Este mes se ha dado a conocer en Lisboa, con motivo de la EASD, una nuevo ensayo publicado en la prestigiosa
revista The Lancet,
en la que los autores de la misma señalan que la monitorización continua de
glucosa debe ser ofrecida a todas las mujeres embarazadas con diabetes tipo 1
para reducir el riesgo de complicaciones para los recién nacidos.
Para las mujeres con diabetes tipo 1,
monitorizar los niveles de azúcar en la sangre continuamente durante el
embarazo a través de un dispositivo implantado ayuda a manejar mejor la
enfermedad y mejora los resultados del parto en comparación con las pruebas
tradicionales de pinchazos.
Uno de cada dos recién nacidos de
mujeres con diabetes tipo 1 puede sufrir complicaciones como resultado de estar
expuesta a niveles elevados de azúcar en la sangre materna. Las complicaciones
pueden incluir anomalía congénita, parto prematuro, muerte fetal, necesidad de
cuidados intensivos después del nacimiento, y mayores tasas de pre-eclampsia y
cesárea para la madre.
Los autores del ensayo internacional
dicen que, como resultado de estos hallazgos, este tipo de monitorización
continua de glucosa debería ser ofrecido a todas las mujeres embarazadas con
diabetes tipo 1 para ayudar a mejorar los resultados de los recién nacidos, y
de las propias madres.
En el estudio, los investigadores
ensayaron con un dispositivo de monitorización continua de glucosa (CGM) implantado
que proporciona 288 registros de glucosa al día, lo que permite a los usuarios
reconocer y responder los cambios en los niveles de azúcar en la sangre a
medida que ocurren. Compararon esto con la monitorización tradicional, usado
4-8 veces al día, que consiste en pinchar el dedo y poner la sangre en una tira
de prueba para medir los niveles de azúcar en la sangre.
El estudio incluyó a 214 mujeres
embarazadas con diabetes tipo 1 de 18 a 40 años que manejaban su condición con
insulina diaria (bombas de insulina o inyecciones diarias múltiples). La mitad
fueron asignados al azar para usar el dispositivo CGM, y la otra mitad para
usar el método de monitorización tradicional. El dispositivo se usó durante
aproximadamente 24 semanas. El estudio se llevó a cabo en 31 hospitales de
Canadá, Inglaterra, Escocia, España, Irlanda, Italia y Estados Unidos.
El dispositivo de monitorización
continua de glucosa ayudó a reducir los niveles de azúcar en la sangre en una
pequeña cantidad [0,2% (-0,34 a -0,03)]. En comparación con la monitorización
tradicional, las mujeres que usaron el dispositivo pasaron más tiempo en el
rango normal de niveles de azúcar en la sangre (68% vs 61% – equivalente a 100
minutos más por día) y pasaron menos tiempo con altos niveles de azúcar en la
sangre (27% % – equivalente a 1 hora menos por día). El número de episodios de
hipoglucemia grave y el tiempo de hipoglucemia fue comparable en los dos grupos
(18 vs 21 y 3% vs 4% respectivamente).
Es importante destacar que los
resultados del parto mejoraron para aquellas mujeres con diabetes que usaron
monitorización continua de glucosa, reduciendo el número de bebés que nacen más
grande que el promedio (53% vs 69%), el número de bebés admitidos a cuidados
intensivos por más de 24 horas (27% vs 43% , y el número de bebés nacidos con
niveles bajos de azúcar en sangre (15% vs 28%). En promedio, los bebés cuyas
madres habían utilizado el dispositivo de monitorización continua de glucosa
también salieron del hospital un día antes que los bebés cuyas madres usaron el
control tradicional (3,1 vs 4 días).
