1. Magnesium sulphate for fetal neuroprotection of the preterm infant - a managed KT (Knowledge Translation) project
Steering Committee:
LA Magee, A Synnes, R Liston
V Allen, MJ Ansermino, F Audibert, J Barrett,
R Brant, E Bujold, J Crane, P von Dadelszen,
N Demianczuk, KS Joseph, B Piedboeuf, GN Smith,
D Sawchuck, M Walker, W Whittle, S Wood

2. There is a need for KT
The uptake of evidence does not happen as quickly or as well as it should
In obstetrics, a notable example of failure to take up definitive information is the 22 year gap between the Liggins & Howie publication on antenatal corticosteroids use (1972) and the National Institutes of Health consensus conference and ACOG Committee Opinion on the topic (1994)
Importantly, active KT and audit of practice (as opposed to simple dissemination) have been effective in increasing rates of antenatal corticosteroid use

3. Knowledge translation (KT) - definition
“KT is a dynamic and iterative process that includes the synthesis, dissemination, exchange and ethically sound application of knowledge to
improve the health of Canadians,
provide more effective health services and products, and
strengthen the healthcare system.”
Dr. Ian Graham, Vice President, Knowledge Translation, CIHR

4. MAG CP
Objectives
We aim to actively manage the implementation of MgSO4 into clinical practice (i.e., facilitated KT)
Given their prohibitive cost, further RCTs are unlikely
Our specific goals are to determine, for pregnancies with preterm birth at <29 weeks, whether maternal administration of MgSO4 for fetal neuroprotection:
a) Can be increased to 80% of eligible women over 4 years;
b) Is associated with the anticipated decrease in CP or ‘death or CP’ that was seen in the RCTs; and
c) Is associated with an acceptable safety profile for mothers and babies.

5. MAG CP
Methods
In MAG-CP, we will focus on babies born at <29wk because:
(i) they are at highest risk of CP; and
(ii) they are those for whom maternal interventions (like MgSO4) and maternal and perinatal outcomes are collected directly by the Canadian Perinatal Network (CPN) or through linkage to the Canadian Neonatal (CNN) and Neonatal Follow-Up (CNFUN) that track neurodevelopmental outcomes to 3 years of age
For babies born at <29 weeks, we have a unique opportunity to translate into practice MgSO4 for fetal neuroprotection, monitor outcomes, and settle controversies

6. MAG-CP Methods The primary outcome Secondary outcomes
Rates of MgSO4 utilization
Secondary outcomes
CP (18 mos)
‘Death or CP’
Maternal side effects
Perinatal and paediatric adverse effects, including neurodevelopmental outcomes
Potential covariates to be considered as confounders will include maternal pre-eclampsia and gestational age

7. MAG-CP
Methods
A DSMB will review results for adverse maternal or paediatric outcomes every 6 months
Over 4 years of managed KT, we anticipate recruitment of 3752 mothers and 2497 children evaluated at 18 mos, based on: ongoing CPN enrollment of 940 babies/yr born at <29 weeks’, 83% survival to 18 mos, and 80% consent to 18 mos follow-up.
We are adequately powered to detect anticipated or important changes in adverse outcomes, even if MgSO4 is only administered to 50% of eligible women by the end of year 4.

9. MAG-CP 4. Adapt knowledge to local context,
select and tailor interventions,
implement interventions
Today!

10. MAG CP ‘Managed’ KT Review the evidence to avoid misinformation
Identify and overcome barriers to, and facilitators of, implementation of the evidence
Monitor ‘real-world’ effectiveness and safety

11. KT methods – effectiveness
Most effective
Mass media campaign
Clinical practice guidelines* - SOGC
Computerized decision support tools
Interactive small group* - KT site visits
Financial incentives (other incentives *) – CME credits
Have inconsistent effects
Didactic presentations* - today!
Educational materials* - e-learning module, reference material
Performance feedback* - audit of practice through Networks
Limited effects
Continuous quality improvement

