Recurrent spontaneous early pregnancy loss and low dose aspirin

Miscarriage is the most common complication of pregnancy, occurring in 10-15% of pregnant women. Accurate figures on prevalence are not available but it has been estimated that 2-5% of women have 3 or more miscarriages. The lack of methodological rigour in controlled trials of treatment efficacy in women with recurrent miscarriage makes it difficult to estimate the efficacy of treatment for this condition. To date, there is no evidence of improved outcome with aspirin compared to placebo or no treatment. Furthermore, animal data and limited human data suggest that prenatal use of aspirin may be associated with increased bleeding tendency, congenital malformations and cognitive and behavioural defects in the offspring. Seen and considered the lack of efficacy of low-dose aspirin and the potential for harm to the female and her offspring, the practice of recommending aspirin to women with recurrent miscarriage should be discontinued.     

A randomised trial comparing low dose vaginal misoprostol and dinoprostone for labour induction

Objective   To compare vaginal misoprostol with dinoprostone for induction of labour.
Design   Randomised multicentre trial.
Setting   Labour wards of one university hospital and two teaching hospitals.
Population   Six hundred and eighty-one women with indication for labour induction at ≥36 weeks of gestation, singleton pregnancy and no previous ceasarean section.
Methods   Misoprostol (25 mcg, hospital-prepared capsule) in the posterior vaginal fornix, every four hours, maximum three times daily or dinoprostone gel (1 mg) every four hours. Oxytocin was administered if necessary.
Main outcome measures   Primary: 'adverse neonatal outcome' (5-minute Apgar score <7 and/or umbilical cord pH <7.15). Secondary: labour duration, mode of delivery and patient satisfaction.
Results   Three hundred and forty-one women received misoprostol and 340 dinoprostone. The median induction–delivery interval was longer in the misoprostol group compared with the dinoprostone group (25 versus 19 hours, P = 0.008). The caesarean section rate was lower in the misoprostol group: 16.1% versus 21%, but this difference was not statistically significant RR = 0.8 (95% CI 0.6–1.04). 'Adverse neonatal outcome' was found to be similar in both groups: 21% in the misoprostol and 23% in the dinoprostone groups. Significantly fewer neonates were admitted to NICU in the misoprostol group compared with dinoprostone 19% versus 26% (RR = 0.7, 95% CI 0.5–0.98).
Conclusions   Misoprostol in this dosing regimen is a safe method of labour induction. NICU admission rates were lower in the misoprostol group. No difference could be detected in patient satisfaction between groups.     

ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women

Objective To determine the effectiveness of low dose aspirin in women at high risk of adverse outcomes associated with pre-eclampsia.
Design A collaborative randomised trial comparing the effects of low dose aspirin (60 mg) with placebo on pre-eclampsia and other materno-fetal complications associated with hypertension.
Setting Twelve teaching maternity hospitals and 182 obstetricians' offices in Brazil.
Subjects One thousand and nine women considered to be at high risk for the development of pre-eclampsia, or its complications, entered the study between 12 and 32 weeks of gestation. They were randomly allocated to receive aspirin (498 women) or placebo (511 women) until delivery, and follow up was obtained for 96%.
Results There were no significant differences between the treatment groups in the incidence of proteinuric pre-eclampsia (6.7% aspirin-allocated compared with 6–0% placebo-allocated women), of preterm delivery (22.3% compared with 26.1%), of intrauterine growth retardation (8.5% compared with 10.1%), or of stillbirth and neonatal death (7.3% compared with 6.0%), nor were there significant differences in the incidence of proteinuric pre-eclampsia in any subgroup of women studied, including those who had systolic blood pressures of 120 mmHg or above at entry (8.5% compared with 7.3%) or those who were chronically hypertensive (10.0% compared with 7.1%). Aspirin was not associated with a significant excess of maternal or fetal bleeding.
Conclusion The results of this study do not support the routine prophylactic administration of low dose aspirin in pregnancy to any category of high risk women (even those who have chronic hypertension or who are considered to be especially liable to early onset pre-eclampsia).     

A trial of low-dose aspirin therapy in high-risk pregnancy]

Intra-uterine growth retardation, intra-uterine fetal death and pre-eclampsia have common abnormalities: A reduction of uteroplacental perfusion, lack of vasodilation of spiral arteries and subsequent thrombosis. These physiological processes have been explained by an imbalance between prostacyclin and thromboxane A2 production. Many studies have suggested that treatment with low-dose aspirin and steroids is effective in preventing pregnancy loss or pre-eclampsia, but the mechanism has not been established. We evaluated the effectiveness of these therapies in patients at risk for pregnancy loss with the aspect of intracellular ionized calcium mobilization. Low-dose aspirin directs the prostacyclin/thromboxane A2 balance to the dominance of prostacyclin and steroids suppress the activities of lupus anticoagulant or antiphospholipid antibodies. The intracellular ionized calcium concentration in platelets is decreased significantly after these therapies. Concerning the pathological examination of placenta, there were deposits of fibrin in only 2 out of 8 cases and there were no abnormal findings in the other 6 cases. These data show that the aggregation of platelets is suppressed in microvascular circulations. These therapies do not cause any adverse effect on the mother or fetus. It is concluded that low-dose aspirin therapy with steroids is useful for patients with a poor obstetrical history.     

