We read with interest the article by Ainsworth et al regarding referrals for MMR immunisation in hospital(1). We have had a similar experience in Ireland with many children being unnecessarily referred for hospital MMR, and unsuccessful reassurance of parents and GPs that MMR can safely be given to egg allergic children in the community(2).

During 2007 and 2008, 47 of 91 referrals to Cork University Hospital for vaccination were for MMR in egg allergic children, 6 of whom had previous anaphylaxis. One third of children were referred despite the receiving consultant writing to the family doctor to advise routine immunization in the community. In 2009 we started to include the 2007 BSACI guideline(3) with these letters, we circulated this advice in a Public Health bulletin that is sent to all doctors in our region, and we regularly covered the topic in education sessions for family doctors and hospital trainees. Hospital administration of MMR to egg allergic children fell to 5 in 2009, and 3 in the first half of 2010. Govindaraj et al also reported a similar reduction in hospital MMR when they introduced a structured approach to these unnecessary referrals(4).

Advocacy for adherence to best practice requires more than enthusiasm and personal conviction; changing mindsets and fixed cultures requires systematic, multi-faceted approaches. The BSACI advice is just one part of this approach and we recommend that paediatricians continue to use it while engaging positively with colleagues in primary care and directly with parents who may be misinformed about vaccination risks(5).

1. Ainsworth E, Debenham P, Carrol ED, Riordan FA. Referrals for MMR immunisation in hospital. Arch Dis Child. 2010 Aug;95(8):639-41.

2. Hawkes CP, Mulcair S, Hourihane JO. Is hospital based MMR vaccination for children with egg allergy here to stay? Ir Med J. 2010 Jan;103(1):17-9.

3. British Society of Allergy and Clinical Immunology Paediatric Allergy Group. Recommendations for combined measles, mumps and rubella (MMR) vaccination in egg-allergic children. 2007.

4. Govindaraj P, Alfaham M, Davies C, Tuthill D. Decline of hospital admissions for MMR vaccinations in children with egg allergy. Arch Dis Child. 2009 Nov;94(11):914-5.

5. Jessop LJ, Kelleher CC, Murrin C, Lotya J, Clarke AT, O'Mahony D, et al. Determinants of partial or no primary immunisations. Arch Dis Child. 2010 Aug;95(8):603-5.

Conflict of Interest:

None declared

We thank Professor Ahmed and colleagues for adding a substantial number of new cases of vitamin D deficiency to the national and international literature [1]. Hopefully, this new information will add further strength to the calls for a more coordinated and effective Public Health intervention that will, once again, lead to the control of this preventable condition. Vitamin D deficiency has been linked with a multitude of problems such as type 1 diabetes mellitus, cardiovascular morbidity and mortality, certain cancers and multiple sclerosis [2]. The cost-effectiveness of supplementation with vitamin D in children has been demonstrated even in studies considering acute treatment costs incurred to deal with rickets alone [3].

Even though there is good evidence for supplementation, in the 2003 antenatal guideline, NICE did not consider vitamin D supplementation as a routine part of antenatal care. Fortunately, the 2008 version of the guideline [4] suggests that all women should be informed at the booking appointment about the importance, for their own and their baby's health, of maintaining adequate vitamin D stores during pregnancy and the breastfeeding period. The guideline also goes on to identify certain characteristics that would place women into a high-risk category for vitamin D deficiency.

This latest guideline from NICE [4] has been adopted by our institution (Central Manchester Foundation Trust). Further, the DoH recommends supplementation of children with vitamin D to the age of 5 [5]. After obtaining approval from the Trust's Audit Department, we undertook a prospective audit over 1 week in January 2010, in St. Mary's Hospital, Manchester. Our aims were to assess maternity team awareness of the aforementioned guidelines. Using specifically designed proformas, we collected information from 50 new mothers and 52 midwives selected at random.

36/50 (72%) of the mothers we approached had at least one factor putting them in the high-risk category (12/50 (24%) were in the high-risk age group; 7/50 (14%) had a pre- pregnancy BMI>30; 24/50 (48%) had dark skin; 16/50 (32%) dressed conservatively). Only 8/50 (16%) of the mothers had been informed about vitamin D supplements and/or Healthy Start multivitamins. 19/50 (38%) had been taking vitamin D supplements ( 3 from their GPs and the rest over the counter). The majority (14/19; 74%) started their supplementation in the first trimester, with smaller numbers starting in the second (3/19; 16%) and even third (2/19; 10%) trimester.

