Vitamin K deficiency bleeding in Australian infants
1993–2017: an Australian Paediatric Surveillance
Unit study
Yvonne Zurynski,1,2 Cameron J Grover,
1
Australian Paediatric
Surveillance Unit, The University
of Sydney, Sydney, New South
Wales, Australia
2
Australian Institute of Health
Innovation, Partnership Centre
in Health System Sustainability,
Macquarie University, Sydney,
New South Wales, Australia
3
Faculty of Medicine and Health,
University of Sydney, Sydney,
New South Wales, Australia
4
Population Health Intelligence,
Healthy People and Places Unit,
South Western Sydney Local
Health District, Liverpool, New
South Wales, Australia
5
School of Public Health and
Community Medicine, University
of New South Wales, Sydney,
New South Wales, Australia
6
Faculty of Medicine and
Health, Discipline of Child and
Adolescent Health, University
of Sydney, Sydney, New South
Wales, Australia
7
Kids Research, Sydney
Children’s Hospitals Network
Randwick and Westmead,
Sydney, New South Wales,
Australia
Correspondence to
Professor Elizabeth J Elliott,
Faculty of Medicine and
Health, Discipline of Child and
Adolescent Health, University
of Sydney, Sydney, New South
Wales 2006, Australia;
[email protected].
gov.au
3
Bin Jalaludin,4,5 Elizabeth J Elliott1,6,7
ABSTRACT
Objective To undertake surveillance of vitamin
K deficiency bleeding (VKDB) in Australia from
1993 to 2017, during a time of change to national
recommendations and available vitamin K formulations.
Methods Paediatricians reported cases of VKDB in
infants aged <6 months and provided demographic,
clinical and biochemical information via the Australian
Paediatric Surveillance Unit.
Results 58 cases were reported, of which 5 (9%)
were early, 11 (19%) classic and 42 (72%) late VKDB.
53 (91%) were exclusively breast fed. Seven (12%)
received oral prophylaxis, the majority (86%) of whom
did not receive all three recommended doses. The overall
reported incidence was 0.84 per 100 000 live births
(95% CI: 0.64 to 1.08) and the incidence of late VKDB
was 0.61 per 100 000 live births (95% CI: 0.44 to 0.82),
which are similar to rates reported by other countries
where intramuscular vitamin K is recommended. VKDB
rates were significantly higher (2.46 per 100 000
live births; 95% CI: 1.06 to 4.85) between 1993 and
March 1994 when oral prophylaxis was recommended
(p<0.05). Vitamin K was not given to 33 (57%) cases,
primarily due to parental refusal, and the number of
parental refusals increased significantly after 2006
(p<0.05). There were six deaths, all due to intracranial
haemorrhage, and three associated with home delivery
and parental refusal of vitamin K.
Conclusions Incidence rates of VKDB in Australia
are among the lowest in the world; however, we have
identified an increasing trend of parental refusal.
Ongoing surveillance and educational campaigns for
health professionals and parents are needed to prevent
VKDB.
YZ and CJG are joint first
authors.
Received 28 October 2018
Revised 13 August 2019
Accepted 19 August 2019
© Author(s) (or their
employer(s)) 2019. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Zurynski Y, Grover CJ,
Jalaludin B, et al.
Arch Dis Child Epub ahead of
print: [please include Day
Month Year]. doi:10.1136/
archdischild-2018-316424
INTRODUCTION
Vitamin K deficiency bleeding (VKDB) of infancy
is a rare but potentially fatal disorder that affects
4.4–10.5 per 100 000 live births, most of whom do
not receive vitamin K prophylaxis at birth.1 Vitamin
K is required for coagulation, but only small quantities cross the placenta and are found in breast milk
so vitamin K prophylaxis is recommended routinely
at birth to prevent VKDB.2 VKDB is classified
according to the age of onset of bleeding: ‘early’
occurs within the first 24 hours of life; ‘classic’
between 1 and 7 days and ‘late’ presents between
1 week and 6 months of age, with intracranial
haemorrhage in approximately 50%.3
Prophylaxis with intramuscular vitamin K was
introduced in 1961. In 1992, an association between
What is already known?