“Durante mucho tiempo ha habido un
progreso limitado en la mejora de los resultados de parto para las mujeres con
diabetes tipo 1, por lo que estamos contentos de que nuestro estudio ofrece una
nueva opción para ayudar a las mujeres embarazadas con diabetes y sus hijos”,
dice el Dr. Denice Feig, Universidad de Toronto y Sistema de Salud de Sinaí,
Canadá. “Mantener los niveles de azúcar en la sangre dentro del rango normal
durante el embarazo para las mujeres con diabetes tipo 1 es crucial para
reducir los riesgos para la madre y el niño. Sin embargo, con el proceso
tradicional, esto puede ser difícil ya que la sensibilidad a la insulina
fluctúa durante el embarazo, lo que significa que el ajuste exacto de las dosis
de insulina es complejo. Como resultado de nuestros hallazgos, creemos que este
tipo de monitorización debe ser ofrecido a todas las mujeres embarazadas con
diabetes tipo 1.
La profesora Helen Murphy, de la
Universidad de East Anglia, Reino Unido, agrega: “Aunque la monitorización
continua de glucosa es costosa, los costes adicionales probablemente serán
compensados por las estancias hospitalarias más cortas para los bebés y la
reducción en las admisiones de la unidad de cuidados intensivos neonatales.
Sólo necesitamos tratar a seis mujeres embarazadas para evitar que un bebé pesa
más de lo normal al nacer y una unidad de cuidados intensivos neonatales “.
El estudio también analizó los
efectos del dispositivo sobre los niveles de azúcar en la sangre para las
mujeres que planeaban el embarazo, pero no encontró el mismo grado de beneficio
para estas mujeres.
CONCEPTT: Continuous
Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A
multi-center, multi-national, randomized controlled trial - Study protocol
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on behalf of the CONCEPTT
Collaborative Group
Abstract
Background
Women with type 1 diabetes strive for
optimal glycemic control before and during pregnancy to avoid adverse obstetric
and perinatal outcomes. For most women, optimal glycemic control is challenging
to achieve and maintain. The aim of this study is to determine whether the use
of real-time continuous glucose monitoring (RT-CGM) will improve glycemic
control in women with type 1 diabetes who are pregnant or planning pregnancy.
Methods/design
A multi-center, open label, randomized,
controlled trial of women with type 1 diabetes who are either planning
pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to
≤ 86 mmol/mol) or are in early pregnancy (<13 weeks
6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to
≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside
conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible
women will wear a CGM which does not display the glucose result for 6 days
during the run-in phase. To be eligible for randomization, a minimum of 4 HGM
measurements per day and a minimum of 96 hours total with 24 hours
overnight (11 pm-7 am) of CGM glucose values are required. Those
meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women
will be recruited (110 planning pregnancy, 214 pregnant). This takes into
account 15 and 20 % attrition rates for the planning pregnancy and
pregnant cohorts and will detect a clinically relevant 0.5 % difference
between groups at 90 % power with 5 % significance. Randomization
will stratify for type of insulin treatment (pump or multiple daily injections)
and baseline HbA1c. Analyses will be performed according to intention to treat.
The primary outcome is the change in glycemic control as measured by HbA1c from
baseline to 24 weeks or conception in women planning pregnancy, and from
baseline to 34 weeks gestation during pregnancy. Secondary outcomes
include maternal hypoglycemia, CGM time in, above and below target (3.5–7.8 mmol/l),
glucose variability measures, maternal and neonatal outcomes.
Discussion
This will be the first international
multicenter randomized controlled trial to evaluate the impact of RT- CGM
before and during pregnancy in women with type 1 diabetes.
Trial registration:ClinicalTrials.gov
Identifier: NCT01788527 Registration
Date: December 19, 2012.
Keywords
Diabetes
mellitus type 1 Pregnancy Preconception Continuous glucose monitoring Randomized controlled trial
Background
Despite all efforts, women with type 1
diabetes in pregnancy continue to have increased rates of adverse pregnancy
outcomes. Women aiming for optimal glycemic control are at substantially
increased risk of severe hypoglycemia (episode of low blood glucose requiring
third party assistance) as well as pregnancy related complications of
gestational hypertension, preeclampsia and delivery by caesarean section.
