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Rapid Responses: Rapid Responses published:
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A physiological approach to reducing neonatal morbidity in elective Caesarean Section
- David J R Hutchon (24 August 2005)
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Commentary on antenatal betemethasone at term
- David J Garry (27 August 2005)
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confusing trials
- nick brown (23 September 2005)
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There is no longer any such thing as caesarean section without medical reasons.
- Jonathan H West (24 September 2005)
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reducing SCBU addmissions for elective C Section
- Chris J Griffin (28 September 2005)
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Caution is still needed.
- Celestin O. Selo-Ojeme (3 October 2005)
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Why would antenatal steroids prevent transient tachypnoea of the newborn?
- Humberto Fiori (4 October 2005)
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No benefit for steroids
- David J R Hutchon (7 December 2005)
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A clearer explanation of no benefit for steroids
- David JR Hutchon (8 December 2005)
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Elective Caesarean Section at Term
- Peter Roy Stutchfield, Rhiannon Whitaker (9 December 2005)
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An answer please
- David J R Hutchon (10 December 2005)
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Elective Caesarean Section at Term -References Rapid Response 9th December
- Peter Roy Stutchfield, Rhiannon Whitaker (11 December 2005)
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Informed consent for cord clamping?
- David J R Hutchon (12 December 2005)
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Admissions to Special Care Baby Unit in the Antenatal Steroids for Term Elective Caesarean Section Trial
- Peter Roy Stutchfield, Rhiannon Whitaker (14 December 2005)
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A trial of physiological delivery at Caesarean
- David J R Hutchon (19 December 2005)
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Increased risk of neanatal death with corticosteroids after 36 weeks
- David JR Hutchon (23 October 2006)
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Reduction in neonatal death with corticosteroids
- Peter R Stutchfield, Rhiannon Whitaker, (14 December 2006)
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Not an intentional error
- David JR Hutchon (18 December 2006)
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David J R Hutchon, Locum Consultant Obstetrician and GYnaecologist Grey Base Hospital, Greymouth, New Zealand
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Sir, The authors hypothesise that the increased incidence of transient tachypnoea and respiratory distress in the control group is due to the lack of corticosteroid normally produced during labour. They have the admirable aim of trying to mimic this physiological event by administering betamethasone and by delaying delivery until as close to the average length of normal pregnancy as possible. (40 weeks) Clearly a totally physiological birth would be ideal but this is not always safe for the baby or mother. With the current high Caesarean Section rate however it is still appropriate to try to mimic physiology as close as the process allows. Apart from labour, what other differences are there between Caesarean Section and vaginal delivery? One obvious difference is the acoucheur who is always an obstetrician. The majority of obstetricians do not think there is any harm in immediately clamping the cord in pre-term deliveries. (1) Even paediatricians are sceptical. (2) Unfortunately unless the cord is left unclamped for at least 30 seconds there is an increased risk of neonatal anaemia requiring transfusion and of ventricular haemorrhage. Hopefully the practice of immediate cord clamping will stop once information from the Cochrane review becomes more widely available. (3) Is it possible that immediate cord clamping is also contributing to the increased incidence of transient tachypnoea and respiratory distress in elective Caesarean Section? Immediate cord clamping deprives the baby of 25% to 40% of its circulating blood volume in these first few moments of extra-uterine life as it transfers from fetal to adult circulation. Such a massive change occurs at no other time in one's life without serious consequences, even death. Early cord clamping may impede a successful transition and contribute to hypovolemic and hypoxic damage in vulnerable newborns. Kimmond et al found a reduced severity in respiratory distress when cord clamping was delayed in preterm delivery. (4) However little the intervention of immediate cord clamping contributes to respiratory problems in Caesarean Section it should be stopped in favour of delayed clamping of at least 30 seconds This adheres to the principle of mimicking the physiological process as closely as possible and of avoiding the unproven intervention of immediate cord clamping. The authors report five studies which have shown no adverse effects from a single course of antenatal corticosteroids. They failed to mention however that there are concerns about the safety of repeated courses of steroids. (5) Such a dramatic effect on pulmonary metabolism is unlikely to have no other effect elsewhere in the fetus. According to the figures provided in the paper the relative risk of a respiratory problem was reduced by 0.47 with steroid treatment. However because the incidence was low in both groups this requires 37 babies to be treated to save one admission with