1 Lorenzo D. Botto, MD Division of Medical Genetics University of Utah, USA Pierpaolo Mastroiacovo, MD International Center on Birth Defects Rome, Italy Birth Defect Prevention: Global Issues WHO, Geneva, 16 January 2012: Hosts, Dr. Mario Merialdi, Dr. JP Pena‐Rosas International Clearinghouse for Birth Defects Surveillance and Research ICBDSR WHO Collaborating Center WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐ Mastroiacovo |1 42 Members in 38 Countries, and one Centre (ICBD, Rome) 42 Members in 38 Countries, and one Centre (ICBD, Rome) Utah Atlanta Texas California Canada National British Columbia Alberta Cuba Japan (China) Russia Ukraine Western Europe 21 Registries 14 Countries I l India Mexico Costa Rica Chile Maule ECLAMC 10 Countries Western Australia Victoria New Zealand Iran Israel Colombia WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐ Mastroiacovo |2
35
Embed
Birth Defect Prevention: Global Issues - who.int · in folic acid pathway RCT Case Control Fortification MTHFR Fol Receptor etc Blood folate B6 Homocysteine etc more NTDs fewer NTDs
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Lorenzo D. Botto, MDDivision of Medical GeneticsUniversity of Utah, USA
Pierpaolo Mastroiacovo, MDInternational Center on Birth Defects
Rome, Italy
Birth Defect Prevention: Global Issues
WHO, Geneva, 16 January 2012: Hosts, Dr. Mario Merialdi, Dr. JP Pena‐Rosas
International Clearinghouse for Birth Defects Surveillance and Research ICBDSR
WHO Collaborating Center
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 1
42 Members in 38 Countries, and one Centre (ICBD, Rome)42 Members in 38 Countries, and one Centre (ICBD, Rome)
Utah
Atlanta
Texas California
Canada National
British ColumbiaAlberta
CubaJapan
(China)Russia
Ukraine
Western Europe21 Registries14 Countries
I lIndia
Mexico
Costa Rica
Chile Maule
ECLAMC10 Countries
Western AustraliaVictoria
New Zealand
IranIsrael
Colombia
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 2
2
Key Points
• 65th World Health Assembly Resolution: call to global action for birth defect surveillance, treatment, prevention
• Modifiable risk factors: what can we do now that works?
• Global opportunities: surveillance, training, prevention
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 3
Key Points
• 65th World Health Assembly Resolution: call to global action for birth defect surveillance, treatment, prevention
• Modifiable risk factors: what can we do now that works?
• Global opportunities: surveillance, training, prevention
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 4
3
65th World Health Assembly Resolution
The call to action: urges Member States
• To raise awareness of the importance of birth defects asTo raise awareness of the importance of birth defects as cause of child morbidity and mortality
• To develop and strengthen registration and surveillance of birth defects
• To strengthen research and studies on etiology, diagnosis and prevention of major birth defectsand prevention of major birth defects
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 5
The call to action: requests the Director‐General
• To promote the collection of data on the global burden
65th World Health Assembly Resolution
of mortality and morbidity due to birth defects
• To continue to collaborate with the ICBDSR to improve collection of data on birth defects
• To support Member States in developing national plans for implementation of effective interventions to prevent and manage birth defects.
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 6
4
Birth DefectsBirth Defects3% of all births :3% of all births :
burden of disease is high :burden of disease is high :aand increasing everywhere:nd increasing everywhere:
minimum estimateminimum estimatemortality, morbidity, disability, costmortality, morbidity, disability, costalso middle/low income also middle/low income countriescountries
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 7
Global Issues in Birth Defects = Gaps and Opportunities Global Issues in Birth Defects = Gaps and Opportunities
EvaluationEvaluation ::Prevention :Prevention :
Capacity :Capacity :
llimited/no surveillance programsimited/no surveillance programsknown causes not addressedknown causes not addressedlimited training/expertiselimited training/expertise
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 8
5
Three congenital conditions account for 25% to 60% of under‐5 mortality, and share many risk factors
Congenital conditions: birth defects (malformations, genetic conditions, developmental disabilities of prenatal origin), preterm birth/IUGR, and birth asphyxia
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 21
[Source: Vollset and Botto, 2001]
Recommendations for folic acid supplementation had limited or no effect in Europe
BMJ 2005;330:
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 22
12
Estimated number of pregnancies with neural tube defects preventable by folic acid in study area, 1993‐8. Estimates assume three scenarios of effectiveness (30%, 60%, 90%), which
encompass a reasonable range from low dose fortification to highly effective supplementation
Source: BMJ 2005;330:
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 23
Fortification with folic acid
No fortification
Planning
Voluntary
Mandatory
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 24
13
Folic acid reduces the risk of NTD probably down to ~ 0.6 per 1,000 pregnancies
Black vertical line: drop in NTD occurrenceo after FA fortification in 24 areas o after FA supplementation in in 3 RCT and cohort studies
5 0er 1,000
valence of NTD
x 10,000 Dotted blue line: possible threshold of FA‐preventable NTD
5.0
l prevalence of NTD
, p
4.0
3.0
2.0
1 0
Prev
Total 1.0
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 25
0
Neural tube defect rates per 10,000 population, by race/ethnicity and fortification period status ‐‐‐National Birth Defects Prevention Network,* 1995—2007 (MMWR August 13, 2010 / 59(31);980‐984)
Source: BMJ 2005;330:
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 26
14
Preventing congenital conditions: NTDsmitigating risk factors and promoting protective factors
• Folate antagonists (meds) associated with increased risk of OFC
• Hungarian RCT: too small, ‘controls’ took trace elements (incl. Zn)
• Inconsistent findings in case‐control studies of MV with folic acid, maternal dietary folate intake, and red cell and plasma folate
• Fortification: North America, ?small decline in CL/P, not so in Australia (voluntary). For all clefts combined, small decrease in US b i C d Chilbut not in Canada or Chile.
