2018/2019

Joana Rita Lopes de Abreu

O Uso Da Vitamina K nas Salas de Parto Portuguesas: Estudo Transversal

The use of Vitamin K in Portuguese Delivery Rooms: A Cross-Sectional Study

março, 2019

Joana Rita Lopes de Abreu

O Uso Da Vitamina K Nas Salas De Parto Portuguesas: Estudo Transversal

The use of Vitamin K in Portuguese Delivery Rooms: A Cross-Sectional

Study

Mestrado Integrado em Medicina

Área: Neonatologia

Tipologia: Artigo Original

Trabalho efetuado sob a Orientação de:

Dr. Henrique Edgar Correia Soares

E sob a Coorientação de:

Prof. Doutora Maria Hercília Ferreira Guimarães Pereira Areias

Trabalho organizado de acordo com as normas da revista:

Portuguese Journal of Pediatrics

março, 2019

Ao meu orientador, Dr. Henrique Soares, pela sua dedicação, amizade e admirável

paciência. Pelo trato simples, correto e científico.

À Professora Doutora Hercília Guimarães, por ter aceite o convite para ser minha

coorientadora.

À Dra. Filipa Flor de Lima pela ajuda preciosa na reta final.

Ao meu pai, à minha mãe, ao Gabriel e restante família que me ajudam todos os

dias a ser quem sou.

Dedico este trabalho aos meus avós Marcial, Gracinda e José Augusto e ao meu

tio Aristides que decerto teriam ficado felizes por este momento.

A todos, o meu sincero agradecimento.

O Uso Da Vitamina K Nas Salas De Parto Portuguesas: Estudo Transversal

The use of Vitamin K in Portuguese Delivery Rooms: A Cross-Sectional

Study

Joana Rita Abreu1, Henrique Soares1,2, Mariana Adrião2, Filipa Flor de Lima1,2,

Mário Mateus2, Hercília Guimarães1,2

Interest conflicts

The authors declare the absence of conflicts of interest in the accomplishment of the present work.

Financing source

There were no external sources of funding for this article.

Data Confidentiality

The authors state that they have followed the protocols of their work center on the publication of data.

1 Faculdade de Medicina da Universidade do Porto | Porto | Portugal 2 Neonatology Service | Centro Hospitalar de São João, EPE | Porto | Portugal

Corresponding Author Joana Rita Abreu up20140056@med.up.pt Avenida da República, nº290, apt 201, 4430-188 Vila Nova de Gaia

ARTIGO ORIGINAL / ORIGINAL ARTICLE

Resumo

Abstract

Introduction: Vitamin K deficiency bleeding prophylaxis is one of the first medical care in the delivery room,

and the incidence of this deficiency would be significantly higher without this practice. The purpose of this

study is to investigate the knowledge of Portuguese practitioners about prophylaxis of vitamin K deficiency

bleeding, and to examine their regular practice when working in the delivery room.

Methods: A multiple-choice questionnaire (attachment 1) was sent to the members of the Portuguese

Society of Neonatology by electronic e-mail. All the properly answered and returned questionnaires were

included in the study. Statistical analysis was performed using the Statistical Package for the Social Sciences

(SPSS Statistics, version 25), and included descriptive statistics, ANOVAs, Chi-square test and Spearman

correlations. A p-value lower than 0.05 was considered statistically significant.

Results: A total of 366 questionnaires were sent. Fifty-two (14.2%) questionnaires were answered and

submitted. From the 22 questions that evaluated the level of knowledge, a mean of 12.96 ±2.46 were correct.

Most participants showed average or high level of knowledge (65.3%). From the 7 questions that evaluated

the clinical practices, the mean of correct answers was 4.3 ±1.35. Approximately half of the participants

showed moderately or highly adequate clinical practices.

Conclusion: Our study highlighted the relevance of updated clinical protocols and reinforce that is essential

that physicians renew their scientific knowledge in topics relevant for the everyday practices. To evaluate and

subsequently improve practices in the delivery rooms is crucial to a better clinical practice.

Kew-words: haemorrhagic disease of the newborn, prevention and control; vitamin K deficiency bleeding,

Newborn, Portugal

Introdução: A profilaxia com vitamina K é um dos primeiros cuidados médicos na sala de parto, e sem o qual a

incidência da hemorragia do recém nascido por défice de vitamina K seria significativamente maior. Este estudo

pretende investigar o conhecimento dos neonatologistas Portugueses sobre esta profilaxia e avaliar a rotina médica

na sala de parto.

Método: Um questionário de escolha múltipla (anexo 2) foi enviado aos membros da Sociedade Portuguesa de

Neonatologia através de correio eletrónico. Todos os questionários corretamente preenchidos foram incluídos neste

estudo. A análise estatística foi realizada através do Statistical Package for the Social Sciences (SPSS Statistics,

versão 25), e incluiu estatística descritiva, ANOVAs, testes de Qui-quadrado e correlações de Spearman. Um valor

de p inferior a 0.05 foi considerado estatisticamente significativo.