12. MAG-CP
Background
MgSO4 is inexpensive and used routinely for eclampsia prophylaxis/treatment, BUT fetal neuroprotection is a new indication
ALSO, there are ongoing controversies that may prevent widespread implementation of MgSO4 into clinical practice, such as:
Inadequately studied outcomes (e.g., overall function at ≥ 2 years)
Known effect of higher doses on newborn respiratory drive and the potential for increased neonatal resuscitation requirements
Lack of understanding about the mechanism of action of MgSO4 12

13. MAG CP
1980s – 2 studies noted that preterm infants born to women with pre-eclampsia had a lower rate of adverse CNS outcomes c/w those without pre-eclampsia
1995 – case control study associated MgSO4 with fewer cases of CP among preterm infants born at < 1500g
Effect was also seen in animal studies
Thereafter – inconsistent effects from observational studies
MgSO4 shown to be effective as eclampsia prophylaxis and treatment, but mechanism unclear from among many potential mechanisms
Cerebral vasodilation, ↓ inflammatory cytokines and/or oxygen free radicals, and/or inhibition of calcium influx into cells

14. MAG CP
2002 to 2008 – 5 randomized controlled trials (6145 babies) compared MgSO4 vs. placebo and studied neurodevelopmental outcome
4 neuroprotective intent (one had a tocolytic arm)
Magpie Trial
Study quality was good
All neuroprotective intent described allocation blinding and double-masking of outcome assessment

15. 4 trials, 4446 infants

16. MAG CP
Background
In 2009, synthesis of RCT evidence (2002-8) showed convincingly that antenatal maternal administration of MgSO4 improves motor outcomes of preterm infants evaluated at 2 yr
SOGC has recommended MgSO4 for fetal neuro-protection in the setting of ‘imminent preterm birth’ at <32 weeks 16

17. MgSO4 for fetal neuroprotection
Let’s focus on the results (outcomes) first
We will return to the gestational age controversy

18. **
The direction of effect was the same for death or substantial GM dysfunction but it did not reach statistical significance
Results were consistent between trials and across the meta-analyses
Use of Mg for neuroprotection was not associated with an increase in paediatric death as seen when Mg was used as a tocolytic; consistent with the tocoloytic arm of one of the trials showing increased mortality but there was confounding by imbalance of multiple births, low quality score and 3/8 deaths were related to congenital anomalies or twin-to-twin transfusion

19. ‘Imminent preterm birth’ defined
‘Imminent preterm birth’ is defined as a high likelihood of birth due to one or both of the following conditions (II-2):
Active labour with ≥ 4 cm of cervical dilation, with or without PPROM
Planned preterm birth for fetal or maternal indications
Definition does NOT include PPROM without labour
These women made up 87% of women in one trial (BEAM), but Committee felt that administration of MgSO4 on antenatal wards as would often be required and this would have the potential to have significant resource implications

21. MgSO4 - background
2009 – a ‘translational flashpoint’ was reached when 3 independent meta-analyses reached the same conclusions
MgSO4 for fetal neuroprotection decreases the risk of childhood CP

23. Key messages Preterm birth is associated with an increased risk of CP
There is no cure so prevention is of primary importance
Three meta-analyses of RCTs have concluded that magnesium sulphate specifically for fetal neuroprotection decreases the risk of childhood ‘CP’ or ‘infant death or CP’
SOGC guidelines recommend that for women with ‘imminent preterm birth’ (at < 32 weeks), antenatal magnesium sulphate administration should be considered for fetal neuroprotection (Grade I-A)
Magnesium sulphate is widely used internationally
Magnesium sulphate adverse effects are
Usually minor for women
Evidence of serious adverse effects for the baby is lacking

24. Strong evidence is lacking for clinical issues:
Antenatal MgSO4 has not been associated with a decrease in CNS pathology associated with CP, cognitive impairment, and other adverse developmental outcomes associated with preterm birth
The gestational age ABOVE which MgSO4 should NOT be offered (e.g., 28 wk, 30, 32 wk, 34 wk)
Whether MgSO4 should be used for threatened preterm birth or PPROM only (without labour)
The optimal loading and maintenance doses of MgSO4
The potential for MgSO4 to increase neonatal resuscitative requirements
How MgSO4 works as a neuroprotective agent