► Vitamin K deficiency bleeding (VKDB) is a rare
but potentially fatal disorder which is almost
entirely preventable by adequate vitamin K
prophylaxis at birth.
► Intramuscular vitamin K is widely considered
the gold standard and is the most reliable and
efficient form of prophylaxis.
► Hepatobiliary disease is a recognised risk factor
for prophylactic failure and early screening
increases survival.
What this study adds?
► The incidence in VKDB decreased significantly
after the national recommendations changed
from oral to intramuscular vitamin K
administration.
► Parental refusal of vitamin K has increased in
the last decade, particularly in areas where
immunisation refusal is most prevalent.
► Failure of intramuscular vitamin K prophylaxis
in four late cases of VKDB in breastfed infants
was reported and requires further research to
identify risk factors.
childhood cancer and intramuscular vitamin K
was reported.4 In response, in 1993, the National
Health and Medical Research Council (NHMRC)
of Australia released recommendations favouring
oral prophylaxis.5 It was soon recognised that the
evidence did not support an association between
intramuscular vitamin K and childhood cancer.6
The revised NHMRC guidelines (1995) recommended intramuscular administration, with an
option for three 1 mg oral doses.7 Current (2010)
NHMRC guidelines recommend 1 mg intramuscular vitamin K at birth, with the alternative of two
to three 2 mg oral doses if parents refuse intramuscular therapy.8 Vitamin K in Australia is primarily
administered via intramuscular injection. There are
no national data collections on the administration
of vitamin K prophylaxis and therefore national
coverage is not known. Estimates from the largest
jurisdiction in Australia, New South Wales (NSW),
suggest that 96% of infants receive intramuscular
vitamin K.9
In addition to changes in recommendations, there
was a change in the vitamin K preparation available
Zurynski Y, et al. Arch Dis Child 2019;0:1–6. doi:10.1136/archdischild-2018-316424
1
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Original article
in Australia over the study period. The cremophore formulation
(Konakion, 1 mg/0.5 mL Roche) which was licensed for intramuscular administration only (but was used for oral administration when parents refused consent for intramuscular) was
replaced by Konakion MM Paediatric (Roche) in the year 2000.8
This formulation continues to be the only vitamin K formulation available in Australia for prevention of VKDB.8 Konakion
MM Paediatric contains 2 mg in 0.2 mL vitamin K1 (phytomenadione) in a mixed-micellar formulation designed to afford better
bio-availability,10 and is licensed for intramuscular and oral use.8
A single dose of 1 mg intramuscular vitamin K is considered
the gold standard because it consistently prevents most cases of
late VKDB11 and is more effective than three 1 mg or 2 mg oral
doses.12 13 It is considered the most reliable method of prophylaxis by the NHMRC because it eliminates risks associated with
oral dosing regimens, including incomplete compliance and
vitamin K malabsorption in babies with cholestasis.8
The Australian Paediatric Surveillance Unit (APSU) has
collected information on cases of VKDB since 1993, providing
unique data to estimate incidence during three policy changes
and a change in the available vitamin K formulation.
METHODS
Case definition
Australian paediatricians and other child health professionals
who participate in APSU surveillance were asked to report any
infant aged <6 months with newly diagnosed VKDB. VKDB
was defined as spontaneous bruising, bleeding or intracranial
haemorrhage associated with prolonged clotting times but not
due to disseminated intravascular coagulation or an inherited
coagulopathy. VKDB was classified according to age of onset
of bleeding: ‘early’ within 24 hours of birth; ‘classic’ between
1 and 7 days and ‘late’ between 1 week and 6 months of age.