Resultados: Um total de 366 questionários foram enviados. Cinquenta e dois (14.2%) foram preenchidos e

devolvidos. Das 22 questões que avaliaram o nível de conhecimento, em média 12.96 ± 2.46 estavam corretas. Dos

participantes, a maioria demonstrou ter um médio ou alto nível de conhecimento (65.3%). Das 7 questões que

avaliaram a prática clínica a média de respostas corretas foi de 4.3 ± 1.35. Aproximadamente metade dos

participantes demonstraram práticas clínicas moderadamente ou altamente adequadas.

Conclusões: Os nossos resultados enfatizam a relevância do uso de protocolos clínicos atualizados e reforçam que

é essencial os médicos renovarem o seu conhecimento científico em tópicos relevantes para as práticas do dia-a-

dia. Avaliar e subsequentemente melhorar as práticas nas salas de parto é determinante para uma melhor prática

clínica.

Palavras-chave: Doença hemorrágica do recém-nascido, profilaxia, hemorragia por deficiência de vitamina K,

recém-nascido, Portugal

Introduction

The role of Vitamin K in normal coagulation was made clear in 1939, shortly after

its discovery [1]. Vitamin K1 (phylloquinone) comes directly from a person’s diet, while

vitamin K2 (menaquinones) is obtained from the intestinal flora and corresponds to 90%

of all the stored Vitamin K in the liver [1]. It is known that Vitamin K deficiency is associated

to reduced levels of coagulation factors directly dependent on it, such as factor II, VII, IX,

and X, as well as protein C and S, that are important anticoagulant factors[2].

Newborns have a deficiency in vitamin K and this makes them vulnerable to

Vitamin K Deficiency Bleeding (VKDB), a life-threatening situation that can be prevented

by prophylactic administration of vitamin K immediately after birth[3].

The American Academy of Paediatrics recommends VKDB prophylaxis with the

intramuscular (IM) administration of a single dose of 0,5-1mg of vitamin K immediately

after birth[4, 5]. However, little is known about the appropriate dose to be administrated to

preterm newborns. Some recent studies evaluated vitamin K in these babies and found

supraphysiologic levels [1, 6-8].

VKDB prophylaxis is one of the first medical care in the delivery room, and the

VKDB incidence would be significantly higher without this regular prophylaxis [4, 9-11].

However, vitamin K administration has some risks. In 1992, a British study linked vitamin

K administration with some cancers. In more recent studies, it has become clear that

vitamin K administration is not linked to solid tumours. However, a small risk of leukaemia

cannot be completely excluded [8]. The main adverse reaction is associated with its local

administration, such as skin infection, or skin reaction and muscular or nerve lesions when

the shot is administered too deep[8]. The pain caused by the shot is also a topic of

discussion since the onset of pain in the early life may have future adverse effects. Despite

the clear benefits of Vitamin K, parents must be consulted and agree to sign an informed

consent form prior its administration by the paediatric specialist[8].

Even though the benefits of vitamin K prophylaxis are widely acknowledged, there

is a limited agreement on the proper protocols, appropriate doses and usual adverse

reactions. The purpose of this study is to investigate the knowledge of Portuguese

practitioners about the prophylaxis of vitamin K deficiency bleeding, and to analyse their

regular practice in the context of the delivery room.

Methods

A search in PubMed was conducted using Key Words “Vitamin K AND prevention

and control AND Infant, Newborn”.

A classified multiple-choice question (MCQ) questionnaire, (attachment 1), was

applied to the neonatologists registered in the Portuguese Society of Neonatology. It

comprised three parts: (1) sociodemographic characteristics; (2) level of knowledge; and

(3) current practices of physicians in prophylaxis of VKDB.

The questionnaire was written in portuguese (attachment 2) and sent to the

neonatologists by electronic e-mail. The answers were submitted anonymously using the

platform googleforms. All the properly answered and returned questionnaires were

included in the study.

The results were graded and categorized as follows: (1) Knowledge (based on

correctly answered questions): low (P25 ;≤ 11), average (P50; 11-15) and high (P75; ≥15);

(2) Practices (based on correctly answered questions): inadequate (P25 ; ≤4), moderately

adequate (P50 ; 5) and highly adequate (P75 ; ≥6).

Statistical analysis was performed using the Statistical Package for the Social

Sciences (SPSS Statistics, version 25). We used descriptive statistics to examine the

sociodemographic variables, and ANOVA, Chi-square test and Spearman correlations to

targeted analysis. A p-value lower than 0.05 was considered statistically significant.

This study was approved by the Ethics Committee of São João´s hospital /Faculty

of Medicine University of Porto and exempted from written informed consent. The collected

data was only handled by the research team.

Results

A total of 366 questionnaires were sent, and 52 (14.2%) were answered by the

members of the Portuguese Society of Neonatology. Thirty-seven (71.2%) were female,

the mean age = 47.6 years ± 10.24; range: 30 - 63 years. These individuals were

predominantly from hospital group III (highly differentiated; n=22, 42.3%). Group I (non-

differentiated) and Group II (differentiated) represented 9 (17.3%) and 21 (40.4%) of the

questionnaires, respectively. It should also be noted that 30 (57.7%) of the physicians who

answered the questionnaire participated in 21 or more births per month (Table 1).

Twenty-two questions evaluated the knowledge of the participants. A mean of

12.96 ± 2.46 questions were answered correctly. The number of correct and incorrect

answers, and the rate are presented in Table 2.

