corticosteroids are beneficial.
To assess the effectiveness and safety of repeat dose(s) of prenatal corticosteroids.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2011), searched reference lists of retrieved studies and contacted authors for further data.
Randomised controlled trials of women who had already received a single course of corticosteroids seven or more days previously and considered still at risk of preterm birth.
Data collection and analysis
We assessed trial quality and extracted data independently.
We included 10 trials (more than 4730 women and 5650 babies) with low to moderate risk of bias. Treatment of women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids with repeat dose(s), compared with no repeat corticosteroid treatment, reduced the risk of their infants experiencing the primary outcomes respiratory distress syndrome (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.75 to 0.91, eight trials, 3206 infants, numbers needed to treat (NNT) 17, 95% CI 11 to 32) and serious infant outcome (RR 0.84, 95% CI 0.75 to 0.94, seven trials, 5094 infants, NNT 30, 95% CI 19 to 79).
Treatment with repeat dose(s) of corticosteroid was associated with a reduction in mean birthweight (mean difference (MD) −75.79 g, 95% CI −117.63 to −33.96, nine trials, 5626 infants). However, outcomes that adjusted birthweight for gestational age (birthweight Z scores, birthweight multiples of the median and small-for-gestational age) did not differ between treatment groups.
At early childhood follow-up no statistically significant differences were seen for infants exposed to repeat prenatal corticosteroids compared with unexposed infants for the primary outcomes (total deaths; survival free of any disability or major disability; disability; or serious outcome) or in the secondary outcome growth assessments.
The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.
Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.
*Obstetric Labor, Premature; Adrenal Cortex Hormones [*administration & dosage; adverse effects]; Betamethasone [*administration & dosage; adverse effects]; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn [*prevention & control]; Retreatment [adverse effects]; Female; Humans; Pregnancy
While most guidelines recommend the use of insulin in women whose pregnancies are affected by pre-existing diabetes, oral agents have obvious benefits for patient acceptability and adherence. It is necessary, however, to assess the effects of these anti-diabetic agents on maternal and infant health outcomes. Additionally, women with previous gestational diabetes mellitus are increasingly found to be predisposed to impaired glucose tolerance and, despite the potential need for intervention for these women, there has been little evidence about the use of oral anti-diabetic agents by these women pre-conceptionally or during a subsequent pregnancy.
To investigate the effect of oral anti-diabetic agents in women with pre-existing diabetes mellitus, impaired glucose tolerance or previous gestational diabetes planning a pregnancy or pregnant women with diabetes mellitus on maternal and infant health.
The use of oral antidiabetic agents for management of gestational diabetes in a current pregnancy is evaluated in a separate Cochrane review.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (March 2010).
We included randomised and quasi-randomised trials.
Data collection and analysis
Two review authors independently assessed trial eligibility for inclusion.
We identified 13 trials published as 25 papers using the Cochrane Pregnancy and Childbirth group literature search, and an additional ongoing trial. We have not included any trials in the review. One trial is awaiting assessment and we have excluded twelve trials because they evaluated treatment of women with gestational diabetes or women with polycystic ovary syndrome, were not randomised controlled trials or data were not available.
Little randomised evidence is available evaluating the use of oral anti-diabetic agents in women with diabetes mellitus, impaired glucose tolerance, previous gestational diabetes mellitus planning a pregnancy or pregnant women with pre-existing diabetes mellitus. Large trials comparing any combination of oral anti-diabetic agent, insulin and dietary and lifestyle advice in these women, reporting on maternal and infant health outcomes, glycaemic control, women’s views on the intervention and long-term health outcomes for mother and child, are required to guide clinical practice.
Administration, Oral; Diabetes Mellitus [* drug therapy]; Diabetes, Gestational [drug therapy]; Glucose Intolerance [* drug therapy]; Hypoglycemic Agents [* administration & dosage]; Female; Humans; Pregnancy
Antenatal day care units have been widely used as an alternative to inpatient care for women with pregnancy complications including mild and moderate hypertension, and preterm prelabour rupture of the membranes.
The objective of this review is to compare day care units with routine care or hospital admission for women with pregnancy complications in terms of maternal and perinatal outcomes, length of hospital stay, acceptability, and costs to women and health services providers.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (February 2009).
Randomised controlled trials comparing day care with inpatient or routine care for women with complicated pregnancy.
