Adverse outcomes of Chinese medicines used for threatened miscarriage: a systematic review and meta-analysis.

BACKGROUND: Threatened miscarriage is very common in early pregnancy. Chinese medicines have been widely used to prevent spontaneous pregnancy loss. However, the safety of Chinese medicines is still unknown. A systematic review was performed to identify and describe adverse events of Chinese medicines used for threatened miscarriage. METHODS: Clinical studies of Chinese medicines for threatened miscarriage were selected. Primary outcomes were occurrence of adverse effects or toxicity of Chinese medicines. Secondary outcomes were failure of treatment and adverse pregnancy and perinatal outcomes. RESULTS: Thirty-two relevant articles included 9 randomized controlled trials, 1 quasi-randomized controlled trial and 2 controlled trials comparing Chinese medicines alone or combined medicines with pharmaceuticals and 20 case series with no controls. Sample sizes of each study were generally small. There was variation in Chinese medicine formulation, dosage and duration of treatment. In the pooled randomized controlled trials, dry mouth, constipation and insomnia (2-10%) and intervention failure (3.1-22.3%), diabetic complications (3%), preterm delivery (5%) and neurodevelopmental morbidity (1.8%) were recorded. Meta-analysis demonstrated that intervention failure was significantly lower in the combined Chinese medicines groups than in the Western medicines controls (relative risk = 0.46; 95% confidence interval: 0.30-0.70, I(2)= 0%). No significant differences were found between these groups for adverse effects and toxicity or for adverse pregnancy and perinatal outcomes. CONCLUSIONS: Studies varied considerably in design, interventions and outcome measures, therefore conclusive results remain elusive. In the absence of placebo-controlled trials, the safety of Chinese medicines for the treatment of threatened miscarriage is unknown. Rigorous scientific and clinical studies to assess the possible risks of Chinese medicines are needed.

Pain management for women in labour: an overview of systematic reviews.

BACKGROUND: The pain that women experience during labour is affected by multiple physiological and psychosocial factors and its intensity can vary greatly.  Most women in labour require pain relief. Pain management strategies include non-pharmacological interventions (that aim to help women cope with pain in labour) and pharmacological interventions (that aim to relieve the pain of labour). OBJECTIVES: To summarise the evidence from Cochrane systematic reviews on the efficacy and safety of non-pharmacological and pharmacological interventions to manage pain in labour. We considered findings from non-Cochrane systematic reviews if there was no relevant Cochrane review. METHODS: We searched the Cochrane Database of Systematic Reviews (The Cochrane Library 2011, Issue 5), The Cochrane Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 31 May 2011) and EMBASE (1974 to 31 May 2011) to identify all relevant systematic reviews of randomised controlled trials of pain management in labour. Each of the contributing Cochrane reviews (nine new, six updated) followed a generic protocol with 13 common primary efficacy and safety outcomes. Each Cochrane review included comparisons with placebo, standard care or with a different intervention according to a predefined hierarchy of interventions. Two review authors extracted data and assessed methodological quality, and data were checked by a third author. This overview is a narrative summary of the results obtained from individual reviews. MAIN RESULTS: We identified 15 Cochrane reviews (255 included trials) and three non-Cochrane reviews (55 included trials) for inclusion within this overview. For all interventions, with available data, results are presented as comparisons of: 1. Intervention versus placebo or standard care; 2. Different forms of the same intervention (e.g. one opioid versus another opioid); 3. One type of intervention versus a different type of intervention (e.g. TENS versus opioid). Not all reviews included results for all comparisons. Most reviews compared the intervention with placebo or standard care, but with the exception of opioids and epidural analgesia, there were few direct comparisons between different forms of the same intervention, and even fewer comparisons between different interventions. Based on these three comparisons, we have categorised interventions into: " What works" ,"What may work", and "Insufficient evidence to make a judgement".WHAT WORKSEvidence suggests that epidural, combined spinal epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve pain when compared with placebo or a different type of intervention (epidural versus opioids). Combined-spinal epidurals relieve pain more quickly than traditional or low dose epidurals. Women receiving inhaled analgesia were more likely to experience vomiting, nausea and dizziness.When compared with placebo or opioids, women receiving epidural analgesia had more instrumental vaginal births and caesarean sections for fetal distress, although there was no difference in the rates of caesarean section overall. Women receiving epidural analgesia were more likely to experience hypotension, motor blockade, fever or urinary retention. Less urinary retention was observed in women receiving CSE than in women receiving traditional epidurals. More women receiving CSE than low-dose epidural experienced pruritus.  WHAT MAY WORKThere is some evidence to suggest that immersion in water, relaxation, acupuncture, massage and local anaesthetic nerve blocks or non-opioid drugs may improve management of labour pain, with few adverse effects.  Evidence was mainly limited to single trials. These interventions relieved pain and improved satisfaction with pain relief (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids) and childbirth experience (immersion, relaxation, non-opioids) when compared with placebo or standard care. Relaxation was associated with fewer assisted vaginal births and acupuncture was associated with fewer assisted vaginal births and caesarean sections.INSUFFICIENT EVIDENCEThere is insufficient evidence to make judgements on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, TENS, or parenteral opioids are more effective than placebo or other interventions for pain management in labour. In comparison with other opioids more women receiving pethidine experienced adverse effects including drowsiness and nausea.  AUTHORS' CONCLUSIONS: Most methods of non-pharmacological pain management are non-invasive and appear to be safe for mother and baby, however, their efficacy is unclear, due to limited high quality evidence. In many reviews, only one or two trials provided outcome data for analysis and the overall methodological quality of the trials was low. High quality trials are needed.There is more evidence to support the efficacy of pharmacological methods, but these have more adverse effects. Thus, epidural analgesia provides effective pain relief but at the cost of increased instrumental vaginal birth.It remains important to tailor methods used to each woman's wishes, needs and circumstances, such as anticipated duration of labour, the infant's condition, and any augmentation or induction of labour.A major challenge in compiling this overview, and the individual systematic reviews on which it is based, has been the variation in use of different process and outcome measures in different trials, particularly assessment of pain and its relief, and effects on the neonate after birth. This made it difficult to pool results from otherwise similar studies, and to derive conclusions from the totality of evidence. Other important outcomes have simply not been assessed in trials; thus, despite concerns for 30 years or more about the effects of maternal opioid administration during labour on subsequent neonatal behaviour and its influence on breastfeeding, only two out of 57 trials of opioids reported breastfeeding as an outcome. We therefore strongly recommend that the outcome measures, agreed through wide consultation for this project, are used in all future trials of methods of pain management.