The knowledge was graded on a range according to the number of correctly

answered questions: low (≤11), average (11-15) and high (≥15). More than one third of

the questionnaires, 18 (34.6%), get a low level of knowledge. However, 15 (28.8%) of the

Portuguese Neonatologists successfully graded in the high range (Table 3).

Seven questions evaluated the clinical practice. The mean of correct answers was

4.3 ± 1.35. The number of correct and incorrect answers, and the rate are presented in

Table 2.

In more than half of the participants, 27 (51.9%), the clinical practice was

inappropriate. Only seven (13.5%) had highly appropriate clinical practices. (Table 4).

Those with more correct answers in the questions about medical knowledge were

also who had more correct answers in the questions related to clinical practices (p

=0.0393).

Neonatologist from highly-differentiated hospitals group had more correct answers

about medical knowledge (p = 0.026) and best clinical practices (p = 0.025) than their

peers from the other hospital groups (Table 5).

There was no association between the level of knowledge and the variables sex,

age, hospital group, number of births and clinical practice. Similarly, there was also no

association between the clinical practice and the variables sex, age, hospital group,

number of births and the level of knowledge (Table 6)

In question (21) - parental informed consent -, and in question (23) - clinical

protocols – the groups from different types of hospitals significantly differed (p = 0.0033,

and p = 0.0314, respectively).

Discussion

VKDB is rare in developed countries due to vitamin K prophylactic administration.

It is divided in three types: early (occurs in the first 24 hours of life), classic (occurs in the

first week of life), and the late form (occurs between the first 2-12 weeks of life until de 6

months of age) [5]. The early form is usually the most dangerous, with intracerebral

3 Anova 4 Spearman Correlation

bleeding being a very common complication, and is related to in utero exposure to

anticonvulsants (carbamazepine, phenytoin and barbiturates), tuberculostatics (isoniazid,

rifampicin), some antibiotics (cephalosporins) and vitamin K antagonists (coumarin,

warfarin) [1, 3, 12]. In this study, we aimed to examine whether Portuguese neonatologists

are familiarized with this classification, as well as if they are able to inform the parents

about the best ways of preventing VKDB. From the 52 neonatologists, 14 did know that

the dangerous form of VKDB was the early form, and not the classic one (P11). Else, 19

identified the in uterus exposure to anticonvulsants, tuberculostatics and vitamin K

antagonists as a risk factor to VKDB (P3).

The oral and parenteral vitamin K applied at birth prevents early VKDB [4, 13],

though, according to the World Health Organization, all newborns should receive 1mg IM

injection of vitamin at birth for its prevention [14, 15]. Oral administration comprises 3

doses (2 mg immediately after birth, 2 mg between the 3rd and 7th day after birth, and 2

mg at 6 weeks of life), but it is not as efficient as the IM route [1]. Additionally, it is not

approved worldwide, and the oral vitamin K formulations are highly dependent on parent’s

compliance, and this highly influences its efficiency [1, 9, 11]. Even when the correct

administration is done, some studies support that the oral prophylactic scheme does not

prevent the late form [11, 16]. However, it can be an alternative when the parents refuse

the IM route [11]. All the participants of our study knew that vitamin K should be

prophylactically administered to all newborns (P14), and not only to those with high risk

(P13). Moreover, they also knew that the best prophylactic scheme was a single dose of

vitamin K via IM route (P16); 11 physicians considered the administration of 3 oral doses

an alternative (P15), and 9 out of 52 referred that the more efficient approach was the

intravenous (P17).

The American Academy of Paediatrics recommends that all newborns receive a

single vitamin K dose of 0.5 to 1 mg, administered intramuscularly[4]. Recent studies

evaluated the blood levels of vitamin K after this dosage administration and concluded to

be supraphysiologic in pre-term newborns. [1, 6, 7, 17, 18]. Accordingly, some studies

recommend that the doses should be adjusted to the newborn weight [1, 6-8]. Newborns

with more than 36 weeks should receive 1 mg of vitamin K. Pre-term newborns should

receive 0.5 mg if the birthweight is superior to 2.5 kg or 0.4mg/Kg when the weight at birth

is inferior to 2.5 Kg [1, 6-8]. In this study, 40.4% of the participants referred that the dose

is the same for all the newborns (1 mg; P18), 15.4% affirmed that in their workplace the

dose did not depend on the newborn being term or preterm (P29), and 25% considered

the dose is independent of the weight (P30). About 40% of the physicians referred that the

information about the correct dose is easily found in the literature (P20).

Vitamin K deficiency in newborns is mainly related to the low level of vitamin K

crossing the placenta (the levels in the umbilical cord are below 0,02ng/mL), as well as

due to the low levels of this vitamin in breastmilk [1, 7]. Mother supplementation with

vitamin K, rich food or supplements are not a solution since they do not cross the placenta.