respiratory distress. (NNT=37 95% confidence 20 – 336) We need to be very confident that the treatment does no harm with such a large NNT. Further although the number of babies admitted to special care for respiratory distress was 11 in the treatment group and 24 in the control group, the total admissions to special care for all reasons was 26 in the treatment group and 32 in the control group. This represents a relative risk of admission of 0.82 in favour of the treatment group but the 95% confidence interval is from 0.5 to 1.37 making it not statistically significant. The benefit described by the authors in “the meaning of the study” of reducing separation of the mother from baby, less disruption of bonding, lower cost of care and the less risk of complications were NOT therefore achieved with antenatal steroids. David J R Hutchon Refernces 1. Hutchon DJR, Houda MR. What is the contribution of delayed cord clamping during delivery of the preterm baby to the reduction in morbidity and mortality of the neonate? Poster. British Congress of Obstetrics and Gynaecology, Glasgow, July 2004. 2. Janet Tucker and William McGuire Epidemiology of preterm birth: Authors' reply BMJ, Nov 2004; 329: 1287. 3. Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. The Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD003248.pub2. DOI: 10.1002/14651858. 4. Kinmond S, Aitchison TC, Holland BM, Jones JG, Turner TL, Wardrop CA. Umbilical cord clamping and preterm infants: a randomised controlled trial. BMJ 1993;306: 172-5. 5. Jobe A, Newnham J, Willet K, Sly P, Ikegami M. Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids. Pediatrics 1998; 102: 1116-1125 Competing interests: None declared |
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David J Garry, Maternal Fetal Medicine Jacobi Medical CenterBronx, NY 10461
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Sir, The incidence of cesarean delivery has been steadily increasing worldwide. Stutchfield et al (1) addressed the use of corticosteroids at term for patients undergoing elective cesarean delivery. Their specific objective was evaluation of the incidence respiratory distress in babies delivered by elective cesarean at term (>37 weeks). The idea of reduction in neonatal respiratory morbidity was suggested by Morrison and colleagues through elective repeat cesarean > 39 weeks. (2) Some degree of neonatal respiratory difficulty will occur despite providing good obstetrical care. (3,4) The authors do not describe the reasons for elective delivery prior to 39 weeks in the patient population nor do they describe the numbers of patients at each given gestational age (37 weeks n=?, 38 weeks n=?, etc). Secondly, the sample size calculated was based on a respiratory distress rate of 8% that would be reduced to 4% in singleton deliveries. The authors fail to reference this high respiratory rate (8%) at term that was utilized in the calculation and remains a serious design flaw. The incidence of respiratory distress in term infants in their study for controls was 0.011. The diagnosis of transient tachypnea in 13 babies was made on discharge without radiographic imaging described in the methods. The authors fail to describe the allocation of these “discharge” transient tachypnea neonates. The pediatricians were not described as blinded to the administration of betamethasone and this confounds the data related to admission in the intensive care unit. I agree that reducing the elective deliveries prior to 39 weeks improves outcome and this practice is recommended by American College of Obstetrics and Gynecology. (5) Figure 3 clearly demonstrates that waiting until 39 weeks is beneficial. I believe the authors correct that there is benefit of antenatal steroids at gestational ages beyond the recommeded 34 weeks and there should be consideration of use in non-emergent situations requiring earlier delivery (between 35 and 39 weeks). Much larger numbers are needed to detect differences in respiratory distress after 35 weeks. References 1. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ,doi:10.1136/bmj.38547.416493.06 (2005). 2. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol. 1995;102:101-6. 3. Andersen HF, Green DW. Commentary on "The Epidemiology of Respiratory Failure in Neonates Born at an Estimated Gestational Age of 34 Weeks or More" by Clark RH, et al. Journal of Perinatology 2005;25:501−502. 4. Clark RH. The Epidemiology of Respiratory Failure in Neonates Born at an Estimated Gestational Age of 34 Weeks or More Journal of Perinatology 2005;25:251−257. 5. American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. Guidelines for Perinatal Care, 5th ed. 2002: p34 Competing interests: None declared |
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nick brown, consultant paediatrician salisbury
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Sir I might be alone in this but surely the two studies published this week to argue the case for antenatal steroids are incomparable and shouldn't be presented together The first (Stutchfiled et al) is for babies in late normal gestation pre caesarean and the outcome the incidence of respiratory distress most of which will be transient tachypnoea in this group (completely diffent to RDS of the preterm). It has no long term neurodevelopmental follow up outcomes The second (New Zealand, Dalziel et al) looks at completely different group, the very preterm babies at much greater risk of RDS and poor neurodevelomental outcomes I'm a rather baffled as to why two such different papers have been printed together-neither particularly helps the argument of the other nor the slant the journal is trying to advocate Competing interests: None declared |
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Jonathan H West, Consultant Obstetrician & Gynaecologist Royal Devon & Exeter Hospital, EX1 2ED
