It remains unclear whether one corticosteroid (or one particular regimen) has advantages over another.Dexamethasone may have some benefits compared with betamethasone such as less IVH, and a shorter length of stay in the NICU. The intramuscular route may have advantages over the oral route for dexamethasone, as identified in one small trial. Apart from the suggestion that 12-hour dosing may be as effective as 24-hour dosing of betamethasone based on one small trial, few other conclusions about optimal antenatal corticosteroid regimens were able to be made. No long-term results were available except for a small subgroup of 18 month old children in one trial. Trials comparing the commonly used corticosteroids are most urgently needed, as are trials of dosages and other variations in treatment regimens.

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BackgroundVenous thromboembolism (VTE), although rare, is a major cause of maternal mortality and morbidity, and methods of prophylaxis are therefore often used for women considered to be at risk. This may include women who have given birth by caesarean section, those with a personal or family history of VTE and women with inherited or acquired thrombophilias (conditions that predispose people to thrombosis). Many methods of prophylaxis carry risks of adverse effects, and as the risk of VTE is often low, it is possible that the benefits of thromboprophylaxis may be outweighed by harms. Guidelines for clinical practice have been based on expert opinion rather than high-quality evidence from randomised trials. ObjectivesTo assess the effects of thromboprophylaxis in women who are pregnant or have recently given birth and are at increased risk of VTE on the incidence of VTE and adverse effects of treatment. Search methodsWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 November 2013). Selection criteriaRandomised trials comparing one method of thromboprophylaxis with placebo or no treatment, and randomised trials comparing two (or more) methods of thromboprophylaxis. Data collection and analysisAt least two review authors assessed trial eligibility and quality and extracted the data.1 Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period (Review)

BackgroundOver the last decade there has been enhanced awareness of the appreciable morbidity of thyroid dysfunction, particularly thyroid deficiency. Since treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes, it is crucial to identify which interventions are safe and effective. ObjectivesTo identify interventions used in the management of hypothyroidism and subclinical hypothyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes. Search methodsWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2013). Selection criteriaRandomised controlled trials (RCTs) and quasi-randomised controlled trials that compared a pharmacological intervention for hypothyroidism and subclinical hypothyroidism pre-pregnancy or during pregnancy with another intervention or placebo. Data collection and analysisTwo review authors assessed trial eligibility and quality and extracted the data. Main resultsWe included four RCTs of moderate risk of bias involving 362 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid (normal thyroid function) women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). Two trials of 30 and 48 hypothyroid women respectively compared levothyroxine doses, but both trials 1 Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy (Review)

Based on the existing evidence, though universal screening for thyroid dysfunction in pregnancy increases the number of women diagnosed with hypothyroidism who can be subsequently treated, it does not clearly impact (benefit or harm) maternal and infant outcomes.While universal screening versus case finding for thyroid dysfunction increased diagnosis and subsequent treatment, we found no clear differences for the primary outcomes: pre-eclampsia or preterm birth. No clear differences were seen for secondary outcomes, including miscarriage and fetal or neonatal death; data were lacking for the primary outcome: neurosensory disability for the infant as a child, and for many secondary outcomes. Though universal screening versus no screening for hypothyroidism similarly increased diagnosis and subsequent treatment, no clear difference was seen for the primary outcome: neurosensory disability for the infant as a child (IQ < 85 at three years); data were lacking for the other primary outcomes: pre-eclampsia and preterm birth, and for the majority of secondary outcomes.For outcomes assessed using the GRADE approach the evidence was considered to be moderate or high quality, with any downgrading of the evidence based on the presence of wide confidence intervals crossing the line of no effect.More evidence is needed to assess the benefits or harms of different screening methods for thyroid dysfunction in pregnancy, on maternal, infant and child health outcomes. Future trials should assess impacts on use of health services and costs, and be adequately powered to evaluate the effects on short- and long-term outcomes.

BackgroundStrong evidence supports administration of magnesium sulphate prior to birth at less than 30 weeks’ gestation to prevent very preterm babies dying or developing cerebral palsy. This study was undertaken as part of The WISH (Working to Improve Survival and Health for babies born very preterm) Project, to assess health professionals’ self-reported use of antenatal magnesium sulphate, and barriers and enablers to implementation of 2010 Australian and New Zealand clinical practice guidelines.MethodsSemi-structured, one-to-one interviews were conducted with obstetric and neonatal consultants and trainees, and midwives in 2011 (n = 24) and 2012–2013 (n = 21) at the Women’s and Children’s Hospital, South Australia. Transcribed interview data were coded using the Theoretical Domains Framework (describing 14 domains related to behaviour change) for analysis of barriers and enablers.ResultsIn 2012–13, health professionals more often reported ‘routinely’ or ‘sometimes’ administering or advising their colleagues to administer magnesium sulphate for fetal neuroprotection (86 % in 2012–13 vs. 46 % in 2011). ‘Knowledge and skills’, ‘memory, attention and decision processes’, ‘environmental context and resources’, ‘beliefs about consequences’ and ‘social influences’ were key domains identified in the barrier and enabler analysis. Perceived barriers were the complex administration processes, time pressures, and the unpredictability of preterm birth. Enablers included education for staff and women at risk of very preterm birth, reminders and ‘prompts’, simplified processes for administration, and influential colleagues.ConclusionsThis study has provided valuable data on barriers and enablers to implementing magnesium sulphate for fetal neuroprotection, with implications for designing and modifying future behaviour change strategies, to ensure optimal uptake of this neuroprotective therapy for very preterm infants.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-015-0618-9) contains supplementary material, which is available to authorized users.

BackgroundAntenatal 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.MethodsBibliographic 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.ResultsA 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.ConclusionsAppropriate 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.

Objective: To report a case of delayed methotrexate (MTX) elimination while receiving concomitant levetiracetam. Case Report: A 46-year-old man with relapsed osteosarcoma of the base of the skull receiving high-dose MTX tolerated his first cycle of MTX with elimination to nontoxic MTX levels (≤0.1 µmol/L) within 90 hours. After hospital discharge, the patient experienced seizures secondary to brain metastasis and started on levetiracetam, which was continued as maintenance therapy. The patient experienced delayed MTX elimination during cycles 2, 3, and 4 while receiving levetiracetam. On average, elimination to nontoxic MTX levels took 130 hours (106-144 hours). Before the fifth cycle of MTX, lorazepam was substituted for the levetiracetam. MTX was eliminated to nontoxic levels within 95 hours. During all cycles, the patient received standard supportive care and serum creatinine remained stable. No other drugs known to interact with MTX were administered. Discussion: This possible drug interaction has only been reported once in the pediatric population. With a score of 6 on the Drug Interaction Probability Scale for evaluating causation of drug interactions, it is probable that the delayed MTX elimination was caused by an interaction with levetiracetam. Conclusion: Coadministration of levetiracetam and MTX may result in delayed elimination of MTX, increasing the likelihood of toxicity. Consideration should be given to temporarily switching from levetiracetam to another antiepileptic (ie, lorazepam) to prevent this interaction. This is particularly important in those experiencing delayed elimination with prior cycles of concomitant MTX and levetiracetam or those at greater risk for MTX toxicity.