During breastfeeding, supplementation does increase the levels of vitamin K in the

maternal milk, but this is insufficient to guaranteed the levels of vitamin K that prevent

VKDB [9, 19, 20]. In our investigation, 26.9% participants supported that VKDB risk could

be lowered by administering vitamin K to the mother during labour (P10). Breast milk has

very low levels of vitamin K, and this makes infants with exclusive breast feeding extremely

vulnerable to severe vitamin K deficiency. Milk formulas have higher levels of vitamin K,

and thus, infants fed with formula are less prone to VKDB. For the same reason, as infants

are introduced to full food diet the risk of VKDB is also reduced [7, 8]. About 25% of the

participants referred that maternal milk had higher levels of vitamin K than other milk

formulas (P7), and 40% assumed that formula fed infants had higher risk of VKDB (P8).

Approximately 70% supported that the risk of VKDB is reduced as new food is introduced

to infants (P9).

In 1992, Golding and colleagues found an association between IM injection of

vitamin K prophylaxis (brand name Konakion) and the incidence of leukaemia [21].

However, this association was not found in larger studies with data from multiple sites and

time periods [22, 23]. Kleanoff and colleagues performed a nested case-control study of

54.795 infants and found no association between vitamin K prophylaxis and childhood

leukaemia or cancer [22]. Furthermore, Ekelund and colleagues compared the rates of

childhood cancer and leukaemia among 1.085.654 infants receiving IM vitamin K with

272.080 infants who received oral vitamin K and found no significant differences between

the groups [23]. Even though the findings from the Golding’s study have not been

supported by later studies, these results may be mentioned in social and internet groups,

creating a false sense of insecurity about the injection [24]. This was the main cause of

parental discussion regarding vitamin K prophylaxis. Despite being highly recommended

by paediatric organizations, the refusal of its administration is increasing among parents

[24-26]. The increase in parental refusal of vitamin K administration was recognized by 11

participants, and those argued that this refusal was supported by literature (P22). Parents

want the labour to be as natural as possible and they believe that IM vitamin K is not only

unnecessary but also harmful [24, 25]. We tried to understand whether Portuguese

neonatologist were aware of this, considering that parents must always be informed about

the risks and benefits of vitamin K prophylaxis. More than 40% considered unnecessary

the explanation of the risks and benefits, as well as collecting informed consent with the

newborn’s parents before its administration (P21). In fact, only 19.2% of the participants

referred to collect informed consent before its administration. Vitamin K administration is

associated with local infection and putative nerve or muscular lesion in the site of

inoculation [8, 25]. Most of the participants recognized infection as a risk associated with

its administration (P2), while 48.1% referred that Vitamin K is completely safe for the

newborn. Leukaemia was considered as a possible adverse effect by 15.4% of the

participants, and solid tumours or jaundice by 3.8% and 5.8%, even if the actual

recommended dose is completely safe for haemolysis [8]. About 69% of the neonatologist

considered that it lacks discussion and information about the dose and administration of

vitamin K prophylaxis for prevent VKDB.

In this study we showed that a better knowledge was correlated with the number

of correct clinical practices. However, when the participants were divided according to their

clinical practice and medical knowledge, this difference was not statistically significant.

This result may be associated to the reduced number of participants in each group, that

is, a lower statistical power.

There was no association between clinical practice and medical knowledge and

the variables age, sex, number or births or hospital group. The most relevant factor should

be the level of knowledge of each participant, though it was not possible to clearly highlight

this relation.

We found a relation between hospital group and the use of a defined protocol;

highly differentiated hospitals had more protocols for vitamin K administration than the

others. The same was true for the information transmitted to parents about the risks and

benefits of its administration.

The limitations of this study are: (1) the lack of questionnaire´s validation, (2) the

bias introduced by the distribution of the questionnaires through the internet, and (3) the

small number of participants, which may lead to misleading conclusions.

In sum, this is the first Portuguese study evaluating knowledge and clinical practice

of Portuguese neonatologists concerning to the vitamin K prophylaxis. This study

highlights the relevance of updating the clinical protocols, as well as of the scientific

knowledge of the physicians that is relevant for the everyday practices. Finally, we should

also note the relevant role of the Portuguese scientific committees on the evaluation and

subsequent improvement of the practices in the delivery rooms.

References

1. Van Winckel, M., et al., Vitamin K, an update for the paediatrician. Eur J Pediatr, 2009. 168(2): p. 127-34.

2. Sutor, M.D.A.H., Vitamin K Deficiency Bleeding in nfants and Children SEMINARS IN THROMBOSIS AND HEMOSTASIS, 1995. 21(3): p. 317-329.

3. Clarke, P. and S. Mitchell, Vitamin K prophylaxis in preterm infants: current practices. Journal of Thrombosis and Haemostasis, 2003. 1(2): p. 384-386.

4. American Academy of Pediatrics, C.o.F.a.N., Controversies Concerning Vitamin K and the Newborn. Pediatrics, 2003. 112(1): p. 191-192.

5. Majid, A., et al., Newborn Vitamin K Prophylaxis: A Historical Perspective to Understand Modern Barriers to Uptake. Hospital Pediatrics, 2019. 9(1): p. 55-60.

6. Kumar, D., et al., Vitamin K Status of Premature Infants: Implications for Current Recommendations. Pediatrics, 2001. 108(5): p. 1117-1122.

7. Ardell, S., et al., Prophylactic vitamin K for the prevention of vitamin K deficiency bleeding in preterm neonates. Cochrane Database of Systematic Reviews, 2018(2).