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EDITOR – Stutchfield et al conclude that the likely benefits of antenatal corticosteroids should be compared with those of delaying delivery until 39 weeks gestation when possible 1. Gestation-specific perinatal mortality due to intrauterine death and stillbirth and birth asphyxia is probably approximately 1:1000 between 38 and 39 weeks 2. On the other hand although transient tachypnoea of the newborn due to Caesarean Section may cause some morbidity and utilise resources (to a degree that is difficult to compare with the morbidity that may arise from events such as infections, placental abruption or intrapartum asphyxia occurring whilst women are awaiting planned Caesarean Section), their study adds to the already large number of series showing effectively zero risk of perinatal mortality among otherwise low-risk women from this cause. It is therefore no longer acceptable to describe some planned Caesarean Section after 38 weeks, to quote from their introduction, as being performed ‘..without medical reasons’. The safety of the baby is a valid medical reason in all cases. 1. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331:662 (24 September). 2. Hilder L, Costeloe K, Thilaganathan B. Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality. Br J Obstet Gynaecol. 1998 Feb;105(2):169-73. Competing interests: None declared |
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Chris J Griffin, obstetrician Heart of England NHS trust B9 5SS
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Excellent paper and re inforcing the issue of waiting until the completion of the 38th week ie within 7 days of the expected date of confinement. For the 15% who labour the risk for SCBU addmissions is dramatically reduced anyway which is of great comfort to many women. The problem is that when the knowledge of this paper becomes widely known by patients it will be used as a fulcrum for manipulating elective dates! However, what would be interesting would be to have a longer term project to examine the women who for medical reasons and are not labouring require earlier C Sections than 38 weeks but after 36 weeks. Should we not start a register to examine these cases as I would imagine that many consultants will feel obliged under current patient choice to administer steroids pre operatively? This could be easily set up on any maternity information system though monies would be needed to monitor the long term outcomes etc which is probably not forthcoming - though perhaps from the savings on SCBU addmissions it may be!! wishful thinking perhaps! Competing interests: None declared |
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Celestin O. Selo-Ojeme, Honorary SHO Department of Obstetrics and Gynaecology, Kings College Hospital, London.
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Dear Sir, In their study, Stutchfield et al[1] have shown that steroids reduce respiratory distress in babies born by elective caesarean section at term. Permit me to make the following observations. (1) As yet, the long term safety of antenatal steroids is not completely certain[2] In New Zealand[3], studies have shown that antenatal exposure to betamethasone might result in insulin resistance in adult offspring at 30 years of age. Another study in Australia[4] has shown a long term association of antenatal steroids with persistent deficit in brain weight. (2) Although the current optimal treatment-delivery interval for administration of antenatal corticosteroids is more than 24 hours but fewer than seven days after the start of treatment, it is believed that there is a trend towards benefit in babies delivered after the optimal period has elapsed[5]. Stutchfield et al[1] did not say if any of the participants had steroids earlier on in pregnancy and, if so whether such women were excluded from the analysis. (3) It appears there is a wide variation in the incidence of RDS in neonates born by elective caesarean section. For example, in some studies[6-8], it ranges from 3.5% to 8%. This would have an impact on the sample size calculated by Stutchfield et al[1]. If say they had based their calculation on the reduction in the percentage of babies admitted to a special baby unit with respiratory distress from 6% to 4%, about 1860 participants would have been needed in each arm i.e. a sample size of 3720. In conclusion, it may well be that the safest strategy for now is to delay, where possible, elective caesarean delivery till beyond 39 weeks gestation as some studies have shown no significant difference in RDS risk after 39 + 0 weeks[9] Reference 1. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and the incidence of neonatal respiratory distress after elective caesarean section: Pragmatic randomised trial BMJ, 2005;331:662-4. 2. Sloboda DM, Challis JR, Moss TJ, Newnham JP. Synthetic glucocorticoids: Antenatal administration and long term implications. Curr Pharm Des, 2005: 11 (11 ) : 1459 - 72 3. Dalziel SR, Walker NK, Parag V, Mantell C Rea HH, Rodgers A, Harding JE. Cardiovascular risk factors after antenatal exposure to betamethasone: 30- year follow-up of a randomised controlled trial. Lancet, 2005; 365:1856 – 62 4. Moss TJ, Doherty DA, Nitsos I, Sloboda DM, Harding R, Newnham JP. Effects into adulthood of single or repeated antenatal corticosteroids in sheep. Am J Obstet Gynaecol. 2005;192:146 – 52. 5. Royal College of Obstetricians and Gynaecologists. Antenatal corticosteroids to prevent respiratory distress syndrome. Guideline No. 7, 2004 6. Alderdice F, McCall E, Bailie C, Craig S, Dornan J, McMillen R, Jenkins J. Admission to neonatal intensive care with respiratory morbidity following ‘term’ elective caesarean section. Ir Med J, 2005; 98: 170 – 2 7. Nicoll AE, Black C, Powls A, Mackenzie F. An audit of neonatal respiratory morbidity following elective caesarean section at term Scott Med J, 2004;49: 22 – 5 8. Morrison JJ, Rennie JM, Milton PJ. Br J Obstet Gynaecol, 1995;102:101 – 6 9. Zanardo V, Simbi AK, Franzoi M, Solda G, Salvadori A, Trevisanuto D. Neonatal respiratory morbidity risk and mode of delivery at term: Influence of timing of elective caesarean delivery. Acta Paediatr, 2004; 93: 643 -7. Competing interests: None declared |
