sample size was not large enough to produce significant P values.One trial6 showed a statistically non-significant trend towardsharm. However, with meta-analysis of all five trials, we were ableto demonstrate a statistically significant benefit of aspirin inpreventing pre-eclampsia, although our estimation of averageeffect was relatively imprecise (pooled odds ratio ¼ 0.55, 95%CI 0.32–0.95, P ¼ 0.03)2.

With the current trial1, we have updated our meta-analysis2 (seeFig. 1) and found results to be supportive of the editorialviewpoint: ‘aspirin does reduce the risk of pre-eclampsia’8. Thereis now substantial evidence that aspirin is of benefit amongwomen with abnormal uterine artery Doppler. Therefore, this testand treatment combination should now be considered for incor-poration into clinical practice in high risk women8. There is atendency for apathy among clinicians towards implementingtreatments recently shown to be effective. There are severalexamples of this; steroids for respiratory distress syndrome isonly one example. We hope this mistake will not occur withaspirin therapy to prevent pre-eclampsia in women with abnormaluterine artery Doppler.

References

1. Vainio M, Kujansuu E, Iso-Mustajarvi M, Maenpaa J. Low dose

acetylsalicylic acid in prevention of pregnancy-induced hypertension

and intrauterine growth retardation in women with bilateral uterine

artery notches. Br J Obstet Gynaecol 2002;109(2):161– 167.

2. Coomarasamy A, Papaioannou S, Gee H, Khan KS. Aspirin for the

prevention of preeclampsia in women with abnormal uterine artery

Doppler: a meta-analysis. Obstet Gynecol 2001;98:861–866.

3. McParland P, Pearce JM, Chamberlain GV. Doppler ultrasound and

aspirin in recognition and prevention of pregnancy-induced hyper-

tension. Lancet 1990;335:1552–1555.

4. Morris JM, Fay RA, Ellwood DA, Cook CM, Devonald KJ. A ran-

domized controlled trial of aspirin in patients with abnormal uterine

artery blood flow. Obstet Gynecol 1996;87:74– 78.

5. Bower SJ, Harrington KF, Schuchter K, McGirr C, Campbell S.

Prediction of pre-eclampsia by abnormal uterine Doppler ultrasound and

modification by aspirin. Br J Obstet Gynaecol 1996;103:625 –629.

6. Zimmermann P, Eirio V, Koskinen J, et al. Effect of low-dose aspirin

treatment on vascular resistance in the uterine, uteroplacental, renal and

umbilical arteries—a prospective longitudinal study on a high risk

population with persistent notch in the uterine arteries. Eur J

Ultrasound 1997;5:17– 30.

7. Harrington K, Kurdi W, Aquilina J, England P, Campbell S. A pros-

pective management study of slow-release aspirin in the palliation of

uteroplacental insufficiency predicted by uterine artery Doppler at 20

weeks. Ultrasound Obstet Gynecol 2000;15:13– 18.

8. Grant JM. Aspirin does reduce the risk of pre-eclampsia (Editor’s

Choice). Br J Obstet Gynaecol 2002;109(2):105.

A. Coomarasamy, H. Gee & K. S. KhanEducation Resource Centre, Birmingham Women’s Hospital, UK

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Sir,Vainio et al. show that low dose aspirin significantly reduces

the incidence of pregnancy-induced hypertension (especially pro-teinuric pre-eclampsia) in women considered to be at high risk,and the Editor, in his Choice, states that the ‘results are convin-cing’, implying perhaps that the findings are clinically relevant.

However, the definitions of hypertension and pre-eclampsia inthe study are the textbook minimum, and the study barely showseven a trend in the direction of benefit to mother or baby in termsof the clinically relevant risks of hypertension or pre-eclampsia,such as severe hypertension, significantly preterm delivery or

Fig. 1. Meta-analysis of randomised trials of aspirin to prevent pre-eclampsia in women with abnormal uterine artery Doppler. m2 test for heterogeneity was

not significant.

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severe intrauterine growth retardation. There were no differenceseven in the number of induced deliveries, let alone caesareansections between the aspirin and the placebo groups. The meangestational age and birthweight at delivery were over 39 weeksand greater than 3500 g in the placebo group. The number ofbabies with birthweight less than 2500 g were 3/43 and 4/43 in theaspirin and placebo groups, respectively.

The authors do not report on the severity of hypertension interms of how many women in each group required de novo anti-hypertensive medication in pregnancy (or an increase in pre-existing medication), nor do they report on the need for closermaternofetal monitoring or hospital admission.

The study shows differences that are statistically significant andacademically interesting, but which do not appear to be quiteclinically relevant, a picture very similar to that shown in thestudy by Chappell et al.1, which extolled the benefits of anti-oxidant supplementation (vitamins C and E) in the reduction ofthe incidence of pre-eclampsia in a high risk population.

