Displaying 1-10 letters out of 126 published
Re:Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case-control studies
In their paper1 Carpenter et al. conclude that bed-sharing of infants under 3 months with their parents even when the latter did not smoke and had no other risk factors the adjusted odds ratio for SIDS was 5.1 (2.3 to 11.4). This risk was greatly increased when the parents smoked, took alcohol or drugs. These findings are not surprising and confirm that co- sleeping is particularly dangerous for babies under three months of age. The main message is that co-sleeping (with or without other risk factors such as alcohol, other drugs or smoking) should never occur, but it is OK to breast feed in the parental bed and then to put the baby to sleep "face up" in its own cot (with clean linen) in the same room as the parent(s). The study pre-supposes that accidental smothering is the reason for these deaths while providing no autopsy evidence to that effect. The paper does not discuss the role of bacterial infection and only briefly alludes to it peripherally in terms of thermal stress (overheating) and the release of lethal toxins. It has been our view, that the theory of respiratory compromise due to smothering may account for only a very small minority of cases. The parental bed or sofa represents a dangerous sleeping surface, as both of these are heavily contaminated with bacteria such as Escherichia coli and Staphylococcus aureus which are equipped with a variety of lethal toxins. A baby sleeping in such a contaminated environment could inhale or ingest shed skin cells covered in these bacteria. A genetically susceptible baby is at risk in the co-sleeping situation. This risk is further increased with every additional risk factor.
Infection has long been recognised as a risk factor for SIDS as shown by symptoms and signs of respiratory and/or gastrointestinal infection in the days preceding SIDS death.2 Infection of normally sterile sites with major bacterial pathogens in SIDS has been independently described by two research groups.3,4 This finding could represent the 'footprint' of a bacteraemic episode prior to death.5,6 Bloodstream infection is a profound inducer of hypoxaemia; the mechanism of which is not fully understood, however, the cytokine storm almost certainly plays a major role7 and the hypoxaemia the storm produces seems to precede the final demise in monitored SIDS cases. In addition, it is plausible that the findings of Vargas et al.8 in relation to Pneumocystis lung colonization/infection, with increased mucus production, could contribute to hypoxaemia.
Not only is infection (via sepsis or toxaemia) an inducer of hypoxaemia, it is also a key thermogenesis inducer and is usually overlooked by SIDS researchers married to linking prone sleep to respiratory physiology. On the other hand, supportive evidence for plausible links between prone sleep position and infection have been proposed based on bacterial colonization and toxin induction with raised nasopharyngeal temperatures prone,9,10 and bacterial contamination of the sleeping surface promoting colonization of the infant's nasopharynx and gut.9-11 From studies in a neonatal ward conducted many years ago, it has long been known that organisms, such as E. coli are shed into the air and onto surrounding furniture by infants and their care-givers and that these bacteria can then colonize other infants and sometimes cause serious infection.12 Furthermore, as skin scales decorated with Staphylococcus aureus, and coliform (e.g. Escherichia coli) bacteria are shed in "dangerous sleeping environments" (parental bed, sofa, etc.) it is not unreasonable to conjecture that prone babies will inhale or ingest these bacteria and thereby provide the first step in a pathway leading to SIDS via the so-called "Common Bacterial Hypothesis of SIDS"13 or via toxigenic effects of these bacteria,5,6,14-24 Hypotheses of pathogenesis fail to adequately link all the known risk factors for SIDS into a holistic, all- encompassing hypothesis. Respiratory and brainstem and cardiac hypotheses compete to explain hypoxemia in the progression to SIDS and therefore do not satisfy a complete pathogenetic mechanism. A microbiological basis needs to be considered as the key for the epidemiological risk factors and the physiological findings provide a plausible explanation for SIDS.
Conflict of Interest: The authors have no conflicts of interest to disclose. Word count: 804 (excluding abstract and references)
Contributors' Statement: Paul N. Goldwater: Professor Goldwater drafted the initial manuscript and approved the manuscript as submitted. Karl A. Bettelheim: Dr Bettelheim conceptualized the article and reviewed and revised the manuscript and approved the manuscript as submitted.