20/52 (38%) of the midwives we interviewed worked in the community, 18/52 (35%) in the postnatal wards, 9/52 (17%) in antenatal clinics, and 5/52 (10%) were in rotation between all sites. The midwives who were aware of the guidelines (22/52; 42%) were giving advice on vitamin D supplementation to expectant women. There was some confusion among the interviewed midwives as to who prescribes the supplements with the majority replying that it was the GP (15/22; 68%), whilst some thought it was the obstetrician (4/22; 18%), or were not sure (3/22; 14%). Of the 22 midwives aware of the local guideline, only 16 knew that supplements should be started in the first trimester.

34/52 (65%) of the midwives interviewed were aware of who is considered high risk. When asked whether they might want to check vitamin D levels on these women, 11 of these midwives (34%) said that they would. For this, some would have referred to the obstetrician (5/11; 45%), others to the GP (5/11; 45%) and there was 1 midwife (10%) who would have checked vitamin D levels with the booking bloods. When asked about supplementation of babies, only 15 of the 52 interviewed midwives (29%) were aware of the DoH guideline.

It is obvious that despite the release of guidelines from respected bodies such as NICE, there is, still, limited awareness of the guidelines and absence of clear pathways of how to deal with this growing problem. We agree with Ahmed et al. [1] that campaigns to raise awareness among both healthcare staff and the general public are mandatory. Further, all women should be provided with written information about vitamin D at their booking appointment and those identified as high-risk (perhaps combining 2 -3 risk factors) need to have their vitamin D levels measured as supplementation at the recommended amounts will not treat deficiency. Clear and funded referral pathways need to be in place in every area so that those with deficiencies are appropriately investigated and treated. All pregnant and breastfeeding mothers, and babies need to be offered vitamin D supplements. Perhaps, the Birmingham model of Public Health interventions [6] should be followed more widely in order to curtail vitamin D deficiency and decrease ill health. We are currently looking to bring in a similar arrangement in Manchester.

References:

1. Ahmed SF, Franey C, McDevitt H, et al . Recent trends and clinical features of childhood vitamin D deficiency presenting to a children's hospital in Glasgow. Arch Dis Child 2010 ; ( in press ).

2. Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta- analysis. Arch Dis Child. 2008 Jun;93(6):512-7.

3. Zipitis CS, Markides GA, Swann IL. Vitamin D deficiency: prevention or treatment? Arch Dis Child. 2006 Dec;91(12):1011-4.

4. National Institute for Clinical Excellence. Antenatal care. Routine care for the healthy pregnant woman. London, NICE, 2008 (available at http://www.nice.org.uk/nicemedia/ pdf/CG62FullGuidelineCorrectedJune2008July2009.pdf).

5. Chief Medical Officer. Meeting the need for vitamin D. CMO Update 2005;42:6 (available at http://www.dh.gov.uk/assetRoot/04/11/56/64/04115664.pdf).

6. Nick J Shaw, et al. Vitamin D supplementation-Easier said than done. BMJ (available at http://www.bmj.com/cgi/eletters/340/jan11_1/b5664#230270)

Conflict of Interest:

None declared

Dear Sir

Response to letter from James P Hoffman of Martek Biosciences Corp.

We completely disagree with Dr Hoffman's statement that "caregivers of preterm infants are not well served by our report of a 10 year follow-up of LCPUFA supplementation in preterm infants". Our study (1) presents the results of the longest follow-up of a randomised trial LCPUFA supplementation during infancy to date. We have explicitly acknowledged the shortcomings of the study (mainly cohort attrition) to a much greater extent than is typical in a study of this type, and we have discussed the limitations of our data and the need for further research into these outcomes. Our responses to Dr Hoffman's specific points are detailed in the Appendix.