• Open questions: high dose vs. low dose, MV vs. folic acid, recurrence vs. occurrence, population susceptibility
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 34
18
Clefts, micronutrients: part 2
• Riboflavin and vitamin A: few data
• Homocysteine: increased [hcy] (determined partly by folatestatus) in mothers of infants with CL, CLP, CPO) , ,
• B6: biomarkers of poor vitamin B6 status associated with increased risk of orofacial clefts in the Netherlands and Philippines. Also, B6 deficiency seen in populations with high intakes of polished rice in Asia, and these groups also seem to have high rates of CL, CLP, CPO
• Zinc: deficiency causes CPO in animals In the NetherlandsZinc: deficiency causes CPO in animals. In the Netherlands Children with CL, CLP, CPO and their mothers had lower [Zinc] in erythrocytes. In the Philippines, widespread zinc deficiency ; and high maternal zinc in plasma associated with low risk of orofacialclefts, with a dose‐response relation
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 35
Congenital heart defects: common, high impact, costly, heterogeneous
Do folic acid supplements influence fever risk ? Trend for lower “fever‐associated” risk among peri‐conceptional supplement users
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 40
21
Summary
1. Several known modifiable risk factors:
• folic acid (protective for neural tube defects)
• smoking (oral clefts)• smoking (oral clefts)
• diabetes (many birth defects, including heart defects)
• some medications (valproate‐NTDs; thalidomide ‐limb defects).
2. Evidence for protective effect of folic acid less clear for birth defects other than neural tube defects: clefts > heart defects > limb anomalies
3. Possible reasons ? Study design, classification, genetic factors in different populations, need for higher folic acid dose, need for multivitamin rather than FA alone (‐> implication for fortification)
WHO 2012 ‐ Global issues in Birth Defect Prevention Botto ‐Mastroiacovo | 41
Modifiable risk factors for birth defects: what evidence is helpful?
• Strength of evidence
– Multiple studies, different design, consistent findings
• Magnitude of risk:
– Relative Risk (how many times higher compared to unexposed?), absolute risk (actual chance of birth defect exposed)
– The higher the risk, the higher the number of affected babies
• Frequency of exposure
– How common among women of childbearing age?
– The more common, the more potential cases
• Types of birth defects and associated health outcomes
– The more severe, the more concerning
• Range of outcomes
– Potential for preventing other birth defects, pediatric disorders?
• Effectiveness of interventions
– Potential for high impact (fortification vs. supplementation)
Modifiable risk factors for birth defects: what evidence is helpful?
• Strength of evidence
– Multiple studies, different design, consistent findings
• Magnitude of risk:
– Relative Risk (how many times higher compared to unexposed?), absolute risk (actual chance of birth defect exposed)
– The higher the risk, the higher the number of affected babies
• Frequency of exposure
– How common among women of childbearing age?
– The more common, the more potential cases
• Types of birth defects and associated health outcomes
– The more severe, the more concerning
• Range of outcomes
– Potential for preventing other birth defects, pediatric disorders?
• Effectiveness of interventions
– Potential for high impact (fortification vs. supplementation)
SEARO 2011 | 54
28
Planning health interventions: quantity, intensity, equality
Quantity IntensityQuantity
Equality
Intensity
Quantity: population impact, people who benefit from the interventionIntensity: effort to provide benefit, over time Equality : just distribution of benefit, without disparities
The Health Impact Pyramid: quantity, intensity, equality
Quantity Intensity
Equality
Quantity: people who benefit from the value of the interventionIntensity: effort to provide benefit, over time Equality : just distribution of benefit, without disparities