Appropriately, Vainio et al. suggest that a larger, probablymulticentre, trial would be required to assess the effect of aspirinon early-onset pre-eclampsia and intrauterine growth retardation,but the virtual absence of trends with regard to these endpoints inthis study leaves room for scepticism.

It would appear that aspirin, and perhaps vitamins, can modifythe clinical course of hypertensive disease and pre-eclampsia inpregnancy slightly, but it is premature to suggest that they areeffective in reducing significantly the important causes of mater-nal and fetal morbidity and mortality.

Reference

1. Chappell LC, Seed PT, Briley AL, et al. Effects of anti oxidants in the

occurrence of pre-eclampsia in women at increased risk: a randomised

trial. Lancet 1999:354:810 –816.

John H. SmithSt Mary’s NHS Trust, London

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Can ultrasound replace ambulatory urodynamics wheninvestigating women with irritative urinary symptoms?

Sir,I read the article by Robinson et al.1 with interest. The authors

should be congratulated in completing this study on a substantialsample of women. However, I would be grateful if one or twopoints in the results and the statistical analysis could be clarified.

The important question is whether ultrasound measurements ofbladder wall thickness can be adequately diagnostic. Central tothis is: How much do these thickness measurements overlapbetween groups diagnosed urodynamically?

The authors give results including those below, and concludethat ‘Examination of the 95% CIs reveals no overlap in thosewomen with a diagnosis of detrusor instability and in those with adiagnosis of GSI’:

This appears to be a non-sequitur. It is perfectly possible to havedifferent means with non-overlapping confidence intervals, butstill have so much overlap between the groups that many individualmeasurements will not be diagnostic. It is essential to distinguishbetween the 95% CI and the spread of values in the group. The95% CI normally refers to the uncertainty in estimating the mean ofthe whole patient group from a limited sample (i.e. there is a 95%chance that the ‘real’ mean lies in this range). The bigger thesample, the smaller this range becomes. In the limit of measuringthe entire population, there is no uncertainty in the mean at all. Thisis quite different to the spread of measurements in the sample,which does not get smaller as the sample size is increased.

If the intervals quoted above are indeed the 95% CIs, then it iseasily shown that the spread should be around five times larger forthe samples in this study. The authors helpfully include areference to an earlier paper from the same centre2, where it isclear (Fig. 3) that corresponding measurements have a range muchnearer 7 mm than 1.4 mm. It would then follow that the overlapbetween the groups is significantly greater than we hoped, and thediagnostic value is correspondingly less.

Ultimately, it would be very helpful to quote the specificity andthe sensitivity of the ultrasound approach for appropriate choicesof threshold bladder wall thickness, such as the 6.0 mm theauthors suggest. This would be firmer ground on which to judgethe usefulness of the ultrasound measurement.

References

1. Robinson D, Anders K, Cardozo L, Bidmead J, Toozs-Hobson P,

Khullar V. Can ultrasound replace ambulatory urodynamics when

investigating women with irritative urinary symptoms? Br J Obstet

Gynaecol 2002;109:145– 148 (February).

2. Khullar V, Cardozo LD, Salvatore S, Hill S. Ultrasound: a noninvasive

screening test for detrusor instability. Br J Obstet Gynaecol 1996;103:

904– 908.

Patrick HillNorth Wales Medical Physics Department, Glan Clwyd Hospital,Rhyl, UK

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A randomised controlled trial of antibiotic prophylaxisin elective caesarean delivery

Sir,Bagratee et al. have published a well done randomised trial

examining the effect of antibiotic prophylaxis on fever and infec-tious outcomes in elective caesarean delivery. This study receivedfurther attention when abstracted in the widely distributed ACOGClinical Review1. The authors found no statistically significantdifferences in the outcomes of post-operative fever (8.3% anti-biotics vs 7.9% placebo, RR 1.05, 95% CI [0.58–1.92]), endome-tritis (0.8% vs 1.7%, 0.5 [0.09–2.70]), and wound infection (12.5%vs 13.3%, 0.94 [0.59–1.49]). They concluded that prophylacticantibiotics do not prevent infection in low risk caesarean delivery.

We think it is important to interpret this study in light of otherpreviously published similar papers. We have previously publisheda meta-analysis of randomised, placebo-controlled studies of anti-biotic prophylaxis for elective caesarean deliveries2. Combiningthe seven studies available at the time, we noted large, statisticallysignificant decreases in the risk of fever (relative risk, 0.25; 95% CI

Diagnostic group No. Mean (mm) 95% CI (mm)

Detrusor instability 21 6.7 6.0– 7.4

GSI 43 4.8 4.4– 5.3

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