It is worth noting here that, although the vast majority of infant formulas now contain LCPUFA, the scientific evidence base for their addition is recognised by most investigators and Key Opinion Leaders in the field to be weak; the most recent update of the Cochrane systematic reviews on LCPUFA supplementation of formulas for both preterm and term infants (encompassing 29 trials) concluded that there is no evidence for outcome benefits of the intervention, at least up to 18 months of age (2,3). We contend this field of research has been driven to an extent by enthusiasm and vested interest. As one of the major groups to do outcomes research in this area, we do not hold a fixed position but are open to the scientific evidence, and we have published on both positive and negative effects of supplementation in different trials. Our experience of publishing in this field has consistently been that publications supporting the addition of LCPUFA to infant formula are more readily accepted and less criticised than those which do not support the intervention, or which raise potential concerns. Thus studies such as that of Birch et al (4), on a small number of subjects, with significant attrition even in infancy but showing apparent large beneficial effects of LCPUFA supplemented formula on cognitive development have been widely cited as supporting the addition of LCPUFA. Indeed, Birch's study, which may have been one of the most influential trials driving the addition of LCPUFA to US formulas, was based on an incomplete follow up where only 19 subjects remained in the relevant intervention group, providing inadequate power to provide any realistic estimation of the treatment effect. It is odd then that our much larger study with more complete longer-term follow-up and a range of outcomes not previously examined should attract such critical comment, as that from Dr Hoffman. We have previously received criticism for other trials where we found potentially unfavourable effects of LCPUFA supplementation. For example, in one preterm trial we found preterm infants supplemented with LCPUFA had a long term reduction in linear growth (5) - yet another group that found the same thing but appeared nevertheless to favour single cell oil supplementation, received no such adverse comment (6). In contrast, whenever we have generated positive results, these have been accepted with enthusiasm. If our contention that there may be some underlying bias in this area, is true, this would not "well serve the caregivers of preterm infants" - or term infants - who are best served by objective reporting of scientific data in the interests of child health.

We note that we also measured cognitive outcomes during the follow-up of our current study and will be interested to see whether publication of these findings, which suggest some long term beneficial effects of LCPUFA supplementation, but in the same cohort with the same attrition rate and limitations, will attract the same level of scrutiny and criticism, which we doubt.

We hope that Readers will appraise our current manuscript in a critical, but importantly, open-minded manner, considering the limitations we have highlighted; and that eventually these data can be considered alongside those from other similar studies examine the long-term health effects of LCPUFA supplementation of infants formulas, in order to strengthen the evidence-base for future products.

Kathy Kennedy, Mary Fewtrell, Alan Lucas

Appendix. Response to Dr Hoffman's specific comments and questions:

1. We have not claimed in the paper that LCPUFA supplementation has programmed preterm girls to later obesity and hypertension! This was deliberate, so as not to cause alarm or extrapolate beyond our findings. As stated in our discussion, the girls in our study all had blood pressure and BMI currently within the normal range, and we merely speculated on the potential longer-term significance of our findings, for example, given data showing tracking of BP. 2. We have noted the greater height of the LCPUFA supplemented girls at follow-up in our paper, along with higher weight, skinfold thicknesses and fat mass etc. Fat mass and fat free mass adjusted for height (FMI and FFMI) were indeed not significantly different between groups, as reported in the manuscript. The difference in stature (and potentially more advanced pubertal development, as we have discussed) could explain the greater skinfold thickness and weight of the supplemented girls; however, it is equally possible that LCPUFA supplementation has resulted in greater fatness, which is recognised to be associated with increased stature and earlier pubertal development. We consider it inappropriate to adjust for height (an outcome measure potentially influenced by the intervention) in our main analyses. 3. Dr Hoffman asks for the baseline and follow-up characteristics of the girls who were followed up and those who were not seen to be presented; in the interests of brevity these results were not presented in the paper. However, we can confirm that girls who were seen were more preterm (30.4 wk vs 31.6 wks, p = 0.001), had lower birth weights (1379g vs 1500g, p = 0.05), spent longer in hospital (46 days vs 36 days, p = 0.013), were more likely to have required ventilation (52% vs 29%, p = 0.009), and their mothers were less likely to have been educated to degree level (0% vs 8%, p = 0.04) compared to those who did not take part in the follow-up. This will affect the generalisability of our findings to the original cohort. However, of greater relevance to the preservation of randomisation for those seen at follow-up, there were no significant differences between supplemented and control girls studied for baseline or follow-up characteristics, with the exception of the number of days of ventilation (4.4 days vs 1.1 days, p = 0.013). We did not record details of the timing of the introduction of solids nor of subsequent diet or physical activity in this study. The randomisation procedure should mean that these factors are equal in the two groups, although we accept that with attrition at follow-up, this may be questioned to some extent. 4. We do not 'ignore the importance of LCPUFA in preterm infant nutrition'; rather we question the evidence that adding LCPUFA to infant formulas in the manner used for formulas tested in clinical trials to date produces clinical benefit. The ESPGHAN Committee on Nutrition paper cited here itself acknowledges that 'the long-term effects on visual and neural development are not fully known', and the Expert group providing advice during the recast of the EU Directive on the composition of infant formulas in Europe (EFSA) concluded that there was insufficient evidence on which to make the addition of LCPUFA to infant formulas compulsory; the addition of LCPUFA to infant formulas is currently optional under EU regulations. A significant number of Key Opinion Leaders in this field have this view.