25. Strong evidence is lacking for clinical issues:
Antenatal MgSO4 has not been associated with a decrease in CNS pathology associated with CP, cognitive impairment, and other adverse developmental outcomes associated with preterm birth
Gestational age ABOVE which MgSO4 should NOT be offered
Whether MgSO4 should be used for threatened preterm birth or PPROM only
Optimal loading and maintenance doses of MgSO4
Potential for MgSO4 to increase neonatal resuscitative requirements
We do not understand how MgSO4 works as a neuroprotective agent

26. Controversy: MgSO4 does not decrease other important CNS pathology associated with CP
KEY point to note is that we are not anticipating that long-term problems will be increased.
Rather, we hope that they will be DECREASED.
As such, if there remains no difference, then the effect on CP or ‘death or CP’ will remain clinically important.
Severe IVH - CIs wide: consistent with a 38% ↓, 13% ↑, or no effect at all.
Developmental delay - There was follow-up to age 2 yr, but there were no differences in neurocognitive testing outcomes. Learning disabilities and developmental co-ordination disorder (that are prevalent among extremely low birth weight babies born preterm) cannot be reliably detected until school age (planned for 2 of the trials).

27. Strong evidence is lacking for clinical issues:
Antenatal MgSO4 has not been associated with a decrease in CNS pathology associated with CP, cognitive impairment, and other adverse developmental outcomes associated with preterm birth
Gestational age ABOVE which MgSO4 should NOT be offered
Whether MgSO4 should be used for threatened preterm birth or PPROM only
Optimal loading and maintenance doses of MgSO4
Potential for MgSO4 to increase neonatal resuscitative requirements
We do not understand how MgSO4 works as a neuroprotective agent

28. Controversy: Gestational age above which MgSO4 should NOT be offered?
The recommendation to use MgSO4 at ≤ 316 weeks is designed to limit overuse, and based on:
Higher prevalence of CP at earlier gestational ages
These women are fewer in number compared with those at later gestational ages

29. Controversy: Gestational age above which MgSO4 should NOT be offered?
Death or CP: 14.9% [Mg] vs. 17.2% [placebo]
CP: % [Mg] vs. 5.0% [placebo]
NNT=50 to prevent one eclamptic seizure among women with severe pre-eclampsia
Best analysis would be to compare gestational age strata
In BEAM trial, randomisation was stratified by gestational age

30. P > 0.05 for all comparisons (Breslow-Day test).
BEAM Trial - NEJM 2008
P > 0.05 for all comparisons (Breslow-Day test).
“Institutions may choose different thresholds (at <34 weeks) according to other considerations, including the accuracy of gestational age determination and resource allocation”
[SOGC Guidelines, May 2011]

31. Strong evidence is lacking for clinical issues:
Antenatal MgSO4 has not been associated with a decrease in CNS pathology associated with CP, cognitive impairment, and other adverse developmental outcomes associated with preterm birth
Gestational age ABOVE which MgSO4 should NOT be offered
Whether MgSO4 should be used for threatened preterm birth or PPROM only
Optimal loading and maintenance doses of MgSO4
Potential for MgSO4 to increase neonatal resuscitative requirements
We do not understand how MgSO4 works as a neuroprotective agent

32. Magnesium Sulfate for Fetal Neuroprotection:
A Cost-Effectiveness and Cost-Utility Analysis
Celeste Bickford, BSc.
PhD Student
University of British Columbia
Faculty of Medicine
School of Population & Public Health

33. Cost-Effectiveness/Cost-Utility Analyses
Quadrant I:
New treatment is more costly + more effective
Quadrant IV:
New treatment is more costly + less effective
∆ effectiveness
Quadrant III:
New treatment is less costly + less effective
Quadrant II:
New treatment is less costly + more effective
Cost-Effectiveness Plane