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Humberto Fiori, Associate Professor of Pediatrics Hospital São Lucas, PUCRS, Av. Ipiranga, 6690, 5 andar, CEP 90610-000, Porto Alegre, RS, Brazil
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In a recent issue of the British Medical Journal, Stutchfield and co- workers published a provocative article showing a reduction in the incidence of transient tachypnoea (TT) in infants of mothers submitted to elective caesarean section receiving antenatal betamethasone.[1] Although the routine use of steroids in this situation is probably not justified, it provides important information on their effects beyond the 34th week of gestation. In their paper, the authors attribute the reduced incidence of TT of the newborn to the effect of the steroid on the expression of the epithelial channel gene, allowing the lung to switch from fluid secretion to fluid absorption. Although this mechanism may be involved, the possible role of enhanced surfactant production was not mentioned. We believe, however, that surfactant deficiency and/or dysfunction is a major determinant of respiratory distress in these infants diagnosed as having TT and that enhanced surfactant production by betamethasone may explain its reduced incidence, independent of other effects. Low levels of phosphatidylglycerol in the lung fluid and in amniotic fluid were reported in patients with TT in more than two studies.[2,3] Reduction of bubble clicking in tracheal and gastric aspirates of these infants were also reported.[4] Our own case-control study on term or near-term infants with clinical and radiological initial diagnosis of TT of the newborn showed that two thirds of these infants had a low stable microbubble count, suggesting surfactant deficiency and/or dysfunction. Nearly all infants with TT and high microbubble count had a mild and brief clinical course of less than 24 hours, suggesting normal surfactant function, while nearly all those with a low microbubble count had a more severe and prolonged course, suggesting surfactant deficiency and/or dysfunction.[5] We believe that there is not a single aetiology for the so-called TT of the newborn and that in most cases the aetiology is multifactorial. The activation of the surfactant system may explain at least in part the reduction of TT in term babies born to women submitted to elective caesarean section treated with antenatal steroids. 1. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662-4. 2. James DK, Chiswick ML, Harces A, Williams M, Hallworth J (1984) Non- specificity of surfactant deficiency in neonatal respiratory disorders. Br Med J 1984;288:1635-8. 3. Bourbon JR, Francoual J, Magny JF, Lindenbaum A, Leluc R, Dehan M. Changes in phospholipid composition of tracheal aspirates from newborns with hyaline membrane disease or transient tachypnoea. Clin Chim Acta. 1990;189:87-94. 4. Bhuta T, Kent-Biggs J, Jeffery HE (1997) Prediction of surfactant dysfunction in term infants by the click test. Pediatr Pulmonol 1997;23:287-91. 5. Fiori HH, Henn R, Baldisserotto M, Bica IG, Fiori RM. Evaluation of surfactant function at birth determined by the stable microbubble test in term and near term infants with respiratory distress. Eur J Pediatr. 2004;163:443-8. Competing interests: None declared |
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David J R Hutchon, Locum Cons Obstetrician Greybase Hospital, Greymouth, New Zealand
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sir I accept that there is limited space in the BMJ and difficult decisions have to be made on which letters to publish. However in my letter I point out that according to the results given in this study there were actually no more babies admitted to the SCBU and separated from parents in the control group than there were in the treatment group. Why was this not discussed in the paper and why did the BMJ editorial not think it important enough to publish my letter? Do other readers agree with the analysis I have made on the figures provided or have I completely misread the paper? Either way a rapid response would have been helpful. David Hutchon Competing interests: None declared |
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David JR Hutchon, Locum Consultant Obstetrician and Gynaecologist Grey Base Hospital, Greymouth, New Zealand
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The authors rightly state that admission to a special unit separates mother and baby, potentially disrupting bonding, and increasing the cost of care and the risk of complications. From table 3 we can see that there were 26 out of 467 babies admitted to the SCBU in the treatment group and 32 out of 475 in the control group. This gives an incidence of admission to SCBU of 0.067 in the control group and 0.056 in the treatment group (relative risk 0.83, 95% confidence interval 0.5 to 1.36). Therefore although there were slightly fewer babies admitted to special care in the treatment group the difference was not statistically significant. The meaning of the study of reducing the separation of the mother and baby, together with the costs and risks of admitting a baby to special care, were NOT met. This fact was missed completely by the authors. Readers should note that these figures are only clear in the electronic version of the paper. It is true that the primary outcome, respiratory distress requiring admission to special care is unlikely to be susceptible to maternal influence, however there is little doubt such diagnosis and admission are susceptible to bias by doctors. My apologies for my rather confusing previous letter. Competing interests: None declared |