References 1. Kathy K, Ross S, Isaacs EB, Weaver LT, Singhal A, Lucas A, Fewtrell MS: Ten year follow-up of a randomised trial of long-chain polyunsaturated fatty acid supplementation in preterm infants: Effects on growth and blood pressure. Arch Dis Child 2010; 95: 855-595

2. Simmer K, Patole SK, Rao SC. Long-chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane database of systematic reviews 2008; 23 (1) CD000376

3. Simmer K, Schulzke SM, Patole S. Long-chain polyunsaturated fatty acid supplementation in preterm infants. Cochrane database of systematic reviews 2008; Issue 1. Art No: CD000375. DOI: 10.1002/14651858.CD000375.pub3.

4. Birch E, Garfield S, Hoffman D, Uauy R, Birch D. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neur 2000; 42: 174-181.

5. Fewtrell MS, Morley R, Abbott R, Singhal A, Isaacs E, Stephenson T, MacFadyen U, Lucas A. Double-blind, randomised trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics 2002; 110: 73-82.

6. Vanderhoof J, Gross S, Hegyi T. A Multicenter Long-Term Safety and Efficacy Trial of Preterm Formula Supplemented with Long-Chain Polyunsaturated Fatty Acids. JPGN 2000; 30: 121-127. Dear Sir

Reply to Dr Lapillone

We thank Dr Lapillone for his comments. We do not agree that our conclusions will confuse the readers of the Archives of Disease in Childhood, and this was certainly not our intention. The results are clearly presented (and summarised by Dr Lapillone). As he states, we assessed 'adiposity' in a number of ways - skinfold thicknesses, BMI, %fat and fat mass and fat free mass from deuterium dilution and normalised for height. We have clearly set out in the results and abstract which of these measures were significantly different between the supplemented and control groups; and in the abstract we do not claim that fat mass (or fat mass index) were significantly different.

Dr Lapillone is correct that our group has recommended using measures of fat and fat free mass normalised for height, rather than using % fat; however, this applies to whole body measurements. We have also advocated using skinfold thickness measurements as raw values to measure regional fat mass, and it is entirely plausible to have differences in regional adiposity not reflected in whole body measurements. Thus, we stand by our conclusion.

Kathy Kennedy, Mary Fewtrell, Alan Lucas

Conflict of Interest:

None declared

We read with great interest the article by Hunt and Ernst (1) on their critical overview of the systematic reviews of various complementary and alternative medicine (CAM) therapies for children. While Hunt and Ernst are to be lauded for their contribution to the pediatric CAM literature, we wish to address issues raised by the authors. Similar to other chiropractors, other CAM providers and orthodox medical practitioners, we aspire to care for children following the principles of evidence-base medicine (EBM). That is, integrating our individual clinical expertise with the best available external clinical evidence such as systematic research while at all times respecting the needs and wants of patients (or parents in the case of children) (2). It is from this point of view that we wish to address their critical overview of the literature on chiropractic and their comments regarding the recommendation of a trial of chiropractic care (or other types of CAM therapies) for children. Of the various practitioner-based CAM therapies, chiropractic has been found to be the most popular for children (3).