The use of transcutaneous electrical nerve stimulation (TENS) for pain relief in labour: a review of the evidence.

OBJECTIVE: to assess the effects of transcutaneous electrical nerve stimulation (TENS) for pain relief in labour. SEARCH METHODS: studies were identified from a search of the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2008). SELECTION CRITERIA: randomised controlled trials comparing women receiving TENS for pain relief in labour vs routine care or placebo devices. All types of TENS machines were included. DATA COLLECTION AND ANALYSIS: two review authors assessed all trials identified by the search strategy, carried out data extraction and assessed risk of bias. RESULTS: 14 studies including 1256 women were included: 11 examined TENS applied to the back, two to acupuncture points and one to the cranium. Overall, there was little difference in satisfaction with pain relief or in pain ratings between TENS and control groups, although women receiving TENS to acupuncture points were less likely to report severe pain (risk ratio 0.41, 95% confidence interval 0.32-0.55). The majority of women using TENS would use it again in a future labour. There was no evidence that TENS had any impact on interventions and outcomes in labour. There was little information on outcomes for mothers and infants. No adverse events were reported. CONCLUSIONS: there is only limited evidence that TENS reduces pain in labour and it does not seem to have any impact on other outcomes for mothers or infants. The use of TENS at home in early labour has not been evaluated. Although the guidelines of the National Institute for Health and Clinical Excellence recommend that TENS should not be offered to women in labour, women appear to be choosing it and midwives are supporting them in their choice. Given the absence of adverse effects and the limited evidence base, it seems unreasonable to deny women that choice. More robust studies of effectiveness are needed.

Vitamin A supplementation during pregnancy for maternal and newborn outcomes.

BACKGROUND: The World Health Organization recommends routine vitamin A supplementation during pregnancy or lactation in areas with endemic vitamin A deficiency (where night blindness occurs), based on the expectation that supplementation will improve maternal and newborn outcomes including mortality, morbidity and prevention of anaemia or infection.   OBJECTIVES: To review the effects of supplementation of vitamin A, or one of its derivatives, during pregnancy, alone or in combination with other vitamins and micronutrients, on maternal and newborn clinical outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 July 2010). SELECTION CRITERIA: All randomised or quasi-randomised trials, including cluster-randomised trials, evaluating the effect of vitamin A supplementation in pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all studies for inclusion and resolved any disagreement through discussion with a third person. We used pre-prepared data extraction sheets. MAIN RESULTS: We examined 88 reports of 31 trials, published between 1931 and 2010, for inclusion in this review. We included 16 trials, excluded 14, and one is awaiting assessment.Overall when trial results are pooled, Vitamin A supplementation does not affect the risk of maternal mortality (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.55 to 1.10, 3 studies, Nepal, Ghana,UK ), perinatal mortality, neonatal mortality, stillbirth, neonatal anaemia, preterm birth or the risk of having a low birthweight baby. Vitamin A supplementation reduces the risk of maternal night blindness (risk ratio (RR) 0.70, 95% CI 0.60 to 0.82, 1 trial Nepal). In vitamin A deficient populations and HIV-positive women, vitamin A supplementation reduces maternal anaemia (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.43 to 0.94, 3 trials, Indonesia, Nepal,Tanzania ). There is evidence that vitamin A supplements may reduce maternal clinical infection (RR 0.37, 95% CI 0.18 to 0.77, 3 trials, South Africa, Nepal and UK).In HIV-positive women vitamin A supplementation given with other micronutrients was associated with fewer low birthweight babies (< 2.5 kg) in the supplemented group in one study (RR 0.67, CI 0.47 to 0.96). AUTHORS' CONCLUSIONS: The pooled results of two large trials in Nepal and Ghana (with almost 95,000 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality.