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Peter Roy Stutchfield, Consultant Paediatrician Conwy and Denbighshire Trust, LL18 5UJ, Rhiannon Whitaker
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We reported the outcome of a randomised trial of antenatal betamethasone before elective caesarean section at term demonstrating >50% reduction in admission with respiratory distress for those delivered between 37-39 weeks (1). Of the 35 babies admitted with respiratory distress, 19 control babies had transient tachypnoea (TTN), 5 with respiratory distress syndrome (RDS), compared to 10 babies with TTN in the intervention group and 1 RDS. 14 control babies required intensive care, 3 with RDS requiring ventilation for between 2 and up to 5 days with length of stay 12-18 days, whereas only 2 in the intervention group received intensive care. We postulated that the reduced incidence of TTN with antenatal betamethasone may result from an effect on the expression of the epithelial channel gene allowing the lung to switch from fluid secretion to fluid absorption . Professor Fiori’s rapid response(2) provides evidence for an additional factor, enhanced surfactant production. The presence of lung fluid is likely to delay surfactant production leading further to a decrease in lung compliance seen in TTN. Professor Steer in the editorial in the same issue (3) raises concerns about the long term consequences of giving antenatal steroids by reporting the outcome of follow-up studies where multiple 2 weekly courses of antenatal steroids were given from 24 weeks gestation onwards and high- dose intravenous postnatal courses of corticosteroid prescribed for the very preterm to prevent chronic lung disease. He then raised the example of thalidomide and diethylstilboestrol in pregnancy where mass prescribing and the lack of long term follow up research lead to well reported serious consequences. These drugs were used early in pregnancy during early embryogenesis. Professor Steer concludes that “giving steroids whose long term safety, even as a single course, remains questionable.” Though we understand Prof Steer’s concern, the Cochrane review in 2003 (4) and the evidence based guideline of Royal College of Obstetrics & Gynaecology (5) on the use of antenatal corticosteroids to prevent respiratory distress syndrome, concludes that a single course of antenatal corticosteroid has no adverse effect on physical growth, neurological or cognitive outcome or infection in child or mother .The Royal College’s guidelines synthesises five papers following more than 1500 survivors from randomised trials or cohort studies of antenatal corticosteroids for up to 20 years. Concerned that Prof Steer might know of a flaw in this guideline from his own College, we have reviewed all five papers, together with another published since the RCOG guideline (6) and Dalziel’s follow up paper (7) which extends follow up to 31 years. However we find the College guideline rigorous and appropriate. The risk of Prof Steer’s recommendation is that he may discourage others from discussing and offering a simple, safe and effective evidence based preventative measure to women who, for whatever reason require or plan an elective section before 39 weeks. Competing interests: None declared |
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David J R Hutchon, Locum Consultant Obstetrician Grey Base Hospital, Greymouth,New Zealand
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I saw the response from the authors with the expectation of an explanation or at least recognition of the main points of my previous letters. The authors failed to point out in their original publication that although there was a significant reduction in SCBU admissions for TTN and RDS, there was no significant difference in the number of babies admitted to SCBU overall. Perhaps there has been a misprint in which case a response would have been easy. I have copied and pasted the figures in the paper directly to ensure there is no error. Total No of babies admitted in betamethosone group 26/467 Total No of babies admitted in control group 32/475 I therefore repeat from my letter “From table 3 we can see that there were 26 out of 467 babies admitted to the SCBU in the treatment group and 32 out of 475 in the control group. This gives an incidence of admission to SCBU of 0.067 in the control group and 0.056 in the treatment group (relative risk 0.83, 95% confidence interval 0.5 to 1.36).” This is a non-significant difference. How does it fit into the meaning of the study as stated by the authors. David Hutchon Competing interests: None declared |
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Peter Roy Stutchfield, Consultant Paediatrician Conwy and Denbighshire Trust LL18 5UJ, Rhiannon Whitaker
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The references for our rapid response dated 9th December entitled Elective Caesarean Section at Term are detailed below. 1. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005: 331: 662- 664.(electronic publication 22.8.05) 2. Fiori H. Why should antenatal steroids prevent transient tachypnoea of the newborn? – rapid response letter BMJ posted 04.10.05. 3. Steer P J. Giving steroids before elective caesarean section. BMJ 2005; 331: 645-646. 4. Crowley P, Roberts D, Dalziel S, Shaw BNJ. Antenatal corticosteroids to accelerate fetal lung maturation for women at risk of preterm birth. (Protocol) The Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454. 5. Royal College of Obstetricians and Gynaecologists Scientific Advisory Committee. RCOG guidelines. No 7: Antenatal corticosteroids to prevent respiratory distress syndrome. 2nd Ed.London: RCOG Press, 2004: 1-9 6. Dalziel SR, Liang A, Parag V, Rodgers A, Hardin JE. Blood pressure at six years of age after prenatal exposure to betamethasone: follow up results of a randomised controlled trial. Pediatrics 2004; 114. 7. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, Harding JE Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in randomised controlled trial BMJ, Sep 2005; 331: 665 Competing interests: None declared |