Infants of mothers with diabetes face increased risk of preterm delivery,
macrosomia, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress and
neonatal intensive care unit admissions. Macrosomia itself is associated with
shoulder dystocia, birth injury, asphyxia and death. In a study of over
1,000,000 deliveries in Ontario, Canada, the rates of perinatal mortality and
congenital anomalies among women with pre-existing diabetes in pregnancy were
found to be approximately twice the rates of women without diabetes [1].
Numerous studies have shown that adverse
pregnancy outcomes can be reduced with improved glycemic control. Pre-pregnancy
care has been shown to assist women to improve glycemic control during the
crucial period of organogenesis, and has been associated with reduced rates of
adverse pregnancy outcomes including major congenital malformation, stillbirth
and neonatal death. However, even motivated women who attend pre-pregnancy
clinics still struggle to achieve and maintain optimal glycemic control [2].
CGM systems contain a subcutaneous
glucose-sensing device which measures interstitial glucose and provide detailed
information about the frequency and duration of glucose excursions, which is
either unavailable to the user at the time of collection but available after
(masked CGM) or available at the time (RT-CGM). One study comparing conventional
home glucose monitoring (HGM) with masked CGM, found that CGM detected
substantial hyperglycemia (>3 hours/day) and overnight hypoglycemia
(1–4 hours) missed by conventional glucose monitoring [3].
Another study demonstrated that pregnant women with type 1 diabetes are still
far from achieving the recommended glucose control target range of
3.9–7.8 mmol/l [4].
During the first trimester, masked CGM demonstrated that women spent 10–12 h
per day hyperglycemic (>7.8 mmol/L) and 2–3 h hypoglycemic
(<3.9 mmol/l). By the third trimester maternal hyperglycemia improved
only slightly even with frequent antenatal clinic visits.
RT- CGM use provides additional information
for the user to consider when adjusting diet, activity and insulin doses. A
systematic review in non-pregnant adults, demonstrated that RT- CGM use is
associated with modest improvements in glycemic control (a mean HbA1c reduction
of 0.3 %), with maximal impact (up to 1.0 % reduction in HbA1c) in
those with poor glycaemic control who use CGM at least 6 days per week [5].
However data from two randomized trials in pregnancy are conflicting. In a UK
trial of 71 women with type 1 and type 2 diabetes, randomized to wearing a
masked CGM every 4–6 weeks compared to standard care with HGM, the use of the
CGM was associated with both reduced HbA1c (0.6 %) and reduced risk of
macrosomia (OR 0.36, 95 % CI 0.13-0.98) [6].
A subsequent Danish trial of 154 women, randomized to use RT-CGM intermittently
(six days x five times) or standard care with HGM found no difference in glycemic
control or neonatal outcomes [7].
This may have been because women had good glycaemic control at baseline and
were not particularly compliant with RT- CGM, with only 60 % of women
using it intermittently. A systematic review thus concluded that more research
is needed to identify the most effective techniques of blood glucose monitoring
in pregnant women [8].
The aim of this study is to determine
whether the use of continuous RT- CGM will improve glycemic control in women
with type 1 diabetes who are a) planning pregnancy and b) in early in
pregnancy, without substantially increasing the rate of hypoglycemia.
Methods/design
Overall
study design
CONCEPTT is a multicenter, randomized, open label, controlled
trial with an intention-to-treat analysis of two parallel trials: one trial in
women planning pregnancy, and one in women in early pregnancy. Thirty trial
centers are located across six countries: Canada (11), UK (15), Spain (1),
Italy (1), USA (1) and Ireland (1). Women with type 1 diabetes in pregnancy who
are ≤13 weeks 6 days gestation with an HbA1c of 6.5 % to
≤10.0 % (48 to ≤86 mmol/mol), and women with type 1 diabetes planning
pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to
≤86 mmol/mol), will be eligible for the run-in phase (see Fig. 1).