Transcutaneous electrical nerve stimulation (TENS) for pain relief in labour.

BACKGROUND: Transcutaneous nerve stimulation (TENS) has been proposed as a means of reducing pain in labour. The TENS unit emits low-voltage electrical impulses which vary in frequency and intensity. During labour, TENS electrodes are generally placed on the lower back, although TENS may be used to stimulate acupuncture points or other parts of the body. The physiological mechanisms whereby TENS relieves pain are uncertain. The TENS unit is frequently operated by women, which may increase sense of control in labour. OBJECTIVES: To assess the effects of TENS on pain in labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2008). SELECTION CRITERIA: Randomised controlled trials comparing women receiving TENS for pain relief in labour versus routine care, alternative pharmacological methods of pain relief, or placebo devices. We included all types of TENS machines. DATA COLLECTION AND ANALYSIS: Two review authors assessed for inclusion all trials identified by the search strategy, carried out data extraction and assessed risk of bias. We have recorded reasons for excluding studies. MAIN RESULTS: The search identified 25 studies; we excluded six and included 19 studies including 1671 women. Fifteen examined TENS applied to the back, two to acupuncture points and two to the cranium. Overall, there was little difference in pain ratings between TENS and control groups, although women receiving TENS to acupuncture points were less likely to report severe pain (risk ratio 0.41, 95% confidence interval 0.32 to 0.55). The majority of women using TENS said they would be willing to use it again in a future labour. Where TENS was used as an adjunct to epidural analgesia there was no evidence that it reduced pain. There was no consistent evidence that TENS had any impact on interventions and outcomes in labour. There was little information on outcomes for mothers and babies. No adverse events were reported. AUTHORS' CONCLUSIONS: There is only limited evidence that TENS reduces pain in labour and it does not seem to have any impact (either positive or negative) on other outcomes for mothers or babies. The use of TENS at home in early labour has not been evaluated. TENS is widely available in hospital settings and women should have the choice of using it in labour.

Cochrane Update: Effect of timing of umbilical cord clamping at birth of term infants on mother and baby outcomes.

BACKGROUND: Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord greater than one minute after the birth or when cord pulsation has ceased. OBJECTIVES: To determine the effects of different policies of timing of cord clamping at delivery of the placenta on maternal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Child Birth Group's Trials Register (December 2007). SELECTION CRITERIA: Randomized controlled trials comparing early and late cord clamping. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: We included 11 trials of 2,989 mothers and their babies. No significant differences between early and late cord clamping were seen for postpartum hemorrhage or severe postpartum hemorrhage in any of the five trials (2236 women) which measured this outcome (relative risk (RR) for postpartum hemorrhage 500 mls or more 1.22, 95% (CI) 0.96 to 1.55). For neonatal outcomes, our review showed both benefits and harms for late cord clamping. Following birth, there was a significant increase in infants needing phototherapy for jaundice (RR 0.59, 95% CI 0.38 to 0.92; five trials of 1,762 infants) in the late compared with early clamping group. This was accompanied by significant increases in newborn hemoglobin levels in the late cord clamping group compared with early cord clamping (weighted mean difference 2.17 g/dL; 95% CI 0.28 to 4.06; three trials of 671 infants), although this effect did not persist past six months. Infant ferritin levels remained higher in the late clamping group than the early clamping group at six months. AUTHORS' CONCLUSION: One definition of active management includes directions to administer an uterotonic with birth of the anterior shoulder of the baby and to clamp the umbilical cord within 30-60 seconds of birth of the baby (which is not always feasible in practice). In this review delaying clamping of the cord for at least two to three minutes seems not to increase the risk of postpartum hemorrhage. In addition, late cord clamping can be advantageous for the infant by improving iron status which may be of clinical value particularly in infants where access to good nutrition is poor, although delaying clamping increases the risk of jaundice requiring phototherapy.