34. Cost Effectiveness Ratio
Societal Perspective, QALYs
Societal Perspective, Cases of CP Averted
Cost
QALYs
 Cost
 QALYs
ICER
% Cases w/o CP
 Cases w/o CP
MgSO4
22,965
6.1
-13,362
0.1
-234,668 95 2
-598,109
No MgSO4
36,327
6.0
 No MgSO4 93
Health System Perspective, QALYs
Health System Perspective, Cases of CP Averted
403
-234
-4,108
-10,470
637

35. Incremental Cost-Effectiveness Plot
Cost-saving regardless of the outcome used (cases of CP averted or QALYs) or the perspective taken (societal or health system)

36. Moderate -severe CP cases prevented
AJOG 2011;205:542.e1-7
Moderate -severe CP cases prevented
QALY gained
Total $ saved
Threatened preterm birth at wk * 32 52
$1.8 million
PPROM only at wk 28 50
$1.5 million
Preterm birth at wk 23 56
$1.0 million

37. Outcomes: Moderate-severe CP and NND Effectiveness as QALYs
AJOG 2011;205:542.e1-7
Women at high risk of preterm birth at wk d/t PTL or PPROM with the risk of preterm delivery being 25% (95% CI 10-40%)
Also looked at two subgroups at risk for preterm birth:
With PPROM only at wk
Specifically at wk
Risk of preterm birth at wk MgSO4 as administered in the BEAM Trial as this was the only trial to individually find a decrease in CP
6g iv then 2g/hr for 12hr or until delivery
Efficacy estimated from meta-analysis of 4 trials that gave MgSO4 specifically for fetal neuroprotection, assumed to be constant over range of gestational ages
Outcomes: Moderate-severe CP and NND
Effectiveness as QALYs

38. For 10,000 eligible women treated with MgSO4
Moderate -severe CP cases prevented
QALY gained
Total $ saved
Threatened preterm birth at wk * 32 52
$1.8 million
PPROM only at wk 28 50
$1.5 million
Preterm birth at wk 23 56
$1.0 million
* Model revealed that even if only 10% of women admitted with threatened preterm birth went on to deliver at <32 wk, MgSO4 would be cost-effective

39. Sensitivity analysis on RR of CP with MgSO4
Model was sensitive to estimates of effect of MgSO4 on:
Risk of mod-severe CP is ≥ 0.87
ref : 0.71 [0.55, 0.91]
Risk of NND is ≥ 1.16
ref: 0.95 [0.80, 1.12]

40. Monte Carlo simulation (multivariate sensitivity analyses)
MgSO4 was the preferred strategy*
87% of time for women at high risk for preterm birth at wk
100% of time for women with PPROM at wk
100% of time for women delivering at wk
* Based on willingness to pay of $100,000/QALY

41. Strong evidence is lacking for clinical issues:
Antenatal MgSO4 has not been associated with a decrease in CNS pathology associated with CP, cognitive impairment, and other adverse developmental outcomes associated with preterm birth
Gestational age ABOVE which MgSO4 should NOT be offered
Whether MgSO4 should be used for threatened preterm birth or PPROM only
Optimal loading and maintenance doses of MgSO4
Potential for MgSO4 to increase neonatal resuscitative requirements
We do not understand how MgSO4 works as a neuroprotective agent

42. MgSO4 dosing
4 hours is the median time from administration to delivery

43. Optimal loading and maintenance dose?
4 hours is the mean time from randomization to birth in subgroup analysis

44. What about re-treatment?
One trial (BEAM) performed re-treatment but this enrolled primarily women with PPROM without labour
59.1% of women were re-treated when delivery was again considered to be imminent (which could have been within 24 hr)
These women are excluded from the definition of ‘imminent preterm birth’

47. What about other obstetric outcomes?
Caesarean section
822 (42.9%) MgSO4 vs. 834 (42.8%) placebo
RR 1.0 [0.9, 1.1]
Severe PPH
28 (3.4%) MgSO4 vs. 26 (3.2%) placebo
RR 1.1 [0.6, 1.8]
Length of labour - ?
Augmentation of labour - ?