A randomised controlled trial comparing low dose vaginal misoprostol and dinoprostone vaginal gel for inducing labour at term

OBJECTIVE: To compare the efficacy of low dose vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term. DESIGN: A single-blind randomised controlled trial. SETTING: Antenatal and labour ward of a UK district general hospital. PARTICIPANTS: Two hundred and sixty-eight women requiring induction of labour at term (>37 weeks of gestation) with no significant fetal or medical condition, no previous uterine surgery and no contraindication to prostaglandin. METHODS: Misoprostol 25 microg (one-quarter of a 100 microg tablet) was inserted into the posterior vaginal fornix every 4 hours (to a maximum of six doses) or dinoprostone vaginal gel 1-2 mg 6 hourly (maximum of 3 mg in 24 hours). MAIN OUTCOME MEASURE: Induction-to-vaginal delivery interval. SECONDARY OUTCOME MEASURES: Requirements for oxytocin, mode of delivery, number of women delivering < 24 hours, incidence of uterine contraction abnormalities, incidence of abnormal cardiotocograph (CTG) recordings, 5-minute Apgar scores, umbilical cord pH recordings, analgesia requirements, admission to NICU and blood loss at delivery. RESULTS: There were no significant differences between the two groups in induction-to-vaginal delivery interval, mode of delivery, number of women delivering within 24 hours and neonatal outcomes. The incidence of uterine contraction abnormalities (tachysystole and hyperstimulation) and the incidence of abnormal CTG recordings were also similar for both groups. CONCLUSION: Low dose vaginal misoprostol is as effective as dinoprostone gel for inducing labour at term. There would be substantial cost savings, estimated at around 3.9 million UK pounds per annum, for maternity services if low dose misoprostol became the agent of choice for inducing labour in the UK.     

A meta-analysis of low dose aspirin for the prevention of intrauterine growth retardation

Objective To determine more precisely the effect of prophylactic low dose aspirin on intrauterine growth retardation and perinatal mortality.
Design Meta-analysis of 13 published randomised clinical trials.
Methods We searched 18 medical databases, including MEDLINE since 1964 and EMBASE since 1974, review articles and the references from each retrieved report to identify all studies evaluating the effect of aspirin in pregnancy and including both intrauterine growth retardation and perinatal mortality as outcome measures.
Results Among 13,234 women from 13 studies between 1985 and 1994, aspirin showed a significant reduction in intrauterine growth retardation (IUGR) (OR 0.82; 95% CI 0.72–0.93;   P = 0.003  ) and a nonsignificant reduction in perinatal mortality (OR 0.84; 95% CI 0.66–1.08;   P = 0.18  ). Subgroup analyses revealed that aspirin was effective at lower doses between 50 and 80 mg/day (IUGR: OR 0.87; 95% CI 0.76–0.99; mortality: OR 0.90, 95% CI 0.70–1.16), but that the preventive effect was greater at higher doses between 100 and 150 mg/day (IUGR: OR 0.36, 95% CI 0.22–0.59; mortality: OR 0.40, 95% CI 0.16–0.97) and among women entered before the 17th week of gestation (IUGR: OR 0.35, 95% CI 0.21–0.58; mortality: OR 0.43, 95% CI 0.17–1.06). We did not identify any specific subgroup of women most likely to benefit from aspirin treatment.
Conclusion The results of this meta-analysis showed that early aspirin treatment reduced the risk of intrauterine growth retardation. Low dose aspirin should not be used routinely in pregnant women until those most likely to benefit from aspirin treatment have been clearly identified.     

Bemiparin versus low dose aspirin for management of recurrent early pregnancy losses due to antiphospholipd antibody syndrome

Study objective  

To compare the live birth rate of women presented with recurrent miscarriages in the first trimester due to antiphospholipid antibody syndrome (APS), randomized to either low molecular weight heparin (Bemiparin) or low dose aspirin (LDA) and to determine the maternal and fetal adverse effects in both treatment groups.     

A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia

OBJECTIVE: To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition. STUDY DESIGN: Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up. RESULTS: The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%). CONCLUSION: These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR.     