With respect to the chiropractic care of patients with asthma, our review of the literature on the subject revealed 6 review articles (4-9). Three of the reviews support a trial of chiropractic care for patients with asthma (4,6-7) while two do not (8,9) with one neither supporting or refuting its use (5). A closer examination of the involved clinical trials on chiropractic SMT and asthma reveal a failure on the part of Hunt and Ernst (1) to critically appraise the literature. As we pointed out in response to a systematic review by Ernst (1), the clinical trials on asthma and subsequent reviews failed to consider the challenges and pitfalls of designing a randomized controlled clinical trials (RCT) with chiropractic SMT (10). In the clinical trials on chiropractic SMT and asthma (11-13), the investigators failed to ensure the veracity of the sham therapies employed and therefore all subsequent interpretations from these studies are questionable. Consider the clinical trial by Balon and colleagues (12), touted by Ernst and other reviews as the study of highest methodological quality. The design of the simulated treatment incorporated massage and various maneuvers reminiscent of both chiropractic and osteopathic manipulative techniques. Massage has been demonstrated to benefit asthmatic patients (14-16). Furthermore, the assumption on the part of Balon and colleagues (12) that regardless of the maneuver employed, a high velocity, low amplitude thrust type SMT devoid of joint cavitation or audible release has no therapeutic effect could not be further from the truth (17). A number of mechanically assisted SMT instruments are used by chiropractors with reported benefits by patients (18-19). Their use do not result in joint cavitation or audible release. The clinical trials on asthma are arguably comparison trials of chiropractic SMT versus another type of SMT technique (10). The use of spirometry as the objective outcome measure for these studies is also questionable given that their utility as diagnostic instruments for asthma have been found inadequate (10,20).

On the literature examining chiropractic SMT and infantile colic, again Hunt and Ernst (1) failed to critically appraise the literature. Our review found 4 review articles on the subject (21-24). Talmage and Resnick (21) addressed the definition, etiology, prevalence and management strategies utilized by MDs and DCs and advised that proper management should focus on making the correct diagnosis, reassuring the parents, and in addition to medical care, a conservative approach with chiropractic SMT. As with their findings on asthma, Hawk and colleagues (22) concluded that evidence from controlled studies and usual practice supports chiropractic care (i.e., the entire clinical encounter) as providing benefit for patients with infantile colic. Bronfort et. al. (23) concluded that chiropractic SMT for colic is not effective when compared to sham SMT. Ernst (24) reviewed the randomized clinical trials on colic and chiropractic SMT (25-27) and concluded that the evidence for chiropractic SMT for colic is not based on rigorous clinical trials and therefore fails to demonstrate effectiveness. A critical appraisal of these reviews again require a closer examination of the clinical trials on colic. Wiberg et.al. (25) compared chiropractic SMT versus the established medical treatment using dimethicone. Chiropractic was demonstrated to be superior to dimethicone in decreasing hours of crying in colicky infants. Olafsdottir et.al. (26) compared a poorly characterized and unproven chiropractic technique versus no care. Olafsdottir et.al. (26) found the subjects in both groups responded similarly and therefore concluded that chiropractic SMT is no more effective than placebo. No study has ever been published (i.e., not even a case report) to demonstrate some semblance of effectiveness with this unproven technique. Browning and colleague (27) examined the effects of two manual techniques (i.e., chiropractic SMT and occipito-sacral decompression) on infantile colic. Both manual techniques were capable of decreasing the hours of crying in infants when compared to baseline measures. Based on our summary of the clinical trials on colic, Bronfort et.al. failed to recognize the study designs involved and their interpretation must be examined with caution.