REFERENCES 1. Carpenter R, McGarvey C, Mitchell EA, Tappin DM, Vennemann MM, Smuk M, Carpenter JR Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case-control studies. BMJ Open Access Research, May 21, 2013.
2. Hoffman HJ, Damus K, Hillman L, Krongrad E: Risk factors for SIDS. Results of the National Institute of Child Health and Human Development SIDS Cooperative Epidemiological Study. Ann N Y Acad Sci. 1988; 533: 13- 30.
3. Weber MA, Klein NJ, Hartley JC, Lock PE, Malone M, Sebire NJ: Infection and sudden unexpected death in infancy: a systematic retrospective case review. Lancet 2008; 371: 1848-1853.
4. Goldwater PN: Sterile site infection at autopsy in sudden unexpected deaths in infancy. Arch Dis Child. 2009;94(4):303-7. Epub 2008 Sep 15.
5. Goldwater PN. A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence. BMC Medicine 2011;9:64. http://www.biomedcentral.com/1741-7015/9/64.
6. Highet AR, Berry AM, Goldwater PN. Novel hypothesis for unexplained sudden unexpected death in infancy (SUDI) Arch Dis Child 2009; 94:841-843.
7. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. New Engl J Med. 2003; 348(2): 138-150.
8. Vargas SL, Ponce CA, Gallo F, Felipe Astorga J, Bustamante R, Chab? M, Durand-Joly I, Iturra P, Miller RF, Moukthar Aliouat EI, Dei-Cas E. Near universal prevalence of Pneumocystis and associated increase in mucus in the lungs of infants with sudden unexpected death. Clin Infect Dis 2013; 56: 171179.
9. Blackwell CC, Gordon AE, James VS, MacKenzie DA, Mogensen-Buchanan M, El Ahmer OR, Al Madani OM, T?r? K, Csuk?s Z, S?tonyi P, Weir DM, Busuttil A. The role of bacterial toxins in sudden infant death syndrome (SIDS). Int J Med Microbiol 2002; 291:561-570.
10. Molony N, Blackwell CC, Busuttil A. The effect of prone posture on nasal temperature in children in relation to induction of staphylococcal toxins implicated in Sudden Infant Death Syndrome FEMS Immunol. Med. Microbiol. 1999; 25: 109-114.
11. Goldwater PN. Sudden infant death syndrome: A critical review of approaches to research Arch Dis Child 2003, 88:1095-1100
12. O'Farrell SM, Lennox-King SMJ, Bettelheim KA, Shaw EJ, Shooter, RA. Escherichia coli in a maternity ward. Infection 1976, 4:146-152.
13. Morris JA. The common bacterial toxins hypothesis of sudden infant death syndrome. FEMS Immunol Med Microbiol 1999; 25:11-17.
14. Bettelheim KA, Dwyer BW, Smith DL, Goldwater PN, Bourne, AJ. Toxigenic Escherichia coli associated with sudden infant death syndrome. Med J Aust. 1989; 151:538.
15. Bettelheim, KA, Goldwater, PN, Dwyer, BW, Bourne, AJ & Smith, DL. Toxigenic Escherichia coli associated with Sudden Infant Death Syndrome. Scand J Infect Dis.1990; 22:467-476.
16. Bettelheim, KA, Smith, H, Goldwater, PN, Morris, JA, Murrell, TGC, Sweet, C, Weaver, SA. Sleeping position and cot deaths Lancet 1991; 338:192.
17. Bettelheim KA, Chang BJ, Elliott SJ, Gunzburg ST, Pearce, JL. Virulence factors associated with strains of Escherichia coli from cases of sudden infant death syndrome (SIDS). Comp Immunol Microbiol Infect Dis. 1995; 18:179-188.
18. Bettelheim KA, Luke RKJ, Johnston N, Pearce JL, Goldwater, PN. A Possible Murine Model for Investigation of Pathogenesis of Sudden Infant Death Syndrome Curr Microbiol 2012, 64:276-282.
19. Goldwater, PN, Bettelheim, KA. Curliated Escherichia coli, soluble curlin and the sudden infant death syndrome (SIDS): J Med Microbiol 2002; 51:1009-1012.