A pilot randomised controlled trial (RCT) investigating the effectiveness of reflexology for managing pregnancy low back and/or pelvic pain

Many pregnant women with low back and/or pelvic pain (LBPP) use pain medications to manage this pain, much of which is self-prescribed and potentially harmful. Therefore, there is a need to find effective nonpharmacological treatments for the condition. Reflexology has previously been shown to help nonspecific low back pain. Therefore; a pilot RCT was conducted investigating reflexology in the management of pregnancy-LBPP. 90 primiparous women were randomised to either usual care, a reflexology or footbath intervention. Primary outcome measures were; the Pain Visual Analogue Scale (VAS). 64 women completed the RCT; retention rates for the reflexology group were 80%, usual care group 83.33% and footbath group 50%. The reflexology group demonstrated a Clinically Important Change (CIC) in pain frequency (1.64 cm). Results indicate it is feasible to conduct an RCT in this area, although a footbath is an unsuitable sham treatment. Reflexology may help manage pregnancy-LBPP; however a fully powered trial is needed to confirm this.     

A randomised comparison of hydralazine and mini-bolus diazoxide for hypertensive emergencies in pregnancy: the PIVOT trial

AIMS: Diazoxide is one of few available agents for treatment of hypertensive emergencies in pregnancy. From previous studies, there is a question concerning safety after moderate-dose administration caused episodes of hypotension. Rapid control of severe hypertension is necessary to reduce maternal morbidity, for example, stroke and placental abruption. This study was designed to compare the efficacy of mini-bolus diazoxide with intravenous (i.v.) hydralazine. DESIGN: A randomised controlled trial. SETTING: Tertiary referral maternity hospital, Royal Prince Alfred Women and Babies, Sydney Australia. POPULATION: Antenatal and postnatal women with severe hypertension. METHODS: One hundred and twenty-four hypertensive women were randomised to either i.v. hydralazine (5 mg doses) or mini-bolus diazoxide (15 mg doses). PRIMARY OUTCOME MEASURE: Achievement of target blood pressure reduction; secondary measures included requirement for Caesarean section because of fetal deterioration as determined by non-reassuring cardiotocograph (CTG). RESULTS: Reduction in systolic and diastolic blood pressure was 34 min for hydralazine and 19 min for diazoxide (P < 0.001). There were no episodes of hypotension after diazoxide and one after hydralazine (after epidural). Episodes of persistent severe hypertension were more common with hydralazine (38%) than with diazoxide (16%), P < 0.01. The Caesarean section rate for no-reassuring CTG was no different between the two groups. Neonatal outcomes were similar. CONCLUSION: Diazoxide and hydralazine are safe and effective antihypertensives, showing a controlled and comparable blood pressure reduction in women with hypertensive emergencies in pregnancy. The mini-bolus doses of 15 mg of diazoxide did not precipitate maternal hypotension as previously described and reduces episodes of persistent severe hypertension.     

A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception

Objective To compare 100 mg mifepristone with the standard Yuzpe regimen for emergency contraception.
Design Randomised controlled trial.
Setting Family Planning Clinic, Aberdeen.
Sample One thousand women seeking emergency contraception within 72 hours after an episode of unprotected sexual intercourse.
Methods Women were randomised to receive either 100 mg (half tablet) of mifepristone as a single dose or the Yuzpe regimen (two tablets each with 50 μg ethinyloestradiol and 0.25 mg levonorgestrel, to be repeated 12 hours later).
Outcome measures Crude pregnancy rates, proportion of pregnancies prevented, side effects and patient acceptability.
Results The crude pregnancy rates (95% CI) for the Yuzpe regimen and mifepristone were 3.6% (2.3–5.7) and 0.6% (0.2–1.8), respectively, with a significant difference between the two groups (RR 6.04; 95% CI 1.75–20.75). Mifepristone prevented 92% of pregnancies and the Yuzpe regimen preventing 56%. An increasing coitus to treatment interval was associated with contraceptive failure in the Yuzpe group (   P = 0.03  ) with no association seen with mifepristone. Following administration of mifepristone 24.5% and 13.1% given the Yuzpe regimen had a delayed period (RR 2.14; 95% CI 1.46–3.15). Overall, mifepristone was better tolerated than the Yuzpe regimen with significantly fewer side effects. More women were satisfied (   P < 0.0001  ) with mifepristone as an emergency contraceptive and would recommend it to a friend (   P = 0.02  ).
Conclusion Mifepristone administered in a 100 mg dose is a highly effective post-coital contraceptive with high patient acceptability and fewer side effects compared with the standard Yuzpe regimen. Delay in the onset of menstruation did not decrease patient acceptability.