8. Guideline, N.S.C., Vitamin K prophylaxis and Vitamin K Deficiency Bleeding. Health Board, August 2013.

9. Phillippi, J.C., et al., Prevention of Vitamin K Deficiency Bleeding. J Midwifery Womens Health, 2016. 61(5): p. 632-636.

10. Miller, H., B. Wheeler, and N. Kerruish, Newborn vitamin K prophylaxis: an analysis of information resources for parents and professionals. N Z Med J, 2016. 129(1446): p. 44-52.

11. Darlow, B.A., A.A. Phillips, and N.P. Dickson, New Zealand surveillance of neonatal vitamin K deficiency bleeding (VKDB): 1998-2008. J Paediatr Child Health, 2011. 47(7): p. 460-4.

12. Ng, E. and A.D. Loewy, Position Statement: Guidelines for vitamin K prophylaxis in newborns. A joint statement of the Canadian Paediatric Society and the College of Family Physicians of Canada, 2018. 64(10): p. 736-739.

13. Sutor, A.H., et al., Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/Perinatal Subcommittee. International Society on Thrombosis and Haemostasis. Thromb Haemost, 1999. 81(3): p. 456-61.

14. Hutton, A.R.J., et al., Transdermal delivery of vitamin K using dissolving microneedles for the prevention of vitamin K deficiency bleeding. Int J Pharm, 2018. 541(1-2): p. 56-63.

15. Organization, W.H., WHO recommendations on newborn health: guidelines approved by the WHO Guidelines Review Committee. No. WHO/MCA/17.07, 2017.

16. von Kries, R., A. Hachmeister, and U. Gobel, Repeated oral vitamin K prophylaxis in West Germany: acceptance and efficacy. Bmj, 1995. 310(6987): p. 1097-8.

17. Clarke, P., et al., Vitamin K prophylaxis for preterm infants: a randomized, controlled trial of 3 regimens. Pediatrics, 2006. 118(6): p. e1657-66.

18. Costakos, D.T., et al., Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg. Am J Perinatol, 2003. 20(8): p. 485-90.

19. Greer, F.R., et al., Improving the vitamin K status of breastfeeding infants with maternal vitamin K supplements. Pediatrics, 1997. 99(1): p. 88-92.

20. von Kries, R., et al., Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition, and vitamin K1 supplements given to the mother. Pediatr Res, 1987. 22(5): p. 513-7.

21. Golding, J., et al., Childhood cancer, intramuscular vitamin K, and pethidine given during labour. Bmj, 1992. 305(6849): p. 341-6.

22. Klebanoff, M.A., et al., The Risk of Childhood Cancer after Neonatal Exposure to Vitamin K. New England Journal of Medicine, 1993. 329(13): p. 905-908.

23. Ekelund, H., et al., Administration of vitamin K to newborn infants and childhood cancer. BMJ (Clinical research ed.), 1993. 307(6896): p. 89-91.

24. Hamrick, H.J., et al., Reasons for Refusal of Newborn Vitamin K Prophylaxis: Implications for Management and Education. Hosp Pediatr, 2016. 6(1): p. 15-21.

25. Block, S.L., Playing newborn intracranial roulette: parental refusal of vitamin K injection. Pediatr Ann, 2014. 43(2): p. 53-9.

26. Eventov-Friedman, S., et al., Parents' knowledge and perceptions regarding vitamin K prophylaxis in newborns. J Pediatr Hematol Oncol, 2013. 35(5): p. 409-13.

Tables

Table 1- Sociodemographic characteristics of the participants (n=52)

Sex, n (%)

Female 37 (71.2)

Male 15 (28.8)

Age group, n (%)

≤40 years old 17 (32.7)

41-49 years old 20 (19.2)

≥50years old 25 (48.1)

Hospital group, n (%)

Non-differentiated 9 (17.3)

Differentiated 21 (40.4)

Highly-differentiated 22 (42.3)

Number of births per month, n (%)

≤10 3 (5.8)

11-20 19 (36.5)

21-30 12 (23.1)

≥30 18 (34.6)

Table 2- Incidence of correct and incorrect answers

QUESTION INCORRECT CORRECT RATE(%) QUESTION INCORRECT CORRECT RATE(%)

P1 50 2 3.8 P16 0 52 100

P2 52 0 0.0 P17 9 43 82.7

P3 33 19 36.5 P18 21 31 59.6

P4 27 25 48.1 P19 29 23 44.2

P5 5 47 90.4 P20 23 29 55.8

P6 49 3 5.8 P21 22 30 57.7

P7 12 40 76.9 P22 11 41 78.8

P8 21 31 59.6 P23 10 42 80.8

P9 16 36 69.2 P24 0 52 100

P10 14 38 73.1 P25 42 10 19.2

P11 38 14 26.9 P26 26 26 50.0

P12 24 28 53.8 P27 38 14 26.9

P13 0 52 100 P28 16 36 69.2

P14 0 52 100 P29 8 44 84.6

P15 11 41 78.8 P30 13 39 75.0

Table 3- Knowledge of the participants.

KNOWLEDGE

n (%)

Low level 18 (34.6)

Average level 19 (36.5)

High level 15 (28.8)

Table 4 – Practices of the participants.