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David J R Hutchon, Locum Consultant Obstetrician Grey Base Hospital, Greymouth, New Zealand
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Is it surprising that the neonate sometimes fails to adapt properly to extra-uterine life when it is suddenly removed from the uterus and then its placental circulation immediately obstructed by a clamp? The authors do not describe in any detail the method of delivery by Caesarean Section so we can presume the method was that routinely used in England and Wales at present. The cord is routinely clamped immediately a Caesarean Section and, if resuscitation is required, the neonate is passed to a member of the paediatric team. (personal communication) A delay of at least 30 seconds is recommended before the cord is clamped at delivery of the preterm infant.(1) Preterm infants typically are at risk of developing respiratory distress syndrome. A delay of at least 30 seconds in the preterm neonate reduces neonatal anaemia and the need for transfusion as well as the risk of intraventricular haemorrhage. (1) There is also a decrease in the severity of respiratory distress.(2,3,4) Although clamping the pulsating cord immediately at delivery may be common practice, it is an intervention which requires informed consent. It would appear that such informed consent was not obtained in this study. David Hutchon Refernces 1. Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. The Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD003248.pub2. DOI: 10.1002/14651858. 2. Kinmond S, Aitchison TC, Holland BM, Jones JG, Turner TL, Wardrop CA. Umbilical cord clamping and preterm infants: a randomised controlled trial. BMJ 1993;306: 172-5. 3. Dunn P M. Stress failure of pulmonary capillaries at birth. The Lancet 1993;342:120 4. Dunn P M. Postnatal placental respiration. Developmental Medicine and Child Neurology. 1966;8:607 Competing interests: None declared |
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Peter Roy Stutchfield, Consultant Paediatrician Conwy and Denbighshire Trust LL18 5UJ, Rhiannon Whitaker
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The Antenatal Steroids for Term Elective Caesarean Section randomised trial (1) was established to determine whether giving 2 doses of betamethasone before delivery reduced the number of admissions of babies with respiratory distress to Special Care Baby Unit. Using data from a 2 year review of outcome of term elective caesarean sections at our hospital, we found that 8.9% of babies were admitted with respiratory distress. Recruiting 1100 mothers would have yielded 80% power of detecting a reduction in the percentage of babies admitted to special baby unit with respiratory distress from 8% to 4% using a 5% significance level. We successfully demonstrated a 50% reduction (from 5% to 2.4%) in admissions to special care for respiratory distress with the 942 patients we recruited. Mr Hutchon (2) correctly points out from Table 3 in the electronic version of our paper that the total number of babies admitted in the betamethasone group was 26/467 and in the control group 32/475, with no statistically significant difference in the overall rate of admissions to Special Care. The study was not powered or designed to show a difference in the total admission rate, merely the difference in the numbers admitted with respiratory distress. If a larger study was designed and adequately powered to show an overall difference in all admissions , we are confident that a reduction would be seen as a direct result of fewer admitted with respiratory distress. To assist readers to assess the results of the trial we supply the following additional information. Of those babies admitted in the betamethasone group, 11 had respiratory distress. The other 15 were admitted with a range of diagnoses : 4 jaundice, 2 poor feeding, 1 birth asphyxia, 1 hypoglycaemia, 2 normal neonates, 4 no diagnosis and 1 hyponatraemia. There were 32 admitted in the control group of whom 24 had respiratory distress and 8 admitted for other reasons: 1 feeding difficulties with hypoglycaemia, 1 dysmorphism – Prader Willi syndrome, 1 auto-immune thrombocytopenia, 1 jaundice, 1 unproven infection, 1 normal neonate and 2 no diagnosis given. This demonstrates that the admission of babies without respiratory distress was not related to antenatal corticosteroids. As is good practice our analysis was by intention to treat. Out of the eleven babies admitted with respiratory distress in the treatment group, four had not received betamethasone as they were delivered by emergency caesarean section before the betamethasone would have been administered. This further strenthens the findings of our study. We trust that this further information clarifies the situation. References 1. Stutchfield P, Whitaker R, Russell I. Antenatal Betamethasone and Incidence of Neonatal Respiratory Distress after Elective Caesarean Section: Pragmatic randomised trial. BMJ 2005: 331: 662-664. (Electronic publication 22.8.05) 2. Hutchon D J R. A clearer explanation of no benefit for steroids. BMJ e-letter 08.12.05. Competing interests: None declared |
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David J R Hutchon, Locum consultant obstetrician Greybase Hospital, Greymouth, New Zealand.