20. Highet, AR, Goldwater PN. Staphylococcal enterotoxin genes are common in Staphylococcus aureus intestinal flora in Sudden Infant Death Syndrome (SIDS) and live comparison infants. FEMS Immunol Med Microbiol. 2009; 57:151-155.
21. Pearce JL, Luke RKJ, Bettelheim KA. Sudden infant death syndrome: What questions should we ask? FEMS Immunol Med Microbiol 1999; 25:7-10.
22. Pearce JL, Luke RKJ, Bettelheim KA. Extraintestinal Escherichia coli isolations from SIDS cases and other cases of sudden death in Victoria, Australia FEMS Immunol Med Microbiol 1999; 25:137-144.
23. Pearce JL, Luke RKJ, Bettelheim KA. Infection and food: a factor in sudden infant death syndrome? FEMS Immunol Med Microbiol 2004; 42:66- 75.
24. Pearce JL, Bettelheim KA, Luke RKJ, Goldwater, PN. Serotypes of Escherichia coli in Sudden Infant Death Syndrome. J Appl Microbiol 2010; 108:731-735.
Conflict of Interest:
Re: Bed sharing when parents do not smoke: is there a risk of SIDS?
Charlotte K Russell - Research Associate, Department of Anthropology, Durham University
Helen L Ball - Professor of Anthropology, Department of Anthropology, Durham University; Director of the Parent-Infant Sleep Lab
This publication analyses SIDS-risks associated with bed-sharing under different circumstances using data from five historical SIDS studies. Unlike previous analyses of these data, this analysis includes data on feeding type. It promises, at last, to enable those of us working with parents and the staff who support them to be able to answer complicated but commonly asked questions about SIDS, and allow parents to make informed decisions about any potential risk associated with their personal and cultural infant care beliefs and behaviours.
Because this analysis is based on old data, however, it can only inform us as to the risks as they existed 15-26 years ago: knowledge both of bed-sharing behaviour and safety issues not considered here have advanced considerably in the intervening period. The authors present analysis of a dataset in which 'safer' bed-sharing is considered as distinct from bed-sharing in conjunction with known hazards (that is, breastfeeding infants bed-sharing in the absence of smoking, alcohol, drugs and sofa-sharing). Babies were categorized as bed-sharing if they were found dead in the parental bed, or woke up in the parental bed in the morning following the 'index night' (deviating from the original analyses which used many different definitions for 'bed-sharing'). This definition under-estimates the number of 'control' babies who bed-shared as some infants bed-share for a portion of the night and are placed in a cot following the last feed, so would not wake up in the parents' bed (and would be classed here as 'room-sharers'), however babies who die would not be returned to the cot. 'Accidental' (and consequently unplanned) bed- sharing is therefore also likely to be overrepresented in the SIDS group (Ball 2012). Both factors would inflate the risk associated with bed- sharing.
The authors predict a SIDS-rate of approximately 1 per 10,000 babies for room-sharers, and 2 per 10,000 babies for bed-sharers. The current rate of SIDS in UK is 1/3000, or 3.4/10,000, which means that both sleep locations for breastfed infants of non-smoking parents in the absence of alcohol experience very few SIDS deaths. It is curious, therefore, that the authors focus attention only to this small difference in predicted SIDS rates for breastfed babies of non-smoking parents who bed-share compared to room-sharing-while ignoring the hugely inflated risks associated with hazardous bed-sharing environments. It appears as though the authors choose to target breastfeeding mothers in this way as they are a sub-group with strong opinions about the benefits of bed-sharing, even though the infants of these mothers contribute negligibly to UK SIDS rates.
The recommendations of the authors that parents are advised to 'simply avoid bedsharing' indicates a worrying lack of cultural awareness or sensitivity to childrearing beliefs of different groups of parents on the part of these SIDS researchers. Such a recommendation does not allow parents, especially those whose infants are at low risk for SIDS (healthy term births, breastfed, not exposed to parental smoking or alcohol consumption), to make an informed choice to bed-share or not. While single message recommendations may have been appropriate and effective in previous campaigns targeting simple infant care practices such as supine vs. prone sleep position, they are inappropriate and ineffective for addressing infant care issues involving relational behaviours and cultural beliefs (Ball and Volpe 2012). Closing down all discussion of the reasons why parents might bed-share with their infant by issuing a dogmatic recommendation inhibits health professionals from raising the topic, causes parents to lie about their behavior, and stifles the provision of information about hazardous sleeping environments and the degrees of risk involved (Fetherston and Leach, 2013).