The run-in incorporates a 6-day period during which women wear a masked CGM
(Medtronic iPro®2 Professional CGM with Enlite2 sensor) to ensure that they can
tolerate wearing a CGM device. Women who pass the run-in (>96 hours
total with ≥24 hours overnight [11 pm-7 am] of CGM data and at
least 4 HGM measurements per day) are eligible for randomization. Eligible
women are randomized to CGM (Medtronic MiniMed Guardian®, Medtronic MiniMed
Paradigm® Veo™ or Medtronic MiniMed® 640G system as per participant insulin
delivery method) along with usual HGM, or continue HGM without CGM. The primary
outcome is the change in HbA1c from baseline to 24 weeks or conception in
women planning pregnancy, and from baseline to 34 weeks gestation in women
who are pregnant.
Primary outcome
Pre-pregnant
cohort
The primary outcome is glycemic control as
measured by a change in HbA1c from randomization to 24 weeks. If the
participant becomes pregnant before 24 weeks, her final HbA1c is measured
post-confirmation of a positive pregnancy test.
Pregnant
cohort
The primary outcome is glycemic control as
measured by a change in HbA1c from randomization to 34 weeks gestation. In
women who do not progress to 34 weeks gestation, the latest measured HbA1c
is used to contribute to the primary outcome.
Secondary
outcomes
Pre-pregnant
cohort
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CGM time in target at
baseline, 12 and 24 weeks.
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HbA1c at baseline, 12 and
24 weeks.
Pregnant
cohort
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CGM time in target at
baseline, 24 and 34 weeks gestation.
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HbA1c at baseline, 24 and
34 weeks gestation
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Incidence of gestational
hypertension/preeclampsia
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Caesarean section:
pre-labour and intrapartum
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Gestational weight gain
(randomization to 36 weeks)
Pre-pregnant
and pregnant cohorts
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Hypoglycemia
o Episodes of ‘severe hypoglycemia’ requiring third party
assistance
o Mild-moderate episodes of hypoglycemia from CGM data
<3.5 mmol/L (mild) and <2.8 mmol/L (moderate) for 20 min
duration
o Nocturnal hypoglycemia: CGM glucose <3.5 mmol/L (mild)
and <2.8 mmol/L (moderate) for 20 min duration between
23.00–07:00 h
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Measures of glucose
variability:
o Mean amplitude of glycemic excursions
o SD of CGM measurements
o Mean absolute rate of change of CGM based on one week of sensor
values
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Length of hospital stay
associated with delivery
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Questionnaires
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Insulin requirements
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Safety outcome:
o A substantial increase in hypoglycemia will be defined as
>10 % increase in hypoglycemic episodes (<3.5 mmol/L for at
least 20 min duration) over and above the HGM group.
Infant Outcomes.
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Birth weight:
o Infant birth weight >90th centile using national growth
curves
o Infant birth weight >90th centile using customized centiles
o Infant birth weight <10th centile, using national growth
curves
o Infant birth weight <10th centile using customized centiles
o Infant birth weight ≥4 kg
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Pregnancy loss:
miscarriage, stillbirth, neonatal death (death ≤28 days of life)
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Preterm birth (<37 weeks
and early preterm <34 weeks)
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Birth injury
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Shoulder dystocia
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Neonatal hypoglycemia
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Hyperbilirubinemia
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Respiratory distress
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High level neonatal
care > 24 h
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Cord blood gas
pH < 7.0
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Hyperinsulinemia (using
cord c-peptide)
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Composite fetal outcome:
Pregnancy loss: miscarriage, stillbirth, neonatal death (death ≤28 days of
life), birth injury, neonatal hypoglycemia, hyperbilirubinemia, respiratory
distress, high level neonatal care > 24 h.