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The letter from Stutchfield (4) raises some very important issues and I am grateful for the authors’ rapid response now more than three months after I queried the figures. (1) My concern is to ensure that neonatal morbidity after elective Caesarean Section is minimised. The authors admit that the meaning of the study, that is reduced separation of the mother and baby, less interference with bonding and decresased cost of treatment in the special care baby unit, was not met overall by the administration of steroids. The criterion of reduced morbidity was only met for the babies admitted to special care with a diagnosis of respiratory distress or transient tachypnoea. However the treatment group was not blinded and there is a possibility of bias on the part of the doctor making the diagnosis. The fact that there were nine babies admitted to SCBU in the whole series with either no diagnosis or considered “normal” shows how tenuous admission to special care may be. A similar reduction in admissions to special care can be obtained by postponing delivery to at least 39 weeks. (2) The authors point out that there were four patients in the treatment arm who did not receive steroids because of emergency Caesarean Section before the betamethasone would have been completed. Although they do not state the reason, most likely this was because of the onset of spontaneous labour. The stress of labour in itself may reduce neonatal respiratory morbidity. The authors also point out that the results were analysed according to intention to treat as is the correct protocol. This mimics the real world since no doubt there would be a number women who go into labour before steroids could be effectively administered steroids before elective caesarean section was standard practice. I have raised the issue of minimising the pathological intervention of Caesarean Section by ensuring that it is not compounded by immediate cord clamping. (1) Delay of at least 30 seconds has been shown to have a beneficial effect on lung function. (3) This should be practiced routinely and of course can be applied even when caesarean section is an emergency. (4) A physiological approach must be preferable to a pharmacological approach. A single course of antenatal steroids may be fairly safe and justified to reduce the risk of respiratory morbidity in the small number of neonates in which elective caesarean delivery is necessary before 39 completed weeks. However it should not be used to make a more convenient earlier delivery. I accept that Stutchfield et al have made the effort to organise a randomised trial to investigate the use of steroids in elective caesarean section. A similar trial to determine the effect of physiological management of the third stage is urgently required. The end point must be morbidity associated with neonatal admission as it would be ridiculous to provide a solution for respiratory morbidity at the expense of overall morbidity. Investigators must approach such studies without preconceived opinions and with an open mind. Statements like “If a larger study was designed and adequately powered to show an overall difference in all admissions , we are confident that a reduction would be seen as a direct result of fewer admitted with respiratory distress” (4) do not fit with an open mind. References. 1. A physiological approach to reducing neonatal morbidity in elective Caesarean Section David J R Hutchon BMJ eletter 24 August 2005 2. Steer P J. Giving steroids before elective caesarean section. BMJ 2005; 331: 645-646. 3. Kinmond S, Aitchison TC, Holland BM, Jones JG, Turner TL, Wardrop CA. Umbilical cord clamping and preterm infants: a randomised controlled trial. BMJ 1993;306: 172-5. 4. Stutchfield P R and Whitaker R. Admissions to Special Care Baby Unit in the Antenatal Steroids for Term Elective Caesarean Section Trial. BMJ eletter 14 December 2005 Competing interests: I beleive in physiology before pharmacology |
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David JR Hutchon, Consultant Obstetrician and Gynaecologist Memorial Hospital, Darlington. DL3 6HX
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Sir, Stutchfield et al state in their rapid response that they are confident that a larger study, designed and adequately powered would show an overall difference in all admissions to the special care baby unit following antenatal steroids. (1) The study involved mothers in whom elective caesarean section was planned at 37 weeks' gestation or beyond. The most recent update of the Cochrane review (2) on antenatal corticosteroids showed a significantly increased relative risk of neonatal death of 3.25 (95% CI 0.99 – 10.66) following antenatal steroids given after 36 weeks gestation. I wonder how this risk could be justified in any future trial.
