Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Smoking does NOT cause preterm birth
- Carol AS Thompson (13 September 2003)
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Positive predictive value
- Peter S. Millard, MD, PhD (13 September 2003)
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Fish Oil Far More Effective Than Aspirin For Pre-eclampsia
- Joseph M. Mercola (13 September 2003)
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Re: Smoking does NOT cause preterm birth
- David Carvel (13 September 2003)
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Preventive strategies of pre-eclampsia
- Sudhir Kumar (14 September 2003)
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Re: Positive predictive value- wrong again!
- GH Hall (14 September 2003)
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Reference please
- David JR Hutchon (16 September 2003)
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Positive predictive value wrong
- David JR Hutchon (17 September 2003)
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Risk assessment of pre-eclampsia with uterine artery doppler
- Christoph C Lees, Andrew C. Breeze, and Gerald A. Hackett (22 September 2003)
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tocolytics for preterm labor in cardiac patient
- manan vasenwala (25 September 2003)
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Calcium-channel blockers have neonatal benefits
- Emma C Parry (3 November 2003)
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Carol AS Thompson, none not relevant
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Shennan's claim that "in the mean time the biggest impact to prevent prematurity is probably simple: avoid smoking" is an outright lie. His cited reference is nothing but a review of worthless studies which ignored the role of infection in order to falsely blame smoking. Women of lower socioeconomic class are more likely to carry these infections as well as more likely to smoke, and that form of specious analysis is deliberately intended to exploit confounding to concoct anti-smoking propaganda. You are not fooling us. We know that there has been no change in the rates of preterm birth since your anti-smoking persecution began, and your steadfast refusal to acknowledge this fact is proof of your dishonesty. We are sick and tired of your lies! http://ourworld.compuserve.com/homepages/CarolASThompson/perinata.htm Competing interests: None declared |
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Peter S. Millard, MD, PhD, Family Practice Residency Program Bangor, Maine, USA
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The author states that: "Positive predictive values are similar in both high and low risk groups, so 20% of women with an abnormal Doppler result will develop pre-eclampsia." This statement seems to violate Bayes' theorem that positive predictive value increases as pretest probability increases. Do other readers understand how this is possible? Competing interests: None declared |
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Joseph M. Mercola, Medical Director Optimal Wellness Center Schaumburg, IL 60194 USA
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The authors provide a current review of advancements in gynecology but fail to acknowledge one of the most important developments in the field of obstetrics. They correctly point out that pre-eclampsia affects around 3% of pregnant women and accounts for 25% of all babies with a very low birth weight(< 1500 g).
However they offer a drug (low dose aspirin) as the solution to this problem. They point out that aspirin reduces pre-eclampsia by 15% but they fail to acknowledge one of the most radical innovations to obstetrical care, the use of high quality fish oil. (1) Williams showed that a mere 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of pre-eclampsia. This is over a 300% improvement relative to aspirin. Additonally, last year Olsen (2) showed very clearly that randomised trials confirmed that the consumption of fish oil in pregnancy can increase birth weight by prolonging gestation and reduce the risk of recurrence of preterm delivery. It is likely the mechanism of action of fish oil is similar to that of aspirin in that they both favorably optimize prostaglandin production. The only caution in using fish oil is to avoid the use of fish as most fish are heavily contaminated with mercury. A study published earlier this year (3) by US government scientists showed that one in 12 U.S. women of childbearing age have potentially hazardous levels of mercury in their blood as a result of consuming fish. Most high quality fish or cod liver oil supplements use molecular distillation techniques which effectively remove nearly all the mercury and PCB contaminants and offer a highly cost effective solution to the prevention of the devastating consequences of premature delivery and pre-eclampsia. 1. Williams MA, Zingheim RW, King IB, Zebelman AM. Omega-3 fatty acids in maternal erythrocytes and risk of preeclampsia. Epidemiology. 1995 May;6(3):232-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=7619928&dopt=Abstract 2. Olsen SF, Secher, NJ; Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study BMJ 2002;324:447 ( 23 February ) http://bmj.bmjjournals.com/cgi/content/full/324/7335/447?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1023497823688_13918&stored_search=&FIRSTINDEX=0&volume=324&firstpage=447&resourcetype=1,2,3,4,10 3. Schober SE, Sinks TH, Jones RL, et al. JAMA. 2003 Apr 2;289(13):1667-74. Blood mercury levels in US children and women of childbearing age, 1999-2000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12672735&dopt=Abstract Competing interests: None declared |