·
Sum of skin-folds
>90th percentile for gestational age – triceps, sub scapular, biceps and
suprailiac skin-folds
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Anthropometric measures -
infant birth weight, head circumference, chest circumference, abdominal
circumference, left and right upper-arm circumference, crown-heel length,
crown-rump length
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Length of hospital stay
until first discharge home
Statistical
analysis
Primary Outcome: The primary analysis will
compare the treatment groups on the 24-week HbA1c for the pre-pregnant cohort
and on the 34-week HbA1c for the pregnant cohort, controlling for baseline
HbA1c in an analysis of covariance that includes the treatment modality
(pump/MDI) and strata used in randomization as covariates. We will obtain point
and interval estimates of the treatment effect (the mean adjusted difference in
follow-up HbA1c between treated and control groups) and also test the null
hypothesis that the treatment effect is zero. The primary analysis will follow
the intention-to-treat principle with all participants analyzed in the group to
which they were randomized, regardless of actual sensor wear. In the analysis
of the pre-pregnant cohort, in women who become pregnant before 24 weeks,
the final outcome will be a measurement of HbA1c taken post-confirmation of
pregnancy. In the analysis of the pregnant cohort, in women who do not reach
34 weeks gestation, the last HbA1c taken prior to 34-weeks will be used
for the primary outcome. If important covariates remain imbalanced between
treatment groups despite the stratified randomization, these covariates will be
added to the regression model and the difference between adjusted and
unadjusted estimates will be examined to assess the impact of this imbalance.
Multiple imputation using earlier HbA1c measurements will be used to deal with
HbA1c values that are missing at the final assessment.
Sample
size estimation
The trial will include 324 participants,
with 110 in the pre-pregnant cohort (women planning pregnancy), and 214 in the
pregnant cohort.
In both cohorts, the sample size is based on
a clinically relevant difference in HbA1c of 0.5 %. For pregnant women, a
cross-sectional standard deviation (SD) of 1.1 was used, as it is towards the
upper limit of published HbA1c SD values ([9, 10, 11].
In pre-pregnant women, a SD value of 0.8 was used, based on reported SD values
in a trial of CGM in young adults [12].
As this latter study also reported the SD of change over 26 weeks, it was
possible to compute the correlation between repeated measurements. In the
various study groups, these correlations ranged from 0.4 to 0.7. To be
conservative, we used the lower value of 0.4 in our sample size calculations.
In both cohorts (pre-pregnant and pregnant), sample size was computed for an
analysis of covariance with the final HbA1c as the outcome and baseline HbA1c
and treatment group as predictors. Power was set at 90 % and the
two-tailed significance level was set at 5 %.
Data
management
The continuous glucose monitoring data
management and analyses will be handled by the Jaeb Center for Health Research,
Tampa, Florida. All other data and statistical aspects will be handled by the
Clinical Trials Services/Centre for Mother, Infant and Child Research, Toronto,
Ontario, and the trial statistician.
Trial
steering committee
A trial steering committee will be
responsible for the conduct of the trial. They will meet by teleconference on a
quarterly basis to review the progress of the trial or on an ad hoc basis
should the need arise.
Safety
considerations
A Data Safety Monitoring Board (DSMB) will
be established and will include experts in or representatives of the fields of
endocrinology, obstetrics, epidemiology, and clinical trials methodology. They
will meet after the initial safety analysis is completed, which will be done
after 50 % of the pregnant group has been recruited. Serious unanticipated
adverse events will be reported to the DSMB should the need arise.
Discussion
Implications
of the findings
We aim to evaluate the impact of RT- CGM on
glycemic control in two groups of women, those who are planning pregnancy and
women in early pregnancy. If we find an improvement, the use of the RT-CGM will
be encouraged and potentially reimbursed. We may also be able to determine if
RT-CGM is more helpful in certain subsets of participants (e.g. those using
pump or MDI), and whether the use of RT-CGM will affect maternal and neonatal
outcomes. If we do not find that RT-CGM is beneficial, then other technologies
such as closed-loop insulin delivery, may be indicated to facilitate optimal
glycemic control in type 1 diabetes pregnancies.