In terms of the research on the chiropractic care of patients with nocturnal enuresis, otitis media or any other childhood conditions for that matter, what becomes painfully obvious is the supremacy of practice empiricism over research. One can argue that this is not unique to chiropractic but it is also the case for other CAM therapies or orthodox medicine. Hunt and Ernst (1) admonish that rigorous testing of CAM therapies for their effectiveness and safety are a requisite prior to their recommendation. If this applies to all therapies (CAM of orthodox medicine), we would argue that a large part of pediatric care would cease. Off-label use in pediatric care comes to mind (28-29). We concur that more research is needed on the safety and effectiveness of pediatric care (CAM or orthodox medicine), both in quantity and quality. However, the decision to recommend or pursue a trial of care is not so simple as Hunt and Ernst would want us to believe. Safety and effectiveness are of the utmost consideration as well following the principles of biomedical ethics. In defining EBM, Sackett and colleagues leave no doubt about the integration of research in the clinical decision making process. According to Sackett and colleagues (2), "external clinical evidence can inform, but can never replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision." Sackett and colleagues (2) further commented that, "evidence based medicine is not restricted to randomised trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions." Hunt and Ernst (1) failed to consider these very important aspects of EBM in their myopic examination of the evidence base. As an example, consider the chiropractic perspective on the care of infants with infantile colic. The literature demonstrated that chiropractic SMT is superior to dimethicone (25), there is benefit to patients receiving chiropractic SMT and occipito-sacral decompression26 while using light finger tip pressure SMT as Olafsdottir and colleague performed is not effective for infantile colic (27). From the parent's perspective, mothers of infants with colic have multidimensional psychological distress resulting in more bodily dysfunctions, fears, disordered thinking, depression, anxiety, fatigue, hostility, impulsive thoughts and actions, and stronger feelings of personal inadequacy or inferiority (30). A colicky infant adversely affects the family dynamics and inter-relationships (31-32) and may place the infant at risk for abuse. Thoughts and fantasies of aggression and infanticide have been reported by mothers (33). Our experience with parents of infants with colic has been a demand for chiropractic care. Typically, their child has been attended to by a medical doctor but the parents are at their wits end. Medical care for infantile colic has not been proven effective (34). Two clinical trials comparing semithicone (a surfactant to facilitate passage of gas in the gastrointestinal tract) to placebo demonstrated no benefit (35). Anticholinergic drugs (given to infants with colic to relax the smooth muscles of the gut to prevent spasms) have reported adverse events such as drowsiness, diarrhea and constipation, apnea, seizures and coma (35). Methylscopolamine, a muscle relaxant to treat gastric or intestinal hypersensitivity or secretions, has been found to exacerbate colic and may be unsafe (35). In terms of safety, we acknowledge that adverse events associated with pediatric chiropractic SMT may be under-reported. However, based on the available evidence, adverse events are rare and when they do occur, they are minor, self-limiting and does not require the attention of a medical doctor (36-37). A trial of chiropractic care for the infant with colic is therefore warranted in light of the principles of EBM and the principles of biomedical ethics that respects the right of the parent to choose the care for their child, placing their interest above all others, avoiding harm and providing them access to all therapies available. Hunt and Ernst missed these important principles of patient care in their critical appraisal of the literature on CAM therapies.

References

1. Hunt K, Ernst E. The evidence-base for complementary medicine in children: a critical overview of systematic reviews. Arch Dis Child. 2010 Jul 6. [Epub ahead of print]

2. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. 1996. Clin Orthop Relat Res. 2007;455:3-5.

3. Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report. 2008 Dec 10;(12):1-23.

4. Balon J, Mior SA. Chiropractic care in asthma and allergy. Annal of allergy, asthma and immunology 2004;93(2Suppl 1): s55-60.

5. Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev. 2005;(2):CD001002\

6. Hawk C, Khorsan R, Lisi AJ, Ferrance RJ, Evans MW. Chiropractic care for nonmusculoskeletal conditions: a systematic review with implications for whole systems research. J Altern Complement Med. 2007;13(5):491-512.

7. Kaminskyj A, Frazier M, Johnstone K, Gleberzon BJ. Chiropractic care for patients with asthma: A systematic review of the literature. J Can Chiropr Assoc 2010;54(1):24-32.

8. Bronfort G, Haas M, Evans R, Leininger B, Triano J. Effectiveness of manual therapies: the UK evidence report. Chiropr Osteopat. 2010;18:3

9. Ernst E. Spinal manipulation for asthma: A systematic review of randomised clinical trials. Respir Med 2009; [Epub ahead of print]

10. Alcantara J, Alcantara JD, Alcantara J. Chiropractic treatment for asthma? You bet! J Asthma. 2010 Jun;47(5):597-598.

11. Nielsen NH, Bronfort G, Bendix T, Mansen F, Weeke B. Chronic asthma and chiropractic spinal manipulation: a randomized clinical trial. Clin Exp Allergy. 1995;25:80-88.

12. Balon J, Aker PD, Crowther ER, et al. A randomized controlled trial of chiropractic manipulation as an adjunctive treatment for childhood asthma. N Engl J Med. 1998;339:1013-1020.

13. Bronfort G, Evans R, Kubic P, Filkin P. Chronic pediatric asthma and chiropractic spinal manipulation: a prospective clinical series and randomized clinical pilot study. J Manipulative Physiol Ther. 2001;24:369-377.

14. Field T. Massage therapy for infants and children. J Dev Behav Pediatr. 1995;16(2):105-111

15. Field T, Henteleff T, Hernandez-Reif M, Martinez E, Mavunda K, Kuhn C, Schanberg S. Children with asthma have improved pulmonary functions after massage therapy. J Pediatr. 1998;132(5):854-858.

16. Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C. Cortisol decreases and serotonin and dopamine increase following massage therapy. Int J Neurosci. 2005;115(10):1397-1413.