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David Carvel, GP Biggar ML12 6BE
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Carol A S Thompson's rapid response is one of the angriest letters I have read in several weeks and yet she declares no competing interests. Either she is a current smoker as her mildly offensive and intemperate letter would suggest or she is a recent ex-smoker in which case nicotine replacement would be strongly recommended. Competing interests: Doctor & non-smoker |
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Sudhir Kumar, Consultant Neurologist, Department of Neurological Sciences Christian Medical College Hospital, Vellore, India-632004
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Sir, I read with interest the recent review by Professor Shennan (1). An excellent account of recent developments in obstetrics is provided. However, I would like to make certain comments on the preventive strategies of pre-eclampsia. The importance of low-dose aspirin has already been highlighted (1). However, the exact period when it should be started is not clear. It is almost certain that it is of no use when taken in the inter-pregnancy interval. However, it should be started in early second trimester in women with past history of pre-eclampsia or among those detected to be at high- risk by transvaginal Doppler ultrasound study of the uterine arteries at 12 to 14 weeks of gestation (2). Another interesting aspect to note is the time-dependent effects of aspirin on lowering of blood pressure. Aspirin has been shown to have the maximum effect on lowering of blood pressure when taken before bedtime or eight hours after awakening as compared to just after awakening (3). The role of Vitamins C and E has also been highlighted (1). The effect is believed to be due to their antioxidant properties. While on this point, we should also note the effects of smoking. Maternal smoking was found to be protective against pre-eclampsia in nulliparous women (4). In another study, a significantly increased risk of pregnancy-induced hypertension was found among women who never smoked (5). The protective effect of smoking could be due to its antioxidant properties. However, smoking may adversely affect maternal and foetal outcomes due to its other ill effects and hence cannot be recommended. Role of calcium has not been discussed in the present review. Calcium supplementation is beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake (6). Pre-eclampsia is more common in first pregnancies. The risk is reduced by half in subsequent pregnancies. However, this reduction in risk of pre-eclampsia is not seen in women who conceive with new partners (7). An immune-based etiologic mechanism is proposed, whereby prolonged exposure to foetal antigens from a previous pregnancy protects against pre -eclampsia in a subsequent pregnancy with the same father. This should be a strong incentive for maintaining long-term relationship with single partners! In conclusion, role of calcium and subsequent conception with same partners in prevention of pre-eclampsia need to be highlighted. The timing of aspirin administration is also important and could explain the lack of efficacy shown in some trials. References 1.Shennan AH. Recent developments in obstetrics. BMJ. 2003; 327: 604- 8. 2.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. BJOG. 2002; 109: 161-7. 3.Hermida RC, Ayala DE, Iglesias M. Administration time-dependent influence of aspirin on blood pressure in pregnant women. Hypertension. 2003; 41: 651-6. 4.Xiong X, Wang FL, Davidge ST, Demianczuk NN, Mayes DC, Olson DM, et al. Maternal smoking and preeclampsia. J Reprod Med. 2000; 45: 727-32. 5.Morris CD, Jacobson SL, Anand R, Ewell MG, Hauth JC, Curet LB, et al. Nutrient intake and hypertensive disorders of pregnancy: Evidence from a large prospective cohort. Am J Obstet Gynecol. 2001; 184: 643-51. 6.Atallah AN, Hofmeyr GJ, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2002;(1): CD001059. 7.Saftlas AF, Levine RJ, Klebanoff MA, Martz KL, Ewell MG, Morris CD, et al. Abortion, changed paternity, and risk of preeclampsia in nulliparous women. Am J Epidemiol. 2003; 157: 1108-14. Competing interests: None declared |
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GH Hall, Retired physician EX1 2HW
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It really is time that a better check be maintained on the use of things like PPV, sensitivity, specificity, etc. Experts like Greenhalgh and Sackett seem to make almost as many mistakes as lesser mortals. The attitude appears to be that no-one understands them anyway so it doesn't matter. But maths isnt like medicine: things can be absolutely wrong or absolutely right.The author and the peer reviewer should be invited to justify or apologise. Competing interests: None declared |
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David JR Hutchon, Consultant Obstetrician and Gynaecologist Darlington Memorial Hospital DL3 6HX