Data collection and analysis
Two review authors independently carried out data extraction and assessed studies for risk of bias.
Three trials with a total of 504 women were included. For most outcomes it was not possible to pool results from trials in meta-analyses as outcomes were measured in different ways.
Compared with women in the ward/routine care group, women attending day care units were less likely to be admitted to hospital overnight (risk ratio 0.46, 95% confidence interval 0.34 to 0.62). The average length of antenatal admission was shorter for women attending for day care, although outpatient attendances were increased for this group. There was evidence from one study that women attending for day care were significantly less likely to undergo induction of labour, but mode of birth was similar for women in both groups. For other outcomes there were no significant differences between groups. The evidence regarding the costs of different types of care was mixed; while the length of antenatal hospital stays were reduced, this did not necessarily translate into reduced health service costs.
While most women tended to be satisfied with whatever care they received, women preferred day care compared with hospital admission.
Small studies suggest that there are no major differences in clinical outcomes for mothers or babies between antenatal day units or hospital admission, but women may prefer day care.
*Day Care; *Hospital Units; *Hospitalization; Cost-Benefit Analysis; Fetal Membranes; Premature Rupture [*therapy]; Hypertension [therapy]; Length of Stay; Pregnancy Complications; Cardiovascular [*therapy]; Randomized Controlled Trials as Topic; Female; Humans; Pregnancy
Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome in preterm infants, there is currently no consensus as to the type of corticosteroid to use; nor the dose, frequency or timing of use or the route of administration.
To assess the effects of different corticosteroid regimens for women at risk of preterm birth.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (January 2008).
Randomised and quasi-randomised controlled trials of antenatal corticosteroid regimens in women at risk of preterm birth.
Data collection and analysis
Two authors assessed trial quality and extracted the data independently.
Ten trials (1089 women and 1161 infants) were included. Dexamethasone decreased the incidence of intraventricular haemorrhage compared with betamethasone (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.21 to 0.92; four trials, 549 infants). No statistically significant differences were seen for other primary outcomes including respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular haemorrhage, periventricular leukomalacia, perinatal death, or mean birthweight. Results for biophysical parameters were inconsistent, but mostly no important differences were seen for these, or any other secondary outcome except for neonatal intensive care unit (NICU) admission. In one trial of 105 infants, significantly more infants in the dexamethasone group were admitted to NICU compared with the betamethasone group (RR 3.83, 95% CI 1.24 to 11.87).
Oral dexamethasone compared with intramuscular dexamethasone increased the incidence of neonatal sepsis (RR 8.48, 95% CI 1.11 to 64.93) in one trial of 183 infants. No statistically significant differences were seen for other outcomes reported.
In one small trial of 69 infants comparing betamethasone acetate and phosphate with betamethasone phosphate no differences were seen for any of the outcomes reported.
Dexamethasone may have some benefits compared with betamethasone such as less intraventricular haemorrhage, although perhaps a higher rate of NICU admission (seen in only one trial). Apart from a suggestion from another small trial that the intramuscular route may have advantages over an oral route for dexamethasone, few other conclusions about optimal antenatal corticosteroid regimens were able to be made. Trials of commonly used corticosteroids are most urgently needed, followed by trials of dosages and other variations in regimens.
*Premature Birth; Adrenal Cortex Hormones [*administration & dosage]; Beclomethasone [administration & dosage]; Dexamethasone [administration & dosage]; Fetal Organ Maturity [*drug effects]; Intracranial Hemorrhages [prevention & control]; Lung [drug effects; *embryology]; Female; Humans; Pregnancy
The optimal glycaemic control target in pregnant women with pre-existing diabetes is unclear, although there is a clear link between high glucose concentrations and adverse birth outcomes.
To assess the effects of different intensities of glycaemic control in pregnant women with pre-existing type 1 or type 2 diabetes.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 April 2012).
We included randomised controlled trials comparing different glycaemic control targets in pregnant women with pre-existing diabetes.
Data collection and analysis
Two review authors assessed trial eligibility and risk of bias, and extracted data.