In addition, definite cases had to meet laboratory criteria:
abnormal clotting time as indicated by international normalised
ratio ≥4 or prothrombin time (PT) ≥four times the laboratory
control value; normal or raised platelet count; normal fibrinogen or absence of fibrin degradation products; and evidence
of normalisation of PT after vitamin K administration, when
available.14
Reporting
Like other paediatric surveillance units, the APSU facilitates
prospective case reporting by paediatricians and other child
health specialists.15–17 From 1993 to 2017, APSU sent a monthly
report card listing conditions of interest including VKDB to
between 990 (in 1993) and 1500 (in 2017) paediatricians and
over 90% of all cards were returned. For each case reported,
clinicians provided information on maternal demographics,
vitamin K prophylaxis, clinical presentation, feeding, coagulation studies and clinical outcome. Minimal identifiers (date of
birth, and the first two letters of the infant’s first and surnames)
allowed identification of duplicate reports. Completed questionnaires were reviewed by the authors and an expert panel of
clinicians, and cases that satisfied case definition criteria were
classified as ‘definite’. Cases with a history of bleeding consistent with VKDB but with incomplete coagulation results were
classified as ‘probable’. Cases with insufficient clinical or laboratory data to allow classification as definite or probable, and
cases that did not satisfy the case criteria, were not included
in analyses. Case criteria remained unchanged throughout the
study.
2
Table 1 Characteristics of definite and probable cases, grouped by
type, n (%)
N, total
Early
Classical
Late
Total
5 (9%)
11 (19%)
42 (72%)
58 (100%)
N, definite
4
7
36
47
N, probable
1
4
6
11
Home birth
2 (40)
0 (0)
11 (26)
13 (22)
Full term (≥37 weeks)
5 (100)
11 (100)
38 (90)
54 (93)
Premature (<37 weeks)
0 (0)
0 (0)
3 (7)
3 (5)
Unknown
0 (0)
0 (0)
1 (2)
1 (2)
39 (67)
Gestational age
Birth weight
Normal (≥2500 g)
5 (100)
9 (82)
25 (60)
Low (<2500 g)
0 (0)
1 (9)
4 (10)
5 (9)
Unknown
0 (0)
1 (9)
13 (31)
14 (24)
Vitamin K prophylaxis given
2 (40)
5 (45)
18 (43)
25 (43)
Intramuscular
1 (20)
1 (9)
12 (29)
14 (24)
Oral
1 (20)
2 (18)
4 (10)
7 (12)
Intravenous
0 (0)
1 (9)
0 (0)
1 (2)
Combination
No vitamin K prophylaxis
0 (0)
1 (9)
2 (5)
3 (5)
3 (60)
6 (55)
24 (57)
33 (57)
Parental refusal
3 (60)
5 (45)
20 (48)
28 (48)
Not offered/error
0 (0)
1 (9)
4 (10)
5 (9)
Exclusively breast fed
4 (80)
10 (91)
39 (93)
53 (91)
Predominately breast fed
1 (20)
0 (0)
1 (2)
2 (3)
Predominately formula fed 0 (0)
1 (9)
1 (2)
2 (3)
Unknown
0 (0)
1 (2)
1 (2)
26 (45)
Feeding
0 (0)
Site of bleeding
Skin bruising
1 (20)
3 (27)
22 (52)
Umbilical
2 (40)
1 (9)
3 (7)
6 (10)
Gastrointestinal
2 (40)
7 (64)
11 (26)
20 (34)
17 (29)
Intracranial
1 (20)
0 (0)
16 (38)
Nasal
1 (20)
0 (0)
4 (10)
5 (9)
Heel prick ooze
0 (0)
2 (18)
1 (2)
3 (5)
Circumcision site
Jaundice in first week of life
0 (0)
0 (0)
3 (7)
3 (5)
0 (0)
0 (0)
17 (40)
17 (29)
Liver disease confirmed
0 (0)
Age of onset of VKDB, mean
<1 day
2.4 days
0 (0)
18 (43)
18 (31)
50.9 days
37.1 days
Outcome at discharge
No ongoing morbidity
4 (80)
10 (91)
20 (48)
34 (59)
Ongoing morbidity
0 (0)
1 (9)
14 (33)
15 (26)
Died
0 (0)
0 (0)
6 (14)
6 (10)
Unknown
1 (20)
0 (0)
2 (5)
3 (5)
Statistical analysis
Incidence rates per 100 000 live births and 95% CIs were calculated using standard methods for rare events assuming a Poisson
distribution. Estimates of live births, published by the Australian
Bureau of Statistics, were used as the denominator.18 Two-tailed
Fisher’s exact test was used to compare incidence rates.