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Professor Shennan states, "A recent randomised controlled trial comparing this with Doppler auscultation has shown that cardiotocograms result in a notable increase in intervention, including oxytocin augmentation and use of epidurals, and cause an increase in operative deliveries without any evidence of improvement in the wellbeing of the newborn. Given the number of women involved in this intervention, withdrawing the routine use of the cardiotocogram on admission is likely to reduce unnecessary intervention considerably." The article is generally well referenced and I would be grateful for a reference of the published trial referred to above. David Hutchon Competing interests: None declared |
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David JR Hutchon, Consultant Obstetrician and Gynaecologist Darlington Memorial Hospital. DL3 8QX
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The two previous responders Hall and Millard are absolutely correct. It is impossible to have the same PPV in a high prevalence (high risk) population as in a low prevalence (low risk) population for a particular test although the PPV will be very close in the two populations with a highly sensitive and highly specific test. The positive predictive value is the number of women with pre- eclampsia (PET) divided by the number of women who have a positive test. PPV=PET num/positive test num It is simple to demonstrate this fact. Take two populations high and low prevalence. By definition there will be more women with PET in the high prevalence population. Adjust population sizes so the number of women with PET is the same in both populations. I.e the numerators are the same. The denominator is the number of women who test positive. The number of true positives will remain the same. The number of false positives however will be much higher because in the low prevalence population. If there are no more false positive results in the low prevalence population then the specificity of the test applied to the two populations is different, that is, it is not the same test. (Specificity and sensitivity define a test) The higher value of the denominator in the low prevalence population will lead to a fall in the PPV. There is no argument, it is trivial maths. From the two references ( reference 2 gives incorrect page numbers) the PPV in the low population is 7.3%, in the high risk population it is 70%. A calculator is available on my website to demonstrate the effects of adjusting prevalence etc. www.hutchon.freeserve.co.uk David Hutchon Competing interests: None declared |
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Christoph C Lees, Consultant in Obstetrics and Maternal-Fetal Medicine Fetal Medicine Service, Box 228, Rosie Hospital, Addenbrooke's NHS Trust, Cambridge, CB2 2QQ, Andrew C. Breeze, and Gerald A. Hackett
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Sir, Professor Shennan's review of recent developments in obstetrics1 is timely, however we would take issue with some of his conclusions in relation to pre-eclampsia. He states that the positive predictive value of abnormal uterine artery Doppler for predicting pre-eclampsia is similar in low and high risk women. Not only is this statistically implausible, but several studies dispute his assertion. Coleman's study2 of uterine Doppler in high-risk women in fact demonstrated a positive predictive value for pre-eclampsia of 37% for a uterine artery resistance index > 0.58, and 58% for a resistance index >0.7 and Parretti3 found a positive predictive value of 44.4% for a uterine artery RI > 0.58 at 24 weeks. In Papageorghiu's large multicentre study4 of over 7000 low-risk women, the PPV of abnormal uterine Doppler for pre-eclampsia with fetal growth restriction 7.2%, and 4.2% for pre-eclampsia in the absence of fetal growth restriction. Most women who develop pre-eclampsia are in their first pregnancy and have no risk factors other than this. A quadratic relationship exists between uterine artery resistance at 23 weeks and the likelihood of a severe adverse obstetric outcome such as pre-eclampsia or growth restriction requiring delivery by 34 weeks5. Risk can therefore be individualised on the basis on uterine artery resistance, allowing women to be allocated appropriately to high or low risk care. Shennan's recommendation that prematurity is best prevented by stopping smoking ignores a potential beneficial effect. A study of over 4000 women suggests that pregnant women smoking at 13-21 weeks had a reduced risk of hypertension (RR=0.8; 95% CI, 0.6-0.9) whereas women who quit smoking before their last menstrual period did not 6. The relationship of pregnancy outcome and smoking is almost certainly more complex than Shennan suggests, in that there may be an optimal gestation to which smoking is beneficial, after which the risk of pre-eclampsia and other obstetric complications increases. Best wishes. Yours, Andrew CG Breeze, Clinical Research Fellow
Fetal Medicine Service, Box 228, The Rosie Hospital, Addenbrooke's NHS Trust, Hills Road, Cambridge, CB2 2QQ 1 Shennan, AH. Recent developments in obstetrics. BMJ. 2003 Sep 13;327(7415):604-8. 2 Coleman MA, McCowan LM, North RA. Mid-trimester uterine artery Doppler screening as a predictor of adverse pregnancy outcome in high-risk women. Ultrasound Obstet Gynecol. 2000 Jan;15(1):7-12. 3 Parretti E, Mealli F, Magrini A, Cioni R, Mecacci F, La Torre P, Periti E, Scarselli G, Mello G. Cross-sectional and longitudinal evaluation of uterine artery Doppler velocimetry for the prediction of pre -eclampsia in normotensive women with specific risk factors. Ultrasound Obstet Gynecol. 2003 Aug;22(2):160-5. 4 Papageorghiou AT, Yu CKH, Bindra R, Pandis G and Nicholaides KH. Multicenter screening for pre-eclampsia and fetal growth restriction by transvaginal uterine artery Doppler at 23 weeks of gestation. Ultrasound Obstet Gynecol 2001; 18:441-449 5 Lees C, Parra M, Missfelder-Lobos H, Morgans A, Fletcher O, Nicolaides KH. Individualized risk assessment for adverse pregnancy outcome by uterine artery Doppler at 23 weeks. Obstet Gynecol 2001;98:369- 373 6 England LJ, Levine RJ, Qian C, Morris CD, Sibai BM, Catalano PM, Curet LB, Klebanoff MA. Smoking before pregnancy and risk of gestational hypertension and preeclampsia. Am J Obstet Gynecol 2002;186:1035-40 Competing interests: None declared |
