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PAPERS: Pat Ansell, Eve Roman, Nicola T Fear, and Mary J Renfrew Vitamin K policies and midwifery practice: questionnaire survey BMJ 2001; 322: 1148-1152 [Abstract] [Full text]

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There is a fundamental bias in all clinical research

Sergio Stagnaro   (14 May 2001)

Neonatal Vitamin K prophylaxis: lack of consensus in the Republic of Ireland

Roy K Philip   (12 June 2001)

Policies on neonatal vitamin K use

Edmund Hey   (3 August 2001)

There is a fundamental bias in all clinical research 14 May 2001
Sergio Stagnaro, Specialist in Blood, Metabolic and Gastrointestinal Diseaes Riva Trigoso (Genoa) Italy Send response to journal: Re: There is a fundamental bias in all clinical research	Sirs, I think that because congenital functional mitochondrial cytopathology is overlooked--a "conditio sine qua non" of the most frequent and dangerous human disorders, including malignancies--all current clinical research is fundamentally biased. That is, it does not consider the existence or assess the seriousness as well as the location of Congenital Acidosic Enzyme-Metabolic Histangiopathy (1, 2). In fact, both environmental risk factors and every drug, including vitamin K in newborn infants, suggested as a risk factor for leukaemia in children, "could" influence some human biological functions and/or bring about different disorders, such as cancers, exclusively in relation to both the presence and intensity of CAEMH in a well-defined biological system. I recently discussed in bmj.com (Fighting tobacco smoking is unavoidable duty for all physicians. Stagnaro Sergio, 4 May 2001, Rapid Responses) this overlooked functional mitochondrial cytopathology. I have called this Congenital Acidosic Enzyme- Metabolic Histangiopathy in previous papers; it is the genetic factor of common human disorders (1, 2). For instance, apart from the well- known negative influence of oral contraceptive use on breast oncogenesis (4) and/or arterial disorders we have to consider the importance of the genetic predisposition ("Oncological Terrain",See http://digilander.iol.it/semeioticabiofisica), as far as the onset of a lot of disorders is concerned, including solid as well as liquid malignancies. At this point, I would emphasise the well-known pathological powerful influence of smoking on tissue oxygen supply to all biological systems (3, 4). This effect varies notoriously in prevalence and intensity among individuals in relation to a congenital mitochondrial cytopathology, i.e. Congenital Acidosic Enzyme-Metabolic Histangiopathy (2). This both "silent" and dangerous action is easy to evaluate at the bed-side with the aid of a stethoscope. I suggest first investigating (i.e., before whatever research) the presence and intensity of CAEMH in the "tested" population, and soon thereafter assessing prevalence and intensity of the "Oncological Terrain", which always develops on the basis of the above-mentioned congenital cytopathology (1-4). In fact, without this alteration of psycho-neuro-endocrine-immunological system, oncogenesis is not possible. The importance of the above-mentioned congenital factor should not be overlooked, particularly when we assess a "possible" risk factor for cancer such as vitamin K and leukemia in children. Stagnaro Sergio MD, Member NYAS and AAAS. Specialist in Blood, Metabolic and Gastrointestinal Diseases, Riva Trigoso (Genoa), Italy. 1) Stagnaro S., Stagnaro-Neri M.Istangiopatia Congenita Acidosica Enzimo Metabolica. Gazz. Med. It.- Arch. Sci. Med. 144, 423, 1985. 2) Stagnaro S., Stagnaro-Neri M. Una patologia mitocondriale ignorata: la Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz. Med. It. - Arch. Sci. Med. 149, 67 1990. 3)Stagnaro-Neri M., Stagnaro S. Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109 1997. 4) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. – Arch. Sc. Med. 152, 447 1993
Neonatal Vitamin K prophylaxis: lack of consensus in the Republic of Ireland 12 June 2001
Roy K Philip, Consultant Neonatologist Regional Maternity Hospital, Limerick, Ireland Send response to journal: Re: Neonatal Vitamin K prophylaxis: lack of consensus in the Republic of Ireland	Editor - Ansell1 et al. in their survey among a sample of midwifes reported a considerable variation in vitamin K policies in the United Kingdom. It is disturbing to see that for an effective preventive measure such as neonatal vitamin K prophylaxis, there are over seven distinct policies that are being followed across the country. With the published data supporting2 and not refuting3 the association of neonatal vitamin K with childhood malignancies, the current practice as reflected in this paper is of major concern. Our recent national survey also revealed a lack of consensus on neonatal vitamin K prophylaxis among the various maternity units and Health Boards in the Republic of Ireland. We have collected information using a simple questionnaire from all the 23 maternity units (both public and private) of the country regarding the dose, frequency, route