RESULTS
Notifications
There were 176 notifications between January 1993 and
December 2017, for which 141 (80%) had complete clinical
data. In all, 38 were errors, 45 were duplicate reports and 58
were cases (47 definite and 11 probable). Two infants born in
late 1992 who presented with VKDB in 1993 were included.
Case summary
Of the 58 cases, 42 (72%) were classified as late VKDB (table 1),
17 of whom had jaundice prior to bleeding; 11 (19%) were
Zurynski Y, et al. Arch Dis Child 2019;0:1–6. doi:10.1136/archdischild-2018-316424
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Original article
Figure 1 Reported cases of VKDB reported each year and grouped by the type of prophylaxis received or not received (1993–2017). 1. Not offered
or omitted due to administrative errors. 2. Combined refers to two or more different routes of administration being used together (eg, oral and
intramuscular, or intravenous and intramuscular, etc). VKDB, vitamin K deficiency bleeding.
classical VKDB and 5 (9%) early VKDB. The majority were born
at term (93%) and exclusively breast fed (91%). All three premature infants were exclusively breast fed: two of these have been
previously described.19 In all, 13 (22%) were delivered at home.
The most common sites of bleeding were cutaneous (45%),
gastrointestinal (34%) and intracranial (29%).
Vitamin K was not administered to 33 (57%) infants: consent
was withheld for 28 (85%) of these; in four (7%), the reasons for
not receiving vitamin K were not reported; and in one there was
no clinician at the home birth to offer vitamin K.
In all, 14 (24%) infants bled after receiving intramuscular
prophylaxis. Eight received the recommended 1 mg dose, three
received 0.1 mg and three received an unknown dose. Of the
eight who received the recommended 1 mg dose, one was a classical case (bleeding at day 5) and the other 7 were late cases
who bled between day 8 and 24 weeks of age. This is the only
case of classic VKDB reported after receipt of 1mg intramuscular
vitamin K in 25 years. The other seven were late cases who bled
between day 8 and 24 weeks of age. Three of the late cases had
liver or biliary disease and four were otherwise-healthy infants
who were exclusively breast fed with no other recognised risk
factors.
The three infants who received intramuscular vitamin K 0.1 mg
were born at term in 1993, 2008 and 2014. One had haematemesis on day 5 and was given one oral dose of 1 mg vitamin K after
which the coagulation studies were normal. The second infant
had an intracranial bleed on day 98: vitamin K corrected the
coagulation studies and biliary atresia was diagnosed. The third
infant had skin bruising and bleeding which stopped after one
dose of 1 mg intramuscular vitamin K. Cases of VKDB following
intramuscular prophylaxis were evenly distributed throughout
the period of surveillance (figure 1).
Seven (12%) infants developed VKDB following oral
prophylaxis. One infant received three 1 mg doses, two
received two doses and four received one dose. All infants
were exclusively (83%) or predominately (17%) breast fed and
four of the five with late VKDB had confirmed liver disease.
Almost half (43%) the infants who received oral vitamin K
were born between January 1993 and March 1994 and during
this period the proportion of cases of VKDB following oral
prophylaxis was significantly higher than after the introduction of the intramuscular recommendation in 1995 (χ2=5.65;
p=0.017).
One infant received two doses of intravenous prophylaxis in
2004. Three infants received vitamin K by combined routes:
two received intravenous and oral vitamin K, and another infant
received intramuscular and oral vitamin K.