PRATICES

n (%)

Inappropriate pratices 27 (51.9)

Moderately adequate pratices 18 (34.6)

Highly adequate pratices 7 (13.5)

Table 5- Number of correct answers by hospital group, and comparison of the three hospital groups.

NUMBER OF CORRECT ANSWERS ABOUT KNOWLEDGE

Mean ± SD p

Non-differentiated (n=9) 11 ± 2.4

0.0261 Differentiated (n=21) 11.57 ± 2.27

Highly-differentiated (n=22) 12.91 ± 1.95

NUMBER OF CORRECT ANSWERS CLINICAL PRATICES

Non-differentiated (n=9) 3.56 ± 1.51

0.0251 Differentiated (n=21) 4.19 ± 1.23

Highly-differentiated (n=22) 4.82 ± 1.3 1ANOVA

Table 6- Association between knowledge and clinical practices and sex, age, hospital group and number of

births per month

KNOWLEDGE

Low Average High p

n (%) n (%) n (%) Sex

Male 4 (28.6) 6 (23.1) 5 (41.7) 0.3712

Female 10 (71.4) 20 (76.9) 7 (58.3)

Age

≤40 years old 5 (35.7) 8 (30.8) 4 (33.3)

0.2812 41-49 years old 2 (14.3) 5 (19.2) 3 (25.0)

≥50years old 7 (50.0) 13 (50.0) 5 (41.7)

Hospital group

Non-differentiated 4 (28.6) 4 (15.4) 1 (8.3)

0.3322 Differentiated 7 (50.0) 12 (46.2) 2 (16.7)

Highly-differentiated 3 (21.4) 10 (38.5) 9 (75.0)

Number of births per month

≤10 2 (14.3) 1 (3.8) 0 (0.0)

0.8622 11-20 6 (42.9) 8 (30.8) 5 (41.7)

21-30 1 (7.1) 8 (30.8) 3 (25.0)

≥30 5 (35.7) 9 (34.6) 4 (33.3)

Clinical pratices

Inadequate 10 (71.4) 11 (42.3) 6 (50.0)

0.1252 Moderately adequate 4 (28.6) 12 (46.2) 2 (16.7)

Highly adequate 0 (0.0) 3 (11.5) 4 (33.3)

CLINICAL PRATICES

Inadequate Moderately Highly adequate p

n (%) n (%) n (%) Sex

Male 7 (25.9) 5 (27.8) 3 (42.9) 0.7662

Female 20 (74.1) 13 (72.2) 4 (57.1)

Age

≤40 years old 8 (29.6) 4 (22.2) 5 (71.4)

0.1422 41-49 years old 4 (14.8) 5 (27.8) 1 (14.3)

≥50years old 15 (55.6) 9 (50.0) 1 (14.3)

Hospital group

Non-differentiated 7 (25.9) 1 (5.6) 1 (14.3)

0.1912 Differentiated 11 (40.7) 9 (50.0) 1 (14.3)

Highly-differentiated 9 (33.3) 8 (44.4) 5 (71.4)

Number of births per month

≤10 2 (7.4) 1 (5.6) 0 (0.0)

0.9062 11-20 12 (44.4) 5 (27.8) 2 (28.6)

21-30 5 (18.5) 5 (27.8) 2 (28.6)

≥30 8 (29.6) 7 (38.9) 3 (42.9)

knowledge

Low level 10 (37.0) 4 (22.2) 0 (0.0)

0.1252 Average level 11 (40.7) 12 (66.7) 3 (42.9)

High level 6 (22.2) 2 (11.1) 4 (57.1) 2Chi-square test

ATTACHMENTS

1- Questionnaire in english

I-CARACTERIZATION OF THE POPULATION

Gender:

Male_ Female__

Age: ___ Years

What Hospital Group does your hospital belong to:

Grupo I – Hospitals with Gynaecologists, obstetricians with labour rooms and paediatrics emergency. Direct Influence area between 75000 and 50000 inhabitants. No indirect influence area.

Grupo II- Hospitals with Gynaecologists, obstetricians with labour rooms and paediatrics emergency. Direct and indirect influence area for their medical specialties.

Grupo III- Hospitals with Gynaecologists, obstetricians with labour rooms, paediatrics emergency, Paediatric Cardiology, Paediatric surgery and genetics as well as all its subspecialties and differentiated units. Direct and indirect influence areas for this medical specialties.

Number of labours you assist per month:

<10

11-20

21-30

>30

II-MEDICAL KNOWLEDGE (choose the correct answer. You can choose more than one option)

P1- Which of the next are risk factors for newborn vitamin K deficiency bleeding

Mothers using corticosteroids

Mothers using anticonvulsants

Mothers with previous surgery

Mothers without vitamin K supplementation during pregnancy

Mothers who cannot breastfeed

P2- Which of the following are adverse effects associated with intramuscular vitamin K

administration.

Increased risk of solid tumours

Increased risk of leukaemia

Risk of infection

Increased risk of haemolysis or jaundice

Its administration has no risk.

P3- Which of this, when taken during pregnancy, is associated with increased risk of vitamin K

deficiency bleeding.