and time of administration of vitamin K prophylaxis and compared the range of practices. Survey was addressed to the Sister / Midwife in-charge of the labour ward and neonatal unit of each Hospital. Data was compiled during February and March of 2001. Particular reference was made about the drug administration policies for the breast and bottle fed infants in both term and preterm categories. All the 23 units among the 8 different Health Boards responded to the survey giving a response rate of 100%. This represents the vitamin K prophylaxis as given to all the in-Hospital deliveries in the country. The most encouraging observation was that vitamin K is being routinely administered to all neonates at or soon after birth. Sadly, even within the maternity units of the same Health Board, no consensus of policies was noted regarding the dose or route of administration. For the term infants 47.8% units administer 1 mg intramuscularly while 0.5 mg intramuscular and 2 mg oral are being given in 30.5% and 21.7% respectively. 78.3 % units preferred intramuscular route while only 21.7% preferred oral administration as a policy. The corresponding percentages for the latter in Ansell's UK survey1 were 51.0% and 14.2% respectively. Among the Hospitals giving intramuscular route to term neonates, no differences in policies were noted based on the infant feeding practices (breastfed or bottlefed). All the units following an oral vitamin K schedule gave an additional dose at 4 weeks of age to the breastfed infants and 40% gave the dose at 4 weeks to the bottlefed as well. In general, intramuscular was the preferred route of administration for both breastfed and bottlefed preterms, 87% and 91.3% respectively. Among the breastfed premature infants 0.5mg intramuscular route is preferred in 14 (61%) of maternity units while 15 (65.2%) gave 0.5mg intramuscular to the bottlefed preterm infants. 1mg (total dose) and 0.4mg / Kg are the preferred policies in 21.6% and 13% of hospitals respectively. Six different policies were followed among the 23 maternity facilities in the country and no two Health Boards shared the same guideline. Our observations suggest a lack of national consensus at the point of delivery of Vitamin K prophylaxis against haemorrhagic disease of the newborn. A similar nationwide survey in France4 reports a range of practices regarding the route of administration and on many occasions at a much higher dose (5mg) than generally recommended. Even though recommendations are available from the Irish Faculty of Paediatrics, a lack of clear guideline from the Department of Health and Children is probably contributing to the diversified policies among the various health providers. By involving the real supervisors at the implementation stage throughout the country, our observations reflect for the first time how prophylactic vitamin K policies are interpreted and delivered in the republic of Ireland. REFERENCES 1. Ansell P, Roman E, Fear N T, Renfrew M J. Vitamin K policies and midwifery practice: questionnaire survey. BMJ 2001;322:1148-52. 2. Golding J, Greenwood R, Birmingham K, Mott M. Childhood cancer, intramuscular vitamin K, and pethidine given during labour. BMJ 1992;305:341-6. 3. Parker L, Cole M, Craft A W, Hey E N. Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case control study. BMJ 1998;316:189-93. 4. Jonville-Bera A P, Autret E. Study of Vitamin K in Neonates in France. Eur J Clin Pharmacol 1997;52:333-37. Roy K Philip Consultant Neonatologist Riswan Gul Registrar in Neonatology Margo Dunworth Sister, Neonatal Intensive Care Unit Noreen Keane Sister, Neonatal Intensive Care Unit Regional Maternity Hospital Limerick, Republic of Ireland Corresponding author: Dr. Roy K Philip roykphilip@yahoo.co.uk
Policies on neonatal vitamin K use 3 August 2001
Edmund Hey, Retired Consultant Paediatrician Newcastle Send response to journal: Re: Policies on neonatal vitamin K use	EDITOR - Ansell's valuable survey of how UK midwives believe vitamin K is given in their unit shows just how variable policy has now become.[1] It also reveals confusion as to which babies are at above average risk of bleeding because of vitamin deficiency. Part of the problem is that different risk factors influence the risk of bleeding at different times. Those who first introduced vitamin K prophylaxis sixty years ago [2] realised that babies were more likely to bleed if subjected to a traumatic assisted, or unassisted, delivery (as 56% and 47% of midwives still realise) but, for a third of midwives, this clear indication has now metamorphosed into a belief that every baby born with instrumental help, or by Caesarean section, is at increased risk. There is also a widespread belief that preterm babies are at increased risk (64%), although studies in countries where babies do not normally get vitamin K prophylaxis at birth provide no support for this belief.