The proportion of parents who refused vitamin K was significantly higher during 2006–2017 (19, 63%) compared with
the period 1993–2005 (9, 32%) (χ2=5.64; p<0.05). In the
5 years 2013–2017, among the 14 cases of VKDB reported in
this period, 10 (71%) did not received vitamin K because their
parents refused consent (figure 2). Parental refusal of vitamin K
occurred at 11 (85%) of the 13 home births. In total, 11 (39%)
cases following parental refusal occurred in Northern NSW and
South-Eastern Queensland.
Zurynski Y, et al. Arch Dis Child 2019;0:1–6. doi:10.1136/archdischild-2018-316424
3
Outcome
Six deaths were reported, all from intracranial haemorrhage
in infants with late VKDB. Three of these infants were delivered at home, were not given vitamin K due to parental refusal
and were exclusively breast fed; one of whom had cholestasis.
The remaining three were delivered in hospital and received
intramuscular prophylaxis: two had confirmed liver disease
and did not receive the recommended dose; the other did not
have liver disease and had received recommended prophylaxis
but was exclusively breast fed. One death occurred in 1993,
1998, 2010 and 2014 and two in 2000. No adverse effects
following vitamin K administration were reported during the
study period.
Arch Dis Child: first published as 10.1136/archdischild-2018-316424 on 13 September 2019. Downloaded from http://adc.bmj.com/ on December 12, 2021 by guest. Protected by copyright.
Original article
Figure 2 Estimated annual incidence rates and 5-year incidence rates of VKDB (1993–2017). †Before April 1994, oral vitamin K was recommended;
from April 1994 intramuscular vitamin K was recommended. ‡The available formulation of vitamin K changed from Konakion, 1 mg/ 0.5 mL (Roche) to
Konakion MM paediatric (Roche) and in the same year the National Health and Medical Research Council joint statement and recommendations on
vitamin K administration to newborn infants to prevent VKDB in infancy, was released. VKDB, vitamin K deficiency bleeding.
Incidence
To our knowledge, we report the longest period of continuous
national surveillance for VKDB, which covered changes in policy
and vitamin K formulation in Australia. The surveillance method
used is similar to other countries.16 The overall annual incidence
of VKDB in Australia, at 0.84 per 100 000 live births, is comparable to rates reported in countries where 1 mg intramuscular or
the three 2 mg oral dosing regimens were used, although international comparison is limited by slightly different surveillance
methods and timing of studies.12 13 20–22
VKDB incidence decreased significantly after the Australian
recommendations were changed from three 1 mg doses of oral
vitamin K to 1 mg intramuscular injection in April 1994. The
1994 recommendations retained an option for parents to choose
the oral regimen and several cases of VKDB were associated with
oral dosing, mostly when fewer than three doses were given. In
2000, the alternative oral regimen was changed from three 1 mg
to three 2 mg doses and only three cases of VKDB following oral
prophylaxis have been reported in the 17 years since.
Cases of VKDB were reported almost every year of the study.