We included three trials all in women with type 1 diabetes (223 women and babies), and all with a high risk of bias. Two trials compared very tight (3.33 to 5.0 mmol/L fasting blood glucose (FBG)) with tight-moderate (4.45 to 6.38) glycaemic control targets, with one trial of 22 babies reporting no perinatal deaths or serious perinatal morbidity. In the same trial, there were two birth defects in the very tight and none in the tight-moderate group with no significant differences in caesarean section between groups (risk ratio 0.92, 95% confidence interval (CI) 0.49 to 1.73). In these two trials glycaemic control was not significantly different between the very tight and tight-moderate groups by the third trimester, although one trial of 22 women found significantly less maternal hypoglycaemia in the tight-moderate group.
In a trial of 60 women and babies comparing tight ( 5.6 mmol/L FBG); moderate (5.6 to 6.7); and loose (6.7 to 8.9) glycaemic control targets, there were two neonatal deaths in the loose and none in the tight or moderate groups. There were significantly fewer women with pre-eclampsia, fewer caesareans and fewer birthweights greater than 90th centile in the combined tight-moderate compared with the loose group.
In a very limited body of evidence, few differences in outcomes were seen between very tight and tight-moderate glycaemic control targets in pregnant women with pre-existing type 1 diabetes, including actual glycaemic control achieved. There is evidence of harm (increased pre-eclampsia, caesareans and birthweights greater than 90th centile) for ‘loose’ control (FBG above 7 mmol/L). Future trials comparing interventions, rather than glycaemic control targets, may be more feasible particularly for pregnant women with type 2 diabetes.
Blood Glucose [*metabolism]; Diabetes Mellitus, Type 1 [blood; *therapy]; Diabetes Mellitus, Type 2 [blood]; Fasting [blood]; Hemoglobin A, Glycosylated [metabolism]; Hyperglycemia [blood; therapy]; Hypoglycemic Agents [therapeutic use]; Infant, Newborn; Insulin [therapeutic use]; Pregnancy in Diabetics [blood; *therapy]; Randomized Controlled Trials as Topic; Reference Values; Female; Humans; Pregnancy
Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it is associated with significant morbidities for mother and baby both perinatally and in the long term. There is strong evidence to support treatment for GDM. However, there is little consensus on whether or not screening for GDM will improve maternal and infant health and if so, the most appropriate protocol to follow.
To assess the effects of different methods of screening for gestational diabetes mellitus and maternal and infant outcomes.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (April 2010).
Randomised and quasi-randomised trials evaluating the effects of different methods of screening for gestational diabetes mellitus.
Data collection and analysis
Two review authors independently conducted data extraction and quality assessment. We resolved disagreements through discussion or through a third author.
We included four trials involving 3972 women were included in the review. One quasi-randomised trial compared risk factor screening with universal or routine screening by 50 g oral glucose challenge testing. Women in the universal screening group were more likely to be diagnosed with GDM (one trial, 3152 women, risk ratio (RR) 0.44 95% confidence interval (CI) 0.26 to 0.75). Infants of mothers in the risk factor screening group were born marginally earlier than infants of mothers in the routine screening group (one trial, 3152 women, mean difference −0.15 weeks, 95% CI −0.27 to −0.53).
The remaining three trials evaluated different methods of administering a 50 g glucose load. Two small trials compared glucose monomer with glucose polymer testing, with one of these trials including a candy bar group. One trial compared a glucose solution with food. No differences in diagnosis of GDM were found between each comparison. Overall, women drinking the glucose monomer experienced fewer side effects from testing than women drinking the glucose polymer (two trials, 151 women, RR 2.80, 95% CI 1.10 to 7.13). However, we observed high heterogeneity between the trials for this result (I2 = 61%).
There was insufficient evidence to determine if screening for gestational diabetes, or what types of screening, can improve maternal and infant health outcomes.
Diabetes, Gestational [*diagnosis; therapy]; Glucose Tolerance Test [adverse effects; *methods]; Infant Welfare; Infant, Newborn; Mass Screening [*methods]; Maternal Welfare; Pregnancy Outcome; Randomized Controlled Trials as Topic; Female; Humans; Pregnancy
As a pregnancy continues beyond term the risks of babies dying inside the womb or in the immediate newborn period increase. Whether a policy of labour induction at a predetermined gestational age can reduce this increased risk is the subject of this review.
To evaluate the benefits and harms of a policy of labour induction at term or post-term compared with awaiting spontaneous labour or later induction of labour.
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 March 2012).
Randomised controlled trials conducted in women at or beyond term. The eligible trials were those comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour. Cluster-randomised trials and cross-over trials are not included. Quasi-random allocation schemes such as alternation, case record numbers or open random-number lists were not eligible.