[3,4] What is true is that babies who are not fed at birth are at substantially increased risk (as only 3% of midwives specifically mention), since all are vitamin deficient at birth and milk provides their only vitamin source. Babies fed breast milk are also at increased risk of classical haemorrhagic disease of the newborn (hypothrombinaemic bleeding in the first week of life) because this milk contains less vitamin K. Maternal treatment with some anticonvulsant drugs also increases the risk of bleeding (as 25% realised),[5] but this can happen at any time in the first 2-3 days of life. The belief that there is something different about cases presenting on the first day of life [6] is ingrained, but gains no support from the available epidemiological evidence.[3-5] Jaundice is not usually a risk factor, but late prolonged jaundice, if it is a sign of disturbed liver function, does increase the risk of late bleeding at 2-12 weeks (as 9% possibly sensed), especially if the baby is exclusively breast fed (as 9% also recognised). These various risk factors do not, however, pick out a group of babies who necessarily merit intramuscular rather than oral prophylaxis. Babies who are not well enough to feed soon after birth, and babies born more hypoprothrombinaemic than most because of maternal medication, clearly merit this, but either approach can be equally effective at preventing vitamin K deficiency bleeding in other babies as long as an appropriate dose is used.[7] The paper by Ansell is misleading, however, when it tries to use the information it has collected to throw doubt on the possible association between intramuscular vitamin K and childhood leukaemia. This aim receives no mention in the body of the paper, but is revealed to have been the main purpose of the study in the introductory paragraph in "This week in the BMJ" where the authors conclude that past "hospital policies were open to individual interpretation and not always followed". The issue is of some importance because case control studies [8] produce conclusions that depend on the assumptions made about treatment when the case notes fail to show whether vitamin K was given or not. The first mistake is to have assumed that the risk criteria used by hospitals that only offered prophylaxis to a minority of babies 10 or more years ago were, or should logically be, the same as those now being used to judge which babies merit intramuscular rather than oral prophylaxis at birth. A second, equally serious, mistake was to ask midwives what those policies were without realising that they cared for very few of the babies meriting selective prophylaxis in the period immediately after birth. A paediatric resident 'stood by' for almost every operative delivery, and for every delivery of a preterm or low birth weight baby thought likely to require admission to special care, and these were the babies being offered prophylaxis. Midwives may have used discretion in deciding which of the babies in their care merited prophylaxis, but that was not how inexperienced paediatric residents were expected to behave. They worked to clear, fixed, protocols, and they gave, or decided who should get, vitamin K at birth. I do not believe that Ansell and her colleagues have produced any evidence to support their concluding statement that "if no written record was made [in the case notes] the most likely reason is that vitamin K was not given." An audit of 1088 case records from 7 units in this region with a long standing policy of universal prophylaxis [9] failed to find any written record that vitamin K was ever given in 178 (16%) of the babies: the staff concerned are quite sure they did not fail to provide such a simple and basic item of care to so many patients. They reject Ansell's extrapolated deductions. Neither does the evidence she has produced justify the statement made in the 'trailer' to the article that their paper "casts doubt on the possible association between intramuscular vitamin K and childhood cancer." It was quite improper for "This week in the BMJ" to include a statement as unequivocal as this when the issue had not been discussed in the article itself. Edmund Hey Retired Consultant Paediatrician, Newcastle. [1] Ansell P, Roman E, Fear NT, et al. Vitamin K policies and midwifery practice: questionnaire survey. BMJ 2001;322:1148-52. [2] Anon. Vitamin K and the newborn. [Editorial] Lancet 1978;i:755- 9. [3] Lulseged S. Haemorrhagic disease of the newborn: a review of 127 cases. Ann Trop Paediatr 1993;13:331-6. [4] Choo KE, Tan KK, Chuah SP, et al. Haemorrhagic disease in newborn and older infants: a study in hospitalized children in Kelantan, Malaysia. Ann Trop Paediatr 1994;14:231-7. [5] Hey E. Effect of maternal anticonvulsant treatment on neonatal blood coagulation. Arch Dis Child 1999;81:F208-10. [6] Lane PA, Hathaway WE. Vitamin K in infancy. J Pediatr 1985;106:351-9. [7] Wariyar U, Hilton S, Pagan J, et al. Six years' experience of prophylactic oral vitamin K. Arch Dis Child 2000;82:F64-8. [8] Passmore SJ, Draper G, Brownbill P, et al. Case-control studies of the relation between childhood cancer and neonatal vitamin K administration. BMJ 1998;316:184-9. [9] Parker L, Cole M, Craft A, et al. Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study. BMJ 1998;316:189-93.