We argue that SIDS is not the only issue that must be taken into consideration when considering parent-infant bed-sharing, and that risk minimization, involving parent education and facilitating informed choice, is a more logical and ethical approach to the bed-sharing issue, than one focusing on risk elimination.
Ball, H. L. (2012). Sleeping with the baby. IBFAN Breastfeeding Briefs, No. 53, September 2012.
Ball, H. L., & Volpe, L. E. (2013). Sudden Infant Death Syndrome (SIDS) risk reduction and infant sleep location - moving the discussion forward. Social Science & Medicine, 79, 84-91.
Fetherston C.M., & Leach, J.S. (2012) Analysis of the ethical issues in the breastfeeding and bedsharing debate. Breastfeeding Review, 20(3): 7-17.
Conflict of Interest:
Ball and Russell run the Infant Sleep Information Source (ISIS), an online source of infant sleep research information for parents and health professionals (www.isisonline.org.uk). They do so as part of their academic outreach activities and do not receive any income from the project.
Inadequate data, too many confounders and a ridiculous analogy!
I am appalled that this paper managed to get past peer review and reach publication. The authors define 'breastfed' as 'partially or completely breastfeeding at time of death or interview'. This implies there were babies entered into the breastfed group who were receiving formula in quantities that are unknown. What exactly is partially breastfed? Is this one, two, three bottles of formula per day? One breastfeed per day? I cannot seem to find any more data about the feeding. They seem to have grouped partial and fully breastfeeding together, so one cannot extrapolate this data to exclusively breastfed infants.
The authors do not have data on maternal alcohol/ drug consumption in the previous 24 hours in three out of five of the studies. They have instead used imputed data to make up for this. How one goes about imputing values from studies conducted across the world with different cultural habits is beyond me!
I am struggling to understand why they looked at 'mothers who took 2 units or more of alcohol in the previous 24 hours'. This implies that there were mothers in the control group who had alcohol on board who co- slept with their babies which is clearly against advice regarding sleeping safely with your baby. Recalling units is also extremely difficult, given that most people (in my professional experience as a GP) cannot accurately estimate how many units they are drinking.
We also have no information on the partners' alcohol and drug consumption. Surely this must be an important variable to include in a study looking at all the hazards of bed-sharing?
If only the authors asked the right question (i.e. what is the risk of SIDS in babies who are exclusively breastfed who co-sleep with parents who do not drink alcohol, smoke or take drugs?), then we may actually have some useful answers.
Oh yes, I also object to being compared to a sow! The authors use the analogy of a sow crushing her piglets to meet the Bradford-Hill criteria. This is really scraping the barrel. If we [breastfeeding mothers] are now to be compared with animals, at least have the decency to compare us to animals of the same order who live in their natural environment and are not intensively farmed!
This study has now been splashed around the media as if it is gospel, despite its many flaws. I am deeply concerned about the message this study will send to exclusively breastfeeding mothers who will now be petrified of bed-sharing so will fall asleep on sofas/ breastfeeding chairs instead. In the meantime, mothers will co-sleep anyway without access to information on safe bed-sharing.
The BMJ Open has a duty to filter out the studies which draw conclusions from inadequate data which is subject to all kinds of bias, where the confounding issues have not been appropriately accounted for. I am disappointed BMJ Open - the consequences of publishing such a study could be disastrous!
Conflict of Interest:
Salaried GP, breastfeeding mother
Incomplete examinations are irrelevant and all too frequent.