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manan vasenwala, consultant-cardiologist (non-invasive) k
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The incidence of preterm delivery is about 10% of all births.more than 60,000 patients receive intravenous tocolytics. The potential injury to the healthy mother is limited. This does not hold true for the cardiac patient for whom the tocolytics represent considerable risk.the prevalence of cardiac disease amongst pregnant population is 0.5-1.0%. There is a gradual rise in maternal age(1) due to late marriage and altered socio-econmic enviroment. Increasingly, there are co-existing risk factors like smoking, obesity, hypertension, diabetes, use of oral contraceptives, and dyslipidaemias.the incidence of coronary artery disease is rising and even deaths from acute myocardial infarction has been reported during pregnancy.(2) The tocolytics in current use are b-mimetics, magnesium sulfate, nifedipine, and indomethacin. An important consideration in cardiac patient is that maternal hypoxia can lead to preterm labor. Here, optimisation of cardiac status is all that is required. Similarly, fetal compromise, like iugr, reduced amniotic fluid, bradycardia etc, are in fact a cry for fetal delivery in an hostile enviroment. Many of the fetuses, of high risk mothers have cardiac or morphological malformations which cause preterm delivery. Intravenous b-mimetics are the current gold standard.all b-mimetics are b2 selective, but have some b1 effects, which cause undesirable side effects. One principal concern for the healthy mother is the appearance of pulmonary edema , myocardial ischaemia or unmasking of latent cardiac disease. In addition, patients on b-mimetic often demonstrate reversible ecg changes of ischaemia and prolongation of QT interval with arrythmogenic potential.any healthy patient developing chest pain with b- mimetic should have it discontinued. Myocardial infarction during ritodrine infusion has been reported in previously healthy woman.(3)the most consistent and serious complication is that of pulmonary edema with an incidence of 1-5%.(4) most cases have been attributed to co-administration of excessive fluids, and concomitant use of steroids, indomethacin and nifedipine.in vast majority of cases there is no pre-existing cardiac disorder. Another worrisome adverse effect is persistent maternal bradycardia after ritodrine withdrawal.research revealed use of ritodrine in treatment of preterm labor had no significant beneficial effect on perinatal mortality, frequency of prolongation of pregnancy to term, or birth weight.(5) a variety of cardiac arrhythmias are also described during terbutaline pump therapy leading to maternal death in one case. In addition, in several patients initial manifestation of cardiomyopathy occurred after ritodrine infusion.some authors claim that this was unmasking of cases of peripartum cardiomyopathy associated with use of b-mimetic.nevertheless, there was complete recovery on cessation of therapy.terbutaline pump is gaining popularity, but it is important to be aware that new onset arrhythmias, pulmonary edema and even death has been attributed to its usage.(6)however, the adverse cardiac effects have not been characterised by large randomised trials despite its widespread use. Other perturbations associated with b-mimetics are hyperglycemia, ketoacidosis, and lactic acidosis.if this is the state of affairs in healthy patients, for cardiac patients more justification would be required for its use.few conditions like pulmonary hypertension, aortic stenosis, pulmonary stenosis ,and hypertrophic obstructive cardiomyopathy are contraindicated. They should be also avoided in ischaemia and arrythmias as both can be aggravated. Profound hypotension has been reported with use of large bolus of magnesium sulfate especially when multi agents are used like ritodrine or nifedipine.magnesium sulfate also have direct cardiac toxicity leading to PR and QRS prolongation.cardiac arrest is the ultimate consequence. Pulmonary edema and unexplained hyperkalemia has also been described. Its use in cardiac patients should be guarded especially when pulmonary hypertension is present. Calcium channel blockers, particularly nifedipine appear to be safe.and
result in significant dimunition of uterine contractions. However, this
drug must not be used in large quantities and must never be given
sublingually as it leads to a catastrophic hypotension.the combination
with magnesium sulfate may potentiate magnesium sulfate’s toxicity. The
reported use of calcium channel blockers in cardiac patient is scatchy,
but not so in healthy gravids.(7)
Others advocate antenatal vit k in preterm labor.although if not
beneficial, this appears to be harmless, except when a cardiac patient has
a prosthesis and is on anticoagulant, coumadin.