Data collection and analysis
Two review authors independently assessed trials for inclusion. Two review authors independently assessed trial quality and extracted data. Data were checked for accuracy. Outcomes are analysed in two main categories: gestational age and cervix status.
We included 22 trials reporting on 9383 women. The trials were generally at moderate risk of bias.
Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths: risk ratio (RR) 0.31, 95% confidence interval (CI) 0.12 to 0.88; 17 trials, 7407 women. There was one perinatal death in the labour induction policy group compared with 13 perinatal deaths in the expectant management group. The number needed to treat to benefit (NNTB) with induction of labour in order to prevent one perinatal death was 410 (95% CI 322 to 1492).
For the primary outcome of perinatal death and most other outcomes, no differences between timing of induction subgroups were seen; the majority of trials adopted a policy of induction at 41 completed weeks (287 days) or more.
Fewer babies in the labour induction group had meconium aspiration syndrome (RR 0.50, 95% CI 0.34 to 0.73; eight trials, 2371 infants) compared with a policy of expectant management. There was no statistically significant difference between the rates of neonatal intensive care unit (NICU) admission for induction compared with expectant management (RR 0.90, 95% CI 0.78 to 1.04; 10 trials, 6161 infants). For women in the policy of induction arms of trials, there were significantly fewer caesarean sections compared with expectant management in 21 trials of 8749 women (RR 0.89, 95% CI 0.81 to 0.97).
A policy of labour induction compared with expectant management is associated with fewer perinatal deaths and fewer caesarean sections. Some infant morbidities such as meconium aspiration syndrome were also reduced with a policy of post-term labour induction although no significant differences in the rate of NICU admission were seen.
However, the absolute risk of perinatal death is small. Women should be appropriately counselled in order to make an informed choice between scheduled induction for a post-term pregnancy or monitoring without induction (or delayed induction).
* Pregnancy, Prolonged; *Watchful Waiting; Cesarean Section [utilization]; Infant Mortality; Infant, Newborn; Labor, Induced [*adverse effects]; Randomized Controlled Trials as Topic; Risk; Female; Humans; Pregnancy
Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy outcomes. Despite awareness of the substantial adverse effects associated with asthma during pregnancy, little has been done to improve its management and reduce associated perinatal morbidity and mortality. The aim of this randomized controlled trial is to evaluate the clinical and cost effectiveness of an Antenatal Asthma Management Service.
Design: Multicentre, randomized controlled trial.
Inclusion criteria: Women with physician diagnosed asthma, which is not currently in remission, who are less than 20 weeks gestation with a singleton pregnancy and do not have a chronic medical condition.
Trial entry and randomization: Eligible women with asthma, stratified by treatment site, disease severity and parity, will be randomized into either the ‘Standard Care Group’ or the ‘Intervention Group’.
Study groups: Both groups will be followed prospectively throughout pregnancy. Women in the ‘Standard Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive additional care through the nurse-led Antenatal Asthma Management Service, based in the antenatal outpatient clinic. Women will receive asthma education with a full assessment of their asthma at 18, 24, 30 and 36 weeks gestation. Each antenatal visit will include a 60 min session where asthma management skills are assessed including: medication adherence and knowledge, inhaler device technique, recognition of asthma deterioration and possession of a written asthma action plan. Furthermore, subjects will receive education about asthma control and management skills including trigger avoidance and smoking cessation counseling when appropriate.
Primary study outcome: Asthma exacerbations during pregnancy.
Sample size: A sample size of 378 women will be sufficient to show an absolute reduction in asthma exacerbations during pregnancy of 20% (alpha 0.05 two-tailed, 90% power, 5% loss to follow-up).
The integration of an asthma education program within the antenatal clinic setting has the significant potential to improve the participation of pregnant women in the self-management of their asthma, reduce asthma exacerbations and improve perinatal health outcomes.
Asthma; Pregnancy; Inhaled corticosteroids; Randomized controlled trial; Antenatal care; Intervention
Babies born very preterm (before 30 weeks gestation) are at high risk of dying in their first weeks of life, and those who survive are at risk of developing cerebral palsy in childhood. Recent high-quality evidence has shown that giving women magnesium sulphate immediately prior to very early birth can significantly increase the chances of their babies surviving free of cerebral palsy. In 2010 Australian and New Zealand clinical practice guidelines recommended this therapy. The WISH (Working to Improve Survival and Health for babies born very preterm) Project aims to bi-nationally improve and monitor the use of this therapy to reduce the risk of very preterm babies dying or having cerebral palsy.