Anticonvulsants (phenobarbital or phenytoin)

Vitamin K antagonists

Tuberculostatica (Rifampicin and isoniazid)

Benzodiazepines

Neuroleptics

P4- According to recent studies, the risk, per 100000 newborns, of vitamin K deficiency bleeding,

without prophylaxis, is approximately:

55

35

20

10

<1

P5- According to recent studies, the risk, per 100000 newborns, of vitamin K deficiency bleeding,

with prophylaxis, is approximately:

55

35

20

10

<1

P6- According to recent studies, the risk of death, per 100000 newborns, of vitamin k deficiency

bleeding is:

55

35

20

10

<1

Y- Yes, N- No, DK, don’t know

Y N DK

P7- Breastmilk has lower levels of vitamin K when compared with other milk formulas.

P8- Vitamin K deficiency is less likely in formula-fed infants

P9- Vitamin K deficiency risk gets lower as other food, other than milk, is introduced to infants.

P10- Vitamin K deficiency bleeding can be prevented by administration of vitamin K to mothers in labour.

P11- Classic vitamin k deficiency bleeding, which happens in the first week of life, is the more dangerous one, with intracranial bleeding as a common complication.

P12- Healthy newborns, with vitamin K prophylaxis at birth, are no longer in danger of bleeding after the first week of life.

P13-Vitamin K should only be administered to high risk newborns (traumatic labour, low weight or biliary atresia).

P14- Vitamin K prophylaxis should be administered to all newborns.

P15- The recommended prophylaxis for prevention of vitamin K deficiency bleeding is three oral doses of vitamin K.

P16- The recommended prophylaxis for prevention of vitamin K deficiency bleeding is one single dose of intramuscular vitamin K.

P17- Intravenous administration of vitamin K is the most efficient form for prophylaxis of vitamin K deficiency bleeding.

P18-The recommended dose of vitamin K to be administered to all newborns, for vitamin K deficiency bleeding prophylaxis, is 1 mg.

P19- The dosage of vitamin K, recommended by the WHO, for prophylaxis of vitamin K deficiency bleeding is supraphysiologic.

P20- The correct dosage to be administered do pre-term neonates is easily found in the literature.

P21- Vitamin K administration, for prophylaxis of vitamin K deficiency bleeding, is the first health related decision parents should take. For this reason, risks and benefits should be explained, and informed consent should be provided.

P22- Parental refuse of vitamin K administration to newborns is increasing and the reasons are supported by the literature.

II- Clinical Practice

Y N DK

P23- In my workplace we have an updated protocol for prophylaxis of vitamin K deficiency bleeding of the newborn.

P24- In my workplace all the newborns receive vitamin K prophylaxis

P25- In my workplace vitamin K prophylaxis is discussed with the parents and informed consent is provided.

P26- In my workplace the physician responsible for the labour decides the vitamin K dosage to be administered.

P27- In my workplace the labour nurse decides the vitamin K dosage to be administered.

P28- In my workplace there is little discussion and information about the correct dosage and administration way for prophylaxis of vitamin K deficiency bleeding of the newborn.

P29- In my workplace vitamin K dosage varies whether a it is a full term or preterm infant.

(Choose whether the statement is true or false)

P30- In my workplace vitamin k dosage varies with newborn weight.

True ___; False ___

(Answer the next two questions only if you choose “True” in the previous question)

The vitamin K dosage administered to term newborns is :

0,1 mg/kg

0,2 mg/kg

0,4 mg/kg

0,6 mg/kg Other, which?

Q The vitamin K dosage administered to pre-term newborns is:

0,1 mg/kg

0,2 mg/kg

0,4 mg/kg

0,6 mg/kg Other, which?

Thank you for answering this questionnaire. All the information collected is confidential. If you want to receive the full article let us know you email.

2- Questionnaire in Portuguese

I-CARACTERIZAÇÃO

Sexo:

F__ M__

Idade: ___ anos

Grupo hospitalar a que pertence o hospital onde exerce a profissão:

Grupo I - Hospitais de Apoio Perinatal (especialidade de ginecologia/obstetrícia com bloco de partos e pediatria com urgência Pediátrica. Área de influência direta para as valências existentes entre 75.000 e 500.000 habitantes, sem área de influência indireta)

Grupo II- Hospitais de Apoio Perinatal- (especialidade de ginecologia/obstetrícia com bloco de partos e pediatria com Urgência Pediátrica. Área de influência direta e indireta para as suas valências).

Grupo III- Hospital de Apoio Perinatal Altamente Diferenciado (especialidade de ginecologia/obstetrícia com bloco de partos, pediatria, Cardiologia Pediátrica, Cirurgia Pediátrica e Genética Médica e todas as subespecialidades ou unidades diferenciadas. Área de influência direta e indireta para as suas valências)

Número de partos que assiste por mês:

<10

11-20

21-30

>30

II-CONHECIMENTO GERAL (escolher a/as respostas corretas)

P1- Dos seguintes qual/quais são fatores de risco comprovado(s) de hemorragia no recém

nascido (RN) por défice de vitamina K:

Mãe sob terapêutica com corticosteroides

Mãe sob terapêutica com anti-convulsionantes

Mãe sujeita a cirurgia

Mãe que não fez suplementação com vitamina K durante a gravidez

Mãe que não pode amamentar

P2- De entre as seguintes selecione a(s) que representa(m) riscos comprovadamente associados