Dissemination
A report will be written for the funding
bodies and for peer-reviewed publication and will be disseminated to international
lay and scientific audiences.
Conclusion
Results from studies in non-pregnant
populations suggest that CGM improves glycemic control. Results from two
randomized studies performed during pregnancy are conflicting, one with and one
without improved glycemic control. This is the first study to look at
continuous use of RT- CGM both in women planning pregnancy and in women during
early pregnancy. It will inform patients, caregivers, and funding agencies
regarding the use of CGM in the pregnant woman with type 1 diabetes.
Abbreviations
AUC, Area under the curve; DSMB, Data Safety
Monitoring Board; HbA1c, Glycated haemoglobin; HGM, Home glucose monitoring;
MDI, Multiple daily injections; RT-CGM, Real-time Continuous glucose
monitoring; SD, Standard deviation.
Acknowledgements: The authors would like to thank the Clinical Trials Services team in particular Jon Barrett, Keitha McMurray, and Tamara Birkenheier at the Centre for Mother, Infant and Child Research, Sunnybrook Research Institute, Toronto, Canada. We would also like to thank Olivia Lou and Marlon Pragnell of the JDRF for their invaluable advice. For assistance with the complex legal and contractual issues we sincerely thank Frances Farnworth Ipswich Hospital NHS Trust and Mary Kasanicki Cambridge University Hospitals NHS Foundation Trust.
CONCEPTT Collaborative Group: Stephanie Amiel, Katharine Hunt, Louisa Green, Helen Rogers,
Benedetta Rossi and, Ben Stodhart, King’s
College Hospital, London, UK. Matteo Bonomo,
Federico Bertuzzi, Giuseppina D. Corica, Silvana Fazio, Roberto Giro, Elena
Mion, Andrea Moletta, Basilio Pintaudi and Rosa Sorrentino, Niguarda ca’ Granda Hospital, Milano,
Italy. Rosa Corcoy, Ana Isabel Chico, Mª José Martínez, Mireia
Sánchez, Diana Tundidor and, Alberto De Leiva, Hospital
de la Santa Creu i Sant Pau, Barcelona, Spain &
CIBER-BBN, Zaragoza, Spain. John Booth, Natalia McInnes,
Adelle Nykamp, Rose Otto, Ada Smith, Irene Stanton and, Tracy Tazzeo, McMaster University, Hamilton,
Canada. Lois Donovan, Carolyn Oldford, Catherine Young and Claire
Gougeon Alberta Health Services,
University of Calgary, Calgary, Canada. Denice
Feig, Barbara Cleave, Diane Donat, Shital Gandhi and, Michelle Strom, Mount Sinai Hospital, Toronto,
Canada. Robyn Houlden and, Adriana Breen Kingston General Hospital,
Queen’s University, Kingston, Canada. Kristin
Castorino, William Sansum Diabetes Center, Santa
Barbara, USA. Erin Keely, Heather Clark, Laura Gaudet, Alan
Karovitch and, Janine Malcolm, The
Ottawa Hospital General Campus, Ottawa, Canada. Julia Lowe
and, Anna Rogowsky, The Ottawa Hospital General Campus, Ottawa,
Canada. Ruth McManus, Anne Kudirka and, Margaret Watson, St. Joseph’s Health Centre, London,
Canada. Damian Morris, Frances Farnworth, Duncan Fowler, Sue
Mitchell and, Josephine Rosier, Ipswich
Hospital NHS Trust, Ipswich, UK. Helen Murphy,
Caroline Byrne, Katy Davenport, Jeannie Grisoni, Sandra Mulrennan, Sandra Neoh,
Esther O’Sullivan, David Simmons, Zoe Stewart, Heike Templin, Cambridge University Hospitals NHS
Foundation Trust, Cambridge, UK.