50. Neonatal side effects?
RCTs raised no concerns about short-term neonatal side effects – no impact on:
Apgar <7 at 5 min RR 1.03 [0.90, 1.18]
Neonatal hypotonia RR 1.02 [0.77, 1.36]
Ongoing vent. support RR 0.94 [0.89, 1.00]
Need for active resuscitation at birth - ?
No correlation between cord blood Mg levels and need for bag-mask ventilation, intubation, or chest compressions
Not known whether MgSO4 would affect the need for ventilation in NICUs using ‘gentle resuscitation’

51. J Peds 2011;Nov 3 [E Pub]
Oxygen only
Bag/mask & oxygen
Intubation
* These data are from the BEAM Trial of women at <316 weeks

52. Cord Mg levels and delivery room resuscitation

53. Emerging literature Nested study within ActoMgSO4
Placebo
Hypotension
40%
31% p=0.40
Volume expanders
42%
21% p=0.03
Inotrope use
26% p=0.20
PDA Rx
38%
28% p=0.40
Pulmonary hemorrhage
17%
5% p=0.30

54. Neonatal side effects - summary
The largest RCTs suggest that there are no significant neonatal short-term effects and overall, there are long-term benefits
Potential for neonatal side effects must be assessed in new era of neonatal resuscitation:
Respiratory depression
Hypotension and need for volume expansion
Now loss of equipoise for future placebo-controlled trials

55. Other guidelines Australia 2010: ACOG 2010:
MgSO4 recommended for fetal neuroprotection at <30 weeks’
No one gestational age subgroup was superior to another, considering <34, <33, <32, and <30
Given uncertainty, it was prudent to limit the impact of their clinical practice guidelines on resource allocation
ACOG 2010:
“…the available evidence suggests that magnesium sulphate given before anticipated early preterm birth reduces the risk of cerebral palsy in surviving infants.”
No official opinion given on gestational age cut-off
Recommended that physicians develop specific guidelines around the issues of inclusion, dosage, concurrent tocolysis, and monitoring in accordance with one of the larger trials
What we have done nationally, and locally here at Women’s

56. CPN site investigator survey (Feb 2011)
Responses were received from 13/16 sites
All sites were comfortable with use of MgSO4 in pregnancy
9 indicated that they plan to follow SOGC recommendations
Opinions seemed to be based on at least some misinformation
Effectiveness based on trial results
3 sites felt that there were no supportive trial data
10 felt that MgSO4 decreased only CP and 7 sites also understood that MgSO4 decreased ‘death or CP’
Adverse effects on baby
6 sites - primarily resuscitative efforts and ventilation
Adverse effects on the mother
8 sites - respiratory depression, volume overload, or death
One site concerned about the paediatric benefit to maternal risk ratio
COST
10 sites were concerned about the demands that MgSO4 implementation for neuroprotection may have on labour and delivery suite staff

57. MAG CP: e-learning module
MAG-CP, like all KT, is about interaction. Our e-learning module not only contains information for you but it is how you can tell us what you think!

58. Issues that at least 20% of respondents answered incorrectly
‘Imminent’ preterm birth will occur within the next 24 hours, whereas ‘threatened’ preterm birth may occur in the next 24 hr or otherwise in the near future
The NNT (with MgSO4) to prevent one case of CP is similar at all gestational ages below 34 weeks, with no significant advantage below 28 weeks
There is no clear interaction between nifedipine and MgSO4
MgSO4 decreases CP and ‘death or CP’, but not death alone
There is no clear evidence that MgSO4 increases the need or intensity of neonatal resuscitation

59. Incorrect answers to pre- & post-test questions for at least 20% respondents
MgSO4 is not a tocolytic
PPROM (without preterm labour or another indication of ‘imminent’ preterm birth) is not an indication for MgSO4 for fetal neuroprotection
The short-term costs of administering MgSO4 for fetal neuroprotection are smaller than the lifetime costs of CP