In conclusion, the management of cardiac patient is similar to non-cardiac
ones, except that vigorous hydration should be avoided and effort made to
understand cause of preterm labor.b-mimetics are contraindicated usually,
magnesium sulfate not given in bolus form.steroids are beneficial for
fetal maturation. Amongst calcium channel blockers, nifedipine or
nicardipine (10) although not extensively studied are useful choices.
The entire treatment with tocolytics in both healthy and cardiac patients
needs to be reviewed.
Ref:
1.rutherford jd: coronary artery disease in the childbearing age. In
elkayam u, gleicher n (eds): cardiac problems in pregnancy. 3rd ed.
2. Roth a, elkayam u: acute myocardial infarction and pregnancy. In
elkayam u, gleicher n (eds): cardiac problems in pregnancy. 3rd ed.
3. Donnelly s, mcging p, sugrue d, myocardial infarction during pregnancy.
Br j obstet gynaecol 1993;100:781-784.
4. Blickstein i, zalel y, katz z, lancet m. Ritodrine induced pulmonary
edema unmasking underlying peripartum cardiomyopathy. Am j obstet gynecol
1988;159:332.
5. Tj benedetti. Treatment of preterm labor with the beta-adrenergic
agonist ritodrin. Engl. J. Med., dec 1992; 327: 1758.
6. Warning on use of terbutaline sulfate for preterm labor
Jama, jan 1998; 279: 9-a.
7. Oral nicardipine inhibits preterm labor
Journal watch women's health, apr 2000; 2000: 10.
8.elimian a et al. Effectiveness of antenatal steroids in obstetrics
subgroups. Obstet gynecol 1999 feb; 93:174-179.[medline abstract][download
citation
9. Neonatal complications after the administration of indomethacin for
preterm laborn. Engl. J. Med., nov 1993; 329: 1602 - 1607.
10. Larmon je et al. Oral nicardipine versus intravenous magnesium sulfate
for the treatment of preterm labor. Am j obstet gynecol 1999 dec; 181:1432
-1437.[medline abstract][download citation]
Competing interests:
None declared |
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Emma C Parry, Senior Lecturer National Women's Hospital, Private bag 92-189, Auckland, New Zealand
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I enjoyed reading Professor Shennan's update article on Obstetrics. Two meta-analyses of the use of calcium-channel blockers as tocolytics have shown a benefit to the neonate which is independant of steroid administration. In a meta-analysis by James King and colleagues, administration of calcium-channel blockers as acute tocolysis, showed a significant reduction in RDS (RR, 0.63; 95% CI 0.46, 0.88), Necrotising enterocolitis (RR, 0.21; 95% CI 0.05, 0.96), IVH (RR, 0.59; 95% CI 0.36, 0.98) and admissions to a NICU (RR, 0.78; 95% CI 0.64, 0.95). Most units in New Zealand have been using nifedipine as an acute tocolytic for the last 12 months and we find it preferable to salbutamol which we were previously using. As Professor Sheenan pointed out in his article, nifedipine is not licensed for this use, although it has been used for many years in pre-eclampsia. As a result, we have a very clear protocol which we developed at National Women's Hospital which guides the use of nifedipine as a tocolytic. We would be happy to share this with colleagues overseas if they were keen to switch over to nifedipine. King, Flenady, Papatsonis, Dekker and Carbonne. Aust NZ J O&G. 2003; 43: 192-198. Competing interests: None declared |
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