à administração de vitamina K via Intra-Muscular(IM) no RN:

Risco de tumores sólidos

Risco de leucemia

Risco de infeção

Risco de aumento de icterícia ou hemólise

A vitamina K é completamente inócua para o RN

P3- Indique o(s) grupo(s) de fármacos que, quando se verifique a exposição in útero, pode(m)

aumentar o risco de hemorragia do RN por défice de vitamina K:

Anti-convulsionantes (fenobarbital ou fenitoína)

Anticoagulantes

Tuberculoestáticos (rifampicina e isoniazida)

Benzodiezepinas

Antipsicóticos

P4- De acordo com os estudos mais recentes, o risco, por 100,000 lactentes, de hemorragia por

défice de vitamina K, no RN que NÃO fez esquema de profilaxia, é de aproximadamente:

55

35

20

10

<1

P5- De acordo com os estudos mais recentes, o risco, por 100,000 lactentes, de hemorragia por

défice de vitamina K, no RN que fez esquema de profilaxia, é de aproximadamente:

55

35

20

10

<1

P6- De acordo com os estudos mais recentes o risco de morte, na hemorragia por défice de

vitamina K, no RN é:

55

35

20

10

<1

(escolher a respostas corretas)

S-sim, N-não, NS- não sei

S N NS

P7- O leite materno tem níveis mais baixos de vitamina K quando comparado com fórmulas de leite adaptado

P8- O défice de vitamina K é menos provável no RN sob aleitamento com leite adaptado

P9- O risco de hemorragia por défice de vitamina K diminui quando o lactente introduz outros alimentos para além do leite materno

P10- O risco de hemorragia por défice de vitamina K pode ser evitada administrando vitamina K a mães em trabalho de parto

P11- A hemorragia por défice de vitamina K na forma clássica, que ocorre na primeira semana de vida, é a forma mais grave, sendo a hemorragia intracraniana uma complicação comum

P12- RN saudáveis, que fizeram profilaxia com vitamina K ao nascimento, deixam de estar em risco de hemorragia por défice de vitamina K ao completarem uma semana de vida

P13- A vitamina K só deve ser administrada a RN considerados de alto risco (parto traumático, baixo peso ou com patologia associada como atresia das vias biliares)

P14- A vitamina K deve ser administrada profilaticamente a todos os RN

P15- A profilaxia recomendada para prevenção da hemorragia por défice de vitamina k consiste na administração de três tomas vitamina K por via oral

P16- A profilaxia recomendada para prevenção da hemorragia por défice de vitamina K consiste na administração de uma toma única de vitamina K por via IM.

P17- A forma mais eficaz de administração de vitamina K para profilaxia da hemorragia é a via IV.

P18- A dose recomendada, em todos os recém nascidos, para profilaxia da hemorragia por défice de vitamina K, é de 1 mg

P19- A dose de vitamina K recomendada pela OMS, no recém nascido, para a profilaxia de hemorragia por défice de vitamina K, corresponde a uma dose plasmática suprafisiológica

P20- A dose de Vitamina K a administrar no recém nascido pré-termo é facilmente encontrada na literatura.

P21- A administração de vitamina K, para profilaxia da hemorragia por défice de vitamina K, é a primeira decisão em saúde que os pais do recém nascido têm que tomar. Devem, por isso, ser meticulosamente explicados os riscos e benefícios da sua administração, clarificar as dúvidas e pedir o consentimento

P22- A recusa pelos pais da administração de vitamina K está a aumentar e os motivos são fundamentados pela literatura

II- PRÁTICAS CLÍNICAS

S N NS

P23- No meu serviço existe protocolo atualizado do esquema profilático de vitamina K para prevenção de hemorragia por défice de vitamina K no recém nascido

P24- No meu serviço todos os recém nascidos recebem profilaxia com vitamina K

P25- No meu serviço a administração profilática de vitamina K é discutida com os pais, aos é pedido o consentimento

P26- No meu serviço o médico responsável pelo parto controla a dose que é administrada de vitamina K

P27- No meu serviço a enfermeira parteira controla a dose que é administrada de vitamina K.

P28- No meu serviço há falta de discussão/informação sobre a dose e via de administração de vitamina K capaz de prevenir a hemorragia do recém nascido por défice de vitamina K

P29- No meu serviço a dose de vitamina K a administrar é diferente caso se trata de um recém nascido de termo ou de um recém nascido pré-termo

(escolher a resposta verdadeira)

P30- No meu serviço a dose a administrar é diferente e depende do peso do recém nascido.

VERDADEIRO ___

FALSO ___

(Responder às duas últimas questões caso tenha escolhido verdadeiro na questão anterior)

Quando se trata de um recém nascido de termo a dose que administro é:

0,1 mg/kg

0,2 mg/kg

0,4 mg/kg

0,6 mg/kg

Outra, qual?

Quando se trata de um recém nascido pré termo a dose que administro é:

0,1 mg/kg

0,2 mg/kg

0,4 mg/kg

0,6 mg/kg

Outra, qual?

O questionário chegou ao fim. Salientar mais uma vez que todos os dados são confidenciais.

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