60. Key messages Preterm birth is associated with an increased risk of CP
There is no cure so prevention is of primary importance
Three meta-analyses of RCTs have concluded that magnesium sulphate specifically for fetal neuroprotection decreases the risk of childhood ‘CP’ or ‘infant death or CP’
SOGC guidelines recommend that for women with ‘imminent preterm birth’ (at < 32 weeks), antenatal magnesium sulphate administration should be considered for fetal neuroprotection (Grade I-A)
Magnesium sulphate is widely used internationally
Magnesium sulphate adverse effects are
Usually minor for women
Evidence of serious adverse effects for the baby is lacking

61. Potential barriers – individual*
Knowledge and understanding:
evidence supporting use MgSO4 for fetal neuroprotection and the impact of MgSO4 on ‘death or CP’ (as opposed to CP alone)
association of CP and gestational age, upper gestational age limit for use
differential diagnosis of “threatened preterm labour” vs. “imminent preterm birth”
Attitudes towards use of MgSO4 in obstetrical practice:
effectiveness as a neuroprotective agent – do you believe it?
beliefs re use of MgSO4 where evidence is weak (e.g. repeat dosing)
safety and maternal / newborn adverse effects
historical use of MgSO4 in obstetrics for tocolysis
perceptions of liability
Habits related to use of MgSO4 in clinical practice:
loading dose and infusion rates when used for seizure prophylaxis and/or treatment
routine use of serum Mg levels
comfort level with MgSO4 administration

62. Potential barriers: social and organizational
Standards of Practice related to MgSO4 for fetal neuroprotection and SOGC Clinical Practice Guidelines
Patient perspectives and expectations
Organizational
LDR Staff and resource impact
NICU and resource impact
Cost of MgSO4
Institutional approval and policy development
Capacity for pre-printed physician orders for MgSO4 for fetal neuroprotection
Capacity for quality assurance related to MgSO4 for fetal neuroprotection
Administrative support or constraints
Specific organizational cultural issues

66. Mg and Newborns “Historic information”
1967 (Lipsitz PJ and English IC. Pediatrics. 40:856):
16 newborn cases of hypermagnesemia with respiratory failure and hyporeflexia
1971 (Lipsitz PJ.Pediatrics. 47:501) :
Case series of 37 infants of mothers Rxed with MgSo4 IV or IM
Mean dose of 35 mg. Mean Mg level 5.0 mEq/l at delivery
No assoc’n between :
Apgar score with cord Mg and maternal MgSO4 dose
Maternal Mg levels with maternal dose and cord Mg
Newborn symptoms and MgSO4 dose BUT after 24 hours of MgSO4 infusion all babies were symptomatic
Birth weight and cord Mg
IV calcium didn’t reverse symptoms
Slow excretion of Mg in newborns (up to 80 hrs)
2003 (Ali A et al. Pediatrics. 112:e70-72)
Two cases of TPN toxicity (Mg level (n= ))
Hypotonia, apnea, bradycardia and hypotension

67. 2009 Cochrane review 5 trials (6145 babies) eligible Antenatal MgSO4
Reduced CP (RR % CI )
Reduced gross motor dysfunction RR 0.61
No effect on: % CI
Pediatric mortality RR
Severe IVH RR
5 Min Apgar < 7 RR
Hypotonia RR
Resp Support RR

68. Neonatal Perspective: Respiratory
1998 (Riaz M et al. J Perinatol 18: )
Case control study (n=26 in each)
Maternal MgSO4: lower median Apgar and more hypotonia (p< 0.001)
2012 (Johnson et al. J Pediatr. 160:573-7)
Secondary analysis of Rouse’s RCT(n=1507)
Cord blood Mg did not correlate with need for delivery room resuscitation (OR % CI )