17. Reggars JW. The therapeutic benefit of the audible release associated with spinal manipulative therapy. A critical review of the literature. Australas Chiropr Osteopathy. 1998 Jul;7(2):80-5.

18. Taylor SH, Arnold ND, Biggs L, Colloca CJ, Mierau DR, Symons BP, Triano JJ. A review of the literature pertaining to the efficacy, safety, educational requirements, uses and usage of mechanical adjusting devices: Part 1 of 2. J Can Chiropr Assoc. 2004;48(1):74-108.

19. Taylor SH, Arnold ND, Biggs L, Colloca CJ, Mierau DR, Symons BP, Triano JJ. A review of the literature pertaining to the efficacy, safety, educational requirements, uses and usage of mechanical adjusting devices: Part 2 of 2. J Can Chiropr Assoc. 2004;48(2):152-61.

20. Schneider A, Gindner L, Tilemann L, Schermer T, Dinant GJ, Meyer FJ, Szecsenyi J. Diagnostic accuracy of spirometry in primary care. BMC Pulm Med 2009; 9:31. 2007;19(8):26

21. Talmage DM, Resnick D. Infantile Colic: Identification and Management Topics in Clinical Chiropractic 1997;4(4): 25-29.

22. Hawk C, Khorsan R, Lisi AJ, Ferrance RJ, Evans MW: Chiropractic care for nonmusculoskeletal conditions: a systematic review with implications for whole systems research. J Altern Complement Med 2007;13:491-512.

23. Bronfort G, Haas M, Evans R, Leininger B, Triano J. Effectiveness of manual therapies: the UK evidence report. Chiropr Osteopat. 2010;18:3 24. Ernst E. Chiropractic spinal manipulation for infant colic: a systematic review of randomised clinical trials. Int J Clin Pract. 2009;63(9):1351-1353

25. Wiberg JM, Nordsteen J, Nilsson N. The short term effect of spinal manipulation in the treatment of infantile colic: a randomized controlled clinical trial with a blinded observer. J Manipulative Physiol Ther 1999;22(8):517-522

26. Olafsdottir E, Forshei S, Fluge G, Markestad T. Randomised controlled trial of infantile colic treated with chiropractic spinal manipulation. Arch Dis Child 2001;84(2):138-141

27. Browning M, Miller J. Comparison of the short-term effects of chiropractic spinal manipulation and occipito-sacral decompression in the treatment of infant colic: A single-blinded, randomised, comparison trial. Clinical Chiropractic 2008;11:122-129.

28. Bavdekar SB, Sadawarte PA, Gogtay NJ, Jain SS, Jadhav S. Off-label drug use in a Pediatric Intensive Care Unit. Indian J Pediatr. 2009;76(11):1113-1118.

29. Koelch M, Prestel A, Singer H, Keller F, Fegert JM, Schlack R, Hoelling H, Knopf H. Psychotropic medication in children and adolescents in Germany: prevalence, indications, and psychopathological patterns. J Child Adolesc Psychopharmacol 2009;19(6):765-770

30. Pinyerd BJ. Infant colic and maternal mental health: nursing research and practice concerns. Issues Compr Pediatr Nurs. 1992;15(3):155-167.

31. Ellett M, Schuff E, Davis JB. Parental perceptions of the lasting effects of infant colic. MCN Am J Matern Child Nurs. 2005;30(2):127-132

32. Rautava P, Lehtonen L, Helenius H, Sillanpaa M. Infantile colic: child and family three years later. Pediatrics. 1995;96(1 Pt 1):43-47

33. Levitzky S, Cooper R. Infant colic syndrome--maternal fantasies of aggression and infanticide. Clin Pediatr (Phila) 2000;39(7):395-400.

34. Roberts DM, Ostapchuk M, O'Brien JG. Infantile colic. Am Fam Physician. 2004;70(4):735-40

35. Garrison MM, Christakis DA. A systematic review of treatments for infant colic. Pediatrics 2000;106(1 Pt 2):184-190).

36. Vohra S, Johnston BC, Cramer K, Humphreys K. Adverse events associated with pediatric spinal manipulation: a systematic review. Pediatrics 2007;119(1):e275-e283.

37. Alcantara J, Ohm J, Kunz D. The safety and effectiveness of pediatric chiropractic: a survey of chiropractors and parents in a practice-based research network. Explore (NY). 2009;5(5):290-295.

Conflict of Interest: None declared