Dear Editor: By design, incomplete examinations provide data that lead to superficial correlations, erroneous inferences, and poor public health policy. Schmidt et al.1, provide an exemplar of this increasingly frequent event. Physical inactivity is a leading cause of death worldwide as well as a principal underlying pathology in most major causes of morbidity and mortality.2 Inactivity affects cardiovascular disease3,4, cancer5, obesity 6,7 and type 2 diabetes.8 Importantly, studies that purport to examine associations between BMI-defined obesity and chronic non-communicable diseases without examining physical activity are by design rendering their conclusions irrelevant by ignoring a major causal factor in their analyses. We have published numerous papers showing that obese individuals who are moderately fit, as assessed by a maximal treadmill test have substantially lower death rates during follow-up than people who are normal weight and unfit.9 We contend that one cannot study the health effects of obesity and diet without properly measuring physical activity or fitness and incorporating them into the analyses. We think because Schmidt et al.,1 explicitly acknowledge the importance of "exercise" when counseling patients on risk management, they should acknowledge that their failure to include physical activity in the analyses does little to advance the science of disease management.
1.Schmidt M, et al. BMJ open. 2013;3(4). 2.Lee IM, et al. Lancet. Jul 21 2012;380(9838):219-229. 3.Archer E, Blair SN. Prog Cardiovasc Dis. May-Jun 2011;53(6):387-396. 4.Blair SN, et al. JAMA. 1995;273(14):1093-1098. 5.Lee CD, et al. Ann Epidemiol. Oct 2011;21(10):749-754. 6.Hankinson AL., et al. JAMA. 2010;304(23):2603-2610. 7.Donnelly JE., et al. Arch Intern Med. 2003;163(11):1343-1350. 8.LaMonte MJ. et al. J Appl Physiol. Sep 2005;99(3):1205-1213. 9.Sui X., et al. JAMA. Dec 5 2007;298(21):2507-2516.
Conflict of Interest:
A lack of data and questionable emphasis
The report by Carpenter et al  on whether there is a risk of SIDS associated with bed sharing when parents do not smoke fails to meet its stated objective because the data needed to resolve any uncertainty is not available from the studies presented. The over-arching argument is whether bed-sharing in itself poses a risk to infants or whether the risk is within the hazardous circumstances in which we bed-share. Parental smoking, recent alcohol consumption, use of illegal drugs and the use of sofas have all been identified in a detailed sleep scene investigation from a more recent SIDS study in the UK.  None of these older studies (data collected between 1987 and 2003) have data on recent parental drug consumption prior to the last sleep, none have data on recent paternal alcohol consumption and only two of the five studies have data on recent maternal alcohol consumption. It is not clear whether the parent who drank alcohol was the parent sleeping next to the infant for the last sleep and trying to impute values of maternal alcohol consumption from different cultures in different countries at different time periods when the question was not even asked makes unreasonable equivalence assumptions about maternal drinking.
The authors do have data on smoking status but conspicuous by its absence is the overall risk associated with bed-sharing amongst smokers and non-smokers. The reported adjusted risk for bed-sharing is 2.7 [95% CI: 1.4 to 5.3] and the age specific breakdown in Figure 2 suggests this risk is much higher amongst smokers (almost ten-fold). Conversely the overall adjusted OR for bed-sharing amongst non-smokers must be considerably lower than 2.7, probably just above unity and possibly not significant. The impression however given from the abstract is a five- fold increase in risk for bed-sharing when neither parent smoked but this is in reference to a group at very low risk of SIDS. The baseline group used in Table 3 is limited to breastfed girls placed on their back to sleep by the side of the parental bed with no other risk factors present serving to inflate subsequent adjusted risks. Thus the risk of bed-sharing when parents smoke is 21.6 and the risk when they also consume alcohol is 151. The lack of emphasis on such findings is quite astounding.
The strategy that parents should avoid bed-sharing as advocated by the authors ignores the fact that parents often fall asleep with their baby whether they intend to or not, particularly when they are feeding or caring for their baby during the night. We also know that some parents choose to bring their baby into bed for cultural reasons. Any guidance that recommends the total avoidance of bed-sharing can end up forcing parents into much riskier practices such as feeding on sofas and armchairs where they can easily fall asleep. It is surprising in this paper that this risk factor has not been explored as 3 of the 5 studies have previously reported on sofa-sharing with a combined univariable risk of almost 30, 10-fold higher than the risk associated with the parental bed.