69. Neonatal Perspective: Hemodynamics
2000 (Barrington KJ et al. J Perinatol. 20:373-8) :
Neonatal piglets with meconium aspiration rec’d MgSO4:
Transient drop in HR, cardiac index, pulmonary and systemic pressures, O2 sats.
2007 (Del Moral T et al. J Perinatol 27:154-7) :
Cohort study of 954 ELBW
PDA incidence higher in babies with MgSO4 exposure, especially GA > 26 weeks

70. Neonatal Perspective: Hemodynamics
2011 (Paradisis et al. J Perinatol.32:665-70) :
Nested study within ActoMgSO4
MgSO4
Placebo
Hypotension
40%
31% p=0.4
Volume expanders
42%
21% p=0.03
Inotrope use
26% p=0.2
PDA Rx
38%
28% p=0.4
Pulmonary hemorrhage
17%
5% p=0.3

71. Neonatal Perspective: Other
2006:
Case report of two triplets with osteopenia and multiple fractures in Mom treated with MgSO4 from weeks GA
2011:
Retrospective study of wk GA n= 475
Serum Mg level > 4.5 increased mortality

72. Life Experiences
Clinicians perceive that MgSO4 is causing respiratory depression and hypotonia
Current emphasis on gentle resuscitation there is concern that MgSO4 will increase need for ventilation

73. Conclusions
Largest RCTs suggest that there are no significant neonatal short term effects and overall long term benefits
Potential for neonatal respiratory depression in a new era
Potential for hypotension and need for volume expansion and other hemodynamic changes

74. Need for Mag-CP
Loss of equipoise for further placebo controlled RCTs of MgSO4
Need to monitor use / short term neonatal effects and long term effects in real world setting

75. Magnesium Present in every cell in every organism
Biological membranes are impermeable so transport proteins needed for Mg
Important for
ATP and energy
DNA and RNA synthesis
Over 300 enzymes

76. Proposed Neuroprotective Mechanism of Action
Unclear
In animals reduces hypoxic ischemic damage by blocking NMDA receptors or glutamate and inhibits Ca influx

77. CNFUN Data Collection

78. Classification of Cerebral Palsy

79. Functional Consequences of Cerebral Palsy: GMFCS
Palisano et al. Dev Med Child Neurol 1997:39:

80. Who may benefit MOST from magnesium sulphate for fetal neuroprotection?

81. Trial sequential analysis

82. Trial sequential analysis
Publication dates: 2002, 2003, 2006, 2008
BJOG 2011 [Doyle, Crowther, Middleton, Voysey, Marret and Rouse]

83. Canadian Neonatal Follow-Up Network (CNFUN)
CNFUN is a voluntary collaboration between Neonatal and Perinatal Follow-Up Programs in Canada
Developed in liaison with the Canadian Neonatal Network
Builds on the work done in Québec by the Consortium de Recherche sur les Enfants Extrêmement Prématurés
Facilitates
Collaboration in research
Integrated data collection
Knowledge translation
Improvement of the quality of care and long-term outcomes of children seen in their programs.
CNFUN Director: Dr. Anne Synnes
A network of health care professionals dedicated to improving the care of newborns and children at high risk of adverse outcome as a result of conditions requiring intensive medical care.

84. 25 participating sites across Canada
Will follow all babies born at ≤ 28 weeks gestation (n = 2400)
Linked to Level-III NICUs (CNN)
Two cohorts:
Pilot: born April 1-Sept 30, 2009
MiCare: born Oct Sept 30, 2011
Sites will complete two neurodevelopmental assessments:
18 months (corrected)
36 months (chronological)

85. Details of CNFUN Assessments
At 18 months corrected age:
Clinic visit
Sociodemographic information and post-NICU discharge health utilization
Growth and physical examination
Gross Motor Function Classification System
Bayley Scales of Infant and Toddler Development (3rd edition)
At 36 months chronological age:
Questionnaire mail out
Identify further post-NICU discharge health utilization and parental concerns
Health Status Classification Pre-School (HSCS-PS)
Ages and Stages Questionnaire
Behaviour Rating Inventory of Executive Function-Preschool (BRIEF-P)