The WISH Project is a prospective cohort study. The 25 Australian and New Zealand tertiary level maternity hospitals will be provided with a package of active implementation strategies to guide the introduction and local adaptation of guideline recommendations. Surveys will be conducted at individual hospitals to evaluate outcomes related to local implementation progress and the use and value of the WISH implementation strategies. For the hospitals participating in the ‘WISH audit of uptake and health outcomes data collection’, the primary health outcomes (assessed through case note review, and 24 month corrected age questionnaires) will be: the proportion of eligible women receiving antenatal magnesium sulphate; and rates of death prior to primary hospital discharge and cerebral palsy at two years corrected age in infants born to eligible mothers. For hospitals wishing to assess factors influencing translation locally, barriers and facilitators will be measured through interviews with health care professionals, to further guide implementation strategies. Study outcomes for the early phase of the project (Year 1) will be compared with the later intervention phase (Years 2 and 3).
The WISH Project will offer insight into the effectiveness of a multifaceted implementation strategy to improve the uptake of a novel neuroprotective therapy in obstetric clinical practice. The successful implementation of antenatal magnesium sulphate for fetal neuroprotection in Australia and New Zealand could lead to over 90 fewer very preterm babies dying or suffering the long-term consequences of cerebral palsy each year.
Evidence-based practice; Implementation; Magnesium sulphate; Neuroprotection; Cerebral palsy; Preterm birth
Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment.
Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively.
A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised trials. Case reports supported an association between iatrogenic overdose of magnesium sulphate and life-threatening consequences.
Appropriate administration of antenatal magnesium sulphate was not shown to be associated with serious maternal adverse effects, though an increase in 'minor’ adverse effects and treatment cessation was shown. Larger trials are needed to determine optimal regimens, achieving maximal effectiveness with minimal adverse effects, for each antenatal indication for use. Vigilance in the use of magnesium sulphate is essential for women’s safety.
Magnesium sulphate; Magnesium sulfate; Antenatal; Adverse effect; Systematic review
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.
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).
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:
Antenatal corticosteroids; Dexamethasone; Betamethasone; Preterm birth; Randomised controlled trial; Neurosensory disability
Postpartum follow up of women who have been found to have gestational diabetes during pregnancy is essential because of the strong association of gestational diabetes with subsequent type 2 diabetes. Postal reminders have been shown to increase significantly attendance for oral glucose tolerance testing postpartum. It is possible that a short message service (text) reminder system may also be effective. This trial aims to assess whether a text message reminder system for women who have experienced gestational diabetes in their index pregnancy will increase attendance for oral glucose tolerance testing within six months after birth.
Design: Single centre (Women’s and Children’s Hospital, South Australia), parallel group randomised controlled trial.
Inclusion criteria: Women diagnosed with gestational diabetes in their index pregnancy (oral glucose tolerance test with fasting glucose ≥ 5.5 mmol/L and/or two hour glucose ≥ 7.8 mmol/L), with access to a mobile phone, whose capillary blood glucose profile measurements prior to postnatal discharge are all normal (fasting glucose < 6.0 mmol/L, postprandial glucoses < 8.0 mmol/L).
Exclusion criteria: Pregestational diabetes mellitus, triplet/higher order multiple birth or stillbirth in the index pregnancy, requirement for interpreter.
Trial entry and randomisation: Allocation to intervention will be undertaken using a telephone randomisation service (computer-generated random number sequence generation, with balanced variable blocks, and stratification by insulin requirement).
Study groups: Women in the intervention group will receive a text reminder to attend for an oral glucose tolerance test at 6 weeks postpartum, with further reminders at 3 months and 6 months if they do not respond to indicate test completion. Women in the control group will receive a single text message reminder at 6 months postpartum.
Blinding: Baseline data collection will be undertaken blinded. Blinding of participants and blinded collection of primary outcome data will not be possible for this study.
Primary study outcome: Attendance for the oral glucose tolerance test within 6 months postpartum.