References Competing interests: None declared |
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Peter R Stutchfield, Consultant Paediatrician Conwy and Denbighshire Trust LL18 5UJ, Rhiannon Whitaker,
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We recently reported (1) that antenatal betamethasone is effective in reducing admissions to special care baby unit with respiratory distress after elective caesarean section at term. The recent Cochrane review (2) of 21 studies (3885 women and 4269 infants) concludes that a single course of antenatal corticosteroids should be considered routine for preterm delivery with few exceptions. A reduction in the number of babies with respiratory distress syndrome was found with fewer babies dying and a reduction in the incidence of cerebroventricular haemorrhage and necrotising enterocolitis. There was no evidence of a negative effect on the mother with good long term outcomes for mother and baby. The recent “rapid” response by D Hutcheon 23 October 2006 to our paper is misleading and incorrect. He reports that “The most recent update of the Cochrane review (2) on antenatal corticosteroids showed a significantly increased relative risk of neonatal death of 3.25 (95% CI 0.99 – 10.66) following antenatal steroids given after 36 weeks gestation.” The report actually states this relative risk as a “nonsignificant trend towards an increase in combined fetal and neonatal death”. One may argue that this is but a semantic difference, so it is educational to consider the evidence further. Of the 14 relative risks quoted in the relevant paragraph of the Cochrane report, six showed statistically significant benefits in reducing fetal and neonatal deaths, and seven showed no difference. Cochrane concluded that the combined fetal and neonatal death rate was significantly reduced in antenatal corticosteroid treated infants before 32 weeks ( RR 0.71 95% CI 0.57 to 0.88 ),before 34 weeks RR 0.75, 95% CI 0.58 to 0.91 ) ,and before 36 weeks (RR 0.75, 95% CI 0.61 to 0.94 ). The data which was combined to give the reported “nonsignificant trend” in relative risk of neonatal death of 3.25 (95% CI 0.99 – 10.66),following antenatal corticosteroids after 36 weeks gestation, is drawn from two studies. One of the two (3) included 37 babies and witnessed only one event (RR 1.88 95% CI 0.08 to 43.10). The second trial (4), of 211 cases and 250 controls dates back to a publication date of 1972, (RR 3.55 95% CI 0.97 to 12.96) reporting data which is now over 35 years old. They report 12 neonatal or fetal deaths in babies born at least 36 weeks (i.e. a 2.6% mortality). The very wide confidence limits in Cochrane reflect this limited data. Our study included 932 babies with a gestation 37 weeks or greater and observed a mortality rate of zero. Relative risks alter over time as medical practice develops. Our randomized trial shows that the widely demonstrated beneficial use of antenatal corticosteroids in preterm babies extends to those 37 weeks and greater. In planning an elective caesarean section, the risk of respiratory distress should be considered and the likely benefit of antenatal corticosteroids should be compared with those of delaying delivery until 39 weeks when possible. Outdated evidence should be viewed with caution, and statistical evidence should be read for what it is, an estimate of probability, not a guarantee of certainty. References 1) Stutchfield P,Whitaker R ,Russell I. Antenatal betamethasone and the incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331:662 (24 September 2005) 2) Roberts D,Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006,Issue 3 Art.No. CD 004454. 3)Doran TA, Swyer P,MacMurray B, Mahon W , Enhorning G, Bernstein A et al. Results of a double blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome American Journal Obstetrics and Gynaecology 1980;136 : 313 -20. 4)Liggins GC,Howie RN, A controlled trial of antepartum glucocorticosteroid treatment for the prevention of respiratory distress syndrome in premature infants. Pediatrics 1972;50:515 - 25 Competing interests: None declared |
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David JR Hutchon, Consultant Obstetrician and Gynaecologist Memorial Hospital, Darlington. DL3 6HX
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I am grateful for the response by Stutchfield et al (1) and I did misinterpret the 95% confidence interval (0.99 – 10.66) as significant. However I still feel that considerable caution needs to be exercised in view of the NON-significant trend. For my comment I relied upon, and misinterpreted the actual figures provided by the review (2) which showed a relative risk of fetal or neonatal death of 3.25 with 95% confidence intervals that I now realise do touch/cross unity. I did not appreciate that the authors considered this a non-significant trend. In my defence I quote from another Cochrane review comparing inhaled and systemic steroids. In the main results “There was an increase in the incidence of CLD at 36 weeks CGA in the inhaled steroid group amongst all randomised infants, which was of borderline statistical significance: [RR 1.45 (95% CI 0.99,2.11) “ Although the confidence interval also just crosses/touches unity the authors describe the result as borderline statistical significance. I recommend readers to check the facts for themselves. It is difficult to understand consistency as the word “trend” is also used three other times in the review(2). First in relation to proven neonatal infection ( RR 0.83, 95%CI 0.66-1.03), then in relation to a reduction in the need for surfactant (RR=0.72, 95%CI 0.51 – 1.03) and also in relation to having cerebral palsy (RR=0.60, 95%CI 0.34-1.03). The confidence intervals for all these conditions DO cross unity yet there is no mention of “non-significance” in these results. As we are all aware statistics can be manipulated to fit our prejudice. I agree that the numbers are small and the studies quite old. However data from the Auckland trial was recently analysed to demonstrate the long-term safety of antenatal steroids. If the data is good enough for this analysis it should be good enough to question the safety of corticosteroids after 36 weeks. Re-analysis of this trial data by Dalzeil et al showed, contrary to the original Liggins and Howe reports, “similar numbers of neonatal survivors with much the same perinatal morbidity in both … groups.” (3) It is not good enough for Stutchfield et al to quote their own results. The principle of systematic review is to include all controlled trial results including looking for unpublished data. Perhaps when the next update is published the Stutchfield et al data will be included. Stutchfield et al in their carefully worded rapid response referred to the reduced admissions to special care with respiratory distress after caesarean section, but as I previously pointed out there was no reduction in admissions overall. Surely we need to find a way of reducing all morbidity from caesarean section and I would welcome a response about cord management. A delay of a minute from birth to clamping the cord is now recommended by the UK neonatal resuscitation council. If this advice was implemented much of the neonatal morbidity might be avoided.
The correct spelling of my name is HUTCHON
Competing interests: None declared |
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