Incidence rates increased in the year 2000, coinciding with a
change in the vitamin K preparation available in Australia from
the Cremophor EL formulation (Konakion, Roche) for intramuscular injection to the mixed-micellar Konakion MM Paediatric
(Roche) for either intramuscular or oral dosing.8 The increased
incidence is unlikely to be related to the introduction of the
mixed-micellar vitamin K formulation, which has not been associated with increasing rates of VKDB elsewhere.23 A possible
explanation may be increased awareness and reporting of VKDB
with the release of the new NHMRC guidelines on vitamin K
prophylaxis in 2000.8
According to our data, a single 1 mg intramuscular dose of
vitamin K at birth continues to prevent almost all cases of late
VKDB. The higher incidence rates of late VKDB compared with
other countries with similar prophylactic regimens might be
explained by the increase in parental refusals in Australia; only
New Zealand reported a higher incidence of late VDKB which
was almost exclusively attributed to parental refusal of vitamin
K.22 The number of VKDB cases following parental refusals
doubled in the second half of the study and further increased
in the last 5 years. Increasing rates of parental refusal have
been reported worldwide,24 25 and Busfield reported parental
refusal in 45% of VKDB cases between 2006 and 2008 in the
UK.20 In NSW, the most populous jurisdiction of Australia, it
is estimated that approximately 1.1% of babies do not receive
vitamin K prophylaxis because of parental refusal.9 Analysis of
the geographical distribution of the infants with VKDB whose
parents refused vitamin K showed a cluster in Northern NSW
and South East Queensland, areas where immunisation refusal
rates are highest in Australia.26 Correlation between refusal of
vitamin K and refusal of routine vaccinations has been previously
reported.27 The reasons for parental refusal are manifold: vitamin
K is considered unnatural, potentially painful, incongruous with
an ‘alternative’ lifestyle and concerns about the increased risk of
cancer persist.28 In New Zealand, midwives were half as likely
as doctors to support vitamin K prophylaxis.29 Home births are
4
Zurynski Y, et al. Arch Dis Child 2019;0:1–6. doi:10.1136/archdischild-2018-316424
The overall annual incidence of VKDB was 0.84/100 000 live
births (95% CI: 0.64 to 1.08) and, for late VKDB, 0.61/100
000 live births (95% CI: 0.44 to 0.82). Incidence rates peaked
in 1993, 2000 and 2013 (figure 2). Between January 1993 and
March 1994, when oral vitamin K was recommended, the incidence per 100 000 live births was significantly higher than during
the remainder of the study when intramuscular prophylaxis was
recommended, both overall (2.46, 95% CI: 1.06 to 4.85 vs
0.76, 95% CI: 0.56 to 1.00; p=0.011) and for late VKDB (1.85,
95% CI: 0.68 to 4.02 vs 0.5, 95% CI: 0.38 to 0.76; p=0.026).
DISCUSSION
Arch Dis Child: first published as 10.1136/archdischild-2018-316424 on 13 September 2019. Downloaded from http://adc.bmj.com/ on December 12, 2021 by guest. Protected by copyright.
Original article
associated with higher rates of refusal of vitamin K,30 and home
births accounted for over a third (39%) of parental refusals while
only representing 0.3% of all Australian births.31
There were four infants with VKDB in our study who were
born in hospital and did not receive vitamin K despite parental
consent. Furthermore, three infants with VKDB received a lower
than recommended dose of 0.1 mg intramuscular instead of 1 mg
intramuscularly. These errors are rare but highlight the need for
verification protocols to ensure neonates are not inadvertently
overlooked or given the wrong dose. Education and awareness campaigns for parents and for health professionals who
attend births are needed. Strategies requiring the involvement
of senior paediatricians in all cases where parents refuse vitamin
K have been suggested in the UK and could be implemented in
Australia.32
Failure of vitamin K prophylaxis is rare, with an estimated
incidence rate of 0–0.25 per 100 000 live births.33 Of the seven
cases of late VDKB following 1 mg intramuscular vitamin K,
three had confirmed liver or biliary disease, which is associated
with prophylactic failure,11 but four exclusively breastfed infants
without other risk factors had VKDB after 1 mg intramuscular
vitamin K prophylaxis. Prophylaxis failure has been reported in
healthy breastfed infants.21 34 Exclusive breastfeeding is widely
recommended until 6 months of age,35 so the relationship
between breastfeeding, mothers’ nutritional status and VKDB in
infants who received intramuscular vitamin K at birth warrants
further investigation.