Sample size: 276 subjects will be required to show an 18% absolute increase in the rate of attendance (α=0.05 two tailed, β=80%, 5% loss to follow up) from 37% to 55% in the intervention group.
Given the heightened risk of impaired glucose tolerance and type 2 diabetes in women who have had gestational diabetes, ensuring the highest possible rate of attendance for postpartum glucose tolerance testing, so that early diagnosis and intervention can occur, is important. A text message reminder system may prove to be an effective method for achieving improved attendance for such testing. This randomised controlled trial will assess whether such a system will increase rates of attendance for postpartum oral glucose tolerance testing in women who have experienced gestational diabetes.
Australian New Zealand Clinical Trials Registry - ACTRN12612000621819
Gestational diabetes mellitus; Reminder system; SMS text reminder; Randomised controlled trial; Postpartum care; Oral glucose tolerance test; Type 2 diabetes mellitus
Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks’ gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages.
The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks’ gestation reduces the risk of death or cerebral palsy in their children at two years’ corrected age.
Design: Randomised, multicentre, placebo controlled trial.
Inclusion criteria: Women, giving informed consent, at risk of preterm birth between 30 to 34 weeks’ gestation, where birth is planned or definitely expected within 24 hours, with a singleton or twin pregnancy and no contraindications to the use of magnesium sulphate.
Trial entry & randomisation: Eligible women will be randomly allocated to receive either magnesium sulphate or placebo.
Treatment groups: Women in the magnesium sulphate group will be administered 50 ml of a 100 ml infusion bag containing 8 g magnesium sulphate heptahydrate [16 mmol magnesium ions]. Women in the placebo group will be administered 50 ml of a 100 ml infusion bag containing isotonic sodium chloride solution (0.9%). Both treatments will be administered through a dedicated IV infusion line over 30 minutes.
Primary study outcome: Death or cerebral palsy measured in children at two years’ corrected age.
Sample size: 1676 children are required to detect a decrease in the combined outcome of death or cerebral palsy, from 9.6% with placebo to 5.4% with magnesium sulphate (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2).
Given the magnitude of the protective effect in the systematic review, the ongoing uncertainty about benefits at later gestational ages, the serious health and cost consequences of cerebral palsy for the child, family and society, a trial of magnesium sulphate for women at risk of preterm birth between 30 to 34 weeks’ gestation is both important and relevant for clinical practice globally.
Australian New Zealand Clinical Trials Registry - ACTRN12611000491965
Magnesium sulphate; Neuroprotection; Preterm birth; Randomised controlled trial; Cerebral palsy
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.
A conclusive trial outcome will provide reliable evidence of relevance for the care of women with borderline glucose intolerance in pregnancy and their infants.
Australian New Zealand Clinical Trials Registry - ACTRN12607000174482
Borderline gestational diabetes; Gestational diabetes mellitus; Randomised controlled trial; Diet; Lifestyle; Large for gestational age
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.
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).
Data analyses are expected to commence in 2011 with results publicly available in 2012.
Clinical practice guidelines are an important element of evidence-based practice. Considering an often complicated body of evidence can be problematic for guideline developers, who in the past may have resorted to using levels of evidence of individual studies as a quasi-indicator for the strength of a recommendation. This paper reports on the production and trial of a methodology and associated processes to assist Australian guideline developers in considering a body of evidence and grading the resulting guideline recommendations.
In recognition of the complexities of clinical guidelines and the multiple factors that influence choice in health care, a working group of experienced guideline consultants was formed under the auspices of the Australian National Health and Medical Research Council (NHMRC) to produce and pilot a framework to formulate and grade guideline recommendations. Consultation with national and international experts and extensive piloting informed the process.
The FORM framework consists of five components (evidence base, consistency, clinical impact, generalisability and applicability) which are used by guideline developers to structure their decisions on how to convey the strength of a recommendation through wording and grading via a considered judgement form. In parallel (but separate from the grading process) guideline developers are asked to consider implementation implications for each recommendation.
The framework has now been widely adopted by Australian guideline developers who find it to be a logical and intuitive way to formulate and grade recommendations in clinical practice guidelines.
Recruitment of eligible participants remains one of the biggest challenges to successful completion of randomised controlled trials (RCTs). Only one third of trials recruit on time, often requiring a lengthy extension to the recruitment period. We identified factors influencing recruitment success and potentially effective recruitment strategies.