UNICEF's leaflet and accompanying health professional guidelines on 'Caring for your baby at night'  do not actively promote bed-sharing but acknowledge that some parents will choose to sleep with their baby and fall asleep whether they intend to or not. Carpenter et al are not suggesting the baby is never brought into the bed so some parents, especially in the first months after the baby is born, will inevitably fall asleep. It is therefore important to emphasise risks that are a magnitude greater than other infant care practices and alcohol consumption, drug consumption, smoking and sofas fall into this category.
The risk of bed-sharing when the parents do not smoke appears quite negligible (when using the whole dataset) in comparison with the almost inestimably large risk of bed-sharing under hazardous circumstances.
References 1. Carpenter R, McGarvey C, Mitchell EA, Tappin DM, Vennemann MM, Smuk M, Carpenter JR. Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case-control studies. BMJ Open 2013;3:e002299. doi:10.1136/bmjopen-2012-002299 2. Blair PS, Sidebotham P, Evason-Coombe C, Edmonds M, Heckstall-Smith EM, Fleming P. Hazardous cosleeping environments and risk factors amenable to change: case-control study of SIDS in south west England. BMJ 2009;339:b3666. doi: 10.1136/bmj.b3666. 3. http://www.unicef.org.uk/BabyFriendly/Resources/Resources-for- parents/Caring-for-your-baby-at-night/
Dr Peter S Blair, Prof Peter J Fleming & Sue Ashmore
Conflict of Interest:
Maternal choice and macrosomia are likely significant contributors to CS rates
In the UK, the rate of maternal request caesareans is also higher in private hospitals, and up until November 2011 (when NICE guidance on Caesarean Section changed) maternal request was not on its own supported as an indication for CS in public (NHS) hospitals; therefore many women, who could afford to, paid for their maternal request caesarean privately.
Unfortunately, despite the fact that NICE guidance now supports maternal request following an individual's risk and benefit consultation (and the offer of counseling in cases of tokophobia), a blanket refusal of maternal request still occurs in many NHS hospitals.
This is largely because UK maternity recommendations push for caesarean rate reduction and an increase in what is ideologically described as 'normal birth', which is obviously a very difficult environment for women who want a caesarean to actually have a caesarean.
While it is not my intention to suggest that maternity care in the private sector is necessarily better than the public sector, or in any way to advocate that a planned caesarean is the best birth plan for all women, I do believe it's worth noting the findings of two Australian research papers in this context.
First, a survey of four public hospitals that found one in three women (33%) identified a traumatic birthing event and reported the presence of at least three trauma symptoms, and second, a survey of 78 women who had requested and planned a cesarean birth in private maternity hospitals, which found the women were highly satisfied with their delivery. On a scale from 1 (totally unsatisfied) to 10 (completely satisfied), the mean score was a significantly high 9.25.
Perhaps maternal request is contributing to rising caesarean rates more than has been traditionally considered, and because private health care offers women a greater freedom of maternal autonomy over how they give birth, maternal request rates can be seen most clearly there.
Finally, it is worth considering obstetricians' attitudes to risks associated with macrosomic babies, as this may be contributing to increased rates of caesarean births too. Research carried out in 2001 in Australia and New Zealand found that the proportion of doctors who would choose a caesarean rose from 11% to 26% if the baby was believed to weigh 8.8 pounds, and as high as 55% if 9.9 pounds or more, mainly due to fear of fecal and urinary incontinence. If these concerns are more readily communicated to women in the private sector, then this may influence women's final birth plan choice, and in an environment of increased maternal weight and birth weights at full term, again, it could very well be a significant factor.
References  National Institute for Clinical Excellence. Caesarean Section CG132 Guideline.  New RCOG guidance urges CCGs to increase births without epidurals and reduce caesarean rates to 20% August 24, 2012 electivecesarean.com [and] Making sense of commissioning Maternity Services in England - some issues for Clinical Commissioning Groups to consider. August 14, 2012 RCOG  D. K. Creedy, i. M. Shochet, and J. horsfall, "Childbirth and the Development of Acute trauma Symptoms: incidence and Contributing Factors," Birth 27, no. 2 (June 2000): 104-11.  Stephen Robson et al., "Elective Caesarean Delivery at Maternal request: A Preliminary Study of Motivations influencing Women's Decision Making," Australian and New Zealand Journal of Obstetrics and Gynaecology 48, no. 4 (August 2008): 415-20.  R. land et al., "Personal Preferences of Obstetricians towards Childbirth," Australian and New Zealand Journal of Obstetrics and Gynaecology 41, no. 3 (August 2001): 249-52.