There was one report of classic VKDB following prophylaxis
with the recommended 1 mg intramuscular dose. The data available to the APSU are not extensive enough to further investigate in detail the cause of VKDB in this rare case, and failure of
prophylaxis cannot be confirmed. It is more plausible that the
apparent failure of intramuscular prophylaxis in one classic case
reported by us and another case reported by the British Paediatric
Surveillance Unit (BPSU) 36 is instead a failure of administration
of vitamin K or a reporting error by the clinicians. Comparison
of the number of cases of VKDB after apparent administration
of 1 mg intramuscular vitamin K between the BPSU and APSU
is difficult because the APSU data represent continuous surveillance over 25 years (1993–2017) while the four BPSU studies
covered several disjointed periods: 1988–1990, 1993–1994,
2001–2002 and 2006–2008.20 36 37 Furthermore, as both the
APSU and BPSU rely on voluntary reporting by clinicians, there
is possible over-reporting or under-reporting in either system.
Since the return to the recommendation for intramuscular
prophylaxis in 1994, there have been four cases of VKDB after
incomplete oral dosing. Lack of compliance with three oral
doses is recognised as a potential problem in Australia38 and
elsewhere,39 but has been dismissed by others.40 Intravenous
vitamin K prophylaxis does not provide the lasting protection
achieved with intramuscular vitamin K19 and has never been
recommended in Australia, although it was given alone to one
infant in 2004, and in combination with other modes of administration to three children between 1993 and 1994.
(PIVKA-II; undercarboxylated prothrombin) is not routinely
used in Australia and no information was collected on this
measure during our study. This should be considered for future
surveillance protocols, especially if PIVKA-II testing becomes
more common.32 Despite these limitations, we achieved a high
monthly return rate of report cards (93.5%) suggesting a high
level of participation among clinicians enrolled in the APSU.15
CONCLUSION
Parents continue to withhold consent for vitamin K prophylaxis
and VKDB following refusal has increased in the last 5 years.
Research about community perceptions regarding the importance of vitamin K prophylaxis and education is needed. Clinicians should be aware of the risk of VKDB in infants with liver
or biliary disease. Education about national guidelines is needed
for health professionals involved in perinatal care and for the
community regarding the importance of vitamin K prophylaxis
and potential consequences of vitamin K refusal.
Acknowledgements We thank all paediatricians and other child health clinicians
who have participated in APSU surveillance activities since 1993 and contributed
information about cases of VKDB. We acknowledge funding support from the
Australian Department of Health, in-kind support from the Royal Australasian
College of Physicians, Division of Paediatrics and Child Health; Kids Research at
the Sydney Children’s Hospital at Westmead and The University of Sydney, Faculty
of Medicine and Health, Discipline of Child and Adolescent Health. We thank
Professor Henderson-Smart who was the driving force in establishing surveillance
for VKDB in Australia, and Dr Peter Loughnan, Dr Kerry Chant, Dr Greta Ridley and
Dr Lee Taylor for their assistance with the surveillance study. We thank Ms Amy
Phu who developed an electronic data capture form in REDCap for use from 2013
onwards. This surveillance study was sponsored by Roche Pty Ltd between the years
2000–2005. YZ was supported in-part by a Sydney Medical School Foundation
Fellowship; EE was supported by NHMRC Practitioner Fellowships (# 457084,
1021480 and 1135959).
Contributors EE and BJ developed the original study protocol and have been
involved in collection, analysis and interpretation of data since 1993. CG,YZ and BJ
analysed and interpreted data and drafted the manuscript which has had input from
all authors.CG and YZ are joint first authors.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study received approval from the Sydney Children’s Hospitals
Network Human Research Ethics Committee (Approval number: 2006–062).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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The APSU relies on reporting by clinicians and there is likely
case under-ascertainment in our study. The reported incidence
rates must be considered as minimum estimates only. In all,
35 cases could not be classified because of incomplete data.
As most of these cases were from 1993, the incidence may be
significantly under-estimated for that year. Testing for protein
induced by vitamin K absence/antagonism of clotting factor II
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Arch Dis Child: first published as 10.1136/archdischild-2018-316424 on 13 September 2019. Downloaded from http://adc.bmj.com/ on December 12, 2021 by guest. Protected by copyright.
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