We searched MEDLINE and EMBASE from 1966 to December Week 2, 2006, the Cochrane Library Methodology Register in December 2006, and hand searched reference lists for studies of any design which focused on recruitment to maternal/perinatal trials, or if no studies of maternal or perinatal research could be identified, other areas of healthcare. Studies of nurses' and midwives' attitudes to research were included as none specifically about trials were located. We synthesised the data narratively, using a basic thematic analysis, with themes derived from the literature and after discussion between the authors.
Around half of the included papers (29/53) were specific to maternal and perinatal healthcare. Only one study was identified which focused on factors for maternal and perinatal clinicians and only seven studies considered recruitment strategies specific to perinatal research. Themes included: participant assessment of risk; recruitment process; participant understanding of research; patient characteristics; clinician attitudes to research and trials; protocol issues; and institutional or organisational issues. While no reliable evidence base for strategies to enhance recruitment was identified in any of the review studies, four maternal/perinatal primary studies suggest that specialised recruitment staff, mass mailings, physician referrals and strategies targeting minority women may increase recruitment. However these findings may only be applicable to the particular trials and settings studied.
Although factors reported by both participants and clinicians which influence recruitment were quite consistent across the included studies, studies comparing different recruitment strategies were largely missing. Trials of different recruitment strategies could be embedded in large multicentre RCTs, with strategies tailored to the factors specific to the trial and institution.
The aims of this study were to assess women's knowledge and experiences of dental health in pregnancy and to examine the self-care practices of pregnant women in relation to their oral health.
Women in the postnatal ward at the Women's and Children's Hospital, Adelaide, completed a questionnaire to assess their knowledge, attitudes and practices to periodontal health. Pregnancy outcomes were collected from their medical records. Results were analysed by chi-square tests, using SAS.
Of the 445 women enrolled in the survey, 388 (87 per cent) completed the questionnaire. Most women demonstrated reasonable knowledge about dental health. There was a significant association between dental knowledge and practices with both education and socio-economic status. Women with less education and lower socio-economic status were more likely to be at higher risk of poor periodontal health compared with women with greater levels of education and higher socioeconomic status.
Most women were knowledgeable about oral and dental health. Lack of knowledge about oral and dental health was strongly linked to women with lower education achievements and lower socioeconomic backgrounds. Whether more intensive dental health education in pregnancy can lead to improved oral health and ultimately improved pregnancy outcomes requires further study.
Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract.
Methods and Findings
We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item.
CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help authors of abstracts of these trials provide the detail and clarity needed by readers wishing to assess a trial's validity and the applicability of its results.
The authors extend the CONSORT Statement to develop a minimum list of essential items to consider when reporting the results of a randomized trial in any journal or conference abstract.
To assess the quality of Cochrane reviews.
Ten methodologists affiliated with the Cochrane Collaboration independently examined, in a semistructured way, the quality of reviews first published in 1998. Each review was assessed by two people; if one of them noted any major problems, they agreed on a common assessment. Predominant types of problem were categorised.
Cyberspace collaboration coordinated from the Nordic Cochrane Centre.
All 53 reviews first published in issue 4 of the Cochrane Library in 1998.
Main outcome measure
Proportion of reviews with various types of major problem.
No problems or only minor ones were found in most reviews. Major problems were identified in 15 reviews (29%). The evidence did not fully support the conclusion in nine reviews (17%), the conduct or reporting was unsatisfactory in 12 reviews (23%), and stylistic problems were identified in 12 reviews (23%). The problematic conclusions all gave too favourable a picture of the experimental intervention.
Cochrane reviews have previously been shown to be of higher quality and less biased on average than other systematic reviews, but
improvement is always possible. The Cochrane Collaboration has taken steps to improve editorial processes and the quality of its reviews. Meanwhile, the Cochrane Library remains a key source of evidence about the effects of healthcare interventions. Its users should interpret reviews cautiously, particularly those with conclusions favouring experimental interventions and those with many typographical errors.
What is already known on this topicCochrane reviews are, on average, more systematic and less biased than systematic reviews published in paper journalsErrors and biases also occur in Cochrane reviewsWhat this study addsToo often, reviewers' conclusions over-rated the benefits of new interventionsReaders of Cochrane reviews should remain cautious, especially regarding conclusions that favour new interventionsThe Cochrane Collaboration has taken steps to improve the quality of reviews