Conflict of Interest:
Co-author of Choosing Cesarean, A Natural Birth Plan
Re:Maternal age as a confounder
I think you very much for your comment on the article. In response to your comment I have now re-analysed the pre-labour caesarean section rates according to age group, ie for women under the age of 30 and women over 29.
The separate results for these two age groups showed exactly the same pattern as for the groups combined. For example, the caesarean section rate for women over 29 years of age increased by 5.4% annually (CI=3-8%) for private patients, but was stable at 1.4% for public patients. Similarly, for women under 30 years of age, caesarean sections increased by 6% annually (CI=1-12) for private patients, but were again stable at 0.5% for public patients.
We therefore believe that there is minimal, if any, confounding by age as the effect exist for both older and younger women.
Conflict of Interest:
Omega-3, omega-6 and vitamin treatment for relapsing-remitting multiple sclerosis
Dr. Pantzaris and colleagues (1) have recently performed a study on a dietary intervention consisting of omga-3, omega-6 and vitamin A and -E in various formulations in relapsing-remitting multiple sclerosis (RR-MS). The authors suggested that a special combination of omega-3, omega-6 and fat soluble vitamins could have profound effects on magnetic resonance (MR) disease activity and disease progression. The main problem in intervention studies, where different compounds and interventions are combined, is to determine which substance actually had a therapeutic effect. There have been a number of both randomised controlled trials and cohort studies published on dietary intervention in MS, which could have helped to explain the findings in this study (for two excellent reviews, see Geldern et al. (2) and Farinotti et al (3)). Unfortunately, these studies have not been cited or discussed in the article. We think these newly published data should be taken into account when interpreting their results, as this will be of great importance for future larger randomised controlled clinical trials.
As one of their findings, the authors suggest that omega-3 intervention, in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), could have therapeutic effects in MS. Although omega-3 has a theoretic anti-inflammatory effect, recently performed RCTs have not detected any positive effects on relapse-rate (4, 5) or MRI activity (6). Further, experimental studies in different animal models for MS have indicated conflicting results, with most studies actually reporting a negative effect of omega-3 intervention (7). Thus, there seems to be little rationale for choosing EPA and DHA as interventional substances. The fact that the authors did not detect any positive effect in treatment arm A, where these substances were given, further suggests that EPA and DHA did not have any treatment effect in this study either.
The authors also gave the patients in two of the experimental groups omega-6 fatty acids in the form of gamma-linoleic acid (GLA) and linoleic acid. Some studies have indicated a possibly reduced relapse severity and lower increase in disability in those receiving GLA than placebo (8), but the results are difficult to interpret because of lacking information on dropouts and patient characteristics. One recently published Cochrane review, based on all published studies on omega-3 and omega-6 supplementation, concluded that PUFA supplementation seemed to have no effect on disease progression (3). Although it is possible that the omega- 6 supplementation given to the MS-patients in two of the treatment groups could have had a beneficial effect on MRI disease activity, this seems less likely, as both group A and B also received the same dosage of omega- 6 supplementation.
Recently performed cohort-studies indicate that both vitamin A and E could have important disease modifying effects in MS (9, 10). Further, both vitamins have biological properties and have demonstrated positive effects in animal models for MS, which make them interesting candidates for future intervention studies (11). In one cohort study, where patients were followed for two years, we found that each 1 ?mol/L increase in serum -retinol reduced the odds ratio for new T1 gadolinium enhanced lesions by 49%, new T2 lesions by 42%, and combined unique activity by 46% in simultaneous MRI scans (9). We were also able to control for serum-levels of EPA, DHA and 25-hydroxyvitamin D, and found that they did not affect this association. Also higher serum levels of Retinol Binding Protein (a surrogate marker for vitamin A) has recently been demonstrated to be associated with decreased MS risk (OR=0.38) (12). In Pantzaris' and colleagues study (1), vitamin A was given to the patients in intervention group A and B, but the amount was rather moderate (0.6 mg), which is below the recommended dietary allowance for men and women of 0.9 and 0.7 mg, respectively. For vitamin E, we have demonstrated that during interferon beta (IFNB) treatment, each 10 ?mol/L increase in alpha-tocopherol reduced the odds ratio for simultaneous new T2 lesions by 36.8%, and for combined unique activity by 35.4% (10). As for vitamin A, we were also in this study able to control for serum-levels of EPA, DHA and 25-hydroxyvitamin D, without detecting any interaction. Since the patients in group B received both vitamin A and high dose vitamin E, this combination seems to be the most plausible explanation for the positive effect in this study, and not EPA and DHA, which were also given to the treatment arm where no effect was detected.