Helen Murphy, Jeremy Turner, Gioia Canciani, Niranjala (Nilu) Hewapathirana,
Louise Jones, Leanne Piper, Rosemary Temple and, Tara Wallace, Norfolk and Norwich University Hospital, Norwich,
UK. Rahat Maitland, Anita Banerjee, Annette Briley, Anna
Brackenridge, Pam Gilby, Carolyn Gill, Anna Reid, Claire Singh and, Sara White, Guys and St Thomas’ NHS Foundation
Trust, London, UK. Maria Wolfs St. Michael’s Hospital, Toronto,
Canada. Eleanor Scott, Del Endersby, Leeds
Teaching Hospitals NHS Trust, Leeds, UK. Michael Maresh,
Gretta Kearney, Juliet Morris, Susan Quinn and, Prasanna Rao-Balakrishna, Central Manchester University Hospitals
NHS Foundation Trust, Manchester, UK. Malcolm
MacDougall, Royal Victoria Infirmary, Newcastle
Upon Tyne, Newcastle, UK. Rudy Bilous,
Mary Bilous, Shilpa Mahadissu, Deepika Menini and, Rasha Mukhtar, South Tees Hospitals, NHS Foundation
Trust, Middlesbrough, UK. Richard
Holt, Jane Forbes, Nicki Martin, and, Fiona Walbridge, Southampton General Hospital, Southampton,
UK. Peter Mansell, Gayna Babington, George Bugg, Tasso Gazis, Nia
Jones and, Dawn Spick, Queen’s Medical Centre, Nottingham,
UK. Simon Heller, Rebecca Bustani, Val Gordon, Priya Madhuvrata,
Sue Hudson, Chloe Nisbet, Peter Novodvorsky, Alexandra Solomon and, Karen
Towse, Sheffield Teaching Hospitals NHS
Foundation Trust, Sheffield, UK. Sam Philip,
Anne Booth, Ann Cadzow, Martyna Chlost, Lynne Murray, Karen Norris and, Katrina
Shearer, Grampian Diabetes Centre, Aberdeen,
UK. Anna Dover, Frances Dougherty, Susan Johnston, Jill Little and,
Liz McKay, Royal Infirmary of Edinburgh, Edinburgh,
UK. Robert Lindsay, David Carty, Isobel Crawford, Fiona Mackenzie
and, Therese McSorley, Glasgow Royal Infirmary, Glasgow,
UK. Fidelma Dunne, Elizabeth Brosnan, Sharon Conway, Michelle
Courcy Byrnes, Linda Duane, Niamh Duffy, Aoife Egan, Geraldine Gaffney, Grainne
Higgins, Caroline Kelly, Collette Kirwan, Aaron Liew, Kevin Normoyle, Christina
Roarty and, Mairead Waldron, Galway
University Hospitals, Galway, Ireland. John
Weisnagel, Christyne Allen, Martin D’Amours, Marie-Christine Dubé and,
Valérie-Eve Julien, Centre hospitalier universitaire de
Québec, Quebec City, Canada. Ariane
Godbout, Sylvie Daigle. Centre Hospitalier de Université de
Montréal, Hôpital St. Luc, Montreal, Canada. Thomas
Ransom, Jill Coolen and Darlene Baxendale. Izaak
Walton Killam Health Sciences Centre (IWK), Halifax,
Canada. Jill Newstead-Angel, Royal
University Hospital, Saskatoon, Canada.
Alexandra L. Soloman, Karen Gorton, Margaret Jackson, Kirsty Miller and, Julie
Taylor, The Dudley Group NHS FT, Russells Hall
Hospital, Dudley, UK. Sonya Mergler,
Asma Qureshi, Adriana Rodriguez, Kathryn Mangoff, The Centre for Mother, Infant and Child
Research (CMICR), Toronto, Canada.