The authors of the present study reported a dropout rate of 49%, making it difficult to draw firm conclusions about their results. As most patients discontinued because of unpleasant taste and smell of the interventional treatment with fatty oils, we would suggest that future studies could primarily aim at detecting a possible protective effect of vitamin A and E treatment. This would probably greatly influence the compliance in future studies. The biological rationale for choosing these substances are stronger than for the PUFA-supplementation, which based on what we know from previous studies, probably have no beneficial effects in MS (3).
References: 1 Pantzaris MC, Loukaides GN, Ntzani EE, Patrikios IS. A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double- blind, placebo-controlled proof-of-concept clinical trial. BMJ Open. 2013; 3 (4).
2 Geldern G, Mowry EM. The influence of nutitional factors on the prognosis of multiple sclerosis. Nature Reviews Neurology. 2012; 8, 678- 689
3 Farinotti M, Vacchi L, Simi S, Di Pietrantonj C, Brait L, Filippini G.Dietary interventions for multiple sclerosis. Cochrane Database Syst Rev. 2012; 12: CD004192.
4 Bates D, Cartlidge NE, French JM, et al. A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 1989; 52 : 18-22.
5 Weinstock-Guttman B, Baier M, Park Y, et al. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot Essent Fatty Acids. 2005; 73: 397-404.
6 Torkildsen O, Wergeland S, Bakke S, Beieske AG, Bjerve K, Bjornar? B, Bjorn? IK, Bru A, Dalene F, Eikeland R, Henriksen OA, Hovdal H, Kierulf H, Kleveland G, Kristensen T, Lilleaas F, Midgard R, Olsen IC, Pedersen T, Schepel J, Myhr KM. Omega-3 Fatty Acid Treatment in Multiple Sclerosis (OFAMS study): a randomised, double-blind, placebo-controlled trial. Archives of Neurology. 2012; 69: 1044-1051.
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Conflict of Interest:
Maternal age as a confounder
I acknowledge the authors attempts to correct for confounders such as placenta pravia and breech in this interesting paper, but also think that the significant known confounding effect of maternal age (some references below) and effects on mode of delivery should also have been addressed.
Am J Obstet Gynecol. 1987 Feb;156(2):305-8. Maternal age and primary cesarean section rates: a multivariate analysis. Martel M, Wacholder S, Lippman A, Brohan J, Hamilton E.
Bell, Jacqueline S., et al. "Do obstetric complications explain high caesarean section rates among women over 30? A retrospective analysis." BMJ: British Medical Journal 322.7291 (2001): 894.
Conflict of Interest:
Time Pressure: The Elephant in the Room
This is excellent work, and something most of us, i would like to think,know for a very long time!
Time pressures is the single most important factor, aside from lack of knowledge and skills, that results in acts of commission or omission, sometimes with harm ensuing. Something akin to "system error"
A GMC backed study recently suggested, due to time pressures, GPs find it difficult to achieve the requisite amount of CPD. And then there was the major study on prescribing errors in primary care recently and an important theme there was time pressures disabling GPs from getting it right all the time. The RCGP, unless i am wrong, has called for extension of the consultation time from 10 to 15minutes- i agree.
Can you imagine, comparing us to other professionals like Lawyers or others, which reasonable man on the Clapham Omnibus would consider 10 minutes as anywhere satisfactory for a proper holistic safe consultation? When patients are told they only have 10 minutes they are often shocked to hear this.
Whereas one can appreciate that to get through the workload in ones day,short consultations time are the only way round that, i would argue the end does not justify the means however way you look at it.
Conflict of Interest: